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  • 1
    Electronic Resource
    Electronic Resource
    ras p21 isoprenylation inhibition induces flat colon tumors in Wistar rats (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. 70-75 
    Details
    ISSN: 1530-0358
    Keywords: Pravastatin ; ras p21 isoprenylation ; Colon carcinogenesis ; Flat colon tumor ; Azoxymethane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The effect of pravastatin, an inhibitor ofras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associatedras p21 in colon tumors. CONCLUSIONS: These findings suggest that theras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02237247
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  • 2
    Electronic Resource
    Electronic Resource
    Development of the bones and synovial joints in the rat model of the VATER association (2000)
    Springer
    Journal of orthopaedic science 5 (2000), S. 390-396 
    Details
    ISSN: 1436-2023
    Keywords: Key words Adriamycin ; Rat ; Embryo ; VATER association ; Synovial joint ; Bones ; Limbs ; Vertebra ; Sirenomelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6–9 or 10–13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6–9, while it was low in the GD 10–13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6–9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007760050015
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  • 3
    Electronic Resource
    Electronic Resource
    Induction of adenocarcinoma containing myoepithelial cells in rat submandibular gland by 7,12-dimethylbenz(a)anthracene (2000)
    Springer
    Virchows Archiv 437 (2000), S. 314-324 
    Details
    ISSN: 1432-2307
    Keywords: Keywords 7 ; 12-dimethylbenz(a)anthracene ; Rat ; Submandibular gland ; Adenocarcinoma Myoepithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In an attempt to induce adenocarcinoma containing myoepithelial cells (MECs) in the rat submandibular gland, we injected 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone into the glands of rat pups at the age of 10 days. In both male and female pups, the glands, including their developing terminal secretory units, contained far greater numbers of cells positive for proliferating cell nuclear antigen (PCNA) than did adult glands. A single administration of 1% DMBA (0.05 ml/130 g b.w.) did not produce adenocarcinoma, but did induce occasional sarcomas, such as rhabdomyosarcoma and fibrosarcoma, in 2 months. Most glands regenerated with minimal scar formation. Microscopically, these glands were atypical in that they contained increased numbers of PCNA-positive cells, underdeveloped granular ducts, and striated ducts surrounded by MECs positive for alpha smooth muscle actin (αSMA). Though these features were also observed in the regenerated glands after acetone injection, the number of PCNA-positive cells was relatively high in the glands of DMBA-treated females, especially in the terminal secretory unit. The second DMBA injection at 10 weeks of age produced adenocarcinoma made up of αSMA-positive MECs and keratin 19-positive duct cells. Such MEC-associated adenocarcinoma was induced in the glands of more than half the female but not the male animals. Replacement of either of the double DMBA treatments with acetone, or DMBA treatment, single or double, of adult glands did not produce adenocarcinoma, but did produce sarcoma and squamous cell carcinoma. These results suggest that (1) at least two genetic mutations are necessary for induction of adenocarcinoma with MECs in the rat submandibular gland, (2) the mutation is efficiently introduced to pup glands whose terminal secretory units exhibit extreme proliferative activity, and (3) the second mutation is difficult to introduce in male glands, whose proliferative activity is relatively low, and/or transformed cells need some female hormone after the mutation to propagate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000223
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  • 4
    Electronic Resource
    Electronic Resource
    A study of Italian families with cluster headache (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S165 
    Details
    ISSN: 1129-2377
    Keywords: Key words Cluster headache ; Familial occurrence ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Danish genetic study showed increased risk of cluster headache (CH) among relatives of CH patients. We studied the families of 191 CH patients (118 males, 73 females; mean age 45.9 years) attending the Milan Headache Center. Information on 3589 relatives was collected by direct interview of the probands (n = 118) or by mailed questionnaire (n = 73). The diagnostic criteria of the IHS were used. A positive family history was found in 19% (37 of 191) of the families. A total of 32 first-degree (32 of 1036, 3.1%) and 15 second-degree (15 of 2553, 0.6%) relatives were affected. The relative risk of CH was 26.89 (95% CI, 17.57–36.21) in the first-degree relatives and 4.35 (95% CI, 2.13–5.21) in second-degree relatives. This study shows increased familial risk of cluster headache in an Italian population and confirms that cluster headache is, in some families, and inherited disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070012
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  • 5
    Electronic Resource
    Electronic Resource
    Molecular genetics and migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S135 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Headache ; Genetics ; Serotonin ; Dopamine ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Migraine carries a significant hereditary determination. Familial hemiplegic migraine (FHM) has been recently linked to mutations in the CACNA1A gene on chromosome 19. CACNA1A codes for a subunit of a neural calcium channel. Other linkage loci on chromosome 1q21-23 and 1q31 have been reported. Several linkage and association studies have been performed to determine the role of the CACNA1A gene, and of other candidate genes implicated in the metabolism of serotonin and dopamine, in the more common types of migraine. Co-morbidity of migraine with vascular events has been analysed versus genetic prothrombotic factors and mitochondrial DNA, and genes involved in the inflammatory cascade have been explored. Though no definite conclusions have emerged from these studies as yet, molecular genetics of migraine can be expected to unravel the complex aetiologies of these fascinating diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070007
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  • 6
    Electronic Resource
    Electronic Resource
    Molecular variation within the dopamine receptor DRD2 gene in migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S147 
    Details
    ISSN: 1129-2377
    Keywords: Key words Dopamine ; Migraine ; Genetics ; DRD2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Molecular genetics offers a novel approach to the understanding and management of migraine since the disorder is known to have a strong genetic component. In recent studies, polymorphisms in the genes for dopamine receptors have been evaluated. Both positive and negative association studies have been reported. In particular, these data suggest that activation of the DRD2 receptor plays a modifying role in the pathophysiology of migraine. As a result, existing data provide a molecular rationale for the documented efficacy of dopamine D2 receptor antagonists in the treatment of migraine. Therefore, at the present time, molecular genetic data provide support for the hypothesis that susceptibility to migraine may be modified, in part, by variations in dopamine DRD2 receptor function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070009
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  • 7
    Electronic Resource
    Electronic Resource
    Genetic factors in migraine and chronic tension-type headache (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S157 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Chronic tension type headache ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pathophysiological studies have dominated migraine research for several years. However, these studies are difficult to interpret because it is difficult to decide whether the observed phenomena are primary or secondary to the migraine attack. For that reason it is important that future migraine research focus on studies that concern migrain etiology. Migraine is a paroxysmal disorder. It is most likely and ion-channel disorder like familial hemiplegic migraine. The present paper focuses on genetic factors in migraine and chronic tension-type headache.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070011
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  • 8
    Electronic Resource
    Electronic Resource
    Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease (2000)
    Springer
    Neurosurgical review 23 (2000), S. 1-22 
    Details
    ISSN: 1437-2320
    Keywords: Key words Von Hippel-Lindau disease ; Hemangioblastoma ; Endolymphatic sac tumor ; Angiogenesis ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the cell cycle. A molecular diagnosis of VHL is now available, leading to a transformation in clinical management of patients and their families. Diagnosis of VHL has to be suspected in patients with a VHL-related tumor without familial history and especially in case of hemangioblastoma or endolymphatic sac tumors. Such patients should be systematically investigated for clinical and molecular evidence of VHL disease. Treatment of symptomatic hemangioblastomas remains mainly neurosurgical, often in emergency, but stereotactic radiosurgery is emerging as an alternative therapeutic procedure. In the future, antiangiogenic drugs could represent a potential medical treatment of CNS hemangioblastomas in view of their highly vascular structure. Lastly, visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101430050024
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  • 9
    Electronic Resource
    Electronic Resource
    The need for speed. II. Myelin in calanoid copepods (2000)
    Springer
    Journal of comparative physiology 186 (2000), S. 347-357 
    Details
    ISSN: 1432-1351
    Keywords: Key words Crustacean ; Sensorimotor ; Ultrastructure ; Multilamellar sheath ; Myelinated axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003590050435
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  • 10
    Electronic Resource
    Electronic Resource
    Myocardial enzyme activities in plasma after whole-heart irradiation in rats (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 27-32 
    Details
    ISSN: 1432-1335
    Keywords: Key words Heart irradiation ; Plasma enzyme levels ; Myocardial enzyme levels ; Rat ; AbbreviationsCK creatine kinase ; LDH lactate de-hydrogenase ; AST aspartate aminotransferase ; ALT alanine aminotransferase ; α-HBDHα-hydroxybutyrate dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma levels of myocardial enzymes present after local heart irradiation were studied in a rat model. The purpose was to investigate whether, within days after irradiation, these enzyme levels change to such an extent that they may be helpful in assessing the severity of cardiac damage after radiotherapy. Therefore, activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and α-hydroxybutyrate dehydrogenase (α-HBDH) were determined in the plasma and left ventricular myocardium of rats following local heart irradiation with a single dose of 20 Gy. A dose of 20 Gy is known to cause irreversible cardiac damage and to reduce survival times of the animals. Cardiac enzyme assays were performed directly after and twice daily for up to 2 weeks after radiation. Plasma CK, LDH, AST and α-HBDH levels were increased between 2 h and 24 h after irradiation. Plasma ALT levels remained unchanged. Myocardial enzyme levels, measured between 24 h and 16 days after radiation, did not differ between irradiated and control animals, although acute (first 12 h) reductions were observed in the irradiated group. The elevated enzyme levels in plasma appeared to correlate with the acutely reduced myocardial enzyme levels. Although irradiation with a dose of 20 Gy induced acute rises of cardiac enzyme levels in plasma, it is doubtful that fractionated radiation, as applied clinically for treatment of solid tumors, will induce plasma enzyme elevations that are large enough to indicate the extent of cardiac damage occurring acutely or chronically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008461
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  • 11
    Electronic Resource
    Electronic Resource
    Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia-reperfusion injury (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 74-81 
    Details
    ISSN: 1437-773X
    Keywords: Key words Mitogen-activated protein kinase (MAPK) ; Ischemia reperfusion injury ; Heart ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950070005
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  • 12
    Electronic Resource
    Electronic Resource
    Decreased expression of vascular endothelial growth factor in glomeruli of puromycin aminonucleoside nephrosis (2000)
    Springer
    Clinical and experimental nephrology 4 (2000), S. 29-33 
    Details
    ISSN: 1437-7799
    Keywords: Key words VEGF ; Glomeruli ; Ribonuclease protection assay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Vascular endothelial growth factor (VEGF) is a selective endothelial growth factor which potently enhances microvascular permeability. In the kidney, VEGF mRNA is known to be highly expressed in visceral epithelial cells in glomeruli. However, the physiological role of VEGF in glomerular function and its involvement in the pathogenesis of proteinuria are not clear. The present studies were designed to determine whether altered expression of VEGF mRNA was observed in the course of puromycin aminonucleoside (PAN) nephrosis in rats (a model of human minimal change nephrosis). Methods. The message level of VEGF in isolated glomeruli of PAN nephrosis rats was measured using a ribonuclease protection assay. Results. VEGF expression began to decrease 4 days after PAN injection and could not be detected in the nephrotic stage of PAN nephrosis (on days 8 and 16). In the remission of stage of PAN nephrosis (on day 28), mRNA was restored to the control level. Conclusions. According to our results, a functional defect in the VEGF expression of visceral epithelial cells was observed in PAN nephrosis. VEGF could be a functional marker of visceral epithelial cells, and the loss of normal expression of VEGF after damage to visceral epithelial cells could affect glomerular endothelial cell function in PAN nephrosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101570050058
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  • 13
    Electronic Resource
    Electronic Resource
    Apoptosis in murine duodenum during embryonic development (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 485-487 
    Details
    ISSN: 1437-9813
    Keywords: Key words Duodenum ; Apoptosis ; Fetus ; Rat ; Duodenal atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830000408
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  • 14
    Electronic Resource
    Electronic Resource
    An immunohistochemical and ultrastructural study of a follicle-stimulating hormone-secreting gonadotroph adenoma occurring in a 10-year-old girl (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 25-31 
    Details
    ISSN: 1437-773X
    Keywords: Key words Gonadotroph adenoma ; FSH ; Childhood ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-β monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140–260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000004
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  • 15
    Electronic Resource
    Electronic Resource
    Ultrastructural evaluation of apoptosis induced by Helicobacter pylori infection in human gastric mucosa: novel remarks on lamina propria mucosae (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 82-88 
