Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells.

The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.

Bacterial Infections After Kidney Transplantation: A Single-Center Experience.

BACKGROUND: Bacterial infections significantly affect graft loss and mortality after kidney transplantation (KT). We reviewed the frequencies, risk factors, and sources of bacterial infections after KT and their impact on graft and patient survivals. METHODS: The data of 154 kidney recipients who underwent transplantation from 2010 to 2015 were explored. Donor, recipient, and surgical parameters were collected, and source, type, and frequency of infectious complications, number of infective episodes, multidrug-resistant (MDR) bacteria, and the bacterial spectrum were established. RESULTS: The most common infection was urinary tract infection, which is in line with the literature. Out of the 154 recipients, 72.1% (n = 111) had at least 1 occasion of a bacterial infection episode with clinical symptoms. It occurred 0-43 months (mean, 19.5 mo) after transplantation. Ninety-three KT recipients (67.9%) developed 274 episodes of infection in the postoperative 1st year (1.8 episodes/patient/y), and 42 patients had admission to the hospital ward (5.2 d/patient/y). MDR was detected in 19.8% of the infections. CONCLUSIONS: A bacterial infection had no significant impact on survival by itself. However, in case of sepsis graft and patient survivals were lower compared with normal control subjects.

A Single-center Experience of Allograft Nephrectomies Following Kidney Transplantation.

INTRODUCTION: Approximately 10% of renal allografts fail during the first year after kidney transplantation (KT) and 3%-5% thereafter yearly. The indication and timing of allograft nephrectomy (AN) is still uncertain in some cases. The aim of this study was to reveal the ratio, etiology, and complications of AN at our center. MATERIAL AND METHODS: This is a retrospective study of all patients who underwent KT at our center between January 1, 2004 and December 31, 2014. We analysed the frequency, indications, timing, and complications of ANs. Also early and late ANs were compared. RESULTS: From 417 renal transplantations 49 ANs were performed (11.7%). The most frequent indications were chronic allograft nephropathy (25; 51%), arterial blood supply complications, like arterial thrombosis and stenosis (7; 15%), treatment-resistant acute rejection (3; 6%), and nonreparable ureter complications (3; 6%). The average time of AN since KT was 28 months. ANs were performed as an urgent setting in 16 (33%) cases, whereas it was elective in 33 cases (67%). The AN was executed within 30 days (early) in 11 (22%) cases, and thereafter (late) in 38 (78%) cases. The main indication for early AN was renal artery thrombosis (4; 37%) and chronic allograft nephropathy (25; 66%) for late AN. Surgical complications occurred in 10 cases (20; 4%). The most common was hematoma. CONCLUSION: The majority of the ANs were elective and late (more than 30 days; average time, 47 months). Leading indication was chronic allograft nephrectomy. Early ANs were urgent and life-saving in all cases.

Surgical Complications Following Kidney Transplantations: A Single-Center Study in Hungary.

Surgical complications (SCs) are still high potential causes of graft loss. The incidence has a huge amount of variations depending on many factors. Our aim was to study the postoperative technical complications following kidney transplantations (KTs) during a 5-year period between 2011 and 2015. In the observed time frame there were 47 SCs occurring in 32 (19.4%) patients of 165 KTs. Every complication was classified into 3 groups: vascular (11; 6.6%), urologic (16; 9.7%), and any others (20; 12.1%). The most common postoperative SCs in our center were hemorrhage (14; 8.5%), urinary leakage (12; 7.2%), and renal artery stenosis (6; 3.6%). Twenty-seven patients, 84% of those having had a SC, needed an intervention, mainly a surgical correction (28; 62%). Half of these interventions (21; 51%) were performed due to urologic reasons. As possible predicting factors, we studied the type of arterial and ureter anastomosis in relation to onset of vascular and urologic complications. There was no significant correlation. The same was true for any donor and/or recipient demographic parameters. However, the presence of SCs impaired both patient and graft survival. The cumulative 6-month, 1-, 3-, and 5-year patient survival rates were 97% versus 99%, 93% versus 99%, 84% versus 97%, and 84% versus 97% for patients with/without (w/wo) a SC, respectively (P = .028). The cumulative 6-month, 1-, 3-, and 5-year graft survival rates were 81% versus 96%, 77% versus 94%, 68% versus 86%, and 54% versus 86% for the same 2 groups, respectively (P = .003).

Effects of erythropoietin on glucose metabolism.

