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Biomedical subjects

J R David

Publications and source records attributed to J R David.

At least 199 records · Page 11Linked to original sources
PubMed1979

Abrogation of type II collagen-induced arthritis in rats by psychological stress.

This study shows that psychological stress, produced either by exposure to a predator or by movement and handling, can profoundly suppress the clinical and histologic manifestations of collagen-induced arthritis. In addition, stress can dissociate the development of humoral and cellular sensitivity to collagen from the occurrence of arthritis. Thus stress modalities provide a means of acquiring additional insights into the pathogenesis of collagen-induced arthritis in rats. Such studies may lead to a further understanding of the relationship between emotional states and the functioning of the immunologic system. This study further illustrates the need to identify and control for the effects of stress in animal studies of immunopathology. Finally, the therapeutic implications of this study for autoimmune diseases would appear self-evident (Fig. 7).

Animals↗
PubMed1978

Alteration of some functional and metabolic characteristics of resident mouse peritoneal macrophages by lymphocyte mediators.

Resident mouse peritoneal macrophages were incubated in Sephadex G-100 fractions of supernates from concanavalin A-stimulated lymphocytes. A significant effect of the lymphocyte supernatant fractions containing mediators on macrophage 5'-nucleotidase, glucose-1 14C oxidation, cell maintenance, and migration is reported. The 5'-nucleotidase was depressed to an extent similar to that seen in activated macrophages obtained from Listeria-infected mice. On the other hand, glucose-1-14C oxidation was enhanced, but not to the same degree as seen in the counterparts in vivo. Whereas migration inhibitory factor (MIF) and cell adherence-augmenting activity were found in a number of adjacent fractions, the metabolic effects were found predominantly in a single fraction. Resident peritoneal macrophages or those elicited by the injection of a lymphocyte-derived chemotactic factor were more responsive with respect to the biochemical changes than caseinate-elicited macrophages. On the other hand, caseinate-elicited macrophages appeared to be more sensitive with respect to the effects of mediator(s) on cell retention. A possible dissociation between MIF and cell-adherence augmenting activity, on the one hand, and the entities that stimulate glucose-1-14C oxidation is reported, based on fractionation studies, and loss of the latter activity upon storage of lymphocyte supernates.

Animals↗
PubMed1978

Cellular sensitivity to collagen in rheumatoid arthritis.

We examined patients with rheumatoid arthritis for cellular sansitivity to native human Types I, II and III collagens. Mononuclear cells from 50 patients with rheumatoid arthritis, 21 with other inflammatory arthritides, 20 with osteoarthritis and 20 normal subjects were evaluated for the in vitro production of leukocyte inhibitory factor in response to collagen and a control antigen, streptokinase-streptodornase. By this assay, cells from 37 (74 per cent) and 39 (78 per cent) of the patients with rheumatoid arthritis responded to Types II and III collagens, respectively. In contrast, cells from the 41 patients with other kinds of arthritis and the normal group did not produce this lymphokine to collagens. There was no response to Type I collagen or to denatured alpha chains of these collagens. All four groups responded equivalently to streptokinase-streptodornase. These data demonstrate that most patients with rheumatoid arthritis exhibit cellular sensitivity to Types II and III collagens.

Adult↗
PubMed1978

Interdisciplinary treatment of male sexual dysfunction in a military health care setting.

An interdisciplinary approach to the rapid treatment of male sexual dysfunction is presented. Clinical results for 36 sexually dysfunctional men, ages 20 to 61 are stated. Increased communication between physicians and sex therapists results in improved patient care and increased satisfaction for staff and patients. Interdepartmental cooperation within a health care setting maximizes effective use of personnel and knowledge resources.

Adult↗
PubMed1978

Humoral and cellular sensitivity to collagen in type II collagen-induced arthritis in rats.

We have recently described a new animal model of arthritis induced by intradermal injection of a distinct type of collagen found in cartilage (type II collagen). Since immunologic sensitivity to collagen could play a role in the pathogenesis of this type II collagen-induced arthritis in rats, the ability of purified types of native collagens to induce cellular and humoral responses was quantified by antigeninduced tritiated thymidine incorporation into lymphocytes by collagen and passive hemagglutination, respectively. Rats injected intradermally with native heterologous or homologous type II collagens in adjuvant developed type-specific cellular as well as humoral reactivity. Types I and III collagens were less immunogenic than was type II. The latter collagen induced brisk cellular and humoral responses that were equivalent whether complete Freund's adjuvant or incomplete Freund's adjuvant were employed. Both responses could be induced by native type II collagens modified by limited pepsin digestion, indicating that they are not attributable to determinants in the telopeptide regions of the molecule. Thus, these studies demonstrate the unique immunogenic as well as arthritogenic properties of the type II collagen molecule and indicate that both result from a helical conformation of its structurally distinct alpha-chains. Further, they suggest that type II collagen may, by humoral or cellular mechanisms, provoke or perpetuate inflammation in other arthritic diseases.

Animals↗
PubMed1978

Passive transfer by cells of type II collagen-induced arthritis in rats.

