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J Plum

Publications and source records attributed to J Plum.

At least 91 records · Page 5Linked to original sources
PubMed1994

Developmentally ordered appearance of a functional Fc gamma receptor on TCR V gamma 3 thymocytes. Evidence for stimulation-induced expression.

In the present report, we show that the Fc gamma receptor (Fc gamma R) becomes expressed on mature TCR V gamma 3 thymocytes, but it is absent on immature TCR V gamma 3 cells. Both Fc gamma RIII are Fc gamma RIII are expressed. The in vivo expression of the Fc gamma R on mature TCR V gamma 3 thymocytes coincides with an activated phenotype of the cells. In vitro, anti-CD3 stimulation of Fc gamma R-negative, immature TCR V gamma 3 thymocytes results in the expression of the Fc gamma R. The Fc gamma R of short-term IL-2-cultured, mature TCR V gamma 3 thymocytes is functional in an Ab-mediated cytotoxicity assay. In addition, it is shown that cross-linking of the Fc gamma R induces an increase in cytoplasmic Ca2+. Collectively, our findings show that mature TCR V gamma 3 thymocytes express a functional Fc gamma R; evidence is presented that this could be a result of in vivo activation of these cells.

Animals↗
PubMed1994

Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic microenvironment.

Hematopoietic stem cells differentiate in the thymus to T cells along precisely defined intermediates. This process is thymic epithelium dependent and involves cytokines and cell-cell interactions between thymic stroma and T-cell precursors. Here we report that highly purified human CD34++ fetal liver stem cells differentiate to mature T cells, when seeded into isolated fetal thymic lobes of severe combined immunodeficient mice, and subsequently cultured in vitro. The human stem cells differentiate sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-, CD4+CD8+CD3+, and finally, CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic analysis for additional maturation markers showed that these CD4 and CD8 single-positive thymocytes are fully maturate cells. By immunochemistry, human HLA-DR+ cells with a dendritic morphology could be detected. This novel chimeric human-mouse fetal thymus organ culture offers a tool to study human T-cell ontogeny in vitro and is a rapid and reliable test method for T-cell precursor activity of cultured or transfected human stem cells.

Animals↗
PubMed1994

Results of ultrasound-assisted diagnosis of tunnel infections in continuous ambulatory peritoneal dialysis.

The management of catheter-related infections has become a major challenge in continuous ambulatory peritoneal dialysis treatment. Early recognition and discrimination of mere exit site infections from more invasive and catheter menacing tunnel infections (TIs) are of therapeutic importance. As the diagnosis of TI is still based on clinical signs and only indicates advanced infections, we studied the usefulness of the ultrasound examination (UE) of the continuous ambulatory peritoneal dialysis catheter. Examinations were made by a mobile ultrasound unit using a 7.5 MHz transducer. Sixty-two continuous ambulatory peritoneal dialysis patients with an Oreopoulos Zellermann catheter (Oreopoulos-Zellerman Cathete-THWII, Baxter GmbH, Unterschleissheim, Germany) were studied repeatedly between February 1991 and July 1992. Pericatheter fluid collection (with typical sonographic localization) was consistent with surgical findings and histopathologic examination and proved to be a reliable criterion of TIs. The incidence of TIs was significantly higher when using UE (0.35/patient-year) compared with the usual clinical criteria (0.12/patient-year, P < 0.01). Staphylococcus aureus exit site infections were predominant and had the highest risk of concomitant TIs (83%). Eleven of 25 patients with a positive UE lost their catheter due to infectious complications, while no patient with a negative UE underwent operation for infectious reasons (P < 0.01). The peritonitis rate (0.64/patient-year) was markedly increased when UE indicated a TI (1.7/patient-year, P < 0.01). We conclude that sonography is a sensitive tool for the early diagnosis of unsuspected TIs. Sonography is a bedside method used for screening purposes and allows us to control the treatment regimen.

Adult↗
PubMed1994

Evaluation of proviral copy number and plasma RNA level as early indicators of progression in HIV-1 infection: correlation with virological and immunological markers of disease.

