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Biomedical subjects

G Hoffmann

Publications and source records attributed to G Hoffmann.

At least 109 records · Page 6Linked to original sources
PubMed1995

Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells.

The pteridine compounds neopterin and 7,8-dihydroneopterin serve as valuable indicators for the stimulation of the cellular immune system. Whether they exhibit distinct biochemical functions in the immunological process is at present under discussion. We show that neopterin, but not 7,8-dihydroneopterin, is a stimulus for iNOS gene expression in rat vascular smooth muscle cells in vitro. At a concentration of 20 microM, neopterin leads to an iNOS mRNA expression of 2.5 amol iNOS cDNA/micrograms total RNA. When cells were coincubated with 20 microM neopterin and 5 micrograms/ml lipopolysaccharide derived from Escherichia coli, at least an additive effect on iNOS mRNA expression could be detected (iNOS cDNA concentration was 5.0 amol/micrograms total RNA). We speculate that neopterin enhances the macrophage-induced extracellular toxicity. This might be of relevance in situations associated with excessive release of cytokines, neopterin, and nitric oxide, as observed in septic shock.

Animals↗
PubMed1995

The pulmonary epithelial cell line L 2 as a new model for an inducible nitric oxide synthase expressing distal airway epithelial cell.

Nitric oxide released in large amounts by inducible nitric oxide synthase (iNOS)-containing pulmonary cells plays an important role in many aspects of lung function in health and disease. The aim of this study was to establish a permanent non tumor-derived alveolar epithelial cell line that exhibits the typical characteristics of an iNOS-expressing cell. Therefore, the pulmonary epithelial cell line L2 (adult rat) was incubated with lipopolysaccharide derived from Escherichia coli (serotype 0111:B4) and different cytokines. The strongest effect on iNOS gene expression and nitric oxide release could be detected when L2 cells were coincubated with interferon-gamma + tumor necrosis factor-alpha. iNOS complementary DNA concentration was 25 amol/microliters at 9h, and nitrite/nitrate levels were 99.43 +/- 3.97 nmol/10(6) cells at 24h, respectively. Our results show that L2 cells can be regarded as an appropriate model for investigating iNOS gene expression and nitric oxide functions in alveolar epithelial cells.

Animals↗
PubMed1995

Study of morbidity of personnel with potential exposure to vinclozolin.

OBJECTIVES: To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS: A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5-dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS: The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found.

Adult↗
PubMed1995

Kinetics of Na+/H+ exchange in vascular smooth muscle cells from WKY and SHR: effects of phorbol ester.

The kinetic properties of Na+/H+ exchange were investigated in vascular smooth muscle cells (VSMC) in culture from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Antiport activity was measured in 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein-loaded cells after nigericin-induced cytosolic acidification. Studies were performed without (control) and with pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA; 200 nM). Na+/H+ exchange markedly differed between the two strains with lower Hill coefficients [1.56 +/- 0.17 (SE) vs. 2.62 +/- 0.36] and higher maximal activity (Vmax) values (55.85 +/- 5.24 vs. 31.11 +/- 2.38 mmol H+.l-1.min-1) in SHR compared with WKY cell lines. PMA markedly altered the antiport kinetics in WKY VSMC with a decrease in the Hill coefficient (1.75 +/- 0.14) without affecting Vmax (31.88 +/- 1.55 mmol H+.l-1.min-1). In VSMC from SHR, PMA had no effect on the kinetic variables investigated. Thus two kinetic abnormalities are present with respect to Na+/H+ antiport activity in VSMC from SHR compared with WKY, i.e., increased Vmax and decreased Hill coefficient. The observation that PMA does not affect the kinetics of the Na+/H+ antiport in VSMC from SHR suggests a marked degree of antiporter prestimulation in this animal model of genetic hypertension.

Animals↗
PubMed1995

A multicenter study of phospholipase A2 in patients in intensive care units.

