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Biomedical subjects

M Molnár

Publications and source records attributed to M Molnár.

At least 37 records · Page 2Linked to original sources
PubMed1996

Turn-amplitude analysis in neuromuscular diseases.

The first attempts in computer aided EMG analysis were performed for the automatic evaluation of interference pattern. In the routine work the turn-amplitude analysis (T/A), introduced by Stålberg and Antoni (1981), proved to be an accurate and easily performed procedure, with the advantage of being relatively independent of force. The aim of our study was to determine the diagnostic significance of T/A analysis in various neuromuscular diseases. The recordings were performed with Madaus Amplaid EMG 15, and concentric needles were used. fifty subjects had been investigated. The diagnoses were based on clinical, biochemical and histological findings. Tibialis anterior, quadriceps femoris, extensor digitorum communis and biceps brachii muscles were regularly sampled. In myogenic conditions a distinct correlation was found between the severity of muscle damage and T/A values. The more pronounced abnormalities were observed in Duchenne boys. Except the ALS in neurogenic processes correlation was found between the severity of muscle damage and T/A analysis, too. The central lesions did not have any effect on the T/A results. Examples of the possible sources of technical errors were presented and comparisons to the traditional concentric needle EMG were done.

Adult↗
PubMed1996

Signal transduction in human myometrial cells.

Calcium plays a pivotal role in the contraction-relaxation cycle of uterine smooth muscle. We investigated the effects of three uterine agonists; prostaglandin F2 alpha (PGF2 alpha), oxytocin and platelet activating factor (PAF) on intracellular levels of Ca ([Ca2+]i) in intact human myometrial cells and 45Ca2+ efflux from permeabilized myocytes. We observed that, whereas oxytocin and PAF activated the phosphoinositide cycle, generating inositol triphosphate to mobilize intracellular Ca2+, PGF2 alpha acted mainly to enhance Ca2+ influx. Oxytocin-, but not PGF2 alpha-elicited responses were suppressed by pertussis toxin. It is concluded that all three agonists act by regulating [Ca2+]i in myometrial cells, but the signal transduction mechanism of PGF2 alpha differs from that of oxytocin and PAF.

Calcium↗
PubMed1996

Efficacy and tolerance of 400 MG bezafibrate in diabetic and hyperlipidaemic patients.

The authors report the results of an open clinical study using 400 mg Bezafibrate once a day. Among 25 diabetic patients (type II.) underwent a 4 weeks period with nutritional advice. Average changes from inclusion levels were -24% for total cholesterol, -56% for triglicerides, +11.9% for HDL-cholesterol, -19% for plama fibrinogen. In conclusion, bezafibrate at a daily dose of 400 mg had significant lipid-modifying properties but also exhibited a beneficial effect on other related risk factors such as fibrinogen reduction.

Adolescent↗
PubMed1995

[Oncologic diagnosis of serous effusions in body cavities (cytologic study and evaluation of cholesterol and carcinoembryonic antigen levels)].

Conventional cytological evaluation of serous effusions often yields border line result: apart from positive (malignant) or negative (benign) diagnoses, a relatively large part of the findings are "suspicious for malignancy" (P3). In the present paper the authors have analysed to what extent contributes the determination of cholesterol and CEA levels of ascites and pleural effusion to the diagnostic accuracy of cytologically "suspicious" (P3) cases. In 155 histologically controlled cases, specificity, sensitivity and diagnostic efficiency were assessed on the basis of cytology as well as the determination of CEA and cholesterol levels. Statistical parameters were determined for each method separately and for their combined application. According to the findings, cholesterol and CEA levels over 1.16 mmol/l and 2.5 ng/ml, respectively, indicate malignancy. In 19 out of 29 cytologically "suspicious" cases (66%), which histologically proved to be positive, cholesterol and/or CEA levels were elevated. In all of the 12 non-neoplastic "suspicious" cases the two parameters were under the cutoff values. The application of an easy and inexpensive cholesterol test proves to be a sensitive technique for indicating carcinomatosis and it completes adequately the specific cytological evaluation. If clinical symptoms speak for tumor, but the cytology is negative, the evaluation of CEA level may prove to be useful as far as it can indicate cancer not yet accompanied by carcinomatosis.

Ascitic Fluid↗
PubMed1995

Proposed signaling role of arachidonic acid in human myometrium.