We purposed to determine the impact of erythropoietin on altering glucose metabolism in the settings of in vitro and in vivo experiments. The acute effect of erythropoietin on lowering blood glucose levels was studied in animal experiments. In [³H]-deoxy-D-glucose isotope studies we measured glucose uptake with insulin and erythropoietin using 3T3-L1 cells cultured under normal or high glucose conditions. Altered activation of Akt and ERK pathways was evaluated in immunoblot analyses. Immunocytochemistry was conducted to determine the glucose transporter 4 translocation to the plasma membrane. Addition of erythropoietin significantly lowered blood glucose levels in vivo in rats. The glucose uptake was markedly increased by erythropoietin treatment (at concentrations 0.15, 0.3, and 0.625 ng/ml) in adipocytes grown in high glucose medium (p<0.05), but it remained unaltered in cells under normal glucose conditions. Significant increase of phosphorylation of ERK and Akt was detected due to erythropoietin (p<0.05). Co-administration of erythropoietin and insulin resulted in higher phosphorylation of Akt and [³H]-deoxy-D-glucose uptake in adipocytes than insulin treatment alone. We found that erythropoietin induced the trafficking of glucose transporter 4 to the plasma membrane. Our data showed that erythropoietin significantly decreased blood glucose levels both in vivo and in vitro, in part, by increasing glucose uptake via the activation of Akt pathway. Preliminary data revealed that adipocytes most likely exhibit a specific receptor for erythropoietin.

Measurements of H-->D-->(gamma-->,pi) and implications for the convergence of the Gerasimov-Drell-Hern integral.

We report new measurements of inclusive pi production from frozen-spin HD for polarized photon beams covering the Delta(1232) resonance. These provide data simultaneously on both H and D with nearly complete angular distributions of the spin-difference cross sections entering the Gerasimov-Drell-Hearn (GDH) sum rule. Recent results from Mainz and Bonn exceed the GDH prediction for the proton by 22 microb, suggesting as yet unmeasured high-energy components. Our pi0 data reveal a different angular dependence than assumed in Mainz analyses and integrate to a value that is 18 microb lower, suggesting a more rapid convergence. Our results for deuterium are somewhat lower than published data, considerably more precise, and generally lower than available calculations.

Pattern influence on the fingers.

In this study dermatoglyphic traits in 16 populations in northern Hungary were examined. The occurrence and probability of the manifestation of finger pattern types were analysed. Certain relationships were found that show that if a given pattern type is present on one of the fingers, then, in these cases, the frequency of pattern types on the other nine fingers typically is different from that in the entire sample. We termed this relationship or effect; pattern influence. In most cases there was a strong significant difference in frequency values between the entire sample and the studied cases. We studied the relationship of populations and pattern types using correspondence analysis. In the entire sample, most populations are located around the ulnar loop and the whorl. This arrangement is significantly and typically different in pattern-influence cases. Most populations aggregated around the pattern type in which pattern influence was studied. Pattern influence was found in all populations studied, and in both sexes.

[Hydranencephaly. (Severe cerebral malformations in three newborn infants)]. / Hydranencephalia (a súlyos agyi elváltozásról három újszülött kapcsán).

Three neonatal cases of hydranencephaly are reported. Clinical and radiological characteristics of this disease are also described. Factors which can have any role in the development of hydranencephaly are reviewed. The importance of intrauterine ultrasonography and the quick, early diagnosis is emphasized. Therapeutic approaches are also discussed.

Cefetamet pivoxil treatment causes loss of carnitine reserves that can be prevented by exogenous carnitine administration.

Two groups of pediatric patients receiving cefetamet pivoxil treatment (3 x 500 mg daily) for 7 days were studied. In the first group (Group A) the drug was administered alone; in the second group (Group B) the drug was given in combination with a molar excess of carnitine (3 x 1 g). Medication with cefetamet pivoxil alone was associated with a large urinary excretion of pivaloylcarnitine: Approximately 71% of the daily pivalate intake could be eliminated as carnitine ester in the urine. In this group, the plasma level and the urinary output of free carnitine decreased. By contrast, in Group B, the administration of molar excess of carnitine aided stochiometric elimination of pivalate as carnitine ester, and the plasma levels and carnitine-free urinary output were unchanged. The data show that medication of cefetamet pivoxil results in the formation of pivaloylcarnitine in children; the sustained loss of carnitine esters can ultimately lead to carnitine deficiency. Molar excess of exogenous carnitine aids in the elimination of pivalate derived from cefetamet pivoxil therapy and helps to maintain the carnitine reserves.

Differential Ras-dependence of gene induction by nerve growth factor and second messenger analogs in PC12 cells.

