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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 343 records · Page 19Linked to original sources
PubMed1985

Regulation of human B lymphopoiesis: effect of a urinary activity associated with cyclic neutropenia.

Urine from a patient with cyclic neutropenia was found to contain a lymphopoietic activity that acts as a growth factor for human pre-B cells. This biologic activity was detectable during the week preceding, but not during, the period of neutropenia. This corresponded with a periodic excessive accumulation of pre-B cells in the marrow of this patient. Urine preparations were added to cultures of normal human bone marrow that had been depleted of B cells. Pre-B cells were generated in these cultures but not in cultures containing urine preparations from normal donors. Pre-B cells were also generated from bone marrow that had been depleted of 177.17+ cells and the majority of pre-B cells. This is the first report of a hemopoietic activity which affects human pre-B cells. This activity may represent a normal regulatory molecule that is periodically produced in excess in this patient.

Adult↗
PubMed1985

The influence of thymic abnormalities on the development of autoimmune diseases.

The relationship between thymic abnormalities and development of autoimmune diseases was studied in MRL/l and NZB/NZW F1 (NZB/W F1) mice. Thymic abnormalities, including plasma cell infiltration into the thymus, were observed in 25% of MRL/l mice as early as 1 mo and in all mice after 2.5 mo. The thymic abnormalities preceded both infiltration of lymphoid cells into the kidney and salivary glands, and also preceded an increase in the titer of circulating immune complexes (CIC). When MRL/l and NZB/W F1 mice were divided into two groups for each strain at the critical age when the mice had begun to show thymic abnormalities, the group with abnormal thymuses showed more marked pathological findings in other organs and a higher level of CIC than the group with more normal appearing thymus. In addition, the group with abnormal thymus demonstrated lower responsiveness of their lymphocytes in mixed-lymphocyte culture than the group with normal thymus. Thymus grafts from donors of autoimmune or non-autoimmune strains into nude mice revealed that thymic functions, reconstitutive of immunologic parameters of nude mice, are rapidly lost with age. These results suggest that morphological and functional abnormalities of the thymus are involved in the pathogenesis of autoimmune diseases.

Age Factors↗
PubMed1985

Prevention of leukemia and the increase of plasma levels of lipid-bound sialic acid by allogeneic bone marrow transplantation in mice.

AKR/J (hereafter called AK) mice treated by total-body irradiation plus syngeneic marrow transplantation developed a leukemia-lymphoma complex and concomitantly showed increased levels of lipid-bound sialic acid as was also seen in untreated AK mice between 6 weeks and 6 and 11.5 months of age. C57BL/6J (hereafter called B6) mice did not show a leukemia-lymphoma complex and did not develop elevated levels of lipid-bound sialic acid with aging. B6----AK chimeras, prepared with B6 bone marrow deprived of Thy-1,2-positive cells prior to allogeneic transplantation and kept in laminar flow isolation, did not develop graft-versus-host reactions, lived long lives (observations carried up to 13 months), failed to develop leukemia-lymphoma, and had persistently low levels of lipid-bound sialic acid. These findings indicate that introduction of resistance by marrow transplantation can inhibit development of retrovirus-induced cancer and also prevents an increase in levels of a putative cancer indicator.

Animals↗
PubMed1985

Humoral factors in very young NZB mice that enhance the maturation of normal B cell precursors. Partial purification and characterization.