The objective of this study was to test the hypothesis that, in human myometrial cells (HMC), PGF2 alpha and oxytocin promote the release of arachidonic acid (AA) which, in turn, acts to mobilize intracellular Ca2+. Primary monolayer cultures of HMC were labeled with [3H]arachidonic acid ([3H]AA) to isotopic equilibrium before exposure to PGF2 alpha or oxytocin. Radiolabeled phospholipids were separated on thin layer chromatography and quantitated by scintillation counting. Prostanoids were analyzed by high performance liquid chromatography. Calcium release was quantitated in digitonin-permeabilized myocytes preloaded with 45Ca, in the presence of ATP and ruthenium red. PGF2 alpha (10(-7) M) caused a rapid (peaking at 2 min), and significant (P < 0.01) increase in [3H]AA release that was derived selectively from phosphatidylethanolamine (PE), indicative of phospholipase A2 activation. Oxytocin caused a rapid (30 s) and significant increase in diacylglycerol, concomitant with a drop in phosphoinositides, as well as an increase in [3H]AA and a fall in PE and phosphatidylcholine. Exogenous AA caused a rapid and dose-related efflux of 45Ca2+, which was not inhibited by blockers of AA metabolism, or by heparin that abolished inositol 1,4,5-trisphosphate-induced 45Ca2+ release. It is concluded that PGF2 alpha and oxytocin promote, by different mechanisms, the release of AA, which in turn may amplify their action by enhancing Ca2+ mobilization from the sarcoplasmic reticulum, thereby fulfilling the role of intracellular signaling molecule in human myometrium.

Arachidonic Acid↗
PubMed1995

Becker-like muscular dystrophy in sisters.

Two sisters with muscular dystrophy of Becker-like clinical features presented. Muscle weakness was most prominent in the pelvic girdle, but in the elder sister the distal muscles of the lower extremities were also affected. The progression was different in the siblings: The older sister showed a more pronounced deterioration than the younger. The family history was negative in four generations including their brother and youngest sister. Serum creatinine kinase activities increased considerably. Electromyogram and muscle biopsy specimens revealed myopathic changes characteristic of muscular dystrophy. Chromosomal analysis confirmed normal 46,XX karyotype. DNA analysis with all cDNA probes spanning the entire dystrophin gene failed to reveal any intragenic deletion or duplication on southern blot. Immunohistochemistry for dystrophin using monoclonal antibodies against the rod and C-terminal domains showed normal continuous staining at the sarcolemma of the muscle fibers in the biopsy specimens of both patients. The results practically exclude the possibility of Xp21 myopathy, and it seems reasonable to classify these patients as having autosomal recessive childhood muscular dystrophy.

Biopsy↗
PubMed1995

Correlation dimension changes accompanying the occurrence of the mismatch negativity and the P3 event-related potential component.

The aim of this study was to apply recently developed mathematical tools of chaos theory to the analysis of event-related potentials (ERPs) recorded in paradigms in which the mismatch negativity (MMN) and the P3 component appeared. A new method, the point correlation dimension (PD2i), was used for data analysis, which is more accurate than other algorithms for the calculation of the correlation dimension (D2), which latter is a measure of the complexity of the generator(s) responsible for producing the analyzed time series, i.e., the EEG. ERPs were recorded from Fz, Cz and Pz in 6 subjects. With respect to baseline, the PD2i decreased significantly both during the event-related potentials in which the MMN and also in which the P3 was present, but the pattern and magnitude of this decrease was different between these two situations. The pattern of PD2i changes during the occurrence of deviant stimuli eliciting the MMN suggests the presence of a frontal MMN generator. The conspicuous PD2i decrease during the occurrence of the P3 wave may support the "context closure" hypothesis concerning its functional significance.

Acoustic Stimulation↗
PubMed1995

Signal transduction in rat myometrial cells: comparison of the actions of endothelin-1, oxytocin and prostaglandin F2 alpha.

The objectives of this study were to evaluate and compare the actions of endothelin-1 (ET-1), oxytocin, prostaglandin F2 alpha (PGF2 alpha) and inositol 1,4,5-trisphosphate (IP3) on 45Ca2+ mobilization in permeabilized rat myometrial cells and to examine the activation of the inositol lipid cycle in intact myocytes. Cells were isolated from late pregnant rat myometrium and used as confluent monolayers after a single passage. All four agonists caused a biphasic release of 45Ca2+ from non-mitochondrial pool(s), with the rank order of potency: oxytocin > PGF2 alpha > ET-1 > IP3. Inhibitors of phospholipase C blocked ET-1- and oxytocin-promoted but not PGF2 alpha-promoted 45Ca2+ efflux. Similarly, heparin, an IP3 receptor blocker, failed to inhibit PGF2 alpha-induced 45Ca2+ release while inhibiting the action of the other agonists. Endothelin-1 and oxytocin stimulated inositol phosphate accumulation at concentrations similar to those that promoted 45Ca2+ efflux, whereas about 100 times higher concentrations of PGF2 alpha were needed to activate this signaling pathway in intact cells. It is concluded that the primary action of PGF2 alpha in myometrial cells is to enhance Ca2+ influx, whereas oxytocin and ET-1 receptors are coupled to phospholipase C, generating IP3 and raising the intracellular concentration of free Ca2+ from intracellular as well as extracellular sources.

