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C Thiel

Publications and source records attributed to C Thiel.

At least 19 recordsLinked to original sources
PubMed1999

Fine-structure mapping of the hereditary inclusion body myopathy locus.

The gene responsible for a recessive form of hereditary inclusion body myopathy (HIBM) has previously been mapped to a 10-cM interval on chromosome 9p1-q1. We report the results of further mapping studies using two-point linkage analyses and linkage disequilibrium analyses with 20 HIBM families. We demonstrate that the HIBM gene (HGMW-approved symbol IBM2) lies between loci D9S1791 and D9S50, which are about 1 Mb apart. Genetic analyses in 56 affected individuals of Persian, Afghani, and Iraqi Jewish descent demonstrated a common haplotype at these loci, indicating that a founding mutation accounts for disease in these related ethnic groups. beta-Tropomyosin, an abundant skeletal muscle protein that maps within 1 cM of D9S1791, was excluded as the disease gene because an intragenic polymorphism did not exhibit linkage disequilibrium in HIBM probands. We conclude that the disease gene resides in a 1-Mb interval on chromosome 9 and speculate that a novel muscle protein encoded there is mutated in HIBM.

Chromosomes, Human, Pair 9↗
PubMed1999

A novel isoform of the smooth muscle cell differentiation marker smoothelin.

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease.

Actinin↗
PubMed1998

[Trends in cardiovascular risk factor profiles in East Germany. Three independent population studies as part of the project MONICA East Germany].

OBJECTIVE: To demonstrate trends in cardiovascular risk factors in the population of former East Germany. PATIENTS AND METHODS: As part of the international World Health Organisation's MONICA project ("MONItoring of Trends and Determinants of CArdiovascular Disease"), cross-sectional studies of independent random samples were undertaken, during three periods between 1982 and 1994, among the 24-64 year age groups in the population of East Germany. Those examined were 8470 (1982-1984), 9533 (1987-1989) and 2330 (1991-1994) men and women aged 25-64 years living in 17 regions (until 1989) and three regions (since 1991), respectively. Each person had standardized blood pressure measurements, His/her weight and height were measured, a blood sample was taken, and each was given a standardized interview by trained personnel. RESULTS: The prevalence of hypertension, ca. 30% overall, was relatively high. There was, however, a tendency over time towards a reduced prevalence among the women, from 29% to 25% (P < 0.05). The proportion of effectively treated hypertensives was clearly too low: 12-14% among men, 20-25% among women. There was a slightly downward trend in the frequency of hypercholesterolaemia (> 6.7 mmol/l), but it was statistically significant only for women. The proportion of markedly overweight persons (body mass index > or = 30) was not significantly reduced. The frequency of regular smokers decreased among men from 41% to 35% (P < 0.05), while among women (especially those in the younger age groups) there was a slight increase. CONCLUSIONS: Despite the known importance of risk factors, their prevalence was not significantly changed in East Germany over a period about 10 years. More effort and population-related primary prevention of coronary heart disease will thus be required, particularly in view of the risk factors cigarette smoking and hypertension.

Adult↗
PubMed1998

Homology between human chromosome 2p13.3 and the wobbler critical region on mouse chromosome 11: comparative high-resolution mapping of STS and EST loci on YAC/BAC contigs.

Human Chr 2p13-14 and homologous regions on mouse Chrs 6 and 11 have been subjects of previous studies because they comprise the loci for several neuromuscular diseases. Here we report on high-resolution mapping of 55 STS and EST loci on human Chr 2p13.3 and of 47 markers on the corresponding region on proximal mouse Chr. 11. The maps comprise several known genes, MEIS1/Meis1, RAB1a/Rab1a, MDH1/Mor2, OTX1/Otx1, and REL on human 2p13.3 and mouse Chr 11, respectively, as well as the wobbler (wr) critical region of the mouse. Whereas a perfect correspondence was found in most of the 4-Mb region, a small rearrangement was discovered around the OTX1/Otx1 locus. The detailed STS and EST transcript maps of these regions and a further narrowing down of the mouse wr critical region to the interval between D11Mit79 and D11Mit19 allow for the selection of positional candidate genes for wr, and the exclusion of others.

Animals↗
PubMed1998

Continuous, less invasive, hemodynamic monitoring in intensive care after cardiac surgery.

