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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 73 records · Page 4Linked to original sources
PubMed2000

Characterization of a 300 kbp region of human DNA containing the type II hair keratin gene domain.

Screening of an arrayed human genomic P1 artificial chromosome DNA library by means of the polymerase chain reaction with a specific primer pair from the human type II hair keratin hHb5 yielded two P1 artificial chromosome clones covering approximately 300 kb of genomic DNA. The contig contained six type II hair keratin genes, hHb1-hHb6, and four keratin pseudogenes psihHbA-psihHbD. This hair keratin gene domain was flanked by type II epithelial keratins K6b/K6hf and K7, respectively. The keratin genes/pseudogene are 5-14 kbp in size with intergenic distances of 5-19 kbp of DNA and do not exhibit a single direction of transcription. With one exception, type II hair keratin genes are organized into nine exons and eight introns, with strictly conserved exon-intron boundaries. The functional hair keratin genes are grouped into two distinct subclusters near the extremities of the hair keratin gene domain. One subcluster encodes the highly related hair keratins hHb1, hHb3, and hHb6; The second cluster encodes the structurally less related hair keratins hHb2, hHb4, and hHb5. Reverse transcription-polymerase chain reaction shows that all hair keratin genes are expressed in the hair follicle. Pseudogene psihHbD is also transcriptionally expressed, albeit with alterations in splicing and frameshift mutations, leading to premature stop codons in the splice forms analyzed. Evolutionary tree analysis revealed a divergence of the type II hair keratin genes from the epithelial keratins, followed by their segregation into the members of the two subclusters over time. We assume that the approximately 200 kbp DNA domain contains the entire complement of human type II hair keratin genes.

Amino Acid Sequence↗
PubMed2000

Testing of individual blood donations for HCV RNA reduces the residual risk of transfusion-transmitted HCV infection.

BACKGROUND: To allow cost-effective RNA testing with NAT techniques, the national authorities of several countries have planned or already introduced tests of mixed specimens, that is, plasma pools. STUDY DESIGN AND METHODS: High-throughput extraction, amplification, and detection of HCV RNA from individual blood donations were optimized and validated. The feasibility of the method and the frequency of anti-HCV-negative, HCV RNA-positive donations were determined in a prospective study of 27,745 allogeneic and 792 autologous individual donations. RESULTS: The 50- and 95-percent detection limits of the method were determined at 44 IU per mL and 162 IU per mL, respectively (World Health Organization HCV reference material). When 201 HCV RNA-positive sera were taken as a reference, the sensitivity was 97.5 percent. The assay specificity was determined at 99.77 percent. During a 20-month period, two seronegative blood donors tested positive in HCV PCR. The viral load of these donations was 6 x 10(6) and 3 x 10(7) copies per mL, respectively. Thus, the yield of HCV RNA testing in this study was 7. 63 per 100,000 screened donations (95% CI, 1.25-22.07). In both PCR-positive donors, seroconversion was found in subsequent blood samples. CONCLUSION: This study compares the feasibility of single-donation HCV RNA screening, with the detection of a relatively high percentage of window-phase donations, to data reported from groups using HCV RNA testing of plasma pools. The relative yield of NAT of individual donations versus minipools should be directly investigated in the near future.

Blood Donors↗
PubMed2000

Community treatment orders: relationship to clinical care, medication compliance, behavioural disturbance and readmission.

