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B J Green

Publications and source records attributed to B J Green.

15 recordsLinked to original sources
PubMed1990

Xenoantibodies in the rat against guinea pig tissues.

The role of naturally occurring antibodies in discordant xenograft rejection is poorly defined. This is partly attributable to a lack of information regarding their tissue specificity and titers. Sera from different rat strains were studied for naturally occurring antibodies against guinea pig tissues using immunofluorescence and immunoperoxidase staining techniques. All sera contained IgG and IgM antibodies in low titers against erythrocytes, lymphoid cells, and a variety of tissue structures. Intentional immunizations of adult rats with guinea pig cells resulted in the production of xenoantibody specificities that were not detectable in nonimmunized animals. Immunizations of Munich-Wistar rats with guinea pig skin grafts occasionally resulted in the formation of antibodies that reacted with allogeneic and syngeneic cells of the liver, lung, and lymphoid organs. We conclude that rats have low titers of naturally occurring xenoantibodies against various tissue structures of the guinea pig, but their importance in xenograft rejection remains to be established.

Animals↗
PubMed1989

Serum immunoglobulin E levels in patients with primary biliary cirrhosis.

Serum IgE levels were measured in 22 symptomatic adults with primary biliary cirrhosis (PBC) and 19 asymptomatic female adults with positive serum mitochondrial antibody tests. Control populations included 45 adult patients with chronic liver disease consisting of autoimmune chronic active hepatitis (N = 15), alcoholic liver disease (N = 15), or miscellaneous cholestatic liver disorders (N = 15), and 87 healthy adult hospital personnel. Fourteen of 22 (64%) patients with PBC had low (less than 10 KU/L) or undetectable serum IgE levels, compared to 12 of 45 (27%) control patients with liver disease (p less than 0.005) and 39 of 87 (45%) healthy control subjects (p = 0.09). Low serum IgE levels were also found in most (13 of 19 patients, 68%) asymptomatic individuals with positive serum mitochondrial antibody tests (p less than 0.005 and p less than 0.05 versus liver disease and healthy control subjects, respectively). In vitro IgE production by peripheral blood mononuclear cells after pokeweed mitogen stimulation was determined in eight patients with PBC and in eight healthy control subjects. After pokeweed mitogen stimulation, one of three, patients with PBC compared to four of four healthy control subjects with detectable levels of serum IgE, produced sufficient amounts of IgE to be detected in culture supernatants. Neither the five patients with PBC nor the four healthy control subjects with undetectable serum IgE levels produced sufficient amounts of IgE in vitro to be detected in our assay system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Natural killer-cell activity and the response to interferons alpha, beta, and gamma in patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic, life-threatening disorder that is believed to be immunologically mediated. Abnormal immunologic findings have been detected in T suppressor cell activity, B cell responsiveness, and natural kill (NK)-cell function. NK-cell function has been described as low and to be poorly responsive to high concentrations of interferon (IFN). The present study was initiated to determine the response of NK-cell function of patients with PBC to all forms of IFN (alpha, beta, and gamma) at low concentrations. Ten patients were assessed on two occasions approximately 5 months apart. There was a significant decrease in the NK-cell function in a 4-hour assay but only one patient had low NK-cell function after an 18-hour assay. The augmentation of NK-cell activity secondary to 10 and 50 U/ml of IFN-alpha, beta, and gamma was equivalent in the patients and in the control subjects. The relative increase induced by IFN was higher during the 4-hour assay than in the 18-hour assay. Hence, there may be a kinetic impairment of NK-cell function in patients with PBC, but the ultimate lytic activity, and response to the various forms of IFN, are normal.

Adult↗
PubMed1988

Studies on the mechanism of activation of human natural killer function by interferon and inhibitors of thymidylate synthesis.

Previous publications from this laboratory have demonstrated that agents such as methotrexate (MTX), 5-fluorodeoxyuridine (FUdR), trimethoprim, and D-glucosamine (D-GlcN), which are known to inhibit thymidylate synthesis, can augment human NK activity in vitro. Furthermore, this augmentation was inhibited by exogenous thymidine (TdR) at concentrations of 10(-6) to 10(-7) M. In this report, underlying mechanisms of action of FUdR, D-GlcN, and IFN are compared. Each of these agents increased the lytic activity of effector cells bound to targets but did not increase the percentage of conjugates formed. The augmentation could be induced in a population highly enriched for NK cells (Leu-1 lb positive in phenotype). FUdR and D-GlcN could not induce any augmentation in a Leu-1 lb-negative subpopulation whereas IFN could induce significant lytic activity. alpha-Amanitin, an inhibitor of RNA polymerase II, blocked the activation of NK activity by all three reagents; hence gene expression was required. Comparison of [35S]methionine-labeled proteins by two-dimensional gel electrophoresis revealed that six new proteins were induced in IFN-treated cells. Three of these were similar in pI and molecular weight to the newly synthesized proteins in the D-GlcN-treated cells. One protein was synthesized in increased amounts in the FuDR-treated cells and it was not common to either of the other treatments. Evidence to date is consistent with the hypothesis that separate mechanisms underlie the activation of NK cells by IFN and thymidylate synthesis inhibitors, although the existence of a final common pathway for all NK response modulators cannot be excluded at the present time.

