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  • 1995-1999  (313)
  • 1999  (313)
  • Human  (119)
  • Immunohistochemistry  (100)
  • Life and Medical Sciences  (96)
  • Nuclear reactions
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Material
Years
  • 1995-1999  (313)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells (1999)
    Springer
    Virchows Archiv 435 (1999), S. 496-500 
    Details
    ISSN: 1432-2307
    Keywords: Key words Tenascin-C ; Laryngeal carcinoma ; Immunohistochemistry ; In situ hybridization ; Cell proliferation ; Cell migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tenascin-C (TN-C) is an extracellular matrix glycoprotein upregulated in various pathological processes. In this study, we investigated its distribution in dysplasia and carcinoma of the human larynx using immunohistochemistry and in situ hybridization (ISH) techniques. In all cancer tissues, TN-C immunostaining was markedly increased in the stroma, especially around the cancer cell nests. In addition, cytoplasmic staining of cancer cells was also observed in 62.5% of the invasive cases, the cells being distributed in the periphery of the nests adjacent to the stroma. TN-C mRNA signals in cancer cells were detected in all six cases examined by ISH. Furthermore, in vitro evaluation of the roles of TN-C demonstrated an increase in the proliferating cell fraction in a dose-dependent manner. In a wound closure assay, the addition of TN-C promoted migration. We conclude that TN-C secreted by cancer cells may be involved in their proliferation and migration in an autocrine fashion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050433
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  • 2
    Electronic Resource
    Electronic Resource
    Immunocytochemical investigation of catalase and peroxisomal lipid β-oxidation enzymes in human hepatocellular tumors and liver cirrhosis (1999)
    Springer
    Virchows Archiv 435 (1999), S. 486-495 
    Details
    ISSN: 1432-2307
    Keywords: Key words Peroxisomes ; Hepatocellular tumors ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A significant reduction of catalase activity, a peroxisomal marker enzyme, occurs in human hepatic neoplasias, but no information is available on other peroxisomal proteins. We have studied by means of immunohistochemistry four specific proteins of peroxisomes (catalase and three enzymes of lipid β-oxidation) in human hepatocellular tumors of various differentiation grades from adenoma to anaplastic carcinoma. In all tumors, except the adenomas, the tumor cells contained fewer peroxisomes than extrafocal hepatocytes and the reduction of antigenic sites in the tumor types generally correlated with the degree of tumor dedifferentiation as assessed by classical histopathological criteria. Two poorly differentiated tumors had no detectable peroxisomes at all. There were no major differences in the intensities of the immunocytochemical staining for all four studied peroxisomal antigens in different tumors, suggesting that the neoplastic transformation affects the biogenesis of the entire organelle and not merely the individual peroxisomal enzyme proteins. Some tumors exhibited a distinct peripheral distribution of peroxisomes. In cases with associated liver cirrhosis, the hepatocytes in the adjacent liver showed marked peroxisome proliferation, forming large perinuclear aggregates, occupying occasionally the entire cytoplasm. Taken together, our observations indicate that peroxisomes are significantly altered in both hepatocellular tumors and liver cirrhosis and, thus, could be responsible for some of the metabolic derangements observed in those disease processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050432
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  • 3
    Electronic Resource
    Electronic Resource
    Malignant myoepithelioma of the breast metastasizing to the jaw (1999)
    Springer
    Virchows Archiv 435 (1999), S. 520-523 
    Details
    ISSN: 1432-2307
    Keywords: Key words Breast neoplasms ; Malignant myoepithelioma ; Metastasis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A breast tumor in a 52-year-old female was interpreted as a malignant myoepithelioma based on morphological and immunohistochemical studies. The tumor consisted of elongated cells with clear cytoplasm and lacked glandular components. The tumor cells were stained positively for keratin, S-100 protein, glial fibrillary acidic protein (GFAP) and muscle-specific actin. Distant metastasis in the right jaw developed 8 years after the initial surgery and the metastatic deposit showed a similar morphology and immunoreactivity. Myoepithelial tumors are generally considered as benign or low-grade lesions and distant metastasis has been rarely documented. The present case presents the possibility of delayed occurrence of distant metastasis in myoepithelial tumor of the breast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050436
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  • 4
    Electronic Resource
    Electronic Resource
    Innervation of human adrenal gland and adrenal cortical lesions (1999)
    Springer
    Virchows Archiv 435 (1999), S. 580-589 
    Details
    ISSN: 1432-2307
    Keywords: Abstract Adrenal cortex ; Adrenal tumour ; Innervation ; Immunohistochemistry ; Neuronal markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The innervation of the human adrenal gland and of cortical lesions was studied in sections of cortical tissue (n=10), hyperplastic cortical tissue (n=3), and tissue from cortical adenomas (n=5) and carcinomas (n=6). The presence and distribution of nerve structures containing neuronal markers indicating sympathetic and parasympathetic innervation were studied by immunohistochemistry and the co-existence and co-localization patterns of the different markers by immunofluorescence. The cortex and hyperplastic cortical tissue had a moderate to rich supply of nerve structures containing the typical neuronal markers: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), small vesicle synaptic protein type 2 (SV2), and nerves showing immunoreactivity to the adrenergic marker tyrosine hydroxylase (TH). All these immunoreactive nerves were located predominantly adjacent to blood vessels, but also among parenchymal cells. The cortex showed numerous nerve structures containing the neuropeptide substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal protein (VIP), but few nerves containing these peptides were seen in hyperplastic cortical tissue. Typical markers were occasionally observed in cortical adenomas but were not found in carcinomas, except in a few cases where PGP 9.5 and NSE were present, but only adjacent to necrotic areas. Nerves containing NPY and VIP occurred in varying numbers in both adenomas and carcinomas. NPY- and VIP-immunoreactive nerve structures were seen mostly alongside blood vessels. There were several types of co-existence. For instance, NSE/VIP-, TH/VIP- and TH/NPY-immunoreactive nerve structures were often seen in the same trunk, but were only partly co-localized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050444
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  • 5
    Electronic Resource
    Electronic Resource
    Proliferation marker Ki-S11 – a prognostic indicator for squamous cell carcinoma of the hypopharynx (1999)
    Springer
    Virchows Archiv 435 (1999), S. 590-595 
    Details
    ISSN: 1432-2307
    Keywords: Key words Hypopharynx carcinoma ; Prognosis ; Proliferation ; Ki-S11 ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (〉45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050445
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  • 6
    Electronic Resource
    Electronic Resource
    Mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome: an autopsy case with a 24-year survival period (1999)
    Springer
    Virchows Archiv 435 (1999), S. 606-611 
    Details
    ISSN: 1432-2307
    Keywords: Key words Mixed ductal-endocrine carcinoma ; Pancreas ; Gastrinoma ; Immunohistochemistry ; Zollinger-Ellison syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an autopsy case of mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome. A 38-year-old Japanese male was found to have Zollinger-Ellison syndrome and pancreatic gastrinoma, and gastrectomy and resection of the pancreatic tumor were performed. However, hypergastrinemia persisted, and the patient died of disseminated carcinomatosis at 62 years of age, 24 years after the onset of Zollinger-Ellison syndrome. At autopsy, the main tumor was present in the residual pancreas, and metastases were noted in many organs. In the pancreas and other organs, ductal and endocrine carcinoma areas were mixed and there was a gradual transition between the two. No acinar differentiation was noted. The ductal elements were positive for mucins and carcinoembryonic antigen but negative for neuroendocrine markers, while endocrine elements were positive for chromogranin A and synaptophysin and to a lesser extent for gastrin, but negative for mucins and carcinoembryonic antigen. The ductal elements comprised about 30% of the tumor cells, and endocrine elements 70%. According to the revised World Health Organization classification, our case was diagnosed as mixed ductal-endocrine carcinoma. Our case is rare because the tumor manifested as gastrinoma with Zollinger-Ellison syndrome and the patient survived for 24 years. To the best of our knowledge, no such case has been reported. Our case suggests that pancreatic endocrine tumors may evolve into mixed ductal-endocrine carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050447
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  • 7
    Electronic Resource
    Electronic Resource
    Intimal-type primary sarcoma of the aorta (1999)
    Springer
    Virchows Archiv 435 (1999), S. 62-66 
    Details
    ISSN: 1432-2307
    Keywords: Key words Rhabdomyosarcoma ; Aorta ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5×2×2.5 cm projecting into the lumen. This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as ”intimal” on the basis of their site of origin, and they are not easy to classify from their histological pattern. Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of ”intimal” sarcoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050396
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  • 8
    Electronic Resource
    Electronic Resource
    From molecule to mind: the role of experience in shaping olfactory function (1999)
    Springer
    Journal of comparative physiology 185 (1999), S. 297-304 
    Details
    ISSN: 1432-1351
    Keywords: Key words Odor coding ; Learning ; Enhanced sensitivity ; Rabbit ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The olfactory system is faced with a particular problem – the high dimensionality and inherent unpredictability of the chemical world. Most natural odorants encountered in everyday life are complex mixtures of many different volatiles. This means that from the outset the olfactory system has to contend with a great and often unpredictable diversity of molecules, making it difficult for stable primary features of the chemical world to be mapped onto the sensory surface. One solution to such unpredictability is provided by learning. Learning confers flexibility, enabling individuals of a given species to acquire and make use of the most appropriate information in a particular environment. Two examples of this are presented: learning of maternal odors in neonatal rabbits, including evidence that the sensory surface itself may be influenced by environmental conditions so as to enhance sensitivity to molecules of particular ecological relevance, and cross-cultural human studies suggesting that experience with everyday odors influences not only the way these are evaluated, but also their perceived intensity. It is concluded that an adequate understanding of odor coding and olfactory function will not be possible without taking such experience-dependent factors into account.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003590050390
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  • 9
    Electronic Resource
    Electronic Resource
    Variable expression of heparan sulfate epitopes in crescents of human glomerulonephritis (1999)
    Springer
    Virchows Archiv 434 (1999), S. 145-151 
    Details
    ISSN: 1432-2307
    Keywords: Key words Carbohydrates ; N-Sulfation ; O-Sulfation ; Immunohistochemistry ; Rapidly progressive glomerulonephritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050318
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  • 10
    Electronic Resource
    Electronic Resource
    The interaction of Bcl-2 and Bax regulates apoptosis in biliary epithelial cells of rats with obstructive jaundice (1999)
    Springer
    Virchows Archiv 434 (1999), S. 333-339 
    Details
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Programmed cell death ; Ductular proliferation ; Biliary decompression ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A complex molecular network controls cell homeostasis by inducing apoptosis or proliferation. The balance of Bcl-2 and Bax, members of a protein family, determines whether a cell will become immortal (Bcl-2) or will undergo apoptosis (Bax). To determine the role of Bcl-2 and Bax during proliferation of biliary epithelial cells (BEC) after bile duct ligation (BDL) and their regression after biliary decompression we induced hyperplasia of BEC by BDL in male rats. Regression of hyperplastic BEC by way of apoptosis was induced by biliary decompression through a Roux-en-Y biliodigestive anastomosis. To quantify apoptosis a modified TUNEL assay was used. Expression of Bcl-2 and Bax was visualized by immunohistochemistry and quantified stereologically. BEC increased from 〈1% to 〉20% after BDL; this increase was associated with overexpression of Bcl-2 in up to 30% of hyperplastic BEC. After biliodigestive anastomosis, apoptotic BEC increased from 〈0.1% to a peak of 5.4% after 1 day to reach baseline again 1 week after decompression. This was associated with de novo appearance of Bax. The interaction between Bcl-2 and Bax triggers apoptosis in BEC and acts as a cell rheostat in BEC hyperplasia and its involution after biliary decompression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050349
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  • 11
    Electronic Resource
    Electronic Resource
    Immunohistochemical study of cytochrome P450 2C and 3A in human non-neoplastic and neoplastic tissues (1999)
    Springer
    Virchows Archiv 434 (1999), S. 401-411 
    Details
    ISSN: 1432-2307
    Keywords: Key words Human ; Cytochrome P450 2C ; Cytochrome P450 3A ; Immunohistochemistry ; Neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Organ and cellular distribution and expression constancy of microsomal cytochrome P450 (CYP) 2C and 3A in humans were studied with new polyclonal antibodies to CYP2C (MP-1) and 3A (NF-2) active in formalin-fixed, paraffin-embedded tissues. Antibodies were raised against purified human CYP2C9 and CYP3A4. On western blotting, MP-1 reacted with 2C8, 2C9, 2C18 and 2C19, and NF-2 with 3A4. In both frozen and paraffin sections, hepatocytes showed diffuse immunoreactivity with MP-1 and centrilobular staining with NF-2. Inparaffin sections of 40 kinds of nonneoplastic tissues, epithelium of the small and large intestine, bile duct, nasal mucosa, kidney and adrenal cortex stained positively with both MP-1 and NF-2 antibodies. Epithelium of gastric fundic glands, salivary glands, tracheobronchial glands, Brunner’s glands, the prostate, uterine cervix and nasopharynx showed definite reactivity with MP-1. Epithelium of the gastric mucosa with intestinal metaplasia, duodenum, gallbladder and intercalated ducts of the pancreas and chief cells of the parathyroid and the corpus luteum of the ovary reacted with NF-2. Among the neoplastic tissues, MP-1 reacted with pleomorphic adenoma of the salivary gland and carcinomas of six different organs, and NF-2 with those of 7 different organs. These results indicate that CYP2C and CYP3A are distributed widely and organ specifically, as well as being variably expressed in neoplastic and normal states.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050359
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  • 12
    Electronic Resource
    Electronic Resource
    Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations (1999)
    Springer
    Virchows Archiv 434 (1999), S. 489-495 
    Details
    ISSN: 1432-2307
    Keywords: Key words E-cadherin ; Colorectal cancer ; Immunohistochemistry ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050373
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  • 13
    Electronic Resource
    Electronic Resource
    Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma (1999)
    Springer
    Virchows Archiv 434 (1999), S. 153-158 
    Details
    ISSN: 1432-2307
