Biomedical subjects
T Voss
Publications and source records attributed to T Voss.
Macromolecular organization of natural and recombinant lung surfactant protein SP 28-36. Structural homology with the complement factor C1q.
The macromolecular structure of the pulmonary surfactant apolipoprotein SP 28-36 has been determined. For SP 28-36 isolated from dog lung lavage, a flower bouquet-like hexameric structure with six globular domains connected by short stalks to a common stem was revealed by electron microscopy, using the rotary shadowing technique. This structure is very similar to that published for the subcomponent C1q of the first component of complement C1. The lavage material was compared with the homologous human recombinant SP 28-36 by the same technique. Mostly smaller aggregates like di-, tri- and tetramers as well as very high aggregates were observed. Mild reduction of the recombinant material revealed the lollipop-shaped monomers composed of a globular domain and a tail with a discrete kink in the middle portion. The collagenous nature of the tail was demonstrated by circular dichroism spectroscopy. This implies that the mammalian expression system assembles the monomeric subunits correctly. Assembly into the hexameric structures, however, does not proceed quantitatively.
Regulation of type I collagen mRNA levels in fibroblasts.
Type I procollagen mRNA levels, as well as total RNA and poly(A)-rich mRNA, remain constant when rapidly growing human fetal lung fibroblasts (HFL-1 cells) are compared with quiescent cells. Polysome profiles of cells in both growth states revealed that the distribution of type I collagen mRNA in the mRNP fraction and in polysomes also remained constant even though total RNA and poly(A)-rich mRNA were shifted from polysomes to the mRNP pool in resting cells. Similar results were obtained when RNA fractions in polysomes associated with the cytoskeletal framework were examined. It is known that procollagen production is unaffected by the growth state of cells [Breul, S. D., Bradley, K. H., Hance, A. J., Schafer, M. P., Berg, R. A. and Crystal, R. G. (1980) J. Biol. Chem. 255, 5250-5260] although total protein synthesis is markedly decreased in resting cells. It would therefore appear that the translational control responsible for reduced synthesis of non-collagenous proteins in resting cells does not extend to procollagen and that transcriptional control can account for levels of type I procollagen produced by cultured human fibroblasts.
Transcriptional regulation of fibroblast collagen synthesis by activated mononuclear cell supernatants.
Mononuclear cells elaborate effector substances which regulate growth and synthetic activities of fibroblasts. We have studied the mechanism by which activated mononuclear cell supernatants inhibit collagen production. Activated supernatants were prepared by culturing human peripheral mononuclear cells with phytohemagglutinin. Human fibroblasts were exposed to the activated supernatants and total cellular RNA was isolated. Collagen mRNA levels were measured using a pro alpha [I] probe and poly(A+) mRNA was assayed using polyuridylic acid as the probe. Collagen production was measured as collagenase-digestible radioactivity. The results showed that pro alpha 1 [I] mRNA levels were decreased in cells incubated with the activated mononuclear cell supernatants and that the decrease was dose and time dependent. The reduction in the pro alpha 1 [I] mRNA correlated with the decrease in collagen production. No inhibition in the poly(A+) message was observed. We conclude that inhibition of collagen production by activated mononuclear cell supernatant occurs primarily at the transcriptional level and that the inhibition may be selective to collagen.
Amino acid sequence of the non-collagenous globular domain (NC1) of the alpha 1(IV) chain of basement membrane collagen as derived from complementary DNA.
NC1, the C-terminal non-collagenous globular domain of collagen IV, represents one of the two end regions responsible for the assembly and cross-linking of the extracellular network of basement membrane collagen. Several cDNA clones for the NC1 domain of the alpha 1(IV) collagen chain of mouse have been isolated by using synthetic oligonucleotides as screening probes for mouse libraries. The oligonucleotides were synthesized according to known stretches of the corresponding protein sequence. Sequencing of the overlapping cDNA clones allowed the complete amino acid sequence of the NC1 domain to be deduced as well as the C-terminal 165 amino acid residues of the triple helix. It consists of 229 amino acid residues which comprise two homologous regions with a high content of cysteine. These DNA and protein sequences are compared to the corresponding sequences of other collagens and discussed with respect to their structural and biological significance.
