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Biomedical subjects

D Gilbert

Publications and source records attributed to D Gilbert.

At least 19 recordsLinked to original sources
PubMed1992

Development of the B cell anti-DNA repertoire in (NZB x NZW)F1 mice. Relationship with the natural autoimmune repertoire.

The relationship between pathologic anti-DNA and natural autoantibodies (Auto Ab) remains unclear. In particular, it has not yet been elucidated whether pathologic anti-DNA antibodies originate from and are regulated by the pool of natural Auto Ab. To address this question, a large number of Ig-secreting hybridomas were derived from the unstimulated splenocytes of B/W mice, newborn to 12 mo of age, and their binding activities against a panel of self-Ag (DNA, actin, tubulin, myosin, and myoglobin), isotype, idiotypic determinants, and VH gene utilization were analyzed. A progressive increase in the number of Ig-secreting clones was observed and associated with a constant proportion (approximately 6%) of autoreactive B cell clones. However, dramatic changes in the pool of autoreactive B cell hybridomas were observed as the disease evolved, including the selective maintenance of IgM anti-DNA polyspecific antibodies, reduction in percentage of polyspecific IgM mAb with no DNA-binding activity, and the production of IgG anti-DNA antibodies of the IgG2 class. The kinetics, immunochemical properties, and idiotypic analysis of polyspecific IgM mAb with DNA-binding activity strongly suggest that they belong to natural Auto Ab and constitute the precursors of pathologic IgG anti-DNA antibodies. In addition, and IgM polyspecific antibody was demonstrated to bind IgG anti-DNA mAb through F(ab')2 interactions suggesting a regulatory role of natural antibodies and their participation in the control of pathologic Auto Ab production.

Age Factors↗
PubMed1992

The restricted nature of HIV-1 tropism for cultured neural cells.

Infection of the central nervous system by HIV-1, the agent of AIDS, is characterized by the presence of infected and giant microglial cells as well as astrocytosis, demyelination, and neuronal loss. To determine whether cells of neuroectoderm origin can be infected by HIV-1, we have inoculated primary cultures derived from adult human brain with a lymphotropic virus (LAV) or a neurotropic virus (Jr-FL) isolated from a patient with AIDS dementia. While Jr-FL invariably causes productive infection of cultured brain microglia, neither astrocytes nor oligodendrocytes became productively infected by these viral strains. Moreover, the cultured oligodendrocytes develop a normal network of processes and express differentiation antigens in the presence of an ongoing lytic infection of microglial cells. No HIV-1 proviral DNA was detected in primary astrocyte cultures devoid of microglial after inoculation of either HIV-1 strain. Similarly, the neuronal cell line HCN-1 in its differentiated state did not allow the virus to go through cycles of reverse transcription and replication. LAV, however, was able to replicate in undifferentiated HCN-1 cells. Thus, tropism of HIV-1 appears tightly restricted to only one type of differentiated cell in the CNS, the microglia.

AIDS Dementia Complex↗
PubMed1992

Regulation of microglial function by interferons.

Cultured neonatal rat microglia were pretreated with varying doses of either purified interferon (IFN) alpha/beta or recombinant IFN gamma for 24 or 48 h and the following functional parameters examined; superoxide anion production, interleukin-1 secretion and chemotaxis. IFN gamma produced a marked increase in superoxide anion levels when PMA was used to initiate superoxide anion production but had no effect in OPZ-stimulated microglia. Treatment with IFN alpha/beta potentiated superoxide anion production in both PMA and OPZ-stimulated cells. Interleukin-1 activity was decreased by treatment with IFN gamma for 24 h while IFN alpha/beta increased IL-1 activity at 48 h. Removal of serum from the treatment media prevented the action of IFN alpha/beta on IL-1 production. Treatment with IFN alpha/beta or gamma decreased chemotaxis of microglia in response to zymosan activated serum. The data indicate that IFN gamma and alpha/beta can regulate microglial function and that this regulation may differ from that seen for other monocytically derived macrophages.

Animals↗
PubMed1992

Production of a human monoclonal anti-epithelial cell surface antibody derived from a patient with pemphigus vulgaris.

