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K Vass

Publications and source records attributed to K Vass.

At least 37 records · Page 2Linked to original sources
PubMed1995

New members of the 3 beta-hydroxysteroid dehydrogenase gene family.

Several bands of hydridization are detected when southern blots of human genomic DNA are proved with cDNA of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type I. Two experimental approaches were adopted to estimate the size of the 3 beta-HSD gene family. Firstly, primer designed to amplify 3 beta-HSD type I and II genes were found on occasion to amplify DNA products of appropriate length but which were resolved as distinct sequences by denaturing gradient gel electrophoresis (DGGE). Five of these novel bands were cloned and their sequences were found to be closely related to 3 beta-HSD types I and II. Secondly, 57 genomic clones were selected from two lambda genomic libraries by hybridization with exonic probes of 3 beta -HSD type I. These were screened for novel members of the gene family by pcr amplification using various combinations of PCR primers to the type I and II genes, particularly those primers that previously amplified novel PCR products from genomic DNA. Amplification products from (lambda) clones were screened for novel sequences by DGGE. As a result of these approaches, at least five new members of the 3 beta-HSD gene family were found, one of which locates to the 3 beta -HSD type I and II gene cluster on 1p13. The existence of additional closely related but distinct members of the gene family should be recognized as a potential complication when screening PCR fragments for mutations in the type I and II genes. DGGE was found to be an exceedingly rapid means of screening amplification products from (lambda) clones to search for novel members of the gene family.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Independent mutations at codon 3500 of the apolipoprotein B gene are associated with hyperlipidemia.

The apoB arginine-to glutamine change at codon 3500 has become established as a cause of failure of binding of the LDL particle to its receptor and the consequent hypercholesterolemia of familial defective apoB 100. A search for further similar mutations was undertaken by systematic screening of a candidate region of the apoB gene from individuals with hypercholesterolemia. Polymerase chain reaction and denaturing gradient gel electrophoresis were used. We describe two families in which a different mutation in the codon 3500 causes an arginine-to-tryptophan substitution. Most adults in these families who have this mutation have hypercholesterolemia. LDL derived from all who have inherited the mutation is dysfunctional in that it allows only poor growth of an LDL cholesterol-dependent cell line. We conclude that this arginine 3500 is essential to the function of apoB and that its loss and replacement by glutamine or tryptophan is responsible for the hypercholesterolemia of familial defective apoB 100.

Adolescent↗
PubMed1995

The human 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene cluster on chromosome 1p13 contains a presumptive pseudogene; 3 beta-HSD and CYP17 do not segregate with dominantly inherited hirsutism.

Four hirsute females from a family exhibiting idiopathic dominant hirsutism were examined. Basal blood levels of delta 5 and delta 4 steroids were within the normal range, but ACTH stimulation led to increases in 17-hydroxypregnenolone and dehydroepiandrosterone that were significantly above control levels. Using polymorphic genetic markers, the genes for cytochrome P450c1717 encoded by CYP17, and the type I and II forms of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were found not to segregate with hirsutism in this family, though a base substitution was detected in the 3' end of exon 1 of the gene for 3 beta-HSD type I in three of the four patients investigated. Analysis of PCR patients amplification products by denaturing gradient gel electrophoresis (DGGE) and sequencing revealed a novel homologue of exon 3 of 3 beta-HSD. DNA of one of the affected patients was used to create a genomic library in lambda gem 11 and clones containing the novel homologue were obtained and partially sequenced. The equivalent clone was obtained from a genomic library of an unrelated normal individual. The sequences of the clones from patient and control were identical and homologous to exons 2-4 of human 3 beta-HSD types I and II. No difference was found in the PCR primer sites that flanked the exons 3 homologue which led to its detection on DGGE gels. In both clones, stop codons and deletions were identified in the exon 4 homologue, leading to the deduction that the sequence comes from a pseudogene, which we call 3 beta-HSD psi 1. The pseudogene mapped to chromosome 1p13. It was concluded that dominantly inherited idiopathic hirsutism in this rare kindred was not due to deficiencies in 3 beta-HSD types I, II, or psi or of CYP17).

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Experimental study on the kinetics of mucociliary activity in rabbit airways.

Noninvasive radioaerosol technique was applied to investigate the mucociliary activity of bronchial mucosa using 99mTc-labelled homologous erythrocytes for inhalation. Radioactivity was continuously measured for 60 min with a gamma camera connected online to the computer. Time-activity kinetic parameters were calculated by a monoexponential model. Test substance azelastine and bromhexine were used to demonstrate the validity of experimental method discussed.

Administration, Inhalation↗
PubMed1994

The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity.

