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Biomedical subjects

R Sowinski

Publications and source records attributed to R Sowinski.

At least 19 recordsLinked to original sources
PubMed1985

The acquisition of encephalitogenicity after sensitized cells are conditioned with myelin basic protein or concanavalin A.

When cells from rats immunized against neural antigens are incubated with myelin basic protein or concanavalin A, their ability to transfer experimental allergic encephalomyelitis (EAE) is greatly increased. Using the rapid, localized form of EAE, we have shown that the increased encephalitogenicity of these cells was not manifest, or not fully manifest, in 1 day after passive transfer. Expression of the increased encephalitogenic potency required a period of residence in the recipient animal and this period did not depend on the duration of incubation in vitro. Conditioned cells were fully capable of eliciting the neutrophilic form of EAE, which is consistent with the notion that the recipient's mononuclear cells were not essential for the expression of the encephalitogenic potential of conditioned donor cells.

Animals↗
PubMed1985

Splenic infarcts produced in rats by vasoconstrictor drugs.

Investigation of the role of vasoconstriction in the production of infarcts would be facilitated by a model based on a non-essential and readily accessible organ. Therefore, we investigated the effects of intraperitoneal injections of vasoconstrictor drugs on spleen and liver in the rat. Phenylephrine produced infarcts of the spleen regularly and infarcts of the liver occasionally. Epinephrine was also effective in rats that had been pretreated with tilorone. The lesions were caused by local (topical) effects of the drugs. In support of this conclusion, reduced perfusion of the target areas was demonstrated in vasoconstrictor-treated rats given India ink intravenously. In addition, splenic infarcts were produced either by intraperitoneal injection or by direct application of epinephrine to the surgically exposed spleen. On the contrary, splenic infarcts were not produced by injections of epinephrine outside the peritoneal cavity, or by intraperitoneal injections if the spleen had been transposed outside of the cavity beforehand. Thus, we have produced an experimental model of splenic infarcts caused by topical application of vasoconstrictor drugs which is reminiscent of the speckled spleen (Fleckmilz) of human pathology.

Animals↗
PubMed1984

Essential fatty acid deficiency: a suggestion concerning experimental design.

In experiments on essential fatty acid deficiency, various strategems have been used to balance the deficient and control groups for all nutrients except essential fatty acids. We suggest the use of a single fat-free diet for both groups, with essential fatty acids administered parenterally to the control (nondeficient) group once each week.

Animals↗
PubMed1984

Treatment of experimental allergic encephalomyelitis with myelin basic protein: which route is best?

When myelin basic protein (BP) has been used for the treatment of multiple sclerosis (MS), it has been injected intramuscularly (IM) or subcutaneously (SC). Experimental allergic encephalomyelitis (EAE) is widely used as a model for MS, and the use of BP for MS is based on its efficacy in EAE. The present work shows that BP is more effective in EAE when administered by intravenous (IV) route than by IM or SC routes. These observations may be pertinent to therapeutic trials in MS.

Animals↗
PubMed1983

Tin salts prevent the plasma cell response to metallic tin in Lewis rats.

Inoculation of metallic tin powder produced marked proliferation of plasma cells and Russell body cells in draining lymph nodes. Prior, but not concurrent, administration of a soluble tin salt in the drinking water prevented the plasma cell hyperplasia. Various Na, Zn, Ag, and Cu salts were not inhibitory. The inhibitory effect of tin salts was detected as long as 2 months after the pretreatment was stopped. If the plasma cell response to metallic tin were due to an immunologic reaction, then the inhibition by a soluble tin salt may be a form of immunologic tolerance.

Animals↗
PubMed1983

Plasmacellular and granulomatous splenomegaly produced in rats by tin.

Two intravenous inoculations of metallic tin powder caused a striking, self-limited enlargement of the spleen up to five or six times its normal size. In addition to epithelioid cell granulomas in response to the foreign particles, the spleen contained extensive accumulations of plasmablasts, plasma cells, and plasma cells containing Russell bodies. The proliferative activity of the immature plasma cells was indicated by the high incidence of mitoses and cells labeled with tritiated thymidine. In contrast, the granulomas had no mitoses or labeling. A single intravenous injection of tin usually produced little or no reaction in the spleen despite an abundance of tin particles. Two intravenous injections or one intravenous and one intraperitoneal inoculation were much more effective. Experiments on route, interval, and dose suggested that the first dose of tin prepared the spleen in some manner while the second dose actually elicited the reaction. Pertussis vaccine or glucan could substitute for one of the tin injections. This new model is of interest for the study of plasma cell hyperplasia and also for revealing the pathogenic potential of metallic tin.

Animals↗
PubMed1983

Localization of goldthioglucose and bipiperidyl mustard lesions near artificial disruptions of the blood-brain barrier.