Antibodies, Monoclonal↗
PubMed1988

Procainamide in vivo modulates suppressor T lymphocyte activity.

Autoantibodies to histone and denatured DNA have been found in 80% of patients treated with procainamide. Of these 10 to 20% will eventually develop a Systemic Lupus Erythematosus-like syndrome. Although the mechanism by which procainamide exerts its effect is unknown, in vitro studies suggest that procainamide may inhibit suppressor T cell activity. We have studied the immune function of 18 patients receiving a two hour infusion of procainamide during transvenous catheter electrophysiologic studies. There was no difference between pre and post infusion samples with respect to T and B cell mitogenesis or pokeweed mitogen-induced immunoglobulin secretion. However, in seventeen of eighteen patients, there was a marked decrease in Concanavalin A-inducible suppressor cell activity. This decrease appeared to be related to the amount of procainamide infused as high dose samples showed less suppressor activity than low dose samples. Thus the data show that procainamide, when given in vivo, leads to a rapid and dose dependent decrease in suppressor cell activity.

Adult↗
PubMed1988

Relationship of aluminum to neurocognitive dysfunction in chronic dialysis patients.

Aluminum has been proposed as the causative agent in dialysis encephalopathy syndrome. We prospectively assessed whether other, less severe, neuropsychologic abnormalities were also associated with aluminum. A total of 16 patients receiving chronic dialytic therapy were studied. The deferoxamine infusion test (DIT) was used to assess total body aluminum burden. Neurologic function was evaluated by quantitative measures of asterixis, myoclonus, motor strength, and sensation. Cognitive function was assessed by measures of dementia, memory, language, and depression. There were four patients with a positive DIT (greater than 125 micrograms/L increment in serum aluminum) that was associated with an increase in the number of neurologic abnormalities observed, as well as an increase in severity of myoclonus, asterixis, and lower extremity weakness. Patients with a positive DIT also showed significant impairment in memory; however, no differences were noted on tests of dementia, depression, or language. There was no significant correlation between sex, age, presence of diabetes, mode of dialysis, years of chronic renal failure, years of dialysis or years of aluminum ingestion and any neurologic or neurobehavioral measurement, serum aluminum level, or DIT. These changes may represent early aluminum-associated neurologic dysfunction.

Adult↗
PubMed1987

Defect in production of B cell differentiation factor-like activity by mononuclear cells from a boy with hypogammaglobulinemia.

The case history of a boy who presented at 6 mo of age with pneumocystis carinii pneumonia is described. Hypogammaglobulinemia was detected. His T lymphocytes and B lymphocytes proliferated with mitogens but no immunoglobulin was secreted secondary to polyclonal stimulation with pokeweed mitogen. His peripheral blood mononuclear cells secreted interleukin 2 and B cell growth factor (BCGF) but failed to secrete detectable levels of B cell differentiation factor (BCDF). Studies of his B lymphocytes showed that they would secrete immunoglobulin in vitro after exposure to a supernatant containing BCDF activity. Hence regulatory control of these lymphokines appears to be independent, and this case illustrates the pathologic sequellae of a defect in BCDF-like production.

Agammaglobulinemia↗
PubMed1987

Humoral immune response in patients with hemophilia.

Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses.

AIDS-Related Complex↗
PubMed1987

Modulation of natural killer cell activity by tamoxifen in stage I post-menopausal breast cancer.

Tamoxifen, an antiestrogen which competes for the estrogen receptor, modulates natural killer cell activity in vivo. Seventeen post-menopausal stage I breast cancer patients received tamoxifen for 1 month and a statistically significant increase in NK activity was demonstrated (P = 0.0005). There was a small incremental shift in the number of Leu-11b positive cells. These data demonstrate that tamoxifen functions as a biological response modifier.

Aged↗
PubMed1986

T lymphocytes from hemophiliacs proliferate after exposure to factor VIII product.

Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.

Adult↗
PubMed1986

Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay.

