Search PubMed⌕ Search

Biomedical subjects

K Wolf

Publications and source records attributed to K Wolf.

At least 55 records · Page 3Linked to original sources
PubMed2001

Chlamydia pneumoniae major outer membrane protein is a surface-exposed antigen that elicits antibodies primarily directed against conformation-dependent determinants.

The major outer membrane protein (MOMP) of Chlamydia trachomatis serovariants is known to be an immunodominant surface antigen. Moreover, it is known that the C. trachomatis MOMP elicits antibodies that recognize both linear and conformational antigenic determinants. In contrast, it has been reported that the MOMP of Chlamydia pneumoniae is not surface exposed and is immunorecessive. We hypothesized that the discrepancies between C. trachomatis and C. pneumoniae MOMP exposure on intact chlamydiae and immunogenic properties might be because the focus of the host's immune response is directed to conformational epitopes of the C. pneumoniae MOMP. We therefore conducted studies aimed at defining the surface exposure of MOMP and the conformational dominance of MOMP antibodies. We present here a description of C. pneumoniae species-specific monoclonal antibody (MAb), GZD1E8, which recognizes a conformational epitope on the surface of C. pneumoniae. This MAb is potent in the neutralization of C. pneumoniae infectivity in vitro. Another previously described C. pneumoniae species-specific monoclonal antibody, RR-402, displayed very similar characteristics. However, the antigenic determinant recognized by RR-402 has yet to be identified. We show by immunoprecipitation of C. pneumoniae with GZD1E8 and RR-402 MAbs and by mass spectrometry analysis of immunoprecipitated proteins that both antibodies GZD1E8 and RR-402 recognize the MOMP of C. pneumoniae and that this protein is localized on the surface of the organism. We also show that human sera from C. pneumoniae-positive donors consistently recognize the MOMP by immunoprecipitation, indicating that the MOMP of C. pneumoniae is an immunogenic protein. These findings have potential implications for both C. pneumoniae vaccine and diagnostic assay development.

Amino Acid Sequence↗
PubMed2001

The NO donor molsidomine reduces endothelin-1 gene expression in chronic hypoxic rat lungs.

We investigated the effects of the nitric oxide (NO) donor molsidomine and the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on pulmonary endothelin (ET)-1 gene expression and ET-1 plasma levels in chronic hypoxic rats. Two and four weeks of hypoxia (10% O2) significantly increased right ventricular systolic pressure, the medial cross-sectional vascular wall area of the pulmonary arteries, and pulmonary ET-1 mRNA expression (2-fold and 3.2-fold, respectively). ET-1 plasma levels were elevated after 4 wk of hypoxia. In rats exposed to 4 wk of hypoxia, molsidomine (15 mg x kg(-1) x day(-1)) given either from the beginning or after 2 wk of hypoxia significantly reduced pulmonary hypertension, pulmonary vascular remodeling, pulmonary ET-1 gene expression, and ET-1 plasma levels. L-NAME administration (45 mg x kg(-1) x day(-1)) in rats subjected to 2 wk of hypoxia did not modify these parameters. Our findings suggest that in chronic hypoxic rats, exogenously administered NO acts in part by suppressing the formation of ET-1. In contrast, inhibition of endogenous NO production exerts only minor effects on the pulmonary circulation and pulmonary ET-1 synthesis in these animals.

Animals↗
PubMed2001

Adenosine kinase inhibitor GP515 improves experimental colitis in mice.

