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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

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

Thyroid stimulation by placental factors.

There is now convincing evidence that the human placenta produces factors which have some role in regulating maternal thyroid function during normal pregnancy and are capable of inducing overt hyperthyroidism in some pregnant women and in patients with trophoblastic tumors. As far as the biochemical nature of these placental thyroid stimulators is concerned, a bulk of evidence indicates that hCG, which is abundant in the blood of pregnant women and patients with trophoblastic diseases and shares some structural similarities with human TSH, is the putative thyroid-stimulating factor. However, it is disturbing that most in vitro studies have failed to prove that hCG is truly capable of stimulating the human thyroid. Therefore, factors other than hCG have also to be considered, particularly some molecular variant forms of hCG with enhanced thyrotropic activity. Both the existence of tumor-associated hCG variants in patients with trophoblastic diseases and their ability to stimulate thyroid hormone release in human thyroid tissue have been demonstrated. To complicate things further, other variants of hCG have been identified and purified from pregnancy urine that have a thyroid inhibitory effect in human thyroid membranes. The variant forms of hCG have been shown to differ from the native hormone mainly in the carbohydrate moiety, with the more acidic, more glycosylated variants being the ones capable of stimulating the human thyroid and the more alkaline sialic acidic deficient variants on the other hand, being potent thyroid inhibitors. Future studies should reveal if the different thyroid stimulators and thyroid inhibitors may possibly interact with specific regions of the human TSH receptor that confer their respective functional activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Factors↗
PubMed1993

Structure and localization of O- and N-linked oligosaccharide chains on basement membrane protein nidogen.

The carbohydrate content of mouse nidogen predicts the occupation of two N- and about seven O-linked acceptor sites. The corresponding oligosaccharides were examined by sequential exoglycosidase digestions. The data indicate N-linked substitutions by several bi-, tri- and tetraantennary complex types of oligosaccharides which are further modified by additional lactosamines and terminal alpha-galactose and/or sialic acid. Mannose-rich oligosaccharides were of low abundance. O-linked structures included a di- and tetrasaccharide core structure that were in addition sialylated and may be similar to structures found in fetuin. Evidence is provided that the two sequence-predicted asparagine acceptors are almost fully substituted. Sequence analysis of tryptic peptides identified Thr-271, Ser-303, Thr-309, Thr-317, Thr-320, Thr-892 and Thr-905 as the most likely sites for galactosamine substitutions. These residues are located in the flexible link connecting the N-terminal globular domains G1 and G2 of nidogen and at the border between the rod and the C-terminal globe G3. Four of them showed Pro in the -1 or +3 position. All these Ser, Thr and Pro residues but not the N-linked attachment sites are identical in human nidogen.

Amino Acid Sequence↗
PubMed1993

Prognostic implications of tumour marker analysis in non-seminomatous germ cell tumours with poor prognosis metastatic disease.

86 unselected patients with poor risk metastatic non-seminomatous germ cell tumours (NSGCT) treated from 1979 to 1990 at a single institution were reviewed with regard to the prognostic relevance of tumour marker analysis. The number of elevated tumour markers was not able to distinguish patients into prognostic subgroups. Pretreatment levels of human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) did not have a significant influence on clinical outcome. HCG and AFP half-life analysis during the first chemotherapy cycles also failed to define prognostic subgroups. If early deaths within 90 days after the onset of chemotherapy were excluded, patients with a half-life of HCG decline greater than 3.5 days tended to have a poorer prognosis which did not reach significance.

Adult↗
PubMed1993

Structure and binding properties of collagen type XIV isolated from human placenta.

Collagen XIV was isolated from neutral salt extracts of human placenta and purified by several chromatographic steps including affinity binding to heparin. The same procedures also led to the purification of a tissue form of fibronectin. Collagen XIV was demonstrated by partial sequence analysis of its Col1 and Col2 domains and by electron microscopy to be a disulphide-linked molecule with a characteristic cross-shape. The individual chains had a size of approximately 210 kD, which was reduced to approximately 180 kD (domain NC3) after treatment with bacterial collagenase. Specific antibodies mainly to NC3 epitopes were obtained by affinity chromatography and used in tissue and cell analyses by immunoblotting and radioimmunoassays. Two sequences from NC3 were identified on fragments obtained after trypsin cleavage. They were identical to cDNA-derived sequences of undulin, a noncollagenous extracellular matrix protein. This suggests that collagen XIV and undulin may be different splice variants from the same gene. Heparin binding was confirmed in ligand assays with a large basement membrane heparan sulphate proteoglycan. This binding could be inhibited by heparin and heparan sulphate but not by chondroitin sulphate. In addition, collagen XIV bound to the triple helical domain of collagen VI. The interactions with heparin sulphate proteoglycan and collagen VI were not shared by the NC3 domain, or by reduced and alkylated collagen XIV. No or only low binding was observed for collagens I-V, pN-collagens I and III, and several noncollagenous matrix proteins, including laminin, recombinant nidogen, BM-40/osteonectin, plasma and tissue fibronectin, vitronectin, and von Willebrand factor. Insignificant activity was also shown in cell attachment assays with nine established cell lines.