OBJECTIVE: We compared the proviral DNA level in peripheral blood mononuclear cells (PBMC), viral RNA level in plasma, presence of p24 antigen in serum, viral phenotype, and results of immunological markers of HIV-1 disease. METHODS: Consecutive samples of 62 HIV-1-infected patients, representing all stages of disease were tested for proviral DNA in PBMC and viral RNA in plasma using a semi-quantitative limiting dilution polymerase chain reaction (PCR). The presence of a syncytium-inducing (SI) phenotype was assessed after direct cocultivation of patient PBMC with MT-2 cells. Results of the quantitative PCR and the MT-2 coculture were correlated with the clinical stage of the disease, with the number of CD4+ T cells, and with the results of other virological and immunological markers, such as the level of p24 antigen, beta 2-microglobulin (beta 2M) and neopterin. RESULTS: Significant differences were observed between the results for asymptomatic and symptomatic patients for all markers under study. In the group of asymptomatic patients with a CD4+ T-cell count > 200 x 10(6)/l, patients with high amounts of proviral DNA had significantly higher amounts of beta 2M, neopterin and viral RNA, they were more frequently p24 antigen-positive and harboured more frequently SI strains than patients with low amounts of proviral DNA. A good correlation between the proviral DNA and the viral RNA levels was observed. Significant changes of viral RNA but not proviral DNA levels were observed after initiation of therapy or when therapy failed. CONCLUSIONS: We demonstrated the relationship between high proviral DNA level in PBMC, high viral load in plasma, elevated beta 2M and neopterin concentrations in serum, and the presence of p24 antigen in serum in a group of asymptomatic patients with a CD4+ T-cell count > 200 x 10(6)/l. We suggest the possible usefulness of proviral load as an early indicator of disease progression. The presence of SI strains is highly correlated with disease; however, SI strains were detected in only 46% of symptomatic patients. It also appeared that the measurement of viral RNA levels is a useful marker for therapy monitoring.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Influence of the renin-angiotensin system and atrial natriuretic peptide on renal functional reserve.

We studied the renin-angiotensin system (RAS) and atrial natriuretic peptide (ANP) after amino acid loading in order to elucidate whether or not glomerular hyperfiltration is mediated by these hormones. Eight healthy controls without kidney disease (group 1), 8 renal graft recipients (group 2) and 8 patients after nephrectomy (group 3) were studied. Furthermore, we investigated the influence of amino acid loading on RAS and ANP and glomerular filtration during acute application of captopril in healthy controls. Clearances in insulin (CIn) and para-aminohippuric acid (CPAH) were determined during an infusion of 0.9% saline and during amino acid loading. CIn increased in healthy controls from 96.5 +/- 3.3 to 111.9 +/- 4.4 ml/min (p < 0.01), CPAH rose from 577 +/- 28.7 to 618.9 +/- 38 ml/min (p = NS). During the combined application of amino acid infusion and 25 mg captopril, CIN increased to 125.0 +/- 16.4 ml/min/1.73 m2 (p < 0.01) and there was no significant increase in CPAH which was 595 +/- 77 ml/min/1.73 m2. There was no significant change in renal vascular resistance, but filtration fraction increased from 17 +/- 1 to 19 +/- 1% under amino acid infusion and increased further under the application of captopril to 21 +/- 2% (p < 0.05). In renal graft recipients, CIn had a tendency to increase during amino acid infusion from 78.4 +/- 5.8 to 84.7 +/- 6.5 ml/min (p = NS). In patients after nephrectomy, CIn did not increase (84.5 +/- 6 ml/min) but CPAH did from 345.7 +/- 26.3 to 409 +/- 24.1 ml/min (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Intrathymic differentiation of V gamma 3 T cells.