Adenosine is a potent anti-inflammatory mediator. Through elevation of endogenous adenosine concentrations the adenosine kinase inhibitor GP515 might serve to down-regulate local inflammatory responses. In the present study we investigated the effect of systemic GP515 in the nonacute model of dextran sulfate sodium (DSS)-induced colitis. The clinical score, colon length, histologic score, colon cytokine production, and spleen weight from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving GP515 treatment were determined and compared with untreated control mice. Splenocytes were analyzed for phenotype, interferon-gamma (IFNgamma) production, and CD69 expression. First, GP515 treatment resulted in a significant improvement of clinical score (weight loss, stool consistency, and bleeding) and of histologic score. Second, colon shortening, an indirect parameter for the degree of inflammation, was decreased, consistent with a decreased IFNgamma concentration in the colonic tissue. Third, spleen weight was reduced in GP515-treated DSS mice. And fourth, IFNgamma synthesis and CD69 expression, as a marker for early cell activation, of ex vivo-stimulated splenocytes were suppressed in the GP515-treated DSS mice. These studies show that GP515 is effective in the therapy of DSS-induced colitis. One potential mechanism of action is the suppression of IFNgamma synthesis and CD69 expression. Adenosine kinase inhibition forms a pharmacologic target that should be further investigated for chronic inflammatory bowel disease.

Adenosine Kinase↗
PubMed2001

Free-choice alcohol consumption in mice after application of the appetite regulating peptide leptin.

BACKGROUND: Leptin has been shown to regulate food intake and energy expenditure. Very recently, associations of elevated leptin plasma levels during alcohol withdrawal with alcohol craving have been observed in humans. Therefore, we tested the hypothesis that the application of exogenous leptin modulates voluntary alcohol consumption in mice. METHODS: Sixteen mice (129/Sv x C57BL/6J) were habituated to ethanol consumption over a time period of 3 months. After a basal 2-week free-choice drinking phase, mice were separated into two groups (n = 8) according to weight and alcohol consumption. They received recombinant leptin (1 mg/kg) versus saline intraperitoneally daily for 10 days. After 4 days of free-choice consumption of ethanol (16% v/v) versus water, ethanol was withdrawn at day 4 and replaced at day 6 to test the occurrence of an alcohol deprivation effects. Fluid intake was evaluated by controlling the weight of the drinking tubes daily. RESULTS: Free-choice ethanol consumption after withdrawal was significantly elevated in mice after intraperitoneal injection of 1 mg/kg leptin (alcohol deprivation effect), but not during basal drinking. CONCLUSION: We suggest that leptin may enhance motivation for alcohol consumption in habituated mice after alcohol withdrawal.

Alcohol Drinking↗
PubMed2000

Implementation of a molecular typing system to support epidemiological investigations in the tuberculosis health care system in Vienna.

Tuberculosis continues to be one of the predominant infectious diseases. Effective control of its spread requires that sources of infection and routes of transmission be disclosed as quickly as possible. At present such investigations are still performed by conventional epidemiological methods. In the recent past, however, molecular typing systems were added to the spectrum of epidemiological tools. Unfortunately, they were applied to retrospective investigations rather than used as an aid in the health care system. In this study, 515 Mycobacterium tuberculosis strains isolated during 1997 and 1998 in Vienna were analysed by spoligotyping, a molecular technique requiring no further cultivation of mycobacteria. The study was aimed to assess the suitability of the method as a quick means of disclosing new cases. Thus, clusters obtained by spoligotyping were analysed along with demographic and epidemiological data and compared with clusters obtained by conventional epidemiological techniques alone. In addition, spoligotype-forming clusters were matched with an international database containing spoligotypes from four different studies. Of 515 isolates, 107 showed an unique pattern. The remaining 408 isolates were distributed into two large clusters of 82 and 73 isolates and into 49 smaller ones consisting of 2 to 33 isolates each. The two spoligotypes forming the large clusters were identical with the most prevalent spoligotypes in the world. Therefore, for the tuberculosis authorities, information was only gained by excluding rather than tracing possible ways of transmission. Twenty-two of the 49 spoligotypes forming smaller clusters were identical with strains found in other parts of the world. Seventeen of 22 infection chains assumed by conventional investigations were confirmed by spoligotyping. In small clusters, an additional 24 infections were assumed due to similarities such as living conditions or socioeconomic status. In 27 clusters, all patients sharing the same strain belong to the same country or geographical area. In conclusion, spoligotyping proved suitable as an early guide in conventional investigations to trace routes of M. tuberculosis transmission in a community. However, when a strain isolated from a patient belongs to a spoligotype shared by many isolates, a second molecular typing method is required.

