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M Otte

Publications and source records attributed to M Otte.

At least 37 records · Page 2Linked to original sources
PubMed1993

A Kazal-type inhibitor with thrombin specificity from Rhodnius prolixus.

A thrombin-specific inhibitor with an apparent molecular mass of 11 kDa has been purified from the insect Rhodnius prolixus. Amino-terminal protein sequence analysis allowed the molecular cloning of the corresponding cDNA. The open reading frame codes for a protein of about 103 amino acid residues and displays an internal sequence homology of residues 6-48 with residues 57-101 indicating a two-domain structure. Based on the amino acid sequence the two domains exhibit high homology to protease inhibitors belonging to the Kazal-type family. Model building suggests that the first domain binds to the active site with residue His10 pointing into the specificity pocket. From gel filtration and tight-binding inhibition experiments the inhibitor appears to form 1:1 complexes with thrombin. Periplasma-directed heterologous expression of the rhodniin cDNA in Escherichia coli yields the intact thrombin inhibitor. Natural and recombinant rhodniin both display inhibition constants of about 2 x 10(-13) M.

Amino Acid Sequence↗
PubMed1993

Isolation, sequence analysis, and cloning of haemadin. An anticoagulant peptide from the Indian leech.

A slow, tight-binding inhibitor of thrombin with an apparent molecular mass of about 5 kDa has been isolated from Haemadipsa sylvestris, an Indian leech of the family of Haemadipsidae. The inhibitory activity, called haemadin, is thrombin specific since it does not inhibit other proteases like trypsin, chymotrypsin, factor Xa, or plasmin. NH2-terminal amino acid sequence analysis (residues 1-45) does not reveal any homology to known serine protease inhibitors, including the thrombin-specific inhibitor hirudin. The haemadin cDNA cloned by polymerase chain reaction techniques codes for a polypeptide of 57 amino acid residues preceded by 20 residues of a signal peptide sequence. A synthetic gene coding for the mature haemadin was expressed in Escherichia coli. Recombinant haemadin displays a similar inhibition constant and specific activity as its natural counterpart. Although there is no obvious sequence identity between haemadin and hirudin, both proteins seem to share common mechanisms for thrombin inhibition.

Amino Acid Sequence↗
PubMed1993

Anthranoid laxative abuse--a risk for colorectal cancer?

Anthranoid-containing laxatives--aloe, cascara, frangula, and rheum--may play a role in colorectal cancer. This risk is particularly important in view of the wide abuse of self administered laxatives for chronic constipation. There are data on the genotoxic potential of anthranoids and there is evidence of a tumourigenic potential in rodents. A case report and clinical-epidemiological studies have evaluated the cancer risk in patients who have abused anthranoid laxatives over a long period. Pseudomelanosis coli is a reliable parameter of chronic laxative abuse (> 9-12 months) and is specific for anthranoid drugs. In a retrospective study of 3049 patients who underwent diagnostic colorectal endoscopy the incidence of pseudomelanosis coli was 3.13% in patients without pathological changes. In those with colorectal adenomas, the incidence increased to 8.64% (p < 0.01), and in those with colorectal carcinomas it was 3.29%. This lower rate was probably caused by incomplete documentation of pseudomelanosis coli in those with carcinoma. In a prospective study of 1095 patients, the incidence of pseudomelanosis coli was 6.9% for patients with no abnormality seen on endoscopy, 9.8% (p = 0.068) for patients with adenomas, and 18.6% for patients with colorectal carcinomas. From these data a relative risk of 3.04 (1.18, 4.90; 95% confidence interval) can be calculated for colorectal cancer as a result of anthranoid laxative abuse.

Adenoma↗
PubMed1992

MR imaging of the normal shoulder: variants and pitfalls.

In 30 volunteers with normal shoulders, the following conclusions were made with regard to normal anatomic features at magnetic resonance (MR) imaging: (a) The supraspinatus tendon has low signal intensity, except for a 1-cm area with intermediate signal intensity in the region of the "critical zone." (b) The deltoid tendon attachment on the inferior surface of the acromion may simulate a subacromial spur if not imaged in continuity. (c) Fluid in the long head of the biceps tendon sheath is normal if not completely surrounding the tendon. (d) The anterolateral branch of the anterior humeral circumflex vessels in the proximal bicipital groove adjacent to the biceps tendon mimics fluid in the tendon sheath. (e) Continuity or obliteration of the subacromial-subdeltoid bursal fat plane is an unreliable diagnostic sign since the fat plane is often focally absent. (f) Fluid is not detected in subacromial-subdeltoid bursae. (g) Undercutting of the anterior glenoid labrum by hyaline cartilage or a closely apposed middle glenohumeral ligament may simulate an anterior labral tear.

Adult↗
PubMed1991

Probing the distance between the two binding sites of hirudin for its interaction with the active site and the fibrin(ogen)-binding site of alpha-thrombin.

The interaction of delta (Ser50)-hirudin with alpha-thrombin has been investigated. Deletion of Ser50 of r-hirudin caused a 2.7 fold increase of the Ki for its complex with alpha-thrombin. Determination of the rate constants kon and koff for complex formation showed that this effect was mainly due to a change in koff.

Amino Acid Sequence↗
PubMed1990

Dependence of serum erythropoietin level on erythropoiesis in leukemia.

The dependence of the serum erythropoietin (Epo) level on the blood hemoglobin concentration was compared in patients suffering from leukemia and ulcerative colitis. In leukemia, the level of immunoreactive and bioactive Epo was generally much higher than in ulcerative colitis at comparable degrees of anemia. The highest Epo values were found in patients with severe bone marrow insufficiency of erythropoiesis. These findings support the hypothesis that the plasma level of Epo depends not only on the hemoglobin concentration of the blood but is also influenced by the proliferative activity of the erythron.

