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Biomedical subjects

J Plum

Publications and source records attributed to J Plum.

At least 109 records · Page 6Linked to original sources

Clinical and pathophysiological effects of piretanide treatment in the nephrotic syndrome.

12 patients with the nephrotic syndrome (N.S.) and normal serum creatinine (less than 1.5 mg/dl) were investigated in a follow-up study over 10 days under diuretic treatment with piretanide (29 +/- 24 pg/ml). Clinical effects, parameters of renal clearance and hemodynamics, metabolic changes and the influence on vasoactive and volume dependent hormonal systems were studied. Piretanide markedly increased urine volume and electrolyte excretion (Vu +53%, UNa +24%, p less than 0.05, after 10 days treatment) but did not significantly alter glomerular filtration rate or renal blood flow. While baseline plasma renin activity was in the normal range and regularly stimulated (2.55 ng/ml x h to 7.7 ng/ml x h) plasma ANP values were elevated (152 +/- 107 pg/ml) at the start of the study and did not significantly change under piretanide treatment. This may be an indicator of sodium retention and a high plasma volume in the primary form of the nephrotic syndrome. Thereby piretanide did not significantly alter the intravascular space.

Adolescent↗

Preferential proliferation of T cell receptor V gamma 3-positive cells in IL-2-stimulated fetal thymocytes.

Thymocyte cell suspensions, prepared from mice at different ages, were cultured in vitro with human rIL-2. This stimulation resulted in a cell population that contained almost 50% TCR-gamma delta-positive cells if thymocytes were taken from fetal day 17 until just after birth. Analysis of the variable (V gamma) region used by the TCR-gamma delta cells revealed that 90% of them expressed TCR-V gamma 3, and less than 5% expressed TCR-V gamma 2. Cells positive for TCR-alpha beta were barely detectable. If fetal day 18 organ cultured thymus lobes, instead of a cell suspension, were stimulated with IL-2, no rise in the number of TCR-V gamma 3+ or TCR-delta+ cells was observed, whereas a partial outgrowth of TCR-alpha beta+ cells occurred. From day 1 after birth, the number of TCR-gamma delta cells recovered from an IL-2-stimulated thymocyte cell suspension dropped to reach a plateau of 15% of the total cell number, whereas TCR-V gamma 3+ cells became undetectable in older animals. TCR-alpha beta+ cells, on the other hand, quickly rose in cell number after birth. Kinetic analysis showed that the preferential outgrowth of TCR-V gamma 3+ cells in IL-2-stimulated fetal day 18 thymocyte cell suspensions was present from the onset of the culture; a significant proliferation of CD4 or CD8 single positive TCR-alpha beta cells was never observed. This lack of proliferation of TCR-alpha beta cells was not due to inhibition by the activated TCR-V gamma 3+ cells. Throughout the IL-2 culture, one-fourth of the TCR-V gamma 3+ thymocytes was positive for CD8. Analysis of the DNA content and the IL-2 receptor (IL-2R) p55 expression showed that during the first days of culture the TCR-V gamma 3+ cells had a much higher proliferation rate than the TCR-V gamma 3- cells, although TCR-V gamma 3+ IL2R p55+ cells could not be detected. From day 3 to 4 of culture, the proliferation rate of TCR-V gamma 3+ cells equaled that of the rest of the cells and less than 20% of the TCR-V gamma 3+ cells expressed the IL-2R p55. The biologic significance of our findings is discussed.

Animals↗

Inhibitory effect of murine recombinant IL-4 on thymocyte development in fetal thymus organ cultures.

