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Biomedical subjects

M Nowicki

Publications and source records attributed to M Nowicki.

At least 91 records · Page 5Linked to original sources

[Relation between erythropoietin production and plasma renin activity in patients with essential hypertension].

Regulation of renal erythropoietin (EPO) production has not yet been clearly established in physiologic as well as in pathologic conditions. Recent studies suggest a possible role for renin-angiotensin system in control of EPO production. An elevation in blood pressure occurs commonly in patients with various forms of anaemia treated with recombinant human EPO. Furthermore it has been found that EPO can alter secretion of hormones engaged in regulation of intravascular fluid volume and vascular resistance. The aim of this study was to determine whether patients with essential hypertension (EH) and healthy subjects differ in EPO secretion and whether EPO serum level is related to renin response to dietary sodium restriction and upright position of the body. 63 patients with EH and 12 healthy subjects were investigated. Patients with EH were divided into subgroups on the following criteria: renin response to dietary sodium restriction and upright position of the body. 63 patients with EH and 12 healthy subjects were investigated. Patients with EH were divided into subgroups on the following criteria: renin response to dietary sodium restriction and upright position of the body and severity of existing hypertension. In all subjects haematocrit value, haemoglobin concentration, erythrocyte count, sodium, potassium, creatinine, iron, ferritin serum levels, total iron binding capacity, plasma renin activity (PRA), erythropoietin serum level and mean arterial blood pressure (MAP) were measured in basic conditions (normal sodium diet). Additionally PRA, EPO and MAP were measured after dietary sodium restriction for three days and upright position of the body for three hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of Legionella spp. in bronchoalveolar lavage fluids by DNA amplification.

By using Taq polymerase, DNA amplification of a specific fragment of the macrophage infectivity potentiator (mip) gene from Legionella pneumophila was used to detect Legionella spp. in bronchoalveolar lavage (BAL) fluid specimens. We were able to detect DNAs from all 30 L. pneumophila strains tested (serogroups 1 to 14), L. micdadei, and L. bozemanii serogroup 1. DNA from bacteria of other species tested and DNA from human leukocytes were not amplified by this procedure. After optimization of the conditions for DNA extraction from BAL fluid, a 2-ml sample of BAL fluid seeded with 25 CFU/ml tested positive after DNA amplification. A total of 68 frozen BAL fluid specimens sent to the laboratory because of suspected legionellosis were tested in a retrospective study. The eight culture-positive samples were all positive after specific DNA amplification. Among 60 culture-negative samples, 7 were positive after amplification. Of these seven samples, four were from patients who had presented a typical clinical history of legionellosis; the samples had antibody titer increases of 2 dilutions. For the three remaining samples, serological diagnosis of legionellosis in the patients from whom the samples were obtained could not be documented, and although the causative agent of these pulmonary infections was not determined, the clinical features of the patients were in accordance with legionellosis.

Bacteriological Techniques↗

[The role of erythropoietin in blood pressure regulation in patients with arteritis].

Renal erythropoietin production is dependent on local oxygen content of blood which activates so called "oxygen sensors". Taking into consideration altered local renal blood supply in patients with arterial hypertension in the course of arteritis (HA) and from the other side contribution of the renin-angiotensin system in both pathogenesis of hypertension and regulation of erythropoietin production it seemed plausible to undertake this study. The aim of the study was to determine whether and in what extent patients with HA and healthy subjects differ in EPO secretion and whether EPO serum level is related in this patients to renin response to dietary sodium restriction and upright position of the body. 18 patients with HA and 12 healthy subjects were investigated. In all subjects haematocrit value, haemoglobin concentration, erythrocyte count, sodium, potassium, creatinine, iron, ferritin serum levels, total iron binding capacity, plasma renin activity (PRA), erythropoietin serum level and mean arterial blood pressure (MAP) were measured in basic conditions (normal sodium diet). Additionally PRA, EPO and MAP were measured after dietary sodium restriction to 10-20 mmol Na/24 hrs for three days and upright position of the body for three hours. Patients with HA had insignificantly lower serum EPO concentrations than healthy subjects and both studied groups did not differ in haematocrit value and determinants of iron metabolism except of significantly higher ferritin concentration in HA. After dietary sodium restriction and upright position of the body significant rise in PRA and no significant changes in EPO level were found in studied groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Estimation of renal tubular function after uropoline administration in certain disease states].

