Biomedical subjects

K Vass

Publications and source records attributed to K Vass.

At least 19 recordsLinked to original sources

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↗

PubMed1991

[Inflammatory demyelinating diseases if the peripheral nervous system: immunological concepts and experimental models].

Some inflammatory diseases of the peripheral nervous system, most prominently the Guillain-Barré syndrome, are currently regarded to be of autoimmune origin. Experimental models show clearly that the balance between cellular and humoral autoimmune reaction against peripheral myelin components significantly determines the appearance of the disease. Yet, important questions, such as target antigens of the antimyelin reaction are still unresolved.

Animals↗

PubMed1991

Inflammation in the nervous system. Basic mechanisms and immunological concepts.

The basic questions in the pathogenesis of inflammation in the nervous system are how inflammatory cells reach the brain, where they recognize their antigen, how the nervous system interacts with local immune regulation in the lesion, and how inflammatory cells induce irreversible tissue damage. These questions have been addressed by studying the pathogenesis of experimental models of encephalomyelitis. The minimal requirement to start brain inflammation is the presence of activated circulating T-cells directed against a brain antigen and of antigen presenting cells in meninges and perivascular spaces of the nervous system. Such a constellation, however, only results in the disease after hypersensitization, i.e. in the presence of very high numbers of circulating autoreactive T-cells. Other local and systemic immunological factors may profoundly lower the threshold for the induction of brain inflammation. They include antigen recognition on cells in the brain parenchyma (microglia, astroglia), local upregulation of MHC antigens and possibly adhesion molecules (by cytokines or as a consequence of brain injury) and the presence of additional humoral immune responses against brain antigens (autoantibodies). Focal production of cytokines by inflammatory cells as well as by resident cells of the brain plays an important role in determining the activity of the inflammatory process and in inducing effector cells and inflammatory mediators, responsible for tissue destruction. Whereas in pure T-cell mediated auto-immune encephalomyelitis these activated effector mechanisms have low selectivity and mainly induce a "bystander" damage of CNS tissue, additional presence of autoantibodies may focus the immune reaction to specific targets, thus inducing, in high sensitivity, very selective tissue destruction. The present experimental data suggest that different immunological pathways may finally lead to quite similar inflammatory demyelinating lesions. Thus, brain lesions in individual multiple sclerosis patients may develop on a quite diverse immunological background.

Animals↗

PubMed1990

Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system.

Intrathecal injection of interferon-gamma induced a significant increase of the number of class I and class II major histocompatibility complex (MHC)-expressing cells within the rat nervous system. A progressive appearance of MHC-antigen-positive cells was found by light- and electron microscopic immune histology. The first level comprised cells that constitutively expressed MHC antigens in normal animals (meningeal and endoneural monocytes, some perivascular dendritic cells, and few parenchymal microglia cells, especially in the lumbar spinal cord and in the cerebellar white matter). The second level represented cells readily expressing MHC antigens after stimulation with interferon-gamma (all perivascular, dendritic cells, and microglia). The third level included ependymal cells, astrocytes, and Schwann cells. After stimulation with interferon-gamma, these neuroectodermal cells expressed MHC antigens inconsistently, usually in a low density and patchy distribution. The progressive appearance of MHC antigens may be reflected by the variances of lesional patterns found in experimental allergic encephalomyelitis of different histologic severity.

Animals↗

PubMed1990

Cumulative effect of repeated ischemia on brain edema in the gerbil. Biochemical and physiological correlates of repeated ischemic insults.