BACKGROUND: Multiple organ failure (MOF) is becoming the most common cause of death in patients in surgical intensive care units. In this respect, a multicenter study in four different groups of patients in surgical intensive care units was done to evaluate the role of phospholipase A2 (PLA2) in comparison with C-reactive protein (CRP) and polymorphonuclear (PMN) elastase. STUDY DESIGN: A total of 223 patients entered the study: 73 patients with multiple injuries, 46 patients with diffuse peritonitis, 52 patients with sepsis, and 52 patients in a control group who were at a higher risk for postoperative sepsis after defined surgical interventions. The patients underwent a daily monitoring of PLA2, CRP, and PMN elastase for seven days. RESULTS: Phospholipase A2 activity remained within the normal range in patients with multiple injuries and patients in the control group, indicating that this parameter is not influenced by the postaggression metabolism. In contrast, in patients with peritonitis, high PLA2 values were found from the beginning. The efficiency for predicting a lethal MOF was 85 percent for PLA2 (cut-off 80 U/L) in patients if determined at the day of operation. A comparably favorable efficiency (84 percent) was demonstrated for PMN elastase in patients with multiple injuries (cut-off 205 micrograms/L) measured at day one. CONCLUSIONS: These efficiency rates of PLA2 in peritonitis and PMN elastase in multiple injuries were comparable or even better than multifactorial scoring systems used in the study. C-reactive protein did not contribute to an early estimation of the prognosis in all groups analyzed. Therefore, the measurement of PLA2 in patients with diffuse peritonitis and PMN elastase in patients with multiple injuries, as single parameters, is recommended to estimate the individual risk for the occurrence of lethal MOF.

Adolescent↗
PubMed1994

Hypertonic saline infusion induces activation of the lymphocyte Na+/H+ antiport and cytosolic alkalinization in healthy human subjects.

The Na+/H+ antiport is a membrane transport protein that extrudes intracellular protons in exchange for extracellular sodium. Some details of its physiological and pathophysiological role remain poorly defined. Experimental evidence suggests that the antiporter is involved in the regulation of cell volume. In the present study, we therefore investigated the activity of the lymphocyte Na+/H+ antiport in nine healthy volunteers following acute hypertonic (2.5%) saline infusion (4 mmol NaCl/kg over 120 min). Antiport activity was measured after acidifying the cells with Na+ propionate (5-40 mM) using the fluorescent dye bis-carboxyethyl carboxyfluorescein. Hypertonic saline induced significant increases in plasma osmolality (308.4 +/- 2.3 vs. 293.5 +/- 2.7 mOsm/kg; P < 0.01), serum Na+ (150.8 +/- 3.7 vs. 138.9 +/- 0.5 mmol/kg; P < 0.01), and Cl- concentrations (118.0 +/- 3.9 vs. 101.1 +/- 1.0 mmol/kg; P < 0.01). Extracellular hypertonicity was followed by a stimulated activity of the lymphocyte Na+/H+ antiport with an increase in the apparent Vmax values from 2.44 +/- 0.16 to 3.27 +/- 0.34 10(-3) s-1 (P < 0.01) and a slight rise in pK, from 6.81 +/- 0.03 to 6.87 +/- 0.03 (P < 0.05) after hypertonic saline. In addition to antiport activation, cytosolic alkalinization was observed with cytosolic pH values averaging 6.90 +/- 0.02 before and 6.99 +/- 0.02 (P < 0.01) after hypertonic saline. Our results show for the first time that acute extracellular hypertonicity in man due to hypertonic NaCl loading is associated with a stimulated lymphocyte Na+/H+ antiport activity and cytosolic alkalinization.

Adult↗
PubMed1994

Establishment of new ovarian and colon carcinoma cell lines: differentiation is only possible by cytokeratin analysis.