Soluble factors that enhance maturation of murine B lineage precursor cells in vitro were partially purified from the serum of very young NZB mice and characterized biochemically and biologically. Activity was initially detected by induction of colony-forming activity and surface immunoglobulin (sIg) on normal sIg- marrow cells as well as responsiveness of a pre-B cell line. Pooled sera from 4- to 5-wk-old NZB mice were initially fractionated on Sephacryl S-300 and Sephadex G-100 superfine columns. Fractions with activity (corresponding to m.w. of 15,000 to 45,000) were pooled and further separated. The activity was eluted as a single peak by hydrophobic (phenyl-Sepharose, with 0.8 M (NH4)2SO4) and lentil lectin affinity chromatography but resolved into three distinct peaks in preparative isoelectric focusing (IEF), with pI values of 3.5, 7.8, and 8.4. The latter two merged into a single peak with a pI value of 8.8 when the sample was further treated with neuraminidase before IEF. These three IEF fractions, each of which were enriched at least 1000-fold in specific activity relative to starting serum, were then characterized. Each was stable at pH 2 but sensitive to trypsin, 10 M urea, and heat treatment (56 degrees C for 1 hr). In nonreduced SDS-poly-acrylamide gel electrophoresis, their mobilities corresponded to m.w. of 17,000 for peak I (pI 3.5), 15,000 for peak II (pI 7.8), and 15,000 for peak III (pI 8.4). Interleukin 1, interleukin 2, interleukin 3, colony-stimulating factor for granulocyte and macrophage progenitors, antiviral, or B cell growth factor type I-like activities were not demonstrable. Peaks II and III, but not peak I, induced Ig secretion of anti-stimulated B cells. Peak I was also less effective than peaks II and III in induction of sIg on an established pre-B cell line. However, all fractions were equally effective in enhancing maturation of normal sIg- B lineage cells. Thus, serum from 4- to 5-wk-old NZB mice contains at least two distinct soluble factors that can enhance the maturation of sIg- B lineage cells in vitro. The biologic and biochemical characteristics of these factors appear to differ from those of previously well-defined cytokines.

Animals↗
PubMed1985

Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution.

Autoimmune-prone mice show premature thymic involution, including morphological and functional abnormalities. To determine why the thymic abnormalities develop in autoimmune-prone mice, transplantation of the thymus and/or bone marrow was performed. When thymuses of newborn MRL/1 (H-2k) mice were grafted into C3H/HeN nu/nu(H-2k) mice, the engrafted thymuses did not show the abnormalities which characterize the thymus in the autoimmune-prone MRL/1 mice. By contrast, when thymuses of newborn C3H/HeN or MRL/n mice were grafted into MRL/1 mice, the engrafted thymuses developed after an interval of 3 months the same morphological abnormalities as were seen in MRL/1 mice. Thus, we can conclude that premature involution of the thymus in autoimmune-prone mice may not be a genetically determined abnormality intrinsic to the thymus, but rather an abnormality secondary to other events occurring in these mice. When bone marrow of young C3H/HeN nu/nu mice was transplanted into irradiated (850 rad) MRL/1 mice, neither thymic abnormalities nor autoimmune diseases developed. Therefore, it seem likely that abnormal stem cells in autoimmune-prone mice induce thymic abnormalities, and these, in turn, are associated with the development of autoimmune diseases.

Animals↗
PubMed1984

Adverse reactions in selected patients following intravenous infusions of gamma globulin.

Fifteen patients with hypogammaglobulinemia or agammaglobulinemia were treated with intravenous gamma globulin preparation over a 17-month period. The patients were selected for treatment if they had chronic antibody deficiency syndromes associated with increased susceptibility to infections. Levels of circulating immune complexes, C1q, C3, and C3d were determined in serum samples obtained before treatment and immediately following treatment with the gamma globulin. In every patient studied, circulating immune complexes were detectable in the postinfusion samples. Two patients had adverse reactions to the intravenous gamma globulin therapy. Analysis of the serum samples of both of these patients showed that one patient had an autoantibody to IgA and the other had an autoantibody to beta-lipoprotein. Both IgA and beta-lipoprotein were present in the intravenous gamma globulin preparations. Therefore, reaction with each of the autoantibodies by the antigens activated the complement system in vivo with production of split products of C3.

Adult↗
PubMed1984

Dietary protein antigenemia in humoral immunodeficiency. Correlation with splenomegaly.

Enhanced gastrointestinal absorption of dietary substances is an important feature of normal neonatal life that also exists in particular disease states such as selective IgA deficiency and atopic allergy. In these studies, it is shown that patients with hypogammaglobulinemia have increased absorption of dietary bovine antigens and that most patients have large amounts of these proteins present in the serum even after an overnight fast. The amounts of such proteins were found to be correlated with spleen size and/or peripheral lymphoid hypertrophy. Interestingly, three patients with X-linked agammaglobulinemia did not have detectable amounts of these proteins in the serum nor did they have splenomegaly or lymphadenopathy. It is speculated that hypogammaglobulinemic patients have a specific gastrointestinal mucosal lesion that permits the chronic excessive absorption of dietary antigens and may result in lymphoid hypertrophy.