Austria↗
PubMed2000

Differential sustained attention/vigilance changes over time in schizophrenics and controls during a degraded stimulus Continuous Performance Test.

The Continuous Performance Test (CPT) is a widely used procedure for sustained attention/vigilance measurement. However, though the key index of vigilance impairment is the decrement of sensitivity over time during the test period, only few studies have examined whether schizophrenics show a larger drop in CPT performance than do healthy controls. 48 schizophrenic inpatients and 48 controls were investigated with the Munich CPT (480 visual stimuli, 25% target stimuli, one stimulus per second). Stimuli were degraded by randomly inverting 40%, 41%, 42%, or 43% of the pixels. Results were calculated separately for three consecutive trial sections. Additionally, PANSS ratings, medication, and other clinical data were documented. Schizophrenics show a vigilance decrement over time, controls show a vigilance increase. Differential vigilance changes were not related to the level of stimulus degradation. Schizophrenics performed worse than controls only at the lowest degradation level. While overall sensitivity correlated negatively with the dose of atypical neuroleptics and benzodiazepines, vigilance shifts over time correlated negatively with the dose of typical neuroleptics. Furthermore, sensitivity was related to the cognitive PANSS syndrome, number of admissions/duration of illness. Differential sensitivity decrements of schizophrenics and controls can be shown if suited CPT procedures are used. The need for basic research on experimental conditions of the CPT as well as examination of the relationship between sustained attention/vigilance decrements and clinical features of schizophrenia is suggested.

Adult↗
PubMed2000

[The Eppendorf Schizophrenia Inventory (ESI). Development and evaluation of a questionnaire for assessment of characteristic self perception of cognitive dysfunctions by schizophrenic patients].

This study explored characteristic subjective experiences of schizophrenia. A questionnaire for self-assessment of disturbances in several cognitive and perceptual areas (the Eppendorf Schizophrenia Inventory, or ESI) was constructed and administered to first-episode schizophrenics (SCHe, n = 45), negative syndrome schizophrenics (SCHn, n = 45), remitted schizophrenics (SCHr, n = 24), depressives (DEP, n = 43), alcoholics (ALK, n = 48), obsessive-compulsive patients (ZWA, n = 46), and healthy controls (KON, n = 57). Comparisons between the SCHe, SCHn, DEP, ALK, and ZWA groups and a subsequent factor analysis revealed four schizophrenia-specific dimensions: attention and speech impairment (AS), ideas of reference (IR), auditory uncertainty (AU), and deviant perception (DP). Further analyses suggested that the AS syndrome may represent a mediating vulnerability factor while IR, AU, and DP probably are reversible episode indicators. The results may contribute to refinements in the measurement of specific prepsychotic signs, thus facilitating the development of early intervention approaches.

Adult↗
PubMed2000

Interaction of phloretin with membranes: on the mode of action of phloretin at the water-lipid interface.

The interaction of phloretin with single lipid bilayers on a spherical support and with multilamellar vesicles was studied by differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). The results indicated that phloretin interacts with the lipid layer and changes its structural parameters. In DSC experiments, phloretin in its neutral form strongly decreased the lipid phase transition temperature and slightly reduced the cooperativity of the phase transition within the lipid layer. In NMR measurements, phloretin led to an increase of the transverse relaxation time constant but had no effect on the spin-lattice relaxation time constant. The overall dipole moment of phloretin was experimentally determined and was found to be roughly 40% lower than has been published previously. This result suggested that the size of the dipole moment of phloretin does not provide such a high contribution to the effect of phloretin on the dipole potential of monolayers and bilayers as has been published previously. To understand the discrepancy between phloretin adsorption and dipole potential change, we performed computational conformational analysis of phloretin in the gas phase. The results showed that a wide distribution of the dipole moments of phloretin conformers exists, which mainly depends on the orientation of the OH moieties. The adsorption of phloretin as determined from its binding to solid supported bilayers differed from the one determined from dipole potential measurements on black lipid membranes. The difference between the phloretin dissociation constants of both types of experiments suggested a change of its dipole moment normal to the membrane surface in a concentration-dependent manner, which was in agreement with the results of the computational conformational analysis.

