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Biomedical subjects

M Molnár

Publications and source records attributed to M Molnár.

At least 19 recordsLinked to original sources

Survival of mouse blastocysts after low-temperature preservation under high pressure.

Cryoinjuries are almost inevitable during the freezing of embryos. The present study examines the possibility of using high hydrostatic pressure to reduce substantially the freezing point of the embryo-holding solution, in order to preserve embryos at subzero temperatures, thus avoiding all the disadvantages of freezing. The pressure of 210 MPa lowers the phase transition temperature of water to -21 degrees C. According to the results of this study, embryos can survive in high hydrostatic pressure environment at room temperature; the time embryos spend under pressure without significant loss in their survival could be lengthened by gradual decompression. Pressurisation at 0 degrees C significantly reduced the survival capacity of the embryos; gradual decompression had no beneficial effect on survival at that stage. Based on the findings, the use of the phenomena is not applicable in this form, since pressure and low temperature together proved to be lethal to the embryos in these experiments. The application of hydrostatic pressure in embryo cryopreservation requires more detailed research, although the experience gained in this study can be applied usefully in different circumstances.

Animals↗

Impaired speech perception in aphasic patients: event-related potential and neuropsychological assessment.

The mismatch negativity component (MMN) of auditory event-related potentials (ERP) was recorded in four aphasic patients and in age, gender and education matched controls. The MMN changes elicited by tone, vowel, voicing stop consonant and place-of articulation contrasts were recorded over both hemispheres. The results of MMN amplitude, latency and distribution differences between aphasics and controls were analyzed in detail. An extensive neuropsychological investigation was performed in order to highlight the assumed dissociation and possible interactions between the impaired acoustic/phonetic perception and deficient comprehension in aphasic patients. Our principal finding was that MMN elicited by pitch deviations is not enough sensitive to distinguish between patients and age-matched controls. The MMN elicited by consonant contrasts was found to be the most vulnerable in aphasic patients investigated. The MMN elicited by voicing ([ba:] vs. [pa:]) and place-of-articulation ([ba:] vs. [ga:]) could be characterized by total lack, distorted or very limited distribution and correlated with the patients' performance shown in the behavioral phoneme discrimination task. The magnitude of the deficient phoneme (vowel and consonant contrasts) processing shown by MMN anomalies was proportionally related to the non-word discrimination and did not interact with the word discrimination performance. The impact of deficient speech sound processing on higher level processes may depend on the type of aphasia, while the presence of perceptual deficits in processing acoustic/phonetic contrasts seems to be independent of the type of aphasia.

Adult↗

Interleukin-1beta-induced prostaglandin E2 production in human myometrial cells: role of a pertussis toxin-sensitive component.

PROBLEM: The objective of this study was to evaluate the possible role of pertussis toxin (PTX)-sensitive G-protein(s) in interleukin-1beta (IL-1) signaling in human myometrial cells (HMC). METHOD: Primary cultures of HMC were stimulated with human recombinant IL-1 alone or in combination with PTX. Prostaglandin (PG) E2 in the medium was measured by radioimmunoassay, cyclooxygenase type 2 (Cox-2) and IkappaB by western analysis, and the activities of two members of the mitogen-activated protein kinase (MAPK) family of enzymes, ERK-2 and JNK, by the phosphorylation of appropriate substrates. RESULTS: IL-1 increased PGE2 output during an 18-hr long incubation by 21.7-fold (n = 5 experiments). This increase was inhibited by 57% after pretreatment overnight with PTX. IL-1-induced expression of Cox-2 protein was also suppressed to a similar degree in PTX-treated HMC cultures. Degradation of the nuclear factor kappa B (NF-kappaB)-inhibiting protein (IkappaB), a critical step in IL-1 signaling to the nucleus, was significantly inhibited by PTX, as was IL-1-induced activation of ERK-2 and JNK. CONCLUSIONS: It is suggested that the occupied IL-1 receptor-generated signal in HMC is transmitted by multiple pathways. One is coupled to a PTX-sensitive G-protein upstream from the MAPK phosphorylation cascade. This, in turn, may interact with another signaling pathway, the activation of NF-kappaB, via the phosphorylation of the IkappaB kinase complex.