Adenosine Triphosphate↗
PubMed1994

[Muscle involvement in Crohn disease].

A 41-years-old man with ileitis terminalis was presented. He was operated on for chronic abdominal pain, and the histological investigation revealed the Crohn's disease. From among the extraintestinal complications the rare muscle involvement joined the inflammatory bowel disease. The leading symptoms were the progressive muscle pain and tenderness presented early before the verification of intestinal problems. His complaints referred mainly to the calf muscles. The electromyography (EMG) was normal, the serum creatinine-kinase (CK) activity has not increased. The most characteristic histological findings were the slight mononuclear cell infiltrations with large histiocytic cells in the perimysial connective tissue. Occasionally the infiltrations were more prominent resembling granuloma formations. The oxidative enzyme reactions and the electron micrographs showed mild mitochondrial changes. Neither non-steroid antiinflammatory nor steroid medication subsided the complaints.

Adult↗
PubMed1994

Signal transduction in avian granulosa cells: effects of protein kinase C inhibitors.

We evaluated the effects of two protein kinase C (PKC) inhibitors, staurosporine (ST) and H-7, on LH-activated phospholipase C and adenylate cyclase activity by measuring the production of inositol phosphates (IP) and cAMP in freshly dispersed granulosa cells from mature preovulatory follicles of laying hens. ST and H-7 dose-dependently potentiated LH-stimulated IP generation, whereas a protein kinase A (PKA) inhibitor (H-8) had no effect. The PKC activator, phorbol ester TPA (50 nM), significantly inhibited LH-stimulated IP production, which was completely prevented by ST. Both ST and H-7, while having no effect on basal cAMP levels, significantly and dose-dependently potentiated LH-stimulated, but not forskolin-stimulated cAMP production. However, progesterone production in response to LH, forskolin, and 8-Br-cAMP was inhibited in granulosa cells preincubated for 30 min with H-7 or ST. H-7 and ST had no effect on 25-hydroxycholesterol- and pregnenolone-supported progesterone production. These results support a negative feedback role for PKC in LH-initiated signal transduction in avian granulosa cells. PKC blockade removes the inhibitory effect on LH-stimulated phospholipase C and adenylate cyclase activity. The inhibitory effect of H-7 and ST on progesterone synthesis could be attributed to inhibition of PKA and/or steps proximal to cholesterol side-chain cleavage.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

On the origin of the P3 event-related potential component.

Human findings indicate that the most important brain regions in the electrogenesis of the P3 event-related potential component are the junction of the parieto-temporal lobes, parts of the limbic system and some parts of the thalamus. Data collected in animal experiments support the results of the human studies emphasizing the role of the association cortical areas, that of limbic structures and possibly of some thalamic nuclei. It is not clear as yet how the activity of these hypothesized generators are integrated and to what extent, and how they contribute to the scalp-recorded P3.

Animals↗
PubMed1994

Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation.

OBJECTIVE: Our purpose was to test the hypothesis that chronic inhibition of nitric oxide synthesis in pregnant rats can produce a preeclampsia-like syndrome. STUDY DESIGN: Pregnant rats were instrumented on day 14 of gestation (parturition day 21 to 22) and infused continuously through a venous catheter with L-nitro-arginine, a potent inhibitor of nitric oxide synthase, or with sterile saline solution from day 18 until 24 hours post partum. A group of virgin rats was treated identically. Blood pressure was recorded in unrestrained animals with an aortic catheter for 30 minutes before infusion and repeated each day throughout the experiment. Urinary albumin, platelet count, weight of newborn pups, blood chemistry, and several other parameters were determined. Data were analyzed by one-way, repeated-measures analysis of variance, with Dunnett's t test or by Student t test. RESULTS: Mean arterial pressure increased from 102.6 +/- 2.8 to a mean maximum of 152.5 +/- 7.3 on the second day of infusion and remained in this range until delivery, after which it fell significantly, in spite of continuing infusion of L-nitro-arginine. This treatment increased urinary albumin (milligrams per 24 hours) from 8.3 +/- 1.5 to 56.3 +/- 14.3 in gravid and from 8.2 +/- 0.8 to 18.2 +/- 2.4 in virgin rats. Weight of newborn pups was reduced by L-nitro-arginine from 5.62 +/- 0.10 to 3.37 +/- 0.32 gm (p < 0.005) without affecting time of delivery or litter size. Platelet count was reduced 58% in gravid and 50% in virgin rats. CONCLUSION: Chronic inhibition of nitric oxide synthesis in gravid rats leads to sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation, providing a simple animal model for preeclampsia.