Administration of goldthioglucose (GTG) or bipiperidyl mustard (BPM) causes obesity and lesions in hypothalamus, medulla, and other regions of the brain. Each of these lesions is adjacent to one of the specialized circumventricular areas that differ from the remainder of the brain in their natural lack of a blood-brain barrier. In the present work, the blood-brain barrier was artificially disrupted by a large thermal injury of the cerebral cortex. In rats and mice prepared in this manner, both chemicals induced lesions in the viable brain tissue adjacent to the thermal injury. This provides strong support for the role of the blood-brain barrier in the localization of GTG and BPM lesions in hypothalamus and medulla. Localization of lesions near thermal injuries was much less with GTG than with BPM. This suggests that factors other than blood-brain barrier are also involved in the localization of GTG lesions. These findings not only help to elucidate the pathogenesis of the hypothalamic lesions, but they also open a new approach to work on the role of receptors, vasoactive substances, and other intermediaries in the mechanism of GTG damage.

Animals↗
PubMed1983

Suppression of experimental allergic encephalomyelitis by tilorone: cell transfer and interferon studies.

Tilorone is known to induce interferon and to suppress experimental allergic encephalomyelitis (EAE) produced by active immunization. In the present work, tilorone was given to donors or recipients of the passive transfer form of EAE, using a localized variety of 1 or 4 days duration and a nonlocalized form of 8 days duration. The results indicated that tilorone inhibited EAE by retarding the clonal expansion in response to antigen, by a reversible inhibition of EAE effector cells, and probably by an effect on nonspecific reactive cells in the perivascular inflammatory infiltrates. Inhibition of EAE was not mediated by the induction of interferon, but was associated with depletion of T lymphocytes.

Animals↗
PubMed1983

Inhibition of passive localized experimental allergic encephalomyelitis by interferon.

Recently it has been reported that interferon (IFN) suppresses experimental allergic encephalomyelitis (EAE) in actively immunized Lewis rats. In the present study the effect of IFN on a localized form of passively transferred EAE has been investigated. Localization and acceleration of the disease was obtained by injection of EAE lymph node cells into rats which had, 3 days previously, been prepared with a thermal brain injury. Within 24 h of cell transfer perivenular lymphocytic infiltrates (EAE lesions) were observed in the brain. Administration of IFN (40,000 U/kg) right after EAE lymph node cell injection resulted in a significant reduction or elimination of EAE lesions. The possibility that IFN is acting exclusively on the afferent arc is eliminated, and the results suggest that IFN may be acting, although not solely, through modulations of components of the efferent arc. IFN was equally effective in suppressing EAE in adrenalectomized animals. This demonstrates that the immunosuppressive effects observed in this study are not due to endogenously produced corticosteroids.

Adrenalectomy↗
PubMed1983

Depletion of lymphoid tissues by tilorone. Ultrastructure and synergistic interaction with antilymphocyte serum.

Antilymphocyte serum (ALS) caused lymphocyte depletion and shrinkage of thymus-dependent areas in spleen and lymph nodes of rats. Tilorone also depleted T lymphocytes, but light- and electron-microscopic examination revealed hyperplasia and vacuolation of the interdigitating cells that remained in the thymus-dependent areas, rather than shrinkage. These changes were not mediated by the adrenal gland. The combination of agents had a synergistic effect on the thymus-dependent areas in the spleen, lymph nodes, Peyer's patches, and bronchial-associated lymphoid tissue, all of which were severely depleted but maintained their normal dimensions. The combination of ALS and a tilorone analog that was capable of depleting lymph node but not spleen, gave a synergistic effect only in lymph node and not in spleen. Tilorone effects were transient, whereas ALS produced a long-lasting depletion. Administration of the two drugs at different times were synergistic only during the brief period of tilorone's effectiveness. The synergistic effects on T lymphocytes correlated well with immunosuppressive potency of the combined drugs on a T-lymphocyte-mediated auto-immune disease.

Animals↗
PubMed1982

Experimental allergic encephalomyelitis: simple method for producing the localized form.

In the past, the lesions of experimental allergic encephalomyelitis (EAE) have been induced to localize around brain tissue damaged by anoxia or direct physical or chemical attack. The procedure for producing the requisite antecedent brain injury has been simplified by use of a single subcutaneous injection of a neurotoxic chemical, thereby eliminating the need for surgery. The EAE lesions are concentrated in a very small area and can be obtained in one day after the passive transfer of a relatively small number of lymph node cells from immunized donors.

Animals↗
PubMed1982

Periventricular localization of a toxic encephalopathy induced by a mechanism involving choroid plexus.

