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P Sotonyi

Publications and source records attributed to P Sotonyi.

At least 19 recordsLinked to original sources
PubMed2001

Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective.

The recently discovered hormone, ghrelin, has been recognized as an important regulator of GH secretion and energy homeostasis. Orexigenic and adipogenic ghrelin is produced by the stomach, intestine, placenta, pituitary, and possibly in the hypothalamus. The concentration of circulating ghrelin, principally derived from the stomach, is influenced by acute and chronic changes in nutritional state. To date, most studies focused on the role of ghrelin in GH secretion or its function in complementing leptin action to prevent energy deficits. The potential significance of ghrelin in the etiology of obesity and cachexia as well as in the regulation of growth processes is the subject of ongoing discussions. A large quantity of information based on clinical trials and experimental studies with ghrelin and previously available synthetic ghrelin receptor agonists (GH secretagogues) must now be integrated with a rapidly increasing amount of data on the central regulation of metabolism and appetite. In this overview, we summarize recent findings and strategies on the integration of ghrelin into neuroendocrine networks that regulate energy homeostasis.

Animals↗
PubMed1999

Preprotachykinin-A mRNA expression in the human and monkey brain: An in situ hybridization study.

The mRNA expression for preprotachykinin-A (PPT-A) was studied throughout the human and cynomolgus monkey brain to assess the neuroanatomical expression pattern of the PPT-A gene in primates. In situ hybridization showed that the PPT-A mRNA is expressed highly in specific regions of the postmortem human brain, including the striatum, islands of Calleja, hypothalamus (posterior, premammillary, medial mammillary, and ventromedial nuclei), superior and inferior colliculi, periaqueductal gray, and oculomotor nuclear complex. PPT-A mRNA-expressing neurons also were present in the paranigralis (ventral tegmental area) and were scattered in the bed nucleus stria terminalis throughout the sublenticular substantia innominata region, including the diagonal band of Broca and the nucleus basalis of Meynert. In the hippocampus, high PPT-A mRNA expression was localized predominantly to the polymorphic layer of the dentate gyrus; no labeled cells were present in the granular layer. Positively labeled cells also were found scattered in the CA regions as well as in the amygdaloid complex. Neocortical expression of PPT-A mRNA was localized mainly to the deep laminae (layers V/VI), except for the striate cortex (labeling was seen also in superficial layers). The subiculum, thalamus, globus pallidus, ventral pallidum, substantia nigra pars compacta, red nucleus, pontine nuclei, and cerebellum were characterized by very weak to undetectable expression of PPT-A mRNA. An expression pattern was evident in the monkey forebrain similar to that observed in the human, except for the absence of PPT mRNA-expressing cells in the medial mammillary nucleus despite intense expression in supramammillary, lateral mammillary, and premammillary nuclei. Overall, more similarities than differences are apparent between primate species in the expression pattern of the PPT-A gene. J. Comp. Neurol. 411;56-72, 1999.

Adult↗
PubMed1998

Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides.

The aim of this study was to investigate whether the previously observed adaptive changes in the monoaminergic receptors in post-mortem brains of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from ten brains of antidepressant-free depressed suicide victims and ten matched controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC isoenzymes by Western blotting with monoclonal antibodies specific for these proteins. A major finding of the study was a significant decrease in GAP-43 protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and 34%, respectively) of suicide brains compared to controls. No significant changes were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala, substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional distribution but were not significantly altered in any of the regions examined. Given the role of GAP-43 in the establishment and reorganization of synaptic connections, the finding of selective reduction of this protein in prefrontal cortex suggests that a dysfunctional synaptic organization in this region may be associated with depression and suicidal behaviour. This study provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.

Adult↗
PubMed1996

Cardiac nuclear hormone receptor mRNA in heart failure in man.