In this study the effect of the anti-inflammatory drugs indomethacin, ibuprofen, ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), and BW755C (3-amino-1-(m-(trifluoromethyl-phenyl)-2-pyrazoline) on kainic acid (KA)-induced behavioral and neurochemical changes in rats was investigated. Rats injected with KA (10 mg/kg s.c.) developed seizure activity with a 20% mortality within the first 4 h and neuronal degeneration in the limbic system after 3 days. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.) augmented KA-induced epileptic activity and increased the mortality in status epilepticus to 80%. Another cyclooxygenase inhibitor, ibuprofen (20 mg/kg i.p.), and the lipoxygenase inhibitor ebselen (20 mg/kg i.p.) showed no effect on KA-induced symptoms and neurochemical changes. Application of the cyclooxygenase/lipoxygenase inhibitor BW755C (40 mg/kg i.p.) reduced the severity of seizures and protected significantly from irreversible brain lesions induced by KA. The marked reduction of glutamate decarboxylase (GAD; 53.3 +/- 12.2% of control) and choline acetyltransferase (ChAT; 60.9 +/- 9.1% of control) activities in amygdala/pyriform cortex and GAD activity in hippocampus (69.4 +/- 5.6% of control) observed 3 days after KA injection was abolished by BW755C treatment. Histopathological analyses of brain tissue showed that treatment with BW755C prevented the KA-induced nerve cell degeneration, edema, hemorrhages, and tissue necrosis in amygdala/pyriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1994

A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women's Health Study.

The present article prospectively examines the effect of change in menopause status on depression, while controlling for prior depression. This is a longitudinal follow-up of previous cross-sectional analyses reported by McKinlay, McKinlay, and Brambilla who examined the relative contribution of menopause to depression. The data derive from the Massachusetts Women's Health Study, a 5-year longitudinal study of a cohort of 2565 women aged 45 to 55 years at baseline (1981 to 1982). Results show that prior depression is the variable most predictive of subsequent depression, as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. Onset of natural menopause was not associated with increased risk of depression. Experiencing a long perimenopausal period (at least 27 months), however, was associated with increased risk of depression. The association between a long perimenopause and depression appeared to be explained by increased menopausal symptoms rather than by the menopause status itself. The observed increase in depression during a lengthy perimenopause appears to be transitory.

Climacteric↗
PubMed1993

Naturally occurring deuterium is essential for the normal growth rate of cells.

The role of naturally occurring D in living organisms has been examined by using deuterium-depleted water (30-40 ppm D) instead of water containing the natural abundance of D (150 ppm). The deuterium-depleted water significantly decreased the growth rate of the L929 fibroblast cell line, and also inhibited the tumor growth in xenotransplanted mice. Eighty days after transplantation in 10 (59%) out of 17 tumorous mice the tumor, after having grown, regressed and then disappeared. We suggest that the naturally occurring D has a central role in signal transduction involved in cell cycle regulation.

Adenocarcinoma↗
PubMed1993

Bone marrow derived elements and resident microglia in brain inflammation.

Infection of the central nervous (CNS) system by the human immunodeficiency virus (HIV) depends on the migration of infected hematogenous cells into the brain. We thus used quantitative light and electron microscopic immunocytochemistry to study the homing and turnover of bone marrow derived cells in the CNS in radiation bone marrow chimeras under normal conditions and in experimental autoimmune encephalomyelitis (EAE) as an experimental model of brain inflammation. Our studies suggest the following conclusions. First, the central nervous system is continuously patrolled by a small number of T-lymphocytes and monocytes. Meningeal and perivascular monocytes are slowly replaced by hematogenous cells under normal conditions, and this turnover is accelerated in the course of inflammation. In contrast, resident microglia represent a very stable cell pool, which in adult animals is only exceptionally replaced by hematogenous cells, even after recovery from severe brain inflammation. Second, although in bone-marrow-chimeric animals resident microglia, astrocytes, and ependymal cells are not able to present antigen to Lewis T-lymphocytes, the inflammatory reaction in EAE is qualitatively and quantitatively similar in these animals compared to fully histocompatible Lewis rats. Finally, resident microglia express the macrophage activation antigen ED1. Thus, microglia cells appear to function as effector cells in EAE lesions.

Animals↗
PubMed1993

Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis.

