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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 37 records · Page 2Linked to original sources

Regulation of Epha4 expression in paraxial and lateral plate mesoderm by ectoderm-derived signals.

Somitogenesis in all vertebrates involves a mesenchymal to epithelial transition of segmental plate cells. Such a transition involves cells altering their morphology and their adhesive properties. The Eph family of receptor tyrosine kinases has been postulated to regulate cytoskeletal organization. In this study, we show that a receptor belonging to this family, EphA4, is expressed in the segmental plate in a region where cells are undergoing changes in cell shape as a prelude to epithelialization. We have identified the ectoderm covering the somites and the midline ectoderm as sources of signals capable of inducing EphA4. Loss of EphA4 results in cells of irregular morphology and somites fail to form. We also show that when somites fail to develop, expression of EphA4 in the lateral plate is also lost. We suggest that signaling occurs between the somites and the lateral plate mesoderm and provide evidence that retinoic acid is involved in this communication.

Animals↗

Transcriptional complementarity in breast cancer: application to detection of circulating tumor cells.

BACKGROUND: We used a combination of genetic subtraction, silicon DNA microarray analysis, and quantitative PCR to identify tissue- and tumor-specific genes as diagnostic targets for breast cancer. METHODS AND RESULTS: From a large number of candidate antigens, several specific subsets of genes were identified that showed concordant and complementary expression profiles. Whereas transcriptional profiling of mammaglobin resulted in the detection of 70% of tumors in a panel of 46 primary and metastatic breast cancers, the inclusion of three additional markers resulted in detection of all 46 specimens. Immunomagnetic epithelial cell enrichment of circulating tumor cells from the peripheral blood of patients with metastatic breast cancer, coupled with RT-PCR-based amplification of breast tumor-specific transcripts, resulted in the detection of anchorage-independent tumor cells in the majority of patients with breast cancer with known metastatic disease. CONCLUSION: Complementation of mammaglobin with three additional genes in RT-PCR increases the detection of breast cancers in tissue and circulating tumor cells.

Breast Neoplasms↗

Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras.

Mutation of the K-ras gene is thought to be an early and important event in pancreatic carcinogenesis. In order to study the role of this molecular alteration in the transition from the normal to the neoplastic pancreatic cell, bovine pancreatic duct cells were first immortalized by SV40 large T antigen (Ag) complementary (c)DNA transfection and then transfected with a mutated K-ras gene. As did primary duct cells, the immortalized duct cells (more than 100 passages) expressed cytokeratins, carbonic anhydrase type-II, cystic fibrosis transmembrane conductance regulator (CFTR), and multidrug resistance (mdr). They grew as a single layer after transplantation under plastic domes and formed three-dimensional structures resembling ducts when grown on Matrigel. Cell growth was stimulated by insulin, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, but cells did not respond to gastrin and CCK-8. They did not form colonies in soft agar nor did they form tumors in nude mice. Immortalized cells transfected with mutated K-ras acquired the ability to form tumors after orthotopic injection into the nude mouse pancreas. It is concluded that SV 40 immortalized bovine pancreatic

Animals↗

Pyodera gangrenosum after aortic valve replacement.

A 68-year-old male patient developed pyoderma gangrenosum after elective aortic valve replacement. Treatment with steroids and clofazimine was initiated, which resulted in rapid cessation of the necrotic process. Due to thoracic instability, stabilization of the sternum was performed followed by surgical debridement and atraumatic wound closure. Postoperatively, immunosuppression with cyclosporine A was added; the patient recovered completely. Pyoderma gangrenosum is a potential life-threatening complication that must be considered in patients with severely impaired wound healing after cardiac operation.

Aged↗

Diagnosis and treatment of nonocclusive mesenteric ischemia after open heart surgery.