    Keywords: Key words Cyclin B1 ; Esophageal squamous cell carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9 % (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P〈0.005) and with venous invasion (P〈0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P〈0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P〈0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050319
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  • 14
    Electronic Resource
    Electronic Resource
    Immunohistochemical localization of α- and βA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system (1999)
    Springer
    Virchows Archiv 434 (1999), S. 29-36 
    Details
    ISSN: 1432-2307
    Keywords: Key words Activin A ; Inhibin A ; Endocrine tumors ; Digestive system ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one α-subunit and one βA-subunit (α-βA), while activin A is a homodimer of the βA-subunit (βA-βA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the α- and βA-subunits of inhibin/activin. Immunoreactivity for the βA-subunit, but not for the α-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. βA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The α-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the βA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050301
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  • 15
    Electronic Resource
    Electronic Resource
    Reconstruction of pleomorphic adenoma of the salivary glands in three-dimensional collagen gel matrix culture (1999)
    Springer
    Virchows Archiv 434 (1999), S. 137-143 
    Details
    ISSN: 1432-2307
    Keywords: Key words Salivary gland ; Pleomorphic adenoma ; Collagen ; Cell culture ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and α-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multi-directional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050317
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  • 16
    Electronic Resource
    Electronic Resource
    Systemic granulomatous arteritis associated with Epstein-Barr virus infection (1999)
    Springer
    Virchows Archiv 434 (1999), S. 249-254 
    Details
    ISSN: 1432-2307
    Keywords: Key words Systemic granulomatous arteritis ; Epstein-Barr virus ; Virus-associated haemophagocytic syndrome ; In situ hybridization ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 61-year-old woman initially presented with symptoms and findings reminiscent of infectious mononucleosis, and her illness then took a rapidly fatal course. Autopsy revealed widespread granulomatous arteritis, with multinucleated giant cells but without eosinophils and fibrinoid necrosis, affecting small arteries and arterioles and infiltration of haemophagocytic histiocytes into many organs. In situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide probes showed positive signals in the infiltrating immune cells and epithelial and endothelial cells of the affected organs. EBV-associated haemophagocytic syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the immunophenotypes of the infiltrating immune cells, a possible role of CD4+ T-cells in the pathogenesis of this haemophagocytic syndrome and granulomatous vasculitis was suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050336
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  • 17
    Electronic Resource
    Electronic Resource
    High-grade carcinoma component in epithelial-myoepithelial carcinoma of salivary glands clinicopathological, immunohistochemical and flow-cytometric study of three cases (1999)
    Springer
    Virchows Archiv 434 (1999), S. 291-299 
    Details
    ISSN: 1432-2307
    Keywords: Key words Epithelial myoepithelial carcinoma ; Salivary gland tumours ; Immunohistochemistry ; Flow cytometry ; MIB-1 (Ki 67) ; Proliferative markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Three cases of epithelial-myoepithelial carcinoma (EMC) with coexisting areas of high grade carcinoma are reported. In two of the cases there was a previous recurrence, and in all three patients there had been a sudden increase in size before final surgery. The typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of wide spectrum cytokeratins, Cam 5.2 and EMA in the ductal part, and muscle-specific actin, smooth muscle actin, S-100 protein, vimentin and cytokeratins in the myoepithelial component. These areas also had a low mitotic count and low proliferation rate as measured by immunohistochemistry and by flow cytometry. Conversely, areas of high-grade tumour had the features of a large cell carcinoma, with focal mucin secretion in two cases. This high-grade component showed an epithelial immunophenotype in two cases, and was negative for all tested markers in the third one. The mitotic counts and the proliferation rates were much higher in these anaplastic areas. One of the patients died 3 months after treatment; another developed lymph node metastases 1 year later and was alive after 6 years of follow-up. The third patient was alive without evidence of disease 7 months after wide surgical resection of the tumour. The possibility of anaplastic transformation in EMC makes thorough sampling mandatory in this type of neoplasm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050344
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  • 18
    Electronic Resource
    Electronic Resource
    Cerebrovascular involvement in systemic AA and AL amyloidosis: a clear haematogenic pattern (1999)
    Springer
    Virchows Archiv 434 (1999), S. 551-560 
    Details
    ISSN: 1432-2307
    Keywords: Key words Systemic amyloidosis ; Brain ; Circumventricular organs ; Choroid plexus ; Immunohistochemistry ; Aβ colocalization.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Amyloid deposits in cerebral vessels are common in β-amyloid diseases (Alzheimer’s disease, congophilic amyloid angiopathy, Down’s syndrome and hereditary cerebral amyloidosis with haemorrhage of the Dutch type). We report of 20 autopsies on patients who had died with systemic amyloidosis of the AA, Aλ and Aκ types: the brains were examined for the occurrence of amyloid. Vascular amyloid was detected in choroid plexus (in 17 of 20 cases), infundibulum (5 of 8), area postrema (6 of 11), pineal body (3 of 7) and subfornical organ (2 of 3), but not in cortical and leptomeningeal vessels. Immunohistochemical classification of the cerebral amyloid and the systemic amyloid syndrome showed identity proving the same origin of both. The distribution is indicative of a haematogenic pattern of amyloid deposition in systemic amyloidosis and is different from that in Alzheimer’s, prion, ATTR and cystatin C diseases. It corresponds to areas of the brain with a ”leaky” blood–brain barrier. Additionally, all the cases with AA amyloidosis exhibited an Aβ coreactivity in choroid plexus vessels. In one exceptional case, Aβ reactivity of AA amyloid also occurred outside of the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050383
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  • 19
    Electronic Resource
    Electronic Resource
    Myoepithelial cells and basal lamina in poorly differentiated in situ duct carcinoma of the breast (1999)
    Springer
    Virchows Archiv 434 (1999), S. 227-234 
    Details
    ISSN: 1432-2307
    Keywords: Key words Ductal carcinoma in situ ; Immunohistochemistry ; Myoepithelial cells ; Basal lamina ; Smooth muscle actin ; Calponin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A retrospective study was made of 38 selected brest tumours with a poorly differentiated in situ duct component. These were classified on haematoxylin and eosin (H&E) as ductal carcinoma in situ (DCIS; 10 cases), DCIS with invasion (17 cases) and DCIS with features suggestive of for stromal invasion (11 cases). The last were these lesions composed of neoplastic ducts with irregular outlines and a myoepithelial layer that was not clearly evident or large neoplastic ducts growing close together or surrounded by inflammatory desmoplastic stroma. Cases of DCIS involving areas of sclerosing adenosis were included in this category. Consecutive sections obtained from each case were studied with a panel of antibodies against myoepithelial cells (alpha smooth muscle actin and calponin) and basal lamina (BL) components (laminin and type IV collagen). It was found that in situ lesions showed well-formed basal lamina and/or an evident myoepithelial layer. These features were lacking in the invasive areas. Nine of the 11 cases with suggestive features of stromal invasion were reclassified as invasive duct carcinoma (5 cases)and DCIS (4 cases), according to the absence or presence of a continuous myoepithelial layer and/or basal lamina. In 2 such cases immunohistochemistry yielded equivocal results and the label ”suggestive of invasion” was therefore pertinent. Immunohistochemistry facilitates the diagnosis of breast DCIS; myoepithelial and basal lamina markers are useful in differentiating microinvasive from in situ ductal carcinomas of the breast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050332
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  • 20
    Electronic Resource
    Electronic Resource
    Autonomic nerve tumour with skeinoid fibres: ultrastructure of skeinoid fibres examined by quick-freezing and deep-etching method (1999)
    Springer
    Virchows Archiv 434 (1999), S. 267-276 
    Details
    ISSN: 1432-2307
    Keywords: Key words Autonomic nerve tumour ; Small intestine ; Immunohistochemistry ; Quick-freezing ; Deep-etching
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A case of gastrointestinal autonomic nerve tumour with skeinoid fibres (SFs) of the jejunum in a 79-year-old Japanese man, was examined by the quick-freezing and deep-etching (QF-DE) method. The tumour consisted of spindle cells with immunohistochemical reactions for vimentin, NSE and CD34. Electron microscopically, features of the neural cells of the myenteric plexus were observed. The QF-DE method demonstrated intercellular meshwork structures, consisting of thin filaments (7–15 nm), with granular deposits. Fully developed parts of the deposits formed nodular aggregates composed of irregularly surfaced thick fibrils (30–48 nm) with a tendency to linear arrangement (SFs). We detected many interconnecting thin filaments (ICTFs) between the SFs, which were pre-existing components in the meshwork, avoiding the granular deposits. The focal thickening formed by the connection between SFs and ICTFs revealed a periodicity typical of SFs (33–45 nm). We conclude that SFs are formed by decoration of the granular deposits along pre-existing intercellular meshwork structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050340
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  • 21
    Electronic Resource
    Electronic Resource
    Control of mesenteric arterial tone in vitro in humans and rats (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 322-330 
    Details
    ISSN: 1432-1912
    Keywords: Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K+ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca2+ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca2+-induced contractions in human arteries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005358
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  • 22
    Electronic Resource
    Electronic Resource
    Pathologie der Rhabdo- myosarkome des Kindes- und Adoleszentenalters Ein Bericht des Kindertumorregisters bei der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) (1999)
    Springer
    Der Pathologe 20 (1999), S. 87-97 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notes: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050326
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  • 23
    Electronic Resource
    Electronic Resource
    Pleomorphes Adenom (Mischtumor) des äußeren Gehörgangs Zur Differentialdiagnose der Tumoren der Zeruminaldrüsen (1999)
    Springer
    Der Pathologe 20 (1999), S. 125-129 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Pleomorphes Adenom ; Äußerer Gehörgang ; Zeruminom ; Differentialdiagnose ; Immunhistochemie ; Key words Pleomorphic adenomas ; Meatus acusticus externus ; Ceruminoma ; Differential diagnosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A tumor was removed from the right external auditory canal of a 69-year old female patient. The histopathological and immunhistochemical evaluation revealed a pleomorphic adenoma (mixed tumor). The differential diagnosis of the tumors derived from the ceruminal glands, their clinical and prognostic implications as well as the histogenesis of pleomorphic adenomas in this localization are discussed.
    Notes: Zusammenfassung Bei einer 69jährigen Patientin wurde aus dem rechtsseitigen äußeren Gehörgang ein Tumorknoten exstirpiert. Die histopathologische und immunhistochemische Untersuchung ergab ein pleomorphes Adenom (Mischtumor). Die Differentialdiagostik der von den Zeruminaldrüsen abgeleiteten Tumoren, deren klinisch-prognostische Konsequenz sowie die Histogenese der pleomorphen Adenome in dieser besonderen Lokalisation werden erörtert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050331
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  • 24
    Electronic Resource
    Electronic Resource
    Cellular localization of cyclo-oxygenase isozymes in Crohn’s disease and colorectal cancer (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 212-218 
    Details
    ISSN: 1432-1262
    Keywords: Key words Cyclo-oxygenase ; Colon carcinogenesis ; Crohn’s disease ; Familiar adenomatous polyposis coli ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Deregulation of cyclo-oxygenase isozyme expression has been shown to be a consistent feature of inflammatory bowel diseases and colorectal cancer in humans. This study investigated the cellular localization of aberrant cyclo-oxygenase expression in normal and diseased colon. Biopsies of seven normal colonic tissues, eight tissue samples from patients suffering from Crohn’s disease, five polyps from patients with familiar adenomatous polyposis coli, and ten sporadic adenocarcinomas were analyzed using isozyme-selective immunoprecipitation, western blotting, and immunohistochemistry. Cyclo-oxygenase-1 expression was demonstrated in normal human colon, Crohn’s disease, and colorectal tumors. In normal colon and also in adenomatous polyps, cyclo-oxygenase-1 specific immunosignals were localized to epithelial cells of the upper part of the crypts and endocrine cells of the lower part. In Crohn’s disease cyclo-oxygenase-1 expression was restricted to cells of the inflammatory infiltrate. While barely detectable in normal colon, cyclo-oxygenase-2 protein was strongly increased in epithelial cells located in the uppermost part of the crypts, in surface epithelial cells, and in mononuclear cells of the lamina propria of Crohn’s disease. The constitutive overexpression of cyclo-oxygenase-2 protein observed in the majority of the adenomatous polyps and all adenocarcinomas was attributed to both epithelial and interstitial cells in that the latter predominated in adenomas, and epithelial cells were the prevailing cyclo-oxygenase-2 expressing cell type in adenocarcinomas. In conclusion, both autocrine and paracrine effects of aberrant cyclo-oxygenase-2 expression may contribute to the development of Crohn’s disease and colonic tumor development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003840050213
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  • 25
    Electronic Resource
    Electronic Resource
    The prognostic significance of tumor vascularization in patients with localized colorectal cancer (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 272-276 
    Details
    ISSN: 1432-1262
    Keywords: Key words  Colorectal cancer ; Angiogenesis ; Vessel density ; Prognosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a ×200 field in the area of the most dense neovascularization. Vascular density was found to be 75±27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (〉75) than in those of less vessel density (〈75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003840050227
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  • 26
    Electronic Resource
    Electronic Resource
    Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics (1999)
    Springer
    Archives of toxicology 73 (1999), S. 7-14 
    Details
    ISSN: 1432-0738
    Keywords: Key words Organophosphates ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t 1/2 3.7 h) and spontaneous reactivation (t 1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10−6 M (paraoxon-methyl) and 10−4 M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 μM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t 1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050580
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  • 27
    Electronic Resource
    Electronic Resource
    Immunohistochemical, conventional and immunoelectron microscopical characteristics of periodic acid-Schiff-positive granules in the mouse brain (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 31-38 
    Details
    ISSN: 1432-0533