    Details
    ISSN: 1437-773X
    Keywords: Key words Apoptosis ; Helicobacter pylori ; Fibroblasts ; Smooth muscle cells ; Ultrastructure ; Gastroduodenal ulcer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been considered that Helicobacter pylori (H. pylori) infection is a major cause of human gastritis and gastroduodenal ulcers (G-DU). Many investigations of the relationship between H. pylori and apoptosis have been reported recently. However, these studies focused mostly on epithelium, using the TUNEL method. In the present study, we evaluated by electron microscopy the occurrence of apoptosis in the mesenchymal cells of lamina propria mucosae infected with H. pylori. Gastric biopsy specimens from 37 H. pylori-infected G-DU patients and 8 noninfected volunteers were examined with both light and electron microscopy and analyzed by the TUNEL method. The TUNEL method showed no significant difference between H. pylori-infected and noninfected cases. In contrast, electron microscopy revealed significant numbers of apototic fibroblasts and smooth muscle cells in H. pylori-infected lamina propria mucosae, with a diminished number of collagen fibers in surrounding areas. These areas showed edematous changes histopathologically. These results indicated that H. pylori infection induces apoptosis of fibroblasts and smooth muscle cells in lamina propria, with decrease in the numbers of collagen fibers, suggesting that these alterations may be affected by exaggerate acid secretion, decrease mucus protecting factors, and result in ulcer formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950070006
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  • 16
    Electronic Resource
    Electronic Resource
    Ciliogenesis and ciliary abnormalities (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 109-114 
    Details
    ISSN: 1437-773X
    Keywords: Key words Ciliogenesis ; Ciliated cell ; Abnormal cilia ; Basal body ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cilia are motile processes extending from the basal bodies, playing important roles in the mucociliary clearance in the respiratory tract and the transport of the ovum from the ovary to the uterus in mammals. Ciliogenesis is divided into four stages: (1) duplication of centrioles; (2) migration of centrioles to the apical cell surface to become basal bodies; (3) elongation of cilia containing the axoneme; and (4) formation of accessory structures of basal bodies. The orderly course of ciliogenesis appears to be disturbed by various internal and external factors and, as a result, various unusual forms of the ciliary apparatus develop in the cell. Inhibition of basal body migration results in development of intracytoplasmic axonemes, cilia within periciliary sheaths, and intracellular ciliated cysts. Swollen cilia and the bulging type of compound cilia are formed during ciliary budding and elongation. This review also discusses the origin, composition, and function of the centriolar precursor structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000009
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  • 17
    Electronic Resource
    Electronic Resource
    Abnormal elastic system fibers in fibrotic human liver (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 135-142 
    Details
    ISSN: 1437-773X
    Keywords: Key words Elastic system fiber ; Ultrastructure ; Fibrotic human liver ; Oxytalan fiber ; Elaunin fiber
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The network of elastic system fibers in human fibrotic liver was investigated by histological methods, immunohistochemical staining, and electron microscopy. Type III collagen was seen not only in regions of portal fibrosis but also in the sinusoidal wall. However, elastic system fibers were not found in the Disse space of the sinusoidal wall. Elastic system fibers including oxytalan, elaunin, and elastic fibers were found successively in the course of elastogenesis. A few normal oxytalan fibers and abnormal oxytalan fibers were observed in the periportal tracts. Few normal elaunin and abnormal elaunin fibers were observed in regions of portal fibrosis but not in the surrounding margin. Elastic fibers, only in scarce amounts, were observed around the portal veins in the case of chronic active hepatitis but not in acute hepatitis. Abnormal oxytalan fibers were seen as a bundle of wavelike microfibrils and had an irregular arrangement. Abnormal elaunin fibers were not associated with bundles of microfibrils. Abnormal elaunin fibers in large amounts were found interspersed with spiraled collagen, which most likely indicates that the oxytalan fibers degenerated in the course of elastogenesis. Thus, in a fibrotic liver it is possible that synthesis of normal elaunin and elastic fibers does not occur or that the quantity of such fibers synthesized may be small because of the effect of the degenerated oxytalan fibers. As a characteristic of liver fibrosis, the composition of abnormal elastic system fibers and spiraled collagen differs from that in other fibrotic organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000013
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  • 18
    Electronic Resource
    Electronic Resource
    Organ-specific distribution of major histocompatibility antigens in rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 285-292 
    Details
    ISSN: 1437-9813
    Keywords: Key words Major histocompatibility complex (MHC) ; Rat ; Immunohistochemistry ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050746
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  • 19
    Electronic Resource
    Electronic Resource
    Proliferation, zonal maturation, and steroid production of fetal adrenal transplants in adrenalectomized rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 293-296 
    Details
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Proliferation ; Adrenal glands ; Addisonian crisis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated the histologic maturation, proliferative capacity, and steroid production of fetal adrenal transplants (Tx) in adrenalectomized rats. A pair of fetal adrenal glands (18–20 days of gestation) was transplanted into the omentum of syngeneic Lewis rats (n=45). Four weeks later, in 5 animals the grafts were excised for morphologic evaluation. Proliferation was investigated by immunohistochemical staining for KI-67 protein and quantified by the proliferation index (PI = positive cells/100 counts). All other hosts (Tx; n = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis. Postoperatively, survival and concentrations of potassium, sodium, aldosterone, and corticosterone were recorded for 6 months. These data were compared to controls (C = only AE; n = 30) and a sham group (S; n = 10). At the end of the study period all surviving hosts were killed for histologic examination of grafts. At 4 weeks post-Tx the adrenal grafts demonstrated a distinct zona glomerulosa and frequent proliferation with a PI of 0.084, comparable to normal control (0.092). Following AE survival was significantly prolonged in Tx (86% vs 12% of C, P 〈 0.05). Control animals developed severe hyponatremia and hyperkalemia, whereas in Tx only transient signs of Addisonian crisis were recorded. Levels of aldosterone dropped within 7 days in the Tx and C groups, but returned to normal for Tx within 8 weeks. Corticosterone levels of Tx animals fell to 25% within week, but steadily increased to 70% by the end of the study. At 6 months, grafts revealed a mature adrenocortical structure with little proliferative activity, which was comparable to controls. In a syngeneic rat model fetal adrenal transplants thus mature and proliferate to provide sufficient steroid production for adrenalectomized hosts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050747
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  • 20
    Electronic Resource
    Electronic Resource
    Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 414-416 
    Details
    ISSN: 1437-9813
    Keywords: Key words Congenital diaphragmatic hernia ; Hypoplastic lung ; Bromodeoxyuridine (BrdU) ; Antenatal glucocorticoids ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 ± 3.01) compared to groups I (9.16 ± 2.20) and III (6.83 ± 1.70) (P 〈 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003839900336
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  • 21
    Electronic Resource
    Electronic Resource
    Adenoid basal carcinoma of the uterine cervix: a case report with ultrastructural findings (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 241-245 
    Details
    ISSN: 1437-773X
    Keywords: Key words Adenoid basal carcinoma ; Uterine cervix ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000024
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  • 22
    Electronic Resource
    Electronic Resource
    Variation among giant rice bodies: report of four cases and their clinicopathological features (2000)
    Springer
    Skeletal radiology 29 (2000), S. 525-529 
    Details
    ISSN: 1432-2161
    Keywords: Key words Giant rice body ; Ultrastructure ; Immunohistochemistry ; Histogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. Design and patients: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. Results: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. Conclusion: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560000258
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  • 23
    Electronic Resource
    Electronic Resource
    Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance (2000)
    Springer
    Transplant international 13 (2000), S. S532 
    Details
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Split tolerance ; FK 506 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0–5 in the rejection model and from days 0–9 in the long-term functional model. Mean survival time in the rejection model was 98 ± 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term ( 〉 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely ( 〉 70 days). In vitro, mixed leukocyte reactivity of CD4 + T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050396
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  • 24
    Electronic Resource
    Electronic Resource
    Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model (2000)
    Springer
    Transplant international 13 (2000), S. S528 
    Details
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050395
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  • 25
    Electronic Resource
    Electronic Resource
    Hypoxia-reoxygenation differentially stimulates stress-activated protein kinases in primary-cultured rat hepatocytes (2000)
    Springer
    Transplant international 13 (2000), S. S597 
    Details
    ISSN: 1432-2277
    Keywords: Key words Hypoxia-reoxygenation ; JNK1/SAPK1 ; Rat ; Hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 μM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050410
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  • 26
    Electronic Resource
    Electronic Resource
    Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis) (2000)
    Springer
    Virchows Archiv 436 (2000), S. 257-270 
    Details
    ISSN: 1432-2307
    Keywords: Key words Arteriogenesis ; Collateral vessels ; Ultrastructure ; Cell adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the canine heart had shown that the growth of collateral arteries occurs via proliferative enlargement of pre-existing arteriolar connections (arteriogenesis). In the present study, we investigated the ultrastructure and molecular histology of growing and remodeling collateral arteries that develop after femoral artery occlusion in rabbits as a function of time from 2 h to 240 days after occlusion. Pre-existent arteriolar collaterals had a diameter of about 50 µm. They consisted of one to two layers of smooth muscle cells (SMCs) and were morphologically indistinguishable from normal arterioles. The stages of arteriogenesis consisted of arteriolar thinning, followed by transformation of SMCs from the contractile- into the proliferative- and synthetic phenotype. Endothelial cells (ECs) and SMCs proliferated, and SMCs migrated and formed a neo-intima. Intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) showed early upregulation in ECs, which was accompanied by accumulation of blood-derived macrophages. Mitosis of ECs and SMCs started about 24 h after occlusion, whereas adhesion molecule expression and monocyte adhesion occurred as early as 12 h after occlusion, suggesting a role of monocytes in vascular cell proliferation. Treatment of rabbits with the pro-inflammatory cytokine MCP-1 increased monocyte adhesion and accelerated vascular remodeling. In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event. We conclude that the process of arteriogenesis, which leads to the positive remodeling of an arteriole into an artery up to 12 times its original size, can be modified by modulators of inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050039
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  • 27
    Electronic Resource
    Electronic Resource
    Real-time monitoring of nitric oxide in ischemia-reperfusion rat kidney (2000)
    Springer
    Urological research 28 (2000), S. 141-146 
    Details
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Nitric oxide ; Ischemia-reperfusion injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we attempted to clarify the release of nitric oxide (NO) and its role in the ischemia-reperfusion rat kidney. After right nephrectomy, male Wistar rats were divided into four groups: one sham operated and three groups who underwent ischemia (30 min) and reperfusion of the left renal artery. Thirty minutes prior to ischemia-reperfusion, two groups were injected intraperitoneally with 10 and 30 mg/kg of NG-nitro-l-arginine methylester (L-NAME). Real-time monitoring of blood flow and NO release in the rat kidney was measured with a laser Doppler flowmeter and an NO-selective electrode, respectively. Serum creatinine and blood urea nitrogen (BUN) levels were measured 1 and 7 days after the induction of ischemia-reperfusion. Clamping of the renal artery decreased blood flow to 1–5% of the basal level measured before clamping. After removal of the clip, the blood flow of the 30 mg/kg L-NAME rats was significantly lower than that of the controls. Immediately following the clipping of the renal artery, NO release rapidly increased. After removing the clip, NO release immediately returned to three-quarters of the basal level. Serum creatinine and BUN levels of the ischemia-reperfusion rats were slightly but not significantly higher and those of 30 mg L-NAME rats were significantly higher than those of the control or ischemia-reperfusion rats 1 day and 7 days after ischemia-reperfusion. Our data suggest that NO acts as a cytoprotective agent in ischemia-reperfusion injury of the rat kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050153
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  • 28
    Electronic Resource
    Electronic Resource
    Systemic treatment with epidermal growth factor but not insulin-like growth factor I decreases the involution of the prostate in castrated rats (2000)
    Springer
    Urological research 28 (2000), S. 75-81 
    Details
    ISSN: 1434-0879
    Keywords: Key words Castration ; Epidermal growth factor ; Insulin-like growth factor I ; Prostate ; Testosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated Wistar rats were treated with growth factors (EGF 35 μg/rat per day; IGF-I 350 μg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme-linked immunosorbent assay (ELISA). Treatment with EGF inhibited the involution of the prostate (P 〈 0.05), whereas treatment with IGF-I did not affect the prostate involution as compared to castrated controls. EGF treatment significantly increased the endogenous rat EGF in the ventral prostate, but cellular proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration. Compared with testosterone, the effects of EGF treatment on the prostate involution were moderate, and the effects of EGF were not related to cellular proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050141