Amino Acid Sequence↗
PubMed1993

Inhibition of functional and immunological responses to thyroid-stimulating antibodies from patients with Graves' disease by blockade of the thyrotropin receptor.

Thyrotropin (TSH) receptor is the main autoantigen and the target of thyroid-stimulating antibodies in Graves' disease. In the present studies, in order to shed further light on the role of TSH receptor in thyroid autoimmune disease, we investigated the effects of TSH receptor blockade on functional and immunological responses to thyroid stimulation by Graves' immunoglobulins in the nude mouse bearing human thyroid transplants. Injecting the nude mice with purified Graves' immunoglobulins G resulted in a dose-dependent stimulation of thyroid hormone production, an inducement of cellular hypertrophy of transplant thyrocytes, and an expression of the HLA-DR antigen by up to 75% of the transplant thyroid follicular cells. Treatment of the animals with the TSH receptor antagonist asialoagalacto-hCG was able to inhibit the stimulation by Graves' immunoglobulins G of thyroxine production, cellular hypertrophy of transplant thyrocytes, and HLA-DR expression by thyroid follicular cells in the human transplants. The present data provide direct evidence for an involvement of the human TSH receptor in mediating both the functional disturbance (hyperthyroidism) and the immunological disorder in Graves' disease and add further support to the concept of using TSH receptor antagonists in the management of the disease.

Animals↗
PubMed1993

The reversibility of alcoholic brain damage is not due to rehydration: a CT study.

Alcoholic brain damage is reversible when the patients are continually abstinent. An increase of brain water content was the putative explanation for this phenomenon. We tested the rehydration hypothesis using CT density measurements in 29 alcohol-dependent male inpatients. During a 5-week period of controlled abstinence, CT density measures did not decrease in any of the investigated regions of the brain as one would expect with an increase in brain water. Although the volumetry of the ventricular system and the subarachnoidal spaces revealed a significant reduction of CSF volume, we found a slight increase in CT density measures. Thus, our results are in contradiction to the rehydration hypothesis. Under discussion is whether neuronal plasticity might be the explanation of the reversibility of alcoholic brain damage in abstinent patients.

Adult↗
PubMed1993

Multiple binding of type 3 streptococcal M protein to human fibrinogen, albumin and fibronectin.

M proteins are major virulence factors of group A streptococci which enable the bacteria to resist phagocytic attack. Their binding capacity for different plasma proteins seems to be one reason for the antiphagocytic activity of M protein. In the present study we demonstrate that M3 protein, isolated from the streptococcal culture supernatant of strain 4/55, and the recombinant form (rM3), purified from an E. coli lysate after cloning in phage lambda-EMBL3, show a multiple binding to fibrinogen, albumin and fibronectin in Western blot and dot binding assays. Binding of M3 protein to the multifunctional extracellular matrix and plasma protein fibronectin may not only influence phagocytosis but may also contribute to the adherence of these bacteria to endothelial and epithelial cells.

Amino Acid Sequence↗
PubMed1993

Extrapituitary effects of corticotropin-releasing hormone and thyrotropin-releasing hormone.

Besides their regulation of the pituitary-adrenal and pituitary-thyroidal axis, respectively, the neurohormones CRH and TRH act within the central nervous system to evoke and modulate a number of behavioral and physiological processes. In particular, an increase in the sympathetic nervous system and respiratory activity has been observed. The data communicated in this review article emphasize the role of these neurohormones with regard to the neuroendocrine regulation of the autonomic nervous system, sleep and cognitive performance. Moreover, a possible therapeutic role is suggested by the beneficial effects in patients at risk of hypoventilation-associated disorders.

Animals↗
PubMed1993

Variants of human chorionic gonadotropin from pregnant women and tumor patients recognized by monoclonal antibodies.

