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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 379 records · Page 21Linked to original sources

Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment of schizophrenic outpatients.

Plasma and red blood cell levels of haloperidol, thioridazine, and thioridazine's main metabolite mesoridazine were measured in schizophrenic outpatients during treatment with fixed doses of haloperidol or thioridazine for several months. These drug levels were compared to those in schizophrenic inpatients treated with fixed doses of the same neuroleptics. There were large interpatient variations in plasma and red blood cell levels at a given dose for schizophrenic outpatients as well as for inpatients. The intrapatient day-to-day fluctuation was much greater in the outpatients. The mean coefficient of variation of thioridazine or mesoridazine levels was about two-fold higher in schizophrenic outpatients than in inpatients. Differences in blood sampling time or compliance in medication ingestion do not fully explain the issue. The factors accounting for the increased intrapatient variability of plasma levels of thioridazine, mesoridazine, and haloperidol in schizophrenic outpatients remain unclear.

Erythrocytes↗

Rocket-ship psychophysics. Assessing visual functioning in young children.

A set of psychophysical procedures is described for rapidly measuring visual functions such as spatial contrast sensitivity, flicker fusion, and rod and cone two-color increment thresholds in young children. The psychophysical procedures, disguised as electronic space games, use a forced-choice paradigm combined with the method of descending limits. Because children enjoy the tasks and are highly motivated, the tests yield good sensory thresholds in a short period of time. However, when thresholds from 6-8-year-old children are compared with those of adults, the children have slightly higher thresholds for all of the functions tested. The differences are ascribed to the tendency of children to adopt a guessing strategy when stimuli are close to threshold.

Adolescent↗

TPA (12-O-tetradecanoyl-phorbol-13-acetate) activation and differentiation of human peripheral B lymphocytes.

The effect of the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate) on normal human peripheral blood and tonsil B lymphocytes was investigated. A strong DNA-synthesis response with the maximum at day 4 was detected. This response was, however, inhibited by increasing concentrations of serum in the medium. The membrane Ig expression was changed with a rapid decrease in IgD expression and a slower decrease in IgM and IgG expression. TPA-induced Ig secretion was detected in 12 out of 22 tested donors and the response was found to be independent of T cells and macrophages. The expression of four monoclonal antibody-detected B cell activation and differentiation markers, B1, B2, LB1 and BB1, was followed. The results indicate activation and differentiation of the B cells.

Antibodies, Monoclonal↗

Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens.

Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.

Antigens, Neoplasm↗

Utilization of mental health services by the aging.

A descriptive study of persons 55 years of age and older who were newly admitted (60 cases) or in ongoing treatment (30 cases) in a mental health center was done as an outgrowth of a utilization review study. The total population of 461 was studied from July 1, 1977, to June 30, 1978. A chart review of 90 cases was performed. The newly admitted subsample was married, was diagnosed as depressed, and had a broad range of dispositions into various treatment modalities. The chronic subsample was single, diagnosed as schizophrenic, and in treatment in a single community-support unit. These differences were statistically significant at the P<.01, P<.001, and P<.001 levels, respectively. Although the newly admitted subsample had no previous contact with psychiatric services, 44 of the 60 patients (73 percent) were on psychoactive medication prescribed by nonpsychiatric physicians. Implications for the training of general medical practitioners and mental health center staff, and the need for ongoing assessment of patients in community support units are discussed, as well as the significant risk to patients from potentially harmful drug interactions.

Aged↗

Characterization of the phorbol 12,13-dibutyrate (P(Bu)2) induced binding between human lymphocytes.

The mechanisms, cell surface structures, and cell types involved in the phorbol 12,13-dibutyrate (P(Bu)2)-induced binding between human lymphocytes were studied. Induction of cell aggregation by 20 min treatment with P(Bu)2 required Ca2+, an intact membrane, functional microfilaments, and the possible participation of an esterase or, less likely, a protease. Trypsin-sensitive cell surface structures were needed and neuraminidase (NANase) treatment slightly increased the intercellular binding. Retinoic acid, an anti-tumor promoting agent, was inhibitory. Calmodulin-dependent processes, microtubules, phospholipid methylation, intracellular levels of cyclic adenosine monophosphate, and cellular secretion did not seem to be involved. Cell conjugation between 24 hr P(Bu)2-treated and untreated cells required participation of trypsin-sensitive cell surface structures in each of the interacting cells and NANase treatment of one partner slightly increased the intercellular binding. Thymocytes, T cells, mature B and Epstein-Barr virus-transformed B cells aggregated while pre-B, early B, and intermediate B lymphocytes derived from representative malignancies did not. The lack of aggregation was not due to the absence of phorbol ester receptors. It is concluded that the P(Bu2)-induced intercellular binding is mediated by cell surface proteins, depends on certain enzymatic activities and metabolic events and involves certain cell types.

Amino Acids↗

A multidot immunobinding assay for autoimmunity and the demonstration of novel antibodies against retroviral antigens in the sera of MRL mice.

