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R Schmidt

Publications and source records attributed to R Schmidt.

At least 289 records · Page 16Linked to original sources
PubMed1997

[Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)].

The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects aged 50 to 75 years during a 3-year period of enrollment. The response rate of the study was 32.4%. A telephone interview with 200 randomly selected non-responders yielded no differences to responders regarding the frequency of major vascular risk factors known to the subjects. Besides demographics, the study assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a complete lipid status including the apolipoprotein-E genotype, serum fibrinogen and anticardiolipin antibodies as well as various natural antioxidants such as vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus, cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and in 53.2% of study participants. The rate of treatment of major risk factors known to the subjects prior to study entry were 60.3% and 70% for arterial hypertension and diabetes mellitus, but only 37.1% and 6.3% for cardiac disease and hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but was almost neglected in the treatment of other vascular risk factors. These data provide an orientation on the prevalence of risk factors and the use of primary preventive measures for stroke treatment in our community.

Adult↗
PubMed1997

Surgical therapy of malignant thymoma.

OBJECTIVE: To give a modern concept for treating tumours of the thymic gland. EXPERIMENTAL DESIGN: Retrospective analysis of all patients treated for thymic disease in the last 6 years with a mean follow-up of 22.3 months (range: 3-71 months). SETTING: All patients were admitted to the Department of Surgery of the University of Cologne with an average hospitalisation period of 14 days. Patients with myasthenia gravis were transferred to the intensive care unit postoperatively. PATIENTS: A total of 34 patients were treated by radical thymectomy. All patients had a routine chest roentgenogram and a computed tomography. In 13 patients a malignant tumour of the thymic gland was diagnosed. In 6 patients the main symptom was myasthenia gravis. INTERVENTIONS: All tumours were successfully resected by an upper median sternotomy which was extended through a Kocher incision (n = 2) or a complete sternotomy (n = 3). In one patient the tumour was unresectable. RESULTS: In four patients histological examination showed a thymic carcinoma and in 9 patients an invasive thymoma. Four patients died during follow-up period. Stage II to IV thymoma should receive postoperative radiotherapy and an additionally chemotherapy in stage IV. Cumulative survival rate for a five years follow-up independent of the tumour stage was 46%. CONCLUSIONS: Malignant tumours of the thymic gland are a rare entity and should be treated by radical resection of the tumour and the adjacent tissue. In stage II and III postoperative radiation can lower the risk of recurrence. In stage IV radiation should combined with chemotherapy. Long-term follow-up is mandatory.

Actuarial Analysis↗
PubMed1997

Yolk sac tumor of the anterior mediastinum: the role of palliative surgery.

Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is a very rare extragonadal germ-cell neoplasm. Most patients are young and male. Since initial description of the endodermal sinus tumor in 1959, this neoplasm has been found more and more frequently. alpha-Fetoprotein is an important tumor marker. The treatment consists of multimodal therapy. A combined approach with chemotherapy followed by surgical resection of residual tumor seems to be the optimal management of this tumor. Even a palliative surgical resection in advanced tumors is indicated. We describe the case of a patient with an advanced yolk sac tumor that was refractory to chemotherapy. This patient was treated by palliative surgical resection.

Adult↗
PubMed1996

Structure/activity relationships of polyfunctional diterpenes of the tigliane type. A pharmacophore model for protein-kinase-C activators based on structure/activity studies and molecular modeling of the tumor promoters 12-O-tetradecanoylphorbol 13-acetate and 3-O-tetradecanoylingenol.

For protein kinase C (PKC), a family of isoenzymes with serine/threonine-kinase activity identified as the major cellular receptor for certain skin irritants and tumor promoters, a new pharmacophore model is presented. By structure/activity relationship studies of naturally occurring and synthetic diterpene esters of the tigliane type (PKC activators) it is demonstrated that in addition to the oxygen at C20 it is the O-acyl function in position C13 which is critically essential for skin-irritant and tumor-promoting bioactivities rather than other oxygen atoms. This result is confirmed and extended by computer-assisted molecular modeling of tigliane-type and ingenane-type tumor promoters. It is contrasted to certain features attributed to the pharmacophore based upon the recently determined crystallographic structure of the effector-binding domain Cys2 of PKC delta complexed with the pseudo-agonist phorbol 13-acetate.

