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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 199 records · Page 11Linked to original sources

Molecular oxygen and the state of geometric isomerism of intermediates are essential in the carotene desaturation and cyclization reactions in daffodil chromoplasts.

The membrane-bound carotenogenic reaction sequence in daffodil chromoplasts can be subdivided in vitro into three reaction segments by varying the incubation parameters O2 and light. In the first segment, 15-cis-phytoene is desaturated to 15-cis-zeta-carotene (trans elimination of hydrogen) in the dark and in the presence of O2 as an essential cofactor. A photoisomerization of the 15-cis double bond of the accumulated zeta-carotene to trans is the prerequisite for the function of the second segment, the desaturation to 7,9,9',7'-tetra-cis-lycopene (prolycopene, cis elimination of hydrogen). The role of O2 as an electron acceptor is discussed and evidence for an oxidoreductase acting as a redox mediator between the desaturase (forming the polyene chromophore) and O2 is presented. A certain analogy to the desaturation of stearoyl-carrier protein, which also occurs in plastids, is proposed. The third segment, the cyclization of prolycopene, is active only in the absence of O2 and involves additional cis-trans isomerization reactions.

Carbon Radioisotopes↗

Effects of penicillins and 6-aminohexanoic acid on the kinetics of human plasmin.

Human plasmin activity is inhibited by various penicillins in a dose-dependent manner. Ampicillin and cloxacillin produce a 50% inhibition of the globinolytic activity of plasmin at 4.5 and 5.3 mM respectively. A lower inhibitory capacity is displayed by carbenicillin. Assay of plasmin by its amidolytic activity on D-valyl-L-leucyl-L-lysine p-nitroanilide dihydrochloride showed that ampicillin at a concentration producing half-maximal inhibition converted the hyperbolic activity-substrate concentration curve into a sigmoidal curve. A similar conversion occurred in the presence of ampicillin when plasmin was assayed with an alternative chromogenic substrate, L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride 6-Aminohexanoic acid at 7.5 microM abolished the inhibition of plasmin induced by ampicillin. The present observations suggest that ampicillin interacts with plasmin at a regulatory site different from the active site of the enzyme. The effect of 6-aminohexanoic acid indicates that the lysine-binding site may be part of a regulatory site. It is possible that modulation of plasmin activity by ligands plays a role in the control of fibrinolysis.

Aminocaproates↗

Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin.

Immobilized vitronectin was found to bind both purified plasminogen activator inhibitor type 1 (PAI-1) and the PAI-1 in conditioned culture medium of human sarcoma cells. Similarly, immobilized PAI-1 bound both purified vitronectin and vitronectin from normal human serum. These interactions were demonstrated using both enzyme immunoassay and radioiodinated proteins. Solid-phase vitronectin bound PAI-1 with Kd 1.9 x 10(-7) M, and the reverse interaction gave a Kd 5.5 x 10(-8) M. Evidence was also found for a second type of binding with a Kd below 10(-10) M. The molar ratios of the two proteins in the complex at the saturation levels were approximately one molecule of soluble PAI-1 bound per three molecules of immobilized vitronectin and approximately one molecule of soluble vitronectin being bound per one molecule of immobilized PAI-1. Binding of PAI-1 to vitronectin did not lead to an irreversible loss of the ability of PAI-1 to inhibit urokinase (u-PA) and tissue-type plasminogen activator (t-PA). Active u-PA released vitronectin-bound 125I-labeled PAI-1 radioactivity, suggesting that u-PA interacts with the complex. The Mr 50,000 urokinase cleavage product of PAI-1 also bound to vitronectin, but this bound fragment did not inhibit u-PA. Binding of PAI-1 to vitronectin did not interfere with the ability of vitronectin to promote the adhesion and spreading of cells. These results suggest that the interaction between vitronectin and PAI-1 may serve to confine pericellular u-PA activity to focal contact sites where cells use proteolysis in regional detachment.

Glycoproteins↗

Contractile activity of the N-acylated C-terminal part of substance P7-11 in guinea pig trachea. Effect of epithelium removal.

