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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 217 records · Page 12Linked to original sources
PubMed1985

Estimating the economic costs of schizophrenia.

The economic costs of schizophrenia in New South Wales, Australia, were estimated using an incidence-based approach. The incidence of the disease was obtained from a case register. Direct treatment costs were calculated from length of stay data, the probability of readmission, and a direct costing of inpatient and outpatient care. Indirect costs were calculated from tables of average weekly earnings and work-force participation rates modified for the expected types of outcome. The prodrome was costed similarly. Costs were $139 million (in 1975 U.S. dollars), or $29 per head of the population of the State. A sensitivity analysis indicated that the likely margin of error of the estimate was plus or minus 15 percent. Comparison with the costs of myocardial infarction (in the same State at the same time and costed by the same methods) demonstrated that schizophrenia is a costly disease.

Adolescent↗
PubMed1985

OKT4 and OKT4A antibody treatment as immunosuppression for kidney transplantation in rhesus monkeys.

A mixture of OKT4+4A monoclonal antibodies (reactive with T4 cells) was tested for its immunosuppressive potential in rhesus monkeys receiving a kidney allograft. The kidney transplant model used in this study was designed to mimic the clinical situation. Therefore, all animals received a low dose of azathioprine and prednisolone, and the effectiveness of monoclonal antibody treatment was assessed in nontransfused and transfused recipients. The treatment very effectively suppressed acute graft rejection in untransfused recipients. In transfused recipients, which show an improved graft survival, no additional favorable effect of OKT4 + 4A treatment was seen when this treatment was given at the time of transplantation. It is possible that transfused recipients that reject their kidney in an acute fashion do not benefit from the OKT4 + 4A treatment because they have generated primed effector cells that belong to a T4-negative subpopulation or a T4-positive subpopulation with high affinity for donor cells. When the OKT4 + 4A treatment was given at the time of graft rejection in transfused recipients, thus treating chronic rather than acute rejection, a modest improvement in graft survival was observed. It seems, therefore, that anti-T4 antibodies will be of limited value for clinical transplantation and should be used in combination with other immunosuppressive drugs.

Animals↗
PubMed1985

Regulatory influence of thymopentin on splenic T cell sets of thymectomized and aged mice.

Thymectomy of mice aged 6-8 weeks causes a disproportion of splenic T cell sets, the Ly123 set being relatively decreased and the Ly23 set relatively increased (Ly123 decrease: Ly23 increase). A similar disproportion of splenic T cell sets was found to occur spontaneously with advancing age (12-18 months). By PA-SRBC assay, the total number of splenic Lyt+ cells is not appreciably reduced by thymectomy or by aging, but the Thy-1+ cell count falls by about 40% according to both PA-SRBC and cytotoxicity assays. Thus there is an increase in the number of Lyt+ cells expressing sub-threshold amounts of Thy-1. The following observations show that thymopentin (TP-5), a synthetic pentapeptide analogue of thymopoietin, counteracts these changes in thymectomized and aged mice. As reported previously, the capacity of C3H/HeJ female mice to reject C3H/HeJ male skin was raised by thymectomy, or with age, and treatment with TP-5 substantially normalized the rejection response. Here we correlate these findings with changes in the profile of splenic T cell sets. The splenic T cell set profile of thymectomized B6-Tlaa male and female mice was essentially restored by TP-5. The Ly123 decrease: Ly123 increase change caused by thymectomy was not associated with obviously altered proportions of Qa-1+ and Qa-1- subsets. Treatment of aged mice with TP-5 also prevented the onset of changes in splenic T cell sets that occur spontaneously with age. Thus thymectomy and aging give rise to disproportions of splenic T cell sets, and in C3H female mice to a heightened capacity for male skin rejection, both effects being largely abrogated by the TP-5 derivative of thymopoietin.

Aging↗
PubMed1985

Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation.

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.

Adolescent↗
PubMed1985

The impact of mild head injury on neuropsychological capacity in chronic alcoholics.

A series of neuropsychological tests known to be sensitive to the effects of chronic alcoholism was administered to 25 detoxified alcoholic patients with histories of mild head injury and 25 detoxified alcoholics matched for age, race, socioeconomic status, education and drinking history parameters, but without histories of head injury. None of the tests was performed at significantly different levels by the two groups. It was concluded that mild head injury did not compound the effects of chronic alcoholism among these patients, although it was noted that both groups demonstrated the anticipated impairments on the tests. It was also suggested that researchers need not exclude alcoholic subjects with mild head injury histories from studies involving the use of standard neuropsychological tests.