    Keywords: Key words Polyglucosan body ; Periodic ; acid-Schiff-positive granules ; Mouse brain ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Periodic acid-Schiff-positive granules (PGs) appear in the mouse brains in relation to advancing age. The exact location and pathophysiological significance of PGs, however, are not fully understood. The incidence, staining properties, and topographical distributions of PGs in the brains of 17 AKR mice ranging in age from 7 to 18 months were examined histochemically and immunohistochemically using antibody KM279 raised against a polyglucosan. In addition, to define the precise site of PG formation, we investigated the brains of 4 AKR mice of 24 months of age using conventional and immunoelectron microscopy. PGs were seen in all mice examined and the levels were increased with age. The PGs were located predominantly in the hippocampus and, to a lesser extent, in the cerebellum and olfactory bulb. Immunohistochemically, PGs in the hippocampus and cerebellum were labeled uniformly with KM279. On immunoelectron microscopy with this monoclonal antibody, the fibrillar or membranous structures corresponding to PGs seen using light microscopy were labeled specifically with gold particles. With conventional electron microscopy, fibrillar or membranous structures were seen along with synaptic vesicles and dense-core granules. Moreover, around the cells containing PGs, a few synaptic junctions with neighboring cells were observed, indicating that the cells contributing to formation of PGs were neuronal cells. The positive immunoreactivity of AKR mouse PGs for the antibody KM279 suggests that the PGs and similar structures in other species may share a common antigenicity. Thus, it is assumed that PGs in AKR mice might result from some abnormalities in glucose metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051048
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  • 28
    Electronic Resource
    Electronic Resource
    Nebulin is normally expressed in nemaline myopathy (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 433-436 
    Details
    ISSN: 1432-0533
    Keywords: Key words Congenital nemaline myopathy ; Nebulin ; α-Actinin ; Immunohistochemistry ; Western blot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the nebulin gene is located in the candidate gene locus of autosomal recessive nemaline myopathy, 2q21.2–q22, we examined five muscle biopsy specimens with monoclonal and polyclonal antibodies against nebulin in combination with the modified Gomori trichrome stain. We were able to demonstrate immunohistochemically that there was no abnormality in nebulin in the muscle fibers both with and without nemaline bodies. Although the molecular weight of nebulin was normal, it was slightly reduced in amount on immunoblotting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051011
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  • 29
    Electronic Resource
    Electronic Resource
    Nitric oxide synthase-containing neurons in the myenteric plexus of the rat gastrointestinal tract: distribution and regional density (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 99-112 
    Details
    ISSN: 1432-0568
    Keywords: Key words Autonomic ; Wholemounts ; Immunohistochemistry ; Myenteric ganglia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nitrergic (NO) neurons play crucial inhibitory roles in the control of gut motility. Variations in the density of these neurons within the gastrointestinal tract (GI) may provide useful functional information, but, most surveys available have employed limited and/or highly localized samples. It remains unclear to what extent (a) NO neurons are concentrated disproportionately in particular GI regions, or (b) variations in NO cell number merely reflect changes in overall myenteric neuron density. This experiment surveyed the distributions of neuronal nitric oxide synthase-positive (NOS+) and other myenteric neurons in the GI tract, using immunohistochemical and Cuprolinic blue counterstaining techniques. Adjustable sampling grids superimposed on wholemounts were used to investigate the topographic patterns in the stomach (90 sampling sites; 45 per side) and proximal duodenum (63 loci). We present four major findings: First, variations were detected in the number of NOS+ neurons in specific regions of the stomach (e.g., corpus〉antrum@forestomach) and along both longitudinal (oral〉anal) and circumferential (mesenteric〉antimesenteric) axes in the duodenum. Second, the variations in NOS+ neuronal counts within each organ covaried with the total number of myenteric neurons at different locations (stomach, r=0.77; duodenum, r=0.59), suggesting that local myenteric plexus density is a factor determining NOS+ cell concentrations. Third, in contrast to such a principle of covariation within each organ, NOS+ neurons constituted a consistently smaller proportion of gastric (20%) than of duodenal (28%) myenteric plexus neurons, suggesting that a second principle controls the characteristic percentages of the myenteric plexus that express NOS in different organs. Fourth, the regional samples were used to extrapolate the overall number of NOS+ and total myenteric cells in the rat stomach (43,000; 217,000) and first 3.5 cm of the small intestine (29,000; 103,000). These results, taken together, also suggest that the surveying protocol used is capable of detecting subtle differences in cellular distributions, thus providing a practical strategy for investigating patterns of chemical phenotypes within the GI tract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050213
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  • 30
    Electronic Resource
    Electronic Resource
    Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbed proliferation (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 93-99 
    Details
    ISSN: 1432-069X
    Keywords: Key words Chronic diabetic wounds ; Human ; fibroblasts ; Wound healing ; Cell culture ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with diabetes mellitus experience impaired wound healing often resulting in chronic foot ulcers. Hospital discharge data indicate that 6–20% of all diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower extremity ulcer. Maintaining glucose levels at acceptable levels (below 10 mmol/l) is considered to be an important part of the clinical treatment, but the exact mechanism by which diabetes delays wound repair is not yet known. We studied this phenomenon by determining the potential of fibroblasts isolated from the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to proliferate in vitro. Controls were fibroblasts isolated from normal skin of the upper leg of five healthy age-matched volunteers and of six non-insulin-dependent diabetes patients. Proliferative capacity was analysed by evaluation of plates after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was studied by light and transmission electron microscopy. Diabetic ulcer fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly more slowly than the nonlesional control fibroblasts (P 〈 0.00047) and age-matched control fibroblasts (P 〈 0.00003). After culturing the fibroblasts for a prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e. physiological) medium, this difference in proliferation rate between diabetic ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P 〈 0.0001 for high-glucose and P 〈 0.0009 for low-glucose on day 7). Fibroblast proliferation in all three groups was slightly lower in high-glucose than in low-glucose medium, although not significantly at any time-point. Light microscopy showed diabetic ulcer fibroblasts to be large and widely spread. Transmission electron microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin fibroblasts revealed a large dilated endoplasmic reticulum, a lack of microtubular structures and multiple lamellar and vesicular bodies. These results show a diminished proliferative capacity and abnormal morphology of fibroblasts derived from diabetic ulcers of non-insulin-dependent diabetes patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050389
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  • 31
    Electronic Resource
    Electronic Resource
    Stratum corneum chymotryptic enzyme in psoriasis (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 195-200 
    Details
    ISSN: 1432-069X
    Keywords: Key words Epidermis ; Immunohistochemistry ; Protease ; Psoriasis ; Stratum corneum chymotryptic ; enzyme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stratum corneum chymotryptic enzyme (SCCE) is a serine protease which may function in the turnover of the stratum corneum by means of degradation of intercellular adhesive structures between corneocytes. It is also potentially an epidermal activating enzyme for cytokines such as interleukin-1β. The aim of this work was to study the expression of SCCE in psoriatic epidermis by means of immunohistochemistry, and to elucidate the nature of the SCCE present in psoriatic scales by means of biochemical analyses. In comparison to normal skin the number of cell layers expressing SCCE in psoriatic lesions was consistently increased. In nonlesional psoriatic skin the pattern of SCCE expression varied. It was similar to the pattern in normal skin in some biopsies, whereas in other biopsies evidence of an increased expression of SCCE was found. By means of zymography and immunoblotting, extracts of psoriatic scales were found to contain active SCCE as well as enzymatically inactive SCCE precursor. Also the effects of inhibitors on the activity towards a chromogenic protease substrate in the extracts after partial purification by gel exclusion chromatography were compatible with the presence of enzymatically active SCCE. We conclude that the expression of SCCE in psoriasis may be upregulated, and that the conversion of inactive SCCE-precursor to active SCCE occurs in the psoriatic lesion. The possible role of SCCE in the pathophysiology of psoriasis remains to be elucidated, but should be considered in future studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050393
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  • 32
    Electronic Resource
    Electronic Resource
    Immunohistochemical localization of the neutral cysteine protease bleomycin hydrolase in human skin (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 238-240 
    Details
    ISSN: 1432-069X
    Keywords: Key words Cysteine protease ; Bleomycin hydrolase ; Keratinocyte ; Skin cancers ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050400
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  • 33
    Electronic Resource
    Electronic Resource
    Nickel-induced activation of T cells in individuals with negative patch test to nickel sulphate (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 247-252 
    Details
    ISSN: 1432-069X
    Keywords: Key words T cell activation ; Nickel ; Human ; Interferon-gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Contact hypersensitivity to nickel is the most common form of allergic contact dermatitis. To gain insight into the induction of this frequent disease, T cell reactivity towards nickel was investigated in “nonallergic” individuals defined as those with no skin manifestations and a negative patch test towards NiSO4. Surprisingly, we found that nickel induced proliferation of peripheral blood mononuclear cells (PBMC) from 16 of 18 adult individuals tested. This activation was specific, and no stimulation of PBMC was observed using control stimulants at equimolar concentrations. Furthermore, the NiSO4-induced activation required the presence of professional antigen-presenting cells. To describe the functional capacity of the nickel-inducible T cells, cytokine release was investigated in both nickel-allergic and nonallergic individuals. The T cells from both groups released interferon-γ but no interleukin-4 upon stimulation with nickel, suggesting that the functional capacities of these cell populations were similar in nickel-allergic and nonallergic individuals. Thus, at this level, no qualitative differences could be demonstrated between T cells obtained from nickel-allergic and nonallergic individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050404
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    Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 269-274 
    Details
    ISSN: 1432-069X
    Keywords: Key words Serotonin ; Allergic contact dermatitis ; Immunohistochemistry ; High-performance liquid ; chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P 〈 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050407
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    Langerhans cells enclosing sunburn cells in acute UV erythema in vivo (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 303-305 
    Details
    ISSN: 1432-069X
    Keywords: Key words Langerhans cells ; Sunburn cells ; UV ; erythema ; Apoptosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050413
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    Human melanocytes grown in epidermal equivalents transfer their melanin to follicular outer root sheath keratinocytes (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 325-332 
    Details
    ISSN: 1432-069X
    Keywords: Key words ORS cells ; Melanocytes ; Human ; Organotypic cultures ; Melanosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred “through racial barriers”. Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050417
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    Bunina bodies in amyotrophic lateral sclerosis on Guam: a histochemical, immunohistochemical and ultrastructural investigation (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 150-156 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Bunina body ; Guam ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An investigation of Bunina bodies is important when studying the pathoetiology and pathomechanisms involved in amyotrophic lateral sclerosis (ALS). It may serve as a clue essential for the study of the pathogenesis of Guamanian amyotrophic lateral sclerosis (ALS-G), and it may provide a means of answering the question of whether ALS-G is the same disease as classical ALS or a different entity. In ALS-G, however, no precise histochemical, immunohistochemical, or detailed ultrastructural examination has been published to date. To elucidate the pathological differences/similarities of Bunina bodies between classical ALS and ALS-G, we performed histochemical, immunohistochemical, topographic and ultrastructural examinations. Histochemically, hematoxylin and eosin, Masson’s trichrome, methylgreen-pyronin, phosphotungstic acid-hematoxylin, Klüver-Barrera, Bodian and periodic acid-Schiff staining were utilized. Immunohistochemical examination was performed using antibodies for cystatin C, ubiquitin, Tau-2, Cu/Zn superoxide dismutase, phosphorylated neurofilament and glial fibrillary acidic protein. Histochemical findings were consistent with those previously described for classical ALS. The immunohistochemical study showed that in ALS-G Bunina bodies were intensely labeled by an anti-cystatin C antibody. Topographic examination demonstrated that Bunina bodies were distributed in the spinal anterior horns and Clarke’s column in the spinal cord. Ultrastructurally, Bunina bodies were composed of electron-dense amorphous/ granular material accompanied by vesicular structures and neurofilaments. The results of the present study have revealed that the pathological features of Bunina bodies in ALS-G are identical to those seen in classical ALS. These findings strongly suggest that a similar degenerative process occurs in the spinal anterior horn cells in both ALS-G and classical ALS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051063
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    Correlation of survival time with size of axonal swellings in diffuse axonal injury (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 197-202 
    Details
    ISSN: 1432-0533
    Keywords: Key words Diffuse axonal injury ; Head injury ; β-amyloid precursor protein ; Immunohistochemistry ; Forensic neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Widespread damage to axons in the white matter of the brain is a well-recognised consequence of non-missile head injury. This diffuse axonal injury is characterised by a gradual swelling of the axon associated with an accumulation of cellular organelles and proteins. We have investigated the relationship between the size of the swellings of the damaged axon with survival time in post-mortem brain tissue. Sixty-six cases of head injury with known length of post-traumatic survival were selected for study, and immunohistochemistry for β-amyloid precursor protein (βAPP) was carried out. The minimum diameter of the βAPP-immunolabelled damaged axons was measured in micrometers using the IBAS image analysis system. There was a strong, positive and significant relationship between the mean size of axonal swelling and survival time which plateaued at around 85 h post injury. With longer survival times the situation becomes more complex. βAPP immunolabelling of damaged axons can contribute evidence about trauma and post-injury survival time in the forensic setting but should always be assessed with other evidence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051069