24 h urinary excretion of beta-microglobulin (beta 2M) and Tamm-Horsfall protein (THP) before and after administration 40 ml of 75% Uropoline were assessed, as a specific markers of proximal and distal tubular dysfunction respectively. 22 patients without renal diseases and hypertension (C), 22 hypertensive patients (HP), 14 patients with renal stone disease (RSD) and 16 patients with pyelonephritis (PN) were examined. Administration of Uropoline did not change beta 2M and THP urinary excretion in C, but increased beta 2M excretion in HP and decreased THP urinary excretion in patients with RSD. It is concluded, that Uropoline shows a noxious effect on the proximal tubule in HP and on the distal tubule in patients with RSD.

Adult↗

[Urinary excretion of Tamm-Horsfall protein by patients with acute renal failure].

Urinary excretion of Tamm-Horsfall protein (THP), sodium and potassium was assessed in 12 patients 5, 8, 11, 14, 17, and 22 days after the onset of acute renal failure (ARF) and in 23 control subjects. In patients with ARF at the oliguric phase urinary excretion was significantly reduced but significantly increased (when compared with controls) at the onset of the polyuric phase. In contrast to healthy subjects in patients with ARF no significant correlation was found between urine volume and urinary excretion of THP. Normalization of THP excretion was noticed prior to normalization of serum creatinine level. Results obtained in this study prove absence of the physiological relationship between urinary excretion of THP and urine volume in patients with ARF.

Acute Kidney Injury↗

Nicotinamide and 3-aminobenzamide interfere with receptor-mediated transmembrane signaling in murine cytotoxic T cells: independence of Golgi reorientation from calcium mobilization and inositol phosphate generation.

The two competitive inhibitors of ADP-ribosylation, nicotinamide and 3-aminobenzamide, have been reported to interfere with TNF-induced cell apoptosis, and there is evidence that they inhibit killer-induced target cell lysis as well. There are very few drugs known to specifically interfere with target apoptosis induced by killer cells. We therefore sought to explore the effects these inhibitors have on CTL-mediated cell lysis. Here we show that TcR-mediated transmembrane signaling in CTL, measured by Ca2+ mobilization and generation of inositol phosphates, is inhibited by nicotinamide. The possibility that all cell functions are suppressed by the drug is excluded by the finding that constitutive secretion of BLT serine esterase is not inhibited, whereas stimulated secretion of this enzyme is suppressed. We also show that nicotinamide does not interfere with CTL target cell binding or reorientation of the Golgi apparatus toward the target binding site. It is concluded that nicotinamide inhibits transmembrane signaling in CTL and thereby interferes with delivery of the lethal hit to targets.

Animals↗

Effects of stress on lysability of tumor targets by cytotoxic T cells and tumor necrosis factor.

The effects of stress on four tumor cell lines are analyzed in view of the possibility that stress protects tumor cells against immune attack. We show that stress causes resistance to CTL and TNF in two cell lines. Induction of resistance is time dependent and reversible and not due to failure of killer cells to interact with stressed targets. It is shown that stress induces stress proteins concomitant with induction of resistance to killer cells and TNF. Moreover experiments are presented suggesting that resistance to either immune effector is due to independent mechanisms. The conclusion that stress can induce mechanisms in targets that interfere with the action of TNF as well as with target lysis following a lethal hit by CTL is discussed.

Animals↗

Induction of tolerance to parental marrow grafts in F1 hybrid mice. Evidence for recognition of self-antigens.