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  • 29
    Electronic Resource
    Electronic Resource
    Effect of aging on bladder function and the response to outlet obstruction in female rats (2000)
    Springer
    Urological research 28 (2000), S. 33-37 
    Details
    ISSN: 1434-0879
    Keywords: Key words Bladder ; Rat ; Aging ; Obstruction ; Cystometrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050007
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  • 30
    Electronic Resource
    Electronic Resource
    Ganglioglioma with a tanycytic ependymoma as the glial component (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 310-316 
    Details
    ISSN: 1432-0533
    Keywords: Key words Ganglioglioma ; Ependymoma (tanycytic variant) ; Neurofibrillary tangle ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied a cystic ganglioglioma (GG) located in the right frontal lobe of the brain. Interestingly, the fibrillary spindle glial cells were often arranged in a fascicular pattern, and the generally uniform, round-to-oval delicate nuclei appeared to resemble those of ependymoma; and the neoplastic neurons often contained neurofibrillary tangles (NFTs). The glial component was positive for glial fibrillary acidic protein and occasionally contained granular or microvesicular structures positive for epithelial membrane antigen. Ultrastructural investigation revealed that the glial cells were ependymal in nature; intracytoplasmic lumina and intercellular microrosettes lined with cilia and microvilli, as well as long zonulae adherentes, were evident. In addition, chromogranin A-positive granular staining, neurosecretory-granule-like structures, and parallel arrays of microtubules were sometimes associated with the blood vessels. We considered the present case to be an unusual example of GG with an ependymoma, more precisely a tanycytic ependymoma, as the glial component; to our knowledge, the existence of ependymoma as the main glial component of this particular tumor has not been described before. The occurrence of NFTs, which has been reported in several cases of GG, was an additional, unusual feature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007443
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  • 31
    Electronic Resource
    Electronic Resource
    Eosinophilic inclusions in ependymoma represent microlumina: a light and electron microscopic study (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 214-218 
    Details
    ISSN: 1432-0533
    Keywords: Key words Eosinophilic inclusion body ; Inclusion ¶body ; Ependymoma ; Microlumina ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was undertaken to determine the pathological significance of previously unrecognized intracytoplasmic eosinophilic inclusions (IEIs) in ependymoma. The study group consisted of 58 ependymomas, all of which were pathologically characterized and graded according to the 1993 WHO classification. Electron microscopic studies were performed in 16 cases. The study showed that 33 (57%) ependymomas had IEIs and that in 8 cases these were abundant. Round and eosinophilic, their sizes varied from 10 μm to a tiny dot. Similar eosinophilic bodies were also observed between tumor cells. The inclusions were weakly PAS positive. On immunostains, IEIs were frequently positive for glial fibrillary acidic protein, less often for S-100 protein, and for epithelial membrane protein and CAM 5.2. They were negative for AE1/AE3, carcinoembryonic antigen and Ber-EP4. Ultrastructurally, IEIs represented intracytoplasmic lumens containing microvilli and cilia. These microlumina also frequently contained granulo-tubular materials. With reference to tumor subtypes, IEIs occurred most frequently in ordinary and clear cell ependymomas. IEIs were also present in 4 of 6 anaplastic ependymomas studied. In conclusion, IEIs represent microlumina and occur in more than a half of ependymomas including malignant examples. Their finding is a helpful diagnostic feature of ependymoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007427
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  • 32
    Electronic Resource
    Electronic Resource
    Ultrastructure of the normal adult human female prostate gland (Skene’s gland) (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 51-61 
    Details
    ISSN: 1432-0568
    Keywords: Key words Female prostate (Skene gland) ; Ultrastructure ; Secretory (luminal) cells ; Basal (reserve) cells ; Intermediary cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The predominant cells of female prostatic glands lining their lumen were found to be tall cylindrical secretory cells with short stubby microvilli, protuberances of the apical cytoplasm, and with bleb formation. Abundant secretory vacuoles and granules, rough endoplasmic reticulum, developed Golgi complexes and numerous mitochondria are characteristic of their active secretory configuration with apocrine (apical blebs) and merocrine (secretory vacuoles and granules) type of secretion. Basal (reserve) cells were seen to be located between the secretory (luminal) cells and the basement membrane. Their ground cytoplasm is dense with rough endoplasmic reticulum and mitochondria. Their nuclei, unlike those of secretory cells, possess more peripheral condensed chromatin, denser dispersed chromatin and sporadic nucleoli. Besides the two basic types of mature prostatic cells intermediary cells were also seen, located between the basal and secretory cells or in their close vicinity. Their cytoplasm exhibits numerous profiles of rough endoplasmic reticulum and free ribosomes. Secretory vacuoles and granules were mostly practically absent (type 1 intermediary cells) so that they resembled basal (reserve) cells. In some of them, however, as in secretory cells, such secretory elements do gradually appear (type 2 intermediary cells). The finding of intermediary cells in the lining of prostatic glands supports the role of basal (reserve) cells in the renewal of cells in glands of the female prostate. The first ultrastructural analysis of the normal female prostate performed by transmission electron microscopy showed that, as in the postpubertal male, the prostatic glands in the adult female display mature secretory and basal cells. The results of the presented study further corroborate the contemporary concept of the female prostate as a functional genitourinary organ.
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    URL: http://dx.doi.org/
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  • 33
    Electronic Resource
    Electronic Resource
    Morphological analysis of peripheral nerve regenerated by means of vein grafts filled with fresh skeletal muscle (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 475-482 
    Details
    ISSN: 1432-0568
    Keywords: Key words Nerve repair ; Nerve fiber regeneration ; Sciatic nerve ; Muscle-vein-combined graft ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050334
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  • 34
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    Electronic Resource
    Immunocytochemical distribution of the GABAB receptor splice variants GABAB R1a and R1b in the rat CNS and dorsal root ganglia (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 1-13 
    Details
    ISSN: 1432-0568
    Keywords: Key words GABAB receptor ; CNS ; Dorsal root ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The anatomical distribution of the GABAB receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008224
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    NK1, NK2 and NK3 tachykinin receptor localization and tachykinin distribution in the ileum of the mouse (2000)
    Springer
    Anatomy and embryology 202 (2000), S. 247-255 
    Details
    ISSN: 1432-0568
    Keywords: Key words Enteric neurons ; Interstitial cells of Cajal ; Smooth muscle cells ; Guinea-pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tachykinin receptors NK1r, NK2r and NK3r bind tachykinins with different affinities and share pharmacological and molecular differences among animal species. NK1r, NK2r, NK3r and tachykinin (SP/NKA) distribution was studied by immunohistochemistry in the ileum of mouse since no data are available for this species. The results were then compared to those obtained in the rat and guinea pig either by us or by others to ascertain interspecies similarities and/or differences. NK1r- and NK3r-immunoreactivity (IR) were detected in neurons and NK1r-IR in the interstitial cells of Cajal at the deep muscular plexus. At variance with rat and guinea pig, NK1r-IR was also found in the myoid cells of the villi, while NK2r-IR was never detected in nerve varicosities. This latter datum suggests that the NK2r does not play a presynaptic role in the mouse. Unexpectedly, a high NK2r-IR and the presence of NK3r-IR were observed at the inner portion of the circular muscle layer in the mouse as well as in the rat and guinea pig, demonstrating a subregional distribution of these receptors. Tachykinin distribution did not show noticeable species-related differences. The present findings show species-related differences in the tachykinin receptor distribution that might be related to a different tachykinin controlof intestinal motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290000106
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    Dopamine genes and migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S153 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Genetics ; Dopamine ; Hypersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070010
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  • 37
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    Electronic Resource
    HLA and migraine genes (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S141 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Genetics ; Human leukocyte antigens ; Heredity ; Susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human leukocyte Antigens (HLA) are encoded by genes located on chromosome 6p21. Genes important in migraine are being recognized in two basic ways: association studies and linkage analysis. One of the strongest associations is with the HLA region. Actually, genome scan studies suggest that multiple genes are involved in both migraine without aura (MWoA) and migraine with aura (MWA). However, both MWoA and MWA are disorders in which multiple factors, including environmental and genetic factors, confer disease susceptibility. Linkage analysis is identifying new candidate genes that will help to explain the etiology of migraine. In this review previous studies regarding genetic susceptibility to migraine are analyzed, particularly those related to the HLA region. I discuss evidence that HLA shared-hyplotypes in MWoA-affected pairs in different than that expected, that HLA-DR2 antigen provides additional basis for the proposed genetic heterogeneity between MWoA and MWA, and lastly that TNFB gene studies seem to play an important role in the susceptibility to MWoA. In the past years, major advances hae been made in understanding the genetic foundation of MWoA and MWA. Our reported genome-scan studies support the concept that MWoA/MWA are coinherited with a particular HLA region. However, the examination of candidate genes (Ca2+ channel, vascular, CNS, etc.) in a large migraine population seems to be the correct direction in which we have to move. More MWoA/MWa gene studies are needed to test this developing hypothesis and to further establish the complete genetic scenario of migraine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070008
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    Progress in the clinical and molecular genetics of familial parkinsonism (2000)
    Springer
    Neurogenetics 2 (2000), S. 207-218 
    Details
    ISSN: 1364-6753
    Keywords: Key words Parkinson's disease ; Familial Parkinson's disease ; Synuclein ; Parkin ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT¶Parkinson's disease (PD) is a neurodegenerative disease with clinical features resulting from deficiency of dopamine in the nigrostriatal system. Most PD cases are sporadic and the primary cause of the disease is still unknown. Recently, familial PD and parkinsonism have received much attention because these forms of the disease might provide clues to the genetic risk factors involved in the pathogenesis of idiopathic PD. To date, two causative genes, α-synuclein and the parkin gene, have been identified. α-Synuclein is involved in the pathogenesis of an autosomal dominant form of PD and constitutes a major component of the Lewy body, which is a pathological hallmark of idiopathic PD. In addition, mutations in the parkin gene have been identified as the cause of autosomal recessive juvenile parkinsonism (AR-JP). AR-JP manifests itself as a highly selective degeneration of the substantia nigra and the locus coeruleus, but without Lewy body formation. In addition to these two genes, four chromosomal loci have been linked to other forms of familial PD. Furthermore, there are a number of other pedigrees of familial PD in which linkage to known genetic loci has been excluded. Molecular cloning of these disease genes and elucidation of the function of their gene products will greatly contribute to our understanding of the pathogenesis of idiopathic PD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100489900083
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    Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 546-552 
    Details
    ISSN: 1432-0533
    Keywords: Key words Hypothermia ; Immunohistochemistry ; Microtubule-associated protein 2 (MAP2) ; Rat ; Spinal cord injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000206
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    Microglial cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plaque degradation (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 356-364 
    Details
    ISSN: 1432-0533
    Keywords: Key words Alzheimer disease ; Fibrillar amyloid-β ; Astrocytes ; Microglial cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-β (Aβ) deposition. The amount of fibrillar Aβ released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Aβ deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar, diffuse-like plaques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000199
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    GM1-gangliosidosis in a cross-bred dog confirmed by detection of GM1-ganglioside using electrospray ionisation-tandem mass spectrometry (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 409-414 
    Details
    ISSN: 1432-0533
    Keywords: Key words GM1-gangliosidosis ; Ultrastructure ; Electrospray ionisation tandem mass spectrometry ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels of GM1-ganglioside within the tissue using the novel technique of electrospray ionisation tandem mass spectrometry. Electron microscopic examination of ultrathin sections of resin-embedded tissue revealed cytoplasmic inclusions (membranous cytoplasmic and zebra bodies) in brain stem and cerebellar neurons that were characteristic of a gangliosidosis. Glycolipids were extracted from the fixed tissue and analysed by tandem mass spectrometry. Two major ions were detected, which corresponded to GM1 (d18:1–C18:0) and GM1 (d20:1–C18:0). Their identity was confirmed by comparison of their fragmentation patterns with those of authentic standards. The concentration of GM1 was approximately sixfold higher on a wet weight basis than in the brain of a normal control dog, confirming the diagnosis of GM1-gangliosidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000187
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    Changes of Fas and Fas ligand immunoreactivity after compression trauma to rat spinal cord (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 75-81 
    Details
    ISSN: 1432-0533