BACKGROUND: Acute nonocclusive mesenteric ischemia (NOMI) is a rare but often fatal event after cardiac surgery. METHODS: Twenty patients with ongoing ileus after cardiac surgery despite maximal laxative treatment underwent selective mesenteric angiography. In cases of pathological radiographic findings, papaverine was continuously administered via an intraarterial perfusion catheter. RESULTS: Severe NOMI was confirmed in seven patients (mean lactate: 6.9 +/- 8.3 mg/dL), mild to moderate findings in another seven (mean lactate: 1.4 +/- 1.1 mg/dL). One patient had thromboembolic occlusion of the superior mesenteric artery; five patients demonstrated normal imaging findings. In nine of fourteen patients (64%) treated with papaverine, symptoms improved within hours (defecation occurred after 4-29 hours, mean 13 +/- 8.1 hours). No side effects or complications occurred in connection with the papaverine treatment. The clinical condition of five patients deteriorated. Four patients underwent laparotomy with creation of an ileostomy or colostomy, two of whom presented with severe intestinal ischemia and later died. One patient died prior to laparotomy. CONCLUSIONS: Selective mesenteric angiography with continuous papaverine administration is a simple, fast, and effective diagnostic and therapeutic tool to reduce the need for laparotomy for symptoms of ileus after open-heart surgery.

Aged↗

[Influence of age and physical activity on isokinetic characteristics of hamstring and quadriceps muscles of young gymnasts and soccer players].

OBJECTIVE: The aim of this work is the assessment of age and sport influences on the isokinetic knee muscle characteristics. SUBJECTS AND METHOD: Subjects performed a bilateral knee flexion/extension test on an isokinetic device at 60 and 180 degrees.s(-1) speed in concentric mode. The three parameters studied in this work were the Peak Torque, Average Power and hamstring/quadriceps ratio. Thirty-eight soccer players (16,6 +/- 1.4 years old) and 22 gymnasts (18 +/- 2.8 years old) were tested. The population was separated into three groups : 15 years old, 17 years old, 20 years old. RESULTS: The isokinetic values of soccer players were significantly higher (p < 0.0001) than those of the the gymnasts. The isokinetic values of the oldest soccer players were significantly higher (0.005 < p < 0.05) for hamstrings than those of the younger soccer players. The isokinetic values of the oldest gymnasts were significantly higher (0.005 < p < 0.05) for the quadriceps than those of the younger gymnasts. There were no significant differences between dominant and non dominant limbs in soccer players. CONCLUSION: In the present study, the muscular maturation improves the absolute strength of the older sportsmen in comparison to the younger. Soccer favor most the absolute strength of the inferior member in comparison to the gymnastics.

Adult↗

Mammalian exocrine secretions XV. Constituents of secretion of ventral gland of male dwarf hamster, Phodopus sungorus sungorus.

In a study aimed at the chemical characterization of constituents of the ventral gland secretion of the male dwarf hamster, Phodopus sungorus sungorus, 48 compounds, including saturated alcohols, saturated and unsaturated ketones, saturated and unsaturated straight-chain carboxylic acids, iso- and anteisocarboxylic acids, 3-phenylpropanoic acid, hydroxyesters, 2-piperidone, and some steroids were identified in the secretion. The position of the double bonds in gamma-icosadienyl-gamma-butyrolactone and gamma-henicosadienyl-gamma-butyrolactone, and the position of methylbranching in seven C16-C21 saturated ketones could not be established. Several constituents with typically steroidal mass spectra also remained unidentified. The female dwarf hamster's ventral gland either does not produce secretion or produced so little secretion that it was impossible to collect enough material for analysis.

Alcohols↗

Mammalian exocrine secretions XVI. Constitutents of secretion of supplementary sacculi of dwarf hamster, Phodopus sungorus sungorus.

As a first step in a study of the role of the secretion of the supplementary sacculi (buccal secretion) of the dwarf hamster, Phodopus sungorus sungorus, almost complete chemical characterization of the secretion was achieved. The 35 compounds identified include carbon dioxide, hydrogen sulfide, a large number of carboxylic acids (representing the bulk of the organic volatile fraction of the secretion), phenol, 2-piperidone, indole, two long-chain hydroxyesters, cholestrol, desmosterol, and lanosterol. The position of the double bonds in gamma-icosadienyl-gamma-butyrolactone and gamma-henicosadienyl-gamma-butyrolactone could not be determined, and these two compounds remained only partially characterized. Large variations were found in the relative concentrations in which the short-chain carboxylic acids are present in the secretions of individual animals, and although this aspect was not investigated in sufficient detail in the present investigation, the difference in the carboxylic acid profiles of the secretions of individual animals could play a role in individual recognition in this animal.