Adult↗
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

Autologous and allogeneic mixed-lymphocyte responses following thermal injury in man: the immunomodulatory effects of interleukin 1, interleukin 2, and a prostaglandin inhibitor, WY-18251.

A group of 30 burn patients with 36-87% total body surface area (TBSA) burns was studied at 24-48 hr postburn. These included studies of (1) autologous and allogeneic mixed-lymphocyte reactions (MLR); (2) the immunoregulatory influence of mitomycin C-treated T cells, non-T cells, and unfractionated peripheral blood lymphocytes (PBL) on allogeneic MLR; and (3) correlation between the proportions of T-cell subsets defined with monoclonal antibodies (OKT4 and OKT8) and autologous MLR. Studies concerning adherent cell production of thromboxane, prostaglandin E2, and prostaglandin F2a and the immunomodulatory effects of Interleukin 1 (IL-1), Interleukin 2 (IL-2), and a prostaglandin inhibitor, WY-18251, on autologous MLR are presented. The autologous mixed-lymphocyte reaction was depressed in 60% of the burn patients tested. This depressed response correlated closely to the extent of third-degree injury (P less than 0.025) and to TBSA injury greater than 60% (P less than 0.025). A linear correlation was observed between the depression in autologous MLR and a decrease in both the percentage of OKT4+ T cells and the OKT4+/OKT8+ ratio. The response of T cells from burn patients in allogeneic MLR was normal. Age, sex, TBSA of the burn, and size of second-degree burn did not correlate with the abnormalities observed in MLR. Mitomycin C-treated mononuclear cells, purified T cells, or non-T cells from burned patients did not demonstrate any suppressive influence on MLR in normals. Monocyte number and arachidonic acid metabolism were investigated. In addition to increased numbers of monocytes following thermal injury, adherent cells produced increased quantities of thromboxane, prostaglandin E2, and prostaglandin F2a. The effects of Interleukin 1, Interleukin 2, and a prostaglandin inhibitor, WY-18251, were studied in autologous MLR (AMLR) of burned and normal patients. Interleukin 1 and WY-18251 did not induce any significant changes in proliferation in burned patients or normal controls. When compared to cultures without exogenous IL-2, an increase in AMLR was observed following the addition of IL-2 to burn patient cultures at Day 6 and Day 7 of culture. Although the addition of IL-2 did increase proliferation in AMLR of normal controls at Day 6 and Day 7, the enhancement observed for the burn patient cultures represented a restoration to the level of normal control cultures without IL-2. A dose-dependent increase in AMLR was observed in T cells isolated from normal and burned patients in the presence of purified Interleukin 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Appearance of cytotoxic antibody to viral gp70 on feline lymphoma cells (FL-74) in cats during ex vivo immunoadsorption therapy: quantitation, characterization, and association with remission of disease and disappearance of viremia.

Fifty cats with feline leukemia virus (FeLV) infection and leukemia-lymphoma complex were treated by ex vivo immunoadsorption with Staphylococcus protein A-bound filters. Most cats responded to therapy. Twelve showed tumor regression, including disappearance of tumor cells, but died later of other complications. Three have had long-term remission of more than 1 year and remain healthy. A consistent finding in these three cats was the appearance during treatment of a complement-dependent cytotoxic antibody against cat lymphoma cells (FL-74). The cytotoxic antibody increased substantially during treatment. Appearance and increase of the cytotoxic antibody was associated with disappearance of FeLV from blood and remission of leukemia. By electroblot analysis, antibody to FeLV protein (Mr, 70,000) was detected in serum prior to detection of the cytotoxic antibody. The cytotoxic antibody was found by immunofluorescence to be specific for antigens on membranes of viable FL-74 cells. By using monoclonal antibodies to FL-74 cells and to components of FeLV, the cytotoxic antibody was shown to be directed against gp70, a glycoprotein of Mr 70,000, but not against p27 of FeLV or other membrane antigen(s) of FL-74 cells. The development of a high concentration of cytotoxic antibody to FeLV gp70 may play an important role in tumor regression and in disappearance of FeLV infection.

Animals↗
PubMed1984

Influence of early or late dietary restriction on life span and immunological parameters in MRL/Mp-lpr/lpr mice.

