Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 307 records · Page 17Linked to original sources

PubMed1986

Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.

Animals↗

PubMed1986

Calories versus protein in onset of renal disease in NZB x NZW mice.

Autoimmunity-prone (NZB x NZW)F1 (B/W) female mice are used as a model of human lupus erythematosus. When full-fed, these mice die of glomerulonephritis between 7 and 11 (average 9) months of age. When food intake is restricted to 60% of calories, the onset of this disease is delayed and the mice live greatly prolonged lives free of disease. Since high protein intake is commonly associated with acceleration of kidney damage in humans and experimental animals, the current experiments were designed to employ diets in which protein concentration was as high as possible. The observations demonstrate clearly that with this model of autoimmune disease, total calorie intake (from whatever source) exerts an overriding influence on life span. A higher calorie intake leads to early death and restricted-calorie intake leads to an increased life span. When B/W mice are full-fed, with respect to calories, feeding diets of greatly differing protein composition did not influence life span significantly. By contrast, calorie restriction of diets, even of very high protein content or of lower protein content, greatly prolonged life of B/W mice. Even with exceedingly high protein intake (greater than 83% of the calories) it is not protein per se but the total calorie intake that exerts the greatest influence that determines length of life in mice of this autoimmunity- and glomerulonephritis-prone strain.

Animals↗

PubMed1986

Stimulatory and inhibitory influences of human immunodeficiency virus on normal B lymphocytes.

B-lymphocyte dysfunction is a characteristic feature of the acquired immunodeficiency syndrome (AIDS) and of the AIDS-related complex. The aim of the present study was to further examine the influences exercised by the human immunodeficiency virus (HIV; formerly called human T-lymphotropic virus type III or lymphadenopathy-associated virus, HTLV-III/LAV) on normal human B lymphocytes. An unfractionated protein preparation, made from HIV purified by density gradient centrifugation, was previously shown to induce differentiation of normal human B lymphocytes into immunoglobulin-secreting cells. In the present analyses, this B-lymphocyte response peaked on day 6 or 7 after culture initiation and was found to be independent of the requirement for monocytes but to require T cells. Responses could also be elicited in cultures of purified B cells by the addition of T cells that had been exposed to HIV antigen. Inhibitors of protein synthesis (puromycin and cycloheximide) abrogated the responses. In contrast to its stimulatory effects, the same virus preparation was previously shown to inhibit polyclonal responses that are normally elicited in peripheral blood lymphocyte cultures by a T-dependent stimulus (pokeweed mitogen) and T-independent stimulus (Epstein-Barr virus). The present studies suggest that the inhibitory effects of the HIV antigen studied herein are targeted primarily at the B lymphocytes. The role of T lymphocytes in the HIV antigen-mediated inhibitory effects, although demonstrated, could not be conclusively established as an essential pathway. These findings elucidate mechanisms by which components of HIV exert stimulatory as well as inhibitory effects on human B lymphocytes and thereby lead to the dysfunction of these cells in HIV infection.

Antibody-Producing Cells↗

PubMed1986

Partial purification and characterization of feline gamma-like interferon.

Feline interferon (IFN) was produced from spleen cells stimulated by Staphylococcus enterotoxin A (SEA). The IFN was purified by a three-step procedure using controlled pore glass adsorption chromatography, concanavalin A (ConA)-agarose column chromatography and gel filtration. The final product of these procedures which had activity of an IFN appeared as a single peak of activity with molecular weight of approximately 50,000. It was sensitive to acid and heat, suggesting that the isolated material was a gamma IFN. The total recovery of feline gamma IFN was 8.2%. Specific activity was 2.95 X 10(4) unit/micrograms protein and was concentrated 2.8 X 10(4) times. This preparation of purified feline gamma IFN was destroyed completely by 0.1% sodium dodecyl sulfate within 20 min. As an inducer of feline gamma IFN, SEA appeared to produce a more uniform IFN product than did ConA. Further, the presence of 10% ethylene glycol in the sample applied to ConA-agarose column as well as its absence in the elution buffer was effective in reducing contaminating acid- and heat-resistant IFNs in the preparation.

Animals↗

PubMed1986

Effects of genetic diabetes and zinc nutriture on in vivo cell-mediated immunity in the mouse.

