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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 19 recordsLinked to original sources
PubMed1992

Expression of human collagen type IV genes is regulated by transcriptional and post-transcriptional mechanisms.

The molecules of the basement membrane specific collagen type IV are heterotrimers consisting of two alpha 1(IV) and one alpha 2(IV) polypeptide chains. Comparison of the ratios of transcription by nuclear run-on analysis and mRNAs by RNAse protection assay indicates the involvement of transcriptional as well as post-transcriptional events in the control of overall collagen type IV expression. The relative ratios of transcription of the respective genes COL4A1 and COL4A2 remained near 2:1 in most cells, whereas the ratio of mRNA steady-state levels alpha 1(IV)/alpha 2(IV) varied from 0.3:1 to 1:1 and did not parallel the subunit structure of the protein. Nevertheless, secreted protein shows a 2:1 ratio of the subunit polypeptides. This indicates that post-translational processes during chain selection, aggregation and secretion finally determine the amount of secreted protein.

Cells, Cultured↗
PubMed1992

Chicken vigilin gene organization and expression pattern. The domain structure of the protein is reflected by the exon structure.

Chicken vigilin was identified as a member of an evolutionary-conserved protein family with a unique repetitive domain structure. 14 tandemly repeated domains are found in chicken vigilin, all of which consist of a conserved sequence motif (subdomain A) and a potential alpha-helical region (subdomain B) [1]. We have established the physical structure of the chicken vigilin gene by restriction-fragment analysis and DNA sequencing of overlapping clones isolated from a phage lambda genomic DNA library. The chicken vigilin gene is a single-copy gene with a total of 27 exons which are distributed over a region of some 22 kbp. Exon 1 codes for a portion of the 5' untranslated region, exon 2 contains the translation start point and forms, along with exons 3 and 4, the N-terminal non-domain region. Exons 5-25 encode the vigilin domains 1-14 and the remaining exons 26 and 27 contain the non-domain C-terminal as well as the untranslated regions. The domain structure of the protein is reflected in the positioning of introns which demarcate individual domains. While domains 1-3 and 8-10 are each encoded by a single exon (5-7, 16-18); all other domains are contained in a set of two exons which are separated by introns interspersed at variable positions of the DNA segment coding for the conserved sequence motif. In conclusion, the data presented suggest that the chicken vigilin gene evolved by amplification of a primordial exon unit coding for the fundamental bipartite vigilin domain.

Animals↗
PubMed1992

Complete cDNA sequence of chicken vigilin, a novel protein with amplified and evolutionary conserved domains.

The complete cDNA (4375 bp), coding for a new protein called vigilin, was isolated from chicken chondrocytes. The cDNA shows an open reading frame of 1270 amino acids which are organized in 14 tandemly repeated homologous domains. Each domain consists of two subdomains, one with a conserved sequence motif of 35 amino acids (subdomain A) and another one with a presumptive alpha-helical structure of 21-33 amino acids (subdomain B). 149 amino acids at the N-terminus and 71 amino acids at the C-terminus of vigilin do not show the characteristic domain structure. No sequence characteristic of a signal peptide has been found, which argues for an intracellular localisation of vigilin. Vigilin is highly expressed in freshly isolated chicken chondrocytes but little in chondrocytes after prolonged time in culture. Vigilin mRNA exists in two size species, 4.4 kb and 6.5 kb in length due to the usage of different polyadenylation sites. Comparison of the vigilin sequence with data bases showed a remarkable similarity to protein HX from Saccharomyces cerevisiae [Delahodde, A., Becam, A. M., Perea, J. & Jacq, C. (1986) Nucleic Acids Res. 14, 9213-9214]. The yeast protein consists of eight homologous domains with 11 conserved amino acid residues within a set of 35 amino acids. The N-terminal and C-terminal regions of vigilin and protein HX do not reveal any sequence similarity. These results, together with the demonstration of the characteristic vigilin sequence motif in a human cDNA clone, suggest that the repeats represent evolutionary conserved autonomous domains within a family of proteins found in yeast, chicken and man.

Amino Acid Sequence↗
PubMed1992

[A minor epidemic due to Legionella pneumophila serogroup 1].

