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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 163 records · Page 9Linked to original sources
PubMed1999

The amino acid sequence of ovocleidin 17, a major protein of the avian eggshell calcified layer.

The amino acid sequence of ovocleidin 17, a major protein of the chicken eggshell calcified layer, contains 142 amino acids including 2 phosphorylated serines. Data base searches show that ovocleidin belongs to a heterogeneous group of proteins consisting of a single C-type lectin domain (CTL). The most similar sequences with an average of 30% identical amino acids were those of pancreatic stone protein (lithostathine) and lectins and anticoagulant proteins from snake venom.

Amino Acid Sequence↗
PubMed1999

Treatment outcome in alcoholism - a comparison of self-report and the biological markers carbohydrate-deficient transferrin and gamma-glutamyl transferase.

The primary source for evaluating treatment outcome in alcoholism is usually verbal self-report. Because the validity of self-report is often doubted, more objective markers for treatment outcome are needed. In this study, we compared self-report data from 238 male alcohol-dependent patients participating in a combined 6-week inpatient followed by a 1-year outpatient treatment program with the biological markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT). According to self-report, over 70% of the patients had a positive treatment outcome (57% abstinence, 16% intermediate relapse). These results are supported by the general reduction of CDT and GGT during the treatment period (p < 0. 001). When we performed a cross-sectional analysis at 6 months during the outpatient program, there was a high consistency of self-report data with the biological markers (CDT 93%, GGT 91%, CDT/GGT 85%). Our results support the hypothesis that in abstinence- oriented treatment programs, self-reports are valid and can be used as the basis of measurement for treatment outcome.

Adult↗
PubMed1999

Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group.

OBJECTIVE: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas. METHODS: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test. RESULTS: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result. CONCLUSIONS: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum.

Biomarkers, Tumor↗
PubMed1999

Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease.

Detection of autoantibodies to the TSH receptor (TSH-R) in Graves' disease has found widespread use in clinical routine and is performed mostly by commercial RRAs measuring TSH binding inhibitory activity. We report in this study on a second generation TSH binding inhibitory assay using the human recombinant TSH-R with two major improvements: 1) superior diagnostic sensitivity for Graves' disease, and 2) for the first time, nonradioactive and radioactive coated tube (CT) technology. Full-length human recombinant TSH-R was expressed in the K562 leukemia cell line and grown in suspension at a high density. A murine monoclonal antibody was selected for binding to the native TSH-R without interfering with autoantibodies or TSH and was coated to polystyrene tubes. After detergent extraction, TSH-R was affinity immobilized on antibody-coated tubes. The binding of TSH to the TSH-R could be demonstrated by the addition of 125I- or acridinium ester-labeled bovine TSH, and this binding could be inhibited by sera from patients with Graves' disease up to 95%. Subsequently, these novel assays, a CT RRA and a CT luminescence receptor assay, were compared to the conventional RRA based on porcine antigen in a blinded clinical multicenter trial. Sera from 328 patients with Graves' disease (86 untreated, 116 treated, and 126 in remission) and 520 controls (comprised of healthy blood donors and patients with autoimmune diseases or goiter) were tested in all 3 assays. Receiver-operating characteristic plot analysis resulted in a specificity of 99.6% with a sensitivity of 98.8% for both CT assays, compared to 99.6% specificity and 80.2% sensitivity for the conventional RRA (P < 0.001). In all 3 groups of patients with Graves' disease, the 2 CT assays were significantly more sensitive for the disease than the conventional assay, without loss of specificity in the control groups. This increase in sensitivity and the nonradioactive or radioactive CT format constitute a significant improvement over the currently available assays.

Adolescent↗
PubMed1999

Localized proton magnetic resonance spectroscopy of the cerebellum in detoxifying alcoholics.