In biological fluids, hCG and its free alpha- (hCG alpha) and beta-subunits (hCG beta), occur in multiple forms. These various forms differ at the molecular level primarily in glycosylation, but also differ in protein backbone modifications corresponding to the urinary low molecular weight fragment of the hCG beta-subunit (beta-core fragment). This microheterogeneous nature can be demonstrated by isoelectric focusing in which variants are separated into bands with different isoelectric points (pI). To determine whether such isoelectric variants differ in antigenicity and consequently might escape immunoassay detection due to overspecificity of monoclonal antibodies (MCA), urinary pregnancy hCG (NIH, CR123) and tumor hCG preparations, such as a tumor-specific acidic variant of hCG (hCGav) and the hCG beta-core fragment, were separated by isoelectric focusing in the absence or presence of 8 M urea, or by sodium docedyl sulfate-polyacrylamide gel electrophoresis and enzymatically immunostained using an MCA panel directed against 17 different hCG epitopes. MCA against 14 different epitopes accessible on holo-hCG recognized all pI variants of pregnancy holo-hCG or tumor-derived hCGav, as was true for the three MCA recognizing epitopes hidden on holo-hCG but accessible on the free subunits after hCG dissociation by urea. We conclude that each individual pI-isoform of holo-hCG and its free subunits expresses the entire set of epitopes recognized by our MCA panel. The carbohydrate moieties that form a biochemical basis for hCG heterogeneity seem to be neither of major antigenic relevance, nor are they structurally related to any particular epitope. Thus, various glycosylation forms of hCG, hCG alpha, hCG beta, and hCG beta-core in normal as well as in pathological samples should safely be detectable and measureable by immunoassays employing MCA with appropriate subunit specificity.

Antibodies, Monoclonal↗
PubMed1993

Identification of porcine oocyte 55 kDa alpha and beta proteins within the zona pellucida glycoprotein families indicates that oocyte sperm receptor activity is associated with different zone pellucida proteins in different mammalian species.

Porcine zona pellucida (pZP) glycoprotein 55 kDa is composed of two core polypeptides, denominated alpha and beta. Sperm receptor activity has been shown to be associated with the oligosaccharide structures attached to the pZP55 alpha component. Here, we report a simple one-step HPLC procedure for the isolation of the alpha- and beta-components of the 55 kDa pZP proteins after enzymatic partial deglycosylation. N-Terminal sequence and protein chemical analysis of native proteins and of internal peptides from the alpha and the beta forms has established their homology with the rabbit 55 kDa zona pellucida glycoprotein and mouse ZP3, respectively. This, in turn, is relevant for a standardization of the ZP nomenclature in mammalian species. Moreover, our results imply that the sperm receptor activity in diverse mammalian species reside on oligosaccharide chains attached to nonhomologous zona pellucida glycoproteins. We hypothesize that acquisition of species-specific activity on the oocyte zona pellucida may thus be related to a species-specific glycosylation process.

Amino Acid Sequence↗
PubMed1993

Dynamical properties of the sleep EEG in different frequency bands.

The information concerning the dynamic behavior of the sleep process gained by the usual evaluation of sleep EEGs according to the criteria of Rechtschaffen and Kales is limited. Therefore a new methodical approach is presented, which is a special case of spectral analyzed data processing. After digital band-pass filtering of the sleep EEG the root-mean-square (RMS) value of successive 20 s EEG epochs is calculated in defined frequency ranges. This procedure ensures to take into account the influence of the phase relation between different frequency components. The temporal course of these RMS values during the night reveals smooth curves with continuous transitions between different sleep states. In all frequency bands slow oscillations according to the sleep cycles are observable. Whereas the slow frequency bands have a temporal course with local maxima during non-REM and local minima during REM sleep, the fast frequency bands beta and gamma show the opposite behavior revealing higher RMS values during REM sleep. The relationship between the activities in different frequency bands is evaluated calculating the cross correlation coefficient. Taken together the procedure allows an objective and automated quantitative analysis of the sleep EEG. The main advantage of this approach is the characterization of the sleep cycle as a dynamic and continuous process. Compared to the classical analysis it provides a more detailed analysis of the sleep process, especially concerning the dynamics and microstructure of sleep.

Adult↗
PubMed1993

Clinical use of HCG and hCG beta determinations.