OBJECTIVE: The objective of this study was to investigate the readmission rate, and the level of patient disturbance and community care associated with readmission following Community Treatment Orders (CTOs) in New South Wales, Australia. METHOD: The readmission rates of all patients given CTOs within a 4-year period and a matched comparison group were investigated. The following factors were compared before, during and following a CTO: medication non-compliance, number of clinical services and duration of disturbed behaviour preceding hospitalisations. RESULTS: Of 123 patients on CTOs (mean length, 288 days; SD, 210 days), 38 were readmitted during the CTO, the majority in the first 3 months and a further 21 patients were readmitted following termination of the CTO. Evidence of lower severity of illness in the comparison patients prevented meaningful evaluation of the readmission rates of the two groups. While on CTOs, patients receiving depot medications showed high compliance and a significantly reduced readmission rate compared with that of patients receiving oral medications. In the 2 months prior to hospitalisations during CTOs, compared with those before or after CTOs, patients received more frequent consultations and showed a shorter duration of medication non-compliance and disturbed behaviour. The level of services in the 3 months following discharge were comparable for patients on CTOs and the comparison group. CONCLUSIONS: CTOs may reduce rehospitalisations by use of depot medication. Earlier and possibly more frequent readmissions in the CTO group shortened the disturbance associated with illness recurrence. It would appear that to establish a control group with equivalent severity of disorder necessary to evaluate the impact of CTOs requires a random allocation design.

Adolescent↗
PubMed2000

Role of cholesterol in embryonic development.

We showed previously that 3 distal inhibitors of cholesterol synthesis are highly teratogenic in rats. AY 9944 and BM 15766 inhibit 7-dehydrocholesterol reductase, which catalyzes the last step of cholesterol synthesis, and triparanol inhibits Delta(24)-dehydrocholesterol reductase, which catalyzes the last step in another pathway. These molecules cause holoprosencephalic brain anomalies. Under certain experimental conditions, other anomalies (of the limbs and male genitalia) are also observed. Assays performed by gas chromatography-mass spectrometry (GC-MS) show hypocholesterolemia and an accumulation of precursors. These data indicate that this animal model can be considered a model of Smith-Lemli-Opitz syndrome. Smith-Lemli-Opitz syndrome is a recessive autosomal genetic disease characterized by malformations (microcephaly, corpus callosum agenesis, holoprosencephaly, and mental retardation), male pseudohermaphroditism, finger anomalies, and failure to thrive. The syndrome has been attributed to a deficit in 7-dehydrocholesterol reductase. As assayed by GC-MS, the sterol status of these patients indicates severe hypocholesterolemia and an accumulation of precursors: 7-dehydrocholesterol, 8-dehydrocholesterol, and oxidized derivatives. The presence of 7-dehydrocholesterol in the serum of patients is pathognomonic of the disease. The developmental gene Shh (sonic hedgehog) plays a key role in brain, limb, and genital development; it was shown recently that the Shh protein has to be covalently linked to cholesterol to be active. This is the first time that a posttranslational function has been attributed to cholesterol. There is an obvious relation between Shh dysfunction and the malformations observed in our experiments and in patients with Smith-Lemli-Opitz syndrome. However, the exact relation remains to be clarified. It is clear, however, that the role of cholesterol in embryonic development must be taken into account.

Animals↗
PubMed2000

Sulthiame as monotherapy in children with benign childhood epilepsy with centrotemporal spikes: a 6-month randomized, double-blind, placebo-controlled study. Sulthiame Study Group.

PURPOSE: To evaluate the efficacy and tolerability of sulthiame (STM) as monotherapy in children with benign childhood epilepsy with centrotemporal spikes (BECTS). METHODS: Sixty-six BECTS patients entered a 6-month double-blind trial and were randomized to receive either STM (5 mg/kg/day) or a placebo. All patients had had two or more seizures during the 6 months preceding the trial and were aged 3-11 years. Seizures were recorded by parents in a diary. STM plasma levels and electroencephalograms (EEGs) were overseen by patient-blinded observers. The primary effectiveness variable was the rate of treatment failure events (TFEs) per group. TFEs consisted of a first seizure after a 7-day run-in period, intolerable adverse events (AEs), development of another epileptic syndrome, or termination of the trial by parents or patient. RESULTS: Twenty-five of the 31 STM-treated patients (81%) and 10 of the 35 placebo-treated patients (29%) completed the trial without any TFEs (p = 0.00002). Most TFEs were seizures (n = 4 for the STM patients, n = 21 for the placebo group). Parents requested termination for two placebo-treated patients. Four patients were terminated for administrative reasons. No patient was withdrawn for AEs. While all patients displayed at least one specific focus in either the awake or asleep EEG initially, 11 STM-treated patients had a normal awake EEG and 10 had a normal asleep one after 6 months. CONCLUSIONS: STM was remarkably effective in preventing seizures in patients with BECTS. Patients suffering from > or = 2 seizures during the past 6 months had a high risk of early recidivism. STM was well tolerated and should be considered for children with BECTS who are in need of treatment.