Ten days after starting military service in a police barracks a 25-year-old man developed left middle and lower lobe pneumonia which did not respond to ampicillin (8 g daily) and gentamycin (120 mg daily). Parenteral administration of doxycycline (100 mg daily) was equally ineffective. However, the fever fell on administration of cefotiam (4 g daily). Antibody tests demonstrated Legionella pneumophila serogroup 1 as the causative organism. Because of the confined accommodation of the conscripts the source of the infection was thought to be the hot water system in the barracks. In two other policemen the demonstration of antibodies and of urine antigens confirmed Legionella infection as cause of an acute respiratory illness (Pontiac disease). Legionella pneumophila serogroup 1 subtype Philadelphia, 1-8 colony-forming units per ml, was isolated from six of 14 hot water samples in the barracks. This subtype possesses a virulence-associated antigen which is found in the majority of patient isolates of Legionella pneumophila serogroup 1.

Adult↗
PubMed1992

Sequence variation of cytotoxic T cell epitopes in different isolates of Epstein-Barr virus.

Previous results have identified two distinct cytotoxic T lymphocyte (CTL) epitopes encoded by Epstein-Barr virus (EBV), TETA (ORF BLRF3/BERF1 residues 329-353) and EENL (ORF BERF3/BERF4 residues 290-309). Measurement of the specificities of CTL clones (TETA-specific clone 13 and EENL-specific clone 7) directed against these epitopes indicated that the EENL epitope is conserved in all strains of EBV tested while the TETA epitope varied between individual virus strains. Sequencing of the DNA regions encoding these two CTL epitopes in different EBV isolates confirmed these interpretations and demonstrated that different TETA epitope sequences were encoded by B-type EBV strains and by the B95-8 isolate of EBV compared to the other A-type EBV strains. Titration of synthetic variants of the TETA epitope revealed that the epitope encoded by B95-8 was 15-fold less efficient as a T cell epitope than the sequence encoded by other A-type viral strains while the TETA variant encoded by the B-type strains displayed essentially no activity as a T cell epitope.

Amino Acid Sequence↗
PubMed1992

Transdermal drug delivery systems of albuterol: in vitro and in vivo studies.

In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/- 118 mL.h-1.kg-1. The average concentrations in serum after application of single- and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Contractile properties of single motor units in two multi-tendoned muscles of the cat distal forelimb.

The contractile properties of motor units (MUs) in two multi-tendoned forelimb muscles were investigated. In anesthetized cats single MUs of the extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) muscles were selectively activated by stimulation of cervical ventral root filaments. MUs were characterized by various tests including single twitches, series of tetanic contractions providing a tension-frequency relation and a fatigue test. They were classified by the parameters contraction time (CT, time-to-peak within unpotentiated single twitches) and fatigue-index (RB, according to Burke). The ECU muscle is composed of 38% type FR MUs (fast, fatigue-sensitive; CT less than 38 ms; RB less than 0.5), 35% type FR MUs (CT less than 38 ms, RB greater than 0.5) and 27% type S MUs (slow; CT greater than 38 ms, RB greater than 0.5). 46% of the EDC MUs were classified as FF (RB less than or equal to 0.25), 29% as FI (fast, intermediately fatiguable; 0.25 less than RB less than 0.75) and 25% as FR/S (fatigue-resistant, fast or slow; RB greater than or equal to 0.75). The latter group was devised since most MUs appeared as fast and the unequivocal presence of slow MUs could neither be demonstrated nor excluded. Normalized tension-frequency relations of fast ECU and EDC MUs were nearly identical and similar to those reported for fast MUs of other muscles. In contrast to this, the tension-frequency relation of slow ECU MUs has a different shape supporting the use of this function to distinguish fast from slow MUs. The distribution of different types of MUs is discussed with regard to the structure and function of the parent muscles and in relation to hindlimb muscles of comparable architecture. As revealed by comparison to EMG data gained in behaving animals (Fritz et al. 1985; Hoffmann et al. 1986, Botterman et al. 1985), the three muscles of the cat distal forelimb investigated so far seem to be adapted to different tasks: the EDC to rapid movements with a high proportion of type FF MUs, flexor carpi radialis to sustained contractions during the body support with a high proportion of fatigue-resistant MUs; the ECU which changes synergism between both muscles has an intermediate composition.

