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Biomedical subjects

N Wolf

Publications and source records attributed to N Wolf.

At least 37 records · Page 2Linked to original sources
PubMed1995

Phenotypic development of neonatal rat chromaffin cells in response to adrenal growth factors and glucocorticoids: focus on pituitary adenylate cyclase activating polypeptide.

We have investigated the regulation of the morphological phenotype of chromaffin cells cultured from 6-day-old rat adrenal glands. We show that pituitary adenylate cyclase activating polypeptide (PACAP), which is present in and released from nerves innervating chromaffin cells, rapidly induces neuritic growth, affecting 25% of tyrosine hydroxylase-positive chromaffin cells after 3 days at an optimal concentration of about 20 nM. PACAP does not synergistically act with other factors known to promote neurite growth, including nerve growth factor (NGF), basic fibroblast growth factor (bFGF, FGF-2), and ciliary neurotrophic factor (CNTF). The neurite promoting effect of PACAP and FGF-2 is entirely overridden by dexamethasone (2 x 10(-8) M) suggesting that, despite the presence of these promoting factors in the adrenal medulla, glucocorticoids from the adrenal cortex are probably sufficient to prevent the development of neuronal traits in adrenal chromaffin cells.

Adrenal Glands↗
PubMed1995

Effects of inhalative exposure to dioxins in wood preservatives on cell-mediated immunity in day-care center teachers.

The study investigated the effects of chronic inhalative low-level exposure to dioxins in day-care centers containing wood treated with preservatives on (1) the number of peripheral CD4 and CD8 cells and the CD4:CD8 ratio in peripheral blood and (2) the delayed-type hypersensitivity reaction of the skin (Multitest Méreux). The study population consisted of 221 exposed and 189 unexposed employees of day-care centers in or near Hamburg. A status of decreased skin test reagibility was operationalized as hypoergy I (score < 5 mm), hypoergy II (< or = 1 positive reaction), and anergy (no positive reaction). Taking the fading during postexposure time into account, a surrogate for the dioxin burden based on the concentration of dioxins in indoor air (measured using the 2,3,7,8-TCDD TEF followed by the Federal Republic of Germany) was modeled. No effect was found regarding the number of CD4 cells, CD8 cells, and CD4:CD8 ratio. However, some evidence for an increasing dose-response relationship between inhalative exposure to dioxins and the risk of hypoergy and anergy was found, both in the total study population and among subjects with a short postexposure time (< or = 6 months). Subjects with a short postexposure time and a dioxin burden > 0.6 pg/m3 had a significantly higher risk of hypoergy than unexposed subjects (hypoergy I: OR = 9.51, 95% CI = 1.96-42.02; hypoergy II: OR = 2.92, 95% CI = 1.14-7.5). It is concluded that a suppressive effect of inhalative exposure to dioxins in wood preservatives on human cell-mediated immunity cannot be ruled out.

Adolescent↗
PubMed1995

Enzymatic peptide synthesis by the recombinant proline-specific endopeptidase from Flavobacterium meningosepticum and its mutationally altered Cys-556 variant.

Proline-specific endopeptidase (PSE) (EC 3.4.21.26) was investigated for its potential as a catalyst in peptide synthesis. Using an activated peptide ester or a peptide amide as the acyl component, the enzyme catalyzed kinetically controlled aminolysis and transpeptidation respectively, with various amino acid amides as acyl acceptors. To a certain extent the nucleophile preference reflected the amino acid preference in the S1'-position of the enzyme in peptide hydrolysis: the highest fractions of aminolysis were obtained using amino acid amides with hydrophobic side-chains (e.g. Leu-NH2, Phe-NH2). PSE also catalyzed the thermodynamically controlled condensation of short peptides with a free carboxyterminus and various amino acid amides. This enabled us to examine the acceptance of different acyl components in the substrate-binding site of the enzyme with regard to their amino acid composition: In the S1 position proline was clearly favored, but alanine was also accepted, whereas the S2 subsite accepted various amino acids rather unspecifically. Since PSE was shown to be extremely sensitive against water-miscible organic solvents, an alternative approach was used to increase yields in enzymatic peptide synthesis: a derivative of PSE in which the catalytic Ser-556 is converted to a Cys was constructed by protein engineering. This mutant (PSEcys) exhibited a dramatically increased peptide ligase activity in aqueous solution.