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    Immunocytochemical demonstration of oncocytes in normal adenohypophysis (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 40-44 
    Details
    ISSN: 1432-0533
    Keywords: Key words Pituitary gland ; Immunohistochemistry ; Mitochondria ; Oncocytes ; Oncocytomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunocytochemical examination for mitochondrial protein and cytochrome oxidase was performed to demonstrate oncocytes in normal adenohypophysis obtained from 28 patients of various age. A small number of solitary large epithelial cells showed intense cytoplasmic granular immunoreactivities for mitochondrial protein and cytochrome oxidase. The proportions of the cells positive for the former and the latter ranged from 0% to 5.9% (mean ± SD; 1.5 ± 1.7%) and from 0% to 4.9% (1.4 ± 1.6%), respectively. These cells were either absent or extremely rare in young patients (under 10 years) but tended to increase in number with age (P 〈 0.0001). On the other hand, the mirror section technique showed that most of these cells were negative for adenohypophysial hormones, but a few of them were faintly positive for: α-subunit (8.0%), β-subunits of follicle-stimulating hormone (4.8%), luteinizing hormone (2.5%), thyroid-stimulating hormone (1.0%), and growth hormone (0.5%), and were negative for prolactin and adrenocorticotropic hormone. We considered that these cells represent oncocytes that exist in varying numbers in normal adenohypophysis. It was suggested that oncocytes in normal adenohypophysis share various common features with tumorous oncocytes of pituitary oncocytomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050953
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    Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 240-246 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Advanced glycation endproducts ; Immunohistochemistry ; Superoxide dismutase ; Hyaline inclusions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N ɛ-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050980
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    Changes in serotonergic neurons in the brain of pyrithiamine-induced acute thiamine-deficient mice (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 614-621 
    Details
    ISSN: 1432-0533
    Keywords: Key words Serotonin ; Thiamine deficiency ; Immunohistochemistry ; Vulnerability ; Degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined changes in 5-hydroxytriptamine (5-HT, serotonin) neurons in pyrithiamine-induced thiamine deficiency in mice immunohistochemically. Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus. Most remarkably, degenerative winding fibers were detected between the deep mesencephalic nucleus and the ventral tegmental area. Increases in intensity of 5-HT immunoreactivity in the dorsal raphe nucleus and decreases in the number of 5-HT-immunoreactive cell bodies in the dorsal and the median raphe nuclei were detected. These results demonstrated the differential vulnerability of 5-HT neurons in thiamine-deficient mice. This is the first report to demonstrate changes in 5-HT neurons immunohistochemically throughout the brain of pyrithiamine-induced thiamine deficient mouse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051126
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    Immunohistochemical study of some cytoskeletal proteins in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 177-184 
    Details
    ISSN: 1432-0533
    Keywords: Key words Cytoskeletal proteins ; Immunohistochemistry ; Myofibrillar myopathy ; Hereditary myopathy ; Holstein-Friesian cattle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the expression, using immunohistochemical and Western blot methods, of some cytoskeletal proteins including desmin, vimentin, actin, α-actinin, and ubiquitin in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle (the histochemical and electron microscopical aspects have been previously reported). Immunohistochemically, the expression of desmin was observed strongly in the subsarcolemmal regions, but was lacking or faint in the area corresponding to the core-like structures. Vimentin showed almost the same localization as desmin, but no activity could be observed in the core-like structures. In addition, the core-like structures showed strong immunoreactivity for actin and ubiquitin, but no immunoreactivity for α-actinin. F-actin stained with phalloidin-tetramethyl-rhodamine was strongly positive in irregular spots that corresponded to the core-like structures, but was negative for desmin-positive regions. Western blot analysis of the diseased muscles revealed a significant increase in the amount of desmin and vimentin immunoreactivities and similar amounts of actin and α-actinin compared with the control muscles. Two-dimensional electrophoresis revealed no isoforms of desmin, suggesting the absence of abnormal phosphorylated forms of desmin. Since the co-localization of desmin and vimentin and the absence of phosphorylated desmin suggest that the overexpression of desmin may be reflected in the reactive change or regenerating process, the present myopathy should be regarded as an entity separate from desmin-storage myopathy or desmin-related myopathies. We also discuss the possibility that the present myopathy could be considered as myofibrillar myopathy, a recently proposed nosological entity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050971
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    Inducible nitric oxide synthase expression in human cerebral infarcts (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 215-220 
    Details
    ISSN: 1432-0533
    Keywords: Key words Cerebral ischemia ; Inflammation ; Immunohistochemistry ; Nitrotyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inducible or “immunological” isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli and synthesizes toxic amounts of NO. In rodent models of focal cerebral ischemia, iNOS is expressed in neutrophils invading the injured brain and in local blood vessels. Studies with iNOS inhibitors and iNOS null mice indicate that NO produced by iNOS contributes to ischemic brain injury. In the present study, we sought to determine whether iNOS is also expressed in the human brain after ischemic stroke. Studies were conducted using immunohistochemistry on autopsy brains with neuropathological evidence of acute cerebral infarction. iNOS immunoreactivity was observed in neutrophils infiltrating the ischemic brain and in blood vessels within the ischemic territory. iNOS-positive cells also were immunoreactive for nitrotyrosine, reflecting protein nitration by NO-derived peroxynitrite and nitrites. iNOS or nitrotyrosine immunoreactivity was not detected outside the region of the infarct. These observations provide evidence that iNOS is expressed in the human brain after ischemic infarction and support the hypothesis that iNOS inhibitors may be useful in the treatment of ischemic stroke in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050977
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    Electronic Resource
    Immunoreactivity of β-amyloid precursor protein in amyotrophic lateral sclerosis (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 463-468 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; β-Amyloid precursor protein ; Immunohistochemistry ; Fast axonal transport ; Anterior horn neuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the localization and extent of β-amyloid precursor protein (β-APP695) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of 21 patients with amyotrophic lateral sclerosis (ALS), paying special attention to anterior horn neurons. Specimens from 18 patients without neurological disease served as controls. Increased β-APP immunoreactivity was frequently recognized in the anterior horns of the ALS patients with short clinical courses or with mild depletion of anterior horn cells, while no β-APP immunoreactivity was demonstrated in those with severe depletion of anterior horn neurons or with long-standing clinical courses. Increased β-APP immunoreactivity in the anterior horn neurons was mainly confined to the perikarya and no immunoreactivity was recognized in the dendrites or proximal axons directly emanating from the somata, except some spheroids (proximal axonal swellings) which showed increased immunoreactivity of β-APP. Increased β-APP immunoreactivity was spotted or focally aggregated in the perikarya of normal-looking large anterior horn neurons, while it was frequently diffuse in that of degenerative neurons such as central chromatolytic cells and or those with simple atrophy. On the other hand, the controls showed no immunostaining with β-APP in the spinal cord. These findings suggest that increased immunoreactivity of β-APP in neuronal perikarya of the anterior horn cells and in some proximal axonal swellings is an early change of ALS, and may be a response of the increased synthesis of β-APP resulting from neuronal damage, or the impairment of fast axonal transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051015
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    Extracellular matrix and development of lamination in the dorsal lateral geniculate nucleus in the tree shrew (Tupaia belangeri) (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 549-561 
    Details
    ISSN: 1432-0568
    Keywords: Key words Visual system ; Immunohistochemistry ; In situ hybridization ; PNA ; Tenascin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the tree shrew (Tupaia belangeri), the cytoarchitectonic lamination of the lateral geniculate nucleus cannot be detected at birth; it only appears during the early postnatal period. However, a laminated pattern was revealed with rapid Golgi staining and retinal afferents were segregated into the appropriate laminae well before cytoarchitectonic lamination could be seen. Both observations indicate that the extracellular matrix may play a role in the separation of lateral geniculate nucleus cells into laminae. In the present study, the organization of the extracellular matrix was investigated during development using immunohistochemical and in situ hybridization techniques. For immunohistochemistry, peanut agglutinin (PNA) lectin and antibodies against tenascin (TN) were chosen, while for in situ hybridization, mTN riboprobes were used, simultaneously, with antibodies against Vimentin (Vim) and microtubule associated protein (MAP-2). The results showed that the pattern of PNA-binding glycoproteins and that of tenascin were relatively similar, although tenascin appeared later and disappeared earlier. The first interlaminar spaces to be detected were those between layers innervated by opposite eyes. The TN specific mRNA was detected in the lateral geniculate nucleus at P0, but was no longer visible at P7. By comparing TN mRNA and Vim or MAP-2 stainings a correspondence could be observed. The extracellular matrix lamination therefore seems to precede cytoarchitectonic lamination, suggesting that the extracellular matrix may play a role in the development of laminated structures. The TN-producing cells seem to be developing astrocytes and neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050252
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    Versican in human fetal skin development (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 45-56 
    Details
    ISSN: 1432-0568
    Keywords: Key words Skin ; Proteoglycan ; Development ; Human ; Fetal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The extracellular matrix of human fetal skin differs substantially from that of adult skin. Fetal skin contains sparse amounts of fibrillar collagen enmeshed in a highly hydrated amorphous matrix composed of hyaluronan and sulfated proteoglycans. Both fetal and adult skin contain two major interstitial proteoglycans that are extracted by chaotrophic agents and detergents. These are the large chondroitin sulfate proteoglycan versican and the small dermatan sulfate proteoglycan decorin. For this study, proteoglycans extracted from fetal and adult skin were compared on Western blots to determine the relative amounts of versican. Decorin present in the same samples provided an internal standard for these studies. Fetal skin differed from adult skin in that it contained a significantly higher proportion of versican than did adult skin. Immunohistochemical studies compared early-fetal with mid-fetal skin and found that versican was a significant component of the interstitial extracellular matrix at both of these stages of skin development. However, by the mid-fetal period, interstitial versican became restricted to the upper half of the dermis, although versican also continued to be highly expressed around hair follicles, glands, and vasculature in the lower half of the dermis. Fetal skin extracts differed from an adult skin extract by the presence of a 66-kDa protein immunologically related to versican and by the absence of a 17-kDa core protein of a proteoglycan related to decorin. Both of these molecular species may represent degradation products of their respective proteoglycans. Monoclonal antibodies which detect epitopes in native chondroitin sulfate glycosaminoglycan chains recognized versican extracted from fetal skin. However, the tissue distribution of these antigens did not entirely conform to that for versican core protein, suggesting that versican in different regions of the skin may be substituted with glycosaminoglycan chains with different microchemistries. The results of these studies indicate that human fetal skin is structurally different from adult skin in terms of both the distribution and the composition of the large, aggregating chondroitin sulfate proteoglycan versican.
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    URL: http://dx.doi.org/10.1007/s004290050208
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    Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 9-14 
    Details
    ISSN: 1432-0533
    Keywords: Key words Prostaglandin H2 synthase ; Stroke ; Inflammation ; Immunohistochemistry ; Prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2) is up-regulated in the brain of rodents during cerebral ischemia and contributes to ischemic brain injury. This study sought to determine whether COX-2 is also up-regulated in the human brain in the acute stages of cerebral ischemic infarction. Paraffin-embedded sections from patients who died 1–2 days following infarction in the middle cerebral artery territory were processed for COX-2 immunohistochemistry. COX-2 immunoreactivity was observed in infiltrating neutrophils, in vascular cells and in neurons located at the border of the infarct. The data suggest that COX-2 up-regulation is also relevant to cerebral ischemia in humans and raise the possibility that COX-2 reaction products participate in the mechanisms of ischemic injury also in the human brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051045
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    Variable histological expression of dystrophinopathy in two females (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 657-660 
    Details
    ISSN: 1432-0533
    Keywords: Key words Xp21 muscular dystrophy carriers ; Muscle biopsy ; Immunohistochemistry ; X chromosome ; inactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two carriers of Xp21 muscular dystrophy with unusual clinical manifestations and striking variability of dystrophin deficiency within the same muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle biopsy disclosed slight alterations in one sample and severe dystrophic changes in another; dystrophin was absent in 7% fibers in the former specimen and in 60% in the second. X inactivation was skewed with 90% cells inactivating the same X chromosome. The second patient was a 17-year-old girl with hyperCKemia, learning disability and a family history of X-linked muscular dystrophy. Muscle biopsy displayed slight fiber size variability and some internal nuclei; dystrophin was absent only in one muscle fiber. A second sample with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These cases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling errors in muscle biopsy.
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    URL: http://dx.doi.org/10.1007/s004010051043
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    The N-methyl-d-aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 85-90 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amantadine ; Human ; N-methyl-d-aspartate ; Phencyclidine ; Postmortem brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer’s, Parkinson’s or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment.
