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Biomedical subjects

M Maier

Publications and source records attributed to M Maier.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of tissue kallikrein by protein C inhibitor. Evidence for identity of protein C inhibitor with the kallikrein binding protein.

We studied the inhibition of tissue kallikrein by protein C inhibitor (PCI), a relatively unspecific heparin-dependent serine protease inhibitor present in plasma and urine. PCI inhibited the amidolytic activity (cleavage of H-D-valyl-L-leucyl-arginine-p-nitroaniline) of urinary kallikrein with an apparent second order rate constant of 2.3 x 10(4) M-1 s-1 and formed stable complexes (85 kDa) with urinary kallikrein as judged from silver-stained sodium dodecyl sulfate-polyacrylamide gels. Complex formation was time-dependent and was paralleled by a decrease in the intensity of the main PCI protein band (Mr = 57,000) and an increase in the intensity of the lower Mr (54,000) PCI form (cleaved inhibitor). Heparin interfered with the inhibition of tissue kallikrein by PCI and with the formation of tissue kallikrein-PCI complexes in a dose-dependent fashion and completely abolished PCI-tissue kallikrein interaction at 300 micrograms/ml. This is in contrast to findings on the interaction of PCI with all other target proteases studied so far (i.e. stimulation of inhibition by heparin) but is similar to the reaction pattern of 125I-labeled tissue kallikrein with so called kallikrein binding protein described in serum and other systems. To study a possible relationship between PCI and this kallikrein binding protein we incubated 125I-labeled urinary kallikrein in serum and in PCI-immunodepleted serum in the absence and presence of heparin and analyzed complex formation using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In normal serum, formed complexes co-migrated with complexes of purified PCI and 125I-kallikrein and were less intense in the presence of heparin. No complex formation at all was seen in PCI-depleted serum. Our data indicate that PCI may be a physiologically important endogenous inhibitor of tissue kallikrein and provide evidence that PCI may be identical to the previously described kallikrein binding protein.

Amides↗
PubMed1992

Possible identity of kallikrein binding protein with protein C inhibitor.

Protein C inhibitor (PCI) inhibits tissue kallikrein by forming stable 1:1 complexes (k1 = 2.3 x 10(4)M-1s-1). Heparin inhibits the tissue kallikrein/PCI-interaction and complex formation of 125I-tissue kallikrein in serum. 125I-tissue kallikrein complexes formed in plasma can be immunoprecipitated with monoclonal anti-PCI IgG suggesting that PCI might be identical to the kallikrein binding protein described previously (J. Chao et al. 1986, Biochem. J. 239, 325-331).

Carrier Proteins↗
PubMed1992

Determination of human low molecular weight kininogen by immunoassay.

It was the aim of the present investigation to develop a convenient method for determination of human kininogens. Using mono- and polyclonal antibody preparations an ELISA-system for specific determination of LMWK could be developed. In addition, the specificity of the monoclonal antibody suggests that their epitope in HMWK and its heavy chain is different to that in LMWK.

Antibodies, Monoclonal↗
PubMed1991

[Pearson's syndrome. Pancytopenia with exocrine pancreatic insufficiency: new mitochondrial disease in the first childhood].

Pearson's syndrome is a lethal disorder of a still unknown cause, responsible for pancytopenia and exocrine pancreatic dysfunction in the first months of life. Permanent hyperlactacidemia and increased mitochondrial and cytoplasmic oxidoreduction ratios were observed in 6 unrelated children presenting with this disease. This led to study the oxidative phosphorylation in lymphocytes and thus to relate Pearson's syndrome to an enzymatic disease of the respiratory chain (NADH oxidase activity deficiency). The study of the mitochondrial genome allowed identifying major changes in mitochondrial DNA in all patients and all studied tissues. Thus, Pearson's syndrome is the first mitochondriopathy with a non neuromuscular expression reported to date.

DNA, Mitochondrial↗
PubMed1990

[Erythrocyte morphology in asymptomatic microhematuria: experimental studies and clinical significance].

