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Biomedical subjects

D Gilbert

Publications and source records attributed to D Gilbert.

At least 91 records · Page 5Linked to original sources
PubMed1995

During HIV infection, CD4+ CD38+ T-cells are the predominant circulating CD4+ subset whose HLA-DR positivity increases with disease progression and whose V beta repertoire is similar to that of CD4+ CD38- T-cells.

Three-color automated flow cytometry was carried out on peripheral blood CD4+ and CD8+ T-lymphocytes of 42 HIV-positive patients using tri-color anti-CD4 or anti-CD8, phycoerythrin-anti-CD38, and fluorescein-anti-HLA-DR, mAbs to elucidate further the T-cell activation hypothesis recently proposed to explain CD4+ T-cell abnormalities observed during HIV infection. CD4+ CD38+ T-cells constituted the major part of circulating CD4+ T-cells in HIV-infected patients and their HLA-DR molecule positivity increased as their disease progressed. The level of CD38 and HLA-DR expression on CD4+ T-cells was positively correlated to that of CD8+ T-cells and to the level of beta 2-microglobulin. Next, to determine whether CD38 expression was associated with a selective expansion or deletion of V beta gene-defined subsets, we compared the V beta gene frequencies between CD38+ and CD38- T-cells from HIV-infected CDC stage II patients using 13 mAbs specific to V beta families. While selective expansion of certain V beta families was observed in CD4+ and CD8+ T-cells the T-cell receptor V beta subset distribution was similar among CD38+ and CD38-, CD4+ and CD8+ T-cells, suggesting that CD38+ expression was either independent of an HIV-encoded antigen-driven process or rather indicative of T-cell immaturity. It is proposed that the phenotype of circulating CD4+ and CD8+ T-cells of HIV-infected patients is a feature of two different mechanisms: (i) an in vitro activation state responsible for increased DR expression and selective expansion of V beta gene-defined subsets, and (ii) T-cell immaturity due to an increased turnover of these cells and accounting for increased CD38 expression.

ADP-ribosyl Cyclase↗
PubMed1995

An idiotype D23-bearing polyspecific, murine anti-DNA monoclonal antibody forms glomerular immune deposits. Pathogenic role of natural autoantibodies?

Identification of the immunochemical and structural properties of pathogenic anti-DNA antibodies is a major goal for understanding their origins and the mechanisms whereby they induce tissue lesions. Herein, we report on the production of an IgG2a,k anti-DNA monoclonal antibody (4B1), derived from a 12-month-old (NZB x NZW)F1 lupus mouse, able to form glomerular immune deposits. mAb 4B1 is a polyspecific antibody able to bind to ssDNA, actin, tubulin, cardiolipin and to laminin as shown by solid phase ELISAs. Indirect immunofluorescence labeling of HEp-2 cells gave a cytoplasmic staining pattern similar to that obtained with anti-cytoskeleton antibodies. Western blot analysis demonstrated that mAb 4B1 bore idiotype D23, previously shown to be characteristic of natural antibodies derived from normal mice. After injecting the 4B1-secreting hybridoma intraperitoneally into normal (NZW x BALB/c)F1 mice, glomerular immune deposits were observed along the capillary wall. These deposits contained mainly IgM, IgG2a and mAb 4B1, as demonstrated by direct immunofluorescence using a biotinylated-rat anti-4B1 idiotype mAb and kidney eluate analysis. Nucleotide sequence analysis of the VH and VL genes showed that mAb 4B1 is encoded by VH Q52, DSP2.9 and JH2 genes with minimal mutations and by VK8 very similar to the canonic D23 light chain, and JK1 germline genes. No arginine residues were observed in the VH CDR and both chains lacked N-segment addition. Thus, no structural characteristics deduced from the primary structure of mAb 4B1 could explain its pathogenic potential. However, the immunochemical and structural properties suggest that autoantibodies closely related to natural autoantibodies may be pathogenic.

