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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 217 records · Page 12Linked to original sources

Effects of cisplatin on parathyroid hormone- and human lung tumor-induced bone resorption.

We have previously shown that dichlorodiamine platinum (DDP), or cisplatin, a cancer chemotherapeutic agent, is effective in the treatment of malignancy-associated hypercalcemia. In the present studies, we evaluated its effects on bovine parathyroid hormone (PTH)- or tumor-induced bone resorption in vitro in the neonatal mouse calvarial bone resorption assay. PTH alone or tumor extract (TE) of a human squamous cell lung cancer alone caused a significant increase in the bone resorption and in the number of osteoclasts in the calvaria. The addition of 3 and 10 micrograms/ml DDP inhibited the PTH- or TE-induced bone resorption. Lower doses of 1 and 2 micrograms/ml DDP, although not effective in inhibiting the PTH-induced bone resorption, were effective in lowering the TE-induced bone resorption. The number of osteoclasts was also reduced by DDP treatment. We therefore conclude that DDP is effective in the treatment of malignancy-associated hypercalcemia by virtue of its inhibitory effects on osteoclast numbers and on bone resorption.

Animals↗

Plasminogen activator inhibitor type 1: cell-specific and differentiation-induced expression and regulation in human cell lines, as determined by enzyme-linked immunosorbent assay.

We have performed a comparative study of the regulation by glucocorticoids and phorbol 12-myristate 13-acetate (PMA) of the production of type 1 plasminogen activator inhibitor (PAI-1) by 12 human cell lines. A sandwich-type enzyme-linked immunosorbent assay (ELISA) for PAI-1 that measures free PAI-1 as well as complexes between PAI-1 and both types of plasminogen activators has been used. Basal PAI-1 accumulation varied more than 5000-fold between the cell lines. No correlation was found between the PAI-1 level and other characteristics of the cell lines, except that three lines of SV40-transformed fibroblasts produced more PAI-1 than two non-transformed fibroblast cell lines. Three out of the 12 cell lines responded to glucocorticoids by an increased PAI-1 production. Four cell lines responded to PMA by an increased PAI-1 production. In addition, PMA-induced differentiation of the monocyte cell line U937 and the promyelocytic cell line HL-60 into macrophage-like cells was found to be correlated with an up to 100-fold increase in PAI-1 accumulation. The PMA-dependent differentiation of HL-60 cells led to acquisition of glucocorticoid inducibility of PAI-1. These findings provide information for future studies of the molecular mechanism of cell-specific expression and regulation of PAI-1.

Cell Line↗

Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation.

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.

Abdomen↗

Plasminogen activator activity and urokinase inhibitor activity in human amniotic fluid and fetal membranes.

This study reports on the presence of latent plasminogen activator (PA) activity in human amniotic fluid (HAF). To measure PA, HAF was incubated with plasminogen, and the formation of plasmin was followed by its ability to cleave globin. The latent proenzyme in HAF was converted to active PA by treatment with sodium dodecyl sulphate (SDS) but not by tryptic digestion. The level of SDS-activatable PA activity in HAF increased with increasing gestational age. In an alternative, direct assay of PA based on its amidolytic activity upon L-pyroglutamyl-glycyl-L-arginine-p-nitroanilide (S-2444), HAF PA activity could be demonstrated even without prior exposure to SDS. Medium conditioned with either chorion or amnion produced PA activity suggesting that HAF PA is derived from the fetal membranes. Treatment of the conditioned medium with SDS or trypsin further increased the enzyme activity. The fetal membranes also produce inhibitory activities towards exogenous trypsin, plasmin, and urokinase. The inhibition of plasmin could be separated from the inhibitory activities towards trypsin and urokinase by DEAE-sephadex ion-exchange chromatography. The function of PA in the normal physiology and in pathological processes involving HAF and the fetal membranes remains to be elucidated.

Amniotic Fluid↗

Mezlocillin in pleural effusions--analysis by HPLC.

Mezlocillin concentrations in the pleural fluid of six patients (42-76 years of age, suffering from cytologically confirmed malignant pleural effusions) were determined after intravenous infusion of 10 g mezlocillin. Serum and pleural fluid samples were withdrawn 15, 30, 45, 60 min, 2, 4, and 8 h post infusion. Detection of mezlocillin and its metabolites penicilloic acid and penilloic acid was carried out by means of high performance liquid chromatography (HPLC). Mezlocillin concentrations in serum increased up to 778 +/- 270 micrograms/ml after 15 min, steadily decreasing to 55 +/- 50 micrograms/ml (8 hours post infusion) comparable to the known pharmacokinetic behaviour of mezlocillin; in the pleural effusions mezlocillin levels increased up to 100 +/- 38 micrograms/ml after 1 h. This concentration was maintained throughout the following 7 h. Penicilloic levels ranged about 2-4% within serum, whereas levels below 1% were measured in the pleural fluid.