Recent advances in our understanding of hCG/hCG beta synthesis by trophoblastic and nontrophoblastic tissues together with improved techniques for measuring hCG have helped to define the role of hCG as a clinical marker. HCG determination by sensitive immunometric assay enables detection of hCG immunoreactivity in normal men and women. It facilitates early detection of normal pregnancy and significantly contributes to the diagnosis of various pregnancy-related disorders, such as ectopic pregnancy, spontaneous abortion, hydatidiform mole, choriocarcinoma or Trisomy 21. Further, determination of this marker is immensely helpful to guide curative intervention in testicular cancer. For diagnosis and follow-up of patients with testicular cancer, a method measuring both hCG and hCG beta or separate methods for each component are recommended, because a significant portion of seminoma exclusively secrete free hCG beta. Also, hCG beta production by other than trophoblastic malignancies has been well recognized. A possible clinical use of hCG beta as a marker of cancers of the bladder, pancreas or biliary tract is currently debated.

Biomarkers, Tumor↗
PubMed1993

Structural basis of beta 1 integrin-mediated cell adhesion to a large heparan sulfate proteoglycan from basement membranes.

In a cell attachment assay, several cell lines were found to adhere and spread on heparan sulfate proteoglycan purified from a basement membrane-producing tumor. This adhesion was clearly distinct from that on laminin. Cell adhesion to the proteoglycan was completely inhibited by three different antibodies against integrin beta 1 subunit, while inhibitory antibodies against beta 3 and alpha 2 to alpha 6 subunits were without strong effects. Removal of heparan sulfate from the proteoglycan diminished cell attachment, but addition of heparin to the cells did not affect adhesion to the proteoglycan. This suggests that both the heparan sulfate side chains and core protein structures are required for efficient cell adhesion. Studies with proteolytic fragments and synthetic RGD peptides showed that the single RGD sequence of mouse proteoglycan is not involved in cellular recognition. Characterization of fragments also allowed to localize cell adhesion and heparan sulfate attachment sites to the same 160 kDa core protein structure but not to fragments derived from the N-terminal portion of the proteoglycan.

Amino Acid Sequence↗
PubMed1993

[Community based management of alcohol dependent patients. Evaluation of a combined inpatient and ambulatory treatment concept].

For a long time, the standard treatment for alcoholics in Germany consisted of a six month inpatient treatment period. Only recently, shorter treatment modalities with more emphasis on outpatient treatment were proposed. We evaluate a community based treatment model which combines a six week inpatient period with one year of outpatient treatment. During eight years, we saw 790 patients. After one year, 68% were globally improved. Ten years after treatment half of the 1976 sample were abstinent. Thus, a subgroup of alcoholics seem to benefit from community based programs. They are characterized by fair social adaptation and the willingness of their relatives to actively participate in the treatment.

Adult↗
PubMed1993

Standardization of protein immunoprocedures. Choriogonadotropin (CG).

The objectives of this report is to improve the quality of immunochemical determinations of proteins. Procedures for determination of the various molecular forms hCG were chosen as the subject of a detailed study, with the aim as using this report as a model for similar future projects. The aim of this undertaking is to improve the reliability and reproducibility of the results and, as a result of this, to enhance the clinical usefulness of hCG determinations. The following means will be used to achieve these goals: (a) establishing uniform nomenclature and abbreviations for various molecular forms of hCG, (b) preparation of new calibrators for these and establishing of methods for determining the amount of substance concentration in mol/L, (c) improving quality assessment materials and procedures, (d) definition of methods for characterization of hCG measurement procedures.

Antibody Specificity↗
PubMed1993

[Methanol level and methanol elimination in alcoholic patients].

A total of 54 male alcoholics aged between 26 and 57 years who had been admitted in an intoxicated state to a psychiatric hospital for acute care and subsequent detoxification were included in the study. The blood ethanol concentration (BEC) and serum methanol concentration (SMC) at the time of admission (n = 49) and the methanol elimination curve during ethanol elimination (n = 19) and after the ethanol concentration had fallen to zero (n = 4) were investigated. On admission, the BEC ranged from 0.21 g/kg to 3.26 g/kg and the SMC ranged from 5 mg/kg to 44 mg/kg. The gamma-alcoholics (n = 28) exhibited higher ethanol concentrations than the delta-alcoholics (n = 11) but no difference was found in the methanol concentrations. The methanol level was found to be related to the ethanol level in gamma-alcoholics (r = 0.671; p < 0.001), but not in d-alcoholics (r = 0.215; p > 0.05). The methanol content of the most recently consumed and generally preferred type of alcoholic beverage was found to influence the SMC in all the alcoholics. The SMC did not fall during ethanol oxidation (BEC > 0.2g/kg). After the ethanol concentration had fallen to zero, methanol elimination was found to follow first order kinetics; the elimination constants ranged from 0.592 h-1 to 0.209 h-1, corresponding to elimination half-life values of 1.2 h to 3.3 h. No differences were found between these values and those of non-alcoholic subjects.

Adult↗