Adsorption↗
PubMed2000

Molecular biology and clinical manifestation of hereditary factor VII deficiency.

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.

Factor VII↗
PubMed2000

Metabolite monitoring in plants with double-quantum filtered chemical shift imaging.

1H spectroscopic imaging in combination with double-quantum filtering with magnetic field gradients is used for in vivo applications in humans and animals. Because of its high selectivity and strong reduction of water signal it is also a useful tool for monitoring the distribution of specific metabolites in plants. The development and application of a double-quantum selective spectroscopic imaging sequence for detecting the sucrose distribution in the stem of sugar cane (Saccharum officinarum L.) is described. The results show that local differences in sucrose distribution can be detected non-invasively with a resolution of 0.4x0.4x6 mm(3) to 0.645x0.645x6 mm(3).

Magnetic Resonance Spectroscopy↗
PubMed2000

Overexpression of chloride channel CLC-K2 mRNA in the renal medulla of Dahl salt-sensitive rats.

OBJECTIVE: The present study aimed to characterize the influence of salt intake on the gene expression of the kidney specific chloride channels CLC-K1 and CLC-K2 in the kidneys of salt-resistant and salt-sensitive Dahl rats. DESIGN: For this purpose Dahl salt-resistant (Dahl-R) and Dahl salt-sensitive rats (Dahl-S) were fed a low (0.02%), normal (0.6%) or high (4%) salt diet for 19 days and CLC-K1 and -K2 mRNA expression was semiquantitated in cortex, outer and inner medulla. METHODS: Kidneys were macroscopically dissected, total RNA was isolated according to the guanidinium-thiocyanate-phenol-chloroform method and messenger RNAs for the kidney specific chloride channels CLC-K1 and CLC-K2 were measured by ribonuclease protection assay. RESULTS: Systolic blood pressure in high salt-treated Dahl-S rats increased to 204 +/- 5 mmHg versus 150 +/- 7 mmHg in Dahl-S controls. Dahl R and low salt Dahl-S rats showed no increase in blood pressure. For CLC-K1 mRNA we found an order of abundance inner medulla >> outer medulla >> cortex. There was no difference in mRNA abundance between Dahl-R and -S, nor any effect of the rate of salt intake on CLC-K1 mRNA abundance in the different kidney zones. CLC-K2 mRNA expression in cortex and outer medulla was similar between Dahl-R and -S rats. In the inner medulla, however, CLC-K2 mRNA was 1.7-fold higher in Dahl-S than in Dahl-R rats. In the cortex we found no influence of salt intake on CLC-K2 mRNA. In outer and inner medulla of Dahl-R rats and Dahl-S rats high salt diet led to a marked downregulation of CLC-K2 mRNA expression. Consequently, CLC-K2 gene expression in the inner medulla was 2.2-fold higher in Dahl-S than in Dahl-R rats in states of high salt diet. CONCLUSION: Given that the CLC-K2 chloride channel in the outer and inner medulla contributes to salt reabsorption, our findings would suggest that Dahl-S rats have an increased medullary salt reabsorption. This may contribute to the inability of these animals to excrete an increased salt load at a normal renal perfusion pressure leading to the development of hypertension.

Animals↗
PubMed2000

Effect of azithromycin plus rifampin versus amoxicillin alone on eradication and inflammation in the chronic course of Chlamydia pneumoniae pneumonitis in mice.

The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue. Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P. Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C. pneumoniae pneumonitis.

Amoxicillin↗
PubMed2000

Ultrastructural analysis of developmental events in Chlamydia pneumoniae-infected cells.