Adult↗
PubMed1985

Ocular dominance in patients with recently and remotely acquired lateralized brain lesions.

This study reports a significantly higher proportion of left-eyedness in patients with remotely acquired right hemisphere brain lesions as compared with patients with recently acquired right hemisphere lesions, as well as patients with left hemisphere lesions, regardless of whether they were recently or remotely acquired. It was determined that this finding could not be attributed to a higher incidence of left-handedness among the patients with remotely acquired right hemisphere lesions. The findings were interpreted in terms of a possible mechanism for adjustment to left field neglect.

Brain Diseases↗
PubMed1985

Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction.

To explore the role of the T3, T4, and LFA-1 molecules in high and low "avidity" interactions between SB2-specific cytotoxic T lymphocyte (CTL) clones and their targets, monoclonal antibody-mediated inhibition of cytotoxicity has been studied in experiments that vary the "avidity" of interaction in three different ways. 1) Previous results have been extended with respect to different CTL clones assayed on the same SB2-positive target cells. Differences between clones in susceptibility to anti-T3 inhibition paralleled variations in anti-T4 inhibition, and both correlated inversely with the "avidity" of the effector-target interaction (inferred previously from studies of conjugate dissociation). 2) A high "avidity" clone, 8.4, was identified that lysed not only SB2-positive cells but also cross-reacted on a few SB2-negative cells. Cold target inhibition studies confirmed the cross-reaction, and together with conjugate dissociation studies, indicated that cross-reaction to be of lower "avidity" than the specific recognition of SB2. Cross-reactive lysis was much more susceptible to inhibition by anti-T3 and anti-T4 than was specific lysis. 3) Anti-T3 and anti-T4 blocking was analyzed in the presence of anti-Ia antibody to reduce the amount of Ia antigen available on the target. Anti-T3 and anti-T4 antibody blocking was more efficient after the addition of anti-Ia antibody concentrations that (by themselves) produced minimal inhibition of lysis. As a control, anti-LFA-1 antibody blocking was analyzed in each of these three experimental systems that compare interactions of different "avidity"; minimal variation was observed in the efficiency of inhibition by anti-LFA-1. Thus, anti-T3 and anti-T4 inhibition correlates inversely with the "avidity" of that CTL-target interaction, but anti-LFA-1 inhibition does not.

Adult↗
PubMed1985

Activated human B cells display a functional IL 2 receptor.

These studies deal with the expression of a functional IL 2 receptor on activated primary human B cells. Antibody against the receptor (alpha-TAC) reacted with 25 to 65% activated B cells, inhibited B cell proliferation by 50% and inhibited B cell secretion of Ig by greater than 90%. These effects were shown to be independent of contaminating T lymphocytes. Anti-TAC immunoprecipitated a molecule of identical size (65,000 daltons) from T and B lymphocytes; B cells were also shown to actively synthesize the IL 2 receptor. The chymotryptic peptide chromatograms of TAC antigen from T and B cells show these molecules to be indistinguishable.

Antibodies, Monoclonal↗
PubMed1985

Null cell identification and characterization with OKT16: an anti-p40 monoclonal antibody.

A murine monoclonal antibody, OKT16, specific for human lymphocytes of T lineage, was isolated by standard immunization and hybridization techniques. The distribution of the antigen defined by OKT16 was similar to the antigen reactive with monoclonal antibodies 3A1 and WT1. This identity of antigen targets was confirmed in an enzyme-linked immunosorbent assay system and by sequential immunoprecipitation. Under reducing conditions, OKT16 reacted with an antigen of 40K daltons; however, under nonreducing conditions this antigen appeared as an 84K-dalton molecule, which suggests that the p40 antigen exists as a disulfide-linked dimer. By indirect immunofluorescence, OKT16 reacted with a greater fraction of nonrosetting, non-B (null) lymphocytes than with antibodies to other T cell-specific proteins. Two-color immunofluorescence demonstrated the coexpression of the T16 antigen and the C3bi receptor on most null cells. The T10 antigen (found on cortical thymocytes and activated peripheral T cells) was restricted to most T16-bearing null cells and expression of the Fc receptor for aggregated IgG (defined by monoclonal antibody 73.1) was restricted to a major subset of T16-bearing null cells. The T cell-specific markers defined by OKT8, OKT11, and OKT17, as well as the monocyte marker defined by OKM5, were expressed by smaller subsets of OKT16-reactive null cells. These studies support by phenotypic analysis the functional heterogeneity ascribed to null cells. The 40K-dalton T16 antigen has the most extensive null cell representation of all the T lineage markers described to date.

Antibodies, Monoclonal↗
PubMed1984

Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.