Animals↗
PubMed1996

A novel repetitive sequence associated with the centromeric regions of Arabidopsis thaliana chromosomes.

The middle repetitive fraction of the Arabidopsis genome has been relatively poorly characterized. We describe here a novel repetitive sequence cloned in the plasmid mi167, and present in approximately 90 copies in the genome of Arabidopsis thaliana ecotype Columbia. Hybridization analysis to physically mapped YAC clones representing Arabidopsis chromosome 4 revealed four mi167-hybridizing loci, all clustered near the centromere. No other loci were detected on YAC clones covering chromosome 4. In situ hybridisation experiments to Arabidopsis chromosome spreads showed that mi167-hybridizing sequences are clustered at the centromeric heterochromatin of all five chromosomes; on two chromosomes the hybridization appeared to be localised on one arm. Additional mi167-hybridizing loci were detected, one of which was adjacent to a non-centromeric, heterochromatic region. This work supports the idea that the majority of middle repetitive DNA in the Arabidopsis genome is clustered. It also adds to our understanding of the organization of the centromere of Arabidopsis chromosome 4.

Arabidopsis↗
PubMed1996

[Polyneuropathy, diarrhea].

A 44-year-old patient with 24 kg reduction of body weight within three years due to recurrent diarrhea was admitted to the hospital. Physical findings of the patient were not remarkable, except for hypesthesia and hypalgesia of the front of the tibia and of the lower legs. Laboratory as well as endoscopic and functional examinations of the gastrointestinal tract did not reveal any remarkable finding. Infectious origins of the disease were excluded. A histological examination of a rectum specimen yielded amyloid deposits in the submucosa of the rectum. In the family history of the patient, relatives with liver and gastrointestinal diseases due to amyloidosis were detected. Amyloid deposits and the positive family history of the patient led to the diagnosis of a gastrointestinal manifestation of familial amyloidosis.

Adult↗
PubMed1996

The listerial exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C synergize to elicit endothelial cell phosphoinositide metabolism.

Exotoxins such as listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PIcA) have been implicated in listerial infection and sepsis. Employing different Listeria strains, mutated in individually known virulence genes, we examined exotoxin-related induction of endothelial cell signaling. Listeria monocytogenes was a potent inductor of phosphatidylinositol (PtdIns) metabolism in HUVEC. This effect was completely absent in a LLO-negative strain. Using a recombinant Listeria innocua strain, engineered to produce high levels of LLO, PtdIns metabolism was restored to approximately 30% of that produced by the parental L. monocytogenes strain. A recombinant L. innocua strain expressing only PIcA did not induce any PtdIns metabolism. Even higher than wild-type levels of PtdIns hydrolysis products were, however, evoked when engineered bacteria secreted both LLO and PIcA. These effects occurred in the absence of bacterial uptake by the endothelial cells. Corresponding results were observed with regard to endothelial diacylglycerol (DAG) generation. The amplification of endothelial cell signaling could be reproduced by engaging purified LLO and PIcA in the absence of bacteria. In these experiments, the unrelated pore-forming agent staphylococcal alpha-toxin, a very weak stimulus for endothelial phosphoinositide metabolism by itself, substituted for LLO to allow marked PtdIns hydrolysis when co-applied with PIcA. We conclude that the listerial exotoxins LLO and PIcA cooperate to provoke potent second messenger synthesis in endothelial cells, in the absence of cell invasion by the bacteria. This is an impressive example of synergism between a pore-forming and an enzymatic bacterial exotoxin in provoking cell signaling and inflammatory events.

Bacterial Proteins↗
PubMed1996

[Is drug dependence an occupational risk for physicians?].

Physicians are probably a high-risk group for the development of dependency. In addition to the particular demands associated with the profession of medicine, another cause is to be sought in the specific aspects of a doctor's personality. Occupational stress and an inability to develop adequate compensatory mechanisms can lead to burnout and addiction. Over and beyond treatment, rational prophylaxis is urgently required, and this should not fail to include a critical consideration of the self-image of the medical profession.

