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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 163 records · Page 9Linked to original sources
PubMed2000

Differential effects of zinc on amyloid precursor protein (APP) processing in copper-resistant variants of cultured Chinese hamster ovary cells.

Previous studies have demonstrated that adding copper to Chinese-hamster ovary (CHO) cells greatly reduced the levels of beta-amyloid (Abeta) peptide in parental CHO-K1 and in copper resistant CHO-CUR3 cells which have lower intracellular copper levels. In the current study, zinc, the zinc chelator 1,10-phenanthroline or copper chelators bathocuproine and D-penicillamine were added to the culture media of stably transfected CHO cells. The data show that zinc up to concentrations of 50 microM or the presence of 1,10-phenanthroline specifically increased the level of secreted APP in CHO-K1 cells. By contrast, the level of secreted APP in CHO-CUR3 cells remained unaffected. APP holoprotein increased dramatically in CHO-CUR3 cells compared with CHO-K1 cells. The large decrease of Abeta release seen in both cell lines at elevated extracellular zinc levels was due to specific inhibition of secretion. These results indicate that a disturbed zinc-homeostasis may be an important factor influencing APP production, transport and processing.

Amino Acid Sequence↗
PubMed1999

Ambulatory care of patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVAD) have revolutionized the treatment of patients with acute and chronic heart failure as they provide a high quality of life. We report on our experience with patients receiving ambulatory care after LVAD implantation. METHODS AND RESULTS: Since July 1995, 46 patients with a mean age of 45+/-11 years underwent implantation of an electrically driven LVAD with portable controller and batteries. Sixteen (35%) patients bridged >30 days were treated in part on an outpatient basis. After LVAD implantation, they were treated in the hospital for 86+/-32 days (range 40 to 153 days). Afterward, they received ambulatory care for 74+/-76 days (range 2 to 301 days, total experience 1206 days). In 13 cases, the outpatient treatment was interrupted by 1.7+/-1.7 readmissions, for a total of 32+/-42 days (median 19 days). Reasons for readmission included systemic or drive line infections (incidence 0.0066 per outpatient day), suspected or true thromboembolic events (incidence 0.0066 per outpatient day), and suspected malfunction of the LVAD. One patient supported as alternative to transplantation died after cerebral bleeding after 244 days, 1 patient with a history of acute myocarditis had ventricular fibrillation during LVAD assist while being at home for 177 days and died in a low output state, 10 patients were given transplantation after a mean support interval of 206+/-88 days, and 4 patients currently await heart transplantation. CONCLUSIONS: Outpatient treatment after LVAD implantation is feasible, and severe complications are uncommon.

Adult↗
PubMed1999

An HLA-A2 polyepitope vaccine for melanoma immunotherapy.

Epitope-based vaccination strategies designed to induce tumor-specific CD8 CTL are being widely considered for cancer immunotherapy. Here we describe a recombinant poxvirus vaccine that codes for ten HLA-A2-restricted epitopes derived from five melanoma Ags conjoined in an artificial polyepitope or polytope construct. Target cells infected with the melanoma polytope vaccinia were recognized by three different epitope-specific CTL lines derived from HLA-A2 melanoma patients, and CTL responses to seven of the epitopes were generated in at least one of six HLA-A2-transgenic mice immunized with the construct. CTL lines derived from vaccinated transgenic mice were also able to kill melanoma cells in vitro. Multiple epitopes within the polytope construct were therefore shown to be individually immunogenic, illustrating the feasibility of the polytope approach for melanoma immunotherapy. Tumor escape from CTL surveillance, through down regulation of individual tumor Ags and MHC alleles, might be overcome by polytope vaccines, which simultaneously target multiple cancer Ags.

Amino Acid Sequence↗
PubMed1999

Redox components of cytochrome bc-type enzymes in acidophilic prokaryotes. II. The Rieske protein of phylogenetically distant acidophilic organisms.

The Rieske proteins of two phylogenetically distant acidophilic organisms, i.e. the proteobacterium Thiobacillus ferrooxidans and the crenarchaeon Sulfolobus acidocaldarius, were studied by EPR. Redox titrations at a range of pH values showed that the Rieske centers of both organisms are characterized by redox midpoint potential-versus-pH curves featuring a common pK value of 6.2. This pK value is significantly more acidic (by almost 2 pH units) than that of Rieske proteins in neutrophilic species. The orientations of the Rieske center's g tensors with respect to the plane of the membrane were studied between pH 4 and 8 using partially ordered samples. At pH 4, the Sulfolobus Rieske cluster was found in the "typical" orientation of chemically reduced Rieske centers, whereas this orientation changed significantly on going toward high pH values. The Thiobacillus protein, by contrast, appeared to be in the "standard" orientation at both low and high pH values. The results are discussed with respect to the molecular parameters conveying acid resistance and in light of the recently demonstrated long-range conformational movement of the Rieske protein during enzyme turnover in cytochrome bc1 complexes.