To examine whether an abnormal zinc status contributes significantly to the impaired in vivo cell-mediated immunity of the genetically diabetic C57BL/KsJ db/db mouse, we measured specific cytotoxicity of spleen cells from db/db and heterozygous (db/m) and homozygous (m/m) control mice fed either zinc-deficient (2 mg/kg) or zinc-adequate (20 mg/kg) semipurified diets. Low serum and femur zinc concentrations were seen after 4 wk in all mice fed the zinc-deficient diet, but impaired cytotoxicity was not seen until later in control mice fed that diet. In contrast, db/db mice fed zinc-adequate diets had diminished spleen weights and markedly impaired cytotoxicity by 4 wk. These mice had normal serum and only mildly decreased femur zinc concentrations. We, therefore, found no evidence to suggest that the mildly altered zinc status of db/db mice fed zinc-adequate diets is a major factor contributing to their markedly impaired in vivo cell-mediated immunity.

Animals↗

PubMed1986

A study on location of synthetic site which mainly synthesizes and delivers fifth component of complement system in vivo.

Tissue sites for synthesis of the fifth component of complement (C5) in vivo have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. Our prior studies have demonstrated that bone marrow chimeras which had been prepared by transplanting marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients lacked detectable levels of C5 in the sera. However, when such potentially C5-deficient [C5(+)---C5(-)] chimeras were introduced into their spleens by means of injections of fully dispersed single cell suspensions of hepatocytes isolated from the C5-sufficient donor strain, they accepted the transplantation of hepatocytes for prolonged periods and developed a measurable amount of C5 in the sera. These results indicate that C5 protein in sera is not synthesized in significant amount by cells that are descendants of bone marrow cells but rather that this complement component is synthesized and delivered to the blood in vivo by somatic cells including liver cells that are not derivatives of the bone marrow.

Animals↗

PubMed1986

C1 esterase inhibitor deficiency in X-linked hypogammaglobulinaemia: an anomaly fostering anaphylactoid reactions following intramuscular gammaglobulin administration.

A patient with apparent X-linked agammaglobulinaemia was found to be inordinately susceptible to anaphylactoid reactions to intramuscular injections of gammaglobulin. The patient was found also to have low levels of C1 esterase inhibitor (C1 INH). The possibility that the C1 INH deficiency and in this patient, whether genetic or acquired, fostered the susceptibility to the production of anaphylactoid reactions after gammaglobulin injections urges further studies of the association of C1 INH deficiency and anaphylactoid reactions to gammaglobulin injections. The possibility that C1 INH levels like C1q levels may be low in hypogammaglobulinaemic patients as a consequence of increased catabolism of this regulator of the complement system when IgG levels are low is considered.

Adult↗

PubMed1986

Augmentation of natural killer cytotoxicity by alpha or gamma natural and recombinant interferons and interferon inducers. Effect of monocytes.

We investigated the effect of human peripheral blood monocytes on the augmentation of natural killer cytotoxicity by alpha or gamma natural and recombinant interferons (IFN) and certain interferon inducers. We observed that: (1) in the majority of the donors examined (75%) human peripheral blood monocytes do not affect natural killer cytotoxicity, determined by a 4-hour chromium-51 release assay, against target cells from hemopoietic human tumor cell lines. (2) Monocytes are not required and do not affect the augmentation of natural killer cytotoxicity by Escherichia coli-derived IFN-gamma, natural human IFN-gamma, E. Coli-derived IFN-alpha 2 or natural human IFN-alpha. E. Coli-derived IFN-gamma and natural human IFN-gamma have been reported to activate monocyte cytotoxicity determined in 72-hour assay. (3) Monocytes are not required for the augmentation of natural killer cytotoxicity against target cells from hemopoietic tumor cell lines by polyinosinic acid-polycytidylic acid or staphylococcal enterotoxin A.

Cells, Cultured↗

PubMed1986

Defective expression of T cell-associated glycoprotein in severe combined immunodeficiency.