    Keywords: Key words Fas ; Fas ligand ; Rat ; Spinal cord ; Trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This immunohistochemical study evaluated Fas and Fas ligand (FasL) in the rat nervous system and their changes in the spinal cord subjected to compression. Normal spinal cord showed a low level of Fas and FasL immunoreactivity in the white matter except in the corticospinal tracts. Fas and FasL immunoreactivity seemed to be located in axons and their myelin sheaths. Other regions of the nervous system did not show immunoreactivity to Fas and FasL. Moderate and severe compression injury of the spinal cord resulted in a reduction of Fas and FasL immunoreactivity in the white matter of injured T8–9 segments at 4 h and a complete loss at 1 day after trauma. This was seen even in the remaining white matter. In contrast, increased immunoreactivity to Fas and FasL was present in the cranial T7, caudal T10 (moderate injury) and T12 (severe injury) segments at day 4 with most intense staining were seen at day 9 after trauma. Increased Fas and FasL immunoreactivity may have pathophysiological implications for the development of secondary injuries after trauma to the spinal cord. Fas-FasL interactions may for instance be involved in apoptosis of oligodendrocytes which occurs as a delayed phenomenon after trauma to the spinal cord. The integrity of myelin sheaths may in this way be jeopardized by apoptosis of oligodendrocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051195
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  • 43
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    Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of acute toxicity in rats (2000)
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 69-73 
    Details
    ISSN: 1432-0843
    Keywords: Key words 7-Hydroxymethotrexate ; Methotrexate ; Maximum tolerated dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD50 for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800000111
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    A polymorphism of the rat T-cell receptor β-chain variable gene 13 (BV13S1) correlates with the frequency of BV13S1-positive CD4 cells (2000)
    Springer
    Immunogenetics 51 (2000), S. 296-305 
    Details
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050623
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    Electronic Resource
    Association of TNFA gene polymorphism at position –308 with susceptibility to irritant contact dermatitis (2000)
    Springer
    Immunogenetics 51 (2000), S. 201-205 
    Details
    ISSN: 1432-1211
    Keywords: Key words Skin ; Genetics ; TNFA ; ¶Inflammation ; PCR-RFLP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) α-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for theTNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050032
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    Electronic Resource
    Constitutive NF-κB activity is modulated via neuron-astroglia interaction (2000)
    Springer
    Experimental brain research 130 (2000), S. 100-104 
    Details
    ISSN: 1432-1106
    Keywords: Key words NF-κB ; p65 ; Hippocampal neurons ; Glia ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  NF-κB is found in many neuronal cell types in different states of activity. This study aimed to define which conditions induce constitutive NF-κB activity in cultured hippocampal neurons using activity-specific antibody staining. In co-culture with astroglia, hippocampal neurons were devoid of activated NF-κB. In these co-cultures, NF-κB could not be activated via kainate or glutamate. In contrast, separating neurons from the glial compartment resulted in a time-dependent increase of activated neuronal NF-κB. In this line, activation of NF-κB by kainate or glutamate is very effective in freshly separated cultures, but inhibited when the cultures are reassembled after stimulation. These findings suggests that a neuronal-glial interaction may regulate gene expression via NF-κB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050011
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    Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat (2000)
    Springer
    Histochemistry and cell biology 122 (2000), S. 507-517 
    Details
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00418-004-0708-7
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    Susceptibility to critical illness: reserve, response and therapy (2000)
    Springer
    Intensive care medicine 26 (2000), S. S057 
    Details
    ISSN: 1432-1238
    Keywords: Key words Critical illness ; Intensive care ; Severity of illness ; Scoring systems ; Genetics ; Susceptibility ; Education
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risk of critical illness is determined both by genetic and environmental influences, particularly those relating to infectious and cardiovascular diseases. Physiologically-based scoring systems cannot measure prior risk because they do not quantify physiological reserve independently of the acute illness. Genetic profiling could be useful for risk assessment. Early detection of critical illness involves identifying physiological ’triggers' for referral; this requires the education of nursing and medical staff in their significance. Analysis of the relationship between risk factors and interventions may need complex modelling techniques. Therapeutic strategies depend on the nature of the underlying problem: the most useful are likely to be those which enhance tissue oxygen delivery and resistance to infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340051120
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    Oligohydramnion, renal failure and no pulmonary hypoplasia in glomerulocystic kidney disease (2000)
    Springer
    Pediatric nephrology 14 (2000), S. 319-321 
    Details
    ISSN: 1432-198X
    Keywords: Key words Glomerulocystic kidney disease ; Oligohydramnion ; Renal failure-neonate ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two newborns with glomerulocystic kidney disease manifesting as late onset oligohydramnion and neonatal anuria, yet without severe respiratory distress, are presented. They had a similar perinatal course and associated clinical manifestations. No associated congenital or inherited malformation syndrome could be defined. Both infants’ parents were first degree cousins and belonged to the same small Bedouin tribe, and neither they nor the infants’ siblings had polycystic kidneys or renal insufficiency, pointing to either a possible genetic etiology or a common external toxic exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004670050767
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  • 50
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    Resistance to growth hormone and insulin-like growth factor-I in acidotic rats (2000)
    Springer
    Pediatric nephrology 14 (2000), S. 720-725 
    Details
    ISSN: 1432-198X
    Keywords: Key words Metabolic acidosis ; Growth ; Growth hormone ; Insulin-like growth factor-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean±SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26±2 vs. 49±6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41±3 vs. 104±10 ADU) transcripts and low serum GHBP (25±1 vs. 32±1 ng/ml) and IGF-I (279±50 vs. 366±6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00013425
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    Apoptosis parallels ceramide content in the developing rat kidney (2000)
    Springer
    Pediatric nephrology 15 (2000), S. 188-191 
    Details
    ISSN: 1432-198X
    Keywords: Key words Apoptosis ; Ceramide ; Development ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004670000444
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    Environmental modulation of the response to amphetamine: dissociation between changes in behavior and changes in dopamine and glutamate overflow in the rat striatal complex (2000)
    Springer
    Psychopharmacology 151 (2000), S. 166-174 
    Details
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900359
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    Human interferon-α increases immobility in the forced swimming test in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 106-110 
    Details
    ISSN: 1432-2072
    Keywords: Key words Interferon ; Depression ; Forced swimming test ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. Methods: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. Results: Single intravenous (IV) administration of human IFN-α (6×104 IU/kg), but not of human IFN-β or -γ, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-α (6×103 IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-α, -β and -γ, 6×104 IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. Conclusions: These findings suggest that human IFN-α has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-β and -γ, and that the effect of human IFN-α might not be mediated through IFN-α/β receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050031
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    Selective mu and delta, but not kappa, opiate receptor antagonists inhibit the habituation of novelty-induced hypoalgesia in the rat (2000)
    Springer
    Psychopharmacology 148 (2000), S. 99-105 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiate receptor ; Antinociception ; Habituation ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia. Methods: In experiments 1–3, different groups of male, Wistar rats (275–300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the µ-selective antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), the δ-receptor selective antagonist naltrindole, or the κ-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5°C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the µ and δ, but not the κ, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050030
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    Acute exposure to saccharin reduces morphine analgesia in the rat: evidence for involvement of N-methyl-d-aspartate and peripheral opioid receptors (2000)
    Springer
    Psychopharmacology 149 (2000), S. 56-62 
    Details
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900337
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    Opiate withdrawal-induced place aversion lasts for up to 16 weeks (2000)
    Springer
    Psychopharmacology 149 (2000), S. 115-120 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900358
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    Role of dopamine in prepulse inhibition of acoustic startle (2000)
    Springer
    Psychopharmacology 149 (2000), S. 181-188 
    Details
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition. Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition. Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition. Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000369
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    Prefrontal dopamine is directly involved in the anxiogenic interoceptive cue of pentylenetetrazol but not in the interoceptive cue of chlordiazepoxide in the rat (2000)
    Springer
    Psychopharmacology 149 (2000), S. 366-376 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000390
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    In vivo estimates of efficacy at 5-HT1A receptors: effects of EEDQ on the ability of agonists to produce lower-lip retraction in rats (2000)
    Springer
    Psychopharmacology 149 (2000), S. 377-387 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000374
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    Bridging the gap between molecular genetics and metabolic medicine: access to genetic information (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S183 
    Details
    ISSN: 1432-1076
    Keywords: Key words Database ; Genetics ; Information services ; Internet ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thanks to the World Wide Web, most results of research in genetics are made available in public databases. At the present time there are resources on genetic diseases, genes and their location, mutations of already cloned genes and on laboratories performing the mutation analysis. The main resources on phenotypes are On-line Mendelian Inheritance in Man (OMIM), Pedbase, GeneClinics, London Dysmorphology Database (LDDB) and Orphanet. The main resources on human genes are, in addition to OMIM, the Genome Database, Genatlas and Genecard. There are also two major sequence databases. All of them can be queried using the OMIM number of the disease. Central databases of mutations, as well as locus specific databases have been created. Their list is maintained at the Human Genome Organisation mutation database initiative website. Several initiative have been taken to integrate all these data and help the clinician to find out quickly what he/she needs. The website of the National Center for Biotechnology Information is the best example of such an effort with sections on diseases, a genome guide, and locus links. Several databases of genetic testing resources have been established. GeneTests is an on-line genetics resource that contains a directory of North American laboratories providing testing for heritable disorders. Orphanet is a similar database on French services which is in the process of becoming a European database. Conclusion Even if clinicians do not have as many services at their disposal as the molecular geneticists, various useful databases already exist and should no longer be ignored in practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014399
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    Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S208 
    Details
    ISSN: 1432-1076
    Keywords: Key words Cardiovascular disease ; Cystathionine β-synthase ; Genetics ; Methylenetetrahydrofolate reductase ; Mild hyperhomocysteinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over the last decade mild hyperhomocysteinaemia has widely been recognised as a new risk factor for arteriosclerosis and thrombosis. Main regulating enzymes of homocysteine (Hcy) metabolism are cystathionine β-synthase (CBS), methionine synthase and methylenetetrahydrofolate reductase (MTHFR). Early studies on patients with vascular disease described elevated Hcy concentrations after methionine loading and decreased CBS activity, resembling heterozygotes for CBS deficiency. Therefore, heterozygosity for CBS deficiency was proposed as the main cause of mild hyperhomocysteinaemia. However, more recent enzymatic and molecular genetic studies have demonstrated that heterozygosity for CBS deficiency is not or only a very minor cause of mild hyperhomocysteinaemia in vascular disease. We discovered two common genetic causes of mild hyperhomocysteinaemia, the 677C 〉 T and the 1298A 〉 C mutations in the coding region of MTHFR. The 677C 〉 T mutation causes reduced enzyme activity with thermolabile protein properties, elevated Hcy and low-normal or decreased plasma folate levels. The 1298A 〉 C mutation relates also to decreased enzyme activity, but not to thermolabile protein, and Hcy and folate levels are not influenced. However, compound heterozygosity for these two mutations, i.e. individuals with the 677CT/1298AC genotype, have elevated Hcy and decreased plasma folate levels. Gene-enviroment interactions between 677C 〉 T and folate is demonstrated in individuals with the 677TT genotype. Those with low-normal folate have elevated Hcy, whereas those with high-normal folate have normal Hcy concentrations. The elevated Hcy levels due to these mutations can be normalised by administration of folate, but whether folate reduces the risk of cardiovascular disease remains to be established. Conclusion Heterozygosity for cystathionine β-synthase deficiency is a minor cause of hyperhomocysteinaemia. The current data on mutations in the methylenetetrahydrofolate reductase gene do not tell us whether elevated plasma homocysteine plays a causal role in vascular disease. Low cellular vitamin status may be a possible cause and homocysteine may just be a marker for this situation.
