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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 397 records · Page 22Linked to original sources
PubMed1991

[Thiamine deficiency and brain atrophy in alcoholic patients].

CT brain scans of 65 alcohol-dependent inpatients were compared before and after 6 weeks of confirmed abstinence. Linear measurements revealed a significant reduction of the enlargement of the ventricular system in accordance with the re-expansion of the brain after alcohol abstinence (ANOVA, significant time effects). 22 patients showed a moderate or severe thiamine deficiency. CT findings on thiamine-deficient patients did not differ from those on patients without thiamine deficiency (ANOVA, no significant group effects). Correlations between thiamine deficiency and subcortical atrophy before treatment were not significant. The results are discussed in relation to the pathogenesis of reversible brain shrinkage in chronic alcoholics.

Adult↗
PubMed1991

[Rate of ethanol elimination in alcoholics with special reference to variants of maximal values for legal calculation of blood alcohol concentration].

The ethanol elimination rate was measured in 15 male alcoholics who had come to the Psychiatric Clinic of the University of Tübingen as in-patients. Over the course of several hours between 3 and 5 blood samples were taken in the post-absorption phase. The hourly elimination rate, calculated by lines of regression, gave a mean value of 0.224 g/kg (s = 0.038 g/kg). This was significantly higher than the elimination rate for non-alcoholics calculated from drinking experiments found in the literature (p less than 0.001). In addition 2 blood samples were taken several hours apart from each of 39 alcoholics. Based on the results of the analysis of the second blood sample, the value of the first blood sample was calculated back using the maximum value formula employed in foro. The calculated maximum values were compared to the analysis values. In 8 cases the analysis value was higher than the calculated maximum value, exceeding it by as much as 0.74 g/kg. It should be considered whether the formula currently employed to calculate the maximum BAC is sufficiently accurate in alcoholic to exclude possible false detrimental values.

Adult↗
PubMed1990

Characterization of a novel calcium-binding 90-kDa glycoprotein (BM-90) shared by basement membranes and serum.

The protein BM-90 was solubilized from the mouse Engelbreth-Holm-Swarm tumor with neutral buffers in molar yields lower (15-30%) than found for other basement membrane proteins (e.g. laminin, BM-40). The purified protein was shown to be rich in cysteine (5 mol%) and to change in SDS electrophoresis from an 84-kDa position to a 95-kDa one upon reduction. BM-90 was also shown to be a calcium-binding protein. The N-terminal sequence of BM-90, as well as those of several internal peptides, showed no identity with any known protein sequences, indicating that it is a new protein. Specific radioimmunoassays showed no or only minor cross-reactions with other known basement membrane proteins. Immunological assays demonstrated BM-90 to be present in neutral salt extracts from mouse heart and kidney, in serum (20-40 micrograms/ml) and in the medium of various cultured cells (0.1-1 microgram/ml). The protein in these samples was identical in size to BM-90 purified from the tumor, indicating that negligible degradation occurs during purification. An extracellular matrix localization of BM-90 was shown by immunofluorescence for Reichert's membrane, lens capsules and other basement membranes. Thus, BM-90 appears to be a novel basement membrane protein whose functions remain to be studied.

Amino Acid Sequence↗
PubMed1990

The primary structure of a triple-helical domain of collagen type VIII from bovine Descemet's membrane.

We have isolated and sequenced a fragment of 469 amino acid residues from bovine type VIII collagen. The sequence was composed of a series of Gly-X-Y repeats which was interrupted 8 times by short imperfections. The number and relative location of these interruptions were similar to those of chicken alpha 1(X) and rabbit alpha 1(VIII) chain triple-helical domains. Comparison to published N-terminal sequences to two triple-helical fragments of bovine type VIII collagen and to the cDNA derived sequence of the rabbit alpha 1(VIII) chain showed that this fragment was the triple-helical domain of a second type VIII collagen chain which we designate alpha 2(VIII).

Amino Acid Sequence↗
PubMed1990

Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors.

Human collagen alpha 3(VI) chain mRNA (approximately 10 kb) was cloned and shown by sequence analysis to encode a 25 residue signal peptide, a large N-terminal globule (1804 residues), a central triple helical segment (336 residues) and a C-terminal globule (803 residues). Some of the sequence was confirmed by Edman degradation of peptides. The N-terminal globular segment consists of nine consecutive 200 residue repeats (N1 to N9) showing internal homology and also significant identity (17-25%) to the A domains of von Willebrand Factor and similar domains present in some other proteins. Deletions were found in the N3 and N9 domains of several cDNA clones suggesting variation of these structures by alternative splicing. The C-terminal globule starts immediately after the triple helical segment with two domains C1 (184 residues) and C2 (248 residues) being similar to the N domains. They are followed by a proline rich, repetitive segment C3 of 122 residues, with similarity to some salivary proteins, and domain C4 (89 residues), which is similar to the type III repeats present in fibronectin and tenascin. The most C-terminal domain C5 (70 residues) shows 40-50% identity to a variety of serine protease inhibitors of the Kunitz type. The whole sequence contains 29 cysteines which are mainly clustered in short segments connecting domains N1, C1, C2 and the triple helix, and in the inhibitor domain. Five putative Arg-Gly-Asp cell-binding sequences are exclusively localized in the triple helical segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Increased epidermal growth factor receptors in gastric carcinomas.