Adult↗

[Myoclonic epilepsy with non-progressive encephalopathy].

We report 6 cases of particular type of myoclonic epilepsy with non-progressive encephalopathy. It consists of a syndrome characterized by an onset of seizures in the first year of life, frequent myoclonic status, generalized spikes and waves on EEG and an unfavourable outcome with encephalopathy. At the beginning, the diagnosis is difficult, the symptomatology later suggests a progressive encephalopathy. In the present study, a detailed analysis of the early electroencephalographic aspects and of the arguments in favour of a non-progressive encephalopathy is proposed. Hypothesis of perinatal vascular lesions mainly involving the central areas is forwarded.

Adult↗

Multiple sclerosis in children: report of clinical and paraclinical features of 19 cases.

We report our experience concerning clinical and paraclinical features of multiple sclerosis in 19 children. The disease was highly variable in its presentation but acute episodes of retrobulbar optic neuritis or transverse myelitis or cerebellitis were commonly observed at the onset. Diagnosis was very often suspected as soon as the first episode when there was clinical evidence of more than one lesion (43%) or study of the cerebrospinal fluid demonstrated a local secretion of immunoglobulins (60%). Evoked potential studies and nuclear magnetic resonance imaging were performed during the course of the disease and exhibited abnormalities of the kind observed in adult patients and with a similar frequency; this suggests that such studies can be very useful in the evaluation of children suspected of having multiple sclerosis. When the initial form of the disease was a chronic myelopathy, the course was progressive from the onset, leading rapidly to a marked invalidity (15%). Most often a succession of relapses and remissions occurred after the first attack and major sequelae appeared 5 to 10 years later. Such features are not very different from those observed in adult patients and suggest that these patients can benefit from the progress resulting from therapeutic trials in adult patients.

Adolescent↗

Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis.

A 12 year old patient who developed clinical, biochemical and histological features of erythrophagocytic lymphohistiocytosis is described. In contrast to previously reported cases, the prominent neurological feature was a subacute sensorimotor polyneuropathy. Sural nerve biopsy showed a marked reduction of myelinated fibres and severe axonal lesions, absence of histiocyte infiltration and deposits of IgM along the epineurium. In addition to the hypertriglyceridaemia previously described in this condition, an elevation of plasma very long-chain fatty acids and phytanic acid was found which suggests a transient impairment of peroxisomal functions.

Biopsy↗

Effect of calcium ionophore A23187 and of leukotrienes B4 and C4 on the adherence of human mononuclear leukocytes.

The adherence changes induced by the ionophore A23187 and by the leukotrienes, respectively, were investigated in 10 healthy persons. The calcium ionophore A23187 in concentrations of 200 nM, 1 microM and 5 microM induced inhibition of mononuclear leukocyte adherence in a concentration-dependent manner, the maximal adherence inhibition being proved with 5 microM ionophore. The leukotrienes did not significantly alter leukocyte adherence in the test system used. The results of this study suggest that the calcium ionophore A23187-induced leukocyte adherence inhibition may serve as a pharmacological model of the leukocyte adherence inhibition phenomenon, thus providing a useful tool for the investigation of the processes associated with some cellular membrane functions.

Calcimycin↗

Effect of calcium ionophore A23187 and of leukotrienes B4 and C4 on the adherence of mononuclear leucocytes in multiple sclerosis.

The disturbances of the arachidonic acid metabolic cascade are supposed to play a significant part in some membrane alterations and in associated immunopathological changes in multiple sclerosis. Since the lipoxygenase derivatives of the arachidonic acid and the calcium ion influx were proved to participate in the mechanisms involved in the leucocyte adherence inhibition phenomenon, the effect of calcium ionophore A23187 and of leukotrienes B4 and C4 upon the adherence of mononuclear leucocytes of multiple sclerosis patients and of healthy controls was investigated in the present study using a modification of the leucocyte adherence inhibition assay. A23187, a potent stimulator of the arachidonic acid metabolism, induced the mononuclear leucocyte adherence inhibition in a dose-dependent manner. In multiple sclerosis patients without corticosteroid treatment and in those treated with lower prednison doses (up to 5 mg/day), the non-adherent response to A23187 stimulation was significantly lower than in the controls, whereas in multiple sclerosis patients treated with prednison doses varying from 20 to 90 mg/day the A23187-induced adherence inhibition reached non-significantly higher values compared to the controls. Leukotrienes B4 and C4 stimulated the adherence of the leucocytes in multiple sclerosis patients treated with higher prednison doses. Compared to controls, statistically significant differences were found using 1 nM and 100 nM LTC4. The findings obtained in this study with all probability reflect alterations of the membrane processes in multiple sclerosis leucocytes associated with calcium ion homeostasis and arachidonic acid metabolic cascade.

Adult↗

Cytogenetic study of Kaposi's sarcoma associated with acquired immunodeficiency syndrome.

