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Biomedical subjects

R Sowinski

Publications and source records attributed to R Sowinski.

At least 37 records · Page 2Linked to original sources
PubMed1980

Lesions of amygdala, pyriform cortex and other brain structures due to dipiperidinoethane intoxication.

Single doses of dipiperidinoethane (DPE) produced symmetrical necrosis in pyriform cortex, amygdala and other areas of gray matter in rats, mice and gerbils. The necrosis was detectable in 10 hours and fully developed in 24 hours. Its distribution and severity were not influenced by carotid artery ligation. DPE was not a cumulative poison. There was a high degree of chemical specificity: neurotoxic activity was present in DPE derivatives modified by methylation of the two piperidine rings, but neurotoxicity was absent in derivatives with different ring systems or different connecting chains.

Amygdala↗
PubMed1980

Enhancement of allergic encephalomyelitis by particulate adjuvants inoculated long before antigen.

Carbonyl iron and several other particulate materials have been reported to enhance the development of experimental allergic encephalomyelitis when injected with neural antigen. In the present work, silicon and silica powders have been added to the list of particulate adjuvants. In addition, several particulate materials, but not carbonyl iron, were effective adjuvants when inoculated four weeks or even six months before the neural antigen. It was necessary for adjuvant and antigen to be injected in the same region, but both intraperitoneal and subcutaneous routes were effective. The long-lasting adjuvanticity of certain particulates in the tissues is probably related to their bland and unabsorbable nature. The reasons for restrictions in the range of adjuvants and antigens that are effective in this system and the possibility of a similar occurrence in nature remain to be investigated.

Adjuvants, Immunologic↗
PubMed1980

Experimental allergic encephalomyelitis. Inhibition of clinical signs and paradoxical enhancement of lesions in second attacks.

Experimental allergic encephalomyelitis (EAE) was induced in rats by immunization with neural antigens, with or without adjuvants. A second attack was induced after an interval of 3-24 weeks. When the second attack was produced by moderately intense active immunization or by passive transfer, the rats were protected from clinical signs. Paradoxically, the second attack regularly produced more lesions in the cerebellum than in naive contols. Inhibition of clinical signs and the accompanying paradoxical enhancement of cerebellar lesions were independent of the type of antigen or adjuvant used for either attack, the severity of the attacks, and the time interval between them. Nor did non-specific adrenal-mediated stress play any role in these phenomena. Even in the absence of clinical signs, the second attack produced many lesions in the spinal cord, but these were sometimes less severe than those produced in naive controls. The observation that an initial attack of EAE had different influences on susceptibility to a second attack in different parts of the nervous system is more readily explained by local tissue factors than by systemic regulatory influences.

Adjuvants, Immunologic↗
PubMed1979

Suppression of experimental allergic encephalomyelitis by EN3638: dependence on adjuvants and treatment schedules.

Oral administration of 2, 3 or 4 doses of 100 or 250 mg/kg of EN3638 during the incubation period of experimental allergic encephalomyelitis delayed the onset and reduced the incidence and severity of clinical signs and histological lesions. Five doses of 50 or 100 mg/kg effected virtually complete and permanent suppression of clinical signs even after cessation of therapy, and five doses of 250 mg/kg eliminated histological lesions as well. Optimum results required coverage of the entire incubation period regardless of dose level. These results were obtained only when carbonyl iron was used as the adjuvant for production of EAE. When complete Freund's adjuvant was used, EN3638 delayed the onset but had little or no influence on late-developing clinical signs and histologic lesions after cessation of therapy. The permanence of suppression when carbonyl iron was used is related to the absence of an oil depot. Carbonyl iron is a superior adjuvant for drug suppression studies.

Adjuvants, Immunologic↗
PubMed1978

Lymphocytic inflammation produced by intracerebral implantation of zinc and other metals.

Sxteen pure metals were implanted as pellets of powder or as wires into the brains of rats. Al, Be, Cr, Fe, Pb, Sn, and W were relatively innocuous. Mg and Mn produced local necrosis. Bi, Cd, Co, Cu and Ni produced more severe local necrosis. Viable tissue adjacent to Co and Ni necrotic lesions had some perivascular lymphocytic infiltrates. Zn implants caused very little necrosis but adjacent areas had prominent perivascular lymphocytic cuffs. The infiltrates persisted for at least 4 weeks but disappeared as soon as the zinc was removed. Some compounds of zinc were also capable of inducing infiltrates. The perivascular infiltrates resembled the lesions of allergic encephalomyelitis, but there was no correlation between the ability of metal powders to induce lymphocytic infiltrates after intracerebral implantation and their adjuvancy after intraperitoneal injection with neural antigen.

Adjuvants, Immunologic↗
PubMed1978

Suppression of experimental allergic encephalomyelitis by 6-hydroxyphthalaldehydic acid, O-(p-chlorobenzyl)oxime (EN3638).