The effect of rIL-4 on early T cell development in fetal thymus organ culture was studied by two-color immunofluorescence and by proliferation assays. Addition of IL-4 to an organ culture of 14-day-old fetal BALB/c thymus resulted in a decreased cell yield (less than 15% as compared to the control culture) and in a complete inhibition of CD4+CD8+ thymocytes after 12 days of culture. This IL-4 effect was time dependent as shorter times (less than 6 days) resulted in a thymic development comparable to the untreated control. When thymuses at later stages of gestation were treated with IL-4, the inhibition was less pronounced. The inhibitory activity of IL-4 was abrogated by the anti-IL-4 mAb 11B11, ruling out the possibility of a contaminant. Organ cultured 14-day-old fetal thymocytes treated with IL-4 during 12 days responded vigorously to IL-2 alone and to IL-4 + PMA + ionomycin. Taken together, these results indicate that IL-4 affects the intrathymic T cell development at an early stage.

Animals↗

Expansion of large granular lymphocytes in IL-2-driven 14-day-old fetal thymocytes in organ culture.

These experiments were designed to evaluate the role of cytokines in early T cell development within the thymus. By using a thymic organ culture model, we have studied the influence of high dose of IL-2 (10 to 1000 IU/ml) on the cell populations that are generated during 12 days starting from a thymic rudiment of 14-day-old mouse embryo. The IL-2 treatment resulted in the expansion of Thy-1+/-, CD4-, CD8-, CD3-, Fc gamma RII+, CD5 (Lyt-1)-, HSA-, Pgp- 1+, Mel-14- population. These cells had the morphology of large granular lymphocytes and displayed broad cytotoxic activity. In addition, IL-2-treated organ cultures had a dramatic decrease in CD4+CD8+ thymocytes, a marked reduction in TCR-alpha beta+ thymocytes--even more pronounced in the TCR-V beta 6+ and TCR-V beta 8+ thymocytes--and no significant changes in the number of TCR-gamma delta+ as compared to control organ cultures.

Animals↗

[Effect of a beta 1-receptor blocker on the plasma level of atrial natriuretic peptide in patients with essential hypertension in the exercise test].

In order to investigate the behaviour of atrial natriuretic peptide (ANP) in untreated mild to moderate essential hypertension and the influence of blood pressure normalisation by a beta 1-receptor blocker a study was conducted in groups of normotensive and hypertensive middle aged subjects. 10 normal subjects and 10 patients with essential hypertension (WHO I-II) without any medication and on betaxolol monotherapy were studied at rest and during graded exercise. In addition the response of ANP, cyclic guanosine monophosphate (cGMP) and the renin-aldosterone-system was investigated. Normal subjects and hypertensive patients did not differ in ANP levels at rest and also responded with a comparable exercise dependent increase at all workload levels. A steady decrease of ANP was noticed during the recovery period in both groups. After beta-blocker treatment in the hypertensive patients ANP concentrations significantly rose, both at rest and more pronounced during exercise. cGMP reacted in a similar way but showed a more inert response. A counter-regulatory behaviour between ANP and PRA or aldosterone, as seen under volume shifts, could not be detected. These findings demonstrate that plasma ANP is not altered in untreated essential hypertension. Increased ANP levels in beta 1-blocker treatment may contribute to its blood lowering effect.

Adult↗

Evaluation of immunoblotting for the detection of Toxoplasma gondii immunoglobulin M antibodies.

Immunoblot analysis was used to detect human IgM antibodies to Toxoplasma gondii in 20 patients with recent toxoplasmosis, 30 immune individuals, 30 non-immune individuals, and 24 children less then two years old. Analysis of the IgM strips revealed that specific IgM antibodies detectable after a recent Toxoplasma gondii infection react with the same antigens as the 'natural' antibodies present in the sera of immune and non-immune individuals and in the sera of young children. These data indicate that immunoblotting is not useful as a reference method for Toxoplasma gondii IgM detection, and suggest that improvement of the specificity of IgM detection will remain difficult.

Animals↗

Prevalence of antibodies to Chlamydia pneumoniae in a pediatric hospital population in Belgium.