Cells, Cultured↗

Oxytocin activates mitogen-activated protein kinase and up-regulates cyclooxygenase-2 and prostaglandin production in human myometrial cells.

OBJECTIVE: The objective of our study was to test the hypothesis that oxytocin promotes prostaglandin production by up-regulating cyclooxygenase-2 via activation of mitogen-activated protein kinase cascade in human myometrial cells. STUDY DESIGN: Confluent cultures of human myometrial cells obtained from uterine specimens of premenopausal women undergoing hysterectomy were serum starved for 48 hours before oxytocin stimulation. Prostacyclin levels, as 6-keto-prostaglandin F(1) (alpha), were measured by radioimmunoassay, and the cellular cyclooxygenase-2 protein content was determined by Western blot. Mitogen-activated protein kinase activity was assessed by measuring the phosphorylation of myelin basic protein. RESULTS: In a time- and dose-dependent manner oxytocin promoted prostacyclin production in human myometrial cells. Maximal responses were observed after 8 hours of stimulation at a dose of 100 nmol/L. This effect was mainly due to the expression of cyclooxygenase-2 protein. Within 5 minutes oxytocin significantly stimulated mitogen-activated protein kinase, as compared with the expression in untreated controls. The maximal increase in enzyme activity (2.5-fold) was obtained at 45 minutes. A selective inhibitor of mitogen-activated protein kinase activation (PD98059), as well as herbimycin, a tyrosine kinase inhibitor, and the transcriptional blocker actinomycin D, suppressed oxytocin-induced cyclooxygenase-2 expression and prostacyclin production. The stimulatory action of oxytocin was also sensitive to inhibition by pertussis toxin but appeared to be independent of protein kinase C activation. CONCLUSION: Our data indicate a largely unrecognized signal transduction mechanism for oxytocin, involving G-protein-coupled activation of mitogen-activated protein kinase and cyclooxygenase-2 gene expression, leading to increased prostaglandin production in human myometrial cells. This signaling pathway complements the rapid activation of the phosphoinositide cycle and may be responsible for sustained release of prostaglandins in uterine tissues, promoting labor and parturition.

Blotting, Western↗

The nuclear transcription factor NF-kappaB mediates interleukin-1beta-induced expression of cyclooxygenase-2 in human myometrial cells.

OBJECTIVE: Up-regulation of prostaglandin production by gestational tissues in the setting of intrauterine infection has been implicated as an important contributor to preterm labor and parturition. In this study we investigated the possible role of the nuclear transcription factor NF-kappaB in interleukin-1 signaling, leading to the expression of cyclooxygenase 2 and prostaglandin production in human myometrial cell cultures. STUDY DESIGN: Human myometrial smooth muscle cells from an immortalized line were used as a model system between passages 20 and 35. Growth-arrested cell cultures were stimulated with human recombinant interleukin 1, and the activation of NF-kappaB was assessed by the degradation of the inhibitory protein IkappaB-alpha (Western analysis), as well as by nuclear binding of NF-kappaB by using an electrophoretic mobility shift assay. The abundance of cyclooxygenase-2 messenger ribonucleic acid and protein was measured by Northern and Western analyses, whereas prostaglandin (prostaglandin I(2 ) and prostaglandin E(2 )) production was determined by specific radioimmunoassays. RESULTS: Within 15 minutes of stimulation with interleukin 1, 90% of IkappaB-alpha was degraded. This was temporally associated with nuclear translocation and binding of NF-kappaB. Within 30 minutes, cyclooxygenase 2 messenger ribonucleic acid appeared, with steady-state levels increasing up to 4 hours. This was followed by an up to 80-fold increase in cyclooxygenase 2 protein and a corresponding time-dependent increase in prostaglandin production. When IkappaB-alpha degradation was blocked with calpain I inhibitor, NF-kappaB translocation, cyclooxygenase 2 messenger ribonucleic acid and protein expression, and prostaglandin synthesis were also inhibited. CONCLUSION: Stimulation of human myometrial cells with interleukin 1 leads to rapid activation of the transcription factor NF-kappaB, which is functionally linked to the expression of cyclooxygenase 2 messenger ribonucleic acid, protein, and prostaglandin synthesis.