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    URL: http://dx.doi.org/10.1007/s004010051054
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  • 50
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    Development of Purkinje cells in humans: an immunohistochemical study using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 226-232 
    Details
    ISSN: 1432-0533
    Keywords: Key words Purkinje cell ; Cerebellum ; Development ; Inositol 1 ; 4 ; 5-triphosphate type 1 receptor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051073
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    Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 240-244 
    Details
    ISSN: 1432-0533
    Keywords: Key words Glioma ; Cyclooxygenase ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of inflammation. While COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Although COX-1 expression is observed in normal tissue, enhanced COX-2 expression has been attributed a key role in the development of edema, impeding blood flow and immunomodulation observed in pathologically altered tissues. Here, we have analyzed the expression of COX-1 and COX-2 in 50 gliomas and 10 control brains with no neuropathological alterations by immunohistochemistry; 22 glioblastoma multiforme, 9 anaplastic astrocytomas, 5 protoplasmic astrocytomas, 1 gemistocytic astrocytoma and 13 fibrillary astrocytomas were included in the study. Compared with control brains, accumulation of COX-1 was detected in 20–50% of all cells in both low- and high-grade gliomas. Double-labeling experiments revealed COX-1 expression in subsets of macrophages/ microglial cells within the tumor parenchyma and in areas of infiltrative tumor growth. Of the COX-1-positive cells, 90% expressed MHC class II antigens. No COX-1 immunoreactivity was observed in tumor cells. COX-2-positive cells accumulated in tumor cells and in single macrophages/microglial cells in the immediate vicinity of necroses. Further studies are required to determine whether COX-2 is involved in the development of necrosis or, more likely, whether COX-2 is a part of the tumor tissue response to necrosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051075
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    Immunohistochemical evaluation of the marbled state in childhood hypoxic encephalopathy (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 257-261 
    Details
    ISSN: 1432-0533
    Keywords: Key words Calcium-binding protein ; Enkephalin ; Hypoxic encephalopathy ; Immunohistochemistry ; Marbled state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have immunohistochemically analyzed the marbled state in 8 cases of perinatal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic encephalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillary acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synaptophysin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. The abnormally myelinated fibers in the marbled state were stained with both Klüver-Barrera and Holzer stainings; however, they were partly immunopositive for MBP and completely immunonegative for GFAP, CaBD, MEnk, PV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities for those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or anti-NF immunostainings in the cerebral cortex and striatum but not in the thalamus. GFAP-positive astrocytes did not show any continuity with the abnormally myelinated fibers. These histological features were seen in the cerebral cortex, striatum and thalamus. Difference of the etiology did not affect the histological features with the exception of anti-PV staining, in which PV-immunopositive neurons were observed only in aged subjects with infantile hypoxic encephalopathy, and seemed to be more severely affected by hypoxic stress during the perinatal period than the early infantile period. These data suggest that the site of lesion or the length of survival period after brain injury might influence the formation of the marbled state rather than the etiology. And the direct relationship between the abnormally myelinated fiber and astrocytic process was not verified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051078
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    Glial expression of presenilin epitopes in human brain with cerebral infarction and in astrocytoma (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 337-340 
    Details
    ISSN: 1432-0533
    Keywords: Key words Presenilin ; Cerebral infarction ; Astrocytoma ; Glial cells ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Presenilins, some gene mutations of which are associated with familial Alzheimer’s disease (AD), are expressed mainly in neurons in normal brains and brains from patients clinicopathologically diagnosed as AD. They are thought to be related to cell death and survival. We studied the immunolocalization of presenilin to investigate its possible relation to cell death and glial proliferation, using two antibodies against different portions of the presenilin 1 protein, in human brains with cerebral infarction and in astrocytoma, where abundant cell death and glial proliferation are present. Expression of presenilin epitopes was more marked in glial cells than in neurons in and around the ischemic focus, and it was also robust in astrocytoma cells. These findings suggest that presenilins are functioning not only in neurons but also in glial cells in reactive and neoplastic proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051090
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    A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 407-413 
    Details
    ISSN: 1432-0533
    Keywords: Key words Hemimegalencephaly ; Tuberous sclerosis ; Large neurons ; Balloon cells ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spectrum of neuronal migration disorders, but consistently includes abnormal large neurons similar to those in the cortical tubers of tuberous sclerosis. Microscopically, there are also cells with homogeneous and weakly eosinophilic cytoplasm with a single eccentric nucleus, sometimes called balloon cells (likewise prominent in tuberous sclerosis). We looked for immunohistochemical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and non-phosphorylated neurofilament and synaptophysin identify the large neurons and distinguish them from balloon cells in both entities. Balloon cells in hemimegalencephaly showed no immunoreactivity for TSC2 gene product, tuberin, and vimentin, but similar cells in tuber tissue showed consistent immunoreactivity. Balloon cells in hemimegalencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfilaments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hemimegalencephaly and tuberous sclerosis is superficial; their immunohistochemistry and electron microscopic profiles show distinct differences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051101
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    Chronological study of the appearance of adenohypophysial cells in the ayu (Plecoglossus altivelis) (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 469-475 
    Details
    ISSN: 1432-0568
    Keywords: Key words Fish ; Pituitary gland ; Developmental biology ; Cell differentiation ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We previously reported the chronological appearance of adenohypophysial cells in freshwater teleosts using an immunocytochemical technique. The present study investigated the chronological appearance of adenohypophysial cells in the ayu, which is spawned and has its early development in brackish water, and the results were compared with those obtained in freshwater and seawater teleosts, as well as in other vertebrates. In the adult teleostean adenohypophysis, seven or eight types of secretory cells have been distinguished, each of which produce different hormones: prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), gonadotropic hormones (GTH I and GTH II), adrenocorticotropic hormone (ACTH), melanophore stimulating hormone (MSH) and somatolactin (SL). In the pituitary of adult ayu, seven distinct types of glandular cells (PRL, GH, TSH, GTH, ACTH, MSH and SL cells) were identified. Chronologically, a few immunoreactive (ir)-PRL and ir-GH cells appeared in the ventral side of the pituitary one day before hatching. Then, just after hatching, ir-GTH cells were observed in the central to dorsal portion; ir-ACTH cells were found distributed in the anterior portion and some ir-MSH and a few ir-SL cells were seen in the posterior portion of the pituitary. Finally, a small number of ir-TSH cells were identified 50 days after hatching. These results differed from those obtained in other fishes previously reported with regard to the times of appearance of the PRL and GH cells. PRL cells appeared first, followed by GH cells in the freshwater teleosts, PRL and GH cells appeared at the same time in the brackishwater teleosts, while GH cells appeared first and PRL cells appeared last in the seawater teleosts. These results reflect the fact that PRL plays a major role in osmoregulation among freshwater teleosts, as compared with GH, which plays a similar role in seawater teleosts. It seems that both PRL and GH may play important roles in osmoregulation in brackishwater fish.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050295
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    A tandem repeat of MUC1 core protein induces a weak in vitro immune response in human B cells (1999)
    Springer
    Cancer immunology immunotherapy 47 (1999), S. 249-256 
    Details
    ISSN: 1432-0851
    Keywords: Key words In vitro immunisation ; MUC1 ; Human ; antibodies ; Phage display ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently described an efficient method to study the human humoral immune response in vitro and to generate isotype-switched, antigen-specific human B cells, which has allowed us to produce high-affinity IgG antibodies against different peptides. In an attempt to study the in vitro immune response against self-antigens, such as tumour-associated antigens, this protocol was used to immunise resting human peripheral blood B cells with a peptide epitope from the human-adenocarcinoma-associated antigen, MUC1. After the two-step in vitro immunisation, the secondary immunised cultures were tested for MUC-1-specific antibodies by enzyme-linked immunosorbent assay (ELISA). Phage molecular libraries were subsequently constructed, using the variable parts of Ig genes derived from cells taken from ELISA-positive wells. The libraries were selected on the MUC1 core peptide. Antigen-specific Fab fragments, specific for the self antigen MUC1, were found in the library of secondary immunised IgG+ B cells and these antibodies were evaluated by BIAcore analysis. The specific Fab fragments exhibited an unusually rapid dissociation rate constant and the overall response frequency was lower, as compared to other antibodies generated by this protocol, which might be explained by the repetitive nature of the core peptide used for immunisation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050528
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    A systematic review of vinpocetine therapy in acute ischaemic stroke (1999)
    Springer
    European journal of clinical pharmacology 55 (1999), S. 349-352 
    Details
    ISSN: 1432-1041
    Keywords: Key words Ischaemic stroke ; Vinpocetine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: To determine whether vinpocetine decreases short- and long-term case fatality and proportion of dependent survivors if administered within 2 weeks of stroke onset. Methods: All published and unpublished trials were attempted to be identified using the standard search strategy of the Cochrane Collaboration Stroke Review Group, using MEDLINE searches performed with all known manufacturer code names and trade names of vinpocetine and by contacting manufacturers of vinpocetine to give information of all randomised controlled trials on vinpocetine in stroke. Researchers who participated in trials on vinpocetine in Hungary were asked for further information. Only truly randomised, unconfounded clinical trials that compared the effect of vinpocetine to either placebo or another reference treatment for acute stroke where treatment started no later than 14 days after stroke onset were eligible for inclusion. Data synthesis and analysis was performed using the Cochrane Review Manager software (RevMan version 3.0). Results: Among the identified studies on vinpocetine in stroke, only one fulfilled the selection criteria for inclusion in the review. No death occurred in the study groups and no statistically significant difference was found in dependency between the treatment and the placebo groups. No adverse effects were reported. Conclusions: Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050639
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    The role of polymorphonuclear leukocyte infiltration in herpes simplex virus infection of murine skin (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 28-36 
    Details
    ISSN: 1432-069X
    Keywords: Key words Herpes simplex virus ; Cutaneous infection ; Immunohistochemistry ; Polymorphonuclear leukocyte ; Anti-PMN antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We undertook the present study to investigate the role of polymorphonuclear leukocytes (PMN) in defending skin against herpes simplex virus (HSV) infection. For this purpose, we established a mouse model of cutaneous HSV infection. The hind limb footpad skin of 4-week-old ICR mice was abraded linearly once with a feather edge file and infected with various strains of HSV with different virulence. In uninfected control mice, PMN appeared at the abraded skin lesion within 24 h, and were eliminated from the epidermis after 3 days. Mice inducted with a highly virulent strain of HSV demonstrated wide and severe erythematous lesions of the footpad skin and histologically, virus antigen-positive ballooning degenerated keratinocytes were observed. However, in infections with attenuated strains of HSV, the epidermis was regenerated and a viral antigen was discharged within 5 days, together with any infiltrated PMN. Macrophages and NK cells numbered less than PMN. In mice treated with anti-PMN antiserum before HSV infection, PMN infiltration was significantly suppressed 1 day after infection, and these animals developed a severe cutaneous disease even if infected with an attenuated virus. These results indicate the importance of PMN in the control of HSV cutaneous infections, especially in the primary infectious phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050380
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    Effects of intrathecal clonidine injection on spinal reflexes and human locomotion in incomplete paraplegic subjects (1999)
    Springer
    Experimental brain research 129 (1999), S. 433-440 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spasticity ; Gait ; Spinal cord ; Human ; Clonidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the effect of the intrathecal (i.t.) injection of clonidine (30, 60 and 90 µg) on the polysynaptic spinal reflexes (PSR) elicited by electrical stimulation of flexor reflex afferents (FRA), monosynaptic reflex and gait of 11 subjects with spinal cord injuries. The effect of clonidine administration on gait velocity, stride amplitude and duration was measured in eight subjects who were able to walk. Five subjects were able to walk after intrathecal injection of clonidine and three were not able to stand up. Three subjects improved their gait velocity after clonidine administration; one (S6) increased his stride amplitude; the two others decreased their cycle durations. The tibialis anterior seemed to be more regularly activated during gait. Spasticity was reduced dramatically (P〈0.0001) after i.t. clonidine injection, but there was no statistically significant difference in the soleus H reflex (no effect on Hmax/Mmax). Clonidine administration decreased the amplitude of the early PSR (90–120 ms, N=4) and the threshold and maximal integrated EMG corresponding to the late response (140–450 ms, N=7). This effect was dose dependent (30, 60 and 90 µg). Placebo injection (N=4) caused no change. The changes in spinal reflexes, with a large reduction in spasticity, no change in motoneurone excitability and a large decrease in PSR, suggest that clonidine acts at a premotoneuronal level, possibly by presynaptic inhibition of group II fibres. The increase in gait velocity in three subjects could have been due to reduced spasticity or activation of spinal circuitry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050910
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    The uncontrolled manifold concept: identifying control variables for a functional task (1999)
    Springer
    Experimental brain research 126 (1999), S. 289-306 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Trajectory formation ; Coordination ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The degrees of freedom problem is often posed by asking which of the many possible degrees of freedom does the nervous system control? By implication, other degrees of freedom are not controlled. We give an operational meaning to ”controlled” and ”uncontrolled” and describe a method of analysis through which hypotheses about controlled and uncontrolled degrees of freedom can be tested. In this conception, control refers to stabilization, so that lack of control implies reduced stability. The method was used to analyze an experiment on the sit-to-stand transition. By testing different hypotheses about the controlled variables, we systematically approximated the structure of control in joint space. We found that, for the task of sit-to-stand, the position of the center of mass in the sagittal plane was controlled. The horizontal head position and the position of the hand were controlled less stably, while vertical head position appears to be no more controlled than joint motions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050738
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    Cortical control of optokinetic nystagmus in humans: a positron emission tomography study (1999)
    Springer
    Experimental brain research 126 (1999), S. 149-159 
    Details
    ISSN: 1432-1106
    Keywords: Key words Optokinetic nystagmus ; Positron emission tomography ; Visual motion ; Area V5 ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Positron emission tomography (PET) was used to address the issue of physiological changes in the cerebral cortex associated to optokinetic nystagmus (OKN) in humans. We studied regional cerebral blood flow in eight volunteers during reflexive induction of OKN by a pattern of dots moving unidirectionally (toward the left side). We used two control conditions, with subjects passively viewing either stationary or incoherently moving dots. This paradigm was designed in order to differentiate the OKN-related activations from blood flow changes related to visual motion. When compared with the stationary condition, OKN activated a set of occipital areas known to be sensitive to visual motion. Bilateral activation was found in the striate cortex (V1) and the parieto-occipital fissure, while area V5, the intraparietal sulcus, and the pulvinar were activated only in the left hemisphere. When compared with incoherent motion, OKN activated the V1 and the parieto-occipital fissure bilaterally and the right lingual gyrus, while a signal decrease was observed in the V5 region in both hemispheres. No significant signal changes were found in areas implicated in saccades or in processing vestibular information. These results indicate that processing of OKN-related information is associated with neural activity in a specific set of visual motion areas and suggest that this network can be asymmetrically activated by a strictly unidirectional stimulation. Results are also discussed in terms of the specific kinds of OKN-related information processing subserved by each area in this network.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050725
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    Listing’s plane rotation with convergence: role of disparity, accommodation, and depth perception (1999)
    Springer
    Experimental brain research 126 (1999), S. 175-186 
    Details
    ISSN: 1432-1106