To evaluate the prevalence of antibodies to Chlamydia pneumoniae in a pediatric hospital population, 207 patients admitted to the pediatric unit of the hospital during the period January to April 1989 were screened. A microimmunofluorescence test was used to measure both Chlamydia pneumoniae specific total antibody and IgM antibody. Fifty-eight (28%) patients were found to have antibodies to Chlamydia pneumoniae. Only one serum contained specific IgM. Analysis of the age specific prevalence of antibody showed a sudden rise in the 10 to 12 year old age group. Cross-reaction in the test with the other Chlamydia species is discussed. It is concluded that the incidence of primary Chlamydia pneumoniae infection during the study period was low, but that the infection occurs in Belgium with about the same prevalence as in other countries.

Adolescent↗

[Plasma level of atrial natriuretic peptide following oral glycerol administration].

Atrial natriuretic peptide (ANP) is a cardiac hormone known to mediate increased capillary permeability, vasodilation, and natriuresis. In 1988 the authors' experimental results indicated the presence of ANP receptors in the inner ear. From this they hypothesized that ANP might be involved in the regulation of inner ear fluids and therefore investigated the effects of orally administered glycerol on ANP and cGMP plasma levels. As regards the initial values, there was no apparent significant difference between the 14 subjects with Ménière's disease and the 34 subjects without. During the first hour after glycerol administration there was a significant hormonal effect: ANP, cGMP (second messenger), and serum osmolality increased, while total serum protein and plasma renin decreased. In addition to this, the hearing ability of ten subjects was positively affected. After the first hour the hormonal levels reapproached their original homeostatic states. But the positive effects on hearing ability continued to increase for another hour before decreasing again. The authors believe that this delayed effect is caused by the blood-perilymph barrier. Further research is required to establish whether glycerol affects hearing improvement directly or by mobilizing ANP.

Atrial Natriuretic Factor↗

Direct evidence for partial target specificity in lymphokine-activated killer thymocytes.

Thymocytes were removed from mice at different times before and after birth, and their phenotype and killing repertoire were analysed after stimulation with human recombinant interleukin 2 (IL-2). Whereas three different tumour targets were killed by all lymphokine-activated killer (LAK) populations tested, EL4 lymphoma cells were only killed by LAK cells derived from thymocytes after, but not before, birth. Cold-target competition tests showed that LAK thymocytes recognized antigenic structures on EL4 cells that are different from those on other tumour targets. Analysis of EL4 target killing after removal of different subsets from LAK cells revealed that the major part of this killing is exerted by CD8+ cells. Our findings are additional and more direct evidence for partial target specificity in LAK cells.

Animals↗

Human immunodeficiency virus (HIV) infection, sexually transmitted diseases and HIV-antibody testing practices in Belgian prostitutes.

From December 1988 to April 1989, 154 female prostitutes in and around Ghent, Belgium, were interviewed about their knowledge, attitudes and practices in relation to the risks for sexually transmitted diseases (STD) and human immunodeficiency virus (HIV) infection in their profession. Thirty four women worked as window prostitutes, 120 picked up their clients in bars, clubs, and saunas. Blood samples were taken from 123 women. One (0.8%) was seropositive for HIV1, 19 (15.4%) had Hepatitis B core antibodies (anti-HBc), eight (6.4%) showed markers of syphilis. None of them were Hepatitis B surface antigen (HBsAg) carriers. Hepatitis C antibodies (anti-HCV) were present in the serum of three women (2.4%). Overall STD seroprevalence was higher in the group of window prostitutes than in the group of club prostitutes. One woman admitted intravenous drug use. Former testing for anti-HIV antibodies had been performed in 102 (66.5%) respondents, of whom 84 (82.3%) were tested in the year preceding the interview. In 74.5% of the cases, these tests were requested by the women themselves. These results suggest that HIV infection is not yet prevalent in non-intravenous drug using prostitutes in Ghent, but that this situation may change considering their higher rates of past STD. Window prostitutes are at higher risk than club prostitutes. Testing for HIV seems to be common practice, mostly at the request of the women themselves. Health education should discourage the notion of testing as an alternative to using condoms.