A pulse-contour-based method for continuous measurement of cardiac output (CO) and systemic vascular resistance (SVR) was tested and arterial thermodilution, used for calibration, was compared to pulmonary artery thermodilution. In 30 patients CO and SVR were measured by pulse contour analysis (COpc, SVRpc) 270 times in 24 h and compared to arterial (COart, SVRart) and pulmonary arterial (COpa, SVRpa) thermodilution measurements. The mean difference between COpa and COart was 0.26 L/min (3.6%) with a standard deviation (SD) of 0.7 L/min, the correlation coefficient was 0.96, and the coefficient of variation was 5.0% and 5.9% respectively. COpc did differ from COpa by 0.11 L/min (1.5%, SD = 0.6 L/min) and from COart by 0.15 L/min (2.1%, SD = 0.7 L/min). Correlation of COpc with COpa was 0.91, correlation of COpc with COart was 0.90. SVRpc did correlate with SVRpa, a coefficient of 0.94, and with SVRart, a coefficient of 0.92. Mean COpc and SVRpc did not differ significantly from COpa or COart and SVRpa or SVRart during the 24 h study period. It is concluded that COart correlates well with COpa and can be used to calibrate COpc. COpc and SVRpc agree with thermodilution-based CO and SVR without recalibration for 24 hours.

Adult↗
PubMed1998

Modern oral contraceptive use and benign liver tumors: the German Benign Liver Tumor Case-Control Study.

OBJECTIVE: To analyze the association between oral contraceptive use and the risk of benign liver tumors. METHODS: Two parallel case-control studies on hepatocellular adenoma and focal nodular hyperplasia. Collaborative study of 15 German liver centers. Cases defined by histology and compared with population controls. RESULTS: Fifty-one hepatocellular adenoma and 143 focal nodular hyperplasia cases (women) were recruited between 1990 and 1997, and compared to 240 population controls with a recent abdominal imaging test. The frequency age-matched odds ratio was 1.25 (95% confidence interval (CI), 0.37-4.22) and 1.96 (95% CI, 0.85-4.57) for hepatocellular adenoma and focal nodular hyperplasia, respectively. For hepatocellular adenoma, there was neither a significantly increased risk with longer duration of oral contraceptive use, nor an association with time since first or last use. For focal nodular hyperplasia, however, a slightly increased odds ratio was found with longer duration of use and more recent last use. CONCLUSION: There is little evidence for an increased risk for hepatocellular adenoma in women using modern oral contraceptives. If there is a risk not detected by the limited study size, hepatocellular adenoma is an extremely rare, and focal nodular hyperplasia a rare, adverse effect potentially associated with long-term oral contraceptive use and likely to be without public health importance.

Adenoma, Liver Cell↗
PubMed1997

Pretreatment with neurokinin substance P but not with cholecystokinin-8S can alleviate functional deficits of partial nigrostriatal 6-hydroxydopamine lesion.

The neuropeptide substance P (SP) has been implicated in the control of various neuro-behavioral functions including reinforcement and learning processes. It also exerts neurotrophic and regenerating effects in vitro and in vivo. A previous study indicated a potential therapeutic effect of SP in rats with partial 6-hydroxydopamine lesions of the nigrostriatal dopamine system when SP was administered after the lesion. The purpose of the present study was to determine whether prelesion treatment with SP would also interact with the effects of unilateral 6-hydroxydopamine lesion of the substantia nigra. Thus, SP (50 micrograms/kg) was administered i.p. on 8 consecutive days prior to unilateral lesion of the substantia nigra. Furthermore, we investigated the effects of prelesion treatment with cholecystokinin-8S (CCK; 1 microgram/kg), another neuropeptide, which is closely related to dopaminergic neurons, and which also can have neurotrophic and neuroprotective functions. Our results show that animals with partial neostriatal dopamine depletions (residual dopamine levels of more than 10%) did not show turning asymmetries when pretreated with SP, whereas animals pretreated with vehicle exhibited an initial ipsiversive asymmetry from which they recovered. In contrast, behavioral asymmetries were most pronounced in animals which had been pretreated with CCK. These peptide treatments did not affect the degree of neostriatal dopamine depletion; however, dihydroxyphenylacetic acid/dopamine ratios were enhanced in the neurostriatum of animals with partial dopamine damage after SP- and CCK-pretreatment, and in the ventral striatum of SP-pretreated animals. These data provide evidence that prelesion treatment with SP, but not with CCK, can alleviate functional deficits induced by a partial nigro-striatal dopamine lesion. This effect may be related to enhanced ventral striatal dopamine activity and/or to the peptide's known effects on learning, motivation, and emotion.