Animals↗
PubMed1992

Biochemical organization of single motor units in two multi-tendoned muscles of the cat distal forelimb.

In anesthetized cats single motor units (MUs) of the extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) muscles were selectively activated by stimulation of cervical ventral root filaments. The distribution of force developed by single MUs at the four distal tendons of the EDC muscle and at three portions of the distal tendon of the ECU muscle was analysed. In general, single MUs of both muscles distributed force over all tendons in a unimodal pattern, with the maximal force levels generated at one specific tendon which was termed the best-tendon. Distributions of force were quantitatively described by a parameter representing the mean direction of force output (output-index) and a further one representing the dispersion of force over the distal tendons (divergence). Generally, these parameters and the best-tendon remained stable when a MU was stimulated at different frequencies, but varied from MU to MU. Despite the general stability of the force distribution, slight systematic changes were regularly found in EDC MUs, when they developed a higher amount of force due to a higher frequency of stimulation: the relative amount of force at the best-tendon increased; e.g. the MUs got more selective for the best-tendon. These changes were partly due to overcoming mechanical cross-coupling between neighbouring compartments of the EDC muscle. Such changes of force distribution were only found in a part of the ECU MUs; other ECU MUs did not change their force distribution at all or became less selective for the best-tendon. The phenomenon that MUs of multi-tendoned muscles distribute their force output to the distal tendons in specific patterns is probably due to mechanical partitioning of the parent muscles: the localization of spatial territories of MUs within different anatomical muscle compartments should correspond to the best-tendon. Complex mechanisms allowing passive transmission of force from limited territories along the transverse axis of both muscles must be assumed in order to explain why most MUs act on all tendons and why force distributions change with increasing stimulus frequency. In addition, specific relations between unit type and force distributions were found within both muscles. Fatigue-resistant EDC MUs have broader force distributions than fatigue-sensitive EDC MUs and slow ECU MUs were found to act predominantly on the most ulnar part of the distal tendon. These biomechanical properties of MUs are discussed as supporting the specific functions of the respective muscles.

Animals↗
PubMed1992

A Barycentremetric study of the sagittal shape of spine and pelvis: the conditions required for an economic standing position.

The standing posture of 17 young men and women were studied using Barycentremeter measurements and full spine radiograph with a single referential system. These procedures provide in vivo measurements of the weight and center of weight supported by each vertebra and the coxofemoral joints. The relationship between the vertebra, the sacrum or the coxofemoral rotation axis and the center of weight they support, is displayed. The moment of the corresponding force may also be assessed. Mean values were computed and the relation with spine sagittal curves and pelvic parameters were studied. The position of the center of weight, in front of or behind the vertebra or the coxofemoral joints, requires an opposing muscle force to ensure mechanical stability. The load exerted on the vertebra cannot be precisely evaluated, but we can describe the way in which these loads vary when the spinal curves and the pelvic slope change. This study provides basic data suggesting that there is a tendency to maintain the body in the most economical position in terms of muscle fatigue and vertebral strain. Individual anatomical shapes and pelvic parameters of the pelvis induce corresponding specific sagittal curves of the spine. This concept is very useful for analysing pathological situations and devising appropriate treatment.

Adult↗
PubMed1992

The electronic fight against the schistosomes.

A DOS-compatible model for use on personal computers has been constructed for teaching in parasite epidemiology. The program is based on the Macdonald model of schistosome dynamics and enables simulation of the effect of a control campaign on a human worm load by reducing four transmission factors in the parasite life-cycle: (1) egg contamination, (2) snail lifetime, (3) exposure to cercariae and (4) adult worm lifetime.

Animals↗
PubMed1992

[Cryptogenetic ascites. Attempts at original pathophysiologic explanation of a monomorphic sonographic image pattern].