An increased daily alcohol consumption results in neurological symptoms and morphological central nervous system changes, e.g. shrinkage of the frontal lobes and the cerebellar vermis. Brain shrinkage can be due to neuronal loss, gliosis, or alterations of (cell) membrane constitutes/myelin. Neuronal, glial, and metabolic changes can be measured in vivo with proton magnetic resonance spectroscopy. A total of 11 alcoholics and 10 age-matched volunteers were examined by magnetic resonance imaging and localized magnetic resonance spectroscopy at an echo time of 135 and 5 msec. Peak integral values were calculated for N-acetylaspartate (NAA), choline (Cho), myo-inositol (ml), glutamate/glutamine (Glx), and normalized to phosphocreatine/creatine (Cr). Patients had a significant shrinkage of the cerebellar vermis. NAA/Cr and Cho/Cr ratios were reduced in both sequences, but the NAA/Cr reduction was only significant in long echo time, although the Cho/Cr reduction was significant in short echo time. The ml/Cr and Glx/Cr ratios did not show any significant difference between volunteers and patients. The decrease of NAA/Cr in alcohol dependent patients is consistent with neuronal loss. The Cho/Cr decrease and an unchanged ml/Cr may reflect cell membrane modification or myelin alterations in alcohol-dependent patients. These changes lead to brain shrinkage, although hydration effects and gliosis are less likely.

Adult↗
PubMed1999

[Etiology and pathophysiology of Graves' disease].

Infectious agents are considered as etiologic factors for the onset of Graves' disease, while psychosocial stress and smoking may amplify the pathogenic cascade. Furthermore, smoking increases the risk of developing Graves' ophthalmopathy. Occasional evidence indicates that the autoimmune process may primarily be induced by foreign antigens, leading to the synthesis of antibodies which, in part, cross-react with thyrocytic TSH receptors. Once initiated, autoimmunity appears sustained within the thyroid by the cooperation of immunomodulated thyrocytes and antigen-presenting dendritic cells, which may, moreover, cause humoral responses against further thyrocytic antigens. Owing to a local increase in cytokine and integrin expression, lymphocytes and monocytes are attracted to the organ. The synthesis of autoantibodies is mainly propagated by T-helper-2 cells, while, at the same time, T-suppressor cells appear to be functionally deficient. Proof for this hypothetical scenario may allow for novel immunotherapeutic onsets in the near future.

Animals↗
PubMed1998

[Non-thyroid illness" or changed thyroid hormone parameter syndrome with non-thyroid illnesses].

BACKGROUND: The multiple effects of systemic illness on thyroid economy are commonly referred to "non-thyroidal illness" (NTI) or "sick euthyroid syndrome". The various aspects of this common syndrome are summarized in this article. STUDIES: Results of the relevant studies published during the past 25 years were evaluated. The influence of the underlying illness and of drug administration was especially emphasized. RESULTS: The most common abnormalities in NTI are 1. the "low-T3 syndrome" due to a decreased T3 generation from T4 by a reduced activity of 5'-deiodinase (a selenoprotein); 2. the "low-T3 low-T4 state", which is associated with a poor prognosis. The low T4-levels are related to a binding inhibitor that displaces T4 from its binding proteins. However, there exists some controversy regarding the character of this binding inhibitor. 3. The high-T4 state is often found in acute psychiatric and liver diseases. The nutritional status of the patients and drugs known to influence thyroid hormone parameters have to be considered when patients with NTI are evaluated. Some difficulties may arise, when there is evidence of coexisting thyroid disease. Here aside from further biochemical evaluation such as thyroid antibodies, thyroid ultrasound and a thyroid scan have to be performed. CONCLUSION: NTI is associated with various alterations in thyroid hormone parameters when no intrinsic thyroid hormone disease exists. The severity of NTI reflects clinical outcome and clinical amelioration is associated with normalization of thyroid hormone parameters. There is no need for specific therapeutic intervention such as the administration of thyroid hormones in patients with the various forms of the NTI-syndrome.

Diagnosis, Differential↗
PubMed1998

Inhibition of glycosaminoglycan modification of perlecan domain I by site-directed mutagenesis changes protease sensitivity and laminin-1 binding activity.

Glycosaminoglycan attachment to perlecan domain I (173 residues) was completely prevented by site-directed mutagenesis of Ser-65, Ser-71 and Ser-76 as shown by recombinant production in mammalian cells. This did not interfere with the proper folding of the domain's SEA module but enhanced its sensitivity to neutral proteases. Lack of substitution also abolished binding to the two major heparin binding sites of laminin-1.

Amino Acid Sequence↗
PubMed1998

Amino-acid sequence and three-dimensional structure of the Staphylococcus aureus metalloproteinase at 1.72 A resolution.