Anticonvulsants↗
PubMed2000

LPA as a paracrine mediator of adipocyte growth and function.

Adipogenesis corresponds to the recruitment of new adipocytes in adipose tissue, and results from the proliferation/differentiation of preadipocytes. Production of paracrine and autocrine factors by adipocytes plays an important role in adipogenesis. We recently demonstrated the existence of adipocyte production of lysophosphatidic acid (LPA) both in vitro and in situ. This production is modulated by catecholamines via alpha 2-adrenergic receptors. Adipocyte-LPA present in conditioned media increases the growth of a preadipose cell line in culture. This growth is associated with an activation of mitogen-activated protein kinases, and of the focal adhesion kinase. Because of the close proximity of preadipocytes and adipocytes within adipose tissue, adipocyte-LPA could play an important role in autocrine/paracrine control of adipogenesis.

Adipocytes↗
PubMed2000

Neutron RBE for induction of tumors with high lethality in Sprague-Dawley rats.

The effectiveness of fission neutrons is compared to that of gamma rays and X rays with regard to the induction of malignancies in male Sprague-Dawley rats. The analysis is based on autopsy results. It is focused on tumors that tend to be present in animals dying early, which is indicative of a high degree of lethality. The relative biological effectiveness (RBE) is deduced from a comparison of the cumulative hazard functions. Different nonparametric models-the constant relative risk model, a time shift model, and an acceleration model-are employed in the comparison, and the resulting values of RBE are seen to be substantially independent of the choice of model. The results are in good agreement with earlier studies of nonlethal lung tumors in the same series of experiments. At neutron doses of 20 to 60 mGy, the RBE of fission neutrons is about 50.

Animals↗
PubMed2000

Cholesterol deficit but not accumulation of aberrant sterols is the major cause of the teratogenic activity in the Smith-Lemli-Opitz syndrome animal model.

Low cholesterol and high 7-dehydrocholesterol (7DHC) levels are associated with a blockade of Delta7-reductase in the Smith-Lemli-Opitz syndrome (SLOS) and in the animals treated with the inhibitor AY9944. The impact of the cholesterol deficit and of the accumulation of 7DHC on the embryo were investigated in AY9944-treated pregnant rats receiving an enriched cholesterol or 7DHC diet. Sterol profiling was performed under the various nutritional conditions. AY9944 caused a severe decrease in the maternal and embryo cholesterol. The deficit in the embryo was sustained by the embryonic uptake of the inhibitor. A cholesterol-rich diet was efficient in restoring the maternal and embryonic cholesterol and phenotype but a 7DHC-rich diet did not modify the sterol status compared with dams treated with only AY9944. The offspring phenotype remained deleterious whether or not the dams received 7DHC-rich diet. Over 80% of the 7DHC was absorbed, as was cholesterol, which was not quantitatively influenced by AY9944. When cholesterol and 7DHC were simultaneously administered, a competition for intestinal absorption enhanced the lowering cholesterol effect of AY9944. Whether or not the dams received a 7DHC dietary supplement, the offspring's phenotype became normal when the diet was supplemented with cholesterol. Under conditions in which the ratio of cholesterol/7DHC is substantially varied, the normal development of embryos can be achieved as long as the cholesterol is sufficient. The phenotype is reversed in vivo by cholesterol which contrasts with the irreversible effects manifested in vitro by oxidized 7DHC by-products.

Abnormalities, Drug-Induced↗
PubMed2000

[Is there an increase of serum antisperm antibodies following surgery in the cervical transformation zone for cervical intraepithelial neoplasia (CIN)?].