Induction of neurite formation by nerve growth factor (NGF) in PC12 pheochromocytoma cells can be efficiently inhibited by expressing a dominant negative mutant form of the small guanine nucleotide binding Ha-Ras protein in these cells. The block in NGF-induced neuritogenesis caused by inhibition of endogenous Ras proteins was found to be partially relieved by simultaneous stimulation of cAMP- or Ca++-dependent signaling pathways. Since expression of certain genes is believed to be involved in NGF-signaling leading to morphological differentiation, we decided to study the combined effects of NGF and second messenger analogs on gene expression in PC12 cell lines expressing different levels of the interfering Ras protein. We found NGF-second messenger combinations that induced normal c-fos, zif268 and nur77 early-response gene expression without neuritogenesis, and, conversely, cell lines in which certain combination treatments caused partial neuronal differentiation in the absence of substantial activation of these genes. Similarly, neurite outgrowth induced by combination treatments does not seem to require the activation of the late-response transin gene. Our results thus suggest a lack of strong correlation between NGF-stimulated early- and secondary-response gene induction and morphological differentiation.

Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway.

Growth factor-dependent survival of a variety of mammalian cells is dependent on the activation of phosphatidylinositol (PI) 3-kinase and its downstream effector, the protein kinase Akt. Glycogen synthase kinase-3 (GSK-3) has been previously identified as a physiological target of Akt, which is inhibited by phosphorylation, so we have investigated the role of GSK-3 in cell survival. Overexpression of catalytically active GSK-3 induced apoptosis of both Rat-1 and PC12 cells, whereas dominant-negative GSK-3 prevented apoptosis following inhibition of PI 3-kinase. GSK-3 thus plays a critical role in regulation of apoptosis and represents a key downstream target of the PI 3-kinase/Akt survival signaling pathway.

Carnitine administration ameliorates the changes in energy metabolism caused by short-term pivampicillin medication.

UNLABELLED: Ten children receiving pivampicillin for 8 days were studied. On the first 4 days the drug was given alone (4 x 500 mg/day), and on the last 4 days in combination with carnitine (4 x 1 g/day). Pivampicillin treatment was associated with formation and urinary excretion of pivaloylcarnitine and administration of carnitine aided the elimination of pivalate as its carnitine ester. The resting respiratory quotient increased from 0.86 +/- 0.01 to 0.96 +/- 0.01 on the 4th day of pivampicillin treatment. A shift was observed in the metabolic fuel consumption: a significant decrease was found in the amount of fats oxidized (0.31 +/- 0.17 vs 1.27 +/- 0.17 g x kg[-1] x 24 h[-1]). while the utilization of carbohydrates increased (6.20 +/- 0.51 vs 4.00 +/- 0.50 g kg[-1] x 24 h[-1]). Administration of carnitine decreased the respiratory quotient to 0.90 +/- 0.01 on the 8th day of treatment, consumption of fats increased, and the oxidation of carbohydrates decreased. The resting energy expenditure was not affected by the treatment. CONCLUSION: Pivampicillin treatment results in inhibited oxidation of fats as metabolic fuel. This drug effect was partially reversed by carnitine which promotes the elimination of the pivaloyl moiety from the body.

Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid.

Energy metabolism was measured in children receiving long-term treatment with valproic acid. In 8 of 10 randomly selected subjects, the resting respiratory quotient was higher than in age- and sex-matched control subjects (0.91 +/- 0.01 vs 0.87 +/- 0.01; p < 0.05). A shift was observed in fuel consumption, and a significant reduction was found in the amount of fats oxidized (0.68 +/- 0.23 vs 1.18 +/- 0.18 gm.kg-1.day-1), which was accompanied by increased utilization of carbohydrates (5.31 +/- 0.79 vs 3.81 +/- 0.39 gm.kg-1.day-1) in comparison with the control subjects. The resting total energy expenditure was not affected by the treatment. The children with an altered energy consumption pattern (n = 8) received carnitine supplementation for a month; the respiratory quotient then decreased (0.87 +/- 0.02), the oxidation of fats increased (1.42 +/- 0.25), and the consumption of carbohydrates decreased (3.87 +/- 0.79), but no changes in resting energy expenditure were observed. We conclude that carnitine depletion, a known adverse effect of valproic acid administration, may result in inhibited fatty acid oxidation, leading to a shift of substrates utilized from fats to carbohydrates.

Relationship of carnitine and carnitine precursors lysine, epsilon-N-trimethyllysine, and gamma-butyrobetaine in drug-induced carnitine depletion.

