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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 235 records · Page 13Linked to original sources

Alkaline proteinase localization in myoblasts.

Recent interest in elucidating the role of non-lysosomal proteases in intracellular protein catabolism in muscle has led to various investigations with three alkaline proteases: a trypsin-like, a chymotrypsin-like, and a high molecular weight cysteine proteinase. Although in vitro biochemical assays have revealed the catabolic potential of at least two of these proteases, confirmation of their presence in muscle cells has been difficult. In this study immunohistochemical techniques were employed to localize each of these proteases in rat myoblasts. Antisera against the trypsin-like and chymotrypsin-like proteinase (both serine proteinases) showed strong localization in the cytoplasm immediately around the nucleus. Both also stained chromatin material in the nucleus of these cells. Fluorescent localization of the high molecular weight cysteine proteinase (Proteinase I) also appeared to be cell-associated in the myoblasts. The use of myoblasts in cell culture sections of whole muscle was advantageous, since localization of the proteases could be assessed in the absence of other cell types.

Animals↗

[Collagenous sprue and ulcerative jejuno-ileitis in a patient with gluten-induced enteropathy].

In a 60-year-old patient with adult celiac disease complete clinical remission was achieved with a glutenfree diet, but symptoms of sprue subsequently recurred despite rigid adherence to dietary restrictions. Further investigations revealed simultaneous occurrence of two severe complications of celiac disease: collagenous sprue and ulcerative jejunoileitis. The patient died after a 2 1/2 year course of refractory, severe, relentlessly progressive malabsorption. In the light of the literature and this observation it is postulated that in every case of primary or secondary refractory celiac disease complications must be sought: to diagnose collagenous sprue, aspiration biopsy from the proximal jejunum, and possibly also from the terminal ileum, may be more efficient than simple endoscopic biopsy from the descending duodenum. If the diagnosis of collagenous sprue can be established, therapy with steroids should be attempted. The diagnosis of ulcerative jejunoileitis is usually missed by radiology and requires exploratory laparotomy.

Biopsy↗

Radionuclide bone imaging in diaphyseal aclasis with malignant change.

Chondrosarcoma is a rare complication in hereditary multiple exostoses. The six patients in this study have had a complete follow-up and constitute the largest group of such cases to have been studied so far. Five patients had histologic evidence of malignancy. Since histologic examination can be very difficult, any other diagnostic features, may it be clinical, radiologic, or scintigraphical, should be taken into account for early surgical treatment. Bone scintigraphic examination is a valuable adjunct to early diagnosis of malignant change by showing highest uptake in malignant areas. It is also very useful for posttherapeutic follow-up.

Adolescent↗

Involvement of both heparanase and plasminogen activator in lymphoma cell-mediated degradation of heparan sulfate in the subendothelial extracellular matrix.

The effect of plasminogen on the ability of highly metastatic ESb mouse lymphoma cells to degrade heparan sulfate (HS) in the subendothelial extracellular matrix (ECM) was studied. A metabolically sulfate-labeled ECM was incubated with the lymphoma cells, and labeled degradation products were analyzed by gel filtration on Sepharose 6B. Heparanase-mediated release of low-Mr (0.5 less than Kav less than 0.85) HS cleavage products was stimulated fourfold in the presence of plasminogen. Incubation of plasminogen alone with the ECM resulted in its conversion into plasmin, which released high-Mr (Kav less than 0.33) labeled proteoglycans from the ECM. Heating the ECM (80 degrees C, 1 hr) abolished its ability to convert plasminogen into plasmin, yet plasminogen stimulated, through its activation by the ESb plasminogen activator, heparanase-mediated release of low-Mr HS fragments. Heparin inhibited both the basal and plasminogen-stimulated degradation of HS side chains but not the total amount of labeled material released from the ECM. In contrast, aprotinin inhibited the plasminogen-stimulated release of high- as well as low-Mr material. In the absence of plasminogen, degradation of heated ECM by ESb cells was completely inhibited by aprotinin, but there was only a partial inhibition of the degradation of native ECM and no effect on the degradation of soluble HS proteoglycan. These results demonstrate that proteolytic activity and heparanase participate synergistically in the sequential degradation of ECM HS and that the ESb proteolytic activity is crucial for this degradation when the ECM-associated protease is inactivated. Plasminogen may serve as a source for the proteolytic activity that produces a more accessible substrate to the heparanase.