Chlamydia pneumoniae is an obligate intracellular parasite with a developmental cycle believed to be common to all members of the genus Chlamydia. We present a detailed description based on transmission and scanning electron microscopy of temporal events and inclusion structures throughout the C. pneumoniae AR-39 developmental cycle.

Chlamydophila pneumoniae↗
PubMed2000

Use of lycorine and DAPI staining in Saccharomyces cerevisiae to differentiate between rho0 and rho- cells in a cce1/delta cce1 nuclear background.

In the yeast Saccharomyces cerevisiae, mutants are viable with large deletions (rho-), or even complete loss of the mitochondrial genome (rho0). One class of rho- mutants, which is called hypersuppressive, is characterised by a high transmission of the mutated mitochondrial genome to the diploid progeny when mated to a wild-type (rho+) haploid. The nuclear gene CCE1 encodes a cruciform cutting endonuclease, which is located in the mitochondrion and is responsible for the highly biased transmission of the hypersuppressive rho- genome. CCE1 is a Holliday junction specific endonuclease that resolves recombination intermediates in mitochondrial DNA. The cleavage activity shows a strong preference for cutting after a 5'-CT dinucleotide. In the absence of the CCE1 gene product, the mitochondrial genomes remain interconnected and have difficulty segregating to the daughter cells. As a consequence, there is an increase in the fraction of daughter cells that are rho0. In this paper we demonstrate the usefulness of lycorine, together with staining by 4',6-diamidino-2-phenylindole (DAPI), to assay for the mitotic stability of a variety of mitochondrial genomes. We have found that rho+ and rho- strains that contain CT sequences produce a large fraction of rho0 progeny in the absence of CCE1 activity. Only those rho- mitochondrial genomes lacking the CT recognition sequence are unaffected by the cce1 allele.

Amaryllidaceae Alkaloids↗
PubMed2000

Chronic granulomatous meningitis with multiple cranial nerve lesions hydrocephalus, stroke, sinus thrombosis, and epilepsy.

Most frequently, chronic granulomatous meningitis (CGM) is caused by infectious agents. However, in some cases the cause of CGM remains undetermined. It is unclear whether antimicrobial agents, including antituberculous drugs, are helpful in such cases. We describe a 61-year-old man who had multiple cranial nerve lesions, epilepsy, sinus thrombosis, stroke, and hydrocephalus attributable to CGM. Repeated extensive search for a causative agent in the cerebrospinal fluid (CSF) and the meninges remained negative. Only a single culture of the sputum revealed growth of Mycobacterium tuberculosis, which prompted antituberculous therapy with isoniazid, rifampicin, and ethambutol. After 6 months of therapy, neurologic abnormalities were slightly improved. We conclude that antimicrobial/ antituberculous agents have only a minor short-term effect in long-lasting CGM of undetermined cause.

Aged↗
PubMed1999

Biosynthesis of phytochelatins in the fission yeast. Phytochelatin synthesis: a second role for the glutathione synthetase gene of Schizosaccharomyces pombe.

By complementation screening of a cadmium-sensitive Schizosaccharomyces pombe mutant deficient in phytochelatin synthesis, but with 44% of the wild-type glutathione content, we cloned a DNA fragment involved in phytochelatin synthesis. Sequence analysis revealed that it encodes the second enzyme involved in glutathione (GSH) biosynthesis, glutathione synthetase (GSH2) (E.C.6.3.2.3, Wang and Oliver, 1997). The mutant allele shows a single base-pair exchange at the 3' end of the reading frame leading to a single amino acid change from glycine to aspartate. This mutation leads to a significant reduction of phytochelatin synthesis, whereas glutathione synthesis is impaired to a far lesser extent. Complementation with the Arabidopsis thaliana GSH2 cDNA led to a partial restoration of phytochelatin synthesis. These data strongly suggest that the GSH2 gene encodes a bifunctional enzyme that is able to catalyse both the synthesis of GSH by adding glycine to the dipeptide (gammaGlu-Cys) and the synthesis of phytochelatins. The sequence has been submitted to EMBL, Accession No. Y08414.

Alleles↗