Renal and postrenal origin of hematuria can be differentiated by analysis of the morphology of the erythrocytes in the urinary sediment. In order to investigate the mechanisms which cause the membrane changes in dysmorphic erythrocytes, indicating renal origin of bleeding, normal red blood cells were exposed in vitro to an osmotic environment similar to that of the nephron. Upon exposure of osmotically challenged erythrocytes to a hemolytic environment, 50 to 90% of the cells became dysmorphic in a time- and dose-dependent manner and were indistinguishable on light and electron microscopy from those obtained in vivo from a patient with proven glomerular microhematuria. The reliability of erythrocyte morphology in differentiating between renal and postrenal microhematuria was evaluated by performing microscopic analysis as the initial step in the investigation of 316 consecutive patients. In 123 patients with eumorphic red cells in their urine complete urological investigation revealed a postrenal source of bleeding in 85%. Out of 193 patients with dysmorphic erythrocytes, 132 were followed up for at least 2 years after only minimal diagnostic evaluation. An additional postrenal source of bleeding developed in two patients, which was easily diagnosed by the change in erythrocyte morphology. Our studies, representing experience over 6 years with asymptomatic microhematuria, show that microscopic examination of erythrocyte morphology as initial diagnostic step is a safe, inexpensive and efficient method which renders invasive investigations superfluous in the majority of patients.

Adolescent↗
PubMed1990

[Myelodysplastic syndrome--a retrospective study of 38 patients].

38 patients diagnosed as myelodysplastic syndrome (MDS) were retrospectively evaluated for clinical course, prognostic factors, diagnostical power of cytology and histology and relevance of hypoplastic myelodysplastic syndrome. Median observation time was 14.5 (0 to 104) months. 15 patients (40%) developed an acute myelogenous leukemia after two to 67 (median eleven) months. Prognosis was negatively influenced by age, suggested myelotoxic agents in prior history and leukemia in first-grade relatives as well as ESR greater than or equal to 30 mm Hg (first hour). FAB-classification and Bournemouth-score reflected prognosis in respect to survival time and development of an acute leukemia. Cytology and histology revealed contradictory results in four of 14 comparable cases (28.6%). Hypoplastic myelodysplastic syndrome was diagnosed by histology in seven out of eight cases. This entity showed significantly lower WBC-values and a considerable longer survival time.

Adult↗
PubMed1990

Release of [hydroxyproline3]-kinins by tissue kallikreins of pig, rat and man.

To determine the susceptibility of kininogens containing the recently described [Hyp3]-bradykinin moiety to cleavage by tissue kallikreins, we have studied the release of [Hyp3]-kinins from heat inactivated human plasma by purified tissue kallikreins. Kallikreins from man and pig were employed and compared with purified rat urinary kallikrein which is known to have a different cleavage specificity. Kinins released were separated by a modified reversed phase HPLC method and quantitated by bioassay and radioimmunoassay. Human urinary kallikrein and hog tissue kallikreins released 85-90% of the total kinins as Lys-bradykinin and 10-15% as [Hyp3]-Lys-bradykinin. In contrast, rat urinary kallikrein released 77% as bradykinin, 22% as [Hyp3]-bradykinin and negligible amounts of [Hyp3]-Lys-bradykinin from the identical substrate source indicating that rat tissue kallikreins prefer the Lys-Arg-bond within both unhydroxylated and hydroxylated kininogens. Therefore, hydroxylation of human kininogens apparently does not affect their ability to serve as substrates for tissue kallikreins with different cleavage specificities.

Animals↗
PubMed1989

Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria.

To assess the value of microscopic analysis of urinary erythrocyte morphology as the initial step in the investigation of patients with isolated symptomless microhaematuria, 316 consecutive patients were grouped according to whether they excreted eumorphic or mixed forms of erythrocytes or only dysmorphic forms. The former group was investigated fully, and urological disease was found in 85% of 123 patients. The 192 patients with exclusively dysmorphic erythrocytes in their urine and normal renal function (benign renal microhaematuria) were assigned to annual follow-up examinations of urinary red cell morphology and renal function, and subjected to invasive diagnostic procedures when a change was noted. In only 2 of the 132 patients followed up for at least 2 years did a new disease develop; this was easily identified at one of the annual examinations. Microscopic analysis of urinary erythrocyte morphology is therefore an effective method for identifying patients with symptomless microhaematuria needing specific diagnostic investigation.

Adolescent↗
PubMed1989

In vitro generation of dysmorphic erythrocytes.

In hematuria, dysmorphic red blood cells found in the urine sediment are known to indicate glomerular origin of bleeding. To better understand the mechanisms which might cause the typical membrane changes in dysmorphic erythrocytes in vivo, we have exposed normal human erythrocytes in vitro to an osmotic and enzymatic environment similar to that of the nephron. In addition, treated or untreated erythrocytes were exposed to a hemolytic environment. The morphology of the cells was evaluated by light and electron microscopy in comparison of that of dysmorphic erythrocytes obtained in vivo. Neither the passage of erythrocytes in sequence through various solutions each simulating the tubule fluid in a different part of the nephron, nor exposure to urinary or renal enzymes or to serum per se causes the typical membrane alterations. Upon exposure of passaged erythrocytes to a hemolytic environment, however, 50 to 90% of the cells become dysmorphic in a time and dose dependent fashion. By light and electron microscopy these dysmorphic erythrocytes obtained in vitro are indistinguishable from those obtained in vivo. In contrast, non-passaged red blood cells are not affected by the same hemolytic environment. We conclude that osmotically challenged erythrocytes exposed to a hemolytic environment develop dysmorphic membrane alterations.