To investigate the role of immunologic hypersensitivity to collagen in the causation of type II collagen-induced arthritis in rats, passive transfer experiments were performed. Wistar/Lewis rats used in these experiments were demonstrated to be histocompatible by prolonged skin graft survival and mixed lymphocyte cultures. Popliteal lymph node weight assays excluded a potential for graft-vs.-host reactivity in this strain. 9 of 32 naive rats developed arthritis after intravenous receipt of pooled spleen and lymph node cells from donors that had been injected intradermally with type II collagen emulsified in incomplete Freund's adjuvant. This passively transferred synovitis was evident clinically as well as histologically. In control cell transfer experiments involving a total of 97 recipients, transfer of arthritis was shown to require viable cells sensitized to type II collagen. These controls included 17 rats receiving cells from unimmunized donors, 20 recipients of cells from donors injected with incomplete Freund's adjuvant alone, and 24 recipients of cells from rats injected with type I collagen in adjuvant. Deliberate addition of solubilized type II collagen to unsensitized cells at the time of transfer or injection of heat-killed sensitized cells also did not cause arthritis in a total of 36 recipients. These latter two control groups indicate that disease transfer was not the result of antigen carry-over. Intravenous injection of sera from arthritic donors was incapable of passively transferring clinical or histologic synovitis in 30 recipients. Thus, these studies directly implicate immunologic sensitivity to the cartilage type of collagen in the etiology of this autoimmune disease.

Animals↗
PubMed1978

Possible role of macrophage glycolipids as receptors for migration inhibitory factor (MIF).

Guinea pig peritoneal exudate cells incubated with water soluble glycolipids obtained from macrophages show an enhanced response to migration inhibitory factor. Incorporation of these glycolipids into liposomes greatly facilitates their interaction with indicator cells. Enhancement of peritoneal exudate cell responsiveness to migration inhibitory factor was specific for glycolipids from guinea pig macrophages. Glycolipids extracted from guinea pig brain and polymorphonuclear leukocytes as well as several bovine and porcine glycolipids had no effect. Specificity of enhancement was not due merely to a preferential association of macrophage glycolipids with indicator cells. The possible role of macrophage glycolipids as receptors for MIF is discussed.

Animals↗
PubMed1978

Cellular sensitivity to collagen in rheumatoid arthritis.

Using an assay to measure antigen-induction of a lymphocyte mediator, LIF, we detected cellular sensitivities to native human types II and III collagens in three-quarters of a group of 50 patients with rheumatoid arthritis. There was no cellular response to type I collagen. Cellular reactivities to collagen were absent in a group of 41 patients who had other kinds of arthritis, such as osteoarthritis, crystalline-induced synovitis, or arthropathies associated with a high prevalence of the HLA-B27 antigen. Lymphocytes, responding to an unknown persistent antigenic stimulus, are thought to play a major role in the pathogenesis of rheumatoid arthritis. It has previously been hypothesized that collagen might function as an autoantigen in this disease. Based on the disease specificity of our findings and the tissue distribution of types II and III collagens, we propose that cellular sensitivities to these structural proteins may be involved in the pathogenesis of rheumatoid arthritis.

Adult↗
PubMed1977

Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.

Animals↗
PubMed1977

Antibody-dependent, eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: effect of metabolic inhibitors and other agents which alter cell function.

The effect of drugs known to inhibit different metabolic pathways or cell functions on antibody-dependent, eosinophil-mediated damage to schistosomula was determined. Eosinophil-mediated damage was completely inhibited by cytochalasin B, inhibitors of glycolysis, aminophylline, and treatment of cells with diazotized sulfanilic acid and tosyl-lysyl-chloromethyl ketone. The effects of cytochalasin and 2-deoxyglucose were reversible. On the other hand, eosinophil-mediated damage was unaffected by agents which inhibit DNA replication, protein synthesis, oxidative respiration, prostaglandin synthesis, and microtubule aggregation. The findings suggest that alteration of the cell surface membrane and microfilaments prevents damage by interfering with cell-target interactions, that energy derived from glycolysis is required for cytotoxicity, that cell-associated esterases are probably involved, and that cytotoxicity may be modulated by cyclic nucleotides. Some of the attributes of eosinophils that allow it and not other cells to mediate this reaction are discussed.

Animals↗
PubMed1977

Identification and purification of immunosuppressive activity in the urine of rats and a human patient treated with niridazole.

Administration of the antischistosomal compound niridazole to mice, guinea pigs, and humans results in the suppression of several manifestations of cell-mediated immunity. Sera from animals treated with niridazole blocked the in vitro production of migration inhibitory factor (MIF) while niridazole itself was inactive, suggesting that these effects are caused by water soluble mediators. We now report that crude extracts prepared from the urine of rats and a patient receiving nirdazole, but not from pretreatment control urine, similarly suppress antigen-induced inhibition of migration of peritoneal exudate cells from sensitized guinea pigs. With immunosuppressive activity monitored by the direct MIF assay, combined solvent extraction and chromatographic techniques were used to fractionate immunosuppressive activity from the urine of niridazole-treated rats and the patient; the most active fractions, purified about 100-to 1000-fold as compared to methanol-water extracts of dried voided urine, inhibited MIF production at 0.1 to 0.01 ng/ml of assay mixture. These purified fractions also showed immunosuppressive activity by an in vivo assay wherein doses as low as 1 mug/kg injected intravenously (i.v.) into mice suppressed cell-mediated granuloma formation around Schistosoma manisoni eggs. Identically purified fractions prepared from urine of rats and the patient before they received niridazole showed no immunosuppressive activity either in the MIF or in the granuloma assay systems.

Acetone↗