Animals↗

Plasminogen activator activity in differentiating rat myoblasts.

Primary cultures of skeletal muscle cells secrete plasminogen activator (PA) activity to the conditioning medium and display membrane-bound PA. Growth of these cells in culture in presence of 10(-7) M dexamethasone resulted in a marked reduction of the membranal and secreted PA activity. The hormone also reduced cytosolic creatine phosphokinase (CPK) activity and cytosolic protein content. However, cell viability and their ability to undergo fusion were uneffected. The extent of hormone-induced reduction in PA activity depended on the time and extend of exposure. Maximal suppression was obtained by exposing the cells to dexamethasone during the first 4 days of culture. The medium conditioned with dexamethasone-treated cells did not inhibit plasmin, endogenous PA or exogenous PA. Exposure of the conditioned medium from hormone-treated cells to sodium dodecyl sulphate (SDS) or trypsin restored the activity to values observed in media from cells not exposed to the hormone. Acidification of the medium failed to reactivate the enzyme. The myogenic cell line L-8 also displayed membrane-bound PA activity, which was of a comparable magnitude in both fusing and non-fusing L-8 cells. However, in contrast to the primary cultures, exposure of L-8 cells to dexamethasone had no effect on their PA activity whether studied under conditions which allowed or prohibited fusion. The present findings imply that PA has no conducive role in the process of fusion associated with maturation of skeletal muscle cells.

Animals↗

The effect of caffeine on fragile X expression.

Caffeine has been reported to enhance the expression of the fragile X [fra(X)] and common fragile sites in peripheral blood lymphocyte cultures (PBLC) treated with 5-fluorodeoxyuridine (FUdR). One of the effects of caffeine on replicating cells is inhibition of DNA repair suggesting that fragile sites may be regions of DNA with a high rate of misreplication under the conditions of thymidylate stress induced by FUdR. We have studied the effect of caffeine on the expression of the fra(X) and common folate-dependent fragile sites in PBLC from two fra(X) expressing individuals and in five lymphoblastoid cell lines (LCL) established from individuals in families in which the fra(X) is segregating. Caffeine did not enhance the expression of the fra(X) in the PBLC or in the three LCL from fra(X) expressing individuals nor did it elicit fra(X) expression in LCL from a non-expressing obligate-carrier female and a transmitting male. However, in all cultures there was a marked increase of common fragile site expression due to caffeine treatment. These data suggest that the mechanism of expression of the common fragile sites and the fra(X) may be quite different.

Caffeine↗

[Clinical experience with imipenem/cilastatin in the treatment of severe infections in general surgery].

In a prospective study 43 patients (19 men, 24 women) suffering from severe bacterial infections such as peritonitis (n = 16), soft tissue infection (n = 12), pneumonia (n = 7), septicemia (n = 6), catheter sepsis (n = 2), cholangitis (n = 4), osteomyelitis (n = 3), complicated urinary tract infection (n = 2) or endocarditis (n = 1) were treated t. i. d. with short-time i. v. infusions of 0.5 g imipenem/cilastatin for five to 37 days (means = 9). All the patients were cured or significantly improved following therapy with imipenem/cilastatin alone or in combination with surgical intervention. The most frequent isolates were Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis. 58 (83%) of the 70 pathogens isolated initially were eliminated. The 12 microorganisms (gram-negative aerobic bacteria) which persisted were non-contributory to the course of the infection and had MICs between 0.32 and 4 mg/l. The MICs for 60 isolates were less than or equal to 1 mg/l; the MICs for nine isolates were in the range of 2 to 8 mg/l. One S. epidermidis isolate presented primary resistance to imipenem (MIC 16 mg/l). The tolerability was good. Phlebitis was observed in one case only. Based on our experience we conclude that monotherapy with imipenem/cilastatin at a dosage of 0.5 g t. i. d. is appropriate for the treatment of severe bacterial infections.

