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C Thiel

Publications and source records attributed to C Thiel.

At least 19 recordsLinked to original sources
PubMed2001

A novel metastatic animal model reflecting the clinical appearance of human neuroblastoma: growth arrest of orthotopic tumors by natural, cytotoxic human immunoglobulin M antibodies.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood is associated with poor prognosis in patients with advanced tumor stages. Natural human cytotoxic anti-NB IgM antibodies present in the serum of healthy humans are discussed as a potential novel immunotherapeutic regimen against human NB because these antibodies have been shown to affect growth arrest of solid s.c. xenografts of human NB in nude rats. Subcutaneously induced tumors, however, exhibit a different growth pattern compared with the typical growth pattern of NB tumors in humans. Therefore, we developed in this study a novel metastatic tumor model in nude rats that reflects the clinical appearance of human NB and used this model to study the therapeutic efficacy of human anti-NB IgM. Intra-aortal injection of human NB cells in nude rats resulted in the development of large invasive adrenal gland tumors and micrometastases in the liver and bones. Apparently, adrenal glands provide most favorable growth conditions for human NB cells, as documented by the preferential and rapid growth of NB cells in this location. We studied three different treatment protocols of natural human anti-NB IgM. Anti-NB IgM completely inhibited tumor formation and metastases when injected simultaneously with human LAN-1 NB cells (P < 0.05). When antibody treatment was started 6 days after tumor cell injection (i.e., micrometastatic stage), tumor growth was inhibited by 90% (P < 0.05). An anti-NB IgM therapy directed against established tumors (14 days after tumor cell injection) shrank adrenal gland tumors by 90% (P < 0.05). Analysis of the tumors revealed both complement activation and an induction of apoptosis as two independent mechanisms of antitumor function. This study strongly suggests human anti-NB IgM antibodies as new agents for the therapy of neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed2001

[Reasons for the change in HRT therapy from the perspective of women. Results of the German Cohort Study on Women's Health].

Acceptance and reasons for changing the HRT play an important role against the background of the efficiency of the therapy and increasing life expectancy. Women in developed, industrialized countries live about one-third of their lives in the peri- and postmenopausal phases.--The frequency of switching and the reasons were examined in an interim analysis of the German cohort study on women's health. This historical analysis was based on over 10,000 women (i.e. about 300,000 man-years of observation), of whom 2,002 women (aged 40-65) were constant users of HRT.--The prevalence of use and the frequency of switching to other HRT preparations were somewhat higher in women above 60 as compared to those aged 40-59. The duration of use had no impact on the prevalence of use or the frequency of switching or cessation. Neither education nor the past use of oral contraceptives showed a clear association with the frequency of switching. The most frequent reasons for switching or cessation were adverse events, i.e. reasons independent of age. Women aged from 40 to 49 more frequently reported weight gains, menstrual disturbances, headaches, and impaired well-being than did older women. A recurrence of menstruation was more frequently reported by women over 60 as the reason for switching or discontinuing HRT.--The knowledge of the reasons for women switching or discontinuing HRT underlines the importance of close collaboration between women and their gynaecologists, as well as that of intensified research for optimal products.

Adult↗
PubMed2001

[Frequency and reasons for switching/stopping use of oral contraceptives. Results of the German Cohort Study on Women Health].

Frequency and reasons for switching/stopping use of oral contraceptives. Results of the German Cohort Study on Women Health. Use of oral contraceptives is the safest and most commonly used method of contraception. The frequency of use underscores the importance of research on benefits, risks, and acceptability of long-term use. - An interim analysis of the German Cohort Study on Women's Health (aged 15-65 years) was performed to analyse frequency and reason of switching or stop of OC-use. We got for this analysis over 10 000 women with almost 100 000 years of observation from first to last (or current) OC use. - The prevalence of ever use of OCs was 85.5 % in our cohort. Switching or stop of OC use was observed in 93 % of the women. The frequency of switching increased with age and duration of use. Social parameter such as education, employment status, and living in the old or the new Federal States were not materially associated with the frequency of switching or stopping OC use. Satisfaction with general health, psychic stability, and sexual life was slightly associated with the frequency of switching: The better satisfaction the lower frequency of switching, but the sequence of cause and consequence is unclear. The most frequent categories of reasons for switching were observed side effects and personal reasons. Desire to get pregnant was the number one single reason, followed by headache/migraine, and bleeding problems. The frequency of more than 50 single reasons is listed. - The frequency and the knowledge of reason for switching or stopping OC use underlines the need for a good collaboration between physician and treated woman. However, also research on long-term compliance is required and the development of OCs with even less side effects.

Adolescent↗
PubMed2000

Conservation of the 3'-untranslated region of the Rab1a gene in amniote vertebrates: exceptional structure in marsupials and possible role for posttranscriptional regulation.