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    URL: http://dx.doi.org/10.1007/PL00014405
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    Aetiology of overweight and obesity in children and adolescents (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S35 
    Details
    ISSN: 1432-1076
    Keywords: Key words Obesity ; Genetics ; Child ; Nutrient balance ; Energy balance ; Environment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The epidemic diffusion of obesity in industrialised countries has promoted research on the aetiopathogenesis of this disorder. The purpose of this review is to focus mainly on the contribution that European research has made to this field. Available evidence suggests that obesity results from multiple interactions between genes and environment. Parents obesity is the most important risk factor for childhood obesity. Twin, adoption, and family studies indicated that inheritance is able to account for 25% to 40% of inter-individual difference in adiposity. Single gene defects leading to obesity have been discovered in animals and, in some cases, confirmed in humans as congenital leptin deficiency or congenital leptin receptor deficiency. However, in most cases, genes involved in weight gain do not directly cause obesity but they increase the susceptibility to fat gain in subjects exposed to a specific environment. Both genetic and environmental factors promote a positive energy balance which cause obesity. The relative inefficiency of self-adapting energy intake to energy requirements is responsible for fat gain in predisposed individuals. The role of the environment in the development of obesity is suggested by the rapid increase of the prevalence of obesity accompanying the rapid changes in the lifestyle of the population in the second half of this century. Early experiences with food, feeding practices and family food choices affect children's nutritional habits. In particular, the parents are responsible for food availability and accessibility in the home and they affect food preferences of their children. Diet composition, in particular fat intake, influences the development of obesity. The high energy density and palatability of fatty foods as well as their less satiating properties promotes food consumption. TV viewing, an inactivity and food intake promoter, was identified as a relevant risk factor for obesity in children. Sedentarity, i.e. a low physical activity level, is accompanied by a low fat oxidation rate in muscle and a low fat oxidation rate is a risk factor of fat gain or fat re-gain after weight loss. Conclusion Further research is needed to identify new risk factors of childhood obesity, both in the genetic and environmental areas, which may help to develop more effective strategies for the prevention and treatment of obesity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014361
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    Repeated dose (28 days) oral toxicity study of flutamide in rats, based on the draft protocol for the `Enhanced OECD Test Guideline 407' for screening for endocrine-disrupting chemicals (2000)
    Springer
    Archives of toxicology 74 (2000), S. 127-132 
    Details
    ISSN: 1432-0738
    Keywords: Key words Flutamide ; Androgen antagonist ; Rat ; Enhanced OECD Test Guideline 407 ; Endocrine disrupters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In association with the international validation project to establish a test protocol for the `Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, serum biochemistry and sperm analysis. Thus, among the parameters tested in the present experimental system, the weight of endocrine-linked organs and their histopathological assessment, serum hormone levels, and estrous cycle stage allowed the detection of endocrine-related effects of flutamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050664
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    Changes in serum α2u-globulin levels in male rats given diethylstilbestrol and applicability to a screening test for endocrine-disrupting chemicals (2000)
    Springer
    Archives of toxicology 74 (2000), S. 48-53 
    Details
    ISSN: 1432-0738
    Keywords: Key wordsα2u-Globulin ; Diethylstilbestrol ; Endocrine disrupter ; Rat ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α2u-Globulin (AUG) is a major rat urinary protein, which has a molecular weight of 16 kDa (kidney type) or 19 kDa (native type). The biosynthesis of this protein is under multi-hormonal regulation. In this study, we investigated changes in serum AUG level and their association with changes in the reproductive organs of male rats after the administration of the estrogenic chemical, diethylstilbestrol (DES) at doses ranging from 0.01 mg/kg per day to 100 mg/kg per day by gavage for 14 days. Our aim was to establish basic data for the development of a new screening method for endocrine disrupting chemicals based on serum AUG levels. DES treatment decreased the weight of testes in a dose-dependent manner; and was accompanied by atrophic histopathological changes in testes. Testis weights were significantly decreased by the group given 1 mg/kg per day DES; however, histopathological abnormalities were found in the group given 0.1 mg/kg per day DES. In four of five animals in the group given 1 mg/kg per day there was no significant decrease in testis weight and only a slight or moderate degeneration of the pachytene spermatocytes. Despite these findings, serum AUG levels in this group decreased markedly, while the serum AUG level markedly decreased even in the animals with no histopathological change in the 1 mg/kg per day or 0.1 mg/kg per day groups with no histopathological change also showed decreased serum AUG level. These results suggest that the serum AUG level may be a sensitive parameter for detecting the activity of estrogenic chemicals in intact male rats. Although a uterotropic assay has been proposed for immature female or ovariectomized female rats and is currently undergoing validation studies internationally, there is no screening method for estrogenic chemicals in intact male animals. More data on AUG changes by treatment with other estrogenic chemicals are needed in order to determine the sensitivity and specificity of this response to estrogens. Nonetheless, an AUG-based screening test for estrogenic chemicals may be useful owing to its applicability to conventional toxicity studies and an apparently higher sensitivity of this parameter compared to organ weight change or histology of testis in intact male rats and applicability to conventional toxicity studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050651
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    Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis (2000)
    Springer
    Journal of neurology 247 (2000), S. 940-942 
    Details
    ISSN: 1432-1459
    Keywords: Key words Amyotrophic lateral sclerosis ; Genetics ; Presenilin-1 intron 8 polymorphism ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P 〈 0.04) and allele (P 〈 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070050
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    Vascular risk factors in dementia (2000)
    Springer
    Journal of neurology 247 (2000), S. 81-87 
    Details
    ISSN: 1432-1459
    Keywords: Key words Dementia ; Vascular ¶dementia ; Alzheimer’s disease ; Risk factors, stroke ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer’s disease. There is also evidence of a direct relationship between Alzheimer’s disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer’s disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050021
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    The monoamine oxidase B gene GT repeat polymorphism and Parkinson’s disease in a Chinese population (2000)
    Springer
    Journal of neurology 247 (2000), S. 52-55 
    Details
    ISSN: 1432-1459
    Keywords: Key words Parkinson’s disease ; Monoamine oxidase B ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB; Xp15.21–4) is a candidate gene for Parkinson’s disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients ¶(90 men, 86 women) and 203 age-matched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (χ2 = 2.48; df = 5, P 〈 0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050010
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    Progressive supranuclear palsy: earlier age of onset in patients with the τ protein A0/A0 genotype (2000)
    Springer
    Journal of neurology 247 (2000), S. 206-208 
    Details
    ISSN: 1432-1459
    Keywords: Key words Progressive ¶supranuclear palsy ; Genetics ; Clinical characteristics ; Parkinsonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic studies have detected an association between the presence of the τ gene A0 allele and patients with progressive supranuclear palsy (PSP). This study examined whether patients with this polymorphism exhibit distinct demographic or clinical characteristics. We studied 26 patients who fulfilled clinical criteria for the diagnosis of PSP, 20 who had the A0/A0 genotype and 6 who had other genotypes. A questionnaire on demographic data, past medical history, familial history, and initial symptoms was completed as part of the consultation. A complete neurological examination was performed and PSP symptoms were quantified following Golbe’s PSP disability scale. We found a significant difference in the age at onset of PSP symptoms, which was 65.9 ± 5.3 years in the A0/A0 group and 71.2 ± 5.6 in the non-A0/A0 group (P = 0.016). There were no significant differences in the years from disease onset between the two groups. Symptom severity did not differ significantly in patients with the different A0/A0 genotypes. The detection of significantly lower age at onset with the A0/A0 alleles is consistent with the known association of this genotype as a risk factor for PSP. No significant differences were detected in symptom severity between the two groups of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050564
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    Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls (2000)
    Springer
    Journal of neurology 247 (2000), S. 616-622 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Siblings ; Genetics ; Oligoclonal bands ; Measles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3–4% recurrence risk for manifest MS reported for sibs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070130
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    Light and electron microscopic examination of endothelial cells from bovine retinal vessels in long-term cultures (2000)
    Springer
    Virchows Archiv 436 (2000), S. 249-256 
    Details
    ISSN: 1432-2307
    Keywords: Key words Endothelial cells ; Cell culture ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of the present work was to examine and compare the ultrastructure of bovine retinal endothelial cells (BRECs) in vitro during several passages in a medium selective for endothelial cells. The identity of the endothelial cells was confirmed immunohistochemically, up to the tenth passage. Changes in their ultrastructure in comparison to endothelial cells in vivo occurred at the onset of culturing and not progressively with repeated passages. The cultured BRECs show high metabolic activity in all passages. While retaining their identity as endothelial cells, they modify their lipid metabolism, so that lipids are stored. This change in lipid metabolism was induced by the medium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050038
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    The T-type calcium channel blocker mibefradil reduced interstitial and perivascular fibrosis and improved hemodynamic parameters in myocardial infarction-induced cardiac failure in rats (2000)
    Springer
    Virchows Archiv 436 (2000), S. 147-157 
    Details
    ISSN: 1432-2307
    Keywords: Key words T-type calcium channel blockade ; Mibefradil ; Myocardial infarction ; Cardiac remodeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dtmax were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dtmax were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008215
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    Perspectives in pediatric neurosurgery (2000)
    Springer
    Child's nervous system 16 (2000), S. 809-820 
    Details
    ISSN: 1433-0350
    Keywords: Keywords Pediatric neurosurgery ; Molecular biology ; Genetics ; Novel therapeutics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The new millennium beckons for novel advances in the diagnosis and treatment of pediatric neurosurgical conditions. Almost every aspect of pediatric neurosurgery has changed over the last decade. Undoubtedly with the application of knowledge in molecular biology to human disease many aspects of neurosurgery, especially neuro-oncology and the field of neuro-developmental anomalies, will change appreciably over the next decade. Overall, the trend in surgery in general and neurosurgery in particular is toward less invasive procedures and possibly non-surgical interventions. This review will briefly cover many of the important areas of pediatric neurosurgery. We will describe the state-of-the-art of our subspecialty and discuss possible future directions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810000345
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    Re-examination of (in)compatibility genotypes of two John Innes self-compatible sweet cherry selections (2000)
    Springer
    Theoretical and applied genetics 101 (2000), S. 234-240 
    Details
    ISSN: 1432-2242
    Keywords: Key words Cherry ; Genetics ; Compatibility ; Incompatibility ; Isoelectric focusing ; Prunus avium ; Ribonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The (in)compatibility genotypes of two self-compatible sweet cherry selections, JI 2420 and JI 2434, originating from the John Innes Institute were re-examined. The selections and seedlings derived from them were analysed for stylar ribonucleases, which are known to correlate with S alleles, and the outcome of test crosses was recorded. JI 2420, which had been reported previously as S 3 S 4 ", where " indicates loss of pollen activity, was deduced to have the genotype S 4 S 4 ’. For JI 2434, which had been reported previously as S 3 S 4 0 , S 3 S 3 0 or S 3 S 3 ", where 0 indicates loss of pollen and stylar activity, two different clones were identified. One, at East Malling, was deduced to be S 3 "S 4 ; the other, at Ahrensburg, appeared to be S 3 S 3 " or S 3 S 3 0 .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051474
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    Characterisation and analysis of microsatellite loci in a mangrove species, Avicennia marina (Forsk.) Vierh. (Avicenniaceae) (2000)
    Springer
    Theoretical and applied genetics 101 (2000), S. 279-285 
    Details
    ISSN: 1432-2242
    Keywords: Key words Avicennia marina ; Microsatellite ; Mangrove ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  An enriched microsatellite library of the mangrove species Avicennia marina was constructed, in which 85.8% of the clones contained microsatellite sequences. Of the microsatellite repeat sequences isolated, 55.0% were di-nucleotides, 34.2% were tri-nucleotides, 50.0% were perfect, 24.2% were imperfect, and 15.0% were compound. Four different di-nucleotide repeats were isolated with repeat lengths ranging from 5 to 33; ten different tri-nucleotide repeats were isolated with repeat lengths ranging from 3 to 25. The most common di-nucleotide was the AC/TG repeat; the most common tri-nucleotide was the CCG/GGC repeat. Sixteen microsatellite sequences were selected for primer design, and 6 primers were selected to investigate the polymorphism detected among 15 individuals of A. marina from three natural populations in Australia. A total of 40 alleles were detected at 6 microsatellite loci. The number of alleles per microsatellite locus ranged from 5 to 13. On average, 7 alleles were detected per locus. All microsatellite loci showed high levels of gene diversity (heterozygosity), with values ranging from 0.53 to 0.88; the mean value of gene diversity was 0.70. Microsatellite loci were also tested for conservation across Avicennia species. There was a decline in amplification success with increasing divergence between Avicennia species. The results indicate that microsatellites are abundant in the Avicennia genome and can be valuable genetic markers for assessing the effects of deforestation and forest fragmentation in mangrove communities, which is an important issue for mangrove conservation and afforestation schemes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051480