Using a bilateral carotid artery occlusion model in the gerbil, we evaluated the cumulative effect of repeated ischemic insults on various physiological and biochemical parameters in brain. The most striking consequence of repeated occlusions is a profound, delayed increase in brain edema between 6- and 24-hr recirculation, after a series of three 5-min occlusions carried out at 1-hr intervals. This increment in brain water is accompanied by morphological evidence of compressed capillaries with increased filling of larger vessels, consistent with impaired microcirculation even though total blood flow and total vascular volume return toward control levels. The effect on edema is most severe when occlusions are repeated during the period of postischemic hypoperfusion, although the mechanisms responsible for this effect remain to be determined. Histograms of cerebral cortical oxygen tension show a shift toward progressively lower values during the recirculation interval after each occlusion, suggesting that secondary hypoxia accompanying hypoperfusion may worsen the impact of successive ischemic intervals. Although levels of PCr and ATP indicate adequate recovery of energy metabolism between occlusions, slight elevations of brain lactate persist, consistent with continued hypoxia. Under the conditions employed in these studies, repeated occlusions give rise to progressively more prolonged deficits in brain protein synthesis activity, which may thus provide a useful index of the severity of the accumulated ischemic insult. Continued studies using this well-defined model should provide further insight into the pathophysiology of ischemic brain edema.

Animals↗

PubMed1989

Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat.

The accumulation of the stress protein HSP70 was found to be an excellent marker for prolonged seizure related metabolic activity of neurons. After kainic acid (KA) induced status epilepticus we observed HSP70 immunoreactivity in the hippocampal CA4 and CA1 sectors, the subiculum, the basolateral and the lateral nuclei of the amygdala, the mediodorsal nucleus of the thalamus, the caudal part of the striatum, the claustrum and in neurons of certain neocortical areas. HSP70-positive nerve cells appeared normal in conventional histological stains. Conversely, degenerating neurons (e.g. in the hippocampal CA3 sector) remained unlabeled.

Animals↗

PubMed1989

[ECG repolarization disorder (QT lengthening) in organophosphate poisoning].

The authors investigated in human and in experimental organophosphate intoxication the features of the toxic ECG repolarisation disturbance, the QT lengthening and its connection with cholinesterase depression. It was concluded that this pathological electrophysiological change in human intoxication does not show close correlation with the decrease of enzyme activity and cannot be influenced by atropine. The ECG alteration can be reproduced in animal experiments, it precedes the toxicologically relevant cholinesterase depression, it is pesticide dose dependent, but it cannot be induced by cholinergic or adrenergic drugs. On the basis of all this it is supposed that in organophosphate intoxication the QT lengthening reflects a direct myocardial pesticide effect and, is independent of cholinergic mediation.

Acute Disease↗

PubMed1989

Observations on cerebral ischaemia in cats at injury threshold levels.

The potential for recovery of brain tissue subjected to ischaemia at a threshold level of injury was evaluated in cats subjected to 20 min middle cerebral artery occlusion. In addition to assessment of regional cerebral blood flow and water content, the permeability of the bloodbrain barrier and morphological changes detected by light microscopy were studied at various time intervals. Our observations revealed that although a similar reduction of blood flow during arterial occlusion was found both in the caudate nucleus and the cerebral cortex, the reactive hyperaemia was consistently higher in the caudate nucleus than in the cortex. After 24 h the caudate nucleus also revealed a significantly higher water content and increased vascular permeability than the cortex. Morphological observations at 24 h in areas affected by ischaemia showed widespread, marked ischaemic neuronal injury, whereas at 3 d there was, in addition, a vigorous proliferative reaction of vascular elements. Cats sacrificed at 14 d revealed a remarkably good preservation of neurons, both in the caudate nucleus and cortex which otherwise showed a few circumscribed, small, infarcts surrounded by normal nerve cells. Our study suggests that neurons injured at threshold level have a considerable capacity for recovery. Otherwise, with a similar degree of ischaemia, the caudate nucleus appears more prone to increased vascular permeability and oedema than the cerebral cortex.

Animals↗

PubMed1988

Localization of 70-kDa stress protein induction in gerbil brain after ischemia.