Eight donor hearts and six explanted hearts due to dilated cardiomyopathy, normal skeletal muscle and liver were analysed. Glucocorticoid receptor (GR) and thyroid hormone receptor (T3R) isoforms beta 1, beta 2, alpha 1 and alpha 2 mRNA abundance were determined by solution hybridization. Both GR and T3R receptor mRNA isoforms were lower in the myocardium as compared to skeletal muscle and in particular to liver. GR mRNA abundance was higher than that of any T3R isoform while the sum of ligand-binding isoforms (beta 1, beta 2 and alpha 1) were similar in the myocardium and in skeletal muscle as opposed to the liver where GR mRNA was higher. GR mRNA abundance was similar in right and left ventricles from donor hearts and in cardiomyopathy. T3R beta 1 showed higher levels in the right ventricle with higher levels in cardiomyopathy as compared to donor heart. T3R isoform alpha 1 and especially the alpha 1/alpha 2 ratio were lower in left ventricle in cardiomyopathy compared to donor hearts. In conclusion, GR and T3R isoforms mRNA abundance are low in the human myocardium. In the failing myocardium GR and T3R beta 2 and alpha 2 show no signs of reactivity while T3R beta 1 and alpha 1 mRNA adapt.

Adolescent↗
PubMed1995

Beta 1 and beta 2 adrenoceptor ligand and mRNA expression in dilated cardiomyopathy.

beta 1 and beta 2 adrenoceptor ligand activity has been shown to be down-regulated in failing myocardium. It is the aim of this study to test the hypothesis that also mRNA levels are down-regulated in dilated cardiomyopathy. beta 1 and beta 2 adrenoceptor ligand activities and mRNA expressions were analyzed in left ventricular biopsies from six organ donor hearts, in papillary muscles from seven patients operated on for mitral regurgitation, and in six explanted hearts as the result of dilated cardiomyophathy. mRNA levels were determined by solution hybridization. beta 1 ligand activity was decreased in the cases of mitral regurgitation (p < 0.01) and dilated cardiomyopathy (p < 0.001). beta 2 ligand activity did not differ between the three groups. mRNA expression was depressed in mitral regurgitation regarding both beta 1 (p < 0.001) and beta 2 (p < 0.01), while no differences were observed in dilated cardiomyopathy as compared to the donor hearts. The regulation of beta 1 and beta 2 adrenoceptor ligand activity and mRNA expression appears to follow a specific pattern in dilated cardiomyopathy. The specific down-regulation of beta 1 ligand activity seems to occur at a posttranslational level.

Adipose Tissue↗
PubMed1995

Na,K-ATPase receptor subunits alpha 1, alpha 2 and alpha 3 mRNA in dilated cardiomyopathy.

Na,K-ATPase receptor density has been shown to be down-regulated with decreasing ejection fraction in patients with chronic heart failure. It was the aim of the present study to determine whether down-regulation is detected also at the mRNA level. Six donor hearts and six explanted hearts due to dilated cardiomyopathy (ejection fraction 23 +/- 5%) were analyzed. RNA was extracted. Quantitative Na,K-ATPase receptor catalytic subunit alpha 1, alpha 2 and alpha 3 mRNA expression was determined by solution hybridization. No cross-reactivity occurred between the three probes. alpha 1 mRNA was expressed at about 5 and 10 times higher (p < 0.001) concentrations than alpha 2 and alpha 3 mRNA, respectively, and alpha 2 mRNA higher (p < 0.001) than alpha 3. There were no differences between right and left ventricles and between donor hearts and patients with dilated cardiomyopathy. In conclusion, Na,K-ATPase alpha 1 mRNA is the predominant subunit expressed in human myocardium. Depressed ejection fraction in dilated cardiomyopathy is not associated with changed mRNA subunit expression. Documented downregulation of Na,K-ATPase activity, therefore, may be associated with the structural and membrane-related beta subunit or posttranscriptional modification of the catalytic subunits.

Adolescent↗
PubMed1993

Vasoactive intestinal polypeptide immunoreactive structures in the mouse barrel field.