AIDS Serodiagnosis↗

Intraindividual comparison of ANP, cGMP and plasma catecholamines between HD and CAPD.

Patients with end stage renal failure have elevated plasma levels of atrial natriuretic peptide (ANP) which seems to be a sensitive parameter of body fluid status. A prospective study comparing patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was still missing. Six identical patients (59 +/- 10 yrs, residual diuresis 1.3 +/- 0.61, 1 data expressed as means +/- SEM) were studied in the predialysis phase and under steady state conditions on HD and on CAPD. Plasma levels of ANP, cyclic guanosine monophosphate (cGMP), adrenaline, noradrenaline and dopamine were determined. Blood and dialysate samples were repeatedly taken. Ultrafiltration-volume, dry weight and blood pressure were not different between HD and CAPD. ANP and cGMP reached the highest plasma levels in the predialysis phase with 421 +/- 180 pg/ml and 19.8 +/- 6.4 pmol/ml and decreased after the onset of dialysis treatment. On HD mean ANP levels of 279 +/- 175 pg/ml were not significantly different from those on CAPD (320 +/- 213 pg/ml). However, cGMP concentrations on CAPD (15.7 +/- 5.4 pmol/ml) surpassed the values measured on HD (10.5 +/- 3.4 pmol/ml, p less than 0.05). Plasma noradrenaline was markedly elevated in the predialysis phase (421 +/- 180 pg/ml) and decreased under dialysis treatment. Differences between HD and CAPD were not found. Adrenaline and dopamine concentrations fell within the normal range.

Atrial Natriuretic Factor↗

[Effect of betaxolol on atrial natriuretic peptide regulation in patients with essential hypertension].

Plasma levels of human atrial natriuretic peptide (ANP) were measured in 10 patients with mild essential hypertension (EH) (WHO I). The renin-angiotensin-aldosterone-(RAA) system and ANP were investigated in a sequential study without treatment and under administration of a cardioselective beta-blocker (betaxolol). We analyzed the RAA system and ANP under conditions of volume loading induced by 2000 ml saline and volume depletion induced by 40 mg furosemide iv. Volume depletion induced a stimulation of the RAA-system but the ANP levels decreased from 87 +/- 13.6 to 55 +/- 7.6 pg/ml. Volume loading induced a suppression of the RAA-system but caused a rise of ANP from 47 +/- 12 pg/ml to 133 +/- 30 pg/ml. Under application of betaxolol the RAA system was suppressed and ANP levels were increased, but physiological volume regulation was maintained. Although blood pressure and heart rate were lowered under administration of betablockers, the ANP levels were increased. These results suggest that increased ANP in plasma under administration of betaxolol may play a role in compensatory mechanisms in response to beta-adrenergic blockade.

Adolescent↗

Comparison of six commercial enzyme linked immunosorbent assays for detecting IgM antibodies against Toxoplasma gondii.

To evaluate the usefulness of different commercial enzyme linked immunosorbent assays (ELISAs) for the detection of IgM antibodies against Toxoplasma gondii the results of six of these assays for a panel of 81 sera were compared. The following tests were selected: Toxoplasma gondii IgM ELISA (Clark Laboratories), Toxoplasma IgM EIA (Labsystems), Toxo-M EIA (Abbott), Toxonostika M (Organon), Toxo M Enzyme Immunoassay (Hybritech) and Platelia Toxo IgM (Diagnostics Pasteur). An antibody capture ELISA developed at our laboratory was used as the reference test. An IgM immunoblotting assay was also performed. Four (Toxoplasma IgM EIA, Tox-M EIA, Toxonostika M, and Platelia Toxo IgM) of the commercial IgM ELISAs gave a high sensitivity and a high specificity. Toxo-M EIA, Toxonostika M, Toxoplasma IgM EIA and the Toxo M Enzyme Immunoassay were too insensitive, and the Toxoplasma gondii IgM ELISA was both insensitive and unspecific. No remarkable differences were observed between the results of indirect or antibody capture ELISAs, and between the results of ELISAs performed with polyclonal or monoclonal antibodies.

