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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 325 records · Page 18Linked to original sources
PubMed1993

Differential effects of DNA-binding proteins on bidirectional transcription from the common promoter region of human collagen type IV genes COL4A1 and COL4A2.

Expression of the heterotrimeric collagen IV (alpha 1(IV))2 alpha 2(IV) is essential for the structural integrity and functional properties of basement membranes. The genes COL4A1 and COL4A2 coding for both subunits are located close to each other on the same chromosome and are transcribed from a common bidirectional promoter element. Binding of at least three different nuclear proteins could be detected within this promoter, a CCAAT-binding protein, Sp1 and a newly identified factor, designated 'CTCBF'. Mutagenesis of binding sites proved that these factors are essential for the efficient transcription of both genes, but revealed differential gene-specific effects. Therefore, the common promoter region of collagen IV does not represent an equally functional bidirectional element, but may be better understood as two overlapping gene-specific promoters with shared elements.

Base Sequence↗
PubMed1993

Identification of a novel sequence element in the common promoter region of human collagen type IV genes, involved in the regulation of divergent transcription.

The expression of the heterotrimeric collagen IV molecule alpha 1(IV)2 alpha 2(IV) is essential for the structural integrity and functional properties of all basement membranes. The two genes COL4A1 and COL4A2 that code for the subunits are found closely linked on chromosome 13 in a head-to-head arrangement and are transcribed in divergent directions. We have identified a novel trans-acting factor that binds in vitro to a unique homopyrimidine/homopurine stretch within the shared promoter region of the two collagen IV genes. Additional binding sites have been identified within the first introns of both genes and the consensus sequence CCCTYCCCC for efficient binding has been deduced; the factor was named therefore 'CTC-binding factor' or 'CTCBF'. Mutations in the binding site of CTC-binding factor within the promoter inhibited binding in vitro and resulted in reduced transcription from both genes. The effect of mutations on the transcription of COL4A2 is more pronounced than on the transcription of COL4A1. CTC-binding factor is a nuclear factor that binds dominantly in vitro to the collagen IV promoter and is involved in regulating the expression of both collagen IV genes.

Base Sequence↗
PubMed1993

Simple and efficient production of embryonic stem cell-embryo chimeras by coculture.

A method for the production of embryonic stem (ES) cell-embryo chimeras was developed that involves the simple coculture of eight-cell embryos on a lawn of ES cells. After coculture, the embryos with ES cells attached are transferred to normal embryo culture medium and allowed to develop to the blastocyst stage before reimplantation into foster mothers. Although the ES cells initially attach to the outside of the embryos, they primarily colonize the inner cell mass and its derivatives. This method results in the efficient production of chimeras with high levels of chimerism including the germ line. As embryos are handled en masse and manipulative steps are minimal, this method should greatly reduce the time and effort required to produce chimeric mice.

Animals↗
PubMed1993

Depressive symptoms as a nonspecific, graded risk for psychiatric diagnoses.

Using data from a 16-year follow-up of a nationally representative sample of 6,913 adults, measures of depressive symptoms were used to predict psychiatric diagnoses taken from hospitalization records. In proportional hazards analyses, two measures of depression were significantly associated with subsequent diagnoses of depression and other psychiatric disorders after statistical control for demographic variables and previous history of psychological problems. Depressive symptoms predicted late as well as early occurrence of psychiatric diagnoses and showed a pattern of increasing risk with increasing scores, even below clinical cutoffs. This pattern of results is consistent with the view that depressive symptoms predict future psychiatric disorders largely because they serve as proxy measures of some chronic vulnerability, such as the normal personality dimension of neuroticism.

Adult↗
PubMed1993

Genomic sequencing by ligation mediated polymerase chain reaction using direct blotting and non-radioactive detection.