Recent advances in fast magnetic resonance imaging (MRI) techniques have allowed quantification of parameters such as T1 relaxation time, which can be modified by changes in the water content of a tissue. We have used this new method to study the evolution of blood-brain barrier (BBB) changes after adoptive transfer of MBP-specific (AT-EAE) and ovalbumin-specific T cell lines in Lewis rats. Measurable changes in T1 relaxation time suggesting widespread increase in BBB permeability were found, starting on day 3 post inoculation (p.i.), in the midbrain and brainstem of AT-EAE rats. In addition, we noted a significant decrease in T1 relaxation time before injection of a paramagnetic agent, in the cisternal cerebrospinal fluid (CSF) of diseased animals, starting on day 5 p.i. In vitro measurement of T1 in CSF containing various concentrations of albumin, IgM and glucose showed that, at physiological concentrations, a T1 decrease is mainly associated with an increase in albumin concentration. A moderate increase in BBB and blood-CSF barrier permeability was found as early as 4-8 h p.i., in rats injected with MBP-specific as in animals injected with ovalbumin-specific T cell lines, suggesting a non-specific mechanism. Experimental MRI may become a powerful tool to sequentially analyse changes in barrier dynamics, for example following pharmacological intervention.

Animals↗
PubMed1993

[Guidelines for drug treatment of multiple sclerosis].

Strategies proposed for the treatment of multiple sclerosis are numerous and sometimes contradictory. This review summarizes the most recent studies on the treatment of multiple sclerosis. Possibilities of influencing progression of the disease and the degree of disability suffered by patients are discussed. The treatment of acute relapses with high-dose intravenous glucocorticoids is now widely accepted because it has been shown that the duration of the relapse is reduced. Interval therapy between relapses and treatment of the chronic progressive variant of multiple sclerosis are still under debate. Immunosuppression, in particular with azathioprine, appears to have a positive effect on the long-term outcome. Whether other regimens, e.g., treatment with recombinant lymphokines, have a therapeutic effect, is difficult to assess at present since these substances have either never been tested in controlled double blind studies or the results of these studies are not yet available.

Antineoplastic Agents↗
PubMed1993

Bone marrow-derived elements in the peripheral nervous system. An immunohistochemical and ultrastructural investigation in chimeric rats.

BACKGROUND: Currently available studies on the peripheral nervous system (PNS) give little information on the presence, distribution, turnover and function of bone marrow-derived cells such as monocytes, macrophages, and dendritic cells. To address such issues, the present investigation of PNS tissues from bone marrow transplanted chimeras was performed. EXPERIMENTAL DESIGN: Inbred DA rats were lethally irradiated and transplanted with (Lewis x DA)F1 bone marrow carrying the non-DA major histocompatibility antigens from Lewis rats. The anti-RT-1A antibody (anti-Lewis MHC class I), I1-69, and the macrophage markers, Ed2 and Ox42 were used to visualize immunohistochemically donor bone marrow-derived cells and resident macrophages of sensory and autonomic ganglia as well as in peripheral nerves. RESULTS: In the ganglia, up to 80% and within peripheral nerves, up to 60% of macrophages were replaced by donor cells within 3 months of established chimerism. Ultrastructurally these cells were located: (a) between the perineurial sheaths, (b) in a perivascular position, or (c) freely dispersed within the endoneurium but outside the basal lamina of Schwann cells and ganglion cells. On the rare occasions where myelin and axonal pathology was noted, or during central chromatolysis of ganglion cells, donor marrow-derived cells became positioned under the basal lamina and incorporated tissue debris. CONCLUSIONS: These data suggest a rapid and significant turnover of bone marrow-derived cells within the PNS. Our observations are relevant to the understanding of the pathogenesis of reactive, immunologic, and HIV-associated processes within the PNS.

Animals↗
PubMed1992

Interferon-gamma potentiates antibody-mediated demyelination in vivo.

The pathogenetic events leading to demyelination in experimental allergic encephalomyelitis and in human multiple sclerosis are still unclear. The involvement of anti-myelin antibodies and activated macrophages as effector cells has been postulated. We investigated the synergistic action of the monoclonal antibody 8-18C5 against myelin/oligodendrocyte glycoprotein and recombinant interferon-gamma on demyelination after simultaneous injection into the subarachnoid space of Sprague-Dawley rats. After combined injection of anti-myelin/oligodendrocyte glycoprotein antibody and interferon-gamma, electrophysiological and morphological evidence for demyelination was found. Cervical somatosensory evoked potentials and cervical short-latency somatosensory evoked potentials were significantly delayed, and the demyelinated area in the spinal cord was significantly enlarged when compared to control rats injected with either compound alone. Injection of either an irrelevant antibody and interferon-gamma or of peritoneal macrophages without anti-myelin/oligodendrocyte glycoprotein antibody and interferon-gamma did not induce demyelination. Our data suggest that the deleterious effect of interferon-gamma on multiple sclerosis may be not only due to its effect on antigen presentation but also due to potentiation of demyelination.