An aliphatic triamine has been reported to cause lesions in rats in the vicinity of the area postrema and the median eminence of the hypothalamus, sites known to lack a blood-brain barrier. The present study revealed that some of the rats developed lesions in the cerebellum as well. The cerebellar lesions were related topographically to the choroid plexus in the underlying fourth ventricle. This periventricular distribution could be due to passage of the triamine from blood to choroid plexus and cerebrospinal fluid and then to parenchyma. In further experiments, the permeability of the plexus was increased by inducing choroid plexitis with cyclophosphamide. Subsequent administration of the triamine induced periventricular cerebellar lesions in higher incidence and at lower dose levels than in normal rats. Thus, the induction of choroid plexitis supported the aforementioned hypothesis and also suggested that it might be a useful model for periventricular localization of other types of lesions or diseases.

Animals↗
PubMed1982

Hypothalamic and medullary lesions caused by an aliphatic triamine unrelated to goldthioglucose.

A single subcutaneous injection of 3.3'-methyliminobis-(N-methylpropylamine) caused edema and necrosis in the hypothalamus and medulla oblongata of rats, mice, and gerbils. Most other aliphatic triamines were ineffective. The lesions were very similar in character and distribution to those caused by goldthioglucose or bipiperidyl mustard. When compared to closely-related analogs, the biological activity of each of these three compounds is determined by a highly specific chemical structure, yet they have no structural similarities to each other. These data cast doubt on the theory that goldthioglucose causes lesions and, eventually, obesity by binding to a hypothalamic glucoreceptor. Alternatively, the localization of brain damage in hypothalamus and medulla has been attributed to proximity to median eminence and area postrema, and to the lack of a blood-brain barrier in the latter structures. This theory is supported by our finding that artificial disruption of blood-brain barrier in the cerebral cortex induced the localization of necrosis from the triamine in that area. Furthermore, these experiments provide evidence for the role of ischemia in the development of necrotic triamine-induced lesions.

Animals↗
PubMed1982

Localization of toxic encephalopathies near lesions of experimental allergic encephalomyelitis.

Bipiperidyl mustard and a neurotoxic triamine are known to cause edematous and/or necrotizing lesions in particular areas of hypothalamus and dorsal medulla but not in spinal cord. Experimental allergic encephalomyelitis (EAR) causes widespread inflammatory lesions that are especially numerous in spinal cord. When the chemical toxicants were administered to rats during the acute phase of EAE, mortality was increased. This was due to a specific interaction between EAE and chemical toxicants leading to the development of necrotizing vasculitis and parenchymal necrosis near EAE lesions in spinal cord or brain. The interaction decreased as the EAE lesions healed. Another neurotoxic chemical, dipiperidinoethane, did not produce this phenomenon. These effects of EAE are probably related to damage to the vessel walls and the blood-brain barrier. The present work may increase the versatility of EAE as a model for multiple sclerosis if the EAE lesions can be enlarged progressively by repeated exposures to the toxicant.

Animals↗
PubMed1980

Thymolysis induced by EN3638 and other drugs and its relation to immunosuppression.

The effect on the thymus of EN3638, an oxime derivative of salicylic acid, was investigated because the drug has immunosuppressive properties. It caused a moderate reduction in thymic weight of normal adult and weanling rats and it retarded the regeneration of the thymus that follows acute corticosteroid-induced involution. These effects of EN3638 were not mediated by the adrenal nor due to the salicylate part of the molecule. At high dose levels, the drug also reduced slightly the weight of spleen and lymph nodes and the rate of body growth. Thymolytic doses of EN3638 were also immunosuppressive for experimental allergic encephalomyelitis (EAE). At doses that caused equivalent degrees of thymolysis. EN3638 was somewhat more potent for suppression of EAE than cyclophophosphamide or hydrocortisone.

Animals↗
PubMed1980

Effect of essential fatty acid deficiency on experimental allergic encephalomyelitis in rats.

Previous claims that experimental allergic encephalomyelitis (EAE) was enhanced by essential fatty acid (EFA) deficiency were reinvestigated. Deficiency was induced in Lewis rats by feeding a fat-free diet starting in late gestation, at weaning or in adult life with or without a previous period of starvation. Retardation of growth, the typical dermatitis, increased water consumption and testicular atrophy gave evidence of EFA deficiency. Control rats were fed a complete diet or a fat-free diet supplemented with corn oil. EAE was induced in EFA-deficient and control rats by conventional active sensitization with neural antigen and adjuvants or by passive transfer of living lymphoid cells from sensitized nutritionally normal donors. Contrary to previous reports, EFA deficiency did not enhance EAE in any of seven experiments, and these results were supported by histological examinations. In fact, we found inhibition of clinical signs, but not histological lesions, when EFA deficiency was moderately advanced. This was accompanied by (and probably related to) thymic atrophy, possibly due to nonspecific stress. Also we found that EFA deficiency had no effect on a non-immunological model of brain inflammation that resembles EAE in the occurrence of lymphocytic infiltrates.

Aging↗