Search PubMed⌕ Search

Biomedical subjects

E Sorkin

Publications and source records attributed to E Sorkin.

16 recordsLinked to original sources
PubMed1979

Role of prethymic cells in acquisition of self-tolerance.

The sequential character of T-lymphocyte development as it pertains to the stage at which self-tolerance is acquired was investigated. Three phases were studied, defined here as prethymic, intrathymic, and postthymic as determined by the timing of thymus implantation. The model utilized was the temporal pattern of skin graft rejection in thymusless BALB/c nude mice implanted with allogeneic, C57BL/6J, or syngeneic thymuses before or after skin grafting; in some instances, F(1) hybrid spleen cells were also given to newborns or young adults. These experiments in nude mice showed that, (a) self-tolerance could be established despite the absence of the host's own haplotype in the implanted thymus; (b) recently emigrated postthymic cells could already discriminate self from non-self; (c) specific neonatal tolerance could be induced in nudes by inoculation of F(1) hybrid cells; (d) nudes showed a higher capacity for induction of neonatal tolerance than did normal littermates. These findings indicate that the process of self-tolerance in the T cell's lineage begins during the prethymic state early in ontogeny.

Animals↗
PubMed1979

Cancer progression and monocyte inflammatory dysfunction: relationship to tumour excision and metastasis.

In a longitudinal study performed before and after surgical resection of a chemically-induced, transplanted rat tumour we found that a monocytosis- and tumour-induced anti-inflammatory effect directed against macrophages was promptly corrected by tumour excision but recurred with metastasis. These observations indicate that the monocyte abnormalities are acquired and related to cancer progression. The anti-inflammatory effect required relatively large primary or metastatic tumour burdens. Our findings support the clinical impression that monocyte abnormalities are associated with a poor prognosis.

Animals↗
PubMed1979

Anti-inflammatory consequences of transplanted tumors.

Rats and mice bearing transplanted chemically induced neoplasms have defective macrophage infiltration of inflammatory sites distant to the tumor. The defect limits concurrently accumulation of macrophages within the tumor, raising dramatically the tumor to macrophage cell ratio. The defect may not compromise host surveillance because it requires relatively large numbers of tumor cells. The abnormality does not appear to result from circulating monocyte depletion, defective monocyte chemotaxis, or the traffic of monocytes into the tumor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Anti-inflammatory effect of spontaneous lymphoma in SJL/J mice.

Histiocytic lymphomas develop spontaneously in about 80% of SJL/J mice between the ages of 8 and 14 months. These animals were used for the determination of whether spontaneously arising cancers compromise monocyte function similar to the monocyte defects described during growth of transplanted tumors. SJL/J mice with tumors accumulated significantly fewer macrophages than did age-matched animals without tumors either on sc implanted filters or in peritoneal exudates induced by phytohemagglutinin. There was no corresponding defect in polymorphonuclear neutrophil responses. Whereas no apparent correlation existed between tumor size and degree of inhibition, animals without demonstrable tumors had no inflammatory defects. Aging did not alter the inflammatory response to implanted filters but increased both the resident peritoneal macrophage population and the total macrophage yield to phytohemagglutinin provocation. When given transplants of histiocytic lymphomas, young SJL/J mice developed similar inflammatory defects. This study represents the first demonstration that spontaneous tumors, in addition to transplanted tumors, produce abnormalities in monocyte inflammatory responses.

Animals↗
PubMed1979

Antigenic competition between horse and sheep red blood cells as a hormone-dependent phenomenon.

Various mechanisms for understanding antigenic competition have been proposed, such as macrophage availability, suppressor cells and their soluble products. In view of the regulatory function of some hormones on the immune system, the role of immunosuppressive adrenal corticosteroids in antigenic competition was investigated. When horse red blood cells (HRBC) were injected into rats a five-fold increase in corticosterone blood levels was measured by day 6 and a strong decrease was noted on day 11. In animals injected with HRBC and on day 6 with a second antigen (sheep red blood cells, SRBC), the corticosteroid level was high on day 11. Such high levels are immunosuppressive. To impede such increases in adrenal hormone levels, rats were adrenalectomized. Adrenalectomized or sham-operated animals receiving SRBC only showed no difference in plaque-forming cell (PFC) numbers. All sham-operated rats injected first with HRBC and 5 days later with SRBC showed the expected antigenic competition. Adrenalectomized rats also injected with both antigens sequentially had a five fold increase in number of PFC when compared with the sham-operated controls which had received both antigens. A detailed analysis of these data revealed that a proportion of adrenalectomized animals had PFC numbers within the normal range. In vitro, hydrocortisone enhances the response of spleen cells when only one antigen (SRBC) is present. Prior addition of the unrelated antigen (HRBC) impedes this enhancement. Thus, in a hydrocortisone-enriched culture medium, the presence of the first antigen can interfere with the immune response to the second unrelated antigen, mimicking in vitro a condition of antigenic competition. These findings indicate that hormones may have a role in antigenic competition.

Adrenal Cortex Hormones↗
PubMed1977

Hypothalamic changes during the immune response.

The immune system is subject to an array of identified autoregulatory processes, but immunoregulation may also have a further basis in a network of immune-neuroendocrine interactions. Two antigens each produced an increase of more than 100% in electrical activity of individual neurones in the ventromedial but not in the anterior nucleus of the rat hypothalamus. Animals that failed to respond to antigen manifested no increase in the firing rate. These findings constitute the first evidence for a flow of information from the activated immune system to the hypothalamus, suggesting that the brain is involved in the immune response.