    Keywords: Key words Listing’s plane ; Vergence ; Binocular ; Eye movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Earlier studies have reported temporal rotation of Listing’s plane with convergence of the eyes causing torsion, which is dependent on eye elevation. The amount by which the planes rotate differs from study to study. To gain insight into the functional significance of the temporal tilt of Listing’s plane for vision, we examined whether the rotation of the plane depends on the visual conditions, namely on the stimuli driving vergence. In different conditions, accommodative vergence, disparity-vergence, combinations of disparity with accommodation or depth perception were used and the resulting rotation of Listing’s plane was measured. Our findings show, for the first time, that the relationship between convergence and Listing’s-plane temporal rotation depends on the stimuli driving vergence. When the stimulus contains only disparity cues, vergence and Listing’s plane rotate immediately and consistently among subjects. Accommodative vergence, the mutual couplings between vergence and accommodation, can influence the orientation of Listing’s plane, but they do so in a idiosyncratic way. The largest rotation was elicited by stereograms combining disparity-vergence with depth perception. These findings support the idea of a functional role of Listing’s plane rotation for binocular vision, perhaps for depth perception.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050727
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    Pathways of interhemispheric transfer in normals and in a split-brain subject A positron emission tomography study (1999)
    Springer
    Experimental brain research 126 (1999), S. 451-458 
    Details
    ISSN: 1432-1106
    Keywords: Key words Corpus callosum ; Interhemispheric transfer ; Positron emission tomography ; Split brain ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied with PET the intra- and interhemispheric pathways subserving a simple, speeded-up visuomotor task. Six normal subjects and one patient with a complete section of the corpus callosum (M.E.) underwent regional cerebral blood flow (rCBF) measurements under conditions of lateralized tachistoscopic visual presentations in a simple manual reaction time paradigm. Confirming previous behavioural findings, we found that on average crossed hand and/or hemifield conditions, i.e. those requiring an interhemispheric transfer of information, yielded a longer RT than uncrossed conditions. This difference (0.7 ms) was dramatically larger (45.6 ms) in the callosum-sectioned patient M.E. In normal subjects the cortical areas selectively activated in uncrossed and crossed conditions were different. In the former condition, most activation foci were anterior to the ventral anterior commissure (VAC) plane, whereas in the latter there was a prevalent parietal and occipital activation. This shows that a simple model in which the cortical visuo-motor pathways are similar in the intra- and the interhemispheric condition, with an extra callosal route for the latter, is too simplistic. Furthermore, these results suggest that the bulk of visuomotor interhemispheric transfer takes place through the widespread callosal fibres interconnecting the parietal cortices of the two hemispheres. The pattern of activation in the two crossing conditions was markedly different in M.E., in whom interhemispheric transfer might take place via his intact anterior commissure or subcortical commissures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050752
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    Motion-responsive regions of the human brain (1999)
    Springer
    Experimental brain research 127 (1999), S. 355-370 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Motion ; Functional imaging ; Human ; Flicker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional magnetic resonance imaging was used to map motion responsive regions of the human brain by contrasting passive viewing of moving and stationary randomly textured patterns. Regions were retained as motion responsive if they reached significance either in the group analysis or in the majority of hemispheres in single-subject analysis. They include well-known regions, such as V1, hMT/V5+, and hV3A, but also several occipito-temporal, occipito-parietal, parietal, and frontal regions. The time course of the activation was similar in most of these regions. Motion responses were nearly identical for binocular and monocular presentations. Flicker-induced-activation introduced a dichotomy amongst these motion responsive regions. Early occipital and occipito-temporal regions responded well to flicker, while flicker responses gradually vanished as one moved to occipito-parietal and then parietal regions. Finally, over a more than four-fold range, stimulus diameter had little effect on the motion activations, except in V1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050804
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    Increased blood flow in the basal ganglia when using cues to direct attention (1999)
    Springer
    Experimental brain research 129 (1999), S. 241-246 
    Details
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Visual attention ; Putamen ; Orienting ; Positron emission tomography ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used positron emission tomography (PET) in ten subjects to study the brain regions involved in voluntary shifts of attention. For six scans, subjects performed a visual target detection task in which the location of the target was indicated in advance on some proportion of trials by the appearance of an arrow cue at fixation. The informative cues were successful in speeding reaction time to the target. Blood flow in the left putamen was correlated with the proportion of informative cues provided within a scan. We discuss this finding in terms of three possible interpretations: attentional shifts, response inhibition, and motor preparation related to the use of the right hand to respond. Blood flow in cortical regions commonly associated with attention was not related to cue ratio, a finding that may reflect automatization of the processes involved in interpreting and using the cues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050894
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    The influence of visual illusions on grasp position (1999)
    Springer
    Experimental brain research 125 (1999), S. 109-114 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Visual pathways ; Illusions ; Prehension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This partial dissociation is discussed in terms of its implications for streams of visual processing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050665
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    Localization of a seen finger is based exclusively on proprioception and on vision of the finger (1999)
    Springer
    Experimental brain research 125 (1999), S. 43-49 
    Details
    ISSN: 1432-1106
    Keywords: Key words Proprioception ; Visual localization ; Visual context ; Multisensory integration ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a previous study we investigated how the CNS combines simultaneous visual and proprioceptive information about the position of the finger. We found that localization of the index finger of a seen hand was more precise (a smaller variance) than could reasonably be expected from the precision of localization on the basis of vision only and proprioception only. This suggests that, in localizing the tip of the index finger of a seen hand, the CNS may make use of more information than proprioceptive information and visual information about the fingertip. In the present study we investigate whether this additional information stems from additional sources of sensory information. In experiment 1 we tested whether seeing an entire arm instead of only the fingertip gives rise to a more precise proprioceptive and/or visual localization of that fingertip. In experiment 2 we checked whether the presence of a structured visual environment leads to a more precise proprioceptive localization of the index finger of an unseen hand. In experiment 3 we investigated whether looking in the direction of the index finger of an unseen hand improves proprioceptive localization of that finger. We found no significant effect in any of the experiments. The results refute the hypothesis that the investigated effects can explain the previously reported very precise localization of a seen hand. This suggests that localization of a seen finger is based exclusively on proprioception and on vision of the finger. The results suggest that these sensory signals may contain more information than is described by the magnitude of their variances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050656
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    Finger opening in an overarm throw is not triggered by proprioceptive feedback from elbow extension or wrist flexion (1999)
    Springer
    Experimental brain research 125 (1999), S. 302-312 
    Details
    ISSN: 1432-1106
    Keywords: Key words Overarm throwing ; Finger opening ; Proprioceptive feedback ; Perturbations ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050686
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    Handedness-related asymmetry in transmission in a system of human cervical premotoneurones (1999)
    Springer
    Experimental brain research 125 (1999), S. 323-334 
    Details
    ISSN: 1432-1106
    Keywords: Key words Corticospinal tract ; Handedness ; Spinal premotoneurones ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles . Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050688
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    Effects of voluntary hyperventilation on cortical sensory responses Electroencephalographic and magnetoencephalographic studies (1999)
    Springer
    Experimental brain research 125 (1999), S. 248-254 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hyperventilation ; Magnetoencephalography ; Somatosensory cortex ; Auditory cortex ; Somatosensory evoked response ; Auditory evoked response ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is well established that voluntary hyperventilation (HV) slows down electroencephalographic (EEG) rhythms. Little information is available, however, on the effects of HV on cortical responses elicited by sensory stimulation. In the present study, we recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs), and somatosensory evoked magnetic fields (SEFs) from healthy subjects before, during, and after a 3- to 5-min period of voluntary HV. The effectiveness of HV was verified by measuring the end-tidal CO2 levels. Long-latency (100–200 ms) AEPs and long-latency AEFs originating at the supratemporal auditory cortex, as well as long-latency SEFs from the primary somatosensory cortex (SI) and from the opercular somatosensory cortex (OC), were all reduced during HV. The short-latency SEFs from SI were clearly less modified, there being, however, a slight reduction of the earliest cortical excitatory response, the N20m deflection. A middle-latency SEF deflection from SI at about 60 ms (P60 m) was slightly increased. For AEFs and SEFs, the center-of-gravity locations of the activated neuronal populations were not changed during HV. All amplitude changes returned to baseline levels within 10 min after the end of HV. The AEPs were not altered when the subjects breathed 5% CO2 in air in a hyperventilation-like manner, which prevented the development of hypocapnia. We conclude that moderate HV suppresses long-latency evoked responses from the primary projection cortices, while the early responses are less reduced. The reduction of long-latency responses is probably mediated by hypocapnia rather than by other nonspecific effects of HV. It is suggested that increased neuronal excitability caused by HV-induced hypocapnia leads to spontaneous and/or asynchronous firing of cortical neurones, which in turn reduces stimulus-locked synaptic events.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050680
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    Neck-proprioceptive influence on auditory lateralization (1999)
    Springer
    Experimental brain research 125 (1999), S. 389-396 
    Details
    ISSN: 1432-1106
    Keywords: Key words Neck muscles ; Vibration ; Proprioception ; Sound localization ; Space perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of transcutaneous vibration of the posterior neck muscles on the lateralization of dichotic sound was investigated in human subjects. Two-alternative forced-choice (left/right) judgements were made on acoustic stimuli presented with different interaural level differences via headphones during neck-muscle vibration. A shift of the subjective auditory median plane toward the side contralateral of vibration was found, indicating that the sound was perceived as shifted toward the side of vibration. The mean magnitude of the vibration-induced intracranial shift was 1.5 dB. The results demonstrate a neck-proprioceptive influence on sound lateralization and suggest that this proprioceptive input is used for a central-nervous transformation of auditory spatial coordinates onto a body-centered frame of reference.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050695
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    Motor plasticity induced by synchronized thumb and foot movements (1999)
    Springer
    Experimental brain research 125 (1999), S. 435-439 
    Details
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Plasticity ; Synchronization ; Motor system ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used focal transcranial magnetic stimulation to examine the effects of 120 synchronized thumb and foot movements on the motor output map of the right abductor pollicis brevis muscle (APB) (experiment 1). To evaluate the performance, the latencies between the onset of the electromyographic activity (EMG) of the two muscles were measured. As control, 120 asynchronous thumb and foot movements were performed (experiment 2). Exclusively in experiment 1, the center of gravity (CoG) of the output map moved medially in the direction of the foot representation area (mean 7 mm, P〈0.05) and returned into its original location within 1 h. In experiment 2, the CoG remained unchanged (mean displacement, 0.68 mm into a lateral direction; not significant). The effect in experiment 1 was independent of an improvement in performance. We conclude that a short-lasting training of synchronous movements induces modulations of motor output maps which probably occur due to interactions between hand and foot representation areas in the motor cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050700
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    The reach-to-grasp movement in Parkinson’s disease: response to a simultaneous perturbation of object position and object size (1999)
    Springer
    Experimental brain research 125 (1999), S. 453-462 
    Details
    ISSN: 1432-1106
    Keywords: Key words Reach to grasp ; Human ; Perturbation ; Kinematics ; Motor control ; Parkinson’s disease ; Elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed the adaptive response of the reach-to-grasp movement of 12 Parkinson’s disease (PD) and 12 control subjects to a simultaneous perturbation of target object location and size. The main aim was to test further the reported dysfunction of PD subjects in the simultaneous activation of movement components. Participants were required to reach 30 cm to grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm) diameter. For a small percentage of trials (20/100) a visual perturbation was introduced unexpectedly at the onset of the reaching action. This consisted of a shift of illumination from the central cylinder to a cylinder of differing diameter, which was positioned 20° to the left (n=10) or to the right (n=10). The subject was required to grasp the newly illuminated cylinder. For the Parkinson’s disease subject group, the earliest response to this ’double’ perturbation was in the parameter of peak reaching acceleration, which was on average 50 ms earlier for ’double’ perturbed than for non-perturbed trials. The grasp component response followed more than 500 ms after the earliest transport response. For the control subjects initial signs of a response to the ’double’ perturbation were seen almost simultaneously in the transport parameter of peak arm deceleration, and in the manipulation parameter of maximum grip aperture, but these changes were not evident until more than 400 ms after movement onset. These results indicate that the basal ganglia can be identified as part of a circuit which is involved in the integration of parallel neutral pathways, and which exercise flexibility in the degree to which these components are ’coupled’ functionally. With basal ganglia dysfunction the activation of integration centres that at first gate the flow of information to the parallel channels of reach and grasp seems inefficient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050703
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    Directional effects of changes in muscle torques on initial path during simulated reaching movements (1999)
    Springer
    Experimental brain research 128 (1999), S. 353-368 
    Details
    ISSN: 1432-1106
    Keywords: Key words Multijoint arm ; Simulations ; Muscle torques ; Kinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Adults are able to reach for an object for the first time with appropriate direction, speed, and accuracy. The rules by which the nervous system is able to set muscle activities to accomplish these outcomes are still debated and, indeed, the sensitivity of kinematics to variations in muscle torques is unknown for complex arm movements. As a result, this study used computer simulations to characterize the effects of change in muscle torque on initial hand path. The same change was applied to movements towards 12 directions in the horizontal plane, and changes were systematically manipulated such that: (1) torque amplitude was changed at one joint, (2) timing of torque was changed at one joint, and (3) amplitude and/or timing was changed at two joints. Results showed that simultaneous changes in torque amplitude at shoulder and elbow joints affected initial speed uniformly across direction. These results add to conclusions from previous experimental and modeling work that the simplest rule to produce a desired change in speed for any direction is to scale torque amplitude at both joints. In contrast, all simulations showed nonuniform effects on initial path direction. For some regions of the workspace, initial path direction was little affected by either a ±30% change in amplitude or a ±100-ms change in timing, whereas for other regions the same changes produced large effects on initial path direction. These findings suggest that the range of possible torque solutions to achieve a particular initial path direction varies within the workspace and, consequently, the requirements for an accurate initial path will vary within the workspace.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050855
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    Stronger occipital cortical activation to lower than upper visual field stimuli Neuromagnetic recordings (1999)
    Springer
    Experimental brain research 124 (1999), S. 287-294 
    Details
    ISSN: 1432-1106
    Keywords: Key words Magnetoencephalography ; V1 cortex ; V2 cortex ; V6 complex ; Horizontal meridian ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We recorded whole-scalp magnetoencephalographic (MEG) responses to black-and-white checkerboards to study whether the human cortical responses are quantitatively similar to stimulation of the lower and upper visual field at small, 0–6°, eccentricities. All stimuli evoked strongoccipital responses peaking at 50–100 ms (mean 75 ms). The activation was modeled with a single equivalent current dipole in the contralateral occipital cortex, close to the calcarine fissure, agreeing with an activation of the V1/V2 cortex. The dipole was, on average, twice as strong to lower than to upper field stimuli. Responses to hemifield stimuli that extended to both lower and upper fields resembled the responses to lower field stimuli in source current direction and strength. These results agree with psychophysical data, which indicate lower visual field advantage in complex visual processing. Parieto-occipital responses in the putative V6 complex were similar to lower and upper field stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050625
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    Antagonist motor responses correlate with kinesthetic illusions induced by tendon vibration (1999)
    Springer
    Experimental brain research 124 (1999), S. 342-350 
    Details
    ISSN: 1432-1106
    Keywords: Key words Vibration-induced kinesthetic illusions ; Antagonist vibratory response ; Motor units ; Wrist extensor muscles ; Human ; Microelectromyography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050631
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    Effects of short-term adaptation of saccadic gaze amplitude on hand-pointing movements (1999)
    Springer
    Experimental brain research 124 (1999), S. 351-362 
    Details
    ISSN: 1432-1106