Plasma concentrations and rates of urinary excretion of carnitine and some of its precursors were studied in three groups of children receiving drugs known to cause carnitine depletion. Patients in group A received pivampicillin and a molar equivalent of carnitine for 7 d. Patients in group B received pivampicillin with a 5.8-fold molar excess of carnitine for 1 wk. Patients in group C were treated chronically with valproic acid and received a molar equivalent (to valproic acid) of carnitine for 14 d. Patients in group A had markedly increased (16-fold) urinary carnitine ester excretion concomitant with diminished urinary free carnitine and gamma-butyrobetaine output and lower plasma free carnitine concentration. Supplementation with one molar equivalent of carnitine (to pivampicillin) was ineffective in preventing the reduction of plasma carnitine concentration observed with pivampicillin treatment alone. For group B patients, administration of excess carnitine resulted in a further increase (35-fold) of urinary carnitine ester output with no decrease of plasma carnitine concentration, urinary gamma-butyrobetaine, or free carnitine excretion. For patients in group C, the initially low plasma free and total carnitine concentrations and urinary output of carnitine and carnitine esters markedly increased with carnitine supplementation, but urinary excretion of gamma-butyrobetaine remained unchanged. The plasma concentrations and urinary output of L-lysine and epsilon-N-trimethyllysine remained unchanged within each group before and after treatment. A positive linear correlation was found between urinary epsilon-N-trimethyllysine and 3-methylhistidine output, indicating that the rate of epsilon-N-trimethyllysine excretion correlates with the amount of 3-methylhistidine liberated by protein turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of religious affiliation on surname repetition in marriages in Tiszaszalka, Hungary.

The repeated-pairs of surnames in marriages (RP) approach is applied to the population of Tiszaszalka in north-eastern Hungary. The results indicate that: (1) lineage-like behaviour in mate choice results in population subdivision in both the Catholics and the Protestants of the village; (2) unlike in some other Tiszahat villages, the isonymous and the repeating unions in Tiszaszalka occur in different lineages so, in neither of these subpopulations are isonymous and repeating unions monopolised by a few lineages; (3) religious affilitation influences the mating structure of the population as measured by RP summary scores.

PIP: Matrix methods have been devised to overcome the limitation of the isonomy method with high sampling errors. The repeated pairs (RP) of surnames in marriages approach proposed by Lasker and Kaplan in 1985 measures the effect of lineage in mate choice. Any excess of RP over the random occurrence (RP1) indicates lineage involvement via surnames. The degree of population subdivision from lineage influence on mate choice was estimated, lineage influence on repeating matings and isonomy was analyzed, and the effect of religion on mate choice in repeating and isonymous unions was explored. Marriage records were obtained in 1986 in Tiszaszalka and from the Genealogical Society in Salt Lake City, Utah (from 1806 for Protestants and from 1936 for Catholics). 1271 first marriages were analyzed: 972 Protestants and 299 Catholics. The RP and RP1 were larger among the Protestants than among the Catholics. The chi-square value for unique and nonunique surname pairs for the 2 religions was statistically significant: for total Protestant vs. incomplete Catholic and for partial Protestant vs. incomplete Catholic. The distribution of Isonymous and nonisonymous marriages of both religions was not significant indicating no inbreeding. After excluding isonymous matings the chi-square values for unique and nonunique surname pairs remained significant for both religious groups. The coefficient of isonomy indicated that both groups avoided isonymous unions since 1936, thus inbreeding was insignificant. In both groups lineage like behavior in mate choice resulted in population subdivision; religion influenced mating structure significantly and genetic variability decreased as a result. The incidence of isonomy was also low in several other villages in the region, and the RP approaches focus on husband's and wife's surnames was valuable regarding marriage patterns and genetic variability.

Surname repetition and isonymy in northeastern Hungarian marriages.

The repeated-pair (RP) approach to surnames in married couples is a measure of population subdivision resulting from the influence of lineagelike behavior in mate choice. An excess of RP over random RP implies limitations in mate choice and a reduction of genetic variability. Here we apply the RP method to data from the rural populations of Csaroda, Tiszaadony, and Tiszavid in northeastern Hungary. The results indicate small differences between RP and random RP for Tiszavid and somewhat larger differences for Tiszaadony and Csaroda. The excess of RP over random RP in Tiszavid, however, derives primarily from marriages simultaneously isonymous and repeating in only one lineage. The discrepancy between RP and random RP implies a small reduction in genetic variability.

Severe growth failure associated with atrophic intestinal mucosa and ring chromosome 15.

Ring chromosome 15 was detected in a boy with severe growth failure and no dysmorphic features who had previously been found to have an atrophic intestinal mucosa, a finding not observed in about 300 patients with ring autosome reported so far. Of the 137 metaphases examined, 8.1% had secondary aneuploidy produced by the structural and behavioural instability of the ring. Ring derivatives could also be seen in lymphocytes after only one cycle in the culture, indicating that such cells are also generated in vivo. We observed an increased cell death rate in fibroblast culture by Trypan Blue exclusion. These results suggest that there is a continuous in vivo generation of cells with increased mortality resulting in both growth failure and atrophic intestinal mucosa in the patient. The atrophic intestinal mucosa might be a manifestation of ring instability.