BACKGROUND: Aureolysin is an extracellular zinc-dependent metalloproteinase from the pathogenic bacterium Staphylococcus aureus. This enzyme exhibits in vitro activity against several molecules of biological significance for the host, indicating that it is involved in the pathology of staphylococcal diseases. RESULTS: Here we report the amino-acid sequence and inhibitor-free X-ray crystal structure of aureolysin, a member of the thermolysin family of zinc-dependent metalloproteinases. This enzyme, which binds one zinc and three calcium ions, comprises a single chain of 301 amino acids that consists of a beta-strand-rich upper domain and an alpha-helix-rich lower domain. CONCLUSIONS: The overall structure of aureolysin is very similar to that of the other three members of this family whose structures are known - thermolysin (TLN) from Bacillus thermoproteolyticus, neutral protease (NP) from Bacillus cereus and elastase (PAE) from Pseudomonas aeruginosa. But an important difference has been encountered: in contrast to what has been observed in the other three members of this family (TLN, NP and PAE), inhibitor-free aureolysin displays a 'closed' active site cleft conformation. This new structure therefore raises questions about the universality of the hinge-bending motion model for the neutral metalloproteinases.

Amino Acid Sequence↗
PubMed1998

Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin.

The C-terminal domain NC1 of mouse collagen XVIII (38 kDa) and the shorter mouse and human endostatins (22 kDa) were prepared in recombinant form from transfected mammalian cells. The NC1 domain aggregated non-covalently into a globular trimer which was partially cleaved by endogenous proteolysis into several monomers (25-32 kDa) related to endostatin. Endostatins were obtained in a highly soluble, monomeric form and showed a single N-terminal sequence which, together with other data, indicated a compact folding. Endostatins and NC1 showed a comparable binding activity for the microfibrillar fibulin-1 and fibulin-2, and for heparin. Domain NC1, however, was a distinctly stronger ligand than endostatin for sulfatides and the basement membrane proteins laminin-1 and perlecan. Immunological assays demonstrated endostatin epitopes on several tissue components (22-38 kDa) and in serum (120-300 ng/ml), the latter representing the smaller variants. The data indicated that the NC1 domain consists of an N-terminal association region (approximately 50 residues), a central protease-sensitive hinge region (approximately 70 residues) and a C-terminal stable endostatin domain (approximately 180 residues). They also demonstrated that proteolytic release of endostatin can occur through several pathways, which may lead to a switch from a matrix-associated to a more soluble endocrine form.

Amino Acid Sequence↗
PubMed1998

The N-terminal globular domain of the laminin alpha1 chain binds to alpha1beta1 and alpha2beta1 integrins and to the heparan sulfate-containing domains of perlecan.

The N-terminal domains VI plus V (62 kDa) and V alone (43 kDa) of the laminin alpha1 chain were obtained as recombinant products and shown to be folded into a native form by electron microscopy and immunological assays. Domain VI alone, which corresponds to an LN module, did not represent an autonomously folding unit in mammalian cells, however. Fragment alpha1VI/V, but not fragment alpha1V, bound to purified alpha1beta1 and alpha2beta1 integrins, to heparin, and to heparan sulfate-substituted domains I and V of perlecan. This localized the binding activities to the LN module, which contains two basic sequences suitable for heparin interactions.

Animals↗
PubMed1998

Conformational constraints for protein self-cleavage in the proteasome.

The proteasome is the central enzyme of protein degradation in the cytosol and the nucleus. It is involved in the removal of abnormal, misfolded or incorrectly assembled proteins, in the processing or degradation of transcriptional regulators in stress response, in degradation of cyclins in cell-cycle control, in the destruction of transcription factors or metabolic enzymes in cell differentiation and metabolic response, and in MHC class I mediated cellular immune response. By the analysis of the crystal and molecular structures of the 20 S proteasomes from the archaeon Thermoplasma acidophilum and from yeast it was shown that the beta-type subunits in which the proteolytic activities reside are members of the N-terminal nucleophile (Ntn) protein family. They are synthesized as proproteins and become active by autoprocessing at a Gly-1-Thr1 bond. The Thr1Ala mutant of subunit beta1/Pre3 of the 20 S proteasome from yeast is unable to autolyse. Its crystal and molecular structure at 2.2 A resolution described here shows that the pro-segment adopts a well-defined gamma-turn conformation at Gly-1 and provides a first view at an autolysis site in Ntn hydrolases. The Gly-1 carbonyl oxygen displays two hydrogen bonds. The modelled Thr1 side-chain is located above the gamma-turn bulge such that addition of its nucleophilic hydroxyl group to the electrophilic Gly-1 carbonyl carbon atom may proceed by very small motions. The pro-segment binding site and the catalytic site provide a rigid structural framework and appropriate hydrogen bond donors for this reaction. The same structure also supports addition of the Thr1 hydroxyl group to the carbonyl carbon atom of Leu-2 as a model for the first step in substrate hydrolysis by the proteasome.