    Keywords: Key words Saccadic adaptation ; Gaze ; Short term adaptation ; Transfer to hand movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated whether and how adaptive changes in saccadic amplitudes (short-term saccadic adaptation) modify hand movements when subjects are involved in a pointing task to visual targets without vision of the hand. An experiment consisted of the pre-adaptation test of hand pointing (placing the finger tip on a LED position), a period of adaptation, and a post-adaptation test of hand pointing. In a basic task (transfer paradigm A), the pre- and post-adaptation trials were performed without accompanying eye and head movements: in the double-step gaze adaptation task, subjects had to fixate a single, suddenly displaced visual target by moving eyes and head in a natural way. Two experimental sessions were run with the visual target jumping during the saccades, either backwards (from 30 to 20°, gaze saccade shortening) or onwards (30 to 40°, gaze saccade lengthening). Following gaze-shortening adaptation (level of adaptation 79±10%, mean and s.d.), we found a statistically significant shift (t-test, error level P〈0.05) in the final hand-movement points, possibly due to adaptation transfer, representing 15.2% of the respective gaze adaptation. After gaze-lengthening adaptation (level of adaptation 92±17%), a non-significant shift occurred in the opposite direction to that expected from adaptation transfer. The applied computations were also performed on some data of an earlier transfer paradigm (B, three target displacements at a time) with gain shortening. They revealed a significant transfer relative to the amount of adaptation of 18.5±17.5% (P〈0.05). In the coupling paradigm (C), we studied the influence of gaze saccade adaptation of hand-pointing movements with concomitant orienting gaze shifts. The adaptation levels achieved were 59±20% (shortening) and 61±27% (lengthening). Shifts in the final fingertip positions were congruent with internal coupling between gaze and hand, representing 53% of the respective gaze-amplitude changes in the shortening session and 6% in the lengthening session. With an adaptation transfer of less than 20% (paradigm A and B), we concluded that saccadic adaptation does not ”automatically” produce a functionally meaningful change in the skeleto-motor system controlling hand-pointing movements. In tasks with concomitant gaze saccades (coupling paradigm C), the modification of hand pointing by the adapted gaze comes out more clearly, but only in the shortening session.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050632
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    Loading during the stance phase of walking in humans increases the extensor EMG amplitude but does not change the duration of the step cycle (1999)
    Springer
    Experimental brain research 124 (1999), S. 363-370 
    Details
    ISSN: 1432-1106
    Keywords: Key words Locomotion ; Load ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Prior work from mammals suggests that load experienced by extensor muscles of the hindlimbs (i.e. Duysens and Pearson 1980; Pearson and Collins 1993; Fouad and Pearson 1997) or cutaneous afferents from the plantar surface of the foot (Duysens and Pearson 1976; Guertin et al. 1995) enhances activity in extensor muscles during the stance phase, and delays the onset of flexor activity associated with the swing phase. The presumed functional significance of this phenomenon is that extensor activity of the supporting limb during walking can: (a) reinforce the supporting function in proportion to the load experienced, and (b) prolong the stance phase until unloading of the limb has occurred. Whether a similar functional role exists for load-sensitive afferents during walking in the human is unknown. In this study, the effect of adding or removing a substantial load (30% of body weight) at the centre of mass was studied in healthy adult human subjects. Loads were applied near the centre of mass to avoid the need for postural adjustments which might confound the interpretation of the results. Subjects walked on a treadmill with either: (a) a sustained increase or decrease in load, or (b) a sudden unexpected increase or decrease in load. In general, subjects responded to the changes in load by changing the amplitude of the extensor electromyographic (EMG) bursts. For example, with sudden unexpected additions in load, the average increase in amplitude was 40% for the soleus across the stance phase, and 134% for the quadriceps during the early part of the stance phase. Extensor EMGs increased with both sustained and sudden increases in load. Extensor EMG durations also increased (average increase in duration of 4% for soleus with sudden loading, and 7% for sustained loading). Cycle duration hardly changed (average increase of 0.5% with both sudden and sustained loading). These results differ from those of infants subjected to a similar perturbation during supported walking. A large change in timing (i.e. an increase in the duration of the stance phase by 30% and the step cycle by 28%) was seen in the infants, with no change in the amplitude of the EMG burst (Yang et al. 1998). These results suggest that the central nervous system can control the timing and amplitude of extensor EMG activity in response to loading independently. Maturation of the two components most likely occurs independently. In the adult, independent control of the two components may provide greater flexibility of the response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050633
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    The development of postural adjustments during reaching in 6- to 18-month-old infants Evidence for two transitions (1999)
    Springer
    Experimental brain research 126 (1999), S. 517-528 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Reaching ; Anticipatory postural control ; EMG ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study focused on the developmental changes of postural adjustments accompanying reaching movements in healthy infants. We made a longitudinal study of ten infants between 6 and 18 months of age. During each session multiple surface electromyograms of arm, neck, trunk and leg muscles at the right side of the body were recorded during right-handed reaching movements in two positions (”upright sitting” in an infant chair and ”long-leg” sitting without support). Simultaneously the whole session was recorded on video. Comparable data were present from the same infants at 3–5 months. Additionally, 18 infants (8–15 months) were assessed once during similar reaching tasks, but in these infants electromyographic activity of the trunk and neck muscles at both sides of the body were recorded. Our data revealed two transitions in the development of postural adjustments. The first transition was present around 6 months of age. At this age the postural muscles were infrequently activated during reaching movements. At 8 months ample postural activity reappeared and the infants developed the ability to adapt the postural adjustments to task-specific constraints such as arm movement velocity or the sitting position at the onset of the reaching movement. The second transition occurred between 12 and 15 months. Before 15 months the infants did not show consistent anticipatory postural activity, but from 15 months onwards they did, particularly in the neck muscles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050760
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    Afferent input and cortical organisation: a study with magnetic stimulation (1999)
    Springer
    Experimental brain research 126 (1999), S. 536-544 
    Details
    ISSN: 1432-1106
    Keywords: Key words Magnetic brain stimulation ; Afferent input ; Motor cortex ; Plasticity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peri- pheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050762
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    The origin of ocular microtremor in man (1999)
    Springer
    Experimental brain research 126 (1999), S. 556-562 
    Details
    ISSN: 1432-1106
    Keywords: Key words Acceleration ; Ocular microtremor ; Eye movements ; Partial coherence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel technique for the study of human eye movements was used to investigate the frequency components of ocular drift and microtremor in both eyes simultaneously. The tangential components of horizontal eye accelerations were recorded in seven healthy subjects using light-weight accelerometers mounted on scleral contact lenses during smooth pursuit movements, vestibulo-ocular reflexes and eccentric gaze with and without fixation. Spectral peaks were observed at low (up to 25 Hz) and high (60–90 Hz) frequencies. A multivariate analysis based on partial coherence analysis was used to correct for head movement. After correction, the signals were found to be coherent between the eyes over both low- and high-frequency ranges, irrespective of task, convergence or fixation. It is concluded that the frequency content of ocular drift and microtremor reflects the patterning of low-level drives to the extra-ocular muscle motor units.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050764
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    Target viewing time and velocity effects on prehension (1999)
    Springer
    Experimental brain research 127 (1999), S. 83-94 
    Details
    ISSN: 1432-1106
    Keywords: Key words Target interception ; Reaching ; Grasping ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The goal of the present study was to understand which characteristics (movement time or velocity) of target motion are important in the control and coordination of the transport and grasp-preshape components of prehensile movements during an interception task. Subjects were required to reach toward, grasp and lift an object as it entered a target area. Targets approached along a track at four velocities (500, 750, 1000 and 1250 mm/s) which were presented in two conditions. In the distance-controlled condition, targets moving at all velocities traveled the same distance. In the viewing-time-controlled condition, combinations of velocity and starting distances were performed such that the moving target was visible for 1000 ms for all trials. Analyses of kinematic data revealed that when, target distance was controlled, velocity affected all transport-dependent measures; however, when viewing time was controlled, these dependent measures were no longer affected by target velocity. Thus, the use of velocity information was limited in the viewing-time-controlled condition, and subjects used other information, such as target movement time, when generating the transport component of the prehensile movement. For the grasp-preshape component, both peak aperture and peak-aperture velocity increased as target velocity increased, regardless of condition, indicating that target velocity was used to control the spatial aspects of aperture formation. However, the timing of peak aperture was affected by target velocity in the distance-controlled condition, but not in the viewing-time-controlled condition. These results provide evidence for the autonomous generation of the spatial and temporal aspects of grasp preshape. Thus, an independence between the transport and grasp-preshape phases was found, whereby the use of target velocity as a source of information for generating the transport component was limited; however, target velocity was an important source of information in the grasp-preshape phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050776
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    The frontal eye field is involved in spatial short-term memory but not in reflexive saccade inhibition (1999)
    Springer
    Experimental brain research 129 (1999), S. 288-301 
    Details
    ISSN: 1432-1106
    Keywords: Key words Frontal eye field ; Saccade ; Efference copy ; Spatial short-term memory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Physiological studies in monkeys have shown that the frontal eye field (FEF) is involved in the preparation and triggering of purposive saccades. However, several questions of FEF function remain unclear: the role of the FEF in visual short-term memory, its ability to update its spatial map and its role in reflexive saccade inhibition. We have addressed these issues in a patient with a small acute ischemic lesion whose location corresponded very accurately to the region of the left FEF according to the most recent cerebral blood flow studies. An initial study was conducted on days 7 and 8 after the stroke, i.e., before substantial recovery. A first group of paradigms (smooth pursuit, simple saccade tasks) was performed to assess FEF dysfunction. In a second group of paradigms, (1) visual short-term memory was tested by means of memory-guided saccade paradigms with short and long delays (1 and 7 s), (2) spatial updating abilities were tested by a double-step saccade task and two memory-guided saccade tasks in which the central fixation point was displaced during the memorization delay, and (3) reflexive saccade inhibition was tested by the antisaccade task. Results show that the FEF is involved in short-term memorization of the parameters of the forthcoming memory-guided saccade encoded in oculocentric coordinates. Normal results in the antisaccade task suggest that the FEF is not involved in reflexive saccade inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050899
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    Changed visuomotor transformations during and after prolonged microgravity (1999)
    Springer
    Experimental brain research 129 (1999), S. 378-390 
    Details
    ISSN: 1432-1106
    Keywords: Key words Manual tracking ; Microgravity ; Visuomotor transformation ; Adaptation ; Human ; Spaceflight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050906
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  • 85
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    Pointing to remembered visual targets after active one-step self-displacements within reaching space (1999)
    Springer
    Experimental brain research 125 (1999), S. 50-60 
    Details
    ISSN: 1432-1106
    Keywords: Key words Pointing errors ; Remembered target Navigation ; Active self-movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied pointing movements to remembered visual targets in a completely darkened room with and without self-made step movements in order to investigate in which coordinate system and to what extent target representations relative to the body are updated for self-induced egomotion. A small red-light-emitting diode on the fingertip provided visual feedback about fingertip position at all times. We asked subjects to make pointing movements that started 2 s after disappearance of a visual target. In this interval of 2 s the subject did or did not make a step. The pointing errors without a step showed that subjects undershot faraway targets in a systematic way, whereas they sometimes overshot nearby targets. We found that the step causes larger pointing errors both in amplitude and direction with a bias in the direction of the step. We explored three different versions of a descriptive model in which polar coordinates were used to describe the pointing movement, and in which either Cartesian or polar coordinates were used to update target position relative to the shoulder for the step. The results suggest that incorporation of the step displacement in the new target position relative to the subject is done in a Cartesian frame of reference. Moreover, the amplitude of the step displacement tends to be underestimated by subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050657
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    Comparison of variability of initial kinematics and endpoints of reaching movements (1999)
    Springer
    Experimental brain research 125 (1999), S. 139-152 
    Details
    ISSN: 1432-1106
    Keywords: Key words Reaching movements ; Direction ; Amplitude ; Initial kinematics ; Spatial variability ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The accuracy of reaching movements to memorized visual target locations is presumed to be determined largely by central planning processes before movement onset. If so, then the initial kinematics of a pointing movement should predict its endpoint. Our study examined this hypothesis by testing the correlation between peak acceleration, peak velocity, and movement amplitude and the correspondence between the respective spatial positions of these kinematic landmarks. Subjects made planar horizontal reaching movements to targets located at five different distances and along five radially arrayed directions without visual feedback during the movements.The spatial dispersion of the positions of peak acceleration, peak velocity, and endpoint all tended to form ellipses oriented along the movement trajectory. However, whereas the peaks of acceleration and velocity scaled strongly with movement amplitude for all of the movements made at the five target distances in any one direction, the correlations with movement amplitude were more modest for trajectories aimed at each target separately. Furthermore, the spatial variability in direction and extent of the distribution of positions of peak acceleration and peak velocity did not scale differently with target distance, whereas they did for endpoint distributions. Therefore, certain features of the final kinematics are evident in the early kinematics of the movements as predicted by the hypothesis that they reflect planning processes. However, endpoint distributions were not completely predetermined by the Initial kinematics. In contrast, multivariate analysis suggests that adjustments to movement duration help compensate for the variability of the initial kinematics to achieve desired movement amplitude. These compensatory adjustments do not contradict the general conclusion that the systematic patterns in the spatial variability observed in this study reflect planning processes. On the contrary, and consistent with that conclusion, our results provide further evidence that direction and extent of reaching movements are planned and determined in parallel over time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050669
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    Mechanism of the silent period following transcranial magnetic stimulation Evidence from epidural recordings (1999)
    Springer
    Experimental brain research 128 (1999), S. 539-542 
    Details
    ISSN: 1432-1106
    Keywords: Key words Silent period ; Transcranial magnetic stimulation ; Motor cortex ; Epidural recordings ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050878
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    Sudden and gradual presentation of distractor objects: differential interference effects (1999)
    Springer
    Experimental brain research 128 (1999), S. 550-556 
    Details
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Kinematics ; Human ; Visual pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In solving the selection-for-action problem, it is believed that attentional mechanisms enable dominance of target over non-target objects. However, under some conditions, information from non-target objects ”interferes” with the action to a relevant target. We investigated the possibility that this interference may result when the irrelevant object activates a specific subset of visuomotor pathways. Participants reached to grasp three-dimensional stimuli while actively attending to a nearby flanker object. The means by which the flanker was presented was manipulated. This relevant object was illuminated either abruptly or gradually. The parvocellular pathway in early visual processing is equally activated in both conditions. The magnocellular pathway is strongly activated by abrupt presentation and weakly activated with gradual presentation of the flanker object. Kinematics of the reach-to-grasp action to the target showed signs of interference only in the sudden illumination condition. This suggests a dissociation between dorsal and ventral cortical streams in terms of relevance for action. Our data suggests that this effect is not due to early visual-pathway differences, but instead reveals a property of a transient object-based visual attention mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050880
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    The use of vergence information in the programming of prehension (1999)
    Springer
    Experimental brain research 128 (1999), S. 578-582 
    Details
    ISSN: 1432-1106
    Keywords: Key words Prehension ; Binocular ; Vergence ; Distance perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Human prehension requires accurate information on the properties of an object and on the position of the object relative to the body. In principle, prehension might be more accurate with binocular rather than monocular vision. Previous studies have shown that the kinematics of prehension are altered when one eye is covered. Unfortunately, the source of the useful binocular information cannot be established using this approach. In the current study, we used a perturbation technique to explore whether the human nervous system uses a signal from vergence in prehension. Perturbing vergence caused predictable changes in the kinematics of prehension. Our results thus provide clear evidence that the nervous system uses vergence information in the programming of prehensile movement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050885