Blotting, Northern↗

Event-related dimensional reductions in the primary auditory cortex of the conscious cat are revealed by new techniques for enhancing the non-linear dimensional algorithms.

The analytic algorithms derived from non-linear deterministic models may be more sensitive to differences in physiological data than those based on linear stochastic models. Among the non-linear algorithms the time-dependent dimensional ones appear to be the most sensitive discriminators. In the present study dimensional responses were examined in both electronically and mathematically generated data and in high-resolution physiological data. The latter were event-related potentials (ERPs) recorded from the primary auditory cortex of cats during classical conditioning. Two techniques were found to lengthen and stabilize the linear scaling region in the correlation integral of the dimensional algorithms: (1) linking trials to increase data length; and (2) gain reduction to lower integer-values of noise, combined with algorithmic setting of slopes < 0.5 to zero. Of the three dimensional algorithms examined, only the time-dependent Point Correlation Dimension (PD2i) showed low error rates when tracking the dimensional shifts in non-stationary generated data. This algorithm also uniquely distinguished between the conditioned and unconditioned physiological responses. The ERPs had corresponding PD2i's that were significantly different from each other as well as from their own randomized-phase surrogates. The brief dimensional reduction that follows a conditioned stimulus is interpreted to be related to 'cooperativity' among the underlying cortical neurons that contribute to its electrogenesis.

Algorithms↗

Scalp distribution of the dimensional complexity of the EEG and the P3 ERP component in stroke patients.

The use of recently developed techniques allows the quantitative investigation of the non-linear properties of the electrical activity of the brain not only in basic but also in applied research. The point correlation dimension (PD2) was used in this study for the analysis of the electroencephalogram (EEG) recorded in patients with unilateral stroke caused by middle cerebral artery occlusion. The scalp distribution of the PD2 and that of the P3 event-related potential component was mapped and frequency spectra were calculated. Compared to normal controls, asymmetrical PD2 distribution was observed with low values on the side of the stroke, the extension of which depended on recording conditions (level of vigilance) and only partially corresponded to the region characterized by slow frequencies. In one case, ipsilateral reduction of the P3 wave was caused by a small subcortical stroke. The efficacy of the linear and non-linear methods in localizing brain pathology are evaluated and compared.

Electroencephalography↗

The dimensional complexity of the P3 event-related potential: area-specific and task-dependent features.

Appropriate methods are needed for the study of the non-linear properties of the nervous system. The correlation dimension, as expressed by the effective point correlation dimension (PD2eff), was used in this study for the analysis of the dimensional complexity of event-related potentials. The ERPs were recorded at Fz, Cz and Pz in an auditory oddball paradigm in which 'easy' and 'difficult' sensory discrimination tasks were applied. The PD2eff was calculated from each EEG epoch used in the process of ERP averaging. The PD2eff significantly decreased during the ERPs in which the P3-component appeared, and this reduction showed area-specific and task-specific patterns. The area-specific PD2eff changes indicated distinctive functional features of the frontal areas in this task. The magnitude of the PD2eff change was found to depend on the degree of task difficulty. Implications of the findings related to theories on the functional significance of the P3-wave in information processing are discussed.

Acoustic Stimulation↗

Auditory evoked potentials reflect serotonergic neuronal activity--a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus.