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.

Adult↗
PubMed1990

Characterization of SV40 T antigen associated with the nuclear matrix.

Simian virus 40 (SV40) T antigen associated with the nuclear matrix of SV40-infected TC7 cells has been characterized. Pulse-chase studies on the turnover of T antigen in the different subcellular fractions show that T antigen turns over most rapidly in its association with the purified SV40 nucleoprotein complexes (NPCs) and undergoes a slower rate of turnover in its association with the nuclear matrix. In contrast, turnover of SV40 T antigen in its association with the other subcellular fractions is not detected during the same period of time. Tryptic peptide maps establish that NPC-associated T antigen and nuclear matrix-associated T antigen are chemically related, in that they have two additional methionine-containing peptides that are not found in the majority of T antigen molecules. The association of T antigen with the nuclear matrix is independent of SV40 DNA replication since T antigen is still present in the nuclear matrix after a 1-hr shift-up of tsA58-infected cells to the nonpermissive temperature. In addition, T antigen is associated with the nuclear matrices of both C6 and Cos7 transformed cells, indicating that the association of T antigen with the nuclear matrix is independent of its ability to initiate and support SV40 DNA replication.

Animals↗
PubMed1990

Evaluation of the ratio of T3 release stimulating antibodies to TSH-binding inhibiting antibodies during the course of Graves' disease.

The mechanisms leading to a remission of Graves' hyperthyroidism are still unknown. One possibility would be that autoantibodies raised during the course of disease could change the composition of the autoantibody spectrum in such a way to counterbalance the action of stimulatory autoantibodies, thereby resulting in an induction of remission. Therefore, in the present study using a rigorous methodological approach we have characterized the portion of T3 release stimulating autoantibodies among the total body of TSH receptor antibodies, i.e. the TSAb/TBII ratio, over the course of a 12 month antithyroid therapy in 25 patients with Graves' hyperthyroidism. Further, we have evaluated the relation of the alteration of the antibody spectrum to the course of disease. The TSAb/TBII ratio was indeed found to be subject to considerable changes. The observed shift in the antibody composition was more often in favor of a relative increase in stimulatory inactive TBII. Nevertheless, the clinical course of patients showing a persistence of TBII despite the decline or even absence of TSAb proved to be variable. In conclusion, our data indicate that the spectrum of autoantibodies may change over the course of antithyroid therapy owing mostly to a relative rise in stimulatory less active autoantibodies. This phenomenon, however, is apparently not closely related to the course of disease.

Adult↗
PubMed1990

Differential increase in topoisomerase II in simian virus 40-infected cells.

The time course of expression of topoisomerase I, topoisomerase II, and simian virus 40 (SV40) large tumor (T) antigen was determined in whole-cell extracts of uninfected versus SV40-infected TC7 cells. After a minor increase, the level of topoisomerase I remained fairly constant throughout the time course in both uninfected and SV40-infected cells. In contrast, the level of topoisomerase II increased markedly in SV40-infected cells but not in uninfected cells following the appearance of SV40 T antigen.

Animals↗
PubMed1990

Evidence for the presence of human chorionic gonadotropin (hCG) and free beta-subunit of hCG in the human pituitary.