Whereas there is considerable information on the phenotypic and functional maturation of T cell receptor (TCR) alpha/beta thymocytes, comparatively little is known of the maturational processes that affect development of TCR-gamma/delta thymocytes. One class of gamma/delta T cells, those bearing the V gamma 3 gene product, are generated only during the early fetal stages of thymic development, and then migrate to the skin. Here we examine the intrathymic differentiation of these V gamma 3+ cells. The earliest V gamma 3 cells to appear in the thymus expressed low levels of TCR (V gamma 3low) and high levels of heat stable antigen (HSA). Over the next few days, V gamma 3+ thymocytes appeared which expressed high levels of TCR (V gamma 3high) and very low levels of HSA. The antigens CD5, CD45RB, and MEL14 were also differentially expressed on V gamma 3low versus V gamma 3high thymocytes, but the shift in expression was the opposite as compared with immature and mature TCR-alpha/beta thymocytes. Transfer experiments of sorted V gamma 3low/HSAhigh thymocytes to SCID thymic lobes showed that these cells were indeed the precursors of V gamma 3high/HSAlow thymocytes. The phenotype of the V gamma 3high thymocytes was similar to that of the postthymic V gamma 3+ cells found in the skin of adult mice. The differentiation of V gamma 3low in V gamma 3high thymocytes was also observed in fetal thymic organ culture. Addition of cyclosporin A (CsA) to these cultures had little effect on the appearance of V gamma 3low/HSAhigh cells, but blocked the appearance of V gamma 3high/HSAlow cells. These results show that, like alpha/beta T cells, V gamma 3+ thymocytes differentiate from TCRlow precursors to cells with a mature phenotype and that CsA inhibits this transition.

Animals↗
PubMed1993

Exogenous IL-7 promotes the growth of CD3-CD4-CD8-CD44+CD25+/- precursor cells and blocks the differentiation pathway of TCR-alpha beta cells in fetal thymus organ culture.

Addition of human rIL-7 to fetal thymic organ culture started at day 13, 14, or 15 did not influence the number of cells generated during a 12-day culture period. However, the IL-7 treatment resulted in a preferential expansion of cells with a phenotype characteristic for cells at an early step of differentiation. The cells were CD4-CD8-CD3-CD2- and SCA-1+. Analysis of the coordinate expression of CD44 and CD25 on these cells showed that the majority of the cells were either CD44+CD25- or CD44+CD25intermediate. TCR-alpha beta cells were present but in a significantly lower number as compared to the control cultures. The cell number of TCR-gamma delta cells was increased. All these effects were moderate after 6 days, but unequivocal after 12 days of culture. Treatment of the fetal organ culture with mAb-neutralizing murine IL-7 resulted in an inhibition of the proliferation of the fetal thymocytes. No particular subset studied was preferentially inhibited. By using a model of reconstitution of 14-day embryonic thymuses depleted of thymocytes by deoxyguanosine and reconstituted with fetal day 13 liver cells and set up in organ culture with or without IL-7, it was shown in a clear cut way that IL-7 indeed promotes expansion of the early precursor cells and TCR-gamma delta cells, but prevents the generation of TCR-alpha beta cells. In addition, reconstitution experiments were set up in the presence of mAb-neutralizing murine IL-7. This treatment resulted in the inhibition of the growth of the fetal thymocytes without inhibiting preferentially a particular subset. These data indicate that IL-7 acts at an early step of T cell differentiation and plays a role to expand precursor cells, but prevents this population from additional differentiation towards the TCR-alpha beta pathways, whereas the differentiation towards TCR-gamma delta cells is not influenced or even enhanced.

Animals↗
PubMed1992

Presence of CD8 alpha-CD8 beta-positive TcR gamma/delta thymocytes in the fetal murine thymus and their in vitro expansion with interleukin-7.