Amino Acid Sequence↗
PubMed1995

Modeling shared health and social care information.

The article describes an analysis of the detailed data used by different groups of health care professionals and their requirements to share data as part of an integrated information systems design project. This systematic recording of their data usage and sharing requirements led to the development of a novel analysis technique: the complex object grid. The use of the complex object grid facilitates the description of information usage and needs at several levels of detail.

Aged↗
PubMed1995

Peripheral tolerance to host minor histocompatibility antigens in radiation bone marrow chimeras abrogates lethal GVHD while preserving GVL effect.

We previously reported that Mls-1a B10.D2 donor preimmunization prevents the development of a lethal graft-versus-host disease (GVHD) directed against host minor histocompatibility antigens (mHAgs) in lethally irradiated (DBA/2 x B10.D2)F1 recipients (LS mice). In the same combination, the graft of T-depleted bone marrow cells also results in no GVHD (TCD BM mice). Both groups of mice exhibit a host specific tolerance. In this paper, we examined whether a graft-versus-leukemia (GVL) effect can still take place without lethal GVHD in LS and TCD BM mice. The i.v. injection of P815 tumor cells into these mice, 2-3 months after the graft, indicates an antitumor activity in LS mice but not in TCD BM mice. When the P815 cells were administered 1 day before irradiation and graft, the leukemic mortality was significantly delayed in mice reconstituted with BM and spleen cells from a preimmunized donor, but not in mice reconstituted with T cell-depleted BM. In LS mice, a subclinical GVHD develops, probably due to CTL alloreactivity against host mHAgs that is observed in vitro. Moreover, cell depletion of the donor inoculum before grafting indicates that the antitumor effect is exclusively mediated by CD8+ T cells. In summary, a beneficial GVL effect, mediated by CD8+ T cells, can be preserved without lethal GVHD.

Animals↗
PubMed1995

[Simple intraparenchymal cysts of the cerebellum. Apropos of 2 cases].

INTRODUCTION: Cysts of the posterior fossa are common in the literature, but the simple cyst is rarely considered in the differential diagnosis of these cysts. METHOD: The cases of two female patients with clinical symptoms of expansive cerebellar lesion are described. These patients were explored by MRI. They were operated upon and an anatomico-pathological diagnosis was made. RESULTS: Both patients had an intraparenchymal cystic lesion of the cerebellum. No mural nodule and no enhancement after gadolinium injection were noted. The anatomico-pathological examination confirmed that the lesion was an intra-parenchymal simple cyst the walls of which showed no tumoral features. CONCLUSION: Although this anatomico-pathological entity has not previously been described in the literature, such rare diagnosis should be borne in mind in patients presenting with a cystic tumour of the posterior fossa. MRI is of paramount importance in the evaluation of these lesions, but the anatomico-pathological diagnosis is indispensable to exclude a possible tumour.

Adult↗
PubMed1995

MR of nonhemorrhagic postpartum pituitary apoplexy.

A 30-year-old woman had uterine bleeding and hypotension after delivery. Hyponatremic seizures and a mild headache prompted early neuroimaging, which disclosed an enlarged nonhemorrhagic pituitary gland with subsequent involution consistent with pituitary apoplexy (Sheehan syndrome). Endocrinologic investigation confirmed a partial pituitary insufficiency with subsequent improvement to almost normal status.

Adult↗
PubMed1994

[Lupus diseases].

Systemic lupus erythematosus is a multifactorial, non organ-specific autoimmune disease. Studies of the disease in humans, of spontaneous murine models and of induced experimental models have made it possible to identify the various factors involved. These factors act on the immune system, the abnormalities of which include polyclonal B cell activation, selection of autoreactive B clones by autoantigen, and intervention of helper T cells. Other abnormalities, such as disturbance of the idiotypic network and alteration of suppressor T cell function, are not excluded.