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    Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal (2000)
    Springer
    Psychopharmacology 149 (2000), S. 170-175 
    Details
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900353
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    The dynamic infusion test in rats (2000)
    Springer
    Child's nervous system 16 (2000), S. 451-456 
    Details
    ISSN: 1433-0350
    Keywords: Keywords Intracranial pressure ; CSF dynamics ; Infusion test ; Rat ; H-Tx rat ; Outflow resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or – as the pressure volume index (PVI) – not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm (”dynamic infusion test”), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the ”dynamic infusion test”, is representative only for the CSF compartment which is directly exposed to the bolus application.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007290
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    Dopamine D3 receptor variant and tardive dyskinesia (2000)
    Springer
    European archives of psychiatry and clinical neuroscience 250 (2000), S. 31-35 
    Details
    ISSN: 1433-8491
    Keywords: Key words Pharmacogenetics ; Genetics ; Risk factor ; Choreoathetotic movements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the search for genetic factors contributing to tardive dyskinesia, dopamine receptor genes are considered major candidates. The dopamine D3 receptor is of primary interest as dopamine D3 receptor knock-out mice show locomotor hyperactivation resembling extrapyramidal side-effects of neuroleptic treatment. Furthermore, Steen and colleagues (1997) recently reported an association between tardive dyskinesia and a dopamine D3 receptor gene variant. In the present study we tried to replicate this finding. We investigated 157 patients with schizophrenia or schizoaffective disorder receiving long-term neuroleptic medication who never or persistently displayed tardive dyskinesia. As advanced age is a main risk factor for tardive dyskinesia, we also compared older patients with a long duration of schizophrenia not displaying tardive dyskinesia to younger patients with a shorter duration of the illness displaying tardive dyskinesia. However, we found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007536
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    Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers (2000)
    Springer
    European archives of psychiatry and clinical neuroscience 250 (2000), S. 203-206 
    Details
    ISSN: 1433-8491
    Keywords: Key words Dopamine receptor D4 ; Genetics ; Personality inventory ; Polymorphism ; Excitement-Seeking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004060070025
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    The ultrastructure of photoreceptor cells in the pineal organ of the blind cave salamander, Proteus anguinus (Amphibia, Urodela) (2000)
    Springer
    Pflügers Archiv 439 (2000), S. r175 
    Details
    ISSN: 1432-2013
    Keywords: Key words Pineal organ ; Photoreceptor cells ; Ultrastructure ; Proteus anguinus ; Regressive evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied ultrastructure of the photoreceptor cells in the pineal organ of blind, depigmented, neotenic cave salamander, Proteus anguinus. Unlike in epigean vertebrates the outer segments of most photoreceptor cells consists of concentrically arranged lamellae, however; in few cells, the outer segments contain 7-9 plasma membrane disks. In both types of photoreceptor cells the outer segments enclose lumps of vesicles of different sizes. The photoreceptor cells of Proteus anguinus are similar to those in other cavernicolous fish species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240000136
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    ICAM-1 gene is not associated with multiple sclerosis in sardinian patients (2000)
    Springer
    Journal of neurology 247 (2000), S. 677-680 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Genetics ; ICAM-1 gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased amount of the intercellular adhesion molecule (ICAM) 1 molecule has been found in the blood of actively relapsing multiple sclerosis (MS) patients, but is unclear whether this enhanced expression is partially causative of the MS process, or whether it is merely an epiphenomenon of the inflammatory-immunological reaction. Using the transmission disequilibrium test (TDT), we studied exon 4 and exon 6 polymorphism of the ICAM-1 gene from 157 families with both parents, one affected and one healthy sib coming from Sardinia, an Italian island having a high incidence and prevalence of MS. TDT did not show variation in the expected 50:50 frequency in transmission in either healthy or affected sibs, using phenotypic or genotypic analysis. Moreover, independence from the predisposing HLA-DRB1-DQA1-DQB1 haplotype was confirmed by TDT analysis performed on the patients stratified according to the presence or absence of the HLA-DRB1, DQA1, DQB1 Sardinian predisposing haplotypes. Our data suggest that the increased expression of the ICAM-1 molecule observed in both blood and periplaque microvessels may be considered a consequence of the inflammatory process rather than the result of a genetic variation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070109
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    Atypical morphological characteristics and surface antigen expression of Burkholderia pseudomallei in naturally infected human synovial tissues (2000)
    Springer
    Modern rheumatology 10 (2000), S. 129-136 
    Details
    ISSN: 1439-7609
    Keywords: Key words Septic arthritis ; Surface antigens ; Ultrastructure ; Burkholderia pseudomallei ; IEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Burkholderia pseudomallei is the causative agent of melioidosis, a disease that frequently runs a protracted course and is very difficult to eradicate. The mechanisms that this organism uses to escape from host defense mechanisms and antibiotics are not well understood. The aim of the study was to compare the morphological characteristics and surface antigen expression of B. pseudomallei in naturally infected human synovial tissues with the characteristics of bacteria grown in culture media. Immunoelectron microscopic study was performed in four synovial biopsies taken from four B. pseudomallei septic arthritis patients. Colonies of pathogenic B. pseudomallei collected from culture media were used as positive controls. Polyclonal antibody to whole cell B. pseudomallei was used as a primary antibody. Complete bacteria-like particles were demonstrated both extracellularly and intracellularly in all four synovial specimens. The intracytoplasmic location of B. pseudomallei and mononuclear phagosome containing microcolony-like structures were demonstrated. B. pseudomallei found in the synovial membrane samples were mostly atypical, with fewer cytoplasmic electron lucent granules. Immunogold staining of bacterial surface antigens was weaker than staining of positive controls. We demonstrated atypical forms of B. pseudomallei and evidence for suppression of its surface antigens in naturally infected human synovial tissues. This adaptation may help bacteria to survive despite host immune surveillance and treatment with antibiotics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101650070019
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    Sensitization of amphetamine-induced wheel running suppression in rats: dose and context factors (2000)
    Springer
    Psychopharmacology 151 (2000), S. 219-225 
    Details
    ISSN: 1432-2072
    Keywords: Keywords Amphetamine ; Wheel running ; Behavioral sensitization ; Pharmacological sensitization ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study explored whether repeated injections of amphetamine (AMP), which increase general locomotion, also increase acute wheel running, a highly structured, rewarding, motor behavior not correlated with other locomotor activities. Objectives: The experiments determine how 1–5 mg/kg d-AMP affects wheel running and see if, over repeated injections, the AMP effects show context specific sensitization. Methods: In experiment 1, 2 mg/kg AMP or saline (SAL) was injected on days 1, 3, 6, 8, and 10 to male Sprague-Dawley rats with either limited or no wheel experience. 20 min after the injection animals were tested in an open field for 5 min and then in a running wheel for 1 h. Rats were injected with SAL or AMP on the days following testing. On days 13 and 15, animals were tested for conditioning (following SAL) and sensitization (following AMP). In experiment 2, the effects on wheel running of repeated 1, 2, or 5 mg/kg AMP were tested. Results: In experiment 1, AMP (2 mg/kg) elevated open field ambulation but suppressed wheel running. Limited wheel experience potentiated the AMP-induced suppression. At test, the suppression of running was found to be context specific. In experiment 2, 1 mg/kg did not affect running, while 2 and 5 mg/kg resulted in dose-dependent running suppression. Acquisition and test AMP dose both influenced the running suppression at test; context had a marginal influence. Conclusions: The degree of running suppression induced by repeated AMP is determined by both psychological (the injection context) and pharmacological (the acquisition dose) factors. This AMP-induced running suppression is consistent with the sensitization of stereotyped behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000446
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    Discriminative stimulus effects of two doses of fentanyl in rats: pharmacological selectivity and effect of training dose on agonist and antagonist effects of mu opioids (2000)
    Springer
    Psychopharmacology 148 (2000), S. 136-145 
    Details
    ISSN: 1432-2072
    Keywords: Key words Fentanyl ; mu opioids ; Drug discrimination ; Training dose ; pA2 analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discriminative stimulus effects of mu opioids vary systematically as a function of training dose. Differences among training doses may arise from multiple mechanisms. Objectives: In vivo apparent pA2 analyses were used to examine the contributions of opioid mechanisms to stimulus control by low and high training doses of the mu opioid fentanyl. Methods: Saline and one of two doses of fentanyl, administered s.c., were established as discriminative stimuli in two groups of rats (low training dose group: 0.01 mg/kg; high training dose group: 0.04 mg/kg). Generalization tests and in vivo apparent pA2 analyses were used to evaluate receptor mechanisms of stimulus control. Results: Fentanyl, etonitazene, methadone, and morphine evoked full fentanyl generalization in both groups but were more potent in the low-dose group. Spiradoline and d-amphetamine did not evoke generalization in either group. Naltrexone antagonized stimulus and rate-altering effects of fentanyl in both groups, with apparent pA2 values of 7.6 in the low-dose group and 7.5 in the high-dose group. Nalbuphine and nalorphine evoked full generalization in the low-dose group but less than 40% generalization in the high-dose group. In the high-dose group, nalbuphine and nalorphine antagonized the stimulus and rate-altering effects of fentanyl with apparent pA2 values of 5.3 and 6.1, respectively, demonstrating lower efficacy mu actions. Conclusions: Changes in fentanyl training dose preserved the mu opioid selectivity of stimulus control but altered the intensity of the transduced mu opioid stimulus required for generalization. These differences in intensity of the fentanyl stimulus determined whether low efficacy mu opioids would evoke or antagonize fentanyl generalization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050035
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    Discriminative stimulus properties of alprazolam (2000)
    Springer
    Psychopharmacology 148 (2000), S. 146-152 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alprazolam ; Drug discrimination ; Benzodiazepines ; Antidepressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants. Objective: In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants. Methods: Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40”-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction. Results: In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), N-methyl-β-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions: These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050036
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    Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 209-216 
    Details
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Drug-discrimination ; Dopamine ; Cocaine ; GBR-12909 ; Nomifensine ; Bupropion ; Chloro-PB ; Chloro-APB ; NPA ; 7-OH-DPAT ; SCH-23390 ; Spiperone ; cis-Flupenthixol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Dopamine plays a major role in the behavioral effects of methamphetamine. Objective: In the present experiments, the effects of different dopaminergic agonists, antagonists, and uptake inhibitors were evaluated in rats discriminating methamphetamine from saline. Methods: In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food delivery, the ability of various dopaminergic agonists and uptake inhibitors to substitute for methamphetamine was evaluated. Subsequently, the ability of various dopaminergic antagonists to block the discriminative-stimulus effects of the training dose of methamphetamine was tested. Results: The dopamine-uptake inhibitors cocaine (10.0 mg/kg), nomifensine (3.0 mg/kg), GBR-12909 (18.0 mg/kg), and bupropion (30.0 mg/kg) fully substituted for the 1.0 mg/kg training dose of methamphetamine. Chloro-APB (SKF-82958), a full agonist at D1 dopamine receptors, produced about 85% methamphetamine-appropriate responding, but the dose required (0.18 mg/kg) markedly decreased rates of responding. Chloro-PB (SKF-81297), another agonist at D1 receptors with a lower intrinsic activity than Chloro-APB, produced only partial generalization (maximum about 55%) at a dose of 1.0 mg/kg. Full substitution for the training dose of methamphetamine was observed with 0.03 mg/kg of the D2 agonist NPA and 0.56 mg/kg of the D3/D2 agonist 7-OH-DPAT. Both NPA and 7-OH-DPAT markedly decreased rates of responding at these doses. The D1 antagonist SCH-23390 (0.056 mg/kg), the D2 antagonist spiperone (0.18 mg/kg), and the mixed D1,D2 antagonist cis-flupenthixol (0.56 mg/kg) all completely blocked the discriminative-stimulus actions of the training dose of methamphetamine. Conclusions: The present findings in rats support previous research findings in other species indicating a major role of dopamine in the discriminative-stimulus effects of methamphetamine. These findings further indicate involvement of dopamine uptake sites as well as D1 and D2 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050044
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    Effects of the competitive nicotinic antagonist erysodine on behavior occasioned or maintained by nicotine: comparison with mecamylamine (2000)
    Springer