Reduced food intake doubles and even triples the life span of (NZB X NZW)F1 (B/W) mice and greatly influences of food intake while keeping vitamin and mineral intake constant in mice of the MRL/Mp-lpr/lpr (MRL/l) strain. Restriction of food intake greatly prolongs life. This influence also was seen when dietary restriction was imposed later in life. Dietary restriction inhibited development of lymphoproliferative disease and greatly decreased the numbers of cells in thymus, lymph nodes, and spleen. It also delayed development of glomerulonephritis and maintained certain immunological responses. Proliferative responses to phytohemagglutinin, pokeweed mitogen, or allogeneic spleen cells were maintained in the mice fed a low-calorie diet from 6 wk. Imposing diet at 12 wk had a lesser influence than earlier restriction. These dietary influences did not depress formation of anti-DNA antibodies or circulating immunocomplexes. MRL/l mice show an apparently extremely low production of interleukin 2, and dietary restriction increased the capacity of lymph node cells but not spleen cells to produce this immunomodulator.

Aging↗
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

Remission of leukemia and loss of feline leukemia virus in cats injected with Staphylococcus protein A: association with increased circulating interferon and complement-dependent cytotoxic antibody.

We have injected purified Staphylococcus aureus protein A intraperitoneally into leukemic cats infected with feline leukemia virus, into cats persistently infected with feline leukemia virus but without hematologic or cytologic abnormalities, and into healthy cats without feline leukemia virus infection. Pre- and post-treatment serum samples were evaluated sequentially for interferon activity and for complement-dependent cytotoxic antibody. Our results indicate that serum interferon increased dramatically (less than 3 to 324 units/ml) during treatment only in cats that responded to staphylococcal protein A therapy. Increase of interferon preceded or was closely associated with increasing levels of cytotoxic antibody, loss of viremia, and correction of cytological and hematological abnormalities of three leukemic cats. The cytotoxic antibody was shown to be specific for envelope glycoprotein gp70 of the feline leukemia virus. One persistently feline leukemia virus-infected cat without leukemia that became nonviremic also developed high levels of interferon and specific cytotoxic antibody. By contrast, interferon levels of cats not responding to treatment had levels of less than 3 to 27 units/ml. Normal healthy cats injected with staphylococcal protein A showed moderate transient increases of interferon but no detectable cytotoxic antibodies to FL-74 cells. These data suggest that interferon and cytotoxic antibody may play important, possibly complementary roles in inducing remission of leukemia and loss of viremia in cats treated with staphylococcal protein A.

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

Calorie source, calorie restriction, immunity and aging of (NZB/NZW)F1 mice.

It is frequently stated that high fat diets are harmful with respect to nutrition and disease development. Herein, (NZB/NZW)F1 autoimmune-prone mice were compared under the influence of different calorie intakes and different calorie sources. Decreased calorie intake prolonged life and delayed onset of glomerulonephritis. This influence of restriction of energy intake was greater than any influences of dietary energy source. Parameters affected strictly by restricted calorie intake were: 1) longevity, 2) delayed onset of glomerulonephritis, 3) greatly decreased circulating immune complexes, 4) decreased production of anti-DNA antibodies, 5) increased thymocyte proliferation in response to exogenous Interleukin-2 (IL-2), 6) increased IL-2 production by spleen cells stimulated by concanavalin A and 7) marked increase of mixed lymphocyte reaction of spleen cells. Parameters affected both by restriction of calorie intake and by high sucrose content in full-fed mice and not obviously related to longevity and protection from glomerulonephritis were: 1) plaque-forming cell response to sheep red blood cells in vitro and 2) cytotoxic cell-mediated immune response generated by in vitro exposure to allogenic antigen.

Aging↗
PubMed1984

Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease.

Twenty-one patients with primary humoral immunodeficiency were treated for 1 year with a chemically intact immunoglobulin, 300 mg/kg body weight given intravenously every 3 weeks, to compare immunoglobulin levels and clinical status with results achieved after standard treatment with intramuscular immunoglobulin given previously for 1 year. A substantial reduction of specific acute illnesses and antibiotic use was found for 18 of the 21 patients, particularly during the second 6 months of treatment. Average IgG levels before intravenous infusion were increased 243 mg/dL over previous intramuscular pre-injection levels. Adverse effects were recorded for 2.5% of infusions.

Absenteeism↗