Several groups have described that a low percentage of in vitro cultured T cell receptor (TcR) gamma/delta cells express CD8. Contrary to TcR alpha/beta cells, however, CD8 on these TcR gamma/delta cells was shown to be a CD8 alpha homodimer. We describe here that addition of interleukin-7 (IL-7) to a short-term in vitro culture of fetal day 14 thymic lobes in an organ culture system or of fetal day 18 fetal thymocytes in cell suspension yields CD8 beta-positive TcR gamma/delta cells. This is not the result of IL-7-induced expression of CD8 beta on previously CD8 beta-negative cells. It is due to IL-7-induced expansion of CD8 alpha-CD8 beta-positive TcR gamma/delta cells which are shown to be present in the starting fetal thymocyte cell population.

Animals↗
PubMed1992

Prevalence of antibodies to Chlamydia pneumoniae in a Belgian population.

To evaluate the prevalence of antibodies to Chlamydia pneumoniae in a healthy adult Belgian population a study group of 150 medical students was chosen. Sera were collected in the period between March and October 1990 and assessed by the microimmunofluorescence test. Sixty-one per cent were found to have IgG antibodies to C. pneumoniae in a titre greater than or equal to 16, which showed evidence of past infection. Twenty-one per cent had IgA in a titre greater than or equal to 8. In none were antibodies of the IgM fraction detected. The same sera were tested for the presence of antibodies to Chlamydia trachomatis. One hundred and thirty-one sera with no or low titres of antibodies to C. pneumoniae tended to have low or no detectable antibodies to C. trachomatis. Nineteen sera with high (greater than 128) titres of antibodies to C. pneumoniae had IgG antibodies in a titre of greater than or equal to 32 to C. trachomatis. This prevalence (13%) is much higher than one would expect in a population at low risk for C. trachomatis infection. The problem of possible cross-reactions between the three species in the micro-immunofluorescence test is discussed.

Adult↗
PubMed1992

Cytokine production and responsiveness of fetal T-cell receptor V gamma 3 thymocytes.

The aim of this study was to examine the cytokine production and cytokine responsiveness of the first T-cell receptor (TcR) positive cells that appear in the murine fetal thymus, namely TcR V gamma 3 cells. It is shown that IL-2-cultured fetal TcR V gamma 3 thymocytes were capable of producing IL-3, GM-CSF, TNF-alpha and IFN-gamma upon TcR triggering. IL-2, IL-4, IL-5 and IL-6 could not be detected. With regard to cytokine responsiveness, TcR V gamma 3 cells proliferated to a high extent when high concentrations of rIL-2 were added. rIL-4 or rIL-7 alone, but not rIL-1 alone, were capable of inducing a modest proliferation of TcR V gamma 3 thymocytes. When combined with low concentrations of IL-2, a synergistic effect could be observed with IL-1, IL-4 or IL-7. It is shown that the synergistic effect of IL-2 with IL-4 was mainly due to induction of IL-2 receptor expression. The synergistic effect of IL-2 and IL-7 on the proliferation of TcR V gamma 3 cells could only be partially inhibited by anti-IL-2 receptor MoAb, and this antibody had no effect on the IL-2 + IL-1 cultures. These observations can explain the extensive proliferation of TcR V gamma 3 thymocytes during fetal life and they indicate that TcR V gamma 3 thymocytes have the potential to play a functional role during fetal thymus development.

Animals↗
PubMed1991

IFN-gamma reverses IL-4 inhibition of fetal thymus growth in organ culture.

IL-4 is known to inhibit the growth and differentiation of 14-day-old fetal mouse thymus in organ culture. Here we report that IFN-gamma reverses this IL-4-mediated growth inhibition. Thymus lobes from 14-day-old fetuses were cultured for 12 days in medium containing 100 IU/ml rIL-4 either in the absence or presence of rIFN-gamma (100 to 1000 IU/ml). After culture, the cell yields and the absolute numbers and frequencies of the major subpopulations according the coordinate expression of CD4 and CD8 were estimated. IL-4 treatment alone was found to result in a seven-fold decrease in cell yield and an almost complete absence of the CD4+CD8+ subpopulation. Addition of IFN-gamma reversed IL-4-mediated inhibition in a dose-dependent fashion, with an optimal dose ranging from 200 to 500 IU/ml. IFN-gamma exerted this effect only when added within the first 48 h of initiating the culture. The specificity of the reversal effect was ascertained by neutralization of the effect by a neutralizing anti-IFN-gamma mAb and by lack of activity of human IFN-gamma. In the absence of IL-4, IFN-gamma had a growth-promoting effect as evident from a threefold increase in cell numbers.