    Psychopharmacology 148 (2000), S. 234-242 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Drug discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The cellular effects of nicotine underlying its addictive liability are thought to be mediated by neuronal nicotinic receptors (nACHRs) in the central nervous system. It is believed that densely expressed β2-containing nACHRs in the central nervous system are responsible for these actions, but few data are available that can directly assess subtype mediation of nicotine’s acute subjective and reinforcing effects. Objective: The present study compared the effects of the competitive nACHR antagonist erysodine and the noncompetitive antagonist mecamylamine in rats trained to discriminate or self-administer nicotine. Methods: Adult male rats were trained to disciminate 0.4-mg/kg injections of nicotine from vehicle in a two-lever procedure of food-maintained behavior, or to self-administer 0.03-mg/kg injections of nicotine under fixed-ratio 5 or progressive-ratio schedules of reinforcement. Additional rats were trained under a food-maintained procedure of lever pressing. Results: Erysodine (0.3–10 mg/kg) and mecamylamine (0.1–1.0 mg/kg) blocked nicotine discrimination, although only erysodine produced the rightward shift that would be predicted of a competitive antagonist. Erysodine (0.32–32 mg/kg) and mecamylamine (0.32–3.2 mg/kg) also selectively reduced nicotine self-administration on a fixed-ratio schedule and lowered break points on a progressive-ratio schedule. Conclusions: Based on the known affinity of erysodine for α4β2 nACHRs and its selectivity relative to α7 and α1β1γδ receptors, the present data support a critical role of β2-containing nACHR constructs in the discriminative and reinforcing actions of nicotine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050047
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    The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 224-233 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Olanzapine ; Clozapine ; Chlorpromazine ; Haloperidol ; Thioridazine ; Raclopride ; Risperidone ; Scopolamine ; Ritanserin ; Atypical antipsychotic ; Neuroleptic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Analysis of the preclinical behavioral effects of atypical antipsychotic agents will provide a better understanding of how they differ from typical antipsychotics and aid in the development of future atypical antipsychotic drugs. Objectives: The present study was designed to provide information about the discriminative stimulus properties of the atypical antipsychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) from vehicle in a two- lever drug discrimination procedure. The atypical antipsychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg OLZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group (99.9% DLR). The typical antipsychotic chlorpromazine also substituted for olanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR); whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzapine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone (60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine’s discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050046
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    The role of nicotinic and muscarinic acetylcholine receptors in attention (2000)
    Springer
    Psychopharmacology 148 (2000), S. 243-250 
    Details
    ISSN: 1432-2072
    Keywords: Key words Attention ; Scopolamine ; Mecamylamine ; Oxotremorine ; Physostigmine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study tried to determine the relative roles of muscarinic and nicotinic cholinergic receptors in attentional processing. Methods: The effects of cholinoceptor agonists and antagonists, and of an anticholinesterase, were studied on performance of rats in a five-choice serial reaction time task. Results: Scopolamine (0.1 mg/kg) and mecamylamine (5.0 mg/kg) produced deficits in accuracy and reaction time, respectively. This may suggest a differential role for the two types of cholinoceptors in information processing. Combinations of sub-threshold doses of scopolamine (0.01–0.03 mg/kg) and mecamylamine (0.5–1.6 mg/kg), which alone did not affect accuracy or reaction time, did not produce significant deficits in attention. However, the pattern of effects after combined treatment suggested that the differential deficits seen with these drugs alone remained. The anticholinesterase physostigmine (0.1 mg/kg) and the non- selective muscarinic agonist oxotremorine (0.03 mg/kg) induced severe behavioural disruption at doses that appeared to be relatively well tolerated in previous studies; this precluded the derivation of accuracy and response time data at these doses. At lower doses, neither physostigmine (0.05 mg/kg) nor oxotremorine (0.003 mg/kg) significantly affected any performance measure; this may reflect the ability of both drugs to indirectly or directly activate presynaptic muscarinic receptors that inhibit acetylcholine release, respectively. Conclusions: Both muscarinic and nicotinic cholinoceptors may be important in attention but they may serve different roles in information processing; this hypothesis could be tested using tasks that place different emphasis on different stages of information processing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050048
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    Behavioral tolerance to the force differentiation effects of diazepam and midazolam in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 327-335 
    Details
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Operant ; Force ; Tolerance ; Chronic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Several benzodiazepines (BZs) have been shown to increase the peak force of operant responses at doses that increased, decreased, or had no effect on response rate, suggesting that operant response force may be a sensitive index of BZs’ effects rather than solely a correlate of rate-dependent effects. In addition, contingent tolerance to the rate-dependent effects of BZs has been reported, but the degree of contingent tolerance that develops when the critical variable of the task is force of the response has not been explored. Objectives: These experiments examined the effects of acute and repeated oral administration of diazepam (DZ) and midazolam (MZ) on a force-differentiation task to explore the importance of task requirements on the development of contingent tolerance. Methods: Two groups of rats were trained to press a force-sensing operandum, and responses having peak forces falling within fixed lower and upper limits [low force (8–10 g) or high force (40–50 g)] were reinforced with water. Acute effects of the oral administration of DZ (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg) and MZ (same doses) were determined for the discriminated-force task before and after a repeated-administration procedure. Results: When administered acutely, both drugs increased the peak force of responses in a dose-related manner and concomitantly reduced the proportion of reinforced responses, with MZ exhibiting greater potency. For the next 36 days, one group received drug before experimental sessions and the other group received drug after the experimental session. A second dose–effect determination demonstrated that rats chronically dosed with DZ or MZ pre-session displayed more contingent tolerance to alterations in peak force than rats that had received 36 drug injections post- session, where there was no opportunity to practice the force-discrimination response while under the drug state. Conclusions: These results suggest that perceptual motor difficulty of the task rather than effort may be an important variable in predicting the degree of contingent tolerance that develops. Additionally, these results suggest that both behavioral and pharmacological mechanisms are involved in the development of drug tolerance to the BZs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050059
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  • 90
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    Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity (2000)
    Springer
    Psychopharmacology 149 (2000), S. 34-40 
    Details
    ISSN: 1432-2072
    Keywords: Key words ACTH ; Corticosterone ; GABA ; Noradrenaline ; Adrenaline ; Stress ; Rat ; Diazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. Objective: The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. Methods: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), and the gamma aminobutyric acid (GABA) content in the hippocampus and the hypothalamus were investigated in male rats which received daily, by an intragastric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 (300 or 1200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%). Six hours after the last force-feeding, the rats were subjected to 3 min ether inhalation or 30 min restraint and killed by decapitation 30 min after ether stress or at the end of restraint. Results: Baseline plasma levels of ACTH, B, NA and A were not affected by either diazepam or PC60. Both ether- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 (1200 mg/kg). Both diazepam and PC60 (1200 mg/kg) deleted restraint-induced NA and A increases. Both treatments also reduced the ether-induced rise of A. Basal levels of GABA were significantly increased in both the hippocampus and the hypothalamus in PC60-treated rats and only in the hippocampus in diazepam-treated ones. In controls, ether inhalation as well as restraint increased GABA content of these two brain structures. In contrast, such stress procedures performed in PC60-treated rats reduced GABA content slightly in the hippocampus but significantly in the hypothalamus. In diazepam-treated rats, GABA content of the hypothalamus was unaffected by stresses but that of the hippocampus was slightly decreased. Conclusions: Present data suggest diazepam-like effects of PC60 on stress responsiveness of the rat pituitary adrenal axis and the sympathoadrenal activity as well as GABA content of the hippocampus and the hypothalamus under resting and stress conditions. These effects of PC60 agree with anxiolytic properties of this nutritional supplement, previously reported in both rats and humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900338
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    The 5-HT1A receptor agonist 8-OH-DPAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT1A receptors (2000)
    Springer
    Psychopharmacology 149 (2000), S. 259-268 
    Details
    ISSN: 1432-2072
    Keywords: Key words 8-OH-DPAT ; WAY 100635 ; 5 ; 7-Dihydroxytryptamine ; Attention ; Impulsivity ; Pre- and postsynaptic 5-HT1A receptor ; Dorsal raphe ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Whilst several studies have investigated the role of serotonergic receptor subtypes in learning and memory, relatively few studies have examined their role in attentional processes. Objective: The present study investigated the role of pre- and postsynaptic 5-HT1A receptors on rats’ attentional performance in the five-choice serial reaction time task (5-CSRT). Methods: Hungry rats were trained in the 5-CSRT task to detect brief (0.5 s) flashes of light presented randomly in one of five locations with a fixed intertrial interval of 5 s paced by the rat. We studied the effects of 8-OH-DPAT, a 5-HT1A receptor agonist, at various subcutaneous (SC) doses (10–100 µg/kg) on measures of rats’ discriminative accuracy (the index of attentional functioning) and various behavioural indices of response control and motivation. Manipulations of basic task parameters, intracerebroventricular (ICV) injections of 5,7-dihydroxytryptamine (5,7-DHT) to deplete forebrain 5-HT and treatments with a selective 5-HT1A receptor antagonist WAY 100635 were made in order to determine the behavioural and neural specificity of the effects of 8-OH-DPAT. Results: A dose of 100 µg/kg, but not lower doses, significantly reduced choice accuracy and increased errors of omission, latencies to respond correctly and to collect food reward and premature responses. All these effects were completely blocked by WAY 100635, injected SC 5 min before 8-OH-DPAT at doses from 10–100 µg/kg. WAY 100635 by itself had no effect in the task. Dimming the visual stimuli to one-third of the usual brightness did not modify the effect of 8-OH-DPAT on choice accuracy. Prolonging the stimuli from 0.5 to 1.0 s reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the other effects on rats’ performance. An ICV injection of 150 µg 5,7-DHT, which depleted forebrain serotonin by 90%, reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the effects on errors of omission and latency to make correct responses. Similar effects were found by infusing 1.0 µg/0.5 µl WAY 100635 in the dorsal raphe 5 min before 8-OH-DPAT. 8-OH-DPAT increased the latency to collect the reinforcement; this effect was attenuated by ICV 5,7-DHT and completely antagonized by WAY 100635 in the dorsal raphe. Rats treated with 5,7-DHT or 8-OH-DPAT showed more premature responses and these effects were markedly reduced by the combined treatment. Conclusions: The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of postsynaptic 5-HT1A receptors.
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    URL: http://dx.doi.org/10.1007/s002139900368
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    Glomus claroideum forms an arbuscular mycorrhiza-like symbiosis with the hornwort Anthoceros punctatus (2000)
    Springer
    Mycorrhiza 10 (2000), S. 15-21 
    Details
    ISSN: 1432-1890
    Keywords: Anthoceros punctatus ; Arbuscular mycorrhiza ; Bryophytes ; Glomus ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Glomus claroideum (Schenck & Smith emend. Walker & Vestberg) were investigated for ability to form arbuscular mycorrhiza-like symbioses with the hornwort Anthoceros punctatus (L.). Spores were transferred to a cellulose acetate filter on water agar and a small portion of an Anthoceros thallus was placed directly upon the spores. Light-microscope observations 20 days after inoculation revealed branched hyphae growing within the thallus. After 45 days, arbuscules and vesicles were studied by light- and electron-microscopy. After 60 days in water agar culture, the colonised Anthoceros thalli were transferred to a low-nutrient medium agar. Hyphae spread in the agar and newly formed spores were observed 5 weeks after the transfer. After 4 months, about 1000 spores were formed in each Petri dish. This is the first report of an experimentally established arbuscular mycorrhiza-like symbiosis between an identified fungus belonging to the Glomales and a bryophyte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005720050282
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    Chronic effects of streptozotocin-induced diabetes on the ultrastructure of rat ventricular and papillary muscle (2000)
    Springer
    Acta diabetologica 37 (2000), S. 119-124 
    Details
    ISSN: 1432-5233
    Keywords: Key words Streptozotocin ; Diabetes ; Ventricular myocyte ; Cardiac muscle ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Contractile dysfunctions have been demonstrated in different experimental models of diabetes which have similar characteristics to many of the abnormalities found in the clinical setting. Administration of streptozotocin (STZ) to young adult rats induces β-cell necrosis of the pancreas which gives rise to hypoinsulinaemia and hyperglycaemia, features which are also seen in untreated type 1 clinical diabetes. We have investigated the chronic effects of STZ-induced diabetes on contraction in rat ventricular myocytes and ultrastructure of cardiac muscle. Diabetes was induced in male Wistar rats (230–270 g) with a single injection of STZ (60 mg kg−1). At 2 and 10 months after STZ treatment, the amplitude of contraction was larger in diabetic compared to control myocytes. Time to peak contraction was significantly longer at 2 months but appeared to normalise at 10 months after STZ treatment. In contrast, time to half relaxation of contraction was not significantly different after 2 months but was significantly reduced at 10 months after STZ treatment compared to control. Transmission electron microscope examination of cardiac muscle showed that the ultrastructure of cardiac muscle, especially structures associated with contraction, were not greatly altered after STZ treatment. Sarcomere lengths were not significantly different in papillary or ventricular muscle at 4 or 8 months after STZ treatment compared to control. Our data provide evidence that morphological defects in contractile myofilaments and associated structures cannot explain contractile dysfunctions seen in ventricular myocytes from STZ-treated animals.