Animals↗
PubMed1994

Risk factors for the development of glaucomatous visual field loss in ocular hypertension.

OBJECTIVE: To detect characteristics of persons with ocular hypertension that are associated with a higher risk of future glaucomatous field loss. METHODS: Annual examinations of the optic disc, nerve fiber layer, and visual field in 647 persons with bilateral intraocular pressure higher than 21 mmHg and initially normal visual field test results with the Goldmann perimeter. RESULTS: Sixty-eight persons developed a field defect on two consecutive Goldmann visual field tests in at least one eye, while 579 others retained normal fields. Moderate or severe nerve fiber layer atrophy at baseline was associated with a seven to eight times greater risk of development of visual field loss. Attributes that were significantly associated with the incidence of field loss included older age, larger cup-disc ratio, smaller rim-disc area ratio, larger cup asymmetry, presence of disc crescent, and higher intraocular pressure. Characteristics found not to be associated with incidence were gender, race, hypertension, diabetes, refractive error, family history of glaucoma, smoking or alcohol drinking history, and disc area. CONCLUSIONS: Increasing nerve fiber layer atrophy judged by a semiquantitative grading system was associated with increasing risk of development of visual field loss among persons with ocular hypertension. The relationship of the development of field loss to race, myopia, family history of glaucoma, and medical history are more complex than has been presumed.

Adult↗
PubMed1994

Structural characterization of an (NZB x NZW)F1 mouse-derived IgM monoclonal antibody that binds through V region-dependent interactions to murine IgG anti-DNA antibodies.

Among B/W-derived IgM mAb, 12.5H was selected because of its ability to recognize, in solid phase ELISAs, IgG mAb with DNA-binding activity. mAb 12.5H bound preferentially to IgG2a mAb and did not react with B/W- or BALB/c-derived IgG2a mAb with no DNA-binding activity, suggesting V region-mediated interactions. mAb 12.5H also bound to IgG2a isolated from the sera of old B/W mice but did not react with Ig present in the sera of young B/W (< 6 months) or BALB/c mice. Further analysis of IgM/IgG interaction showed that the binding of 12.5H to IgG polyclonal anti-DNA antibodies could be inhibited by DNA and that mAb 12.5H bound to the F(ab')2 fragments of B/W-derived IgG2a anti-DNA mAb, demonstrating that the interaction occurred through the variable regions of the molecules. When the antigen-binding capacity of mAb 12.5H was evaluated, it was demonstrated to bind to self-antigens such as myosin, actin, tubulin and histones, to bind poorly to ssDNA and not to react with dsDNA. mAb 12.5H gave a cytoplasmic staining pattern by indirect immunofluorescence on HEp-2 cells. Nucleotide sequence analysis of the H and L V genes showed features previously demonstrated to be recurrent in two categories of SLE autoantibodies, i.e. arginine residues in the VHCDR3 and at position 96 on the light chain, both considered to be characteristic of antibodies reacting with dsDNA and acidic amino-acid residues in VHCDR2 reported to be frequent on antihistone antibodies. Taken together, these results show that the B/W mouse repertoire contains IgM autoantibodies: (i) that react in an idiotypic manner with DNA binding antibodies and (ii) that, because of structural characteristics, may constitute the common precursor of different categories of SLE autoantibodies, and the prototype of the idiotypically connected SLE autoantibodies accounting for the production of autoantibodies upon immunization with cognate idiotype and the experimental model of cross-idiotype-induced lupus.

Amino Acid Sequence↗
PubMed1994

Reality of glove use and handwashing in a community hospital.

