Search PubMed⌕ Search

Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 433 records · Page 24Linked to original sources
PubMed1988

Evidence for free beta-subunit secretion in so-called human chorionic gonadotropin-positive seminoma.

In 349 patients with pure seminoma the authors determined human chorionic gonadotropin (HCG) plus the free beta-subunit (HCG-beta) by a polyclonal radioimmunoassay (RIA) and found elevated serum levels in 42 patients (12%). In addition, each HCG and HCG-beta were specifically measured by monoclonal immunoradiometric assays (IRMA) in 19 of these patients. Overall 12 patients were HCG-beta positive and 12 HCG positive. Elevated serum levels of both molecules were found in five patients, whereas seven patients showed elevation only in HCG and another seven patients only in HCG-beta. In serum samples of patients with high HCG-beta and minimally elevated HCG levels the free beta-subunit could be detected by gel filtration and immunoradiometric assays, whereas both HCG-beta and holo-HCG were found in ultrafiltered and concentrated urinary samples. The authors conclude that HCG-beta can be present as the major form in serum even if both HCG-beta and HCG are detectable in urine. When measuring hormone concentration as a tumor marker in seminoma patients, methods which determine both activities, HCG plus HCG-beta, seem to be the most reliable. Whereas 16 patients with Stage I-IIc had HCG-beta levels between 0.1 and 2.8 IU/l and currently have no evidence of disease, two patients with Stage IV had HCG-beta levels of 18 and 37 IU/l and died. Current investigations have to clarify the prognostic significance of beta-subunit secretion.

Adult↗
PubMed1988

Characterization of proteolytic fragments of the laminin-nidogen complex and their activity in ligand-binding assays.

Some 12 new nidogen and laminin fragments were purified from elastase, thrombin and trypsin digests and characterized by their sizes (22 kDa to greater than 300 kDa), subunit patterns on electrophoresis, partial amino acid sequences, content of specific epitopes and their binding to laminin or nidogen structures in radioligand assays. This permitted the various fragments to be ordered along the dumbbell-shaped structure of nidogen and to compare them with previously described nidogen fragments arising by endogenous proteolysis. Two nidogen fragments (E-50, E-90; 50 kDa and 90 kDa) remain associated with a large laminin fragment in elastase digests of the complex and could be dissociated with 2 M guanidine.HCl. Recombination studies demonstrated Kd = 10-20 nM for this interaction. Nidogen fragments devoid of binding activity included the tryptic peptide T-40 (40 kDa) corresponding to the rod-like domain and several larger fragments extending more to the N-terminus of nidogen. An N-terminal thrombin fragment of about 50 kDa was also inactive. Together the data show a lack of laminin binding to the N-terminal globule and rod of nidogen and provide indirect evidence that this activity is located within or close to its C-terminal globular domain. Nidogen-binding structures of laminin were obtained as two large fragments (greater than 300 kDa), P1X and E1X. They correspond to the short arm structure of laminin with one (E1X) or two (P1X) arms decreased in size to the inner rod-like segment. Shortening in E1X is mainly due to the B1 chain segment including the central globular domain which was identified as a new laminin fragment E10. Binding of E1X and P1X to nidogen was comparable to that of laminin while much lower activity was found for other laminin fragments. A 10-fold lower binding potential was also observed for the laminin-nidogen complex whose structure can now be defined in more precise molecular terms.

Amino Acid Sequence↗
PubMed1988

Cloning and complete amino acid sequences of human and murine basement membrane protein BM-40 (SPARC, osteonectin).

Amino acid sequences of 285 and 286 residues, respectively, were deduced for mouse and human BM-40 from cDNA clones isolated from expression libraries. The sequences showed 92% identity and were also essentially identical to those of bone osteonectin and of the parietal endoderm protein SPARC. About 60% of the mouse BM-40 sequence was confirmed by Edman degradation. Two of the seven disulfide bonds were localized which apparently separate two distinct domains of mouse BM-40.

Amino Acid Sequence↗
PubMed1988

Reversible brain shrinkage in abstinent alcoholics, measured by MRI.