Animals↗
PubMed1996

The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein.

Annexin II binds in a calcium-dependent manner to acidic phospholipids and is a substrate of some protein kinases. An N-terminally shortened form of human annexin II was crystallized and its molecular structure determined. It is very similar to two previously described members of this protein family, annexin I and annexin V. The protein structure is nearly completely alpha-helical organized as four compact domains which consist of five alpha-helices each. The domains surround a hydrophilic pore. The calcium binding sites are located at the convex side of the structure as in annexin V. Recombinant and natural porcine annexin II are active as ion channel with characteristics similar to annexin V, while N-terminally shortened annexin II and the heterotetramer (annexin II-p11)2 are inactive. Two cysteine residues, Cys133 and Cys262, form a disulphide bridge connecting domains II and III, adding further weight to the notion that ion channel activity does not require major structural rearrangements.

Amino Acid Sequence↗
PubMed1996

Generation and reactivation of T-cell receptor A joining region pseudogenes in primates.

Tandemly duplicated T-cell receptor (Tcr) AJ (J alpha) segments contribute significantly to TCRA chain junctional region diversity in mammals. Since only limited data exists on TCRA diversity in nonhuman primates, we examined the TCRAJ regions of 37 chimpanzee and 71 rhesus macaque TCRA cDNA clones derived from inverse polymerase chain reaction on peripheral blood mononuclear cell cDNA of healthy animals. Twenty-five different TCRAJ regions were characterized in the chimpanzee and 36 in the rhesus macaque. Each bears a close structural relationship to an equivalent human TCRAJ region. Conserved amino acid motifs are shared between all three species. There are indications that differences between nonhuman primates and humans exist in the generation of TCRAJ pseudogenes. The nucleotide and amino acid sequences of the various characterized TCRAJ of each species are reported and we compare our results to the available information on human genomic sequences. Although we provide evidence of dynamic processes modifying TCRAJ segments during primate evolution, their repertoire and primary structure appears to be relatively conserved.

Amino Acid Sequence↗
PubMed1996

[Quantitative assessment of amounts consumed using the combined methods of a food frequency questionnaire and a 3-day dietary protocol].

With this paper we attempt to present a possible way of making quantitative estimates of the quantities of selected, preventively important food stuff groups consumed using a food frequency questionnaire together with a 3-day dietary protocol. The 3-day dietary protocol used in the 1984/85 MONICA survey of the former GDR is used as the standard. For large nutritional/epidemiological studies (e.g., cancer or cardiovascular cohort studies) this combination of methods is suggested as a means of arriving at quantitative estimates for nutritional habits in relation to the product groups presented here. Further investigations regarding correction factors are necessary where the food frequency is either very low or very high to detect potential inaccuracy.

Adult↗
PubMed1996

[What is the reliability of conventional ultrasound mammography and color coded ultrasound in diagnosis of breast tumors?].

To establish the diagnostic relevance of sonographic blood supply measurement for tumor's nature evaluation, 192 women with suspect unilateral breast findings were examined on the preoperative day with color coded sonography (MEM color technique). A combination of evaluation in B-scan and color mode resulted in a sensitivity of approx. 96% in cases of malignant tumors (121 histological findings of breast cancer). Specificity in the 71 patients with a histologically benign diagnosis was of over 90%. Despite an essential improvement in dignity diagnosis, histologic proof is, however, necessary, even in cases of benign findings at the diagnosis. Since a 100% certainty in the differentiation of benign and malignant tumors will never be achieved with ultrasound techniques, biopsy specimen will have to be taken. Thus additional measurements of tumor blood flow seems of no clear advantage for the patient. In our opinion, the essential contribution of blood flow diagnosis of malignant tumors lies rather in the evaluation of tumor prognosis, since the differences in the blood supply of malignant growths are indicators for their biological behavior.

Adult↗
PubMed1995

Structure and diversity of the T-cell receptor alpha chain in rhesus macaque and chimpanzee.