Amino Acid Sequence↗
PubMed1995

Immunology of reactive arthritides.

Reactive arthritis (ReA) and Lyme arthritis together comprise a pair of chronic inflammatory diseases of the joints. Although differing in detail, these relatively rare diseases are related in their immunopathology to the much commoner rheumatoid arthritis (RA), for which they serve as both model and control. The trigger for rheumatoid arthritis is unknown, but for these rarer diseases triggering occurs by certain well-defined bacterial infections. Arthritis is an uncommon outcome of these infections, for reasons unknown, and the development of chronic, as distinct from brief, arthritis is even rarer; again, the reasons are unknown. Not only does knowing the trigger greatly assist us in understanding these diseases, so also does knowing the contrasting pattern of Th1 versus Th2 cytokines observed in RA and ReA. ReA and Lyme arthritis are here considered in the wider setting of infections where chronic morbidity arises first from hypersensitivity, and perhaps finally from autoimmunity, such as occurs in some of the major tropical diseases. The immunology of ReA and Lyme disease is surveyed in detail, concentrating on T cells and including an update on the Lyme vaccine(s). Additional sections deal with the enigma of HLA B27, with epidemiological findings relevant to the chronicity of ReA and to the need for enlarged prospective studies of ReA in the setting of a developing country.

Arthritis, Reactive↗
PubMed1995

Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP, and lindane.

The objective of this study was to investigate a broad range of adverse health outcomes and their potential association to wood preservative used in daycare centers. This article focuses on reproductive effects. A sample of 221 exposed teachers was provided by the employer's liability insurers. A comparison group (n = 189) insured by the same two organizations was recruited from nonexposed daycare centers. In a face-to-face interview, job history and reproductive history of 398 female teachers were ascertained. Data on exposure were provided, including measurements on concentration of pentachlorophenol (PCP) and lindane in wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and dibenzofurans in indoor air. An exposure matrix based on individual job history, independent exposure information from each center, and reproductive history was set up with regard to the vulnerable time windows for each pregnancy. Using this approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32 exposed and 386 nonexposed live births. For subgroup analyses the observations were restricted to independent pregnancies, excluding multiple and consecutive births. The data were analyzed with linear regression techniques, taking confounders into account. The crude median difference between exposed and nonexposed was 175 g in birthweight and 2 cm in length. Controlling for confounders, the results show a significantly reduced but weight (p = 0.04) and length (p = 0.02) in exposed pregnancies, even after restricting the data to independent pregnancies and pregnancies for which data could be validated from the mother's health cards. These differences were not explained by differences in gestational age indicating that a toxic effect, which could cause small-for date newborns, might have affected the fetus.

Adult↗
PubMed1995

[Effective prevention of indomethacin-induced gastroduodenal mucosal lesions with roxatidine acetate].

In this randomized single-blind cross-over study the gastroduodenal damaging effect of indometacin 75 mg bid alone and in combination with roxatidine acetate (CAS 78628-28-1, Roxit) 75 mg nocte or 75 mg bid was evaluated in 12 healthy male volunteers. Prior to the start of the three therapeutic periods subjects underwent endoscopic examination to exclude gastroduodenal mucosa lesions. On days 7 and 14 of therapy 2 h after the application of the last indometacin dose subjects underwent endoscopy again. The 7- and 14-days administration of indometacin 75 mg bid, indometacin 75 mg bid plus roxatidine 75 mg nocte and indometacin 75 mg bid plus roxatidine 75 mg bid led to gastroduodenal mucosa lesion scores of 1.67 +/- 0.40 and 2.00 +/- 0.35, 1.33 +/- 0.28 and 1.50 +/- 0.29, 0.42 +/- 0.23 and 1.00 +/- 0.33 (mean +/- SEM), respectively. These differences were statistically significant when comparing indometacin 75 mg bid versus indometacin 75 mg bid plus roxatidine 75 mg bid (p < 0.004 and < 0.008, respectively). This study shows that roxatidine acetate represents an effective alternative in the prophylaxis of NSAID-induced gastroduodenal mucosa lesions.

Adult↗
PubMed1994

Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice.

OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha. STUDY DESIGN: C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide (50 micrograms/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1, 4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 micrograms lipopolysaccharide than in phosphate-buffered saline solution-treated mice (median 15.5 hours, range: 10 to 105 hours vs median 88.5 hours, range: 53 to 105 hours; p < 0.001). In comparison with phosphate-buffered saline solution-treated mice, a distinct serum cytokine pattern was observed in lipopolysaccharide-treated mice. Concentrations of tumor necrosis factor-alpha were detectable 1 and 4 hours after lipopolysaccharide injection (median 874 pg/ml, range: < 100 to 8000 pg/ml, p < 0.001; and median 263 pg/ml, range: < 100 to 927 pg/ml, p < 0.001, respectively). Concentrations of interleukin-6 were elevated at 1, 4, and 10 hours (median 11.8 ng/ml, range: 6 to 500 ng/ml, p < 0.001; median 27.1 ng/ml, range: 4.5 to 192 ng/ml, p < 0.001; median 1.95 ng/ml, range: < 0.05 to 35 ng/ml, p < 0.015, respectively). Concentrations of interleukin-1 alpha were significantly increased 4 hours after lipopolysaccharide injection (median 102 pg/ml, range: < 15 to 306 pg/ml, p < 0.001). A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice. In comparison with controls, concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide (median 0.88 ng/ml, range: 0.40 to 2.7 ng/ml, p < 0.025; and median 4 ng/ml, range: 1.9 to 33.6 ng/ml, p < 0.001, respectively). Interleukin-1 alpha was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-alpha was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha and in amniotic fluid concentrations of interleukin-6 and interleukin-1 alpha.

Amniotic Fluid↗
PubMed1994

Heterologous expression of the clostripain gene from Clostridium histolyticum in Escherichia coli and Bacillus subtilis: maturation of the clostripain precursor is coupled with self-activation.

Clostripain-specific antibodies were used to analyse the maturation of clostripain prepro-enzyme and core protein heterologously synthesized in Escherichia coli and Bacillus subtilis. Core protein purified from E. coli cells harbouring plasmid pHM3-23 underwent calcium-dependent, self-triggered maturation. Concomitantly, the inactive form of the enzyme was converted into an active form, demonstrating the self-activation capacity of the clostripain core protein. As judged from Western blot analysis, the major portion of the protein in E. coli was degraded, presumably by the activated clostripain. The enzyme was not exported to the E. coli periplasm, either by use of the putative Clostridium histolyticum signal peptide or by use of the E. coli OmpA signal peptide. Therefore, the Gram-positive micro-organism B. subtilis was chosen as an alternative host for the expression of the prepro-enzyme and the core protein. BR 151 cells harbouring pHM7-10B secreted clostripain precursor to the growth medium and matured subsequently to the active enzyme. As only a small amount of activity was detected intracellularly, the putative C. histolyticum signal peptide was efficiently recognized by the B. subtilis secretion apparatus. Under optimized conditions, a level of 4500 U I-1 could be obtained in batch cultures.

Bacillus subtilis↗
PubMed1994

Effects of pantoprazole on endocrine function in healthy male volunteers.

METHOD: In a randomized, double-blind, two-period crossover study, pantoprazole 40 mg or placebo were given orally to 12 male volunteers for 2 weeks each. There was a wash-out period of at least 1 week between the two treatment periods. The effects of pantoprazole or placebo on cortisol and testosterone (primary criteria), and tri-iodothyronine, thyroxine, thyroid-stimulating hormone, thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteotrophic hormone, prolactin and somatotrophic hormone were compared. In addition, intragastric 24-h pH, 24-h H(+)-activity, and volume of nocturnal gastric juice were determined by gastric aspiration technique. RESULTS: Pantoprazole did not influence plasma levels of testosterone, circadian cortisol concentrations or plasma cortisol levels after exogenous adrenocorticotropic hormone stimulation, as compared to placebo (P > 0.05, Koch's test). Furthermore, there were no clinically relevant changes with any of the other endocrine parameters. Pantoprazole significantly increased the median 24-h pH (group median 4.3 vs. 1.8; P < 0.001) and decreased 24-h H(+)-activity (4.0 vs. 22.6 mmol/L; P < 0.001). The volume of nocturnal gastric juice did not significantly differ between the two treatments. Pantoprazole was well tolerated and the frequency of adverse events was similar to placebo. No drug-related changes in laboratory values were observed. CONCLUSION: Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Early transcription in Caenorhabditis elegans embryos.