Animal Communication↗

Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up.

OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.

Aged↗

Functional expression of M(1), M(3) and M(5) muscarinic acetylcholine receptors in yeast.

The goal of this study was to functionally express the three G(q)-coupled muscarinic receptor subtypes, M(1), M(3) and M(5), in yeast (Saccharomyces cerevisiae). Transformation of yeast with expression constructs coding for the full-length receptors resulted in very low numbers of detectable muscarinic binding sites (B(max) < 5 fmol/mg). Strikingly, deletion of the central portion of the third intracellular loops of the M(1), M(3) and M(5) muscarinic receptors resulted in dramatic increases in B(max) values (53-214 fmol/mg). To monitor productive receptor/G-protein coupling, we used specifically engineered yeast strains that required agonist-stimulated receptor/G-protein coupling for cell growth. These studies showed that the shortened versions of the M(1), M(3) and M(5) receptors were unable to productively interact with the endogenous yeast G protein alpha-subunit, Gpa1p, or a Gpa1 mutant subunit that contained C-terminal mammalian Galpha(s) sequence. In contrast, all three receptors gained the ability to efficiently couple to a Gpa1/Galpha(q) hybrid subunit containing C-terminal mammalian Galpha(q) sequence, indicating that the M(1), M(3) and M(5) muscarinic receptors retained proper G-protein coupling selectivity in yeast. This is the first study to report the expression of muscarinic receptors in a coupling-competent form in yeast. The strategy described here, which involves structural modification of both receptors and co-expressed G proteins, should facilitate the functional expression of other classes of G protein-coupled receptors in yeast.

Amino Acid Sequence↗

[Measurement of the outcome quality as beginning of total quality management in otorhinolaryngology].

BACKGROUND: The last years are characterized by a change of paradigms in the evaluation of medical therapeutical strategies. The term quality of life (QoL) has been established in oncology and could be demonstrated as a subject of highly qualified investigations which were published during the last years. An extendend quality management is correlated with the possibility of cost-effectiveness measurement and arrangement in a time characterized by decreasing financial resources of the hospitals and university departments. The experiences in the field of quality analysis could offer precious tools to optimize structures, processes and results of treatments. This aim is strongly supported by the expected law "Gesundheitsreform 2000". METHOD AND RESULTS: Therefore reliable, valid tools are needed to calculate the effects of therapies. The combination of global and specific questionnaires include the possibility to compare oncologic data of different entities of malignomas. A couple of questionnaires in otorhinolaryngology were developed in the last decade involving the fields of malignomas of the upper aerodigestive tract, rhinosinusitis etc. CONCLUSIONS: Ishikawa, the founder of "Total Quality Management" and of the "Quality Circ", pointed out the high importance of customer satisfaction. Whereas the patient is in the mid point of medical treatment there are hardly any investigations about customer satisfaction published. Therefore it is necessary to develop and establish validated tools for the measurement of quality dimensions. The short, middle and long-lasting effects of a treatment could be calculated by quality of life measurements. The QoL is here of very strong importance, especially since economic aspects are included.

Germany↗

[The enjoyment of red wine is influenced by the shape of the wine glass].

BACKGROUND: It is frequently claimed that the glass shape has a direct impact on wine aroma. METHODS, PATIENTS: Healthy volunteers (43 m, 46 f, age 19-60 years) tried 3 glasses. Three glasses of different shape but of the same height and of comparable opening diameter were used. Glasses were of "tulip"-like, "beaker"-like, and "egg"-like shapes. Intensity, hedonic tone, and quality of a red wine were rated before and after drinking. RESULTS: Both intensity and hedonic ratings of wines from different glasses were influenced by glass shape. Glass shape also influenced the complexity of wine odors. This appeared not to be related to the esthetic impression the glasses made. CONCLUSIONS: The present data indicate that egg-shaped glasses, compared to "tulip" or "beaker" glasses, appear to produce higher intensity and higher complexity of wine odors. This may relate to the trapping of odors in egg-shaped glasses.