Two human ovarian (OV-MZ-10, OV-MZ-15) and two colon cancer cell lines (CO-MZ-5, CO-MZ-6) were newly established in permanent cell culture. These cell lines have been maintained in vitro for 5-6 years, the passage number varying from 25 to 228. They were established from ascites or solid tumours at the time of primary surgery. By clinical and histopathological judgement alone all four cell lines would have been interpreted as ovarian cancer cell lines. Morphological criteria or the expression of the tumour-associated antigens CA-125 and CEA allowed no differential diagnosis. Only the analysis of the expression of different cytokeratins and vimentin enabled us to verify the different origin of the cell lines. Ovarian cancer cell lines, in contrast to the colon cancer cell lines, are positive for the expression of cytokeratin (CK) 7 and for vimentin. CK 20 proved to be the marker with the best discrimination. CK 20 was found exclusively in the colon carcinoma cell lines, but not in the ovarian carcinoma cell lines. The evaluation of cytokeratin expression is a helpful diagnostic modality in differentiating between adenocarcinoma cell lines derived from ovarian and colon tumours.

Adult↗
PubMed1994

The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading.

Increased activity of the Na+/H+ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130-170 mmol d-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na+/H+ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d-1 (n = 8) and 85 vs. 200 mmol d-1 (n = 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pHi) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na(+)-propionate (5-40 mM). Initial pHi-recovery was taken as the activity of the antiport system and plotted against pHi-values after acidification. Non-linear regression analysis yielded higher 'apparent' maximal transport rates in Ht than Nt (Nt: 2.00 +/- 0.22; Ht: (3.81 +/- 0.59) x 10(-3) s-1; P < 0.025). In contrast, baseline pHi-values and pHi-values at half-maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d-1 for 7 d, 'apparent' maximal transport rates averaged 2.75 +/- 0.20, 2.89 +/- 0.17, 2.81 +/- 0.18 and (3.62 +/- 0.25) x 10(-3) s-1, respectively. Thus, antiport activity was significantly (P < 0.05) stimulated on the 300 mmol d-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d-1) in normotensive volunteers did not affect the erythrocyte Na+/K+ pump, Na+/K+ cotransport and Na+/Li+ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na+/H+ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension.

Adult↗
PubMed1993

Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy.

The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistently observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9 +/- 2.4/78.4 +/- 1.5 mmHg; group 2, 113.9 +/- 3.6/76.1 +/- 1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43 +/- 0.43 10(-3).s-1 in control subjects and was markedly elevated in EH (28.38 +/- 0.62 10(-3).s-1; P < 0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54 +/- 0.57 10(-3).s-1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2 (26.95 +/- 0.73 10(-3). s-1; P < 0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.

Adult↗
PubMed1993

An analysis of the prediction of cephalopelvic disproportion.

Since cephalopelvic disproportion inevitably leads to cesarean section it seems to be mandatory to identify patients with an absolute discrepancy between the size of the fetus and the birth canal in order to avoid unnecessary trials of labour. In a case control study, comparing a group of patients who delivered by cesarean section because of cephalopelvic disproportion with an age matched control group, routinely assessed pelvic measurements and measurements of the newborn were correlated to cephalopelvic disproportion. Multivariate linear regression was applied to each group to determine, which of the maternal and fetal factors had the strongest influence on the mode of delivery. In the study group external conjugate showed the strongest positive relation to maternal body height (P < 0.01), the biparietal diameter of the newborn was negatively correlated (P < 0.01). None of the analyzed variables reached statistical significance in the control group. Differences between the two groups were marginal, thus providing no safe basis for decision making even in a population at high risk for developing cephalopelvic disproportion.

Adult↗
PubMed1993

Receptor binding of norgestimate--a new orally active synthetic progestational compound.

Binding of the new progestagen, norgestimate (D-(-)-13 beta-ethyl-17 beta-acetoxy-17-ethinyl-4-gonen-3-one-oxime), and its metabolites (levonorgestrel-3-oxime, levonorgestrel-17-acetate and levonorgestrel) to the progesterone receptor was investigated by competition experiments using cytosol from human myometrial tissue. Compared to R5020, a highly potent synthetic ligand for progesterone receptor analysis, the L-isomer of norgestimate shows only a weak specific behaviour with regard to binding to the progesterone receptor from uterine cytosol with an RBA value of 0.8%, whereas the D-isomer of this compound is characterized by a lack of binding activity to the progesterone receptor. Levonorgestrel-3-oxime, one of the possible metabolites of norgestimate, binds to the progesterone receptor with an RBA value of 8%, whereas levonorgestrel-17-acetate, the other possible metabolite of norgestimate, binds with a binding affinity of 110% which is in the same order of magnitude as levonorgestrel itself. The competition experiments suggest that norgestimate is a prodrug and that the metabolites, levonorgestrel and levonorgestrel-17-acetate, which actively bind to the progesterone receptor, must first be formed from the parent drug via metabolic processes in vivo. These are the actual biologically active compounds which are responsible for the gestagenic potency.