Magnetic resonance imaging of the intracranial CSF volume was compared before and after 5 weeks of confirmed abstinence in 9 alcohol-dependent patients. All patients showed a highly significant reduction in CSF volume in accordance with reexpansion of the brain after alcohol abstinence. T2 values for white matter, estimated by linear regression from 16 echoes of a CPGM sequence, however, showed no significant increase such as occurs in rehydration. This indicates, that alcohol-induced reversible brain atrophy cannot be attributed to fluctuation of free water in the brain only.

Adult↗
PubMed1988

Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen.

Type VI collagen is a heterotrimer composed of three polypeptide chains, alpha 1(VI), alpha 2(VI), and alpha 3(VI). By immunological screening of an expression cDNA library, human cDNAs specific for each chain were isolated and characterized. Major mRNA species encoding these chains have a size of 4.2 kb (alpha 1), 3.5 kb (alpha 2), and 8.5 kb (alpha 3). The cDNA clones were also used to map the genes on human chromosomes by somatic cell hybrid analysis and in situ hybridization. The alpha 1 (VI) and alpha 2(VI) collagen genes were both located on chromosome 21, in band q223. This represents a third example of a possible physical proximity of two collagen loci. The alpha 3(VI) collagen gene was localized to chromosome 2, in the region 2q37. The alpha 3(VI) collagen gene is the fifth extracellular matrix gene to be localized to 2q, as four other extracellular matrix genes--i.e., the alpha 1(III) and alpha 2(V) collagen genes, the elastin gene, and the fibronectin gene--have been previously mapped to the distal region of the long arm of chromosome 2.

Amino Acid Sequence↗
PubMed1988

Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy of patients with differentiated thyroid cancer.

Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T4), 29 patients with triiodothyronine (T3). In 33/43 patients (77%) under T4- and in 18/29 patients (62%) under T3-treatment basal TSH levels were below 0.1 mU/l and levels stimulated with 200 micrograms TRH i.v. were below 0.5 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment.

Adenocarcinoma↗
PubMed1988

[Results of radioiodine treatment of patients with immunogenic and non-immunogenic hyperthyroidism using different focal doses].

The aim of this study was to check the efficacy of radioiodine (131I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves' disease, Plummer's disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved in only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11% in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves' disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems.

Adenoma↗
PubMed1987

Characterization of three constituent chains of collagen type VI by peptide sequences and cDNA clones.

Pepsin-solubilized collagen VI was prepared from human placenta and used to separate three constituent chains for determining partial amino acid sequences. Antibodies raised against the chains assisted in the identification and purification of several cDNA clones from three expression lambda gt11 libraries. Most of the clones hybridized to either a 3.5-kb or 4.2-kb mRNA species which by matching peptide and nucleotide sequences could be identified as coding for the alpha 2(VI) or alpha 1(VI) chain, respectively. Other clones hybridized to either an 8.5-kb mRNA which very likely encoded the alpha 3(VI) chain or to an unknown 2.0-kb mRNA. Northern blots revealed a considerable variation in the mRNA levels for each collagen VI chain in both skin and cornea fibroblasts and in several tumor cell lines. Limited sequence data generated from peptides and cDNA clones demonstrated a characteristic cysteine pattern at the junction between N-terminal globular domain and triple helix in all three chains. In addition, the data showed occasional interruptions of triplet sequences within the triple-helical domain and the presence of two Arg-Gly-Asp sequences which are potential cell-binding structures.

Amino Acid Sequence↗
PubMed1987

Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties.

This study examines the osteoblastic properties of the established human osteosarcoma cell line Saos-2. Saos-2 cells inoculated into diffusion chambers, which were implanted i.p. into nude mice, produced mineralized matrix in 4 of 6 chambers at 8 weeks. In 5 of 6 chambers there was a strong positive alkaline phosphatase reaction. In culture the alkaline phosphatase levels increased with time and cell density, reaching very high levels at confluence: 4-7 mumol/mg protein/min. The cells show a sensitive adenylate cyclase response to parathyroid hormone, 50% effective dose = 2.8 nM, which increases with cell density and is further raised by dexamethasone treatment. They also exhibit typical binding of 1-25-dihydroxyvitamin D3 to 3.2S receptor protein with an apparent Kd of 0.21 nM; the numbers of sites per cell were 3,300 at 50,000 cells/cm2 and 1,800 at 280,000 cells/cm2. The presence of osteonectin was visualized with a monoclonal antibody which revealed a reticular pattern on the cell surface. Osteonectin was also detected in the medium by Western blots, migrating at around Mr 40,000 in nonreduced gels and Mr 44,000 in reduced gels. The Saos-2 cells thus possess several osteoblastic features and could be useful as a permanent line of human osteoblast-like cells and as a source of bone-related molecules.

