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Biomedical subjects

U Schmidt

Publications and source records attributed to U Schmidt.

At least 73 records · Page 4Linked to original sources
PubMed2001

Capsicum pain plaster in chronic non-specific low back pain.

Topically applied capsaicin (CAS 404-86-4) induces the release of substance P, a neurotransmitter, from sensory C-fibres. In addition, there is a specific blockade of transport and de-novo synthesis of substance P. As a result, repeated applications of capsaicin bring about a long lasting desensitisation to pain (increase of pain threshold). The desensitising effect is fully reversible. The confirmed pharmacodynamic actions and a number of double-blind clinical studies indicate that local capsicum preparations are very suitable for the treatment of neuropathic pain or musculoskeletal disorders, with or without inflammatory components. In a double-blind, randomised parallel-group study a capsicum plaster was compared with a placebo for 3 weeks in 154 patients with non-specific back pain. Inclusion criteria were a history of back pain for a minimum period of 3 months and a degree of pain of 5 or more on an eleven grade visual analogue scale. The principal target variable consisted of the score of 3 combined pain scales. Secondary efficacy measures were tests of mobility, a disability index (in the context of Arhus low back rating scale) and global assessments by physicians and patients. For patients to be rated as responders their total pain score at the final examination after 3 weeks of treatment had to show a reduction by at least 30% of the baseline value. The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219). The sum of the 3 separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%; p = 0.002). Relatively slight improvements of the impaired mobility and the functional status are explained by the characteristics of the disorder treated. The efficacy ratings by observers and patients was definitely in favour of capsicum. Adverse effects--mostly harmless and resolving spontaneously--were reported by 15 patients in the capsicum group and by 9 in the placebo group. The tolerance ratings by investigators and patients were superior to the placebo product. This, however, partly is due to the local pharmacological actions of the drug. As in comparably positive randomised studies with capsaicin cream in patients with osteoarthritis or fibromyalgia it was shown that a capsicum plaster preparation can also be used to advantage in chronic non-specific back pain.

Administration, Topical↗
PubMed2001

[Corneoretinal dystrophy (Bietti)-- Long-term course of one patient over a period of 30 years, and interindividual variability of clinical and electrophysiological findings in two patients].

BACKGROUND: A tapetoretinal dystrophy with crystalline deposits of the retina and limbal cornea was described by Bietti in 1937. To date, only a few cases with long-term follow up have been reported. PATIENTS AND METHODS: Two patients are presented including the clinical findings, fluorescein angiography, electrophysiology [electroretinography (ERG); electrooculography (EOG), multifocal electroretinography (MERG)], adaptometry, and transmission electron microscopy (TEM) of peripheral blood lymphocytes. The clinical findings were at least in part documented over a period of 30 years. RESULTS: The most striking features were deposits in the retina and cornea associated with crystalloid lysosomal inclusions in peripheral lymphocytes, and choroidal atrophy especially in advanced stages of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), the responses of the MERG and visual fields were affected progressively during the course. These advanced changes of the retinal pigment epithelium and choriocapillaris were observed in the 2(nd) decade already. CONCLUSIONS: The findings of deposits in the cornea, retina and lymphocytes may help to differentiate BCD from other chorioretinal dystrophies. The results confirm a variable course in clinical expression of BCD between individuals.

Adult↗
PubMed2001

[Malformation of a bronchial artery with shunt into the pulmonary vascular bed - a rare cause of massive haemoptysis].

We present the case of an otherwise healthy 41-year-old woman, who was admitted after having expectorated bright red blood. While the chest roentgenogram was found to be normal, fiberoptic bronchoscopy revealed mild active bleeding originating from the apicoposterior segmental bronchus of the left upper lobe, which exacerbated during the examination. The bleeding was contained through blockade of the upper lobe bronchus by means of a double-lumen endotracheal tube. After the patient had been referred to our department, we performed a resection of the superior segmental group of the left upper lobe. The histopathological examination of the specimen revealed a malformation of the bronchial artery with an abnormal communication to a branch of the pulmonary artery. The malformation was located in close proximity to the apicoposterior segmental bronchus. Whereas arteriovenous malformations with a pulmonary artery branch as feeding vessel have been described in more than 500 cases and primarily affect patients with hereditary hemorrhagic teleangiectasia (HHT, Rendu-Osler-Weber disease), the 23 reported cases of malformations supplied by a branch of the bronchial artery show no evidence of heredity. Furthermore, clinical appearence and localisation show characteristical differences between arteriovenous malformations with pulmonary arterial supply and malformations arising from a bronchial arterial source. Therefore, it seems appropriate to make a clear-cut distinction between these two patterns of vascular malformation of the lung.