A valid indicator of central serotonergic neurotransmission would be useful for various diagnostic and psychopharmacological purposes in psychiatry. However, known peripheral serotonergic measures only partially reflect serotonergic function in the brain. Previous findings suggest that the intensity dependence of auditory evoked potentials (AEPs) is closely related to central serotonergic activity. The present study examines the effects of microinjection of a 5-HT1A agonist (8-OH-DPAT) and a 5-HT1A antagonist (spiperone) into the dorsal raphe nucleus (DRN) on AEP recorded epidurally from the primary and secondary auditory cortex in behaving cats. We found a stronger intensity dependence only of AEP from the primary auditory cortex after 8-OH-DPAT, which inhibits the firing rate of serotonergic DRN neurons, and a weaker intensity dependence after spiperone, which increases serotonergic cell firing, as compared to baseline measurements. These results demonstrate that the intensity dependence of AEP is inversely related to serotonergic neuronal activity and that it may be a promising tool for assessing central serotonergic function in humans (e.g., identifying patients with low serotonergic neurotransmission).

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Central core and nemaline rods in the same patient.

It is quite rare, that central cores and nemaline bodies occur in the same individual. We describe the case of a 12-year-old girl, who was born with bilateral congenital hip dislocation. Her early motor milestones were delayed. Due to proximal weakness of the lower extremities she has never been able to walk. The family history was negative. Muscle histology, histochemistry and electron microscopic studies showed a central core in nearly all muscle fibers, and nemaline rods in a few. The earlier literature and new genetical findings concerning these muscle abnormalities are also briefly summarized.

Child↗

Auditory-evoked potentials as indicator of brain serotonergic activity--first evidence in behaving cats.

Due to the increasing importance of the central serotonergic neurotransmission for pathogenetic concepts and as a target of pharmacotherapeutic interventions in psychiatry, reliable indicators of this system are needed. Several findings from basic and clinical research suggest that the stimulus intensity dependence of auditory evoked potentials (AEP) may be such an indicator of behaviorally relevant aspects of serotonergic activity (Hegerl and Juckel 1993, Biol Psychiatry 33:173-187). In order to study this relationship more directly, epidural recordings over the primary and secondary auditory cortex were conducted in chronically implanted cats under intravenous (i.v.) administration of drugs influencing the serotonergic and other modulatory systems (8-OH-DPAT, m-CPP, ketanserin, DOI, apomorphine, atropine, clonidine). The intensity dependence of the cat AEP component with the highest functional similarity to this of the N1/P2-component in humans was significantly changed by influencing 5-HT1a and 5-HT2 receptors, but not 5-HT1c receptors. This serotonergic modulation of the intensity dependence was only found for the primary auditory cortex which corresponds to the known different innervation of the primary and secondary auditory cortex by serotonergic fibers. Our study supports the idea that the intensity dependence of AEP could be a valuable indicator of brain serotonergic activity; however, this indicator seems to be of relative specificity because at least cholinergic effects on the intensity dependence were also observed.

Animals↗

[The favorable effect of humic acid based complex micro-element preparations in cadmium exposure].

The authors have studied the effect of consumption of a humic acid based complex microelement preparation (potassium, magnesium, iron, zinc, manganese, copper, vanadium, cobalt, molibden, selenium bound to humic acids) for six weeks (10 ml daily) on the biological exposure indices (blood and urine cadmium levels) and clinical laboratory parameters (liver and kidney tests, blood picture) of men (n = 18; 39.7 +/- 10.4 years of age;) working in cadmium exposure for 8.3 +/- 5.0 years. The initial mean blood and urine cadmium levels of the non-smoking subjects was twice higher than that of the non-smoking male controls living in the same urban area (n = 35), and significantly correlated with the length of exposure. Their mean serum alanin-aminotransferase, gamma-glutamyl-transferase, creatinine, uric acid and urinary N-acetyl-beta-D-glucosaminidase levels were significantly higher than that of the controls. After the six-week treatment blood cadmium level, activity of serum alanin-aminotransferase, serum uric acid and urinary protein concentrations decreased significantly, the abnormal serum iron levels normalized. According to this results, the absorption of cadmium decreased on the effect of the complex microelement supplementation and the adverse laboratory changes attributable partly to cadmium exposure improved. Therefore humic acid based complex microelement supplementation is recommended as an effective tool for prevention and health protection in occupational cadmium exposure as well as for smokers known to be considerably burdened by cadmium.