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    URL: http://dx.doi.org/10.1007/s005920070013
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    A novel hypersensitive resistance response against potato virus A in cultivar ’Shepody’ (2000)
    Springer
    Theoretical and applied genetics 100 (2000), S. 401-408 
    Details
    ISSN: 1432-2242
    Keywords: Key words Complementary genes ; Extreme virus resistance ; Genetics ; Necrotic tubers ; Restricted virus distribution ; Solanum tuberosum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The potato cultivar ’Shepody’ is susceptible to a number of potato viruses including potato virus Y (PVY, potyvirus) but was found to possess extreme resistance to another potyvirus, potato virus A (PVA). ’Shepody’ plants were resistant to PVA infection in manual and graft inoculations. PVA replication was not detected in any of the inoculated plants by ELISA, an infectivity assay and RT-PCR. However, ’Shepody’ plants grafted with shoots containing PVA developed a novel symptomology which resembled a virus infection in appearance and in rate of translocation to the entire plant. Efforts to transmit the symptom-inducing agent manually failed. Graft-inoculation to potato virus indicator plants and PVA-susceptible potato plants showed that the symptom inducer was PVA at an extremely low concentration, detected using RT-PCR followed by Southern blot assay. Tubers from grafted but resistant ’Shepody’ plants had necrotic surfaces and internal spots. PVA was detected from necrotic areas but not from the non-necrotic ones. However, plants resulting from necrotic tubers were free from aerial leaf symptoms observed in grafted plants and produced non-necrotic normal tubers. A trace-back of the parental lineage of ’Shepody’ indicated that the resistance had been introgressed from the cultivar ’Bake King’. Analysis of progeny of a cross of resistant ’Shepody’ to the susceptible ’Goldrus’ indicated that this resistance is controlled by two independent dominant complementary genes in contrast to monogenic resistance reported for other potato viruses.
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    URL: http://dx.doi.org/10.1007/s001220050053
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    Effects of cytomegalovirus infection and prolonged cold ischemia on chronic rejection of rat renal allografts (2000)
    Springer
    Transplant international 13 (2000), S. 54-63 
    Details
    ISSN: 1432-2277
    Keywords: Key words Kidney transplantation ; Rat ; Chronic rejection ; Cytomegalovirus ; Adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that both cytomegalovirus (CMV) infection and prolonged cold ischemia of the allograft (CI) are associated with chronic rejection of renal transplants. The purpose of this study is to investigate the effect of CMV infection, of CI and of the combination of both, on the progression of chronic rejection, and to obtain a more detailed insight in their effects on the expression of adhesion molecules. Therefore, a rat transplantation model was used. Lewis recipients of renal allografts (with and without CI) from MHC-incompatible Brown Norway rats were inoculated with rat CMV or left uninfected. CMV infection alone resulted in an increased influx of CD4+ cells and macrophages early after infection, and in an increase in glomerular sclerosis and intima proliferation. CI caused an increase in infiltrating NK cells and an effect on intimal proliferation, glomerular sclerosis, and tubular atrophy. When CMV infection and CI were combined, an additive effect could be measured. This was however not the case for the function of the kidney. The creatinin showed a synergistic effect of the two influencing factors. Due to the CMV infection, an increase in CD49 d cells was detected. CI resulted in an increase in CD18 cells and an increase in the expression of CD62P on vessels, and CD54 and CD44 on tubules. When CMV infection and CI were combined, all the effects caused by CMV and CI alone were present in an additional way.¶The results of the present study suggest that special attention should be paid to the recipient of an ischemically injured graft when either the donor or the recipient is CMV-infected. The patterns seen in histology, the infiltration of leukocytes and the expression of adhesion molecules, suggest that CI and CMV infection both have an effect on rejection, but act by different mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050009
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  • 96
    Electronic Resource
    Electronic Resource
    Effect of anti-CD4 monoclonal antibody administration on rat small bowel allograft survival and circulating leukocyte populations (2000)
    Springer
    Transplant international 13 (2000), S. 211-217 
    Details
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Monoclonal antibody ; Rat ; Rejection ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effect of an anti-rat CD4 monoclonal antibody (OX38) on heterotopic small bowel allograft rejection. Fully allogeneic small bowel transplants were performed in the PVG-to-DA-rat strain combination. Animals received either i) short course (days –1, 0 and 1) of 1 mg/kg per day OX38, ii) short course of 5 mg/kg per day or iii) extended course (days –2, –1, 0, 1, 2 and twice weekly thereafter) of 1 mg/kg per day. Both the high dose (13 days) and extended low-dose (12 days) courses prolonged graft survival compared to untreated control animals (7 days). The low-dose, short-course treatment had no effect. Similar regimens were given to animals that did not receive transplants and in which peripheral blood CD4+ cell counts fell to between 20 and 55 % of pretreatment levels and 20–30 % of binding sites were blocked. In summary, anti-CD4 monoclonal antibody therapy delayed rejection of rat small bowel allografts; however, long-term survival was not achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050689
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  • 97
    Electronic Resource
    Electronic Resource
    Effect of osmotic stress on tolerance of air-drying and cryopreservation ofArabidopsis thaliana suspension cells (2000)
    Springer
    Protoplasma 214 (2000), S. 227-243 
    Details
    ISSN: 1615-6102
    Keywords: Arabidopsis thaliana ; Cryopreservation ; Dehydration ; Thermal analysis ; Sucrose ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Arabidopsis thaliana suspension cells were preserved in liquid nitrogen for over three years, using embedding of cells in calcium-alginate prior to subculture in sucrose-enriched medium, air-drying, and direct quenching in liquid nitrogen. Survival of cells reached 34%, yielding regrowth at the surface of all cryopreserved beads in less than 7 days. Following pretreatment and dehydration, the water content dropped from 2300% to 34% with respect to dry weight. Differential scanning calorimetry showed that glass transition occurred on cooling, followed by a slight crystallization event on rewarming. The survival of cells was independent of the cooling rate. The tolerance of the acute dehydration step increased progressively with sucrose pretreatment duration, indicating the requirement for adaptative cellular alterations. Ultrastructural studies revealed several changes in cells after sucrose pretreatment prolonged from 1 to 7 days: reversal of the initially plasmolyzed state, microvacuolation, numerous autophagic structures, scarcity of ribosomes, increase in number and size of starch grains. No cell division seemed to occur during this period. After air-drying and after a freeze-thaw cycle, followed by 24 h rehydration, regenerating cells had recovered a high level of ultrastructural organization and contained numerous polysomes suggesting an intense metabolic activity. Trehalose, a cryoprotective disaccharide not considered to be a metabolic substrate, yielded only 70% regrowth after freezing. Biochemical analysis showed that soluble sugars accumulated during the pretreatment, essentially sucrose or trehalose; the monosaccharide content also increased. In the light of these results, the action of sucrose in inducing freezing tolerance is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279067
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  • 98
    Electronic Resource
    Electronic Resource
    Ultrastructure and anatomy of nematode-induced syncytia in roots of susceptible and resistant sugar beet (2000)
    Springer
    Protoplasma 211 (2000), S. 39-50 
    Details
    ISSN: 1615-6102
    Keywords: Beta vulgaris ; Cyst nematodes ; Histology ; Resistance mechanism ; Syncytium ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Using susceptible and resistant sugar beet lines, comparative analyses of root histology and ultrastructure were made during invasion by nematodes and the induction and formation of specific feeding structures (syncytia).The resistant line carried the resistance geneHs1pro−1.Nematodes were able to invade and induce functional syncytia in roots of resistant and susceptible lines. However, syncytia in resistant roots were smaller and less hypertrophied. The vacuolar system of syncytia in susceptible plants contained many small vacuoles. In resistant plants vacuoles were larger but less numerous. Smooth endoplasmic reticulum prevailed in syncytial protoplasts of susceptible plants, whereas almost only rough endoplasmic reticulum occurred in syncytia in resistant plants. The most conspicuous and hitherto undescribed trait of syncytia in resistant roots was the initial appearance of loose, and later compact, aggregations of the endomembrane system which composed most of the endoplasmicreticulum system of syncytia at later stages. Syncytia in resistant plants usually degraded before the nematodes reached their adult stage. The appearance of membrane aggregations and the other resistance-specific features are discussed in relation to their possible effects on syncytium function and role in nematode resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279898
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  • 99
    Electronic Resource
    Electronic Resource
    Structural changes during early embryogenesis in wheat pollen (2000)
    Springer
    Protoplasma 211 (2000), S. 94-102 
    Details
    ISSN: 1615-6102
    Keywords: Androgenesis ; Embryogenesis ; Microspore culture ; Pollen ; Ultrastructure ; Wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have made a detailed cytological examination of the development of wheat embryoids, monitoring their initial divisions from two to ten cells by both light and electron microscopy. According to our observations the first embryogenic division is symmetrical. After the androgenesis induction treatment, there is a decrease in ribosome population with cells that have inactive nucleoli made up almost exclusively of a dense fibrillar component. This population is restored after initial embryogenic divisions. During the initial divisions the embryogenic pollen grains do not appear to change in size and the pollen wall remains intact. The exine undergoes no modification but the intine thickens, and we have observed that the thickness of the intine can be used as a cytological marker of androgenesis. The walls separating the cells obtained after embryogenic division contained numerous plasmodesmata. The beginnings of embryo polarization and cell differentiation could be made out in the very early pollen embryoids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279902
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  • 100
    Electronic Resource
    Electronic Resource
    Regional Spinal Cord Blood Flow and Energy Metabolism in Rats after Laminectomy and Acute Compression Injury (2000)
    Springer
    European journal of trauma 26 (2000), S. 122-130 
    Details
    ISSN: 1615-3146
    Keywords: Key Words Spinal cord compression ; Autoradiography ; Blood flow ; ATP ; Glucose ; Lactate ; Bioluminescence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many data are available concerning spinal cord blood flow (SCBF) and metabolism on various models and timing after spinal cord injury, however, detailed information on their exact relationship in the same injury model is lacking. This relationship is a crucial factor in the understanding of the pathophysiology of spinal cord trauma. Rats were subjected to lumbar laminectomy or lumbar spinal cord compression trauma. 3 hours later, changes in SCBF were evaluated autoradiographically and changes in ATP, glucose and lactate levels were analyzed using substrate-specific bioluminescence techniques. Measurements were performed at the lesion site (segment L4), adjacent segments (L3 and L5) and at remote thoracic segments (Th8 to Th9). Laminectomy alone did not change SCBF, both in thoracic and lumbar segments. In contrast, ATP levels were significantly reduced and lactate levels were increased at the lesion site and in adjacent lumbar segments at 3 hours after laminectomy, whereas glucose levels were not significantly changed. In animal subjected to additional compression trauma, SCBF was significantly reduced in segments L3, L4 and L5 paralleled by a significant ATP reduction and lactate increase. Glucose levels did not differ significantly from controls 3 hours after compression injury. This metabolic profile was also reflected in the remote thoracic segments. In contrast, SCBF was not reduced in thoracic segments of traumatized animals. The observation that ATP was already significantly reduced and lactate increased in laminectomized segments and in remote thoracic regions after trauma signals that metabolic changes are sensitive indicators to spinal stress. The fact that posttraumatic metabolic profile differs from the pattern of hemodynamic and metabolic changes induced by ischemia, suggests posttraumatic mediators may be involved in the different regulation of the energy producing machinery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000680050010
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