OBJECTIVE: This prospective controlled study was performed to investigate whether operative procedures of the uterine cervix lead to a change in the titre of humoral antispermatozoal antibodies. MATERIAL AND METHODS: Humoral antispermatozoal antibodies were measured using an ELISA in 15 patients undergoing cervical scraping, 20 having conisation, 10 having a loop excision before and at least 3 months after surgery as well as in 10 fertile women as a control group. RESULTS: There were no significant differences in age between groups, in the distribution of initial and final levels of humoral antispermatozoal antibodies (IgG, IgA), and no significant change of the antibody titres (pre- and postoperative) within the individual groups. CONCLUSIONS: In patients of fertile age, the formation of humoral isoantibodies does not have to be taken into account in selecting the method of diagnosing and treating cervical intraepithelial neoplasia (CIN).

Adult↗
PubMed2000

Sphingolipids and cholesterol modulate membrane susceptibility to cytosolic phospholipase A(2).

Modulation of cytosolic phospholipase A(2) (cPLA(2)) activity by sphingomyelin (SPH), ceramide (Cer), and cholesterol (Chol) was investigated in CHO-2B cells activated by the calcium ionophore A23187 and epinephrine. Chol depletion of CHO-2B cells by treatment with methyl-beta-cyclodextrin (5 mm) resulted in the inhibition of the release of arachidonic acid whereas the restoration of the level by Chol-loaded cyclodextrin relieved inhibition. Conversion of CHO-2B cellular SPH to Cer by Staphylococcus aureus sphingomyelinase enhanced endogenous cPLA(2) activation as well as uptake by cells of C2- and C6-ceramide analogs. These results were confirmed in vitro with purified human recombinant cPLA(2) acting on a model phospholipid substrate. The enzyme activity was inhibited by SPH but reactivated by Cer as well as by Chol added to glycerophospholipid liposomal substrates containing SPH. The results of this study, which combine in situ and in vivo experimental approaches, indicate that membrane microdomains enriched in SPH and Chol play a role in the modulation of the activity of cPLA2 and in arachidonic acid-derived mediator production.

Animals↗
PubMed2000

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy. A retrospective study of 19 cases.

OBJECTIVE: We studied the clinical and biological effects and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: All cases of ICP treated with ursodeoxycholic acid in our department from January 1st, 1991 to May 31st, 1997 were reviewed. RESULTS: Forty-three patients had ICP, of whom 19 received ursodeoxycholic acid. The first symptoms appeared after a mean of 29.7 weeks of pregnancy (WP). Treatment was started after a mean of 32 WP, and lasted a mean of 28.5 days. Fourteen patients showed a clinical improvement on UDCA, and 11 showed a biological improvement. Two had a biological deterioration with increased liver enzyme concentrations. CONCLUSIONS: Ursodeoxycholic acid appears to be an effective treatment for ICP, but further studies are needed to confirm its safety in pregnancy.

Adult↗
PubMed2000

Hepatitis C virus transmission through quarantine fresh-frozen plasma.