Action Potentials↗
PubMed1977

Hormonal control of neutrophil chemotactic activity in the rat vagina.

A sexual-hormone-dependent neutrophil chemotactic factor(s), operative under physiological conditions, is described. Rat vaginal washouts were shown to be both chemotactic and chemokinetic for rat neutrophils in vitro, whereas macrophages were not attracted. Peak activity was observed at the end of estrus and preceded maximal neutrophil infiltration in the vagina. In order to mimic these events, gonadectomized animals were treated with estradiol for a week. They showed a similar peak of chemotactic activity 30-36 h after estradiol withdrawal, accompanied by a massive neutrophil accumulation. These data suggest that a decrease in estradiol level permits the expression of the chemotactic signal. There was no evidence for chemotaxis and/or migration inhibitors before and during estrus or during long-term estradiol treatment of gonadectomized rats. Induced neutrophil accumulation in the peritoneal cavity and chemotactic responsiveness of these cells in vitro were similar in all stages during the estrus cycle. Estradiol, progesterone, testosterone, and hydrocortisone neither promoted nor significantly inhibited the neutrophil migratory behavior over a wide range of concentrations. Our experiments suggest that the periodic neutrophil accumulation in the rat vagina after estrus is triggered by locally expressed chemotactic mechanisms that are controlled by sexual hormones. The data provide the first evidence that hormonal changes can control chemotactic factors and thus indirectly control cell migration.

Animals↗
PubMed1977

Inhibition of macrophage chemotaxis by neoplastic and other rapidly proliferating cells in vitro.

Culture supernatants from rapidly proliferating cell lines inhibit macrophage chemotaxis. Of the cell lines tested, the supernatant from polyoma virus-induced tumor cells was the strongest inhibitor, although supernatants from simian virus 40-transformed 3T3, dimethylbenzanthracene-induced tumor cells, and Chinease hamster ovary fibroblasts also possessed inhibitory activity. The inhibitory substance(s) bound onto the macrophage cell surface. Although none of the culture supernatants examined were chemotactic for rat macrophages, they did possess weak attractive activity for polymorphonuclear neutrophils. This capacity of rapidly growing cells in culture to generate substances inhibitory to macrophage chemotaxis while attracting polymorphonuclear neutrophils may be relevant to the mechanism by which tumor bearing in vivo produces a cell-specific defect in chronic but not acute inflammation.

Animals↗
PubMed1977

Network of immune-neuroendocrine interactions.

In order to bring the self-regulated immune system into conformity with other body systems its functioning within the context of an immune-neuroendocrine network is proposed. This hypothesis is based on the existence of afferent--efferent pathways between immune and neuroendocrine structures. Major endocrine responses occur as a consequence of antigenic stimulation and changes in the electrical activity of the hypothalamus also take place; both of these alterations are temporally related to the immune response itself. This endocrine response has meaningful implications for immunoregulation and for immunospecificity. During ontogeny, there is also evidence for the operations of a complex network between the endocrine and immune system, a bidirectional interrelationship that may well affect each developmental stage of both functions. As sequels the functioning of the immune system and the outcome of this interrelation could be decisive in lymphoid cell homeostasis, self-tolerance, and could also have significant implications for pathology.

Animals↗
PubMed1976

Cell-specific defect in monocyte function during tumor growth.

Inbred DA rats bearing a syngeneic 7,12-dimethylbenz[a]anthracene-induced neoplasm had an early impairment of chronic inflammation as measured by the numbers of monocytes elicited in a 3-day peritoneal exudative response to a sterile peptone injection. Furthermore, an advanced malignant tumor was associated with a complete block in the rats' capacity to mobilize monocytes, despite the fact that white blood cell counts on peripheral blood showed increased numbers of monocytes and polymorphonuclear leukocytes (PMN) during tumor growth. In contrast to the defect in chronic inflammation, a normal or increased acute inflammatory reponse was observed during tumor growth as measured by the 9-hour peritoneal PMN response to a sodium caseinate injection. Quantitative chemotaxis measurements in vitro made with these same peritoneal exudate cells revealed severe impairment of marcophage chemotaxis but normal migration of PMN. Generation of macrophage chemotactic signals from blood of rats with advanced tumors was not impaired. Since the resident cells of the peritoneal cavity were, chemotactically, a poor-responding population, this defective response in vitro appeared to correlate with the cell defect observed in vivo in the monocyte inflammatory response to peptone.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Changes in blood hormone levels during the immune response.

Injection of three different antigens into rats or mice led in the course of several days to about a threefold increase in serum corticosterone levels and concommitantly to a decrease in thyroxine (rats). In view of the known immuno-suppressive effect of the glucocorticoids the possibility is considered that the endocrine changes induced during the immune response could significantly modulate the subsequent character of the immune response, e.i. magnitude, duration and lymphoid cell proliferation, however, a more complete pattern of hormonal variations and their cause needs to be established. These findings while admittedly preliminary, suffice to provide an indication of a temporal pattern of hormonal change during the immune response which could be important in immunoregulation.

Animals↗
PubMed1975

Relation of lymphoid system and hormones to aging.

Congenital deficiencies of developmental hormones, such as growth hormone and thyroxine, are responsible for the thymus-dependent immunodeficiency disease observed in dwarf mice. Such an immunodeficiency state is associated with early aging phenomena. This fact suggests that lymphoid cells and primarily T-derived cells are involved in the control of aging processes.

Adrenal Glands↗