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Biomedical subjects

G Fernandes

Publications and source records attributed to G Fernandes.

At least 73 records · Page 4Linked to original sources
PubMed1985

Alterations in immunological reactivity in encephalomyocarditis virus-induced murine diabetes. I. Defective primary IgM plaque forming cell responses to sheep erythrocytes: correction by islet cell transplantation.

Increasing data suggest a possible viral aetiology of juvenile onset, insulin-dependent diabetes mellitus. The M variant of the encephalomyocarditis (EMC) virus infects murine pancreatic beta cells and causes a diabetes like syndrome in susceptible strains of mice. Abnormalities in immunological function have been documented in patients with diabetes mellitus and in spontaneous, streptozotocin-induced and alloxan-induced diabetes in animals. The present study documents a significant impairment of the ability of mice with EMC virus (M variant)-induced diabetes to generate a direct, IgM PFC response after in vivo immunization with sheep erythrocytes. This abnormality appears to be a direct consequence of the diabetic state and not EMC virus infection, per se, since mice infected with EMC virus that do not become diabetic have normal direct PFC responses and islet cell transplantation, which cures the diabetes, corrects the defect in PFC responsiveness.

Animals↗
PubMed1984

Suppression of cellular and humoral immunity to T-dependent antigens by calorie restriction.

Calorie restriction is known to preserve the immunologic function and prolong the life span of autoimmune-susceptible mice. In order to determine the influence of calorie restriction on cellular and humoral immunity, we tested lymphocyte proliferative response and antibody response to T-dependent antigens in C57Bl/6 mice maintained on restricted diets. C57Bl/6 mice fed a low-calorie diet demonstrated a marked reduction in T-dependent-antigen-specific lymphocyte proliferation and antibody response when compared to mice fed ad libitum. The depressed lymphocyte response seen in calorie-restricted animals is attributed to a defect in both the macrophages and T cells in antigen processing, presentation, and/or proliferation.

Animals↗
PubMed1984

Age-dependent alterations of peritoneal exudate macrophages in autoimmune-prone and autoimmune-resistant mouse strains.

Comparisons were made with age on phagocytosis, chemotaxis, and esterase staining of autoimmune-resistant and autoimmune-susceptible mouse strains. Consistent increases of each parameter occurred with age. Autoimmune strains generally showed less change with age than autoimmune-resistant mice and the changes with aging were less consistent. These findings suggest that phagocytic cells may play an important role in the autoimmunities or the lymphoproliferative processes that occur in autoimmune-prone mice and/or in loss of immune function with aging.

Age Factors↗
PubMed1984

Alterations in immunological function in streptozotocin-induced murine diabetes mellitus: correction by islet cell transplantation.

Cell-mediated and humoral immune responses of streptozotocin-induced diabetic mice were evaluated using in vivo and in vitro immunological assays. C57BL/6 mice were rendered diabetic by a single intraperitoneal injection of 125-200 mg/kg of streptozotocin. Immunological studies were performed after the mice were diabetic (mean +/- SEM serum glucose 537 +/- 14 mg/dl) for a minimum of 4 weeks. Spleen cells from streptozotocin-induced diabetic mice exhibited significantly diminished direct IgM plaque-forming cell (PFC) responses following either in vivo or in vitro immunization with sheep erythrocytes, markedly impaired cytotoxic cell responses following in vivo or in vitro allogeneic stimulation, and diminished blastogenic response to the T-cell mitogens phytohemagglutinin and concanavalin A. In contrast the blastogenic response of diabetic spleen cells to lipopolysaccharide, a B-cell mitogen, was normal. The defects in in vivo PFC responses and in vivo cytotoxic cell responses were corrected by islet cell transplantation, suggesting that the abnormalities in immunological function of streptozotocin-induced diabetic mice are a consequence of the diabetic state and not of direct streptozotocin toxicity to lymphoid cells.

Animals↗
PubMed1984

Inhibition by restricted-calorie diet of lymphoproliferative disease and renal damage in MRL/lpr mice.

Restriction of calorie intake from the time of weaning greatly prolongs life, and it inhibits development and expression of the lymphoproliferative syndrome, renal disease, and decline of certain immunologic functions with age in MRL/lpr mice. This dramatic influence of diet on mice of this short-lived autoimmunity-prone strain, while associated with decreased rate of growth, is not associated with debilitation or apparent disease in the MRL/lpr mice. The massive lymphadenopathy and splenomegaly that developed in the putatively well-fed animals was prevented by dietary restriction, as were histopathologic abnormalities of thymus, spleen, lymph nodes, and kidneys.

Animals↗
PubMed1984

Functional T cells in athymic nude mice.