A new TSH immunoenzymometric assay was found to be capable of discriminating between the serum TSH values of normal subjects [2.28 +/- 1.02 (+/-SD); range, 0.6-6.5 microU/ml] and those of clinically euthyroid, antithyroid drug-treated (n = 22) or clinically thyrotoxic (n = 34) patients. While a wide spectrum of basal TSH values was found in the antithyroid drug group [ranging from undetectable (less than 0.05 microU/ml: 57%) to 17.9 microU/ml], all clinically thyrotoxic patients had undetectable values. In 33 patients receiving chronic oral T4 therapy for treatment of goiter (n = 15) or thyroid cancer (n = 18), 48% (6 of 33) had undetectable basal TSH levels and no TSH response to TRH stimulation. Detectable TSH levels were found in 42% (14 of 33), and TRH responsiveness was found in 52% (17 of 33). The TSH response to TRH stimulation was less than 2.0 microU/ml in 7 patients. Serum free T4 index, free T3 index, and free T4 levels and oral T4 dosage were inferior predictors of TRH responsiveness compared to the basal TSH value. No patient receiving more than 0.2 mg T4 daily or having a free T4 index above 18, a free T3 index above 205 or a free T4 level above 3.0 ng/dl had a TSH response to TRH. Seventy-six percent (16 of 21) of the patients, when reevaluated 1-6 weeks after increased oral T4 dosage, had a significant reduction in their serum thyroglobulin level. This was true of both patients with initially detectable (11 of 14) as well as undetectable (5 of 7) basal serum TSH levels. These findings support the concept that subnormal and, for that matter, as yet undetectable levels of circulating TSH may exert stimulatory effects on thyroid tissue.

Adult↗
PubMed1986

Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon.

Patients with hemophilia are at risk for the development of acquired immunodeficiency syndrome (AIDS). Patients with AIDS have recurrent infections and/or malignancy and altered immune response, including decreased T lymphocyte counts, decreased T helper lymphocytes, defective T cell blastogenesis, hypergammaglobulinemia, defective natural killer (NK) activity and impaired response of NK to interferon-beta (IFN-beta). It is feasible that chronic antigen stimulation with subsequent release of interferon could be related to the impaired NK reactivity to IFN-beta of patients with AIDS. Because hemophiliacs are subjected to chronic antigen stimulation secondary to the administration of foreign protein, the reactivity of NK cells from patients with hemophilia to IFN-alpha, IFN-beta and IFN-gamma was studied. Eight patients with hemophilia requiring high levels of clotting factor replacement were assessed. Three patients were antibody positive to HTLV-III. All had normal baseline NK cell function. In the first set of experiments, all patients responded normally to in vitro IFN-alpha by increasing NK activity, but four patients had significant failure and two had mild impairment in NK response to IFN-beta. This latter observation was particularly evident at very low concentrations of IFN. In repeated experiments, seven of eight had impaired NK response to IFN-beta and IFN-gamma but normal response to IFN-alpha. Only one patient's NK cells responded better to IFN-gamma. There was no obvious correlation of these findings to antibody status to HTLV-III. Chronic antigen stimulation and the modulation of interferon receptors are discussed as possible mechanisms that could produce these findings.

Adult↗
PubMed1978

A radioimmunoassay for 3',5'-diiodothyronine.

The present report describes a RIA for 3',5'-diiodothyronine (T2) that can be performed on unextracted serum and which has a lower limit of detectability of 2 ng/dl. Cross-reactivity with other iodothyronines was negligible, except for rT3 which began to demonstrate cross-reactivity when rT3 levels were elevated to 180 ng/dl. Employing this RIA for T2, we have determined that 83 healthy individuals had a mean (+/-SE) serum T2 concentration of 5.0 +/- 0.3 ng/dl, thyrotoxic subjects (n = 12) had a mean T2 level that was elevated to 10.8 +/- 0.8 ng/dl, and each of 6 hypothyroid subjects had undetectable (less than 2 ng/dl) concentrations. Athyreotic patients (n = 8), receiving 0.4 mg T4 daily, had serum T2 concentrations of 15.0 +/- 3.0 ng/dl. Fasting in obese subjects was associated with an increase in serum T2 to 6.9 +/- 0.6 ng/dl from a basal level of 4.4 +/- 0.4 ng/dl in the fed state (P less than 0.01). Despite the fact that rT3 levels may be elevated in amniotic fluid and that rT3 is expected to represent the major source from which extrathyroidal T2 arises, T2 levels were low in amniotic fluid, being undetectable (less than 2 ng/dl) in 9 of 19 samples; the mean (+/-SE) T2 concentration in the 10 detectable samples was 5.4 +/- 1 ng/dl. These data indicate T2 is a normal component of serum and that the majority of serum T2 is probably derived from peripheral conversion. Furthermore, these observations suggest that situations associated with elevated rT3 levels (e.g. thyrotoxicosis and fasting) may also have increased T2 values.

Amniotic Fluid↗