Archaeal Proteins↗
PubMed1998

Structural analysis and proteolytic processing of recombinant G domain of mouse laminin alpha2 chain.

Four individual LG modules from the C-terminus of the laminin alpha2 chain (LG1, LG2, LG4 and LG5) and combinations of these modules were prepared as recombinant products from transfected mammalian cells. This demonstrated that LG modules represent autonomously folding protein domains. Successful production depended on proper alignment of module borders and required a sequence correction at the C-terminus which added an extra cysteine. The LG modules were glycosylated and shown by electron microscopy to have a globular shape, indicating proper folding. Evidence is provided for the splicing of a 12 bp exon in LG2, although this did not impair folding. Proteolytic cleavage at the C-terminus of a basic sequence was observed close to the N-terminus of LG3. A similar processing also occurs in tissue-derived laminin-2 and -4 which contain the alpha2 chain.

Amino Acid Sequence↗
PubMed1998

Efficacy and safety of iodine in the postpartum period in an area of mild iodine deficiency.

BACKGROUND: Iodine deficiency (even moderate) plays a major role in pregnancy associated goiter development, which is only party reversible after pregnancy. The prevalence of post partum thyroiditis is reported to be slightly lower in areas of iodine deficiency. Thus iodine supplementation may be effective in decreasing pregnancy associated increase in thyroid volume, but enhances the risk of increasing the prevalence of thyroid dysfunction in the post partum period. Therefore, we evaluated the effect of iodine supplementation (with two different doses: 50 microg and 250 microg) on the prevalence of post partum thyroiditis and the decrease in thyroid volume up to 8 months post partum in an area of mild iodine deficiency. PATIENTS AND METHODS: Thyroid volume of 56 women was evaluated 5 days and 3 months after delivery (study I). In an intervention study (Study II) 70 women were randomized to receive 50 or 250 microg of potassium iodide for a period of 8 months post partum beginning five days after delivery. Thyroid volume, the echogenecity of the thyroid gland, thyroid hormone parameters (T4, T3, fT4, TSH) and thyroid antibodies (TPO and Tg-Ab) were measured 5 days, 3 and 8 months after delivery. RESULTS: A total number of 11 women developed postpartum thyroid dysfunction: 4 women developed manifest thyroid dysfunction (3 hyperthyroidism and 1 hypothyroidism) 3 months post partum. The remaining seven had subclinical hypo- or hyperthyroidism. All changes were clinically mild and transient as evidenced by normalization of thyroid hormone parameters on reexamination at 8 months. Among the eleven, 6 women in the 50 microg iodine group and 5 women of the 250 microg iodine group developed thyroid dysfunction, suggesting that the iodine dose did not affect post partum thyroiditis. The administration of only 50 microg iodine was associated with a significant fall of thyroid size already 3 months after delivery (25.4 +/- 1.5 ml (mean +/- sem) to 18.2 +/- 1.25 p <0.001). The application of 250 microg iodine was equally effective. 8 months post partum a slight but further decrease could be demonstrated. On the other hand, in study I no significant reduction in thyroid volume was observed in women receiving no supplementary iodine (thyroid volume at delivery 29 +/- 2.2 ml; at 3 months 27.5 +/- 3.0 ml. CONCLUSION: The administration of supplementary iodine (up to 250 microg) to an unselected population, residing in an area of mild iodine deficiency, in the post partum period is save as indicated by a prevalence of 5.7% manifest thyroid dysfunction. These changes are clinically mild and transient. Even the amount of 50 microg of iodine supplementation seems to by very efficient in reducing pregnancy associated increments in thyroid volume.

Adult↗
PubMed1998

An analysis of the brain's transfer properties in schizophrenia: amplitude frequency characteristics and evoked potentials during sleep.