In 15,645 consecutive ultrasound examinations of the abdomen (1986 to 1988), free fluid in the peritoneal cavity was found in 247 patients by internal trial during 397 sessions (= 2.5%). Most frequent basic diagnosis for the reason of this symptom were tumorous diseases (99 patients corresponding to 40.1%), cirrhosis of the liver (52 patients corresp. to 22.1%) and heart failure (31 patients corresp. to 12.6%, among these complex gayprooft myocardial insufficiency 24, right heart failure 7). Ovarian cysts or cystomas (7), acute/chronic-recurrent pancreatitis (6), Crohn's disease (3), infections (3), rheumatoid disorders (3), nephrotic syndrome (2), and extra-uterine pregnancy (2) were more rarely represented. In 23 patients (corresp. to 9.3%) the cause of an ascites remained obscure. Among these, a high prevalence of the female sex in the premenopausal age was remarkable with a score of 20:3 (statistically significant difference in terms of the other patients of our group). This observation suggests that an ovarian factor plays a role in the development of ascites in the absence of other evident causes. The literature implies that endometriosis is rather prominent, followed by oligosymptomatic infections or inflammatory diseases.

Adolescent↗
PubMed1992

Cryptococcal disease presenting as cellulitis.

Three immunocompromised patients presented with cellulitis as the primary manifestation of cryptococcal disease. Two were recipients of cadaveric renal transplants who were receiving immunosuppressive drug therapy. The other patient had profound lymphopenia and severe hypoalbuminemia due to intestinal lymphangiectasia. All had failed to respond to empiric therapy for presumed bacterial cellulitis before results of skin biopsy or aspiration were available for the correct diagnosis to be made. With administration of systemic antifungal therapy, two patients survived. Although other forms of cryptococcal involvement of the skin are not rare, cellulitis is seldom considered to be a cutaneous manifestation of the disease. Our cases and a review of the English-language literature indicate that Cryptococcus neoformans must be included in the differential diagnosis of cellulitis in immunocompromised patients and that the presence of cryptococcal cellulitis suggests disseminated cryptococcal disease. Prompt diagnosis and treatment may dramatically reduce mortality.

Adult↗
PubMed1992

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen.

There are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate did not lyse haploidentical B95-8 LCL expressing the HLA-A1, -B8, -DR3 paternal haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11, -B51, -DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95-8 LCL expressing the haploidentical HLA-A1, -B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA-A11, -B51, -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8-associated peptide epitope that interacted with the HLA-B8 allele but failed to lyse B95-8-transformed LCL targets unless the targets were pre-coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+ donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA-B8.

Cell Transformation, Viral↗
PubMed1992

Formation of heterotrimers between the membrane-integrated and the soluble glycoproteins of vesicular stomatitis virus leads to their intracellular cotransport.

BHK cells infected with vesicular stomatitis virus serotype Indiana generate intracellularly two different types of glycoproteins: the authentic membrane-integrated G protein of virions and a smaller soluble Gs protein lacking the transmembrane and cytoplasmic domains which is secreted into the growth medium. A Gs1 protein species which is formed during or shortly after translation in the endoplasmic reticulum lumen is modified in the same way as the G1 protein by endoglycosidase H-sensitive oligosaccharides of the high-mannose type. Both G1 and Gs1 are almost simultaneously transported, trimmed, and processed into G2 and Gs2 species which possess carbohydrate side chains of the complex type, making both glycoproteins resistant to endoglycosidase H cleavage. Secretion of Gs2 protein into the growth medium and arrival of G2 protein on the cell surface occur concomitantly. Membrane-integrated G protein and the soluble Gs protein molecules oligomerize intracellularly into heterotrimers which can be immunoprecipitated after chemical cross-linking. Gs protein seems to contain sufficient structural information for the formation of heterotrimers which are efficiently transported to the cell surface. Heterotrimer formation between G and Gs proteins explains the rapid secretion of Gs molecules.

Clone Cells↗
PubMed1992

Sequence comparison among DNA fragments from different sources with pac site function for the packaging apparatus of Salmonella phage P22.

Two different DNA fragments, deriving from the P22-related bacteriophage LP7 and from the right IS element of transposon Tn10, have been identified which were recognized by the P22-packaging apparatus as pac-like signals. Their nucleotide sequences were compared with the known sequence of P22 gene 3 which contains the P22 pac site. Both sequences show similarity to a particular segment of P22 DNA close to a region identified earlier as part of pac.

Base Sequence↗