Adult↗
PubMed2001

Binding of external ligands onto an engineered virus capsid.

The development of novel delivery systems for therapeutic substances includes targeting of the carriers to a specific site or tissue within the body of the recipient. This can be accomplished by appropriate receptor-binding domains and requires linking of these domains to the carrier. We have used recombinantly expressed polyomavirus-like particles as a model system and inserted the sequence of a WW domain into different surface loops of the viral capsid protein VP1. In one variant, the WW domain maintained its highly selective binding properties of proline-rich ligands and showed an increased affinity but also an accelerated association/dissociation equilibrium compared to the isolated WW domain, thus allowing a short-term coupling of external ligands onto the surface of the virus-like particles.

Animals↗
PubMed2001

Chimeric bovine respiratory syncytial virus with attachment and fusion glycoproteins replaced by bovine parainfluenza virus type 3 hemagglutinin-neuraminidase and fusion proteins.

Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of the Respirovirus genus can together functionally replace their homologs in a Pneumovirus background.

Animals↗
PubMed2001

Future-directed thinking in eating disorders.

OBJECTIVES: The aim of the study was to examine future-directed thinking in individuals with eating disorders, given the possible role of such cognitions in the maintenance of anorexia nervosa and bulimia nervosa. METHOD: Twenty-six anorexics, 18 bulimics and 34 female controls were interviewed using the 'Future Thinking Task', assessing quantitative and qualitative aspects of positive and negative anticipated events. RESULTS: Patients with anorexia nervosa had similar levels of positive future-oriented cognitions and significantly more negative future-oriented cognitions than controls. The most common positive themes in this group concerned the social/interpersonal and leisure/pleasure domains. The negative theme most commonly mentioned by anorexics was that of their own health, followed by the social/interpersonal domain, whereas controls were most preoccupied with achievement/failure and a broad range of other issues. Bulimics had significantly fewer positive future-oriented cognitions and significantly more negative future-oriented cognitions than controls, most commonly concerning the patient's own health. CONCLUSION: In anorexia nervosa, anticipated positive future outcomes may to some extent help to maintain the disorder; however, these patients are also highly preoccupied with the possibility of negative future outcomes, i.e. a failure of recovery. Bulimia nervosa sufferers are relatively hopeless about their future. The clinical implications of these findings are discussed.

Adult↗
PubMed2001

Synergistic inhibition of the glucocorticoid receptor by radicicol and benzoquinone ansamycins.

Radicicol (RAD) and the benzoquinone ansamycin geldanamycin (GA) are potential anticancer drugs known to inhibit heat shock protein 90 (hsp90) and, therefore, the activation of proteins dependent on its function such as proto-oncogenic kinases and nuclear receptors. Using the glucocorticoid receptor (GR) as a model system we analysed the effects of RAD and various benzoquinone ansamycins. All compounds efficiently abolished GR-dependent transactivation. Surprisingly, whenever one of the ansamycins was applied in combination with RAD, synergistic inhibition of GR-dependent transcription and of hormone binding of GR was observed. In contrast, combination of two ansamycins showed no synergy. These findings suggest synergism within the hsp90 dimer and may open new ways to explore hsp90 as therapeutic target.

Anti-Bacterial Agents↗
PubMed2001

Human telomerase reverse transcriptase antisense treatment downregulates the viability of prostate cancer cells in vitro.

Telomerase, a ribonucleoprotein complex is activated in the vast majority of human malignancies, including prostate cancer. Its inhibition is a putative way to affect cancer proliferation and might be used in the therapy of tumors. We analysed the influence of antisense phosphorothioate oligonucleotides (PTO) against the reverse transcriptase subunit of telomerase on prostate cancer cell viability, telomerase activity and telomere length. DU145 prostate cancer cells were cultivated in PTO containing medium. The PTO-incorporation was confirmed by confocal laser scanning microscopy. Cell viability was measured by a WST-1 tetrazolium assay. After 15 days of antisense PTO treatment, a significant inhibition of cell viability occurred. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay and telomere length by Southern blot analysis. Since the long-term telomerase antisense treatment reduces the viability of prostate cancer cells significantly, this antisense approach could be a new therapeutic strategy to treat patients with advanced prostate cancer.

Blotting, Southern↗
PubMed2000

Myofilament calcium regulation in human myocardium.