Substance P, neurokinin A, neurokinin B, and N-acylated pentapeptide X-Phe-Phe-Gly-Leu-Met-NH2 analogs of substance P7-11 were tested for their spasmogenic activities in intact or in epithelium-denuded tracheal strips from guinea pig. Epithelium removal enhanced the efficacies and potencies relative to substance P of all the peptides tested in guinea pig trachea. In epithelium-containing preparations, the presence of a cyclic substituent (o-hydroxyphenyl-acetyl, p-hydroxyphenyl-acetyl, pyroglutamyl) in Phe7 greatly enhanced the potency and efficacy compared to substance P. These substitutions were twice as active as neurokinin A itself. The presence of an aliphatic chain (non-protected and t-butyloxycarbonyl-protected aminopropyl and aminocaproyl) in Phe7 also improved the potency and the efficacy of the synthetic peptides. The aliphatic substituents could favour an increase in local concentration of the peptides in the vicinity of the receptor(s) allowing a more effective ligand-receptor interaction. Thus, lipophilicity could be determinant in the potency of the peptides in intact guinea pig trachea. In epithelium-denuded tracheal strips from guinea pig, all the synthetic peptides were more effective than substance P but less active than neurokinin A which probably reflects the presence of the NK2 receptor subtype, which may be predominant in this type of epithelium-denuded preparation. Our results suggest that hydrophobicity plays a strong role in the interaction of the peptides, namely substance P and its analogues with the membrane and possibly the receptors themselves.

Animals↗

Unchanging clinical picture of coeliac disease presentation in Campania, Italy.

Four hundred and sixty-three new diagnoses of coeliac disease in children were made during 1973 to 1986 in our department. The distribution of new diagnoses per year did not show any decreasing trend in the period 1973 to 1986. No changing trend in breast feeding attitudes was found in the region during the same period. Analysis of the clinical pattern showed a constant distribution of age at diagnosis, onset of first symptoms and nature of symptoms throughout the period studied. These data suggest that coeliac disease is predominantly genetically determined and its expression is modulated by individual and environmental factors. The stability of the observed prevalence of the disease is parallel to the unchanging pattern of breast feeding attitudes in the region.

Adolescent↗

Human follicular fluid protease and antiprotease activities: a suggested correlation with ability of oocytes to undergo in vitro fertilization.

Plasminogen activator activity was determined in human follicular fluids (FFs) obtained during in vitro fertilization procedures. The fibrinolytic activity of plasminogen activator was significantly higher in fluids from follicles that contained oocytes that were later found to fertilize in vitro (group F) as compared with fluids from follicles that contained oocytes that failed to fertilize (NF). To assess whether this difference in overt plasminogen activator activity reflects differences in conversion of an inactive, latent plasminogen activator to the active enzyme, the ability of exogenous trypsin to enhance plasminogen activation was measured. The plasminogen-dependent hydrolysis of the chromogenic substrate S-2444 in presence of trasylol (Bayer, Leverkusen, Germany) was taken as a measure of plasminogen activator activity in these experiments. No activity was found in untreated FFs, while exposure to trypsin resulted in emergence of marked plasminogen activator activity. In addition, FFs exhibited trasylol-sensitive chromogenic activity indicative of serine-protease activity. Both the plasminogen activator and serine-protease levels after tryptic activation were significantly higher in NF than in F samples. Thus, while F samples have most of their plasminogen activator in an active form, NF samples have most of their plasminogen activator in a latent, trypsin-activatable form. Follicular fluids also contain inhibitory activities toward plasmin and trypsin. The inhibition of these enzymes correlates positively with the latency of plasminogen activator. These results suggest a direct relationship between the ability of oocytes to fertilize and the overt to latent plasminogen activator activity ratios in the FFs.

Endopeptidases↗

Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor.

Urokinase plasminogen activator (uPA) interacts with a surface receptor and with specific inhibitors, such as plasminogen activator inhibitor type 1 (PAI-1). These interactions are mediated by two functionally independent domains of the molecule: the catalytic domain (at the carboxyl terminus) and the growth factor domain (at the amino terminus). We have now investigated whether PAI-1 can bind and inhibit receptor-bound uPA. Binding of 125I-labeled ATF (amino-terminal fragment of uPA) to human U937 monocyte-like cells can be competed for by uPA-PAI-1 complexes, but not by PAI-1 alone. Performed 125I-labeled uPA-PAI-1 complexes can bind to uPA receptor with the same binding specificity as uPA. PAI-1 also binds to, and inhibits the activity of, receptor-bound uPA in U937 cells, as shown in U937 cells by a caseinolytic plaque assay. Plasminogen activator activity of these cells is dependent on exogenous uPA, is competed for by receptor-binding diisopropyl fluorophosphate-treated uPA, and is inhibited by the addition of PAI-1. In conclusion, in U937 cells the binding to the receptor does not shield uPA from the action of PAI-1. The possibility that in adherent cells a different localization of PAI-1 and uPA leads to protection of uPA from PAI-1 is to be considered.