After passage of spleen cells from nu/nu mice over a nylon wool column, concanavalin A-responsive cells can be detected in the presence of 2-mercaptoethanol, and specific cytotoxic T lymphocytes can be generated without exposure to interleukin 2 (IL-2). The spleen cells of the nu/nu mice born of nu/nu parents and nursed by nu/nu mothers had significantly fewer Thy-1+ T cells and a lesser capacity to generate cytotoxic T lymphocytes than did the conventionally bred nu/nu mice. Nonetheless, such cells were clearly present. IL-2 may act to cause these post-thymic T cells to proliferate. Therefore, it seems inappropriate to consider IL-2 as an inducer of the differentiation of T cells in the absence of thymic influence on the basis of the capacity of IL-2 to induce the appearance of a T-lymphocyte population in nu/nu mice.

Animals↗
PubMed1984

Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.

Mice of the autoimmune, lymphoproliferative strain MRL/lpr and the congenic, nonlymphoproliferative strain MRL/n were fed one of six diets from weaning on-ward. These mice were sacrificed at 3 or 5 months of age. Low fat diets resulted in lower cholesterol and higher triglyceride levels than did cholesterol-containing high-fat diets. Caloric restriction of MRL/lpr mice was associated with an increased plaque-forming cell response to trinitrophenylated polyacrylamide beads, less lymphoproliferation, and less severe glomerulonephritis. Diet did not affect the incidence of autoimmune vasculitis in MRL/lpr mice sacrificed at 5 months. MRL/lpr mice fed a low-fat, calorically restricted diet from 5 months of age to death lived longer than mice which were fed ad libitum a cholesterol-containing, high-fat diet. At death, MRL/lpr mice fed the former diet had the autoimmune vasculitis which had been evident in mice killed at 5 months, whereas mice fed the latter diet, in addition to the vasculitis, had a high incidence of atherosclerotic lesions of intrarenal and aortic branch arteries.

Animal Nutritional Physiological Phenomena↗
PubMed1984

In vitro immune response of cells of various lymphoid tissues in (NZB X NZW)F1 mice: evidence for abnormality of the mesenteric lymph node cells.

Autoimmune-prone (NZB X NZW)F1 (B/W) mice have been shown to have a variety of immunologic perturbations. However, most studies have been performed with spleen cells. By using the Mishell-Dutton culture system, we examined the in vitro immune response of the various lymphoid tissue to determine whether an imbalance at a selective lymphoid site may exist in B/W mice. It was shown that the ability of mesenteric lymph node (MLN) cells of B/W mice to generate plaque-forming cells (PFC) in response to sheep red blood cells was consistently less than that of the spleen cells. This relationship held true in the aged mice. In contrast, the ability of the MLN cells of other strains not prone to develop autoimmunity to generate PFC was higher than that of the spleen cells. No significant difference in the mitogenic response of the lymphoid cells from various lymphoid tissue in the young B/W mice was seen, as compared with normal lymphoid cells from control mice. However, it was demonstrated that a relative decrease of B cells and immunoregulatory Lyt-123+ cells in the MLN in the B/W mice occurred early in life, and it was concluded that this abnormality may account for the low PFC response observed.

Aging↗
PubMed1983

Deficient T-cell mitogen response in murine experimental autoimmune myasthenia gravis: a defect in the adherent cell population.

T-Lymphocyte number and functions are often reduced, while B-lymphocyte function is often increased in patients with autoimmune disorders. To study the mechanisms responsible for these T-cell malfunctions in autoimmunity we adapted the murine experimental autoimmune myasthenia gravis (EAMG) model. Splenocytes from C57BL/6 mice immunized with acetylcholine receptors (AChR) in complete Freund's adjuvant (CFA) produced approximately half the amount of concanavalin A (Con A)-induced interleukin 2 (IL-2) as did splenocytes of CFA-inoculated controls. Further, AChR plus CFA-immunized splenocytes showed a marked reduction in T-cell proliferative responses induced by Con A or phytohemagglutinin when compared with CFA-inoculated controls. By contrast, lipopolysaccharide-induced B-cell function is preserved. Deficient Con A splenic T-cell response is seen early after secondary inoculation with CFA or AChR in CFA. T-Cell recovery occurs in CFA-inoculated mice but not in AChR plus CFA-inoculated mice. Defective Con A splenic T-cell response seen early after secondary immunization with CFA or AChR in CFA is due to the presence of a defective splenic adherent cell population. Moreover, defective Con A splenic T-cell response seen after established autoimmunity to AChR in EAMG is also due to the presence of a defective splenic adherent cell population.

Animals↗
PubMed1983

Studies of immune responses in mice prone to autoimmune disorders. I. Heterogeneity of the affinities of antihapten antibodies produced by NZB, NZW, and related strains of mice.