Cytochrome b Group↗
PubMed1999

Transient peaks in zinc and metallothionein levels during differentiation of 3T3L1 cells.

A novel role for zinc mediated by metallothionein (MT) is found in the process of differentiation of 3T3L1 mouse fibroblasts to adipocytes. Twenty-four hours after the stimulation of differentiation by hormones, the cells enter into a phase of synchronous proliferation. In this phase the cellular contents of zinc and metallothionein rise rapidly to fivefold and threefold levels, respectively. Simultaneously MT is translocated from the cytoplasm to the nucleus. The rise of intracellular zinc is essential for the transition from G0/G1- to S-phase of the cell cycle. Deprivation of zinc with N,N,N', N'-tetrakis[2-pyridyl]ethylenediamine, a membrane-permeable zinc chelator, inhibited hormonal induced proliferation. After the short phase of proliferation a slower stage of actual differentiation to adipocytes begins. The elevated levels of MT and zinc decline quickly to start levels, and a rapid redistribution of MT to the cytoplasm occurs. We propose that the nuclear translocation of MT mediates the transfer of zinc to nuclear factors in the mitogenic process. The redistribution of MT to the cytoplasm and the decrease of the zinc content are postulated to be required for the start of the actual differentiation.

3T3 Cells↗
PubMed1999

Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: implications for molecular mimicry in autoimmune disease.

The immunodominant, CD8(+) cytotoxic T lymphocyte (CTL) response to the HLA-B8-restricted peptide, RAKFKQLL, located in the Epstein-Barr virus immediate-early antigen, BZLF1, is characterized by a diverse T cell receptor (TCR) repertoire. Here, we show that this diversity can be partitioned on the basis of crossreactive cytotoxicity patterns involving the recognition of a self peptide-RSKFRQIV-located in a serine/threonine kinase and a bacterial peptide-RRKYKQII-located in Staphylococcus aureus replication initiation protein. Thus CTL clones that recognized the viral, self, and bacterial peptides expressed a highly restricted alphabeta TCR phenotype. The CTL clones that recognized viral and self peptides were more oligoclonal, whereas clones that strictly recognized the viral peptide displayed a diverse TCR profile. Interestingly, the self and bacterial peptides equally were substantially less effective than the cognate viral peptide in sensitizing target cell lysis, and also resulted only in a weak reactivation of memory CTLs in limiting dilution assays, whereas the cognate peptide was highly immunogenic. The described crossreactions show that human antiviral, CD8(+) CTL responses can be shaped by peptide ligands derived from autoantigens and environmental bacterial antigens, thereby providing a firm structural basis for molecular mimicry involving class I-restricted CTLs in the pathogenesis of autoimmune disease.

Amino Acid Sequence↗
PubMed1999

hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis.

MutS homologues have been identified in nearly all organisms examined to date. They play essential roles in maintaining mitotic genetic fidelity and meiotic segregation fidelity. MutS homologues appear to function as a molecular switch that signals genomic manipulation events. Here we describe the identification of the human homologue of the Saccharomyces cerevisiae MSH5, which is known to participate in meiotic segregation fidelity and crossing-over. The human MSH5 (hMSH5) was localized to chromosome 6p22-21 and appears to play a role in meiosis because expression is induced during spermatogenesis between the late primary spermatocytes and the elongated spermatid phase. hMSH5 interacts specifically with hMSH4, confirming the generality of functional heterodimeric interactions in the eukaryotic MutS homologue, which also includes hMSH2-hMSH3 and hMSH2-hMSH6.

Amino Acid Sequence↗
PubMed1999

Incorporation of polymeric nanoparticles into solid dosage forms.