Lethally irradiated (C57BL/6xC3H)F1 mice are able to acutely reject parental C57BL/6 but not C3H marrow grafts, a phenomenon called hybrid resistance (HR). In attempts to inactivate this rejection mechanism we found that parental spleen cells activated with LPS are very potent in inducing tolerance to a subsequent C57BL/6 marrow graft. Tolerance is likely due to elimination of effector cells responsible for graft rejection as adoptive transfer of spleen cells from normal into tolerized mice reconstitutes responsiveness. Evidence is presented that the Ag on LPS-activated spleen cells responsible for induction of unresponsiveness are expressed on both C57BL/6 and (C57BL/6xC3H)F1 cells. This suggests that the HR effector cells recognize autoantigens. In support of this, induction of tolerance to C57BL/6 parental marrow grafts leads to a concomitant dramatic increase in endogenous CFU-spleen after a dose of gamma-irradiation. Moreover, elimination of the cells responsible for HR by injection of anti-ASGM1 antibody results in a similar increase of endogenous CFU-spleen after irradiation. It is concluded that HR is a reflection of autoimmunity, able to limit the proliferation of syngeneic marrow stem cells.

Animals↗

Differential effects of protein synthesis inhibition on CTL and targets in cell-mediated cytotoxicity.

The reactions that lead to target cell lysis by cytotoxic T cells (CTL) are despite intensive investigations poorly understood. To examine the relative roles effectors and targets play in the lytic reaction, protein synthesis in either CTL or targets was inhibited before assay of lysis. We show, in agreement with previous results, that de novo protein synthesis is not necessary in either effectors or targets during the cytolytic reaction. However, activation of CTL requires protein synthesis. Activated CTL respond to protein synthesis inhibitors with a cycling of activity, a result that is interpreted to be consistent with a stimulus secretion mechanism. Treatment of targets with protein synthesis inhibitors prior to incubation with CTL leads to a very rapid and irreversible loss of lytic susceptibility. It is shown that the decrease in lysability is not due to lack of proper CTL target interaction: MHC class I antigens are expressed on drug-treated targets and these cells serve as cold targets in competitive inhibition experiments. Moreover, drug-treated targets trigger transient Ca2+ mobilization and generation of inositol phosphates in CTL. It is therefore concluded that drug-treated targets are able to trigger CTL function but lack a component that is required for their successful lysis.

Animals↗

A novel cell type responsible for marrow graft rejection in mice. T cells with NK phenotype cause acute rejection of marrow grafts.

Acute rejection of allogeneic and semiallogeneic marrow grafts has long been considered to be a function of the natural immune system because it shares many features with NK activity in mice. With the use of a recently developed in vivo adoptive transfer assay in which spleen cells are transferred from mice able to reject a particular marrow graft into mice that fail to do so, we show that the cells responsible for induction of marrow graft rejection indeed display the phenotype of NK cells: they lack the T cell Ag CD4 and CD8 but express the NK Ag NK1 and ASGM1. The rejection induced by adoptively transferred cells is exquisitely specific--a feature that points to a specific recognition process by the transferred cells. To elucidate what the recognition structure on these cells may be we found that they express CD3 and most likely the beta-chain of the TCR. Highly purified responder cells with the NK1+, CD3+, CD4-, CD8- phenotype, when transferred into nonresponder recipients, cause specific marrow graft rejection. We conclude that the acute rejection of bone marrow grafts is caused by a cell that expresses NK phenotype but is of T cell lineage. This may suggest the specificity of acute marrow graft rejection is caused by a specific recognition process that involves TCR.

Animals↗

Legionella gratiana sp. nov. isolated from French spa water.