Adult↗
PubMed1989

Regulation of plasminogen activation in isolated perfused rat kidney.

To better understand the mechanism and regulation of plasminogen activation within the kidney, the release and excretion of plasminogen activator activities was studied in the isolated perfused rat kidney in the absence and presence of plasminogen substrate. In the absence of plasminogen, the kidneys released a constant amount of plasminogen activator activity into both the urine and the perfusate. On continuous infusion of purified human plasminogen into the perfusate, the release of plasminogen activator activity into the urine slightly increased, and plasmin generated could be detected in both urine and perfusate. With the use of specific antibodies against the tissue-type (t-PA) and the urokinase-type plasminogen activator (u-PA), respectively, the activity in the perfusate could be identified as t-PA, whereas the activity in the urine could be ascribed to u-PA. A bolus injection of either antibody into the plasminogen-supplemented perfusion medium completely inhibited plasminogen activator activity and generation of plasmin in the vascular or tubular compartment. Furthermore, intrarenal inhibition of t-PA activity by the specific antibody significantly increased the concentration of plasminogen in the perfusate, indicating decreased consumption. This effect was accompanied by increased excretion of u-PA into the urine, suggesting that the availability of intact plasminogen in the renal circulation directly or indirectly might participate in the regulation of u-PA excretion into the urine.

Animals↗
PubMed1989

Acute myocardial infarction in pregnancy and puerperium.

Myocardial infarction during pregnancy and puerperium is very rare. Increased awareness of its possible occurrence is important for diagnosis. A young woman who developed acute myocardial infarction 14 days after labor is described. She had no coronary risk factors; coronary angiography was not done, but ergometric test involving maximal stress done 22 months after confinement did not reveal signs or symptoms of disease. An additional 62 women with myocardial infarction, 51 during pregnancy and 11 in puerperium, reported in the literature were reviewed. The following points were observed: (1) Hypertension was present in 25% of cases. (2) Four out of 6 coronary angiograms performed after the infarct were normal. (3) Fifteen patients died (24% mortality). (4) Coronary atherosclerosis was the main finding in 7 out of 9 post-mortem examinations.

Adult↗
PubMed1988

Correlation of two different assays for urinary kallikrein in normotensive and hypertensive subjects.

Possible differences in structure-function relationship of urinary kallikrein between normotensive and hypertensive individuals were analysed using two different assay systems which detect two distinct entities of the enzyme. A monospecific goat anti-human urinary kallikrein antibody was characterized by inhibition studies with the purified active enzyme and by trypsin activation of endogenous urinary prokallikrein. Analysis of the data revealed that the antibody is directed against active kallikrein by recognizing an epitope which is different from the catalytic site of the enzyme but which is being exposed together with the active site during trypsin activation of the proenzyme. A direct radioimmunoassay for urinary kallikrein was developed and correlated with the kinin generating activity of the enzyme by assessing endogenous active and trypsin activated kallikrein in the urine of normotensive and hypertensive subjects. Significant positive correlations were found between the two assays for both active and total kallikrein in normotensive and hypertensive subjects and the slopes of the respective regression lines were identical. These data do not provide evidence for a defective enzyme, a defective activation of the proenzyme or for the presence of an inhibitor of urinary kallikrein in essential hypertension.

Adult↗
PubMed1988

Identification of [hydroxyproline3]-lysyl-bradykinin released from human kininogens by human urinary kallikrein.

The types of kinins released from purified native, single chain human high and low molecular mass kininogens (HMMKs and LMMKs, respectively) by purified human urinary kallikrein were separated by reverse-phase HPLC and quantitated by the rat uterus bioassay. [Hyp3]-lysyl-bradykinin, a recently discovered kinin, represented up to 58% of the biological activity released from 4 individual HMMK preparations purified from 4 different healthy volunteers. In contrast, the majority of the biological activity released from LMMKs purified from pooled plasma was identified as Lys-bradykinin and [Hyp3]-lysyl-bradykinin represented only 6.4 +/- 3.8%. These findings indicate posttranslation hydroxylation of human kininogens and suggest a preference of HMMKs for this modification.

Amino Acid Sequence↗