Animals↗
PubMed1993

Bioactive furanonaphthoquinones from Crescentia cujete.

Bioassay-directed fractionation of the MeCOEt extract of Crescentia cujete (Bignonaceae) resulted in the isolation of (2S,3S)-3-hydroxy-5,6-dimethoxydehydroiso-alpha-lapachone [1], (2R)-5,6-dimethoxydehydroiso-alpha-lapachone [2], (2R)-5-methoxydehydroiso-alpha-lapachone [3], 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [4], 5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [5], 2-isopropenylnaphtho[2,3-b]furan-4,9-dione [6], and 5-hydroxydehydroiso-alpha-lapachone [7]. Compounds 1-3 are new, and all compounds are bioactive, showing selective activity towards DNA-repair-deficient yeast mutants. The isolation, structure elucidation, and biological activities of these compounds are reported.

Animals↗
PubMed1993

P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster.

P transposon induced modifier mutations of position-effect variegation (PEV) were isolated with the help of hybrid dysgenic crosses (pi 2 strain) and after transposition of the mutator elements pUChsneory+ and P[lArB]. Enhancer mutations were found with a ten times higher frequency than suppressors. The 19 pUChsneory(+)- and 15 P[lArB]-induced enhancer mutations can be used for cloning of genomic sequences at the insertion sites of the mutator elements via plasmid rescue. Together with a large sample of X-ray-induced (48) and spontaneous (93) enhancer mutations a basic genetic analysis of this group of modifier genes was performed. On the basis of complementation and mapping data we estimate the number of enhancer genes at about 30 in the third chromosome and between 50 and 60 for the whole autosome complement. Therefore, enhancer of PEV loci are found in the Drosophila genome as frequently as suppressor genes. Many of the enhancer mutations display paternal effects consistent with the hypothesis that some of these mutations can induce genomic imprinting. First studies on the developmentally regulated gene expression of PEV enhancer genes were performed by beta-galactosidase staining in P[lArB] induced mutations.

Animals↗
PubMed1992

Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium sodium citrate administered as short-, medium- and long-term to male stone patients.

In male patients with idiopathic recurrent calcium urolithiasis (RCU) the effects of oral potassium sodium citrate (PSC) on acid-base, citrate and mineral metabolism were investigated. There were 17 normocitraturic and 15 hypocitraturic patients. The examination time points in our clinical laboratory were prior to medication and after 3, 6 and over 12 months of medication. Urine collection periods were over 24 h, 2 h--after an overnight fast--3 h postprandially. Acceptance by the patients was poor, a large number refusing to take PSC for 12 months. Compliance of the patients continuing with the study was adequate as assessed by the urinary excretion of potassium and sodium. No unwanted side effects were observed. After 3 months of PSC medication a compensated metabolic alkalosis developed; in the urine calcium was decreased, while citrate, pH and oxalate were increased, as were hydroxyapatite supersaturation and calcium phosphate particles. After more than 12 months of PSC medication, citrate and pH tended toward the pretreatment baseline values, while hydroxyapatite supersaturation and calcium had already returned to pretreatment values. Despite ongoing PSC intake, patients with pre-existing hypocitraturia had lower urinary citrate than patients with previous normocitraturia, while the concomitant pH and hydroxyapatite supersaturation in the urine of the former remained at levels close to those of the latter. Under the influence of PSC, parathyroid gland function remained unchanged, but serum levels of bone alkaline phosphatase and osteocalcin were low, and urinary hydroxyproline was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