We have analysed early transcription in devitellinized, cultured embryos of the nematode Caenorhabditis elegans by two methods: measurement of [32P]UTP uptake into TCA-precipitable material and autoradiographic detection of [3H]UTP labelling both in the presence and absence of alpha-amanitin. RNA synthesis was first detected at the 8- to 12-cell stage, and alpha-amanitin sensitivity also appeared at this time, during the cleavages establishing the major founder cell lineages. The requirements for maternally supplied versus embryonically produced gene products in early embryogenesis were examined in the same culture system by observing the effects of alpha-amanitin on cell division and the early stereotyped lineage patterns. In the presence of high levels of alpha-amanitin added at varying times from two cells onward, cell division continued until approximately the 100-cell stage and then stopped during a single round of cell division. The characteristic unequal early cleavages, orientation of cleavage planes and lineage-specific timing of early divisions were unaffected by alpha-amanitin in embryos up to 87 cells. These results indicate that embryonic transcription starts well before gastrulation in C. elegans embryos, but that although embryonic transcripts may have important early functions, maternal products can support at least the mechanics of the first 6 to 7 cell cycles.

Amanitins↗
PubMed1992

Structure of the genes encoding Hordeum vulgare (1----3,1----4)-beta-glucanase isoenzymes I and II and functional analysis of their promoters in barley aleurone protoplasts.

Barley (1----3,1----4)-beta-glucanase isoenzyme II is synthesized in the aleurone cells during germination and secreted into the endosperm for hydrolysis of the cell walls. Its synthesis is stimulated by gibberellic acid (GA3) and repressed by abscisic acid. The gene for isoenzyme I is expressed in the aleurone, scutellum and prominently in young leaves. Close functional relatedness between the two enzymes is attested by 92% identity at the level of the amino acid sequence. The structural genes for the two enzymes each contain a large intron of 2505 bp and 2952 bp, respectively, in the codon for amino acid 25 of the 28-residue signal peptide. During evolution, homologous regions of the two introns have changed position and orientation. Furthermore, a large palindromic sequence of 327 bp in the 5' end of the intron is present only in the gene for isoenzyme II. In transient expression assays using barley aleurone protoplasts and chloramphenicol acetyl transferase as reporter the promoter of the isoenzyme I gene showed no response to GA3. However, removal of a unique 151 bp region extending from positions -402 to -552 upstream of the TATA box permitted low levels of GA3-induced expression of the reporter gene, suggesting a silencer function for this domain. High levels of GA3-responsive expression were obtained in aleurone protoplasts using the promoter of the gene encoding isoenzyme II. Truncation of this promoter revealed that sequences located within 253 bp upstream from the TATA box are sufficient to direct GA3-stimulated expression. Using the homologous barley aleurone protoplast transfection assay, it was possible to reproduce the in vivo expression characteristics of the genes for the barley (1----3,1----4)-beta-glucanase isoenzymes I and II with reporter gene constructs.

Amino Acid Sequence↗
PubMed1992

Vaginal PO2 in healthy women and in women infected with Trichomonas vaginalis: potential implications for metronidazole therapy.

We measured the PO2, pH, and temperature in the vaginal canals of nine patients with symptomatic Trichomonas vaginitis and those of 10 healthy women. The patients included eight women with primary infections caused by metronidazole-susceptible strains and one refractory case that resulted from infection with a metronidazole-resistant Trichomonas vaginalis. The median vaginal PO2, pH, and temperature in the patient group were 1 mm Hg, 6, and 37.3 degrees C respectively; these medians were 1 mm Hg, less than or equal to 4.5, and 37.2 degrees C in the healthy group. These data show that vaginal environment is anaerobic or microaerophilic (it has reduced oxygen tension). Because the activity of metronidazole is reduced under aerobiosis, the vaginal environment should enhance the biologic activity of the drug.

Adult↗
PubMed1992

[Stomach tolerance of various fluoride preparations. An endoscopy controlled single-blind study of healthy probands].