Adenylyl Cyclases↗
PubMed1987

Proteolysis of factor Va by factor Xa and activated protein C.

Bovine Factor Va, produced by selective proteolytic cleavage of Factor V by thrombin, consists of a heavy chain (D chain) of Mr = 94,000 and a light chain (E chain) of Mr = 74,000. These peptides are noncovalently associated in the presence of divalent metal ion(s). Each chain is susceptible to proteolysis by activated protein C and by Factor Xa. Sodium dodecyl sulfate electrophoretic analysis indicates that cleavage of the E chain by either activated protein C or Factor Xa yields two major fragments: Mr = 30,000 and Mr = 48,000. Amino acid sequence analysis indicates that the Mr = 30,000 fragments have identical NH2-terminal sequences and that this sequence corresponds to that of intact E chain. The Mr = 48,000 fragments also have identical NH2-terminal sequences, indicating that activated protein C and Factor Xa cleave the E chain at the same position. Sodium dodecyl sulfate electrophoretic analysis indicates that activated protein C cleavage of the D chain yields two products: Mr = 70,000 and Mr = 24,000. Amino acid sequence analysis indicates that the Mr = 70,000 fragment has the same NH2-terminal sequence as intact D chain, whereas the Mr = 24,000 fragment does not. Factor Xa cleavage of the D chain also yields two products: Mr = 56,000 and Mr = 45,000. The Mr = 56,000 fragment corresponds to the NH2-terminal end of the D chain and Factor V. Functional studies have shown that both chains of Factor Va may be entirely cleaved to products by Factor Xa without loss of activity, whereas activated protein C cleavage results in loss of activity. Since activated protein C and Factor Xa cleave the E chain at the same position, the cleavage of the D chain by activated protein C is responsible for the inactivation of Factor Va.

Amino Acid Sequence↗
PubMed1987

Glycosylation of simian virus 40 T antigen and localization of glycosylated T antigen in the nuclear matrix.

Evidence has been obtained for the glycosylation of simian virus 40 (SV40) T antigen in SV40-infected TC7 cells. Both [3H]mannose and [3H]glucosamine are incorporated into T antigen in cells grown and labeled in medium containing fructose instead of glucose. In addition, T antigen is visualized by a carbohydrate stain specific for mannose and/or glucose residues. Finally, lectin binding studies suggest that T antigen contains galactose and/or galactosamine, since T antigen is specifically eluted from soybean lectin by 0.2 M galactose. When gel-purified, [3H]glucosamine-labeled T antigen is subjected to tryptic peptide mapping, label is found in only one peptide, thought to correspond to the methionine-containing peptide extending from Asn-653 to Arg-691, near the carboxy-terminal end of T antigen. Insensitivity to tunicamycin and the localization of the glycosylation site in the carboxy-terminus of T antigen, and not at Asn-153, suggest that T antigen is not N-glycosylated. Cell fractionation studies show that [3H]glucosamine-labeled T antigen is preferentially associated with the nuclear matrix of SV40-infected TC7 cells.

Antigens, Viral, Tumor↗
PubMed1987

Treatment of akathisia with lorazepam. An open clinical trial.

Sixteen patients with neuroleptic-induced akathisia were treated with lorazepam. A marked improvement in symptoms was observed in 9 of the patient and moderate improvement in 5. Symptoms remained unchanged in 2 patients. The drop in the akathisia score from a pretreatment value of 1.81 to 0.5 after 7 days and to 0.32 after 14 days was statistically significant. Symptoms did not improve significantly during observation of the spontaneous course. No severe side effects were observed. The physiologic mechanisms of action of lorazepam on the akathisia syndrome are discussed.

Adult↗