Alcoholism↗
PubMed1996

Identification and distribution of seven classes of middle-repetitive DNA in the Arabidopsis thaliana genome.

In order to analyse further the genomic distribution of repetitive sequences in the Arabidopsis genome, we have identified and characterized seven novel repetitive sequences. Analysis of genomic representation, genomic location and DNA sequence divided the seven repeated sequences into two classes. The first was represented by three cosmid subclones (182A, 74A, 191A) carrying sequences that hybridised to up to 20 genomic fragments and showed sequence homology to the genes, Arabidopsis CCR2, Arabidopsis MYB and to various ATP-binding transport proteins. These multigene families mapped to various positions within the genome, as judged by hybridization to YAC clones constituting the Arabidopsis physical map. The second class was represented by four cosmid subclones (106B, 164A, 163A, 278A) that hybridised to between 20 and 300 genomic fragments. One of these, 106B, is a diverged, partial copy of the LTR of the Arabidopsis retrotransposon Athila. The other three sequences showed no homology to known genes or proteins. The distribution of these sequences on chromosome 4 was analysed and sequences hybridizing to 106B, 164A and 163A were found exclusively at the centromeric region of this chromosome. Their detailed arrangement at the centromeric region of chromosome 4, relative to other repeated sequence families and single copy sequences, was determined.

Arabidopsis↗
PubMed1996

The cytoskeletal linking proteins, moesin and radixin, are upregulated by platelet-derived growth factor, but not basic fibroblast growth factor in experimental mesangial proliferative glomerulonephritis.

The expression of the two cytoskeletal linking proteins, moesin and radixin, was examined in experimental mesangial proliferative nephritis in rats (anti-Thy1 model). Moesin and radixin mRNA and protein are constitutively expressed in all cell types of normal rat glomeruli, except podocytes. In the anti-Thy1 model the expression of moesin and radixin was increased in infiltrating macrophages and in activated, alpha-smooth muscle actin-positive mesangial cells and was concentrated in the cellular extensions of mesangial cells in areas of glomerular remodelling. Studies using neutralizing antibodies demonstrated that the increase in moesin and radixin expression by mesangial cells is mediated by PDGF, but not bFGF. The increase in these cytoskeletal proteins appears to be regulated primarily (radixin) or partially (moesin) posttranscriptionally. The data suggest that PDGF mediated upregulation of the cytoskeletal proteins, moesin and radixin, is important for cell migration and other changes that accompany the coordinated restoration of glomerular architecture after injury.

Actins↗
PubMed1996

Isolation and identification of peptide conformers by reversed-phase high-performance liquid chromatography and NMR at low temperature.

Peptide conformers with one or more rotationally hindered peptide bonds due to the presence of proline and/or another N-substituted amino acid residue in the molecule were separated by reversed-phase chromatography at low temperatures, isolated and identified by NMR. The scope of this investigation included the cis-trans isomers of the dipeptides Leu-Pro, Phe-Pro and Tyr-Pro as well as conformers of opioid peptides containing proline and/or the proline-like Tic (1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid) residues: Tyr-Pro-Phe (beta-casomorphin 1-3 fragment), Tyr-Tic-Phe-Phe, Try-Pro-Phe-Pro-Gly (beta-casomorphin-5), Tyr-Tic-Phe-Phe-Val-Val-Gly-NH2 and Tyr-Tic-Phe-Gly-Tyr-Pro-Ser-NH2. Chromatography with micropellicular and totally porous octadecylated silica stationary phases and aqueous methanol under isocratic elution conditions resulted in well separated peaks of the rotational isomers at sufficiently low temperatures. Preparative RP-HPLC was carried out with eluents containing water and methanol, both deuterated, and the effluent fractions containing each isomer were collected for further investigation. The conformational states of the peptide isomers upon separation were conserved by storing the effluent fractions in liquid nitrogen. The Leu-Pro, Phe-Pro, Tyr-Pro and Tyr-Pro-Phe conformers were identified by one- and two-dimensional NMR spectroscopy at -15 degrees C. Upon comparing the NMR spectra of the isomers, for these peptides the retention order of the conformers was unambiguously established: in each case the trans, conformer is eluted before the cis conformer. On the basis of NMR data obtained the beta-casomorphin-5, which contains two proline residues, the elution order of its four conformers was established by NMR spectroscopy of the fractions obtained by RP-HPLC at low temperature as trans-trans (least retained), trans-cis, cis-cis and cis-trans (most retained).