We performed cytogenetic studies on direct preparations and short-term cultures from Kaposi's sarcoma cells obtained from malignant pericardial effusion. The patient, a 46-year-old man with human immunodeficiency virus infection, initially presented with metastatic Kaposi's sarcoma. Despite therapy, his tumor proved aggressive, and the patient died of widespread pulmonary involvement nine months after diagnosis. Cytogenetic analysis revealed a predominant karyotype of 48,X,-Y, t(2;7)(q32;q36), +der(5)t(5;15)(q?15;q?15), -7, +del(7)(p15), +del(7)(p15), +der(8)t(8;D or G)(q24;p11.2), del(10)(p13), dup(12)(q24), t(18;20)(q21;q13). This case is described in relation to other published cytogenetic studies of this tumor.

Acquired Immunodeficiency Syndrome↗

[Serum levels of lidocaine as affected by high frequency jet ventilation during bronchoscopies under local anesthesia].

Fiberoptic bronchoscopy is a valuable procedure in the diagnosis and treatment of pulmonary disorders and is usually performed under local anesthesia. The local application and ultrasonic nebulization of lidocaine is widely accepted for inducing topical anesthesia in the respiratory tract. We produced local anesthesia of the trachea and bronchial tree by nebulizing lidocaine via high-frequency jet ventilation (HFJV). At the same time, we measured serial plasma concentrations of lidocaine to determine the potential for toxicity due to systemic absorption from the tracheobronchial tree. METHOD. Twelve adult patients without known heart or liver disease were studied during diagnostic bronchoscopy. As premedication 0.5 mg atropine and diazepam (10 mg) or midazolam (5 mg) were given. After topical anesthesia of the oropharynx, all patients were intubated with a Hi-Lo jet endotracheal tube using a flexible bronchoscope. Spontaneous breathing was supported with a high-frequency jet ventilator (Acutronic MK 800). The humidification ventilator pump was used as a device for local anesthetic administration (lidocaine 0.5%). The following continuous application scheme was used: 0-5 min: 100 ml/h; 5-10 min: 50 ml/h; over 10 min: 5-25 ml/h. Plasma samples for lidocaine levels were taken intravenously 5 min after intubation and then at 5-min intervals. The last sample was taken 30 min after bronchoscopy. The plasma lidocaine concentration was determined by liquid chromatography. RESULTS. In general, this mode of lidocaine administration produced adequate anesthesia and was safe. None of the patients studied required additional lidocaine doses during bronchoscopy. Heart rates and blood pressures were stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytogenetic study of a testicular tumor in a translocation (13;14) carrier.

We performed chromosomal analysis of a primary testicular tumor from an individual who, on subsequent analysis of peripheral blood, was found to have a balanced (13q14q) translocation. Histologically, the tumor was a mixed germ cell neoplasm, predominantly embryonal carcinoma, with some teratomatous elements. The modal chromosome count of the tumor cells was 62, with most counts ranging from 54 to 66. In addition to a t(13q14q) chromosome (of constitutional origin), nine nonrandomly acquired chromosomal abnormalities were identified, including an abnormal chromosome #1 and a probable i(12p). These findings are further discussed and compared with cytogenetic data on human testicular neoplasms from the literature. This case is also discussed with regard to the possible association of a constitutional t(13q14q) and various malignancies and related disorders.

Adult↗

Amniotic fluid protease activity, protease inhibitory activity, and fetal lung maturity.

Amniotic fluid acid protease and acid protease inhibitory activities were examined in normal pregnancies as a function of gestational age. The acid proteolytic activity of the amniotic fluid is almost constant during gestational weeks 16-29 (26 +/- 13 micrograms globin/ml/2 hrs, mean +/- SD, n = 64). The activity sharply increases after 29 weeks in a time-dependent fashion and reaches a value of 302 +/- 89 (mean +/- SD, n = 13) at 39-40 weeks gestation. Under standard conditions, the ability of amniotic fluid to inhibit bovine pepsin declined during gestation in a linear fashion from 44 +/- 13% (mean +/- SD, n = 36) at 16-18 weeks to 9 +/- 10% (mean +/- SD, n = 41) at 36-40 weeks. A correlation coefficient of r = 0.72 was found between pepsin inhibitory activity and gestational age. No consistent change was noted in the extent of inhibition of the endogenous acid protease throughout pregnancy. In 61 amniotic fluid samples, a correlation coefficient of r = 0.70 was found between acid protease activity and the lecithin/sphingomyelin (L/S) ratio. During the course of this study, five cases of respiratory distress syndrome (RDS) were diagnosed clinically. All five infants had a low protease activity (55 +/- 22 micrograms globin/ml/2 hr, mean +/- SD) as well as a low L/S ratio (0.68 +/- 0.20, mean +/- SD). In contrast, no case of RDS of the newborn was observed among 29 pregnancies with high protease activity and a high L/S ratio. The present observations may suggest a predictive value of amniotic fluid acid protease activity in assessment of fetal lung maturity.

Amniotic Fluid↗