A dot immunobinding assay procedure has been developed for autoantibodies, and has been applied to the sera of MRL lpr/lpr mice. The profiles thus obtained include assays for circulating immune complexes, and antibodies against single-stranded DNA, double-stranded DNA, ribosomes, soluble nuclear deoxyribonucleoprotein, and retroviral antigens. Part of the data was compared with ELISA results. The anti-DNA assays were specific, as some individual sera show exclusively anti-double-stranded DNA specificity. The finding of anti-ribosomal antibodies in these mice extended the analogy between the murine disease and human systemic lupus erythematosus. The specificity of the anti-retroviral antibodies was examined following electrophoretic separation of the antigens and blotting on nitrocellulose. Previously undescribed classes of anti-retroviral antibodies were found. Circulating anti-retroviral protein p30 was found in all sera having high anti-retroviral titers.

Animals↗

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice. II. Anti-mu treatment affects the initiation and recruitment of T cells.

Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.

Animals↗

Microbial fermentative preparation of L-[15N2]lysine and its tracer: application to serum amino acid kinetic studies.

The microorganism Brevibacterium flavum 21129 has been used to produce multigram batches of L-[15N2]lysine of high purity and isotopic enrichment by supplementation of the growth medium with (15NH4)2SO4 of 98.0 atom% excess. The doubly 15N-labeled lysine can be detected at dilutions 10 times greater than singly labeled lysine when isotope dilution curves are analyzed by gas chromatography-mass spectrometry. This enhanced sensitivity permits kinetic measurements of plasma free-lysine isotope content over a 300-fold dilution during 6 h following a single oral bolus of 5 mg/kg body wt. This inexpensive preparation method lends itself to the production of highly useful biochemical compounds for kinetic studies of human nutrition.

Absorption↗

In vitro differentiation of chronic lymphocytic leukaemia cells with a small pre-B-like phenotype.

Neoplastic populations from three cases of chronic lymphocytic leukaemia (CLL) which had features consistent with a maturation arrest at the 'small pre-B' stage are described. The cells were small and rounded with a scanty cytoplasm and stained for mu heavy chains but not light chains intracellularly while surface immunoglobulin (SmIg) was either undetectable or expressed sparsely on a minority of cells. Other features included the weak expression of B1, a lack of B2, an absence of the common acute lymphoblastic leukaemia antigen (cALLA), the presence of Ia and a variable expression of the receptors for Fc gamma and C3. Successful induction of in vitro differentiation in all three of the cases allowed the identification of a sequence of events whereby cells initially containing isolated mu heavy chains in their cytoplasm, on commencing light chain synthesis, begin to express stable SmIgM while surplus light chain is secreted without any association with the heavy chain. Although this is followed ultimately by the secretion of intact Ig effector molecules, the export of surplus light chains is apparently maintained throughout the developmental sequence. These findings are discussed with particular emphasis on their relation to normal B-cell maturation.

Aged↗

Spatial and temporal properties of luminosity horizontal cells in the turtle retina.

Luminosity horizontal cells in the turtle retina respond approximately linearly to visual stimuli with contrast levels spanning a large part of the physiological range. We characterized the response properties of these cells under conditions of low photopic background illumination by measuring their spatial and temporal frequency transfer functions. Our experimental results indicate in two ways that, under these conditions, feedback from luminosity horizontal cells to cones does not play a major role in the mechanisms underlying the spatial and temporal tuning of horizontal cell responses. First, the shape of the spatial transfer function depended only weakly on the temporal frequency with which it was measured. Second, the shape of the temporal transfer function depended only weakly on the spatial frequency with which it was measured.

Animals↗

Carcinoma of the tonsillar area treated with external radiotherapy alone.

Seventy patients with carcinoma of the tonsillar area were treated with radiation therapy alone, all with a minimum follow-up of 3 years. Seventeen patients with stages I and II developed six recurrences and three were salvaged by surgery. Fifty-three patients with stages III and IV developed 24 recurrences, and only three could be salvaged by surgery. We conclude that radiation therapy is adequate for stages I and II carcinoma of the tonsillar area. Local control rate is satisfactory and surgical salvage is acceptable. Patients with advanced disease, Stages III and IV, have a poor survival rate with radiotherapy alone. Local recurrence is high and surgical salvage is inadequate. We have decided to offer selected patients with stages III and IV tonsillar carcinoma planned combined radiotherapy and surgery, in an effort to improve the survival rate.

Adult↗

Regulation of lymphocyte production in the bone marrow. I. Turnover of small lymphocytes in mice depleted of B lymphocytes by treatment with anti-IgM antibodies.

To examine the concept that the genesis of lymphocytes in the bone marrow may be regulated by homeostatic feedback signals from peripheral B lymphocytes or their products, lymphocyte production was measured in mice selectively depleted of B lymphocytes by repeated administration of anti-IgM antibodies from birth. The turnover of small lymphocytes was quantitated radioautographically after DNA labeling by continuous infusion of 3H-thymidine. In the femoral marrow of anti-IgM-treated mice, the number of small lymphocytes was reduced and their turnover time was shorter than in control mice, presumably reflecting the premature elimination from the marrow of maturing cells about to express surface IgM. The absolute number of small lymphocytes being produced per femur in unit time, however, was identical in anti-IgM-treated and control mice. Lymphocyte production in the thymus was also unaffected by anti-IgM suppression whereas in the spleen the turnover of small lymphocytes was reduced due to the lack of young immigrant B lymphocytes from the bone marrow. The results demonstrate that the normal large-scale production of lymphocytes in mouse bone marrow is independent of the magnitude of the peripheral pool of B lymphocytes or the level of circulating immunoglobulins, suggesting the process is not subject to feedback control. Some implications for the genesis and diversity of primary B lymphocytes are discussed.

Animals↗