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  • 1
    ISSN: 1432-0533
    Keywords: Olivopontocerebellar atrophy ; Oligodendroglia ; Argyrophilic inclusion ; Ubiquitin ; Leu-7
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We described cytoplasmic inclusions in glial cells in 18 patients with olivopontocerebellar atrophy (OPCA) (multiple system atrophy, MSA). These glial inclusions showed intense argyrophilia with modified Bielschowsky's and Bodian's silver impregnation techniques, and were observed in the pons, cerebellar white matter, midbrain, medulla oblongata and basal ganglia, as well as cerebral white matter and spinal cord. None of the 54 control cases had glial argyrophilic inclusions. Immunohistochemically, these inclusions were intensely labeled by anti-ubiquitin antibody. Some of them reacted with an antibody to Rosenthal fiber (RF) protein. The cytoplasm of ubiquitinated inclusion-bearing glial cells was immunostained by anti-Leu-7 antibody, but not by anti-GFAP antibody. Ultrastructurally, the glial inclusions were composed primarily of approximately 24- to 40-nm fibrils, which were coated with osmiophilic granular material along their length in longitudinal section. These fibrils appeared as annuli in cross section. Often, a central granule approximately 5 nm in diameter was seen in the lucent lumen of a cross-sectioned fibril. The granule-coated fibrils were not seen in the glial filament-containing astrocytes. Electron microscopic examination of silver-impregnated specimens revealed that the granule-coated fibrils had strong affinity for silver. Immunoelectron microscopy using the indirect immunoperoxidase techniques with antibodies to ubiquitin and RF protein revealed that the electron-dense reaction products respective to both were located on constituents of glial inclusions. Our observation that Leu-7-positive glial cells, mainly oligodendroglial cells, had argyrophilic ubiquitinated inclusions may be of significance for the evaluation of the pathology of OPCA(MSA).
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Olivopontocerbellar atrophy ; Argyrophilic inclusion ; Pontine nucleus ; Ubiquitin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Patients with olivopontocerebellar atrophy (OPCA) were studied, and cytoplasmic inclusions were observed in some of the remaining neurons of the pontine nuclei, nuclei reticularis tegmenti pontis and arcuate nuclei. The cytoplasmic argyrophilic inclusions were demonstrated by silver impregnation techniques such as Bielschowsky and Bodian staining. With hematoxylin and eosin stain, the inclusions were sharply demarcated and appeared pale. The inclusions were not stained by the following routine histological methods: Klüver-Barrera, phosphotungstic acid hematoxylin, Holzer, periodic acid-Schiff, Mallory azan, alcian blue, nile blue, Masson trichrome, Congo red, thioflavine S, oil red O and Sudan black B stains. Immunohistochemistry with anti-ubiquitin antiserum showed that these inclusions were ubiquitinated. However, the inclusions did not react with any of the following antibodies (Abs) or antisera: anti-phosphorylated neurofilament (NF) Ab, anti-nonphosphorylated NF Abs (160 and 200 kDa), anti-paired helical filament antiserum, anti-tau antiserum, anti-tubulin Abs (alpha and beta), anti-microtubule-associated proteins antiserum, anti-glial fibrillary acidic protein antiserum, anti-vimentin Ab, anti-desmin Ab, anti-cytokeratin Abs (low and high molecular weights), anti-actin antiserum, anti-skeletal myosin antiserum and anti-myelin basic protein Ab. Ultrastructurally, the inclusion bodies noted in OPCA were composed primarily of fibrils having a width ranging from about 24 to 40 nm, which were entirely coated with osmiophilic granular material along their whole length. They were occasionally intermingled with a few filaments about 10 nm in width. Electron microscopical examination on silver-impregnated specimens revealed that each granule-coated fibril had a great affinity for silver particles. In elucidating the pathogenesis of OPCA, it was considered to be an important neuropathological finding that some of the remaining pontine neurons affected by OPCA developed characteristic cytoplasmic argyrophilic inclusions.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Werdnig-Hoffmann disease ; Extraocular muscle nuclei ; Chromatolytic neuron ; Phosphory-lated neurofilament ; Ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extraocular muscle nuclei in one case of Werdnig-Hoffmann disease were examined immunocytochemically using antibodies against phosphorylated neurofilament (pNF) and ubiquitin (UBQ). The oculomotor and trochlear nuclei showed several chromatolytic ballooned neurons. All ballooned neurons contained epitopes of pNF and UBQ. pNF were present mainly in the periphery of the cell in a ring-like shape and were occasionally seen in the center of some cells. On the other hand, the structures stained by the antibody to UBQ were small vesicles or granules and most of them were aggregated in the center of the cell. These distribution patterns of pNF and UBQ may be unique in Werdnig-Hoffmann disease, since similar patterns were reported in other types of neurons of Werdnig-Hoffmann disease but were not seen in two other motor neuron diseases: classical amyotrophic lateral sclerosis, and familial amyotrophic lateral sclerosis with posterior column and spinocerebellar tract involvement.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 83 (1992), S. 420-422 
    ISSN: 1432-0533
    Keywords: Stress-response protein ; Heat-shock protein ; Brain tumors ; Breast tumor metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report concerns the expression of the low molecular weight stress-response (heat-shock) protein 27 (srp 27) in a variety of human brain tumors. Immunohistochemical techniques were used; cells of the breast cancer line MCF7 served as positive controls. The reaction product was found exclusively in the cytoplasm. Srp 27 was detected in 5/5 breast tumor metastases to the brain and in 5/21 meningiomas. The protein was also detected in 5/11 glioblastomas and 2/5 pituitary adenomas. By comparison, positive staining was observed in only 1/15 astrocytomas and 1/7 medulloblastoma and no reaction was seen with the oligodendrogliomas, schwannomas and gangliogliomas tested. These observations demonstrate that srp 27 is expressed by certain primary intracranial tumors.