Genomic sequencing has become an important tool for analyzing uncloned cellular DNA with regard to the methylation status of cytidines as well as to DNA-protein interactions within cells. The hybridization step of the genomic sequencing procedure requires a very high sensitivity, rendering the method fairly difficult. Using a modified ligation mediated polymerase chain reaction procedure (LMPCR) and a sensitive non-radioactive detection method, we have developed a procedure avoiding the high amounts of radioactivity formerly needed for detection of chemically cleaved genomic DNA. The detection limit of our method of genomic sequencing is less than 1 microgram mammalian DNA, which is much better than the detection limit of the original genomic sequencing method and comparable with the detection limit of radioactive detection after the LMPCR procedure. In addition to the advantages of the non-radioactive detection technique we simplified the blotting step of the genomic sequencing procedure by using the direct blotting electrophoresis method. The method was applied to a region 5' to the human c-myc promoter of HeLa cells and was able to verify the sequence obtained by other authors and to specify the methylation status of five CpG-pairs within this sequence.

Base Sequence↗
PubMed1993

Prediction of an HLA B8-restricted influenza epitope by motif.

Alignment of previously identified HLA B8-restricted cytotoxic T-cell (CTL) epitopes revealed a common motif: x, x, K/R, x, R/K, x, W/Y, x, I/L. Of five motif-conforming peptides tested, ELRSRYWAI was found to represent a new epitope from influenza nucleoprotein (NP). High concentrations of some peptides gave cross-reactive stimulation illustrating the requirement to confirm epitope assignment with recombinant vaccinias and highlighting a potential problem of peptide-based CTL vaccines.

Amino Acid Sequence↗
PubMed1993

Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P.

BACKGROUND: An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. METHODS: Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. RESULTS: Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist NG-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). NG-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.1) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). CONCLUSIONS: Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.

Animals↗
PubMed1993

Segmental trisomy as a mouse model for Down syndrome.

Mice trisomic for Chromosome (Chr) 16 have been used extensively as an animal model for human Down Syndrome (Trisomy 21). This system has drawbacks, however: trisomy for all of Chr 16 is incompatible with postnatal survival and produces trisomy for many more genes than those conserved in human Chr 21. We report here the development and preliminary characterization of mice that are trisomic for only the segment of mouse Chr 16 that is conserved in human Chr 21. While these segmentally trisomic mice, Ts(17(16)) 65Dn, do not appear to have all the features characteristic of Down Syndrome, they represent a mouse model that survives to adulthood and may be useful to study features of Down Syndrome that develop later in life, such as susceptibility to infection, increased incidence of leukemia, and Alzheimer-like neuropathology.

Animals↗
PubMed1993

[Population genetics, immunologic evaluation and Buerger's disease. Projection through a personal study comprising 127 cases of juvenile arteriopathy].

The analysis of anamnestic, clinical and arteriographic parameters in 127 young patients with arterial disease of the lower limbs allowed a definite distinction between thromboangiitis obliterans (TAO) and early-onset atheroma, even if the etiopathogenic of TAO is still obscure. The HLA gene frequency has been determined in 54 patients (14 TAO, 40 early atheroma) and has been compared with local blood donors and with caucased subjects from the IXth Workshop. The results (higher frequency of HLA A28, AX, B53 and BX in the TAO group) have, however, a dubious significance. Furthermore, there were no differences between TAO and early atheroma in a comparative study of immunological parameters (anti-nuclear antibodies, circulating immune complexes, C3, C4 and CH50, cryoglobulin) in 72 patients (22 TAO, 50 early atheroma). So, neither a genetic predisposition nor a dysimmunity could be involved in the pathogenesis of TAO.

Adult↗
PubMed1993

[Therapy of Crohn disease by immunomodulation with 7S immunoglobulins].

Immunoregulatory disturbances play an important role in pathophysiology of Crohn's disease. Because of this fact we tried to improve the situation in therapy-resistant cases by additional intravenous application of 10 g 7S-immunoglobulin (Venimmun) for 10 days. The first patient with active Crohn's disease (CDAI 209) showed a steroid-related psychosis. Therapy had to be changed. During therapy with immunoglobulin Crohn's disease activity index decreased by 97 points. Activity index fell in another patient during therapy from 363 to 150 points. Both patients came into remission by additional therapy with 7S-immunoglobulin. The number of leucocytes decreased and the number of lymphocytes increased. CD4/CD8 ratio in the peripheral blood changed in favour of suppressor cells and soluble interleukin-2 receptors were reduced. Immunoregulatory effects seem to be responsible for successful immunoglobulin therapy in Crohn's disease.