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    Cortical regions contributing to the anterior commissure in man (1999)
    Springer
    Experimental brain research 124 (1999), S. 1-7 
    Details
    ISSN: 1432-1106
    Keywords: Key words Temporal cortex ; Connectivity ; Human ; Interhemispheric transfer ; Talairach coordinates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The human anterior commissure is believed, by extrapolation from data obtained in macaque monkeys, to convey axons from the temporal and orbitofrontal cortex. Reports of interhemispheric transfer and sexual dimorphism related to the anterior commissure, however, make more precise data on the human anterior commissure desirable. We investigated the connectivity of the human anterior commissure in six adults (male and female) that had circumscribed hemispheric lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal white matter using the Nauta for anterogradely degenerating axons. Axons originating in the inferior part of temporal or occipital lobes, occipital convexity and possibly central fissure and prefrontal convexity were found to cross the midsagittal plane in the anterior commissure. The largest contigent of commissural axons originated in the inferior part of the temporal lobe; it displayed a roughly topographic organization, preferentially running through the inferior part of the commissure. The inferior temporal contigent seemed to reach homotopic and heterotopic targets in the opposite hemisphere. Among the latter were the amygdala and possibly the orbitofrontal cortex. The present data suggest that the human anterior commissure conveys axons from much larger territories than expected from work on non-human primates. Similarly to the human and non-human primate corpus callosum, the anterior commissure is roughly topographically organized and participates in heterotopic connectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050593
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    Development of anticipatory postural adjustments in a bimanual load-lifting task in children (1999)
    Springer
    Experimental brain research 126 (1999), S. 200-204 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050729
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    Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation (1999)
    Springer
    Experimental brain research 124 (1999), S. 447-454 
    Details
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Silent period ; Voluntary motor drive ; Motor threshold ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050640
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    Recruitment and sequencing of different degrees of freedom during pointing movements involving the trunk in healthy and hemiparetic subjects (1999)
    Springer
    Experimental brain research 126 (1999), S. 55-67 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Multijoint movement ; Movement synergy ; Stroke ; Laterality ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies have shown that in neurologically normal subjects the addition of trunk motion during a reaching task does not affect the trajectory of the arm endpoint. Typically, the trunk begins to move before the onset and continues to move after the offset of the arm endpoint displacement. This observation shows that the potential contribution of the trunk to the motion of the arm endpoint toward a target is neutralized by appropriate compensatory movements of the shoulder and elbow. We tested the hypothesis that cortical and subcortical brain lesions may disrupt the timing of trunk and arm endpoint motion in hemiparetic subjects. Eight hemiparetic and six age-matched healthy subjects were seated on a stool with the right (dominant) arm in front of them on a table. The tip of the index finger (the arm endpoint) was initially at a distance of 20 cm from the midline of the chest. Wrist, elbow, and upper body positions as well as the coordinates of the arm endpoint were recorded with a three-dimensional motion analysis system (Optotrak) by infrared light-emitting diodes placed on the tip of the finger, the styloid process of the ulna, the lateral epicondyle of the humerus, the acromion processes bilaterally, and the sternal notch. In response to a preparatory signal, subjects lifted their arm 1–2 cm above the table and in response to a ”go” signal moved their endpoint as fast as possible from a near to a far target located at a distance of 35 cm and at a 45° angle to the right or left of the sagittal midline of the trunk. After a pause (200– 500 ms) they moved the endpoint back to the near target. Pointing movements were made without trunk motion (control trials) or with a sagittal motion of the trunk produced by means of a hip flexion or extension (test trials). In one set of test trials, subjects were required to move the trunk forward while moving the arm to the target (”in-phase movements”). In the other set, subjects were required to move the trunk backward when the arm moved to the far target (”out-of-phase movements”). Compared with healthy subjects, movements in hemiparetic subjects were segmented, slower, and characterized by a greater variability and by deflection of the trajectory from a straight line. In addition, there was a moderate increase in the errors in movement direction and extent. These deficits were similar in magnitude whether or not the trunk was involved. Although hemiparetic subjects were able to compensate the influence of the trunk motion on the movement of the arm endpoint, they accomplished this by making more segmented movements than healthy subjects. In addition, they were unable to stabilize the sequence of trunk and arm endpoint movements in a set of trials. It is concluded that recruitment and sequencing of different degrees of freedom may be impaired in this population of patients. This inability may partly be responsible for other deficits observed in hemiparetic subjects, including an increase in movement segmentation and duration. The lack of stereotypic movement sequencing may imply that these subjects had deficits in learning associated with short-term memory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050716
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    Effects of geometric joint constraints on the selection of final arm posture during reaching: a simulation study (1999)
    Springer
    Experimental brain research 126 (1999), S. 134-138 
    Details
    ISSN: 1432-1106
    Keywords: Key words Upper limb ; Posture ; Geometric constraints ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Significant debate exists regarding the neural strategies underlying the positioning and orienting of the hand during voluntary reaching movements of the human upper extremity. Some authors have suggested that positioning and orienting are controlled independently, while others have argued that a strong interdependence exists. In an effort to address this uncertainty, our study employed computer simulations to examine the impact of physiological limitations of joint rotation on the proposed independence of hand position and orientation. Specifically, we analyzed the effects of geometric constraints on final arm postures using a 7 degree-of-freedom model of the human arm. For 20 different hand configurations within the attainable workspace, we computed sets of achievable joint angles by applying inverse kinematics. From each set, we then calculated the locus of possible elbow positions for the particular final hand posture. When the joints were allowed 360° of rotation, the loci formed complete circles; however, when joint ranges were limited to physiological values, the extent of the loci decreased to an average arc angle of 54.6° (±27.9°). Imposition of joint limits also led to practically linear relationships between joint angles within a solution set. These theoretical results suggest a requirement for coordinated interaction between control of the joints associated with hand position and those involved with hand orientation in order to ensure attainable joint trajectories. Furthermore, it is conceivable that some of the correlations observed between joint angles in the course of natural reaching movements result from geometric constraints.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050723
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    The influence of stimulus temperature rise rate, adapting temperature, and stimulus duration on suprathreshold responses evoked by noxious heat in the glabrous skin of the limb Comparison of neuronal discharge in the rat spinal dorsal horn with human sensations (1999)
    Springer
    Experimental brain research 126 (1999), S. 482-494 
    Details
    ISSN: 1432-1106
    Keywords: Key words Suprathreshold heat pain ; Adapting temperature ; Temporal parameters ; Spinal dorsal horn neuron ; Descending control ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of stimulus temperature rise rate (2.5ºC/s, 5.0ºC/s, and 10.0ºC/s), adapting (baseline) temperature (25ºC, 30ºC, and 35ºC), and duration of peak stimulus temperature (1.0 s, 2.5 s, 5.0 s, and 10.0 s) on responses evoked by noxious heat stimuli of suprathreshold intensity was studied in wide dynamic range (WDR) neurons of the rat spinal dorsal horn. The spinal neuronal responses were compared with human psychophysical data obtained using the same stimuli. Noxious heat stimuli with a peak temperature of 54ºC were applied with a contact thermostimulator to the glabrous skin of the hindfoot in rats or to the palmar skin in humans. With the highest ramp rate and the highest adapting temperature, the sensory and spinal neuronal response latencies were decreased more than expected on the basis of the change in physical parameters of the stimulus. The magnitudes of sensory and spinal neuronal response were independent of the stimulus ramp rate, whereas pain magnitude estimates and spinal neuronal impulse counts evoked by the same peak stimulus temperature were increased with an increase in the adapting stimulus temperature. The onset latencies of pain reactions and spinal neuronal responses were independent of the peak stimulus duration, whereas the latency of the maximum discharge in spinal neurons increased with prolongation of the peak stimulus. The sensory magnitude estimate of pain and the neuronal impulse count were increased with increase in stimulus duration. Following spinalization, the spinal neuronal responses were stronger and the stimulus duration-dependent increase in the impulse count developed faster. Moreover, the peak frequency of spinal neuronal response increased significantly with prolongation of the heat stimuli after spinalization, but not in animals with an intact spinal cord. The results indicate that stimulus rise rate, stimulus duration, and the adapting temperature are important factors in determining the sensory and spinal neuronal responses to high-intensity heat stimuli. The changes in the total impulse counts evoked by varying supraliminal heat stimuli in spinal dorsal horn WDR neurons corresponded well with the changes in pain magnitude estimates in humans. Also, the changes in spinal neuronal response onset latencies were accompanied by corresponding changes in onset latencies of human pain reactions but not with pain magnitude estimates. The effect of spinalization indicated that descending pathways control not only the response magnitude in the spinal dorsal horn WDR neurons but also the temporal characteristics of the spinal neuronal response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050756
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    Coordination of reaching and grasping by capitalizing on obstacle avoidance and other constraints (1999)
    Springer
    Experimental brain research 128 (1999), S. 92-100 
    Details
    ISSN: 1432-1106
    Keywords: Key words Reaching movements ; Grasping movements ; Prehension ; Manual control ; Computational model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Reaching and grasping an object can be viewed as the solution of a multiple-constraint satisfaction problem. The constraints include contact with the object with the appropriate effectors in the correct positions as well as generation of a collision-free trajectory. We have developed a computational model that simulates reaching and grasping based on these notions. The model, rendered as an animation program, reproduces many basic features of the kinematics of human reaching and grasping behavior. The core assumptions of the model are: (1) tasks are defined by flexibly organized constraint hierarchies; (2) manual positioning acts, including prehension acts, are first specified with respect to goal postures and then are specified with respect to movements towards those goal postures; (3) goal postures are found by identifying the stored posture that is most promising for the task, as determined by the constraint hierarchy, and then by generating postures that are more and more dissimilar to the most-promising stored posture until a deadline is reached, at which time the best posture that was found during the search is defined as the goal posture; (4) depending on when the best posture was encountered in the search, the deadline for the search in the next trial is either increased or decreased; (5) specification of a movement to the goal posture begins with straight-line interpolation in joint space between the starting posture and goal posture; (6) if an internal simulation of this default movement suggests that it will result in collision with an obstacle, the movement can be reshaped until an acceptable movement is found or until time runs out; (7) movement reshaping occurs by identifying a via posture that serves as a body position to which the actor moves from the starting posture and then back to the starting posture, while simultaneously making the main movement from the starting posture to the goal posture; (8) the via posture is identified using the same posture-generating algorithm as used to identify the goal posture. These processes are used both for arm positioning and, with some elaboration, for prehension. The model solves a number of problems with an earlier model, although it leaves some other problems unresolved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050823
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    The birthdates of GABA-immunoreactive amacrine cells in the rat retina (1999)
    Springer
    Experimental brain research 128 (1999), S. 309-314 
    Details
    ISSN: 1432-1106
    Keywords: Key words GABA ; Bromodeoxyuridine ; Proliferation ; Immunohistochemistry ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The birthdates of GABAergic amacrine cells in the rat retina were investigated by immunocytochemistry using anti-GABA and anti-bromodeoxyuridine (BrdU) antisera. The ratio of co-localization of GABA to BrdU increased gradually from embryonic-day 13 (E13) and showed a peak value on E18 in the central retina and on E20 in the periphery. After birth, until postnatal-day 3 (P3), a few co-localized cells were observed in the inner nuclear layer (INL). However, in the peripheral retina, co-localized cells were observed in the INL and ganglion cell layer until P5. Our results suggest that the birthdates of GABA-immunoreactive cells vary, depending on cell-type and that there is a temporal lag in the GABA-immunoreactive cell production in the peripheral retina relative to the central retina.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050851
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    Hand deviations toward distractors Evidence for response competition (1999)
    Springer
    Experimental brain research 127 (1999), S. 207-212 
    Details
    ISSN: 1432-1106
    Keywords: Key words Attention ; Distractor interference ; Path deviation ; Horse race model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been suggested that, when movements are planned within cluttered environments, competing responses programmed to distracting stimuli are inhibited based on their relation to the action being performed. Further, as a result of this inhibition, the path of the movement made to the target object deviates away from the distractor. In contrast to the object avoidance hypothesis, the results of the present study show that, for aiming movements made in environments in which distractors are present, the path of the movement veers toward the distractor. Moreover, the effects of the distractors on the movement trajectory were independent of the direction of limb movement. These findings suggest that, when a distractor is not a potential physical barrier, a response to the distractor may be activated along with the target response and, owing to temporal advantages, cause a deviation of the movement trajectory toward the distractor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050790
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    Does the coordination between posture and movement during human whole-body reaching ensure center of mass stabilization? (1999)
    Springer
    Experimental brain research 129 (1999), S. 134-146 
    Details
    ISSN: 1432-1106
    Keywords: Key words Coordination ; Posture ; Movement ; Anticipatory postural adjustments ; Axial synergy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The whole-body center of mass (CoM) has been classically regarded as the stabilized reference value for human voluntary movements executed upon a fixed base of support. Axial synergies (opposing displacements of head and trunk with hip segments) are believed to minimize antero-posterior (A/P) CoM displacements during forward trunk movements. It is also widely accepted that anticipatory postural adjustments (APAs) create forces of inertia that counteract disturbances arising from the moving segment(s). In the present study, we investigated CoM stabilization by axial synergies and APAs during a whole-body reaching task. Subjects reached towards an object placed on the ground in front of them in their sagittal plane using a strategy of coordinated trunk, knee, and hip flexion. The reaching task imposed constraints on arm-trajectory formation and equilibrium maintenance. To manipulate equilibrium constraints, differing conditions of distance and speed were imposed. The comparison of distance conditions suggested that axial synergies were not entirely devoted to CoM stabilization: backward A/P hip displacements reduced as head and trunk forward A/P displacements increased. Analysis of upper- and lower-body centers of mass in relation to the CoM also showed no strict minimization of A/P CoM displacements. Mechanical analysis of the effects of APAs revealed that, rather than acting to stabilize the CoM, APAs created necessary conditions for forward CoM displacement within the base of support in each condition. The results have implications for the CoM as the primary stabilized reference for posture and movement coordination during whole-body reaching and for the central control of posture and voluntary movement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050944
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  • 100
    Electronic Resource
    Electronic Resource
    The oculomanual coordination control center takes into account the mechanical properties of the arm (1999)
    Springer
    Experimental brain research 124 (1999), S. 42-52 
    Details
    ISSN: 1432-1106
    Keywords: Key words Ocular tracking ; Oculomanual coordination ; Electromyography ; Internal model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  When the eyes and arm are involved in a tracking task, the characteristics of each system differ from those observed when they act alone: smooth pursuit (SP) latency decreases from 130 ms in external target tracking tasks to 0 ms in self-moved target tracking tasks. Two models have been proposed to explain this coordination. The common command model suggests that the same command be addressed to the two sensorimotor systems, which are otherwise organized in parallel, while the coordination control model proposes that coordination is due to a mutual exchange of information between the motor systems. In both cases, the interaction should take into account the dynamic differences between the two systems. However, the nature of the adaptation depends on the model. During self-moved target tracking a perturbation was applied to the arm through the use of an electromagnetic brake. A randomized perturbation of the arm increased the arm motor reaction time without affecting SP. In contrast, a constant perturbation produced an adaptation of the coordination control characterized by a decrease in arm latency and an increase in SP latency relative to motor command. This brought the arm-to-SP latency back to 0 ms. These results support the coordination control model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050598
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