Besides parenteral delivery, polymeric nanoparticles have been used for oral drug delivery. In this study, model polymeric nanoparticles (aqueous colloidal polymer dispersions: Eudragit(R) RL 30D, L 30D, NE 30D, or Aquacoat(R)) with different physicochemical properties were incorporated into various solid dosage forms (granules, tablets, pellets or films). The compatibility of the nanoparticles with commonly used tabletting excipients and the redispersibility of the nanoparticles after contact of the solid dosage forms with aqueous media were investigated. Ideally, the nanoparticles should be released from the solid dosage forms with their original properties. The addition of polymeric binders (e.g. polyvinylpyrrolidone, Na carboxymethylcellulose or hydroxypropyl methylcellulose) to the aqueous nanoparticle dispersions prior to wet granulation resulted in phase separation (depletion or bridging flocculation) for many nanoparticle/binder systems. Two critical parameters for the complete redispersibility/release of the nanoparticles with the original particle size properties from the solid dosage forms were a (1) high minimum film formation temperature (MFT) of the polymer dispersion and (2) a good wettability of the dried polymeric nanoparticles. Nanoparticle dispersions with a low MFT were not redispersible, they coalesced into larger agglomerates/films during the drying step. Contact angle measurements correlated well with the redispersibility of the nanoparticles, with ethylcellulose particles having high contact angles and poor redispersibility and Eudragit(R) RL, a polymer stabilized with quaternary ammonium groups, having low contact angles and good redispersibility.

Acrylic Resins↗
PubMed1999

Serial determination of tumor necrosis factor-alpha content in rat sciatic nerve after chronic constriction injury.

Wallerian degeneration, induced after injury to a peripheral nerve, is associated with upregulation of proinflammatory cytokines, which are suggested to contribute to the development of lesion-induced neuropathic pain. In chronic constrictive injury (CCI), an animal model of injury-induced painful mononeuropathy, inhibition of synthesis, release, or function of the cytokine tumor necrosis factor-alpha (TNF) results in reduced pain-associated behavior. Here, changes of TNF content in rat sciatic nerves after CCI (days 0, 0.5, 1, 3, 7 and 14) were investigated by enzyme-linked-immunoassay. Low levels of TNF were already detectable in control nerves. Concentrations increased rapidly after CCI, with a maximum (2.7-fold) at 12 h, and remained elevated on a lower level until day 3. Baseline levels were reached again at day 14. These results indicate that TNF is produced at an early time point in the cascade of events resulting in Wallerian degeneration and hyperalgesia following peripheral nerve injury. Given that only prophylactic treatment with TNF inhibitors efficiently reduces hyperalgesia in CCI, TNF seems to contribute to the initiation of neuropathic pain in this model.

Animals↗
PubMed1999

Functional and energetic consequences of chronic myocardial creatine depletion by beta-guanidinopropionate in perfused hearts and in intact rats.

Oral feeding with the creatine analogue beta-guanidinopropionate (beta-GP) reduces myocardial phosphocreatine and creatine concentrations by about 80%in vitro, this is accompanied by reduced contractile performance. We hypothesized, thus, that beta-GP feeding leads to hemodynamic changes in vivo characteristic of heart failure. beta-GP was fed to Wistar rats for up to 8 weeks. In isolated hearts, function was measured isovolumically, myocardial energetics were followed with (31)P-NMR spectroscopy. In vivo hemodynamics were measured with Millar-Tip-catheters and an electromagnetic flow probe. Beta-GP feeding did not alter heart weight. In vitro, diastolic pressure-volume curves indicated structural left ventricular dilatation, and a 36% reduction of left ventricular developed pressure was found; phosphocreatine was reduced by approximately 80%, ATP unchanged and creatine kinase reaction velocity ((31)P-MR saturation transfer) decreased by approximately 90%. The total creatine pool (high-pressure liquid chromatography) was reduced by up to approximately 70%. In contrast to in vitro findings, in vivo cardiac hemodynamics (including left ventricular developed pressure, d P/d t(max), cardiac output and peripheral vascular resistance) at rest and during acute volume loading showed no alterations after beta-GP feeding. The only functional impairment observed in vivo was a 14% reduction of maximum left ventricular developed pressure during brief aortic occlusion. In the intact rat, cardiac and/or humoral compensatory mechanisms are sufficient to maintain normal hemodynamics in spite of a 90% reduction of creatine kinase reaction velocity. However, chronic beta-GP feeding leads to structural left ventricular dilatation.

Adenosine Diphosphate↗
PubMed1999

Quality of life following radical surgical treatment of gastric carcinoma.

Quality of life (QOL) in patients with gastric cancer who underwent total gastrectomy has so far not been studied using the EORTC QLQ-C30 (Quality of Life Core Questionnaire of the European Organization for Research and Treatment of Cancer) as a standardized European QOL instrument. The aim of this study was to evaluate the effect of radical procedures such as extensive lymph node resection and combined resection of adjacent organs on patients' QOL. From 1992 to 1996, 152 patients underwent total gastrectomy. All patients alive on July 1, 1996 were included in the study (77/152). For assessing QOL, the EORTC QOL questionnaire QLQ-C30 version 2.0 and a validated gastric cancer module were sent home to the patients for self-completion. The response rate was 91%. It was possible to evaluate the questionnaires of 62 patients who had undergone resection with curative intent including 13 extended gastrectomies (21%). Of the 62 resections, 50 were combined with D2 lymphadenectomy (80.6%). The global health status was not negatively influenced by D2 lymphadenectomy and extended gastrectomy. Patients with splenectomy were more affected by treatment than patients without splenectomy. Radical gastrectomy combined with D2 lymphadenectomy is the treatment of choice for gastric cancer patients, concerning not just survival but QOL as well.