The YPT1/RAB1 protein, a key regulator of the intracellular vesicle transport in eukaryotes, is highly conserved in function and amino acid sequence. Here we report that the most highly conserved nucleotide sequence of the Rab1a gene of amniote vertebrates corresponds to the 3'-untranslated region (3'-UTR) of the mRNA. Sequences of 27 species ranging from mammals to sauropsida are >91% identical in this region. Secondary structure prediction procedures applied to the 3'-UTR sequences between positions 750 and 984 and 1428 (mouse cDNA: Y00094), respectively, of the RAB1a mRNAs revealed families of alternative structures around nucleotide position 800 as recurrent features. The two hairpin loops are also predicted for marsupials, despite of their exceptional extension of the A-rich sequence in between. Yet, sequence conservation is much higher than required to conserve secondary structure. Implications for posttranscriptional regulation and protein binding are discussed.

3' Untranslated Regions↗
PubMed2000

Poly(3-hydroxyvalerate) depolymerase of Pseudomonas lemoignei.

Pseudomonas lemoignei is equipped with at least five polyhydroxyalkanoate (PHA) depolymerase structural genes (phaZ1 to phaZ5) which enable the bacterium to utilize extracellular poly(3-hydroxybutyrate) (PHB), poly(3-hydroxyvalerate) (PHV), and related polyesters consisting of short-chain-length hxdroxyalkanoates (PHA(SCL)) as the sole sources of carbon and energy. Four genes (phaZ1, phaZ2, phaZ3, and phaZ5) encode PHB depolymerases C, B, D, and A, respectively. It was speculated that the remaining gene, phaZ4, encodes the PHV depolymerase (D. Jendrossek, A. Frisse, A. Behrends, M. Andermann, H. D. Kratzin, T. Stanislawski, and H. G. Schlegel, J. Bacteriol. 177:596-607, 1995). However, in this study, we show that phaZ4 codes for another PHB depolymeraes (i) by disagreement of 5 out of 41 amino acids that had been determined by Edman degradation of the PHV depolymerase and of four endoproteinase GluC-generated internal peptides with the DNA-deduced sequence of phaZ4, (ii) by the lack of immunological reaction of purified recombinant PhaZ4 with PHV depolymerase-specific antibodies, and (iii) by the low activity of the PhaZ4 depolymerase with PHV as a substrate. The true PHV depolymerase-encoding structural gene, phaZ6, was identified by screening a genomic library of P. lemoignei in Escherichia coli for clearing zone formation on PHV agar. The DNA sequence of phaZ6 contained all 41 amino acids of the GluC-generated peptide fragments of the PHV depolymerase. PhaZ6 was expressed and purified from recombinant E. coli and showed immunological identity to the wild-type PHV depolymerase and had high specific activities with PHB and PHV as substrates. To our knowledge, this is the first report on a PHA(SCL) depolymerase gene that is expressed during growth on PHV or odd-numbered carbon sources and that encodes a protein with high PHV depolymerase activity. Amino acid analysis revealed that PhaZ6 (relative molecular mass [M(r)], 43,610 Da) resembles precursors of other extracellular PHA(SCL) depolymerases (28 to 50% identical amino acids). The mature protein (M(r), 41,048) is composed of (i) a large catalytic domain including a catalytic triad of S(136), D(211), and H(269) similar to serine hydrolases; (ii) a linker region highly enriched in threonine residues and other amino acids with hydroxylated or small side chains (Thr-rich region); and (iii) a C-terminal domain similar in sequence to the substrate-binding domain of PHA(SCL) depolymerases. Differences in the codon usage of phaZ6 for some codons from the average codon usage of P. lemoignei indicated that phaZ6 might be derived from other organisms by gene transfer. Multialignment of separate domains of bacterial PHA(SCL) depolymerases suggested that not only complete depolymerase genes but also individual domains might have been exchanged between bacteria during evolution of PHA(SCL) depolymerases.

Acyltransferases↗
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↗
PubMed1999

Less invasive, continuous hemodynamic monitoring during minimally invasive coronary surgery.

BACKGROUND: Minimally invasive coronary surgery has gained more and more clinical acceptance. A clear contrast to the minimally invasive idea is the highly invasive pulmonary artery catheter used for hemodynamic monitoring during the operation. We evaluated a less invasive device which calculates cardiac output (CO) and hemodynamics based on arterial pulse-contour analysis. METHODS: In 20 patients revascularized by the off-pump technique with the octopus system, agreement of CO by pulse-contour was compared to pulmonary arterial and femoral arterial thermodilution and hemodynamic alterations during the operation were recorded. Pulse-contour CO is computed by measuring the area under the arterial pressure waveform and dividing it by aortic impedance. Aortic impedance is determined by an arterial thermodilution at the onset of the system. RESULTS: Correlation of pulmonary arterial and arterial thermodilution CO to pulse-contour CO was 0.91 and 0.90 respectively (both p<0.01). Coefficients of variations were 6.2% and 6.7%. The bias was 0.1 L per minute and standard deviations were 0.42 L per minute and 0.55 L per minute. Hemodynamic changes during the operations were seen mainly during the distal anastomosis of the first diagonal branch; only slight changes occurred during the anastomosis of the left anterior descending coronary artery. CONCLUSIONS: Arterial pulse-contour analysis is easy to use and minimally invasive, thus qualifies as a reliable routine monitoring tool during minimally invasive coronary surgery with tissue stabilizers.

Aged↗
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↗