Anemia↗
PubMed1989

Erythropoietin/haemoglobin relationship in leukaemia and ulcerative colitis.

The erythropoietin level was measured, by bioassay in polycythaemic mice, in the serum of anaemic patients suffering from different types of leukaemia. Comparative measurements were carried out in patients with ulcerative colitis. Serum erythropoietin was less well-correlated with the haemoglobin concentration in leukaemia than in ulcerative colitis. While serum erythropoietin did not exceed 200 mU/ml in patients with ulcerative colitis (lowest blood haemoglobin concentration 56 g/l), several of the leukaemic patients had serum erythropoietin levels above 500 mU/ml at comparable degrees of anaemia. Bone marrow biopsy showed that erythropoiesis was severely impaired in the leukaemic patients whose erythropoietin values were relatively high. These findings are in accord with the hypothesis that the plasma level of erythropoietin depends not only on the haemoglobin concentration of the blood but also on the bone marrow responsiveness to the hormone.

Adolescent↗
PubMed1988

Multicenter evaluation of a specific pancreatic isoamylase assay based on a double monoclonal-antibody technique.

Eleven evaluators from nine laboratories in five countries evaluated a new immunoinhibition method for pancreatic isoamylase determination that is as simple to perform as that for total amylase. The precision at low and intermediate activity concentrations was superior, and at high concentrations it equalled that of the wheat-germ inhibitor method. The test was linear to approximately 2000 U/L, depending on the instrumentation used. The percentage salivary isoamylase activities remaining in specimens after reaction with two monoclonal antibodies ranged from 2 to 4.4%. Comparative studies showed good correlation with the wheat-germ inhibitor (r greater than 0.978) and electrophoresis methods (r = 0.920). Hemolysis, lipemia, and bilirubinemia have no effect on results. Interlaboratory studies demonstrated excellent transferability of the method, if instruments are calibrated with the same calibrator. Reference intervals for pancreatic isoamylase are 13 to 64 U/L (25 degrees C), 13 to 83 U/L (30 degrees C), and 17 to 115 U/L (37 degrees C). A clinical evaluation of patients with acute pancreatitis showed that pancreatic isoamylase has a greater clinical sensitivity than total amylase.

Acute Disease↗
PubMed1987

[In vitro studies of pancreatic enzyme substitution].

In-vitro activity of 14 commercial pancreatin preparations, commonly used in the Federal Republic of Germany, were tested. All had been declared by their manufacturers to contain more than 6000 FIP (Fédération International Pharmaceutique) units of lipase and to be acid resistant. The declared lipase and amylase amounts were found to be present in 11 of the 14 preparations. Three of the 14 preparations, said to be acid resistant were found not to be so in buffer with falling pH values between 4.0 and 2.5, so that there occurred an, at times marked, loss of enzyme activity. Most noticeable was the poor solubility of most preparations at pH 6.6. Only three of the 14 liberated their total enzyme content within 60 minutes, as they should for theoretical reasons, based on the relatively short duodeno-cecal transit time.

Amylases↗
PubMed1987

Autoimmunity to pancreatic juice in Crohn's disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease.

The sera of 59 patients with Crohn's disease (CD) and of 46 patients with ulcerative colitis (UC) were tested for autoantibodies (Aab) by indirect immunofluorescence with modern histochemical techniques using 19 different human tissues as antigenic substrates. Control collectives consisted of 19 patients with coeliac disease and of 100 healthy subjects. It was possible to demonstrate a specific marker for CD: Aab against exocrine pancreas (Pab) were present in 39% of the CD sera (UC 4%, coeliac disease 0%, healthy controls 3%). High Pab titres were only detectable in CD sera (29%). The CD-related autoantigen was demonstrated to be a component of normal pancreatic juice. Pab in CD were fundamentally different from those sometimes occurring in chronic and acute pancreatitis. It is suggested that CD is caused by autoimmune reactions against a component of pancreatic juice. Pab in CD correspond to Aab against intestinal goblet cells (Gab), which occurred exclusively in UC (28%). Pab and Gab, but obviously none of the other Aab investigated in this study, are of diagnostic value in chronic inflammatory bowel disease.

Adult↗
PubMed1985

[Pancreatic secretion in domestic sprue].

Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

Adult↗
PubMed1984

[Autoantibodies against the exocrine pancreas and against intestinal goblet cells in the diagnosis of Crohn's disease and ulcerative colitis].

It was demonstrated by indirect immunofluorescence that Crohn's disease and ulcerative colitis are serologically distinct. In 59 patients with Crohn's disease, confirmed by endoscopy and histology, 23 (39%) had serum autoantibodies against exocrine pancreas; in 17 (29%) the titre was 1 : 100 or higher. In 46 patients with confirmed ulcerative colitis pancreas antibodies were demonstrated only twice, in 100 healthy control subjects only 3 times, with titres less than 1 : 100. Pancreas antibodies do not occur in high concentrations in pancreatitis; titres higher than 1 : 100 therefore suggest Crohn's disease. The pancreas antibodies of patients with Crohn's disease were predominantly immunoglobulins IgA and IgG, twice they were IgD and once IgM, never IgE. In 6 patients the pancreas antibodies fixed complement. Autoantibodies against intestinal goblet cells were found only in patients with ulcerative colitis (13 of 46 = 28%). The titres range was from 1 : 10 to 1 : 1000. The goblet-cell antibodies consisted only of IgA and IgG, never reacting with complement. These results indicate that determining pancreas and goblet-cell antibodies alone will make it possible to diagnose either Crohn's disease or ulcerative colitis in more than a quarter of patients with chronic inflammatory intestinal disease.

Adolescent↗