BACKGROUND: Since the advent of universal precautions and body substance isolation, few studies have examined the relationship between glove use and handwashing. METHODS: During a 5-month period in 1991, 477 structured observations were conducted on 19 patients care units at a community teaching hospital during each of three shifts. Patient care contacts were defined as either high level or low level according to potential for blood or body fluid contact. RESULTS: Health care workers were potentially exposed to body fluids (high-level contact) on 152 occasions. Eighty-eight percent of all high-level contacts were limited to the hands; 47% of these contacts occurred during the night shift. Handwashing occurred after 32% of high-level contacts. Health-care workers wore gloves in 57% of high-level contacts. Rates of handwashing and glove use varied markedly among patient care units. Correct handwashing (> or = 9 seconds) occurred after 20% of contacts when health care workers wore gloves but after only 3% of high-level contacts when gloves were not used (p = 0.004). CONCLUSIONS: Despite universal precautions or body substance isolation, educational efforts, and written policies, rates of handwashing and glove use are inadequate in cases of potential blood and body fluid contact. The perceived need for gloves may encourage handwashing.

Blood↗
PubMed1994

Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris.

Paraneoplastic pemphigus is an autoimmune bullous skin disease in which autoantibodies immunoprecipitate a characteristic antigenic complex. The objective of this study was to analyze by immunoblotting and immunoelectron microscopy the autoimmune response in five patients with clinical and immunohistologic features typical of paraneoplastic pemphigus. In a first series of experiments, immunoblotting and immunoelectron microscopy were performed using anti-human whole Ig. Although immunoblotting results were consistent with the autoantibody specificities previously described in paraneoplastic pemphigus sera, immunoelectron microscopy demonstrated the presence of Ig deposits on desmosomal plaques, on hemidesmosomes and, surprisingly, on both the extracellular part of desmosomes and the keratinocyte plasma membrane. In a second series of experiments, immunoblotting and immunoelectron microscopy were carried out using antihuman IgG subclasses. The major observation was that two sera contained, in addition to the anti-desmoplakins I-II, anti-185-kD and anti-230-kD autoantibodies, autoantibodies that stained the desmoglea by indirect immunoelectron microscopy and bound to a 130-kD polypeptide by immunoblotting. One serum was particularly demonstrative: IgG1 bound to the 250- and 220-kD bands corresponding to desmoplakins I and II on immunoblots and to the desmosomal plaques of keratinocytes in immunoelectron microscopic preparations; IgG3 recognized a 185-kD immunoblotting band and hemidesmosomes and desmosomal plaques by immunoelectron microscopy; IgG4 bound to the 130-kD immunoblotting band of pemphigus vulgaris and labeled the desmoglea and the keratinocyte plasma membrane by immunoelectron microscopy. These results demonstrate that the paraneoplastic-pemphigus autoimmune response involves both intracellular and extracellular desmosomal antigens and suggest an overlapping distribution of autoantibody specificities among autoimmune bullous skin diseases.

Aged↗
PubMed1994

Thiopronine-induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis.

We report a case of herpetiform pemphigus induced by thiopronine. Direct immunoelectron microscopy performed on peribullous skin showed IgG deposits predominantly located in the extracellular portion of desmosomes. By immunoblot analysis using bovine tongue extracts as the antigen, the patient's serum recognized a 160-kDa polypeptide which comigrated with desmoglein I. This study underlines the contribution of immunoblot analysis to the diagnosis of atypical cases of pemphigus, and confirms that herpetiform pemphigus may be a clinical variant of pemphigus foliaceus.

Aged↗
PubMed1994

What is the significance of black-white differences in risky sexual behavior?