Cadmium↗

Dimensional complexity of the EEG in subcortical stroke--a case study.

The conventional electrophysiological methods used for the analysis of the functional characteristics of the nervous system are not able to grasp its non-linear and random features. Of the methods based on the application of chaos-theory the correlation dimension analysis can be used to quantify the complexity of the analyzed signal, such as the electroencephalogram (EEG). The new version (point-correlation dimension, PD2) was used in this study, which is more accurate than the other, currently used algorithms. The purpose of the present investigation was to compare the sensitivity of the methods based on chaos-theory with the traditional electrophysiological ones in a case when no apparent abnormality was present as judged on the basis of this latter methodology. The PD2 was calculated from the EEG recorded in 13 healthy control subjects and in a patient who suffered a small subcortical stroke 2 years prior to the investigation and who was free of neurological symptoms at the time of recording. Compared to that seen in the control group, in the Z-score maps of the scalp distribution of the PD2, a marked asymmetry was seen and the absolute PD2 values showed a low-dimensional area in the parietal region, ipsilateral to the stroke. A relative decrease of the gamma band was found in the frequency power spectra in the same area. It is suggested that the additional information extracted from the EEG by non-linear analysis may increase the sensitivity of electrophysiological methods for detecting brain pathology.

Algorithms↗

Use of harmonic scalpel for division of short gastric vessels at laparoscopic Nissen fundoplication. A new method.

The essential of laparoscopic Nissen fundoplication is creating a loose and tension free wrap requiring mobilisation of the gastric fundus. Division of the short gastric vessels (SGV) is a standard component of that procedure which requires considerable part of the operation time, and despite of a careful dissection sometimes significant blood loss can be occurred. The Ultracision Harmonic Scalpel (HS) makes the process quicker safer and can cause less intraoperative complication. This study compares our original method of vessel control (at 10 cases, Group 1), to the Ultracision Harmonic Scalpel (at 10 cases, Group 2) Times for SGV division, estimated blood loss and intraoperative and postoperative complications were evaluated. In the favour for Group 2 a significant reduction was reached in the time required for division of SGV to mobilize the fundus. As the most common postoperative complication, the dysphagia concerns we found significant difference in the two groups and dysphagia was mild at Group 2. Application of HS provide safer, easier and faster division of SGV resulting significant savings of time and less prone to thermic trauma and recommended at LNF operations to avoid potential intra- and postoperative complications.

Blood Loss, Surgical↗

Intensity dependence of auditory evoked potentials in behaving cats.

The intensity dependence of auditory evoked potentials (AEPs) recorded epidurally over the primary (AI) and secondary (AII) areas of the auditory cortex was studied in behaving cats during wakefulness, sleep and anesthesia. Four kHz tones of 50, 60, 70, and 80 dB SPL, presented in random order every 2 +/- 0.2 s by a bone conductor, elicited clear changes of the AEP amplitudes with increasing stimulus intensity, but individual components displayed different response curves. AEP components from the AI region showed saturation of their amplitude with stimulus intensity (P13, P34) or no amplitude increase (N19), while amplitude and intensity were linearly related in the AII area. The intensity dependence of the first positive component (P12/P13) was consistently stronger for the AEP recorded from the AI than from the AII area, while later components exhibited no difference between AI and AII. During slow wave sleep, the intensity dependence of this first positive component increased in the two areas, while that of later components decreased. Pentobarbital anesthesia abolished almost all later components and depressed the intensity dependence of the first positive component both in the AI and AII area. These results indicate that (I) clear intensity dependence of AEP exists in the cat auditory cortex and (2) this intensity dependence, especially that of the first positive AEP component, shares functional similarities to the human augmenting/reducing phenomenon in the auditory modality concerning regional differences and sleep-waking cycle.

Acoustic Stimulation↗