During an epidemiologic survey, an unidentified strain of Legionella was isolated from water of a thermal spa in France. The strain (Lyon 8420412) had the cultural and biochemical characteristics typical of the genus Legionella. In direct immunofluorescence tests, the strain reacted weakly with fluorescein-conjugated antisera prepared against L. bozemanii serogroups 1 and 2, L. longbeachae serogroups 1 and 2 and L. anisa, and failed to react with sera prepared against 36 other species or serogroups. A fluorescein-conjugated antiserum prepared against strain Lyon 8420412 reacted strongly with the homologous strain and only weakly with the above-mentioned species. The cell-wall fatty acid profile, with a predominance of hexadecenoic (16:1) and hexadecanoic (16:0) acids, ubiquinone Q10 as the major quinone and a characteristic protein electrophoresis profile suggested that the isolate was different from other Legionella species. In DNA-DNA hybridization experiments, the strain was distinct from all named Legionella species, and from all unnamed species currently under study at the Centers for Disease Control. The name Legionella gratiana is proposed for the new species (type strain Lyon 8420412; CDC 1242). A serologic survey of antibodies reacting against L. gratiana indicated that personnel or patients at the spa therapy centre where the organism was isolated had higher antibody titres than a control population.

Antibodies↗

Exposure to Legionellaceae at a hot spring spa: a prospective clinical and serological study.

Following the occurrence of five cases of Legionnaires' disease among patients and therapists at a French hot spring spa, a series of cleansing procedures and an epidemiological study were undertaken. During a 3-month period, the spring water was repeatedly sampled. Serum samples were taken from 689 randomly selected patients, 230 therapists, 134 administrative staff and a control group of 904 blood donors. Legionellaceae were present in the spring water at concentrations of 10(3)-10(5) colony forming units/l. Fifteen different species or serogroups were isolated with Legionella pneumophila serogroups 3 and 1 predominating. No clinical cases of Legionnaires disease were observed during the study. However, 11% of the therapists and 5% of the patients either had a high titre of antibody (greater than or equal to 256) to at least one species or serogroup or seroconverted during the study. Mean antibody titres in the three study groups were significantly higher than those in the blood donors against 11 of the 32 legionella antigens tested. Nine of these 11 antigens corresponded to species or serogroups isolated from the spring water. The highest mean antibody titres in all three study groups were against L. pneumophila serogroup 3, the most common legionella in the spring water. These findings have important implications for the maintenance of adequate standards of hygiene, bacteriological sampling and clinical surveillance in this and similar establishments.

Adult↗

[Diagnostic value of the captopril test in patients with arterial hypertension].

In 30 patients with renovascular hypertension, 50 with hypertension in a course of arteries, 71 hypertensive subjects with coexisting parenchymal nephropathy and in 63 with primary hypertension the captopril test was performed after 8 hours night rest and within high sodium diet. Positive test result was stated in 76.67% of patients with renovascular hypertension, in 70.59% of patients with arteritis, in 53.52% of patients with hypertension and coexisting parenchymal nephropathy and in 63.49% of patients with primary hypertension. Significant correlation between increase of plasma renin activity and blood pressure decrease after captopril administration was only stated in patients with renovascular hypertension and in those with arteritis. Results of performed studies impaired the captopril test value in diagnostics of renin-dependent hypertension.

Adult↗

Cell-mediated and glucocorticoid-mediated target cell lysis do not appear to share common pathways.

Target cell lysis by cytolyic lymphocytes follows a sequence of events that culminate in osmotic destruction of the target. Although it is clear that killer cell derived components play a crucial role in target cell lysis it is not clear to what extent the target itself is involved in its destruction. Recent observations have pointed to the possibility that glucocorticoid mediated and cell mediated lysis may utilize common pathways of cell lysis. In analyzing this question we found that cell lines that have nonfunctional glucocorticoid receptors like S49-78 and S49-88 are good targets for both NK and thymus-derived killer (TK) cells. Cell lines that are glucocorticoid sensitive such as Q1(4)6 are sensitive to NK-mediated lysis as its derivative HL4-6-3 which contains glucocorticoid receptors but is glucocorticoid resistant. An intriguing exception to this is the glucocorticoid-resistant mutant S49-4RD which is relatively resistant to both NK and TK lysis compared with parent S49. The resistance of S49-4RD to cell-mediated lysis we show here is most likely due to a defect in the target which results in its failure to trigger the cytolytic machinery in the killer cell rather than in its resistance to lysis per se. In support of this we demonstrate that lysis of S49-4RD by cytolytic granules from TK cells is normal. Moreover TK cells lyse S49-4RD as efficiently as its parent in the presence of the lectin Con A. The conclusion that S49-4RD has a defect in its ability to induce killer cells to initiate the cytolytic reaction is also in agreement with the finding that TK-S49-4RD conjugates show inefficient reorientation of the Golgi apparatus in the effector.