A sample of African-American and white young adults were classified as having multiple sex partners or one sexual partner. Subjects with multiple sexual partners were more likely to use drugs and practice risky sexual behaviors such as having anal intercourse, having sexual experiences with a prostitute, and having a history of gonorrhea (P < .001) and genital warts (P < .01). Additional analyses were conducted to determine African-American versus white differences in risky sexual behaviors. Results indicated that whites in the multiple partners and single partner groups were more likely to engage in anal and oral sex, while African Americans were more likely to have sex with prostitutes. Attitudes about the use of condoms differed significantly by multiple partner status (P < .004) and gender (P < .007), but not ethnicity. However, angry reactions about the use of condoms occurred more with African Americans (P < .003) and males (P < .05) than with whites or females. While whites reported a greater use of drugs and a significantly higher level of knowledge about HIV/AIDS, African Americans reported a significantly greater perception of risk for being exposed to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (P < .01) and significantly more gonorrhea (P < .10), syphilis (P < .05), and HIV/AIDS (P < .05). No whites in our sample were treated for syphilis nor had they tested positive for HIV/AIDS. On the other hand, 4.5% of the total sample of African Americans reported testing positive for HIV/AIDS. Finally, the results from discriminant analysis indicate that a large number of variables significantly discriminate between subjects who engage in risky sexual behaviors and those who do not. Although there is some similarity in the variables for African Americans and whites, there was tremendous variability between the ethnic groups in the factors that predict risky behaviors. These findings are discussed with reference to the need to develop HIV/AIDS prevention programs for African Americans that are based on data derived from African-American populations rather than from black versus white comparison studies.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Characteristics of African-American college students with HIV/AIDS.

This article examines the risky sexual behaviors, condom and drug usage, sexually transmitted diseases (STDs), and attitudes of African-American college students with the human immunodeficiency virus (HIV), which is the precursor of the acquired immunodeficiency syndrome (AIDS). A total of 408 (199 males, 209 females) African-American college students, representing 75% of the students enrolled in a southern university, were surveyed. The results revealed that 3.18% of the students reported having HIV/AIDS. The students with HIV/AIDS exhibited significant deficits in AIDS knowledge, particularly information concerning the transmission of HIV/AIDS. While subjects with HIV/AIDS did not differ from subjects without HIV/AIDS with regard to their perceived risk of being exposed to AIDS or their attitudes about using condoms, a significantly larger percentage of subjects with HIV/AIDS reported that they "always" used condoms with their partner. Nevertheless, subjects with HIV/AIDS were more likely to engage in anal intercourse, experience sex with prostitutes, and use drugs. Sexually transmitted diseases were more prevalent among subjects with HIV/AIDS, and syphilis was found to be the best predictor of HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Antibodies to Sm, RNP and SSB detected by solid-phase ELISAs using recombinant antigens: a comparison study with counter immunoelectrophoresis and immunoblotting.

Sera from 64 patients with systemic lupus erythematosus (SLE) were tested for the presence of anti-Sm, anti-RNP, and anti-SSB antibodies using commercially available solid-phase enzyme-linked immunosorbent assays (ELISAs) and recombinant nuclear proteins as substrates. The results were compared to those obtained with counterimmunoelectrophoresis (CIE) and immunoblotting (IBT) using a rabbit thymus extract (RTE) as the substrate. The ELISAs detected antibodies to Sm, RNP, and SSB in, respectively, 25%, 36%, and 15% of the SLE sera. Neither IBT-positive/ELISA-negative nor CIE-positive/ELISA-negative sera were found, regardless of the specificity considered, suggesting that ELISAs using recombinant nuclear antigens are highly sensitive. Discrepancies were observed between the results obtained with these different techniques. In addition to sera positive by both IBT and ELISA but negative by CIE, a substantial number of sera had ELISA-detectable anti-Sm, anti-RNP, and anti-SSB antibodies which failed to react with the corresponding polypeptides by IBT. The reasons for ELISA/IBT discrepancies were explored; however, no single explanation was found. Instead, a higher sensitivity of the ELISA to detect antibodies directed against certain polypeptides, the possible inability of IBT using RTE as the substrate to detect antibodies reacting with conformational antigenic determinants, and false-positive reactions in the ELISAs were suggested. Thus, it is still advisable to perform both IBT and ELISAs simultaneously in well-defined autoimmune diseases to further analyze the potential advantages of ELISAs using recombinant antigens.

Animals↗
PubMed1993

The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation.

In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection.

Antibodies, Monoclonal↗