Adolescent↗

Symptomatic reactive hypoglycemia during glucose tolerance test in lithium-treated patients.

Glucose, insulin, glucagon, and cortisol responses during a five-hour oral glucose tolerance test (GTT) were evaluated in nine patients with bipolar affective disorders who were receiving lithium treatment and in seven control patients with bipolar affective disorders who were not receiving any treatment. Both the lithium-treated and the control patients were in stable mood at the time of GTT. During GTT mean nadir serum glucose of 48 +/- 2 mg/dL in the lithium-treated patients was significantly lower (P less than 0.001) than mean nadir serum glucose of 62 +/- 2 mg/dL observed in the control subjects. Seven of these nine lithium-treated patients, but none of the control patients, experienced hypoglycemic symptoms coinciding with low serum glucose concentration. In response to hypoglycemia, mean serum cortisol significantly rose (P less than 0.01) to 22 +/- 3 micrograms/dL in the lithium-treated patients, whereas mean serum cortisol levels gradually declined to 10 +/- 2 micrograms/dL in the control patients at 300 minutes. Despite symptomatic postglucose hypoglycemia, plasma glucagon levels in the lithium-treated patients were similar to those observed in the control patients. These findings suggest that chronic lithium treatment is associated with a symptomatic and biochemical hypoglycemia during GTT, which is characterized by a rise in serum cortisol but by lack of appropriate rise in plasma glucagon concentrations.

Adult↗

Protease inhibitor activity in human skeletal muscle.

Myofibrillar protease activity and activity of inhibitors toward trypsin, chymotrypsin, elastase, and the myofibrillar protease were determined in human skeletal muscle. The protease activity was found to increase in patients with acute and chronic inflammation as well as in patients with metastatic and nonmetastatic tumors. The inhibitory activity directed against trypsin and chymotrypsin was not affected by acute inflammation, while the inhibition of elastase and the myofibrillar protease was increased. Chronic inflammation did not affect the ability of the muscle cytosol to inhibit trypsin and elastase, but increased the inhibition of chymotrypsin and the myofibrillar protease. Nonmetastatic tumors produced an increase in the activity of inhibitors toward trypsin, chymotrypsin, and elastase, while patients bearing metastatic tumors had a high level of cytosolic inhibitors of all the tested proteolytic activities. These results indicate that the myofibrillar protease and the cytosolic protease inhibitors in human skeletal muscle are differentially affected by catabolic conditions.

Abdominal Muscles↗

Suppression of plasminogen activator activity by dexamethasone in cultured cardiac myocytes.

Cardiac rat myocytes in primary culture exhibit a membrane-bound and a secreted form of plasminogen activator (PA). Growth of the cells in presence of 2 X 10(-8) M or 10(-7) M dexamethasone markedly reduced both the membrane-bound and the secreted activities of PA. The extent of reduction depended on the time of addition as well as on the length of exposure to the hormone. A similar concentration of estradiol had no effect on PA activity of the myocytes. Cardiac rat fibroblasts in primary culture showed only the particulate form of the enzyme. Exposure of the fibroblasts to 10(-7) M dexamethasone produced a marked inhibition of this activity. The inhibition of PA activity in medium conditioned by dexamethasone-treated myocytes could be relieved by treatment of the medium with 1% (v/v) sodium dodecyl sulphate (SDS). Digestion with 3.3 micrograms/ml bovine trypsin caused an increase in PA activity of media conditioned with control or dexamethasone-treated cells. The present results indicate that cardiac myocytes and fibroblasts produce PA, and that the modulation of PA by glucocorticoid either involves formation of an inactive PA-protein complex or production of an inactive proenzyme. Since glucocorticoids are often administered in conjunction with fibrinolytic enzymes to re-establish cardial perfusion after thrombosis, the present findings indicate further research to assess potential clinical effects of glucocorticoids through suppression of endogenous PA activity in the heart.