We cloned and sequenced cDNA for the TCRAC1 of a healthy rhesus monkey and chimpanzee. TCRAC1 from both nonhuman primates show extensive conservation compared to the human sequence and to other mammals. A possible primate-specific insertion near the hinge region of the TCRAC1 region is described. Characterization of 18 rhesus macaque and eight chimpanzee TCRA chain cDNA clones derived from inverse PCR revealed 12 different TCRAV and 16 different TCRAJ regions which corresponded closely to known human counterparts. One functional rhesus macaque TCRDV-TCRAJ rearrangement was detected, suggesting a genomic organization of the macaque TCRD locus which is similar to humans. At the genomic level, a single TCRAC1 gene segment was detected in rhesus macaque and chimpanzee. The close phylogenetic relationship between primates shown here for TCRA chain components supports the use of these species as animal models of human immune-mediated disease.

Amino Acid Sequence↗
PubMed1993

Formation of the annexin II2p112 complex upon differentiation of F9 teratocarcinoma cells.

Murine teratocarcinoma F9 cells, which remain undifferentiated under standard cell culture conditions, can form cellular layers resembling early embryonic tissues upon induction of differentiation by retinoic acid and cyclic AMP. We have employed a combination of Northern and Western blot analyses to elucidate the regulation of expression of the tyrosine kinase substrate annexin II and its cellular ligand p11 during this differentiation process. Interestingly, the synthesis of the two subunits of the annexin II2p112 complex is not coregulated during F9 differentiation. Annexin II, which is only very weakly expressed in undifferentiated F9 cells, shows a strong increase in the amount of transcript and protein once the differentiated phenotype is established. The level of this induction does not depend on the type of F9 differentiation. In contrast to the regulated synthesis of annexin II, a significant amount of p11 mRNA and protein is already present in the undifferentiated cells and remains constant during the differentiation of F9 cells. Immunofluorescence analysis reveals that annexin II and p11 are concentrated in the submembranous region of the differentiated F9 cells. In contrast, p11 is uniformly distributed throughout the cytoplasm of undifferentiated cells. p11 is translocated to the submembranous region of the undifferentiated F9 cells upon coexpression of an exogenous annexin II introduced by transient transfection. Thus the localization of annexin II and p11 to the submembranous cytoskeleton depends on the formation of the tight annexin II2p112 complex.

Animals↗
PubMed1992

Mapping of three unique Ca(2+)-binding sites in human annexin II.

Site-directed mutagenesis was employed to map and characterize Ca(2+)-binding sites in annexin II, a member of the annexin family of Ca(2+)- and phospholipid-binding proteins which serves as a major cellular substrate for the tyrosine kinase encoded by the src oncogene. Several single amino acid substitutions were introduced in the human annexin II and the various mutant proteins were scored for their affinity towards Ca2+ in different assays. The data support our previous finding [Thiel, C., Weber, K. and Gerke V. (1991) J. Biol. Chem. 266, 14,732-14,739] that a Ca(2+)-binding site is present in the third of the four repeat segments which comprise the 33-kDa protein core of annexin II. In addition to Gly206 and Thr207, which are localized in the highly conserved endonexin fold of the third repeat, Glu246 is involved in the formation of this site. Thus the architecture of this Ca(2+)-binding site in solution is very similar, if not identical, to that of Ca2+ sites identified recently in annexin V crystals [Huber, R., Schneider, M., Mayr, I., Römisch, J. and Paques, E.-P. (1990) FEBS Lett. 275, 15-21]. In addition to the site in repeat 3, we have mapped sites of presumably similar architecture in repeats 2 and 4 of annexin II. Again, an acidic amino acid which is located 40 residues C-terminal to the conserved glycine at position 4 of the endonexin fold is indispensable for high-affinity Ca2+ binding: Asp161 in the second and Asp321 in the fourth repeat. In contrast, repeat 1 does not contain an acidic amino acid at a corresponding position and also shows deviations from the other repeats in the sequence surrounding the conserved glycine. These results on annexin II together with the crystallographic information on annexin V reveal that annexins can differ in the position of the Ca2+ sites. Ca(2+)-binding sites of similar structure are present in repeats 2, 3, and 4 of annexin II while in annexin V they occur in repeats 1, 2, and 4. We also synthesized an annexin II derivative with mutations in all three Ca2+ sites. This molecule shows a greatly reduced affinity for the divalent cation. However, it is still able to bind Ca2+, indicating the presence of (an) additional Ca2+ site(s) of presumably different architecture.

Amino Acid Sequence↗
PubMed1992

The tight association of the tyrosine kinase substrate annexin II with the submembranous cytoskeleton depends on intact p11- and Ca(2+)-binding sites.