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  • 5
    ISSN: 1432-0533
    Keywords: Stress-response protein 72 ; Heat-shock protein 72 ; Brain tumors ; Tumor metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive controls. The protein was detected in 14/22 meningiomas and in 6/13 glioblastomas. Tumor cells expressing srp 72 were also found in 4/17 astrocytomas, 2/9 pituitary tumors, 2/14 primitive neuroectodermal tumors and 1/10 medulloblastomas. Whereas the majority (8/10) of the breast carcinoma metastases had tumor cells that expressed srp 72, only 2/11 lung tumor metastases were positively stained. These results document srp 72 expression by a variety of primary and metastatic tumors of the CNS.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Stress-response protein 90 ; Heat-shock ; protein 90 ; Brain tumors ; Meningiomas ; Breast tumor metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This retrospective study deals with the expression of stress-response (heat-shock) protein 90 (srp 90) in a series of 148 human brain tumors. Immunohistochemical procedures were employed; cells of the human breast cancer line MCF 7 exposed to hyperosmolar stress served as positive controls. Deposits of reaction products were found in the cytoplasm and they displayed a granular pattern. srp 90 was detected in 14/31 meningiomas and 5/10 breast cancer metastases to the brain. The protein was also present in 6/13 glioblastomas and 7/18 astrocytomas. In addition, a positive reaction was found in 2/10 medulloblastomas, 2/14 primitive neuroectodermal tumors, 1/11 pituitary tumor, 2/21 schwannomas and 2/11 lung tumor metastases; however, oligodendrogliomas and primary malignant lymphomas were not stained. The srp 90 was detected in Western blots of meningioma tissue homogenates. No significant immunohistochemical reaction was seen with sections of normal human cerebra, brain stem, cerebella, pituitary glands and spinal cords. These results document the expression of srp 90 by a variety of primary and metastatic intracranial tumors.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Stress-response protein 90 ; Heat-shock protein 90 ; Brain tumors ; Meningiomas ; Breast tumor metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This retrospective study deals with the expression of stress-response (heat-shock) protein 90 (srp 90) in a series of 148 human brain tumors. Immunohistochemical procedures were employed; cells of the human breast cancer line MCF 7 exposed to hyperosmolar stress served as positive controls. Deposits of reaction products were found in the cytoplasm and they displayed a granular pattern. srp 90 was detected in 14/31 meningiomas and 5/10 breast cancer metastases to the brain. The protein was also present in 6/13 glioblastomas and 7/18 astrocytomas. In addition, a positive reaction was found in 2/10 medulloblastomas, 2/14 primitive neuroectodermal tumors, 1/11 pituitary tumor, 2/21 schwannomas and 2/11 lung tumor metastases; however, oligodendrogliomas and primary malignant lymphomas were not stained. The srp 90 was detected in Western blots of meiningioma tissue homogenates. No significant immunohistochemical reaction was seen with sections of normal human cerebra, brain stem, cerebella, pituitary glands and spinal cords. These results document the expression of srp 90 by a variety of primary and metastatic intracranial tumors.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Key words Insulin release ; intracellular calcium ; exocytosis ; GK rat ; permeabilized islets.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In spontaneously diabetic GK rats, insulin secretion from pancreatic beta cells in response to glucose is selectively impaired, probably due to deficient intracellular metabolism of glucose and impaired closure of KATP channels during glucose stimulation. By using electrically permeabilized islets of GK rats, we explored the functional modulations in exocytotic steps distal to the rise in [Ca2 + ]i in the diabetic condition. At 30 nmol/l Ca2 + (basal conditions) insulin release was similar between GK and non-diabetic control Wistar rats. In response to 3.0 μmol/l Ca2 + (maximum stimulatory conditions), insulin release was significantly augmented in permeabilized GK islets (p 〈 0.01). Raising glucose concentrations from 2.8 to 16.7 mmol/l further augmented insulin release induced by 3.0 μmol/l Ca2 + from permeabilized control islets(p 〈 0.001), but had no effect on that from permeabilized GK islets. The stimulatory effect of glucose on insulin release from permeabilized control islets was partly inhibited by 2,4-dinitrophenol, an inhibitor of mitochondrial oxidative phosphorylation (p 〈 0.01). The hyperresponse to Ca2 + in GK islets may play a physiologically compensatory role on the putative functional impairment both in [Ca2 + ]i rise and energy state in response to glucose in diabetic β cells, and may explain the relative preservation of insulin release induced by non-glucose depolarizing stimuli, such as arginine, from pancreatic islets in non-insulin-dependent diabetes mellitus. [Diabetologia (1995) 38: 772–778]
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  • 9
    ISSN: 1432-0428
    Keywords: Dihydroxyacetone ; ATP-sensitive K+ channels ; GK rat ; glycerol phosphate shuttle ; pancreatic beta cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Key words Dihydroxyacetone ; ATP-sensitive K+ channels ; GK rat ; glycerol phosphate shuttle ; pancreatic beta cell.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle. [Diabetologia (1994) 37: 1082–1087]
    Type of Medium: Electronic Resource
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