Immunohistochemistry for vasoactive intestinal polypeptide was carried out in tangentially cut vibratome sections of the barrel cortex in adult mice. Sections through layer IV have revealed an association between the cytoarchitectonically visible modular organization of barrels and the distribution of immunoreactive axon terminals. These terminals are preferentially localized in the side region of a barrel, whereas the hollow shows a relative scarcity of these structures as shown with image analysis. This finding is the first direct demonstration of a modular distribution of vasoactive intestinal polypeptide-containing axon terminals in the neocortex.

Animals↗
PubMed1993

Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy.

OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.

Adolescent↗
PubMed1992

Increase in functional activity rather than in amount of Gi-alpha in failing human heart with dilated cardiomyopathy.

OBJECTIVE: The aim was to investigate whether or not increased pertussis toxin catalysed ADP ribosylation correlates with increased amount of Gi-alpha in failing human heart. DESIGN: Antisera raised against unique synthetic peptides corresponding to alpha subunits of Gs and Gi 1-3 were used in immunoblotting and ELISA to determine amounts of various G proteins. Adenylyl cyclase activity, beta adrenoceptors, and muscarinic receptors were then measured in cardiomyopathic hearts (n = 6) obtained at transplant in order to study whether or not an altered expression of G proteins has relevance to the integrity and function of the receptor--adenylyl cyclase system. Six non-failing control hearts were also studied. RESULTS: No significant differences in the peptide equivalent amounts of either Gs or Gi were found in the failing human heart as compared to the non-failing heart. However, functional activity of Gi was shown to increase significantly since there was a decrease in basal (57%), isoprenaline stimulated (60%), and guanyliminodiphosphate stimulated (52%) adenylyl cyclase activity. In contrast the density of beta adrenoceptors was markedly decreased (51%) in failing human heart in comparison to non-failing hearts. Neither the density nor the affinity of muscarinic receptors changed in the failing human heart. CONCLUSION: These results suggest that in the failing human heart, there is an increase in functional activity rather than in amount of Gi, and an important part of functional expression of Gi-alpha may be regulated at the post-translational level.

Adenylyl Cyclases↗
PubMed1991

Left ventricular beta 1 and beta 2 adrenoceptor mRNA expression in normal and volume overloaded human heart.

STUDY OBJECTIVE: The aim was to determine gene expressions of beta 1 and beta 2 adrenoceptor subtypes (BAR-1, BAR-2) in normal and volume overloaded human heart. DESIGN: Tissue mRNA levels were determined by excess solution hybridisation using 35S-UTP labelled BAR-1 and BAR-2 cRNA probes. MATERIAL: Atrium, right and left ventricular subendocardium, and papillary muscle from donor hearts and papillary muscle from patients operated for mitral stenosis and mitral regurgitation were studied. MEASUREMENTS AND MAIN RESULTS: The basal levels of myocardial BAR-1 and BAR-2 mRNA expression were similar to the levels in human adipose tissue that have been reported previously from our laboratory (10-15 amol mRNA.micrograms-1 total nucleic acids). No differences in BAR-1 and BAR-2 mRNA expression were observed between various parts of the normal heart. In papillary muscle, BAR-1 and BAR-2 mRNA levels were 8.8 (SEM 5.1) and 10.2(6.6) amol.micrograms-1 total nucleic acids, respectively. Furthermore, no differences in BAR mRNA expression were observed between myocardium subjected to mitral stenosis as compared to normal myocardium. On the other hand, patients with mitral regurgitation expressed significantly lower levels of both BAR-1 and BAR-2 mRNA, at 4.8(1.0) (p less than 0.05) and 2.6(1.1) (p less than 0.001) amol.micrograms-1 total nucleic acids, respectively. The ratio BAR-1/BAR-2 mRNA was higher (p less than 0.01) in mitral regurgitation than in the normal heart. CONCLUSIONS: Myocardium from different parts of the normal human heart, where different pressure work is generated, express similar levels of BAR-1 and BAR-2 mRNA. With volume load a significant decrease in BAR mRNA levels was observed, which was more marked for BAR-2 mRNA. This difference in specific mRNA levels in patients with mitral regurgitation indicates an independent regulation of the expression of these two receptor subtypes.