Adult↗

Primary pigmented malignant schwannoma in the posterior mediastinum.

This paper describes a rare case of primary pigmented malignant schwannoma arising from the sympathetic trunk in the posterior mediastinum. A 30-year-old woman underwent a thoracoscopic tumor extirpation. A primary pigmented malignant schwannoma was diagnosed histologically. The tumor presented fascicles and whorls of pigmented plump spindle cells and positive immunoreactivity to S-100 protein, vimentin, and HMB-45. Postoperative radiotherapy of the mediastinum was performed. Our case demonstrates the successful thoracoscopic resection and postoperative radiation treatment of a malignant schwannoma.

Adult↗

Noncardiac surgery in patients with left ventricular assist devices.

BACKGROUND: Noncardiac surgery, especially abdominal surgical procedures in patients with long-term mechanical circulatory support and strong anticoagulation, is difficult. METHODS: We report on 14 patients (aged 44 +/- 15 years) with a portable Novacor or HeartMate system, who underwent noncardiac surgical procedures while being supported by the device. RESULTS: The patients underwent 20 procedures for noncardiac reasons; most had an intestinal operation or cholecystectomy. Half of the procedures were performed within 30 days after placement of the device (mean interval, 53 +/- 57 days), only 6 interventions were necessary after 100 days of mechanical support. Complications occurred in 8 patients (57%), 5 of whom had undergone cholecystectomy and had unacceptably high sanguineous drainage losses. CONCLUSIONS: An elective surgical procedure can be performed with an acceptable risk if the operation is carefully managed. Postponing resumption of full anticoagulation is advisable as it may reduce bleeding complications without apparently increasing the risk for thromboembolism. Emergency interventions remain a difficult task.

Adult↗

Biochemical engineering of the N-acyl side chain of sialic acid: biological implications.

N-Acetylneuraminic acid is the most prominent sialic acid in eukaryotes. The structural diversity of sialic acid is exploited by viruses, bacteria, and toxins and by the sialoglycoproteins and sialoglycolipids involved in cell-cell recognition in their highly specific recognition and binding to cellular receptors. The physiological precursor of all sialic acids is N-acetyl D-mannosamine (ManNAc). By recent findings it could be shown that synthetic N-acyl-modified D-mannosamines can be taken up by cells and efficiently metabolized to the respective N-acyl-modified neuraminic acids in vitro and in vivo. Successfully employed D-mannosamines with modified N-acyl side chains include N-propanoyl- (ManNProp), N-butanoyl- (ManNBut)-, N-pentanoyl- (ManNPent), N-hexanoyl- (ManNHex), N-crotonoyl- (ManNCrot), N-levulinoyl- (ManNLev), N-glycolyl- (ManNGc), and N-azidoacetyl D-mannosamine (ManNAc-azido). All of these compounds are metabolized by the promiscuous sialic acid biosynthetic pathway and are incorporated into cell surface sialoglycoconjugates replacing in a cell type-specific manner 10-85% of normal sialic acids. Application of these compounds to different biological systems has revealed important and unexpected functions of the N-acyl side chain of sialic acids, including its crucial role for the interaction of different viruses with their sialylated host cell receptors. Also, treatment with ManNProp, which contains only one additional methylene group compared to the physiological precursor ManNAc, induced proliferation of astrocytes, microglia, and peripheral T-lymphocytes. Unique, chemically reactive ketone and azido groups can be introduced biosynthetically into cell surface sialoglycans using N-acyl-modified sialic acid precursors, a process offering a variety of applications including the generation of artificial cellular receptors for viral gene delivery. This group of novel sialic acid precursors enabled studies on sialic acid modifications on the surface of living cells and has improved our understanding of carbohydrate receptors in their native environment. The biochemical engineering of the side chain of sialic acid offers new tools to study its biological relevance and to exploit it as a tag for therapeutic and diagnostic applications.

Azides↗