A T cell surface membrane-associated glycoprotein, Tp40 (40,000 mol wt), also designated as CD-7, was not expressed by the T cells of a patient with severe combined immunodeficiency. In addition to this abnormality, T cell proliferative responses to mitogens were defective and the IL-2 receptor expression was deficient on the patient's T lymphocytes. However, his T cells were found to provide help for the differentiation of normal B cells to Ig-secreting cells. Abundant circulating B cells were detected. These B cells proliferated normally in the presence of anti-mu antibodies and B cell growth factors, but did not differentiate into antibody-secreting cells when provided with the help of normal T cells. In addition, his activated B cells did not proliferate to IL-2 even though IL-2 receptors were expressed. A successful allogeneic histocompatible bone marrow transplantation resulting in T cell engraftment corrected both the T and B cell immunodeficiencies. These findings support the hypothesis that the Tp40 deficiency present in this patient is related to a defect of the T cell precursors, and that Tp40 plays important roles not only essential to T cell interactions but also to certain aspects of T-B cell interaction during the early lymphoid development.

Antibodies, Monoclonal↗

PubMed1986

Studies on lymphocyte homing in autoimmune prone NZB mice.

Lymphocyte homing patterns in young (3-5 months old) and old (10-12 months old) autoimmune prone NZB mice were investigated by transferring 51Cr labelled lymphoid cells into syngeneic and H-2 compatible allogeneic recipients. We confirmed that non H-2 alloantigens as well as H-2 alloantigens can be important determinants of apparent abnormalities of cellular distribution with the techniques employed. No gross abnormalities of lymphocyte traffic were present in the young NZB mice as compared to the autoimmune resistant strains of mice when syngeneic cells are used. Spleen of older NZB mice appeared to be less attractive to lymph node cells than was the spleen from young NZB mice. Splenocytes of older NZB mice localized significantly more in the liver and less in the lymph nodes as compared with splenocytes from young NZB mice. The mechanism underlying abnormalities of lymphoid cell distribution which feature the autoimmune-prone NZB mice are not yet clear and further studies will be necessary before they can be characterized definitively. Our findings, using syngeneic cells, are in disagreement with those of Zatz and Lance since evidence of abnormal distribution of lymphocytes in young NZB mice were not seen when syngeneic cells were employed.

Aging↗

PubMed1986

Fc and C3b receptor expression of phagocytes in poorly controlled diabetic patients.

Attachment, an energy-independent step, of sensitized sheep erythrocytes EA and EAC to Fc and C3b receptors, respectively, on granulocytes and monocytes from poorly controlled diabetic patients was investigated. The results show similar percentages of EA and EAC rosette-forming cells for normal and diabetic human neutrophils. The expression of Fc receptors on normal and diabetic monocytes were also similar in that the former contained 74.5 +/- 9.3% and the latter contained 66.0 +/- 9.4% rosette-forming cells. However, a significantly lower percentage (48.3 +/- 15.2%) of EAC rosette positive cells was found in diabetic monocytes as compared to that (68.1 +/- 8.2%) found in normal controls (p less than 0.001). Incubation of diabetic monocytes with insulin or serum obtained from normal individuals one hour prior to assay corrected the impaired expression of C3b receptors in diabetic monocytes. In addition, we also found that diabetic serum itself is noxious to C3b receptor expression by normal human monocytes and that high concentrations of glucose play no apparent role in the regulation of the receptor function.

Adult↗

PubMed1986

Analysis of synthetic sites of fourth and fifth components of serum complement system in allogeneic bone marrow chimaeras.

Synthetic tissue sites for the fourth and fifth components of complement (C4 and C5) have been investigated using allogeneic bone marrow chimaeras in mice. One group of chimaeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice that produce high levels of C4 into irradiated recipients that are characterized by having low levels of C4 or vice versa. In such chimaeras, lymphoid cells and serum immunoglobulin allotypes were shown to be exclusively of donor origin. However, haemolytic activities of sera from the chimaeras were consistently identical with those of normal mice of the recipient strain. Similar results were obtained when the complement component levels of the sera were evaluated by double diffusion assays. C4 or C5 antigens were detected in sera of the chimaeras only when recipients were strains that are characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 or C5 complement components present in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimaeric mice.

Animals↗

PubMed1986

Interrelationships between zinc and immune function.