Previous studies have indicated that the pituitary gland may produce free alpha-subunit and small quantities of hCG in addition to other glycoprotein hormones. Since synthesis of holo-hCG requires the presence of both subunits, we have investigated the occurrence in human pituitary of free beta-subunit of hCG, in addition to intact holo-hCG. We processed a pituitary extract by fractionated ammonium sulfate precipitation followed by sequential chromatography on Sephadex G-100 and Ultrogel AcA 44. The fractions obtained were assessed for their reactivities with a panel of polyclonal and monoclonal antibodies specific for holo-hCG, beta-subunit of hCG, alpha-subunit, or hCG/LH. In addition to the expected LH and alpha-subunit, we detected materials which eluted from the column in positions very similar to those of cochromatographed 125I-hCG tracer and hCG-beta (NIH CR123-beta), and which showed immunoreactivity in specific immunoradiometric assays for holo-hCG and hCG-beta, respectively. Holo-hCG and hCG-beta material derived from the urine of a postmenopausal woman showed behaviors on the column similar to the pituitary forms. Both the pituitary holo-hCG- and free hCG-beta-subunit activity could be enriched (approximately 500 times) by affinity chromatography on an hCG antibody-coupled Sepharose column. When subjected to isoelectric focusing in granulated gel holo-hCG and hCG-beta-subunit of pituitary origin were focused in the pI-range of pregnancy hCG and pregnancy hCG-beta-subunit, respectively. Like pregnancy hCG, most (75%) of the pituitary hCG was bound to a column of Con A-Sepharose; however, the Con A-nonbinding hCG fraction (approximately 25%) was much higher than that found in pregnancy hCG. On the basis of immunoreactivities, the content of holo-hCG in our pituitary extract was estimated to be 60 micrograms/g, and that of free beta-subunit 45 micrograms/g; for comparison, LH was approximately 20 mg/g, and free alpha-subunit 1.6 mg/g. In addition, we could demonstrate the presence of both holo-hCG- and free hCG-beta-subunit-like immunoreactivity in NaCl-extracts from single pituitaries of two postmenopausal women. In these studies a second hCG-beta-immunoreactive material eluting far behind the hCG-beta-position was found. Chromatography of purified LH-beta-subunit, which crossreacts 1.56% in the hCG-beta IRMA, yielded an elution pattern clearly distinguishable from that of the hCG-beta-immunoreactive substances.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1990

Testicular cancer secretes intact human choriogonadotropin (hCG) and its free beta-subunit: evidence that hCG (+hCG-beta) assays are the most reliable in diagnosis and follow-up.

Human choriogonadotropin (hCG) and free hCG-beta values for 934 serum samples from patients with seminomatous or nonseminomatous testicular cancer were measured by highly specific immunoradiometric assays (IRMAS). In non-seminoma samples, hCG and hCG-beta were highly correlated (r = 0.82, P less than 0.001). Of 112 "marker-positive" seminoma samples, only 46 (41.1%) showed both increased hCG and hCG-beta. In 39 cases (34.8%) only hCG-beta and in 27 cases (24.1%) only dimer-hCG was increased. This makes the determination of hCG and hCG-beta, either by two assays or by a single hCG (+hCG-beta) assay, most reliable in these patients. For all samples, hCG (+hCG-beta) was measured by a polyclonal RIA and a monoclonal IRMA, which differed in their cross-reactivities with hCG-beta (234% and 720%, respectively). The hCG (+hCG-beta) IRMA, as a result of its higher hCG-beta cross-reactivity, was superior to the hCG (+hCG-beta) RIA in detecting slightly increased hCG-beta. Additionally, 11 widely used commercial hCG kits were tested for their hCG-beta cross-reactivities and showed values between less than 3% and 264%.

Antibodies, Monoclonal↗
PubMed1990

[Tumor markers in testicular cancer].

In patients with testicular germ cell tumours, determination of both human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) is mandatory for the diagnosis and the follow-up under treatment. Most so-called hCG-beta kits measure hCG plus the free beta-subunit. This seems to be important, as selectively elevated levels of hCG-beta have been found in some seminoma patients. Diagnosis and follow-up must always be done with the same method, because the kits available differ in specificity. AFP determination with poly- or monoclonal antibodies gives comparable results. A short-lasting increase in hCG and/or AFP during chemotherapy is due to cell necrosis and is not a sign of tumour progression. Highly elevated hCG levels at the beginning indicate a poor prognosis regardless of other parameters and should be borne in mind when decisions on treatment are made. Elevated levels of AFP mean that a pure seminoma cannot be present. In contrast, about 20% of seminoma patients have mildly elevated levels of hCG/hCG-beta, which are synthesized in syncytiotrophoblastic giant cells and only rarely in inconspicuous rounded seminoma cells. Serological hCG determinations are a more sensitive test than immunohistochemistry. The prognosis of this special form of seminoma tends to be similar to that of typical seminoma, and does not presently justify more aggressive treatment. No other highly sensitive and specific markers are available in seminoma. Nevertheless, placental alkaline phosphatase (PLAP) has some significance as a parameter for the follow-up in nonsmokers. False-positive values are found in about 20% of heavy smokers, which reduces the specificity of this test. The sensitivity is said to be about 90%. Lactate dehydrogenase (LDH) is significantly elevated, especially in the presence of advanced tumours. The specificity of LDH is low, as a variety of non-malignant diseases and minimal tissue damage can lead to pathologic serum levels. Nevertheless, LDH is of some value in the follow-up of marker-negative patients and can indicate a persistent tumour or a recurrence. Some authors have found evidence that initially elevated LDH may be an independent prognostic factor. The isoenzyme LDH 1 is easily determined, shows elevated levels in the presence of testicular germ cell tumours even if the total LDH is normal and is possibly more specific. However, the data presently available cannot yet justify its general application.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