EN3638 is a new oxime derivative of salicylic acid that has immunosuppressive properties. Oral administration of the compound to rats during the incubation period of experimental allergic encephalomyelitis (EAE) delayed the onset of clinical signs. EN3638 was effective in both ordinary and hyperacute forms of EAE. Doses of 50, 100, or 150 mg/kg daily, 250 mg/kg three times a week, or 400 mg/kg twice a week suppressed both clinical and histologic evidence of EAE during the course of therapy (as long as 4 weeks) and for 8 or more days thereafter. Clinical EAE developed after a full incubation period after discontinuance of EN3638, probably due to the persisting depot of antigen in oil. When EAE was produced without an oily depot, a single dose suppressed the disease for at least 5 weeks in some rats. EN3638 was effective when given only in the second half of the incubation period but not when given at the time that EAE lesions and signs develop. Passive transfer experiments suggested that the drug prevented and even reversed sensitization to neural antigens. It had only slight effect on fully sensitized lymphoid cells or on the recruitment of nonimmune inflammatory cells in the nervous system, and it was not acting as a source of salicylate or as an adrenocortical stimulator.

Animals↗
PubMed1977

Suppression of the hyperacute form of experimental allergic encephalomyelitis by drugs.

Numerous drugs were tested for ability to suppress the hyperacute form of experimental allergic encephalomyelitis (EAE). This very severe disease produced clinical signs after 7-9 days which progressed rapidly to paralysis and death. Treatment during the first five days of the incubation period with cycloleucine, cyclophosphamide EN3638, 6-mercaptopurine, methotrexate and procarbazine produced important delays in onset. Corticosteroids, nonsteroidal antiinflammatory drugs, antilymphocyte serum, asparaginase, gold, cytarabine and tilorone, all previously reported to suppress ordinary EAE, had moderate, little or no effect in hyperacute EAE. Proteacted treatment was of no avail with some of these drugs, but it revealed the remarkable suppressive effect of EN3638, equal to cyclophosphamide. Hyperacute EAE was a rapid and economical screening test for immunosuppressive drugs, and a highly discriminating tool for comparison of potent agents.

Acute Disease↗
PubMed1977

Experimental allergic encephalomyelitis in the Lewis rat: farther delineation of active sites in guinea pig and bovine myelin basic proteins.

Highly encephalitogenic peptide (37-88), derived from the guinea pig myelin basic protein by peptic digestion, was treated chemically to destroy its tyrosyl and histidyl residues and enzymatically to remove its C-terminal sequence Val-His-Phe. Neither of the modifications resulted in loss of activity in Lewis rats. The enccephalitogenic region within peptide (37-88) was located by examination of derivative peptides obtained by selective proteolytic cleavage. The results showed that peptide (61-88), like peptide (43-88), was fully active at the level of 0.02 nmole whereas peptides (72-88) and (72-84) were fully active at levels of 0.5 and 2.5 nmole, respectively. In contrast, peptides (43-71) and (75-88) were completely inactive. These results demonstrated that the undecapeptide Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro (residues 72-84), although not as encephalitogenic as peptides (43-88) or (61-88), does contain the elements essential for the induction of disease. At the levels tested (10.8 and 2.2 nmole) only peptides (43-88) and (61-88) were capable of inhibiting the induciton of disease by passively transferred lymph node cells; this inhibition, however, was less than that achieved by the intact guinea pig basic protein. Further studies on the encephalitogenicity of the bovine basic protein in Lewis rats demonstrated that the active site in the C-terminal half of this protein is present in its entirety within residues 89 to 115.

Amino Acid Sequence↗
PubMed1976

Experimental allergic encephalomyelitis in aged F344 rats.

Experimental allergic encephalomyelitis (EAE) was produced in 2- to 24-mo.-old F344 rats by active immunization and by passive transfer of lymphoid cells (adoptive immunization) from young rats. With both methods, some 24-mo.-old rats had a reduced ability to develop this autoimmune disease. However, the immunological deficit was related to incidental serious diseases rather than to old age per se. The aged F344 rat is not a suitable model for comparing EAE to multiple sclerosis in man because the decreased incidence of multiple sclerosis after the age of 50 is not related to other serious illnesses.

Age Factors↗
PubMed1976

Endotoxin toxicity in rats is enhanced by tilorone.

The relatively nontoxic drug, tilorone, greatly enhanced the susceptibility of rats to lethal effects of endotoxin. The magnitude of the synergy was similar to that produced by adrenalectomy, but the effect of tilorone was not mediated by the adrenal glands. The histopathologic effects of endotoxin plus tilorone resembled those produced by much larger doses of endotoxin alone, including instances of the generalized Shwartzman reaction.

Adrenalectomy↗