Amino Acid Sequence↗
PubMed1996

The use of diethylaminoethyl-cellulose-membrane filters in a bioassay to quantify melanin synthesis.

Melanins are a class of extremely insoluble granular biopolymers with a yet ill-defined chemical structure, properties which render the isolation and quantification of these molecules very difficult. Based on their strong anionic character, however, a biophysical property shared by all melanins, we have developed a method allowing total recovery of the pigment. Soluble melanin is bound and granular melanin retained by DEAE-cellulose membrane filters. This approach provides an excellent means to quantify melanin synthesis in normal human melanocytes alone and in coculture with normal human keratinocytes.

DEAE-Cellulose↗
PubMed1996

Proton NMR conformational analysis of cyclic beta-casomorphin analogues of the type Tyr-cyclo[N omega-D-Orn-Xaa-Yaa-Gly-].

A conformational study of the cyclic beta-casomorphin-5 analogues H-Tyr-cyclo[-D-Orn-2-Nal-Pro-Gly-] (1) (mu-selective agonist; 2-Nal = 2 naphthylalanine), H-Tyr-cyclo[-D-Orn-2-Nal-D-Pro-Gly-] (2) (mixed mu agonist/delta antagonist) and H-Tyr-cyclo[-D-Orn-Phe-D-Pro-Gly-] (3) (highly potent mu and delta agonist) has been carried out using 1H NMR spectroscopy. A complete assignment of the proton resonances of the three pentapeptides has been achieved. Compound 1 was shown to exist in two conformations, a major one (90%) characterized by a cis amide bond between 2-Nal3 and Pro4, and a minor one (10%) showing cis amide bonds both between D-Orn2 and 2-Nal3 and between 2-Nal3 and Pro4. Peptides 2 and 3 each showed only one conformer with all-trans peptide bonds in both cases. Temperature dependence studies of the amide proton chemical shifts indicated the existence of several intramolecular hydrogen bonds in the case of compounds 2 and 3 but not in the case of peptide 1. The backbone conformations of 2 and 3 were found to be similar, both being characterized by two consecutive gamma turns around the D-Pro4 and D-Orn2 residues, respectively, and by a D-Orn2-CO<--HN delta-D-Orn2 hydrogen bond. Altogether, the overall backbone conformation and the preferred side chain conformation were found to be roughly similar for the three title peptides. For all three compounds a close proximity between the aromatic moiety of the 3-position residue (2-Nal or Phe) and the D(or L)-Pro4 residue was established on the basis of ROESY experiments. The examination of low energy conformations obtained in molecular modelling studies by taking into account the various experimentally found NMR parameters (NOEs, vicinal H,H coupling constants, torsion angles, H-bonds) led to proposals of the solution conformation for each peptide. These conformations are in close agreement with a pharmacophore model for mu opioid receptor binding compounds.

Amino Acid Sequence↗
PubMed1996

Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors.

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.

Animals↗
PubMed1996

Analysis of the occurrence and nature of repeated DNA in an 850 kb region of Arabidopsis thaliana chromosome 4.

The occurrence and nature of repeated DNA sequences has been analysed within an 850 kb YAC contig on Arabidopsis thaliana chromosome 4. Hybridization analysis with seven RFLP markers, six cosmid contigs, 29 YAC end probes and eight YAC clones showed that a least 585 kb of the 850 kb contained only low-copy sequences. One YAC end probe, EG15C8LE, hybridized to multiple genomic fragments and contained a sequence with predicted protein homology to cytochrome P450 monooxygenases. Another one, EG11B7RE, was found to be non-contiguous with the other YAC clones and contained a dispersed repetitive sequence associated with centromeric regions.

Arabidopsis↗
PubMed1996

Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors.

Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.

Cell Transformation, Neoplastic↗
PubMed1996

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Adult↗