Binding, Competitive↗

Early prediction of relapse during gluten challenge in childhood celiac disease.

Thirty-seven children, in whom celiac disease had been diagnosed because of flat mucosa on a gluten-containing diet and recovery on a gluten-free diet, were challenged with gluten powder, 10 g/day, in addition to an otherwise gluten-free diet. A small intestinal biopsy was performed before the challenge; clinical symptoms, a 1-h blood xylose test, and gliadin antibody measurement were used to establish the timing of the confirmatory biopsy. All but one case relapsed within 205 days (mode, 60 days). In no case was the relapse clinically evident. Raised levels of gliadin antibodies, a fall in xylose absorption, or both predicted the relapse in 37%, 7%, and 57% of cases, respectively. Evaluated individually, each test gave a considerable rate of false negative results. Discriminant coefficients produced for each test were used to compute a score that allowed the classification of patients into relapse/no relapse categories with a good degree of accuracy. The discriminant score rose sharply after only 15 days of challenge, indicating that it is possible to predict the relapse long before any clinical symptom appears.

Antibodies↗

[Adherence of mononuclear leukocytes in multiple sclerosis: the effect of the calcium ionophore A 23187 and leukotrienes B4 and C4].

The author assessed the effect of leucotrienes B4 and C4 and the calcium ionophore A23187 on the adherent reactivity of mononuclear leucocytes in patients with multiple cerebrospinal sclerosis and in controls. The calcium ionophore A23187 in concentrations of 200 nmol/1 - 5 mumol/1 induced inhibition of leucocyte adherence, depending on the concentration used. This reactivity was, as compared with controls, significantly lower in patients with multiple sclerosis who did not take cortisoid preparations and in patients taking prednisone in doses up to 5 mg/day. In patients treated with higher prednisone doses (20-90 mg/day) the values of the non-adherence index reached values insignificantly higher than in controls. Leukotrienes B4 and C4 (1 nmol/1 - 100 nmol/1 stimulated leucocyte adherence in patients treated with higher corticoid doses, in the remaining patients and in controls they did not influence the leukocyte adherence. The results of the investigation provide evidence of abnormalities of the membrane properties of the mononuclear leucocytes in patients with multiple sclerosis and draw attention to the association of these changes with metabolic chains of arachidonic acid and with calcium ion homeostasis.

Adult↗

[Carpal tunnel syndrome. Late results following surgical treatment].

Of 64 patients, who had undergone operation because of a carpal tunnel syndrome in the years 1982 to 1984, 39 patients could be reinvestigated. The measurement of the distal motor latency was useful as well in the diagnosis as in the course of the CTS. After operation the distal motor latency was normal in about 70.7% of the cases. A subjective improvement showed 69.9% of the patients. Patients with preoperative normal motor latency reached similar postoperative results. The diagnosis cannot made only on the basis of electrophysiologic pathological values, but has to take into account the clinical picture and neurological findings. Phalen's and Tinel's signs are useful helps in the diagnosis of CTS. The results after decompression of the median nerve depend on the length of history.

Adult↗

[Surgical treatment of fresh subcutaneous rupture of the Achilles tendon and results of its treatment].

In the years between 1981 and 1986 32 patients with a subcutaneous rupture of the Achilles tendon were operated on. Two different surgical techniques were preferred: using the tendon of the m. plantaris as suture according to Streli, and Bunnell's suture. In a clinical exploration 17 patients could be recorded. According to the classification of Trillat, 70.6% of the patients show a very good result. That means that the patients have the same sports and professional efficiency as before the injury and operation, a painless Achilles tendon, a stable heel and unrestricted mobility.

Achilles Tendon↗

Pharmacokinetics of mezlocillin in pleural fluid.