Animals↗
PubMed1993

Mg2+ affects the binding of ADP but not ATP to 3-phosphoglycerate kinase. Correlation between equilibrium dialysis binding and enzyme kinetic data.

The role of Mg2+ in the binding of ADP and ATP to pig muscle and yeast 3-phosphoglycerate kinases has been studied by equilibrium dialysis. Whereas the Kd of ATP binding varies between 0.17 and 0.23 mM (S.E.M. 0.03 mM) for both enzymes, independently of the presence of Mg2+, the Kd values for ADP and MgADP binding are in the range 0.18-0.27 mM (S.E.M. 0.04 mM) and 0.05-0.06 mM (S.E.M. 0.01 mM) respectively. Thus Mg2+ exclusively tightens the interaction of ADP, but not of ATP, with the protein molecule. Although the equilibrium dialysis data are consistent with a model possessing a single site for nucleotides, the existence of a much weaker secondary site (with a Kd value at least two orders of magnitude larger) cannot be excluded. The binding of AMP and adenosine to pig muscle 3-phosphoglycerate kinase is weaker than binding of MgATP; the respective Kd values are 0.36 +/- 0.05 mM and 0.65 +/- 0.05 mM. Thus, in addition to the interaction of the alpha-phosphate that is detectable by crystallography [Banks, Blake, Evans, Haser, Rice, Hardy, Merrett and Phillips (1979) Nature (London) 279, 773-777], the beta- and/or gamma-phosphate(s) of MgATP may also interact with the enzyme molecule. The fact that MgADP binds more tightly than ADP is consistent with its stronger inhibition of the reaction catalysed by the enzyme between 3-phosphoglycerate and MgATP. MgADP is a product of this reaction, and inhibits it competitively with both substrates; as an inhibitor its KI is comparable with the Kd found in binding studies. At the same time, the Km value for MgADP in the reverse reaction (0.18 +/- 0.05 mM; mean +/- S.E.M.) is higher than these constants; this may be due either to a different kinetic mechanism in this direction of the enzymic reaction, or to different binding modes of MgADP as inhibitor and as substrate. The reason why inhibition by MgADP is competitive with 3-phosphoglycerate may be that its binding prevents the specific change in conformation that the enzyme undergoes [Harlos, Vas and Blake (1992) Proteins 12, 133-144] when it binds 3-phosphoglycerate.

Adenosine↗
PubMed1993

Interleukin-1 and tumor necrosis factor stimulate arachidonic acid release and phospholipid metabolism in human myometrial cells.

OBJECTIVE: Our aim was to evaluate the effects of the cytokines interleukin-1 and tumor necrosis factor on arachidonic acid release in human myometrial cells. STUDY DESIGN: Primary monolayer cultures of human myometrial cells prelabeled with tritiated arachidonic acid were exposed to interleukin-1 or tumor necrosis factor for varying periods and the release of tritiated arachidonic acid and its loss from phospholipids were measured by radiochromatography. To gain some information on the biologic action of interleukin-1 the contractile response to oxytocin was measured in myometrial strips preincubated with this cytokine. Data were statistically evaluated with analysis of variance or Student's test. RESULTS: Both cytokines caused a dose-dependent increase in tritiated arachidonate release that was suppressed by the protein synthesis inhibitor cycloheximide. Tritiated arachidonic acid release was maximal after 24 hours of stimulation with interleukin-1. Both interleukin-1 and tumor necrosis factor stimulated the release of the isotopically labeled fatty acid from phosphatidylcholine. In addition, interleukin-1 also increased the loss of arachidonic acid from phosphatidic acid and significantly potentiated the oxytocin-evoked myometrial contractility. CONCLUSIONS: Both interleukin-1 and tumor necrosis factor enhance arachidonic acid release, probably by inducing the synthesis of phospholipase A2 and possibly other enzymes involved in the metabolism of phospholipids. In turn, arachidonic acid itself may act as a second messenger, synergizing with other uterotonic agents, as well as serving as the precursor for prostaglandins and various other bioactive eicosanoids.