Animals↗
PubMed1992

Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic necrotizing encephalopathy and Foix-Alajouanine disease.

A previously healthy 58-year-old man developed neurological illness with progressive dementia, hallucinations, central motor and vegetative impairment which led to death in 14 weeks. Autopsy revealed lesions in a symmetrical centrencephalic distribution. Inner cerebral veins and arteries were surrounded by extravasation of plasma and perivascular haemorrhage and were thickened by fibrous scarring and muscle fibre proliferation. Necrotized blood vessels were also found. The parenchyma was damaged by incomplete to complete necrosis. The age and sex of the patient, the progressive clinical course, the increase of cerebrospinal fluid protein, and the histopathology of the lesion show some similarities to angiodysgenetic necrotizing encephalopathy and spinal Foix-Alajouanine disease.

Angiodysplasia↗
PubMed1992

Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras.

This report defines the bone marrow-derived elements found in the central nervous system of adult rat radiation chimeras. Four cell types were identified which bore the major histocompatibility (MHC) class I molecules of the donor rat strain thereby indicating a marrow origin. They were: meningeal macrophages, perivascular "microglial" cells, lymphocytes and rare cells with parenchymal microglial morphology. These cells were examined by immunohistochemical methods at the light microscopic and ultrastructural levels. Extended descriptions of the perivascular marrow-derived elements and the parenchymal microglial cells are presented. These latter two cell types, which exist in humans, have a significant role in neuroimmune processes and most probably function as the antigen-presenting cells in the central nervous system of mammals.

Animals↗
PubMed1991

Microglial cells are a component of the perivascular glia limitans.

The ultrastructural relation between microglial cells and cerebral blood vessels was studied in rat brains by immune electron microscopy using antibodies against the common leukocyte antigen (Ox1), the complement receptor 3 (Ox42), and against class I and class II histocompatibility antigens (MHC antigens; Ox3, Ox6, Ox18, and I1-69). Microglial cell processes were found incorporated between the astrocytic foot processes of the glia limitans in 4-13% of cerebral microvessels. After intravenous injection of gamma-interferon, either alone or in combination with tumor necrosis factor, these microglial cell processes expressed classes I and II MHC antigens. Studies in (Lewis X DA)F1-DA bone marrow chimeras demonstrated that these cell processes belonged to resident microglia. This study suggests that microglial cells may play an important role in antigen recognition at the blood-brain barrier.

Animals↗
PubMed1991

The effect of widowhood on health: a prospective analysis from the Massachusetts Women's Health Study.

Previous research has consistently demonstrated adverse physical and psychological effects following the death of a spouse. Conclusions regarding the effects of widowhood have been hampered, however, by such methodological limitations as lack of adequate comparison groups, non-random samples of the widowed, and lack of data on pre-widowhood status. This paper examined the physical and psychological effects of widowhood in a randomly sampled cohort of women, aged 45-55 years at baseline, who were followed prospectively for five years. Analyses employed a design in which women whose spouses died during the course of the study (N = 76) were compared to age-matched married controls (N = 1625). The following two questions were addressed: (1) What are the physical and psychological effects of widowhood? and (2) What is the effect of widowhood on socioeconomic factors, social support and health behavior? Following the death of a spouse, the percentage of widows reporting psychological symptoms increased. The widows did not report higher rates of physical symptoms or a decrease in health. Widows had higher rates of health care utilization, in particular, taking prescribed medication, which were in part for mental health reasons. There was no evidence of changes in health behaviors among the widows, but social support increased following widowhood and more widows reported a decrease in income. The results highlight the importance of controlling for pre-widowhood status when studying the consequences of widowhood and provide additional evidence that widowhood may not adversely affect physical health for women.

Female↗
PubMed1991

Expression of adhesion molecules and histocompatibility antigens at the blood-brain barrier.

The migration of inflammatory cells through the blood-brain barrier in health and disease involves complex interactions between hematogenous cells, endothelial cells, the basement membrane and the perivascular glia limitans. Recent evidence is presented, suggesting that part of these interactions involve antigen independent mechanisms, mediated by cellular adhesion molecules. The accessibility of endothelial adhesion molecules in the intact blood-brain barrier is lower compared to vessels in other organs. This may account for the low traffic of hematogenous cells through the normal blood-brain barrier. However, in inflammatory conditions the expression of endothelial adhesion molecules is upregulated, which may lead to recruitment of inflammatory cells into the lesions. Antigen specific activation of T-cells at the blood-brain barrier apparently takes place mainly at perivascular monocytes and microglia cells. In severe inflammatory lesions, however, astrocytes may be additionally involved in antigen presentation.

Animals↗