Mezlocillin concentrations in the pleural fluid and serum of six patients with malignant pleural effusion were determined following administration of 10 g mezlocillin over 30 minutes as a rapid infusion. Thirty minutes and eight hours after the infusion had been completed, concentrations of the active ingredient in the pleural fluid were 36.44 micrograms/ml and 112 micrograms/ml respectively; in the serum the respective values were 777.89 micrograms/ml and 44.22 micrograms/ml. The concentrations of active ingredient in the pleural fluid exceed the MIC for clinically significant pathogenic germs. The elimination half-life of mezlocillin in malignant pleural effusion is prolonged.

Adult↗

[Hydrocephalus of venous origin].

The relationship between intracranial pressure and superior sagittal venous pressure has been often debated. On one side, the observation of patients with achondroplasia or hydrocephalus associated with craniostenosis suggest that the venous hyperpressure could be the cause of the enlarged ventricles; on the other side, reports have demonstrated that an increased superior sagittal venous pressure could be the consequence of increased intracranial pressure. Therefore, the authors undertook a study to determine if there was a test that could distinguish between rare instances of increased superior sagittal venous pressure caused by structural and irreversible narrowing of the sinus, and those caused by increased intraranial pressure. This test is based on the study of venous pressure variation during cerebrospinal fluid withdrawal as compared to simultaneous intracranial pressure variations. The relationship between a sinus venous hyperpressure and an enlargement of the ventricles, the pathology of pericerebral collection occurring in such cases of hydrocephalus are discussed.

Blood Pressure Monitors↗

In vitro inhibition of urokinase by penicillins.

Urokinase activity was assayed by a two-stage globinolytic method and by a direct chromogenic assay. With both methods, the enzyme activity was found to be inhibited by penicillins. The inhibition by penicillin G, carbenicillin, cloxacillin and penicilloic acid was dose-dependent. The Ki of penicillin G and urokinase with the S-2444 as substrate is 4 mM. This compound exhibited a competitive pattern of inhibition. Ampicillin and 6-amino penicillanic acid failed to inhibit urokinase. These results imply that hydrophobic side chains of penicillins interact with the active site of urokinase. The present observation could be relevant in clinical situation in which high doses of beta-lactam antibiotics could modulate the endogenous fibrinolytic activity of circulating urokinase.

Carbenicillin↗

Plasminogen activator inhibitor type-1 protein, mRNA and gene transcription are increased by phorbol esters in human rhabdomyosarcoma cells.

By use of an enzyme-linked immunosorbent assay, we have found that phorbol 12-myristate 13-acetate (PMA) causes an approximately 10-fold increase in the level of type-1 plasminogen activator inhibitor (PAI-1) accumulated in conditioned medium of the human rhabdomyosarcoma cell line. Half-maximal stimulation occurred at approximately equal to 15 nM PMA. The effect was only observed with phorbol esters that are tumor promoting. Maximal levels of secreted PAI-1 were observed 24 h after PMA addition. The increase in secreted PAI-1 was preceded by a transient approximately 10-fold increase in intracellular PAI-1 content, maximal at 8 h after PMA addition. There was a 20-fold increase in the cellular level of two 2.3- and 3.4-kilobase PAI-1 mRNAs and a more than 5-fold increase in the PAI-1 gene transcription rate. The protein synthesis inhibitor cycloheximide (10 micrograms/ml) also increased the level of PAI-1 mRNA, and when both cycloheximide and PMA were used, an additive effect was observed. Cycloheximide changed the ratio between the two PAI-1 mRNAs in favor of the 3.4-kilobase species. Overall, the data show that transcriptional activation of the PAI-1 gene forms part of the pleiotropic responses to tumor-promoting phorbol esters.

Blotting, Northern↗

N-acylated pentapeptides antagonists of substance P on guinea-pig ileum.

Pentapeptides X-D.Trp-Phe-D.Trp-Leu-Y-NH2 (X = H, Boc, parahydroxyphenylacetyl, Y = Met,Leu,Nle,Phe) were tested as antagonists against Substance P and against a specific agonist of the muscular receptor of neurokinins on the guinea-pig ileum. Weak antagonist or agonist activities could be observed with the free or the Boc-protected pentapeptides whilst the acylated compounds could be compared favorably with the best antagonists already described.

Acylation↗