BACKGROUND: We investigated whether decreased myofilament calcium contractile activation may, in part, contribute to heart failure. METHODS AND RESULTS: Calcium concentration required for 50% activation and Hill coefficient for fibers from nonfailing and failing human hearts at pH 7.1 were not different. Maximum calcium-activated force (F(max)) was also not different. However, at pH 6.8 and 6.9, differences were seen in myofilament calcium activation between nonfailing and failing hearts. At lower pH, failing myocardium was shifted left on the calcium axis compared with nonfailing myocardium, which suggested an increase in myofilament calcium responsiveness. Increased inorganic phosphate concentration decreased maximal force development by 56% in nonfailing and 36% in failing myocardium and shifted the calcium-force relationship by 2.01+/-0.22 versus 0.86+/-0.13 micromol/L, respectively (P<0.05). Addition of cAMP resulted in a 0. 56 micromol/L shift toward higher intracellular calcium concentrations in nonfailing myocardium and a 1.04 micromol/L shift in failing myocardium. Protein kinase A in the presence of cAMP resulted in a further rightward shift in nonfailing human myocardium but did not further shift the calcium-force relationship in fibers from failing hearts. cGMP also resulted in a greater decrease in myofilament calcium sensitivity in fibers from failing hearts. CONCLUSIONS: We propose that changes at the level of the thin myofilaments result in differential responses to changes in the intracellular milieu in nonfailing versus failing myocardium.

Actin Cytoskeleton↗
PubMed2000

Neutron polarization induced by radio frequency radiation

We have measured that an unpolarized ultracold neutron beam gets polarized through its interaction with a resonant radio frequency field. Both spin components pass through the field and end up in one single spin state. We present a simple description for this surprising effect together with first experimental results.

Journal Article↗
PubMed2000

Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase.

BACKGROUND: Senescent hearts are characterized by diastolic dysfunction and a decrease in sarcoplasmic reticulum (SR) Ca(2+)-ATPase protein (SERCA2a). METHODS AND RESULTS: To test the hypothesis that an increase in SERCA2a could improve cardiac function in senescent rats (age 26 months), we used a catheter-based technique of adenoviral gene transfer to achieve global myocardial transduction of SERCA2a in vivo. Adult rat hearts aged 6 months and senescent rat hearts infected with an adenovirus containing the reporter gene beta-galactosidase were used as controls. Two days after infection, parameters of systolic and diastolic function were measured in open-chest rats. Cardiac SERCA2a protein and ATPase activity were significantly decreased in senescent hearts compared with adult rats (Delta -30+/-4% and -49+/-5%) and were restored to adult levels after infection with Ad.SERCA2a. At baseline, left ventricular systolic pressure and +dP/dt were unaltered in senescent hearts; however, diastolic parameters were adversely affected with an increase in the left ventricular time constant of isovolumic relaxation and diastolic pressure (Delta +29+/-9% and +38+/-12%) and a decrease in -dP/dt (Delta -26+/-11%). Overexpression of SERCA2a did not significantly affect left ventricular systolic pressure but did increase +dP/dt (Delta +28+/-10%) in the senescent heart. Overexpression of SERCA2a restored the left ventricular time constant of isovolumic relaxation and -dP/dt to adult levels. Infection of senescent hearts with Ad.SERCA2a markedly improved rate-dependent contractility and diastolic function in senescent hearts. CONCLUSIONS: These results support the hypothesis that decreased Ca(2+)-ATPase activity contributes to the functional abnormalities observed in senescent hearts and demonstrates that Ca(2+) cycling proteins can be targeted in the senescent heart to improve cardiac function.

Adenoviridae↗
PubMed2000

Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure.

In human and experimental models of heart failure, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances in calcium metabolism have been shown to contribute significantly to the contractile dysfunction observed in heart failure. We investigated whether increasing SERCA2a expression can improve ventricular function in an animal model of heart failure obtained by creating ascending aortic constriction in rats. After 19-23 wk of banding during the transition from compensated hypertrophy to heart failure (documented by >25% decrease in fractional shortening), rats were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a, n = 13) or beta-galactosidase (Ad.betagal, n = 14) by using a catheter-based technique. The failing hearts infected with Ad. betagal were characterized by a significant decrease in SERCA2a expression and a decrease in SERCA2a activity compared with nonfailing sham-operated rats (n = 11). In addition, these failing hearts had reduced left-ventricular systolic pressure, maximal rate of left-ventricular pressure rise and decline (+dP/dt, -dP/dt), and rate of isovolumic relaxation (tau). Overexpression of SERCA2a restored both SERCA2a expression and ATPase activity to nonfailing levels. Furthermore, rats infected with Ad.SERCA2a had significant improvement in left-ventricular systolic pressure, +dP/dt, -dP/dt, and rate of isovolumic relaxation (tau) normalizing them back to levels comparable to sham-operated rats. In this study, we show that in an animal model of heart failure where SERCA2a protein levels and activity are decreased and severe contractile dysfunction is present, overexpression of SERCA2a in vivo restores both systolic and diastolic function to normal levels.