In 12 healthy volunteers the gastro-duodenal damaging effects of Ossiplex retard tid, Mono-Tridin tid and Ossin bid were investigated in a randomised, single blind cross-over study. Prior to the start of the three therapeutic phases subjects underwent endoscopic examination to exclude gastro-duodenal mucosa lesions. On day 14 of therapy 2 hours after the application of the last fluoride dose subjects underwent endoscopy again. The 14 days administration of Ossiplex retard, Mono-Tridin und Ossin led to gastro-duodenal mucosa lesion scores of 0.42 +/- 0.26; 1.50 +/- 0.54 and 2.08 +/- 0.71 (mean +/- SEM) respectively. These differences were statistically significant when comparing Ossiplex retard vs Ossin (p less than 0.05), but not Ossiplex retard vs Mono-Tridin. Regarding the number and the severity of lesions the differences between the gastro-duodenal mucosa damaging potency of the three fluoride preparations were also evident. With Ossiplex retard only in three subjects petechiae (n = 1) and antral erythemas (n = 2) were observed. Under Mono-Tridin and Ossin, however, a higher grade of lesions i.e. erosions and an ulcer were seen endoscopically. This study shows that the slow release fluoride preparation Ossiplex retard demonstrates a lower gastro-duodenal mucosa damaging potency when compared to the other fluorides Ossin and Mono-Tridin. There was no relationship between serum fluoride concentrations and the grade of gastro-duodenal mucosa lesions.

Adult↗
PubMed1991

[Acidity profile in humans after multiple oral administration of hydrotalcite].

Acid Suppression Profile of Hydrotalcite in Man. In this randomized, double blind, placebo-controlled cross-over study, the effect of hydrotalcite (CAS 12304-65-3, Talcid), 2 tablets qid (neutralizing capacity 122 mmol) on intragastric 24-h acidity was investigated. 12 healthy male and female volunteers were administered hydrotalcite, 2 tablets qid, or placebo on 2 study days, in each case at 10, 15, 20 and 23 h. Daytime (8-22 h) and nighttime (23-7 h) intragastric H+ concentrations (mmol/l) were significantly reduced by hydrotalcite compared with placebo. The following inhibiton rates were obtained: daytime 37.4%, nighttime 31.5% (p less than 0.05). During the 2-h periods immediately after oral application of hydrotalcite or placebo inhibition rates of up to 65% were observed. These results suggest that hydrotalcite may have also antiulcer activity like other antacids which are used in the treatment of peptic ulcer disease in low daily neutralizing capacities (120-280 mmol/die).

Administration, Oral↗
PubMed1990

Two types of genetic interaction implicate the whirligig gene of Drosophila melanogaster in microtubule organization in the flagellar axoneme.

The mutant nc4 allele of whirligig (3-54.4) of Drosophila melanogaster fails to complement mutations in an alpha-tubulin locus, alpha 1t, mutations in a beta-tubulin locus, B2t, or a mutation in the haywire locus. However, wrl fails to map to any of the known alpha- or beta-tubulin genes. The extragenic failure to complement could indicate that the wrl product participates in structural interactions with microtubule proteins. The whirligig locus appears to be haploinsufficient for male fertility. Both a deficiency of wrl and possible loss of function alleles obtained by reverting the failure to complement between wrlnc4 and B2tn are dominant male sterile in a genetic background wild type for tubulin. The dominant male sterility of the revertant alleles is suppressed if the flies are also heterozygous for B2tn, for a deficiency of alpha 1t, or for the haync2 allele. These results suggest that it is not the absolute level of wrl gene product but its level relative to tubulin or microtubule function that is important for normal spermatogenesis. The phenotype of homozygous wrl mutants suggests that the whirligig product plays a role in postmeiotic spermatid differentiation, possibly in organizing the microtubules of the sperm flagellar axoneme. Flies homozygous for either wrlnc4 or revertant alleles are viable and female fertile but male sterile. Premeiotic and meiotic stages of spermatogenesis appear normal. However, in post-meiotic stages, flagellar axonemes show loss of the accessory microtubule on the B-subfiber of outer doublet microtubules, outer triplet instead of outer doublet microtubules, and missing central pair microtubules.

Alleles↗