Mice of the NZB and NZW strains and their F1 hybrid produce antihapten plaque-forming cell (PFC) responses to T-dependent antigens (trinitrophenylated bovine gamma globulin and dansylated keyhole limpet hemocyanin) which are of unusually restricted heterogeneity of affinity, are relatively lacking in low-affinity PFC, and are of relatively high average affinity. Since some low-affinity PFC are present in NZB mice early after immunization, the results suggest a particularly marked down-regulation of low-affinity antibody production by these strains. The non-autoimmune-prone F1 hybrid (NZB X CBA) produces a typical heterogeneous response containing a high proportion of low-affinity PFC. Thus, the tendency to down-regulate low-affinity PFC is not inherited as a simple Mendelian dominant trait. The response of NZB mice to T-independent antigens does not show the same restricted heterogeneity of affinity. In fact, late after injections of trinitrophenylated Ficoll, NZB mice tend to have more heterogeneous responses than nonautoimmune-prone BALB/c mice in which a marked down-regulation of high-affinity antibody-producing PFC is seen. The possible relationship between these unusual features of the immune response of NZB and some related strains and their tendency to develop autoimmune disease is discussed.

Animals↗
PubMed1983

Influence of diet on vascular lesions in autoimmune-prone B/W mice.

Autoimmune-prone B/W mice, which are known to develop severe glomerulonephritis and vasculitis, also are found to develop arteritis and proliferative and fatty-proliferative lesions of the aorta and its branches as well as renal inflammatory lesions. High intake of saturated fat in the diet enhances the development of these atherosclerotic and autoimmune lesions significantly in female mice, whereas restriction of dietary calories and fat inhibits their development. Ad lib feeding of laboratory chow, high in fiber and low in fat, does not foster development of vascular lesions but does permit the development of autoimmune renal disease.

Animals↗
PubMed1983

Interleukin-2 and autoimmune disease.

Interleukin-2 (IL-2) deficiency is a common feature of autoimmune disease in several inbred strains of mice genetically predisposed to a lupus-like illness, including four (MRL, C57Bl/6, AKR/J, and C3H/He) bearing the lpr gene. Defective production of IL-2 in response to concanavalin A can occur even when the proliferative response to mitogens is preserved. In C56Bl/6-lpr mice there is no apparent influence of the lpr gene and IL-2 deficiency on the induction of the experimental autoimmune myasthenia gravis that follows immunization with the acetylcholine receptor. The production of IL-2 by peripheral blood mononuclear cells stimulated with PHA is decreased in patients with systemic lupus erythematosus and rheumatoid arthritis.

Animals↗
PubMed1983

Natural killer and antibody-dependent cytotoxic activities in T cell chronic lymphocytic leukemia.

T cells from a patient with T cell chronic lymphocyte leukemia (CLL) were analysed for natural killer (NK) and antibody-dependent cytotoxicity (ADCC) and surface phenotype using a battery of monoclonal antibodies. T cells from the patient reacted with a pan T cell (9.6) and OKT8 (suppressor/cytotoxic phenotype) monoclonal antibodies and bore receptors for IgG Fc (Tg) but lacked receptors for IgM Fc (Tm) and did not react with OKT4 (helper/inducer phenotype) monoclonal antibody. T cells from the patient demonstrated a significantly higher (p less than 0.01) NK activity when compared to control T cells. T cells from the patient also demonstrated strong but comparable ADCC when compared to healthy controls. The significance of these results is discussed.

Aged↗
PubMed1983

[Influence of the sex factor in weight gain caused by chronic use of lithium].

The use of lithium, in the treatment and prevention of affective disorders, is considered to be one of the most important break through in modern Psychopharmacology. Side effects are frequently associated with its short and long term use. One of those side-effects, which is common after chronic lithium salt treatment, is a considerable increase in body weight. This side-effect appears to be an important factor in prompting some patients, particularly women, to suspend treatment. In this study, confirming our previous work with an animal model, we found a statistically greater weight increase in women treated chronically with lithium than in men. Our results were apparently not explained by abnormalities in thyroid function. The literature describes those thyroid abnormalities, due to lithium, as being more frequent in women than in men. In an animal model, we now found that higher plasma lithium levels are produced in male, when compared to female rats, when this drug is administered for long periods. If the some tendency is present in men, we could expect a greater probability of toxicity in men than in women. Thus, a lower weigh increase in men. Such could be a possible explanation for our clinical results.

Adult↗
PubMed1982

Specific elimination of the T lineage cells: effect of in vitro treatment with anti-Thy 1 serum without complement on the adoptive cell transfer system.

Thymocytes from C57BL/6(B6) mice treated with anti-Thy 1 antiserum without complement in vitro were transferred to lethally irradiated AKR mice. Five days following transfer, the proportion of Thy 1.2(+) cells recovered from the recipient spleen was significantly lower (7%) than that from the control mice which had received untreated cells (64%). the B6 spleen cells were treated in the same manner and transferred with SRBC (T-dependent antigen) or DNP-Ficoll (T-independent antigen) to irradiated syngeneic recipients. The recipients developed a response to SRBC which was significantly lower than that observed in control mice, but showed the same number of plaque-forming cell (PFC) against TNP-SRBC as the control group of mice which had received untreated B6 spleen cells. These results clearly show that in vitro pretreatment of lymphocytes with anti-Thy 1 serum without complement specifically resulted in elimination or inactivation of the T lineage cells in the host environment. The mechanisms of the elimination are discussed in this study.

Animals↗