BACKGROUND: Classical analysis of spontaneous sleep electroencephalogram (EEG) in schizophrenia commonly reveals alterations of sleep continuity, number of awakenings, slow-wave sleep (SWS), and REM sleep compared to healthy controls; however, conventional analysis cannot help understand dynamic differences of the sleep EEG during different sleep stages. METHODS: We measured late components of auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) during different sleep stages of 11 schizophrenic inpatients and in a sex- and age-matched control group from scalp positions FZ, CZ, and PZ. According to linear system theory, we then computed the amplitude-frequency characteristic (AFC) from averaged AEPs and VEPs in different sleep stages. These AFCs describe the input-output relation of the system under study, leading to a characterization of the transfer properties of the schizophrenic brain during sleep. RESULTS: Significant differences could be found for the transfer properties during stage II and SWS between schizophrenics and controls. During REM a marked enhancement of theta resonance was seen in schizophrenics. CONCLUSIONS: The results of the present study point to highly different central nervous system transfer properties in schizophrenics and controls. Compared to previous investigations in depression, the results provide additional information for distinguishing schizophrenia and depression in EEG studies.

Adult↗
PubMed1998

Amino acid sequence, glycan structure, and proteolytic processing of the lectin of Vatairea macrocarpa seeds.

VML is a galactose-binding lectin isolated from Vatairea macrocarpa seeds. By SDS-polyacrylamide gel electrophoresis, VML is a glycoprotein composed of a major 32-34 kDa double band (alpha-chain) and minor 22 kDa and 13 kDa bands. N-terminal sequencing of electroblotted samples showed that the 22 and 13 kDa bands corresponded to C-(beta) and N-(gamma) terminal fragments of the alpha-chain, respectively. The primary structure of VML displays similarity with other leguminous lectins, particularly with Erythrina variegata, Robinia pseudoacacia and Sophora japonica lectins. VML is N-glycosylated at asparagine residues at positions 111 and 183 with one major glycan structure. Tandem mass spectrometry and methylation analysis indicated the presence of Manalpha1-6[(Manalpha1-3)(Xylbeta1-2)]Manbeta1-4 -GlcNAcbeta1-4(Fucalpha1-3)GlcNAc, a typical plant Nglycan. Equilibrium sedimentation analysis by analytical centrifugation showed that VML had a mass of 122-130 kDa, which did not change within the pH range 2.5-8.5. These data indicated that VML is a pH-independent homotetrameric protein and that a small proportion of the alpha-subunits is cleaved into noncovalently associated N- and C-terminal fragments. Mass spectrometric analysis suggested a mechanism for the proteolytic processing of VML. V. macrocarpa lectin contains a mixture of doubly (28,525 Da) and singly (27,354 Da) glycosylated alpha-chains. Deglycosylation of Asn-111 correlates with proteolytic cleavage of the Asn-114-Lys-115 bond yielding glycosylated gamma (residues 1-114, 12,304 Da) and nonglycosylated beta-(residues 115-239, 14,957 Da) chains. Some beta-chain molecules are further deglycosylated and N-terminally processed yielding products of molecular masses of 13,783 Da and 13,670 Da.

Amino Acid Sequence↗
PubMed1998

Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease.

Patients with chronic inflammatory bowel diseases (IBD) are at increased risk to develop osteopenia and osteoporosis. New parameters for the assessment of bone formation and especially bone resorption have significantly improved the diagnostic procedures to characterize bone metabolism. Biochemical characterization of bone turnover in IBD patients may provide important information about the pathogenesis of osteoporosis in this patient population. A cross-sectional study was performed. One hundred forty-nine patients (77 men, 52 premenopausal, and 20 postmenopausal women) with IBD (104 with Crohn's disease [CD] and 45 with ulcerative colitis [UC]) underwent clinical, osteodensitometric, and metabolic bone assessment. Bone mineral density was determined by dual energy X-ray absorptiometry. Bone formation (bone alkaline phosphatase), bone resorption (N-terminal telopeptide of type-I collagen, free desoxypyridinoline, total pyridinoline, and desoxypyridinoline), vitamin D, and parathyroid hormone were assessed. Thirty-six percent of patients with CD and 32% with UC showed osteopenia, 15% with CD and 7% with UC showed osteoporosis. Bone resorption was significantly increased in IBD patients compared to normal controls, whereas bone formation did not show a compensatory increase. Bone formation was even more suppressed in the subset of patients currently treated with corticosteroids. Our data confirm the high prevalence of osteopenia and osteoporosis reported in IBD patients. Furthermore, we provide evidence for an increased bone resorption accompanied by low bone formation in IBD patients. This imbalance of bone metabolism is likely to be one of the reasons for increased bone loss in IBD patients.

Absorptiometry, Photon↗