Aged↗
PubMed1999

Comparison of various imaging methods with particular evaluation of color Doppler sonography for planning surgery for breast tumors.

OBJECTIVE: Color Doppler sonography (CD) was compared with other diagnostic imaging methods [mammography (MG), breast ultrasound (US) and magnetic resonance imaging (MRI)] in the planning of surgery for breast tumors. MATERIALS AND METHODS: 99 patients with breast cancer and 101 with ultimately benign breast lesions were examined preoperatively. The specificity and sensitivity were calculated, as well as the predictive values. Various qualitative and semiquantitative CD parameters were also analysed for their diagnostic value. RESULTS: The sensitivity/specificity of the various methods (in %) was: MG 85/77; US 95/80; CD 82/75; MRI 90/63. The positive predictive value (ppv)/negative predictive value (npv) (in %) was: MG 79/83; US 81/94; CD 72/84; MRI 79/63. The median maximum systolic flow velocity and the resistance index (RI) were significantly higher in breast cancer vessels than in benign lesions. The number of pulsating color pixels detected by CD was significantly higher for breast cancer. In cases of breast cancer significantly more blood flows were detected in the body of the tumor than at its periphery. CONCLUSION: Color Doppler sonography was not superior to other diagnostic methods for preoperative assessment of a breast lesion. The combination of all diagnostic procedures gave a correct classification rate of 93.3% and is much better than the correct classification of any single diagnostic imaging procedure.

Aged↗
PubMed1999

[Diagnostic and therapeutic concepts of canine fossa abscess. Evaluation of a multicenter study of 55 German-speaking departments of oromaxillofacial surgery].

A possible complication of fossa canina infections is reactive thrombosis of the vena angularis, which can lead to cavernous sinus phlebothrombosis. According to the literature there are different opinions about the treatment protocol of fossa canina abscesses. Therefore a multicentre study was undertaken in which 55 departments of oral surgery were interviewed using a standardized questionnaire about their procedures. The basis of diagnosis consists of clinical examination (100%), antibiogram (77.1%) and radiography (97.1%). A total of 28.6% use additional imaging procedures. Sonography is used by 20.0% and is found to be helpful in the diagnosis of vena angularis thrombosis. The painful palpation of the medial angle of the eye is of major diagnostic importance (100%) although anatomic variations of the vena angularis have to be considered. Extraoral incisions are not used in most cases (25.7% in exceptional cases) as well as ligations of the vena angularis in case of thrombosis (8.6% in exceptional cases). There is an agreement in the use of antibiotics (elective administration in 14.3%, obligatory administration in 85.7%); 77.1% don't use heparin to treat thrombosis of the vena angularis. In heparin therapy risks such as bleeding complications and thrombocytopenia have to be considered.

Cavernous Sinus Thrombosis↗
PubMed1999

A comparison of transoesophageal echocardiographic Doppler across the aortic valve and the thermodilution technique for estimating cardiac output.

This study was undertaken in order to elucidate the differences between various planes of measurement and Doppler techniques (pulsed- vs. continuous-wave Doppler) across the aortic valve to estimate cardiac output. In 45 coronary artery bypass patients, cardiac output was measured each time using four different Doppler techniques (transverse and longitudinal plane, pulsed- and continuous-wave Doppler) and compared with the thermodilution technique. Measurements were performed after induction of anaesthesia and shortly after arrival in the intensive care unit. Optimal imaging was obtained in 91% of the patients, in whom a total of 82 measurements of cardiac output were performed. The respective mean (SD) areas of the aortic valve were 3.77 (0.71) cm2 in the transverse plane and 3.86 (0.89) cm2 in the longitudinal plane. A correlation of 0.87 was found between pulsed-wave Doppler cardiac output and the thermodilution technique in either transverse or longitudinal plane. Correlation coefficients of 0.82 and 0.84 were found between thermodilution cardiac output and transverse and longitudinal continuous-wave Doppler cardiac output, respectively. Although thermodilution cardiac output is a widely accepted clinical standard, transoesophageal Doppler echocardiography across the aortic valve offers adequate estimations of cardiac output. In particular, pulsed-wave Doppler cardiac output in both the transverse and longitudinal plane provides useful data.

Aged↗