Adult↗
PubMed1993

[Boerhaave syndrome or spontaneous rupture of the esophagus].

Spontaneous rupture of esophagus is a rare affection resulting from barotrauma to lower esophagus during the effort of vomiting. The diagnosis is suggested by the presence of violent retrosternal pain after a bout of vomiting following the partaking of a copious meal by an alcoholic patient. Prognosis is dependent on the rapidity of treatment, always surgical and completed by long-term antibiotic therapy. Complementary examinations should be limited to a standard chest x ray and esophageal imaging with water-soluble contrast. Recovery is now the rule for patients treated within 24 hours. Mortality is high in patients diagnosed at a late stage, but this could be reduced by improved recognition of the syndrome.

Adult↗
PubMed1993

Minimization of hemolysis in centrifugal blood pumps: influence of different geometries.

Centrifugal blood pumps are of substantial importance for intraoperative extracorporeal circulation and for temporary cardiac assist. Their development and improvement raises many specific questions, especially on mechanical blood properties, flow distribution, and the resulting biocompatibility. In this comprehensive study the influence of various pump geometries on blood trauma was investigated. For this purpose analytical calculations, hydrodynamic performance, numerical simulation, in vitro hemolysis tests and in vivo experiments were used. The gap between rotor and housing was found to be crucial showing a distinct minimum of hemolysis at a gap of 1.5 mm (in vitro increase of plasma free hemoglobin per 100 ml plasma an hour: delta fHb/hour = 2.4 +/- 0.83 mg%/h at 1.5 mm versus 12 +/- 2.2 mg%/h at 2.5 mm; p < 0.05). Housing diameter and shape of the vanes were of less importance for blood traumatization (d = 60 mm: delta fHb/hour = 6.36 +/- 1.8 mg%/h; d = 70 mm: fHb = 7.1 +/- 1.9 mg%/h; straight radial vanes: 5.2 +/- 1.8 mg%/h; straight inclined vanes: 6.8 +/- 1.2 mg%/h; flexed vanes: 6.1 +/- 2.0 mg%/h). Three animal experiments confirmed the optimization of geometry, with a mean fHb of 2.5 to 3.2 mg% in steady state. Hydrodynamic efficiency revealed to be a necessary, but not a sufficient and sensitive criterion for hemolysis minimization (e.g. changes of eta < 10% for changes of fHb > 500%). Numerical simulation gives an improved insight in flow distribution, but can not yet be applied for quantification of blood trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Buerger's disease and juvenile arteriopathy. Analysis and classification based on a series of 127 cases].

The prevalence and even the existence of Buerger's disease or thromboangiitis obliterans (TAO) are still ill-defined. The analysis of a continuous series of 127 young patients with obstructive arterial disease of the lower limbs (mean follow-up 67.7 months, lost to follow-up 13.8%) allows the evaluation of the clinical, radiological and evolutive characteristics of the patients. The positive diagnosis of TAO relies upon the four usual criteria: onset of the disease before 40, no other vascular risk factor than smoking, popliteal or infra-popliteal arterial lesions, migrant superficial thrombosis. The patients are classified in 4 groups: Group I: undisputed TAO, presence of all the criteria, 13 cases (10.2%). Group II: probable TAO, presence of three criteria (no history of superficial thrombophlebitis), 19 cases (14.9%). Group III: tobacco-related atheroma, presence of two criteria (age under 40, no other risk factor than smoking), supra-popliteal lesions, 17 cases (13.4%). Group IV: precocious atheroma, presence of one criterium (age under 40), other risk factors, indifferent level of the arterial lesions, 78 cases (61.4%). The statistical analysis relies upon the comparison of the mean values for measurable parameters (Student-Fisher), for frequencies and percentages (Chi 2 Yates-Fisher) and upon a step by step discriminant analysis between groups I and IV, groups I and II and groups III and IV. The level of significance is 5%. The analysis points to two fundamental results: There is no significant difference either between groups I and II or between groups III and IV. Groups I and IV are significantly different for a lot of clinical, radiological and evolutive criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