Animals↗

Analysis of the cytotoxic function of the thymocytes generated in a 14-day old mouse fetal thymus organ culture with high dose of IL-2.

The target cell specificity of LAK cells generated by addition of rIL-2 to thymic rudiments of 14 day old BALB/C embryo's was compared to the lytic potential of adult BALB/C splenic LAK cells. We used four tumor cell lines as targets, one NK-susceptible (YAC-1) and three NK-resistant tumors (C1300, P815 and EL4), which were all killed by splenic LAK cells. It is shown that fetal thymic LAK cells display a lower lytic activity, while EL4 tumor cells are not killed at all. By elimination of the CD8 positive cells from both the adult splenic and the fetal thymic LAK cells, we demonstrate that the fetal thymic LAK activity is mainly exerted by CD4-CD8- cells, whereas part of the cytotoxicity of splenic LAK cells is due to CD8+ cells.

Animals↗

Influence of antibodies neutralizing cytokines on murine fetal thymic organ cultures.

The role of cytokines in early T cell development was evaluated in a thymic organ culture system. Fetal thymic lobes from 14 day old mouse embryo's were cultured in the presence of antibodies neutralizing either IL-4, IL6 or TNF. In addition antibodies neutralizing TNF were added to cultures supplemented with human recombinant IL-2. The influence of these different treatments were evaluated by analyzing the different subsets generated after 12 days of culture with a panel of monoclonal antibodies. The antibody treatment did not result in dramatic changes in the cell populations nor did the anti-TNF inhibit the significant changes that are induced by the IL-2 treatment. These results show that based on the cellularity and thymocyte subsets no influence can be shown by inhibiting these cytokines. Other criteria, e.g. repertoire specificity have to be evaluated to address the influence of these treatments on early T cell development.

Animals↗

Differentiation of thymocytes in fetal organ culture: lack of evidence for the functional role of the interleukin 2 receptor expressed by prothymocytes.

Thymic rudiments of 14-day-old mouse embryos were put into organ culture in the presence of interleukin 2 (IL2) and PC.61, a monoclonal antibody that binds to the IL2 receptor (IL2R). After 5 and 7 days of culture, we found no influence of PC.61 on the growth of the thymus and the composition of the thymocyte subpopulations as studied with a panel of monoclonal antibodies. High-dose IL2 treatment of the organ culture resulted in a reduction of the number of thymocytes and a decrease in the single CD4+ and CD4+CD8+ thymocytes, whereas the number of CD8+Ly-1+ thymocytes and the number of CD4-CD8-Ly-1- IL2R+ thymocytes increased. The effect of high-dose IL2 treatment was ascribed to the induction of a nonspecific LAK activity. Our findings argue against a functional role of IL2R on prothymocytes during early T cell development.

Animals↗

Detection of IL-2 receptor positive tonsillar lymphocytes by monoclonal antibody and protein A coated erythrocytes.

A sensitive rosette method combining staphylococcal protein A coated rabbit red blood cells and the monoclonal antibody anti-Tac was used to search for the presence of interleukin 2 (IL-2) receptor-bearing T lymphocytes in tonsils from patients with chronic tonsillitis. This method revealed the presence of Tac positive T lymphocytes in the tonsils whereas a conventional immunofluorescence technique was unable to do so. To demonstrate that Tac rosette formation resulted in a selective enrichment of IL-2 receptor-bearing T cells, we measured the proliferative response of these cells to exogenous IL-2. The response of Tac rosette positive cells to recombinant IL-2 was always higher than that of the Tac rosette negative or unselected cells, indicating that this rosette method specifically selects T cells expressing IL-2 receptor.

Adolescent↗