The structure of type IV collagen.
Explore the source record for details and available documents.
Localization of flexible sites in thread-like molecules from electron micrographs. Comparison of interstitial, basement membrane and intima collagens.
A computer method for detecting kinks and flexible sites in thread-like molecules was developed. The method is based on the determination of the local curvature along the digitized electron micrographs of the molecules. The root-mean-square curvature provided a measure for the local flexibility, which is related to the persistence length. The influence of various error sources was assessed using computer-simulated thread molecules. "Flexibility profiles" showing the variation of flexibility along molecules were calculated for interstitial, basement membrane and intima collagens. Approximately uniform stiffness corresponding to a persistence length of 60 nm was found for the triple helices of interstitial and monomeric intima collagen. A highly flexible site in interstitial collagen could be assigned to a non-triple helical segment in the sequence surrounding the linkage site of the N-terminal propeptide. A flexible site in the triple helix of collagen I corresponds to a segment of the sequence lacking proline residues. Flexibility varies strongly along the collagen IV molecule. This is consistent with the fact that a series of non-triple helical interruptions have already been found in the not yet completed amino acid sequence of basement membrane collagen. Most of the detected flexible sites allow random bending about the mean zero, but in one case, at the border of the 7S domain of polymeric collagen IV, a flexible site with a preferential angle of 40 degrees was found.
Macromolecular structure of basement membrane collagens.
Explore the source record for details and available documents.
[Health of schoolchildren in Copenhagen].
Explore the source record for details and available documents.
[Clinical pathology and treatment of upper urinary tract urothelial tumors--a 10-year review (author's transl)].
Fifty-four patients with upper urinary tract urothelial tumors were treated from 1966 to 1975 at the Urologische Klinik und Poliklinik der Universität Erlangen-Nürnberg. The neoplasms were multicentric in 13 patients (24%). All of the tumors were classified according to the WHO classification and the recommendation of the UICC. The correlations between histologic grade of malignancy and local spread are statistically significant. Lymph node metastases were found primarily with grade 3 tumors and infiltration into outer muscle layer. Nephroureterectomy with radical lymphadenomectomy via transabdominal approach and frozen-section histology of marginal nodes are recommended. The overall 5-year survival rate was 65% (+/- 16%) in all patients with malignant disease.
[Dental caries in relation to socio-medical handicap in school children from Copenhagen, Denmark].
Explore the source record for details and available documents.
[Dental caries in relation to socio-medical handicap in local school children from a Copenhagen municipal school].
Explore the source record for details and available documents.
Efficacy of a mixture of medium-chain triglyceride (75%) and long-chain triglyceride (25%) fat emulsions in the nutritional management of multiple-trauma patients.
Ten severely injured patients who were admitted to the intensive care unit and who needed total parenteral nutrition (TPN) were randomly enrolled in a prospective double-blind study comparing two 20%-fat intravenous emulsions: one (MCT-LCT) containing a physical mixture of 75% medium-chain triglyceride (MCT) and 25% long-chain triglyceride (LCT) and another containing 100% LCT. TPN (30 kcal.kg-1.day-1) was given continuously as amino acids (20% of energy) and glucose (50% of energy) over 7 days with the respective lipid emulsion (30% of energy) provided from 0800 to 1600 each day. Plasma substrate concentrations, nitrogen balance, resting energy expenditure, substrate net oxidation rates, whole-body lipolysis rates, and fatty acid reesterification rates were measured or calculated. Plasma concentrations of lipid metabolites (glycerol, triglycerides, and fatty acids) indicated rapid hydrolysis and efficient use of the MCT-LCT emulsion. Whole-body lipolysis rate decreased by 53% in the MCT-LCT group and by 34% in the LCT group. Net fat oxidation was greater and FFA reesterification less with MCT-LCT than with LCT, indicating more efficient and rapid fuel utilization in the post-traumatic period with the MCT-LCT emulsion. In critically ill patients dependent on intravenous nutrition, an MCT-LCT mixture may be useful as an obligate fuel and to limit net hepatic lipogenesis.