Induction of the 70-kDa heat shock protein, hsp70, has been demonstrated in brain following experimental stroke. In the present study, hsp70 was localized in gerbil brain at intervals after transient ischemia using a monoclonal antibody specific for stress-inducible forms of hsp70-related proteins. Induced immunoreactivity was found only in neurons, primarily in hippocampus, striatum, entorhinal cortex and some neocortical regions. Notably hsp70 accumulation was minimal in hippocampal CA1 neurons which die after brief ischemic episodes, but was most pronounced in dentate granule cells and CA3 neurons which are spared. The peak of CA3 immunoreactivity occurred at 48-h recirculation, at the onset of CA1 neuron loss at 2-4 days, demonstrating that hsp70 induction is also a component of this delayed hippocampal pathophysiology rather than a direct response to the metabolic disruption of the initial ischemic episode. These results suggest that hsp70 immunocytochemistry may serve as a marker for neuronal circuitry involved in proposed excitotoxic mechanisms after ischemia and other stresses. Control animals showed immunoreactivity in ependymal cells lining the ventricles, indicating a role for hsp70 in normal functioning of these specialized cells.

Animals↗

PubMed1988

Microvascular disturbances and edema formation after repetitive ischemia of gerbil brain.

Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion.

Animals↗

PubMed1988

Effect of aminophylline on postischemic edema and brain damage in cats.

We attempted to ameliorate postischemic edema and brain tissue injury in cats by administering aminophylline to reduce the reactive hyperemia that supposedly aggravates both these sequelae. Forty-one cats were subjected to 1 hour of middle cerebral artery occlusion and were killed after 3 hours, 3 days, or 14 days of recirculation; one half of the cats received 0.916 ml/kg of a 25 mg/ml solution of aminophylline by infusion at a constant rate via the femoral vein starting 10 minutes before release of the occlusion and continuing for 5 minutes after initiation of recirculation; the other half received saline. Regional cerebral blood flow was monitored by the hydrogen clearance method and water content was evaluated by specific gravity measurements after 3 hours of recirculation; the status of the blood-brain barrier was assessed with Evans blue tracer. Morphologic observations were carried out in cats killed after 3 or 14 days of recirculation. Aminophylline-treated cats killed after 3 hours of recirculation showed significantly reduced hyperemia and edema and no leakage of Evans blue, which was present in all untreated cats killed after 3 hours or 3 days of recirculation. Morphologic observations revealed conspicuously more severe ischemic brain tissue damage in the untreated than in the aminophylline-treated cats after 3 and 14 days of recirculation. Our studies indicate the beneficial effect of administration of aminophylline in the amelioration of postischemic edema and brain tissue injury, which is presumably achieved by reduction of reactive hyperemia.

Aminophylline↗

PubMed1988

Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein.

In this study the authors have developed a model with which can be studied directly the influence of circulating anti-myelin antibody on the clinical and pathologic course of inflammatory T-cell-mediated experimental allergic encephalomyelitis (EAE) in the rat. EAE was induced by passive transfer of either myelin basic protein (MBP)-activated spleen cells derived from sensitized donors or long-term-cultured MBP-specific T-cell lines. At the onset of the disease, monoclonal antibodies against a myelin/oligodendrocyte glycoprotein (MOG) were injected intravenously. This antigen is exposed on the surface of central nervous system myelin and oligodendrocytes. Intravenous injection of the antibody in the course of T-cell-mediated transfer EAE augmented the severity and duration of clinical signs and resulted in the formation of large, confluent demyelinated plaques.

Animals↗

PubMed1988

Comparison of histochemical and biochemical methods in the evaluation of estrogen and progesterone receptor level in human breast cancer. A study of 118 cases.

Unselected surgical specimens from 118 cancerous breasts of female patients were studied by histochemistry for the presence of cellular estrogen (ER) and progesterone (PR) receptors. The receptor tracers used were 17 beta-estradiol-6-carboxymethyl-oxim-bovine serum albumin - fluorescein isothiocyanate and 11 alpha-hydroxyprogesterone-hemisuccinate-bovine serum albumin-tetramethylrodamine isothiocyanate conjugate (Fluoro-CepTM). Out of 118 carcinomas 77 (67%) proved to be positive in the ER and 79 (66%) in the PR test. The histochemical results were compared with the results of the biochemical assay in 70 cases. A positive correlation was found in 57 cases.

Breast Neoplasms↗