Adolescent↗
PubMed1991

Dynamics of creatine kinase shuttle enzymes in the human heart.

Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n = 8) and in papillary muscles of patients operated on for mitral regurgitation (n = 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS (P less than 0.0001), total CK (P less than 0.05) and CKMIT (P less than 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5-1% of total CK and 4-5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P less than 0.02), whereas CKB was 15-20 times higher (P less than 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Myoglobin content and citrate synthase activity in different parts of the normal human heart.

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.

Adolescent↗
PubMed1989

Lactate dehydrogenase and its isoenzyme activities in different parts of the normal human heart.

Activity and distribution of lactate dehydrogenase (LD) and its isoenzymes (LD1-5) were determined and both the heart (H) and muscle (M) subunit activities were calculated in myocardial samples from six brain dead human organ donors with normal hearts. Ten parts of each heart were analysed. LD1-3 were found to be the main LD isoenzymes. The LD1 activity predominated in all parts analysed. The activities of total LD, H subunit and LD1 increased from atria and auricular appendages via the right ventricle to the left ventricle. The H subunit activity varied more than twofold and the M subunit activity by only 20% between different locations of the heart. The left ventricular papillary muscle was found to have higher activities than other locations of both H and M subunits. It is concluded that the isoenzyme profile could be a metabolic adaptation to divergent work demand on the different heart chambers.

Adaptation, Physiological↗
PubMed1989

Immunofluorescence detection of digoxin with monoclonal digoxin specific antibody.

The present study primarily focuses on the analysis of digoxin binding of the heart muscle cells. The primary aim of the investigation was to demonstrate the cardiac glycoside morphologically. The direct immunofluorescence staining technique with digoxin specific monoclonal antibody or Fab fragments and FITC or Texas-Red conjugated antisera are useful for morphological demonstration of digoxin binding and localization in cardiac cells. With the immunofluorescence method, linkage can be observed on the sarcolemma membrane and on the wall of capillaries and arterioles in myocardial cells treated by cardiac glycoside. The specificity of reaction is provided by the negative reaction of cells, not treated by digoxin. Intensity of reaction depends on concentration. The photometric measuring of fluorescence enables the quantitative analysis of cardiac glycoside. It shows the sensitivity of the method in that cardiac glycoside linked to the cell membrane can be detected in the upper sphere of a therapeutic dose. Application of the immunofluorescence method is manifold and relatively simple, and this quick method can be used in diagnoses and in the study of cardiac glycoside receptors of cell membrane. On the basis of our own experiments it is possible to study the kinetics of digoxin linkage. The use of this method is demonstrated for investigation of single cell suspension and cryostat sections.

Animals↗
PubMed1988

Coenzyme Q10 content in different parts of the normal human heart.

Coenzyme Q10 (CoQ10) and citrate synthase (CS) activities were analysed in the myocardium of brain-dead organ donors (14-40 years). Different parts of the heart were studied: right and left auricular appendage, right and left atrium, right ventricle (septum and free wall) and left ventricle (septum, free wall, and papillary muscle). Freeze-dried, dissected myocardial samples were analysed for CoQ10 content by HPLC and CS activity by fluorometric technique. CoQ10 content in the normal human myocardium was lowest in auricular appendages and atria (0.25 +/- 0.06 mg X g-1 dry muscle), intermediate in right ventricle (0.37 +/- 0.05 mg X g-1 dm) and highest in left ventricle (0.42 +/- 0.07 mg X g-1 dm). CS activity showed the same relationship between these locations as CoQ10. The results suggest that there exist differences in CoQ10 content between different parts of the normal human myocardium. These differences were closely related to the differences in CS activity between corresponding parts. The differences between different parts of the heart may be related to divergent work demand, and the constant relationship between CS and CoQ10 may be related to their coupling to the mitochondrial oxidative metabolism.

Adult↗