Annexin II, a member of the annexin family of Ca(2+)- and lipid-binding proteins, is a major substrate of the pp60src kinase. It is unique within the annexin protein family, since it can form a tight heterotetrameric complex with the cellular protein ligand p11, a member of the S100 protein family. Within the cell, the annexin II2p11(2) complex is localized at the cytoplasmic surface of the plasma membrane in the submembranous cytoskeleton. This intracellular localization is thought to be the consequence of a typical annexin II property observed in vitro, its Ca(2+)-dependent binding to phospholipids and cytoskeletal elements (F-actin, non-erythroid spectrin). We employed site-directed mutagenesis to create mutant annexin II molecules with defects either in the p11-binding site or in the Ca(2+)-binding sites present in repeats 2, 3 and 4. The mutated annexin II derivatives were expressed in HeLa and RMCD cells by transfection of the appropriate DNA constructs in order to analyze the importance of p11- and Ca(2+)-binding for the intracellular localization of annexin II. Immunofluorescence microscopy with a monoclonal antibody that specifically detected the transfected annexin II derivatives indicated that the Ca(2+)-dependent incorporation of annexin II into the submembranous network depended on its ability to form the annexin II/p11 complex and on the presence of intact Ca(2+)-binding sites. Neither monomeric annexin II lacking an intact p11-binding site, nor the annexin II mutant with defects in the Ca(2+)-binding sites in repeats 2, 3 and 4 were associated with the Triton X-100-resistant network of the submembranous cytoskeleton.

Amino Acid Sequence↗
PubMed1991

Primary structure and expression of the Xenopus laevis gene encoding annexin II.

Annexin II (AnxII) is one of the Ca(2+)-dependent membrane- and phospholipid-binding proteins (annexins) which are encoded by a multigene family. AnxII was originally described as a major cellular substrate for the tyrosine kinase encoded by the src oncogene, and is also phosphorylated by protein kinase C in vivo and in vitro. To obtain more information about structurally conserved regions in AnxII, which could be of structural and/or functional importance, we have identified AnxII in a nonmammalian species, the clawed toad Xenopus laevis. In a ligand overlay assay, we employed p11, the cellular protein ligand of AnxII, to show that a 36-kDa Anx capable of binding p11 is present in a cellular extract from X. laevis cells. The cDNA cloning and sequence analysis revealed that two types of AnxII mRNA are expressed in X. laevis. The transcripts are highly similar to each other, but are encoded by two different genes. The deduced amino acid sequences show a high degree of conservation when compared to the sequences of mammalian and chicken AnxII. In particular, the p11-binding domain, as well as the protein core, which harbors the binding sites for Ca2+ and phospholipid, are highly similar. However, Tyr23, which is phosphorylated by pp60src in mammalian and chicken AnxII, is replaced by a Leu residue in both X. laevis molecules. Thus, tyrosine phosphorylation is probably not a general mode of regulation of AnxII function(s).

Amino Acid Sequence↗
PubMed1991

Characterization of a Ca(2+)-binding site in human annexin II by site-directed mutagenesis.

Annexin II, a major cytoplasmic substrate of the src tyrosine kinase, is a member of the annexin family of Ca2+/phospholipid-binding proteins. It is composed of a short N-terminal tail (30 residues) followed by four so-called annexin repeats (each 70-80 residues in length) which share sequence homologies and are thought to form (a) new type(s) of Ca(2+)-binding site(s). We have produced wild-type and site specifically mutated annexin II molecules to compare their structure and biochemistry. The recombinant wild-type annexin II displays biochemical and spectroscopical properties resembling those of the authentic protein purified from mammalian cells. In particular, it shows the Ca(2+)-induced blue shift in fluorescence emission which is typical for this annexin. Replacement of the single tryptophan in annexin II (Trp-212) by a phenylalanine abolishes the fluorescence signal and allows the unambiguous assignment of the Ca(2+)-sensitive spectroscopic properties to Trp-212. This residue is located in the third annexin repeat in a highly conserved stretch of 17 amino acids which are also found in the other repeats and known as the endonexin fold. To study the precise architecture of the Ca2+ site which must reside in close proximity to Trp-212, we changed several residues of the endonexin fold in repeat 3 by site-directed mutagenesis. An analysis of these mutants by fluorescence spectroscopy and Ca(2+)-dependent phospholipid binding reveals that Gly-206 and Thr-207 seem indispensible for a correct folding of this Ca(2+)-binding site.

Amino Acid Sequence↗