In 1994, quarantine fresh-frozen plasma (Q-FFP) was introduced in Germany in order to reduce the risk of HIV and HCV transmission. In 1998, an acute HCV infection of a patient was reported to us. The look-back revealed that this patient had received two Q-FFP from a donor who had seroconverted for HCV in the meantime. Recipients of further plasma donations from this donor were identified. Back-up specimens of these donations were investigated in several laboratories. A total of 25 additional HCV-PCR positive plasma units had been transfused to 12 further patients. HCV infections were diagnosed in seven of these recipients, three patients had already been deceased. One of the remaining two recipients was already HCV positive prior to transfusion, in the other patient, no HCV infection was detectable. This patient had received three units of an "early" plasma donation , which was tested negative by PCR in one laboratory, but positive in the other. The subsequent, clinically infectious donation had the same discrepant PCR results. Thus, eight cases of HCV transmission were revealed and classified as "certain" with regard to causality, also due to an identical HCV genotype, i.e. 3e. Some of these infections would have been prevented by application of a different anti-HCV assay. The assay used in the respective plasmapheresis station was in-sensitive in this individual case for more than 400 days after the first PCR positive donation. This caused the release of the above mentioned infectious units. Upon re-testing the backups, three of four other anti-HCV assays revealed a positive result already 104 days after the first PCR-positive donation. The donor had increased ALAT levels (> 23 IU/L) at nine of 28 donations, two of these were higher than 2.5 times the upper normal limit, and two were higher than 68 IU/L, which is the cut-off value for male blood donors in Germany. The results of these (look-back) studies arouse several queries, i.e. differences in the diagnostic sensitivity between current anti-HCV and PCR tests, the accuracy of risk-estimates (especially when based on hemovigilance studies for Q-FFP), the value of ALAT testing, and currently practised release algorithms for Q-FFP.

Adult↗
PubMed1999

Olestra increases faecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Two patients with chloracne had concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) of 144,000 and 26,000 pg/g blood lipids. Olestra, a non-digestible, lipophilic dietary fat substitute accelerated the patients' intestinal excretion of TCDD by eight to ten fold. This is sufficient to reduce the normally observed elimination half life of TCDD from about 7 years to 1-2 years.

Acne Vulgaris↗
PubMed1999

Synthesis and in vitro multidrug resistance modulating activity of a series of dihydrobenzopyrans and tetrahydroquinolines.

A series of dihydrobenzopyrans and tetrahydroquinolines was synthesized and pharmacologically tested for their ability to inhibit P-glycoprotein mediated daunomycin efflux in multidrug resistant CCRF-CEM vcr1000 cells. Several compounds exhibit activities in the range of the reference compounds verapamil and propafenone. Preliminary structure-activity relationship studies propose the importance of high molar refractivity values of the compounds and the presence of an additional basic nitrogen atom.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Pitfalls in prenatal diagnosis of DMD due to placental mosaicism of the X-chromosomes: prenatal and postnatal findings in a fetus with a deletion of exons 67-71 of the dystrophin gene.

Prenatal diagnosis of Duchenne and Becker muscular dystrophy (DMD) is performed as a routine procedure in many laboratories. The major potential problem is an incorrect diagnosis that could be obtained due to contamination with maternal tissue. We report a case of mosaicism of the X-chromosomes confined to the placenta as a possible source of confusing results in prenatal diagnosis of DMD. To the best of our knowledge, this is the first reported case of this problem in a prenatal DMD diagnosis.

Abortion, Induced↗
PubMed1999

[MRI characteristics of spontaneous intracerebral hemorrhage].

We review the signal characteristics of intracerebral hematomas (ICH) on magnetic resonance imaging (MRI), with special emphasis on the diagnosis of intracerebral hemorrhage within the first hours after stroke.The detection of peracute ICH was evaluated in 42 patients of a prospective, MR randomized stroke trial. These patients underwent a protocol of T1 and T2 weighted sequences, diffusion weighted sequences and MR - angiography within 6 hours after onset of acute hemiparesis. The signal behaviour of ICH in any stage after bleeding was additionally reviewed in a retrospective series of 63 patients, who were submitted for MRI over a 12 months period because of known ICH.MRI correctly identified 4 hyperacute ICH in the prospective group and 4 hyperacute ICH in the retrospective group. These ICHs had high signal on T2 weighted images, were isointense in T1 weighted images and had signal voids on the diffusion weighted sequences. The signal intensities of acute, subacute and chronic ICHs correlated to previous experiences as reported in the literature.In conclusion, MRI reliably identified all hematomas even in the hyperacute stage. Diffusion weighted images were most sensitive to the presence of deoxyhemoglobine and helpful for the differentiation and characterization of acute ischemia. Therefore, MRI at 1.5 T can be employed as an alternative to CT for the emergency diagnosis of acute stroke.

Cerebral Hemorrhage↗