The present study examines the potential role of the T4 molecule in functional cell-cell interactions between target cells and human cytotoxic T lymphocyte (CTL) clones that are specific for HLA class II alloantigens encoded by the SB locus. There were marked differences (greater than 30-fold) between the seven SB-specific clones studied with respect to their susceptibility to inhibition by anti-T4 as well as anti-T3 antibodies. We wished to test the hypothesis that such variation among the clones would be due to differences in clonal "affinity" for antigen. To quantitate differences among the CTL clones in the tightness with which they bind target cells, the clones were analyzed using a previously published assay of susceptibility of CTL-target cell conjugates to dissociation in the presence of unlabeled targets. The results revealed that the clones that were most susceptible to inhibition by anti-T4 and anti-T3 were the weakest target cell binders, and vice versa. Anti-T4 antibody could partially induce dissociation of functional CTL-target cell conjugates in the absence of any added cold targets. For the "highest affinity" clone such anti-T4 antibody-induced dissociation could be observed at 4 degrees C but not 23 degrees C. These results indicate that the T4 molecule is functionally involved in target cell binding by CTL, and raise the possibility that although it is easiest to demonstrate the function of the T4 molecule in "low affinity" clones, that function may also be operative in the "high affinity" clones.

Adult↗
PubMed1984

Unusually restricted anti-isotype human immune response to OKT3 monoclonal antibody.

The unusual anti-mouse immunoglobulin (Ig) sensitization of a renal allograft recipient who was treated prophylactically with the anti-T cell monoclonal antibody OKT3 (IgG2a) is reported. Whereas in most patients, the injection of OKT3 (5 mg/day, i.v. for 13 days) induces the rapid appearance of neutralizing anti-OKT3 antibodies, the patient reported here did not show the signs of conventional anti-OKT3 sensitization. High levels of circulating OKT3 persisted and no OKT3+ lymphocytes reappeared during the whole treatment period. Moreover, no IgG or IgM anti-OKT3 antibodies were detected at any time, using a specific enzyme-linked immunosorbent assay. However, an atypical anti-isotype response was evidenced in this subject whose Ig were shown by indirect fluorescence to bind to normal T cells coated with OKT3 or with other anti-T cell murine monoclonal antibodies carrying the IgG2a isotype (no reactivity was observed with IgG1 or IgG2b molecules). The patient's Ig did not bind to normal T cells coated with F(ab')2 fragments of OKT3 and did not inhibit the binding of OKT3 to its target antigen indicating that they reacted with the Fc fragment of the OKT3 molecule. Additionally, and probably explained by this unusual anti-OKT3 response, the patient's Ig were shown to inhibit the phytohemagglutinin-induced proliferation of normal lymphocytes, to bind under selected in vitro conditions to normal T cells and lastly to enhance the antigenic modulation induced in vitro by OKT3 on its membrane receptor.

Antibodies, Monoclonal↗
PubMed1984

Poliovirus and vesicular stomatitis virus replication in the presence of 6-diazo-5-oxo-L-norleucine or 2-deoxy-D-glucose.

The effects of 6-diazo-5-oxo-L-norleucine (DON), 2-deoxy-D-glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined. During a 48-hr replication period, TM, DON, and DOG inhibit VSV plaque formation in HEp-2 cells by 99.9%, 99.8%, and 99.9% respectively. Inhibition of VSV by DON is reversed with glutamine. Although all three agents are known to affect glycoprotein synthesis, DON and DOG also inhibit plaque formation of viruses devoid of structural glycoproteins. Thus, plaque formation of PV types 1 and 3 and Coxsackie B3 virus is delayed in HEp-2 and Buffalo green monkey kidney cells during exposure to these agents. Since these viruses do not contain glycoproteins and since concentrations up to 10 micrograms TM/ml cause no significant inhibition of PV, DON and DOG are affecting another viral or cellular process. Inhibition of PV replication by DON is reversed by addition of 25 mM glutamine or marginally by exposure to a combination of 5 mM concentrations of cytidine, uridine, adenosine monophosphate, and guanosine monophosphate. Inhibition of PV replication by DOG is reversed with 5 mM uridine alone. During DON exposure of HEp-2 cells infected with PV, the amount of 3H-uridine incorporation at 5.5 hr postinfection (pi) is reduced to 53% of untreated controls, an amount 11% greater than incorporation in cultures infected with PV but not treated with DON. These data indicate that the inhibition of PV replication by DON or DOG occurs at the level of viral RNA synthesis, while the primary target of these agents during VSV replication is probably glycosylation.

Animals↗