Animals↗

An electron microscopy study of Legionella pneumophila after in vitro and in vivo culture.

The ultrastructure of Legionella pneumophila serogroup 1 (Philadelphia Strain) was studied by Scanning Transmission Electron Microscopy (STEM) following in vitro and in vivo culture. The results obtained were identical for all the samples tested; the structure belonged to the prokaryotic type, with features consistent with the known structure of Gram-negative rods. A characteristic feature is the loose undulated outer membrane, a peptidoglycan layer which was difficult to visualize and was better seen in lysed bacteria. The outermost layer was stained by ruthenium red for polysaccharides. In guinea-pig lung tissue and in chick embryo yolk sac membranes, the bacteria were more often intracellular in intracytoplasmic ribosome-studded vacuoles.

Animals↗

Comparative efficacy of five antibiotics on experimental airborne legionellosis in guinea-pigs.

The efficacy of preventive and curative treatment of experimental airborne legionellosis in guinea-pigs was studied for erythromycin, rifampicin, minocycline, doxycycline and pefloxacin. The aerosol was produced from a strain of Legionella pneumophila serogroup 1 and dispersed in a chamber maintained below atmospheric pressure. Guinea-pigs were exposed for 30 min to 1 or 10 LD50 (10(3) or 10(4) viable inhaled organisms). Treatment was preventive or curative. Antibiotic concentrations in lungs and serum were evaluated during treatment. The action of the antibiotics on guinea-pigs infected by 1 LD50 resulted in 100% survival. For the 10 LD50 infection, pefloxacin, minocycline and erythromycin were more active (with 87.5% survivors) than doxycycline (75%) and rifampicin (62.5%). Preventive treatment with pefloxacin or doxycycline gave 100% protection, compared with 87.5% for rifampicin, 50% for erythromycin and 37.5% for minocycline. In this study, treatment of experimental legionellosis was improved, compared with previous publications, by early administration of antibiotics and increased dosage and duration.

Animals↗

Efficacy of spiramycin on experimental airborne legionellosis in guinea pigs.

The effect of preventive and curative spiramycin therapy was studied in guinea pigs infected by aerosol with the experimental model previously tested. The infectious aerosol was obtained from a virulent strain of Legionella pneumophila (Philadelphia ATCC 33 152). Male guinea pigs (Dunkin-Hartley) weighing 250-300 g were exposed for 30 min to an aerosol of 1 or 10 LD50 (10(3) or 10(4) viable inhaled organisms). Spiramycin was administered intraperitoneally (150 mg/kg/day) 18 h after infection for five days for curative therapy; for preventive therapy it was administered on the day before and on the day of aerosol administration (10 LD50). The animals were observed during seven days for weight and temperature and 28 days for survival; bacterial (lungs, spleen) and serological tests were performed. Spiramycin levels (lungs, serum) were evaluated during treatment by a microbiological method. The survival rate in the treated guinea pigs after inhalation of 1 LD50 was 100%. For the 10 LD50 aerosol, curative and preventive therapy gave a survival rate of 87.5%; these results are significant when compared with results of non-treated animals, P less than 0.05. Spiramycin merits further study in experimental and human legionellosis.

Animals↗