Analysis of Variance↗
PubMed1992

N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents.

OBJECTIVE: With N omega-nitro-L-arginine, a potent inhibitor of nitric oxide synthesis, we tested the hypothesis that nitric oxide plays a functional role in the blunted pressor responsiveness seen during pregnancy. STUDY DESIGN: A group of six pregnant rats were instrumented on the fourteenth day of gestation and studied on days 19 and 20, as well as 7 days post partum. Another group of six virgin rats were similarly prepared and used 5 days after surgery. Blood pressure and heart rate were monitored in conscious freely moving animals before and during the administration of drugs or placebo. Results were analyzed, by one-way repeated-measures analysis of variance, with Dunnett's t test, or by paired t test where applicable. RESULTS: Basal mean arterial pressure and heart rate were 90.8 +/- 3.0 mm Hg and 330 +/- 6 beats/min in pregnant animals and 107.1 +/- 3.2 mm Hg and 315 +/- 7 beats/min in nonpregnant animals. Pressor responses to angiotensin II, vasopressin, and norepinephrine were attenuated in gravid animals. Infusion of N omega-nitro-L-arginine significantly and in a dose-dependent manner increased mean arterial pressure and reduced heart rate. These effects could be completely reversed by L-arginine administration. Changes in mean arterial pressure were higher during pregnancy as compared with postpartum values. N omega-nitro-L-arginine infusion potentiated pressor responses to all three vasopressors, resulting in dose-response curves that were significantly shifted to the left, making them virtually identical in pregnant and postpartum rats. CONCLUSION: Our data support the emerging view that nitric oxide plays a key role in the regulation of blood pressure during pregnancy.

Angiotensin II↗
PubMed1992

Influence of chicken and human lipoproteins on steroidogenesis in granulosa cells of the domestic fowl (Gallus domesticus).

When freshly dispersed granulosa cells from the largest preovulatory follicle were incubated in the presence of very low density (VLDL), low density (LDL), or high density (HDL) lipoproteins isolated from sera of laying hens, production of both basal and LH-stimulated progesterone was significantly increased in a dose-related manner. VLDL, the principal transporter of cholesterol to the ovum, appeared to be the most efficacious. A highly significant potentiation of the steroidogenic action of 8-bromo-cyclic adenosine monophosphate and forskolin was also observed. Human LDL, and especially HDL, caused significant stimulation of progesterone production by these cells. It is suggested that the release of cholesterol from lipoproteins taken up by granulosa cells raises the precursor pool for steroidogenesis. This mechanism is further enhanced by a cyclic AMP-mediated mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Dual action of arachidonic acid on calcium mobilization in avian granulosa cells.

The primary aim of this study was to evaluate the effects of arachidonic acid (AA) on calcium mobilization from intracellular compartments in digitonin-permeabilized granulosa cells isolated from the largest preovulatory follicles of laying hens. At low concentrations (ED50 0.2 microM) AA released 35% 45Ca from the endoplasmic reticulum (ER), whereas at higher concentrations (ED50 16 microM) it stimulated 45Ca efflux from mitochondria. These effects of AA were mimicked at 10-20 times lower concentration by the calcium ionophore A23187. Inositol 1,4,5-trisphosphate (IP3) also stimulated 45Ca efflux from the ER, with a markedly lower potency than AA (ED50 6.2 microM), as well as exhibiting a biphasic response. Heparin abolished the effect of IP3 and luteinizing hormone (LH), but it had no influence on AA-promoted 45Ca efflux. Moreover, the actions of IP3 and AA were additive, indicating that AA and IP3 access different Ca pools in the ER by different mechanisms. Several other unsaturated fatty acids also stimulated 45Ca mobilization from both ER and mitochondria but, with the exception of eicosapentaenoic acid, were significantly less effective than AA. It is concluded that free AA, at submicromolar concentrations that might be viewed as physiological, is a potent calcium mobilizing agent and thus may play an important role in signal transduction in avian granulosa cells, akin to that of IP3. At high (greater than 10 microM) concentrations AA removes Ca2+ from the mitochondria, an action that may be responsible for its reported inhibitory effects on steroidogenesis and other cellular functions.

Analysis of Variance↗