The production of monoclonal autoantibodies derived from individuals with autoimmune diseases constitutes a powerful tool to analyse an autoimmune process at both the antigen and antibody levels. We established a human anti-epithelial cell surface monoclonal antibody by applying hybridoma technology using peripheral blood lymphocytes from a patient with pemphigus vulgaris using a heteromyeloma as the fusion partner. The F12 monoclonal antibody displays four major characteristics: (1) it belongs to the IgM, kappa class; (2) it binds to the cell surface of stratified squamous and simple epithelia; (3) it recognizes an antigenic determinant associated with the desmosomal complex as demonstrated by indirect immunoelectron microscopy; (4) by immunoblotting analysis, it reacts with a 185 kDa polypeptide which was also recognized by a few pemphigus vulgaris sera. Although the F12 monoclonal antibody does not have the immunochemical properties of classical pemphigus vulgaris autoantibodies, several arguments suggest its relevance to the pemphigus vulgaris autoimmune response and, therefore, the heterogeneity of the antigen/antibody systems involved in this autoimmune disorder.

Adolescent↗
PubMed1992

An evaluation of optic disc and nerve fiber layer examinations in monitoring progression of early glaucoma damage.

From annual examinations of 813 ocular hypertensive eyes, the authors compared optic disc and nerve fiber layer photographs in 2 age-matched subgroups: 37 eyes that converted to abnormal visual field tests at the end of a 5-year period and 37 control eyes that retained normal field tests. Disc change was detected in only 7 of 37 (19%) converters to field loss and in 1 of 37 (3%) controls. Progressive nerve fiber layer atrophy was observed in 18 of 37 (49%) converters and in 3 of 37 (8%) controls. Serial nerve fiber layer examination was more sensitive than color disc evaluation in the detection of progressive glaucoma damage at this early stage of glaucoma. The evaluation of cup-to-disc ratio or of the nerve fiber layer appearance in the initial photograph taken 5 years before field loss were equally predictive of future field damage. The position of nerve fiber layer defects was highly correlated with the location of subsequent visual field loss.

Aged↗
PubMed1992

Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating gamma delta+ T cells is correlated with disease activity.

The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant decrease of the gamma delta+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in patients with active disease. HLA-DR+/gamma delta+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated gamma delta+ T cells were predominantly V delta 1. Taken together, these data support the involvement of gamma delta+ T cells in the pathogenesis of RA.

Adult↗
PubMed1992

Aerobic capacity with two leg work versus one leg plus both arms work in men with peripheral vascular disease.

The purpose of this pilot study was to examine the correlation between ergometry in men with peripheral vascular disease exercising with both legs and with one leg and both arms. Fifteen men with peripheral vascular disease performed three symptom-limited exercise tests on an ergometer that could be operated from a wheelchair with both legs or with one leg and both arms. The three exercise conditions were both legs (arms stabilized), left leg plus both arms, and right leg plus both arms. The exercise parameters compared were maximum oxygen consumption, maximum heart rate, and duration of exercise. Blood pressure was monitored at two-minute intervals and oxygen saturation and electrocardiogram were monitored continuously. The mean VO2 max +/- standard deviation for both legs, right leg plus both arms, and left leg plus both arms were 14.36 +/- 6.15, 14.86 +/- 4.09, 14.01 +/- 4.14 ml O2/kg-min, respectively. The mean duration of exercise +/- standard deviation were 12.01 +/- 5.74, 10.94 +/- 4.68, and 9.81 +/- 4.70 minutes respectively. The mean maximum heart rate +/- standard deviation were 126 +/- 24, 137 +/- 23, 136 +/- 23, respectively for the same exercise conditions. The Pearson Correlation Coefficients for VO2 for both legs versus right leg plus both arms and left leg plus both arms were .639 and .873, respectively. The Pearson Correlation Coefficients for duration of exercise for both legs versus right leg plus both arms and left leg plus both arms were .837 and .877, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Black males who always use condoms: their attitudes, knowledge about AIDS, and sexual behavior.

One hundred six black males completed a questionnaire concerning attitudes and knowledge about the use of condoms and acquired immunodeficiency syndrome (AIDS). Of the 106 males in the study, 27 (26%) reported that they "always" used condoms, 31 (29%) did not use condoms and had low intentions of using them, and 48 (45%) reported high intentions to use condoms. Results indicated that knowledge about AIDS was exceptionally high for black males in all three groups. Black males with low intentions to use condoms reported significantly more negative attitudes about the use of condoms (eg, using condoms is disgusting) and reacted with more intense anger when their partners asked about previous sexual contacts, when a partner refused sex without a condom, or when they perceived condoms as interfering with foreplay and sexual pleasure. A significantly larger percentage of low intenders were treated for gonorrhea, syphilis, herpes, and genital warts than males in the other groups. Drug use did not differentiate the three groups, although marijuana was used more often by males in the low-intender group. Finally, a larger percentage of black males in the low-intender group reported experiences with anal intercourse and sex with a prostitute, but considered themselves at lower risk for AIDS than did their high-intender or steady-user counterparts.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Do African-American men and women differ in their knowledge about AIDS, attitudes about condoms, and sexual behaviors?