Animals↗
PubMed1991

Interleukin 4 induces CD8 alpha expression on T cell receptor V gamma 5 thymocytes.

It is generally accepted that most T cell receptor (TcR) gamma/delta cells are CD4-CD8-. After in vitro culture; however, a low percentage of these cells express the CD8 alpha subunit. We show here that addition of recombinant interleukin (IL) 4 to IL 2-cultured murine TcR V gamma 5 thymocytes induces the expression of CD8 alpha; CD8 beta is not expressed. Co-addition of the anti-IL 4 mAb 11B11 abrogates the induction of CD8 alpha expression, ruling out the possibility of a contaminant. Furthermore, we demonstrate that a substantial part of freshly prepared TcR V gamma 5 thymocytes express CD8 alpha.

Animals↗
PubMed1991

Interleukin-2 stimulated T cell receptor V gamma 3 positive thymocytes do not migrate to the skin.

T cell receptor (TcR) V gamma 3+ thymocytes, which only develop in the fetal thymus, migrate to the skin. IL-2 stimulation of fetal day 18 murine thymocytes results in a cell population of which 45% of the cells express the TcR V gamma 3. In this study, we describe that those IL-2 cultured TcR V gamma 3+ thymocytes have the killing capacity of lymphokine activated killer cells: NK-susceptible as well as NK-resistant tumor cell lines were killed in an MHC-unrestricted manner. Because of these findings, IL-2-expanded TcR V gamma 3+ thymocytes could have a potential use in adoptive immunotherapy for skin-located tumors. Therefore, we analyzed the migration pattern of IL-2-cultured TcR V gamma 3+ thymocytes upon i.v. injection. We describe their initial entrapment in the lungs and subsequent accumulation in the liver. Localization in the skin was practically absent, and did not differ from that of IL-2 cultured adult thymocytes (mainly TcR alpha beta +). The migration pattern was identical in adult and newborn normal mice, and in adult nude mice. Analysis of the expression of asialo-GM1 revealed that it increased strongly after IL-2 culture. The relevance of this change in asialo-GM1 expression with reference to the migration upon i.v. injection is discussed. This study indicates that an improved understanding of the determinants of in vivo localization of IL-2 cultured cells may lead to improved strategies for adoptive immunotherapy of cancer.

Age Factors↗
PubMed1991

Atrial natriuretic peptide in dialysis patients under various conditions of volume homeostasis.

Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD.

Adult↗
PubMed1991

Influence of betaxolol on renal function and atrial natriuretic peptide in essential hypertension.

The hypotensive action of beta-adrenoreceptor blockers is not fully understood, there being a lack of studies focusing on possible relationships between beta-blockers and the secretion of atrial natriuretic peptide (ANP). In 10 patients with essential hypertension, we investigated the influence of betaxolol, a selective beta 1-adrenergic blocking agent, on renal function and on plasma levels of ANP during exercise, volume depletion and volume expansion. Chronic therapy with betaxolol (mean 14.5 mg/day) did not alter glomerular filtration rate and renal blood flow although blood pressure was reduced. Renal vascular resistance decreased from 12795 +/- 1064 dyn/s per cm5 to 10614 +/- 833 dyn/s per cm5 (P less than 0.005). Under betaxolol, basal ANP levels increased from 39 +/- 10 pg/ml to 80 +/- 19pg/ml (P less than 0.01). ANP increased during exercise and volume expansion but was decreased during volume depletion. ANP values observed under betaxolol treatment showed significantly higher values while preserving their dynamic features. We believe that the stimulating effect of betaxolol on ANP may at least partly account for its hypotensive action.

Adolescent↗