Adenoviridae↗
PubMed2000

Chromosome topology and genome size of selected actinomycetes species.

Information about the genome organization of actinomycetes species is restricted to a few genera: Corynebacterium, Mycobacterium, Rhodococcus, Saccharopolyspora and Streptomyces. Streptomyces species and Saccharopolyspora erythraea were shown to contain a single linear 8 Mb chromosome. In contrast, the Corynebacterium, Mycobacterium and Rhodococcus species studied were demonstrated to possess a smaller (3 Mb-6.5 Mb) single circular chromosome. To investigate whether linear chromosome topology and genome sizes above 7 Mb are unique features of Streptomyces and S. erythraea we have started to investigate the chromosome topology, the genome size and the status of accessory elements of additional actinomycetes species: Actinoplanes philippinensis, Amycolatopsis orientalis, Micromonospora chalcea, Nocardia asteroides, Rhodococcus opacus and Streptoverticillium abikoense. Our data which are based on PFGE experiments clearly suggest that large genome sizes and chromosome linearity are seen in mycelium forming actinomycetes genera. In addition we have identified large linear plasmids in Nocardia asteroides, Streptoverticillium abikoense and Rhodococcus opacus.

Actinomycetales↗
PubMed2000

[Effects of an herbal crataegus-camphor combination on the symptoms of cardiovascular diseases].

One hundred and ninety (190) patients presenting with "functional cardiovascular disorders" (ICD 10, F 45.3) received purely herbal combination therapy comprising crataegus and camphor (Korodin Herz-Kreislauf-Tropfen) or a placebo, identical in colour and taste to the active treatment, over a period of four weeks within the scope of a multi-centre, placebo-controlled, double-blind study. The principal criterion was the fall in the overall score obtained for a heart-related symptom complex (HSK) during administration of the herbal combination or randomly allocated placebo. The overall score fell significantly by 5.5 or 4.5 points, respectively, from a baseline value of 10.0 points each (p = 0.0165). The sub-score for exhaustion, joint pain, heart disorders, pain on pressure and the total score on the Giessen discomfort chart (GBB) indicated better efficacy with the crataegus-camphor combination than with the placebo. On completion of treatment, the investigators assessed the efficacy of the active drug as "very good to good" in 70.5% of their patients compared with a similar evaluation in just 49.5% of the placebo patients. The degree of satisfaction with the drug therapy according to physician and patient reflected the objective results obtained. 71.6% of subjects in the active drug group were satisfied with their treatment compared with just 52.7% in the placebo group. Adverse events (undesirable side effects) were recorded in 8.3% and 8.5% of patients, respectively. A correlation with the active drug therapy was established in only two cases. Tolerance was therefore positively assessed.

Adult↗
PubMed2000

Factors affecting nuclear export of the 60S ribosomal subunit in vivo.

In Saccharomyces cerevisiae, the 60S ribosomal subunit assembles in the nucleolus and then is exported to the cytoplasm, where it joins the 40S subunit for translation. Export of the 60S subunit from the nucleus is known to be an energy-dependent and factor-mediated process, but very little is known about the specifics of its transport. To begin to address this problem, an assay was developed to follow the localization of the 60S ribosomal subunit in S. cerevisiae. Ribosomal protein L11b (Rpl11b), one of the approximately 45 ribosomal proteins of the 60S subunit, was tagged at its carboxyl terminus with the green fluorescent protein (GFP) to enable visualization of the 60S subunit in living cells. A panel of mutant yeast strains was screened for their accumulation of Rpl11b-GFP in the nucleus as an indicator of their involvement in ribosome synthesis and/or transport. This panel included conditional alleles of several rRNA-processing factors, nucleoporins, general transport factors, and karyopherins. As predicted, conditional alleles of rRNA-processing factors that affect 60S ribosomal subunit assembly accumulated Rpl11b-GFP in the nucleus. In addition, several of the nucleoporin mutants as well as a few of the karyopherin and transport factor mutants also mislocalized Rpl11b-GFP. In particular, deletion of the previously uncharacterized karyopherin KAP120 caused accumulation of Rpl11b-GFP in the nucleus, whereas ribosomal protein import was not impaired. Together, these data further define the requirements for ribosomal subunit export and suggest a biological function for KAP120.

Active Transport, Cell Nucleus↗
PubMed2000

Mechanism of assembly of recombinant murine polyomavirus-like particles.

VP1 is the major viral coat protein of murine polyomavirus and can be used for the generation of virus-like particles in vitro. Here, we demonstrate that capsid assembly is an equilibrium reaction followed by oxidation of intracapsomere disulfide bonds, which are not essential for the formation of virus-like particles but enable complete particle assembly and prevent capsid disassembly.

Animals↗