This study identified a sample of young African-American men and women classified as having multiple sex partners or one sex partner. Of the 149 men, 71 (47%) were classified as having multiple sex partners and 78 (53%) as having one sex partner. Of the 165 women, 29 (19%) were classified as having multiple sex partners and 126 (81%) as having one sex partner. Results indicated that the groups did not differ in their knowledge about acquired immunodeficiency syndrome (AIDS). However, attitudes about condom use differed significantly by gender (P less than .01) and by multiple sex status (P less than .001). Angry reactions regarding the negotiation of condom use occurred more with men than with women (P less than .05). Men and members of the multiple sex partners group tended to engage in more risky sexual behavior. These two groups also had a significantly (P less than .001) higher incidence of gonorrhea. While the multiple sex partners group had significantly more smokers (P less than .01), drinkers (P less than .01), and crack users (P less than .05), men were significantly higher consumers of marijuana (P less than .001) and alcohol (P less than .01). Overall, the results indicate that African Americans are knowledgeable about AIDS, but there appears to be a gap between knowledge and risky sexual behaviors. Prospective studies are needed to clarify the factors that determine the relationship (or lack of) between knowledge and risky sexual behaviors. Without such studies, a major part of the foundation that is needed for the development of sensitive and effective AIDS prevention programs for African Americans will be missing.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Evidence for an active hydrophobic form of factor H that is able to induce secretion of interleukin 1-beta or by human monocytes.

We studied the capacity of human factor H to promote the secretion of a lymphocyte-activating factor (LAF) by human monocytes cultured under serum-free conditions. Presence of LAF in the culture supernatants was assessed with the mouse thymocyte assay. Highly purified factor H alone had no effect on thymocyte proliferation. When monocytes were cultured with factor H for 24 h, a significant secretion of LAF was observed. The effect was dose dependent over a range of factor H concentrations from 1 to 15 micrograms/ml. Polymyxin B did not abrogate the capacity of factor H to induce LAF secretion. Adsorption of factor H preparations onto anti-factor H-Sepharose completely suppressed the phenomenon. Conversely, the activity was recovered in the acidic eluate. Furthermore, factor H subpopulation phi 2, that was able to bind to phenyl-Sepharose, was a stronger inducer of LAF secretion by monocytes than the subpopulation phi 1 (which did not bind to phenyl-Sepharose). Using a specific radioimmunoassay for interleukin 1-beta (IL 1 beta), we observed a good correlation between the LAF activity and the amount of IL 1 beta secreted by human monocytes stimulated with factor H. We have shown previously that factor H (phi 2) bound specifically on Raji cells whereas factor H (phi 1) did not. These results argue for the participation of the interaction of factor H with its receptor to stimulate the secretion of IL 1 by monocytes and that the phi 2 form of factor H is a ligand for the human factor H receptor.

Cells, Cultured↗
PubMed1991

Anti-myeloperoxidase antibodies: immunological characteristics and clinical associations.

Antibodies directed against myeloperoxidase (anti-MPO) were detected, using a solid-phase ELISA and purified sputum myeloperoxidase as the substrate, in 54 sera from 22 patients. Anti-MPO were present in 17 patients with crescentic glomerulonephritis (CGN), Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA), and thus are associated with different forms of vasculitis. Anti-MPO were also present in five out of 20 patients with systemic lupus erythematosus (SLE). Anti-MPO activity in SLE sera was low, in contrast to the high titers observed in patients with vasculitis. All positive sera had IgG anti-MPO (except two SLE sera) and most of them also contained low-titered IgM anti-MPO. Only three patients had high IgM anti-MPO activities, the significance of which remains to be determined. In patients with CGN, WG or MPA, the anti-MPO titer decreased following therapy and paralleled the disease activity. Thus, anti-MPO constitute a useful diagnostic tool and a sensitive marker of disease activity in this group of patients with vasculitis.

Arteritis↗
PubMed1991

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection.

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.