Zinc deficiency is a common nutritional problem observed both in human and in animal populations that has profound effects on host defense mechanisms. Using the young adult mouse as a model, it has been demonstrated that a moderate period of suboptimal zinc causes thymic atrophy, lymphopenia, and alterations in the proportions of the various subsets of lymphocytes and mononuclear phagocytes. As a result, antibody-mediated responses to both T cell-dependent and T cell independent antigens are significantly reduced. Cytolytic T cell responses, natural killer (NK) cell activity, and delayed-type hypersensitivity (DTH) reactions are also depressed. Suboptimal zinc during in utero development of mice causes persistent states of immunodeficiency in the offspring that can even be transferred to subsequent generations. In regard to human immunological consequences of zinc deficiency, patients with the genetic disorder of zinc absorption, acrodermatitis enteropathica, also exhibit atrophic thymuses, lymphopenia, anergic DTH responses, and reduced NK cell activity. Patients suffering from sickle cell anemia or uremia with associated deficiencies in zinc exhibit similar immune deficiencies. An additional outcome of these studies has been shown to be an essential cofactor for thymulin, one of the thymic hormones. Furthermore, addition of zinc salts to culture can polyclonally activate lymphocytes as well as augment responses to mitogens in adjuvant-like manner.

Acrodermatitis↗

PubMed1986

Immunorestoration.

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Acute Disease↗

PubMed1986

Detection of circulating immune complexes in liver diseases, systemic lupus erythematosus and glomerulonephritis by polyethylene glycol precipitation.

A method for detection and quantitation of circulating immune complexes using precipitation of the complexes by polyethylene glycol (PEG) has been reexamined to determine the influence of pH on the recovery and the reproducibility of the results. Results showed that the pH optimum for these determinations was 7.8. The recovery percentages range from 57.8-146.5% at lower immune complex concentrations, and from 73.9-101.3% at higher concentrations. The reproducibility of the method seems reasonably acceptable with a percent coefficient of variation ranging from 0.5-9.5. This method for quantitation of circulating immune complexes by polyethylene glycol precipitation is consistent and relatively reliable. Using this method, the levels of circulating immune complexes in sera in patients with hepatitis, liver cirrhosis, hepatoma, acute post-streptococcal glomerulonephritis (before and after treatment) and systemic lupus erythematosus have been examined. The results showed that except the patients with treated acute post-streptococcal glomerulonephritis who had a similar amount of immune complexes with normal controls, the level of immune complexes in patients with other types of diseases were all higher than the control. In addition, the composition of IgG, IgA, IgM, C3 and C4 of the precipitable complexes in sera of patients with three types of liver disease has been analyzed and demonstrated that the percentages of IgM were higher than the normal control. However, C3 and C4 in hepatitis and liver cirrhosis patients were lower than those of the control.

Antigen-Antibody Complex↗

PubMed1986

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate.

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, 60Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no difference was observed between 6 MV and 60Co. Using 60Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = 60Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.

Animals↗

PubMed1985

Hypercalcemia in cats with feline-leukemia-virus-associated leukemia-lymphoma.

Three cases of hypercalcemia were recognized among 11 cats presenting with leukemia-lymphoma for ex vivo immunoadsorption therapy using Staphylococcal Protein-A-coated filters. In addition, the initial mean serum calcium concentration of cats with leukemia-lymphoma was significantly higher (P less than 0.005) than that of healthy control cats or feline-leukemia-virus-infected cats without malignancy. During immunotherapy of the hypercalcemic cats, objective reduction in the extent of the malignancies was associated with a small reduction in the serum calcium concentrations. This response to treatment, the lack of skeletal metastasis, and the absence of renal and parathyroid pathologic findings imply that humorally mediated mechanisms may have been responsible for the production of the hypercalcemia.

Animals↗

PubMed1985

Polyclonal induction of immunoglobulin synthesis by feline leukocytes as identified in a reverse hemolytic plaque assay.

Optimal conditions of culture and assay for identification of feline immunoglobulin-secreting mononuclear cells were determined for the staphylococcal protein A-reverse hemolytic plaque assay (SpA-RHPA). Hemolytic plaques were most distinct and numerous when peripheral blood mononuclear cells were stimulated with 6.9 micrograms/ml pokeweed mitogen for 7 days. Immunoglobulin-secreting cells were identified morphologically within a zone of hemolysis utilizing a 1:5 dilution of rabbit anti-cat IgG and a 1:30 dilution of guinea pig complement as developing reagents. The SpA-RHPA system should contribute to an understanding of normal feline T- and B-lymphocyte interactions and will likely aid in the identification and understanding of immune cell dysfunctions associated with chronic feline leukemia virus infection.

Animals↗