Animals↗

Experimental clinical studies on the effect of eburnamonine in cerebrovascular disorders.

Two double-blind, placebo-controlled studies were performed successively to demonstrate the efficacy of Eburnamonine. In the first study, the efficacy of 12 weeks of administration of 3 X 60 mg Eburnamonine per day (n = 25) was investigated in 49 inpatients with cerebrovascular disorders. In the second, the effect of 12 weeks of therapy with 1 X 60 mg Eburnamonine per day (n = 25) was investigated in 50 patients of the same diagnostic category. Results related to the efficacy were analyzed on the basis of the physician's global rating of therapeutic effect, and evaluated by the x2-test. Global therapeutic effect was confirmed and illustrated by effects on specific variables (List of Cerebral Symptoms, function test, NOSIE) evaluated by analysis of covariance. Under the influence of both dosages, therapeutic improvement was observed more frequently than under placebo. The incidence of gastrointestinal side effects was higher under the dose of 3 X 60 mg than under placebo. No effects were observed with respect to parameters of clinical chemistry. In the quasi-experimental comparison of 3 X 60 mg and 1 X 60 mg Eburnamonine, the higher dose was found to yield more therapeutic improvement, but also more frequent side effects than the lower dose, which, in this respect, did not differ from placebo.

Aged↗

Cytogenetic analysis of lymphoblastoid cell lines.

Cytogenetic abnormalities were discovered in more than half of 16 lymphoblastoid cell lines established from fragile X individuals and their relatives upon routine cytogenetic analysis of early passage cultures. Subsequently, a second series of lymphoblastoid lines was analyzed to determine if the aneuploidy was a characteristic of lymphoblastoid cell lines derived from fragile X families or a result of the use of cyclosporin A in the establishment of these lines. In the second series of 33 lymphoblastoid cultures, no aneuploid clones were found in the fragile X group, while two were detected in the control cultures, one in a line initiated with cyclosporin A and the other in a line established without cyclosporin A. We conclude that the abnormal clones in our preliminary series were not a characteristic of lines derived from fragile X families and probably not due to the use of cyclosporin A. However, the finding of chromosome abnormalities in a large proportion of lines during the first 3 mo of culture contrasts with previous reports of chromosome stability for the first 12-18 mo of cultivation and indicates that the chromosomes of lymphoblastoid lines should be monitored in any experiment in which a normal diploid complement is critical.

Adolescent↗

Fatty acyl-CoA oxidase in rat kidney and liver after application of thyroxine.

Male rats were fed a standard diet containing 2.5 mg% L-thyroxine. After 10 and 20 days, in postnuclear fractions of the kidney the specific activity of fatty acyl-CoA oxidase, the enzyme responsible for the rate-limiting first step of peroxisomal fatty acid beta-oxidation, was increased by 100 and 160%, respectively. A similar effect was found in the liver. It is suggested that thyroxine essentially affects only this step of the fatty acid beta-oxidation sequence. Presumably the elevation of fatty acyl-CoA oxidase is one reason for the beneficial action of thyroid hormones in toxic lesions of the kidney.

Acyl Coenzyme A↗

Memory deficits and anticholinergic levels in chronic schizophrenia.

Recent memory correlated inversely with serum anticholinergic levels for verbal recall but not for recognition memory in 17 chronic schizophrenic inpatients taking neuroleptic medications. The results indicate that anticholinergic activity does not impair primary memory functioning in chronic schizophrenia.

Adult↗