Azlocillin↗
PubMed1991

The effect of xanthine/xanthine oxidase generated reactive oxygen species on synaptic transmission.

The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xanthine oxidase produced a significant depression in evoked release, with no change in either resting membrane properties or in the action potential. Addition of catalase to the xanthine/xanthine oxidase-containing media partially blocked the synaptic depression, indicating that H2O2 contributes to the synaptic changes induced by exposure to xanthine/xanthine oxidase. H2O2 applied directly to the perfusing media also produced a decrease in synaptic efficacy. The results demonstrate that reactive oxygen species, in general, depress evoked synaptic transmission.

Action Potentials↗
PubMed1991

Familial and psychological correlates of smoking in black and white adolescents.

Cigarette smoking is considered to be the single most preventable contributor to chronic diseases, but there is still great controversy about the initiation and maintenance of smoking among adolescents. The goal of this study was to examine familial and psychological factors that contribute to the initiation and maintenance of smoking among black and white adolescents. To accomplish this, we tested 602 male (275 black and 327 white) and 460 female (174 black and 286 white) adolescent students enrolled in health classes in Tampa, Florida. Among blacks, 15.6% were currently smoking cigarettes, compared to 34.8% of the white students. Blacks who initiated smoking were most influenced by having a sister who smoked, while maintenance was most influenced by an older brother who smoked. In contrast, white adolescents who initiated smoking were more likely to have an older brother who smoked, while maintenance of smoking was predicted by having a father who smoked. Furthermore, the data show that both the initiation and the maintenance of smoking among blacks is related to the experience of intense feelings of anger and irritability, while among white adolescents, these emotions contribute only to the initiation of smoking. These data indicate that smokers and nonsmokers differ in their emotional reactions to stress, and that ethnicity (black vs white) is an important determinant in the association between smoking and emotional reactions to stress. The overall pattern of the findings in this inquiry suggests that the efficacy of antismoking treatment procedures could be enhanced by targeting exaggerated emotional reactions for modification. The data also suggest that smoking prevention programs for adolescents should take into consideration pressures to smoke that may arise from having family members who smoke. Given the inherent problems of a cross-sectional research design, future research is needed to clarify the interrelationships between smoking, ethnicity, and measures of the experience and expression of anger.

Adaptation, Psychological↗
PubMed1990

[Lupus erythematosus disseminatus, lesional mechanisms, pathogenesis and genetics].

Systemic lupus erythematosus (SLE) is a model of autoimmune disease. Its study, and that of spontaneous murine models, have benefited from new immunological and molecular biology techniques. New hypotheses have been put forward to explain the mechanisms of SLE lesions. The genetic origin of autoantibodies begins to be better known. Auxiliary CD4+ lymphocytes seem to play a capital role in the occurrence of lymphocyte abnormalities. The disease is multigenic. Much work is currently devoted to the identification and characterization of genetic factors.

Autoantibodies↗
PubMed1990

Enhanced production of superoxide anion by microglia from trisomy 16 mice.

Disruption of normal oxygen radical metabolism in the CNS may contribute to the neuropathological changes associated with Down syndrome (trisomy 21) and its mouse counterpart, the trisomy 16 (Ts16) mouse. One potent source of oxyradicals is the CNS-specific macrophage, the microglial cell. We prepared primary glial cultures from the cerebral cortices of Ts16 and normal littermate mice taken at day 15 of gestation. Microglia were isolated from confluent cultures after 14 days in vitro and assayed for superoxide anion production using a cytochrome C reduction assay. Stimulation by either opsonized zymosan (OPZ) or phorbol myristate acetate (PMA), produced significantly higher levels (2.8-20 fold) of superoxide per mg protein in Ts16 microglial cultures. Resting, i.e. unstimulated secretion, was not significantly different from littermate controls. Astrocyte enriched cultures, stimulated by OPZ, exhibited low levels of superoxide production which was higher in Ts16 mice than normal littermates. Microglial enriched cultures from rat neonatal cerebral cortices were exposed for 24 h to medium from the Ts16 glial cultures. Superoxide production in the Ts16 media treated rat microglia was significantly higher than in those treated with littermate conditioned media.

Animals↗
PubMed1990

Significance of "extravascular" protein binding for antimicrobial pharmacodynamics in an in vitro capillary model of infection.

The effect of protein binding in an "extravascular" space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (approximately 96% bound) or cephalexin (less than 5% bound) were administered every 6 h for four doses. A 10-fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P less than 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model.

Anti-Infective Agents↗