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Biomedical subjects

A Nemeth

Publications and source records attributed to A Nemeth.

At least 19 recordsLinked to original sources
PubMed2004

Recurrent spinal ependymoma showing partial remission under Imatimib.

BACKGROUND: There are few treatment options for recurrent spinal ependymoma after surgery and radiation therapy. CLINICAL PRESENTATION: We present a patient with recurrent spinal ependymoma who received radiation therapy after laminectomy and partial tumor resection. Months later, the patient developed gait paresis. MRT showed tumor recurrence and partial resection was again performed. Oral cytotoxic chemotherapy with Temozolomide was initiated. After a short relief, there was clinical worsening and MRT showed progressive disease. As the tumor had stained positively for platelet derived growth factor (PDGF) receptor, treatment with Imatimib was initiated. FINDINGS: The patient experienced improvement in neurological symptoms and the following MRT revealed slight tumor regression. She remained stable for a total of 11 months. CONCLUSION: Imatimib should be considered a potential therapeutic option in recurrent ependymomas expressing PDGF receptor.

Adult↗
PubMed2004

Association between low Apgar score and neonatal cholestasis.

AIM: To investigate the association between low Apgar score and the development of cholestasis. METHODS: Seventy-seven cholestatic infants, all referred to our tertiary centre and born between 1987 and 1996 were studied. Twenty-eight patients had biliary atresia (BA), 36 had various intrahepatic disorders and for 13 patients the aetiology of the cholestasis was unknown. Data on gestational age, mode of delivery, Apgar score and birthweight for the cholestatic infants and 1,118,270 control subjects born during the same time period were obtained from the Swedish Medical Birth Registry. If the Apgar score of the cholestatic patient was <7 at 1 min and/or <9 at 5 min and/or <9 at 10 min of age the available medical records were reviewed for signs of neonatal distress. RESULTS: Five cholestatic patients, all of them premature, fulfilled the Apgar criteria. For two of them the low Apgar score and need for immediate resuscitation were explained by major surgical problems. The other three patients, two with biliary atresia (BA) and one with Alagille syndrome, had clinical signs of neonatal distress. The incidence of low Apgar score in BA patients was 7% and in cholestatic patients without known aetiology 0%, neither figure differing significantly from that of the of the control group (2.6%). CONCLUSION: Low Apgar score is not more common in any of the cholestatic groups than in the general Swedish population of newborns. We suggest that aetiological associations other than low Apgar score need to be considered in infants with cholestasis of unknown cause.

Apgar Score↗
PubMed2004

Surgical strategy in massive colorectal bleeding.

Several pathologic disorders can become a source of severe gastrointestinal bleeding. The most frequently observed entities responsible for massive colorectal bleeding are diverticulae, intestinal angiodysplasias, inflammatory bowel diseases and cancers. In order to choose the bes--surgical method to stop the hemorrhage and cure the disease; it is mandatory to properly identify the origin and location of the bleeding. It is a common experience that the usually advised diagnostic methods often yield disappointing results in urgent cases. The presented case shows that selective angiography can lead to the fastest diagnosis in angiodysplasia and with surgery a definitive result can be obtained.

Adult↗
PubMed2002

Autoantibodies against cytochrome P450s in sera of children treated with immunosuppressive drugs.

Treatment with the immunosuppressive drugs cyclosporin and tacrolimus, the mainstays of anti-graft rejection and autoimmune disease therapy, is limited by their hepato- and nephrotoxicity. The metabolic conversion of these compounds to more easily excretable products is catalysed mainly by hepatic cytochrome P4503A4 (CYP3A4) but also involves extrahepatic CYP3A5 and other P450 forms. We set out to study whether or not exposure to cyclosporin and FK506 in children undergoing organ transplantation leads to formation of autoantibodies against P450s. Immunoblotting analysis revealed anti-CYP reactivity in 16% of children on CyA for anti-graft rejection or treatment of nephrosis (n = 67), 31% of kidney transplant patients switched from CyA to FK506 (n = 16), and 21% of kidney and or liver transplant patients on FK506 (n = 14). In contrast, the frequency of reactive immunoblots was only 8.5% among the normal paediatric controls (n = 25) and 7% among adult kidney transplant patients on CyA or FK506 (n = 30). The CYP2C9+ sera were able to immunoprecipitate in vitro translated CYP2C9 and the immunoblot reactivity showed striking correlation to peaks in the age at onset of drug exposure. Sera were isoform selective as evidenced from Western blotting using human liver microsomes and heterologously expressed human P450s. These findings suggest that anti-cytochrome P450 autoantibodies, identified on the basis of their specific binding in immunoblots, are significantly increased among children on immunosuppressive drugs and in some cases are associated with drug toxicity and organ rejection.

Adolescent↗
PubMed2001

NoRC--a novel member of mammalian ISWI-containing chromatin remodeling machines.

Transcription by RNA polymerase I on nucleosomal templates requires binding of the transcription termination factor TTF-I to a cognate site 160 bp upstream of the transcription start site. Binding of TTF-I is accompanied by changes in the chromatin architecture which suggests that TTF-I recruits a remodeling activity to the rDNA promoter. We have cloned a cDNA that encodes TIP5 (TTF-I-interacting protein 5), a 205 kDa protein that shares a number of important protein domains with WSTF (Williams syndrome transcription factor) and hAcf1/WCRF180, the largest subunits of human chromatin remodeling complexes hCHRAC and WCRF. TIP5 co-localizes with the basal RNA polymerase I transcription factor UBF in the nucleolus and is associated with SNF2h. The cellular TIP5-SNF2h complex, termed NoRC (nucleolar remodeling complex), induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. The results suggest that NoRC is a novel nucleolar chromatin remodeling machine that may serve a role in the regulation of the rDNA locus.

3T3 Cells↗
PubMed2001

Renal function before and long after liver transplantation in children.

BACKGROUND: Renal dysfunction occurs in children with liver diseases and renal function is often further impaired after orthotopic liver transplantation (OLT). Inaccurate methods of determining renal function are used in many cases. We studied renal function with accurate methods before and repeatedly after OLT to analyze the effect of the underlying diseases, hypertension, and the immunosuppressive agents. METHODS: A total of 46 children were studied both before and annually after OLT with clearances of inulin and paraaminohippuric acid to determine the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The clearance of inulin was also compared with the formula creatinine clearance. RESULTS: GFR and ERPF decreased from before to after OLT and decreased further during the first years after OLT. Patients with extrahepatic biliary atresia and with tumours showed higher GFR 1 year after OLT than those with metabolic and miscellaneous disorders. No significant change in GFR of individual patients occurred from the first to the last values determined at around 1 and 6 years after OLT. No difference in renal function was seen during the first years between patients treated with cyclosporine as compared to those treated with tacrolimus, but 4 years after OLT, the GFR was higher in the tacrolimus-treated patients. Patients on antihypertensive agents had lower GFR than the normotensive ones. There was no agreement between GFR, determined by clearance of inulin, and that calculated on the basis of serum creatinine and the height of the patients. CONCLUSIONS: Renal function is reduced by OLT and decreases further during the first years after OLT. Patients with metabolic disorders and those on antihypertensive treatment have the lowest GFR. Determination of GFR by the formula creatinine clearance is inaccurate in children after liver transplantation.

Adolescent↗
PubMed2001

Cryptic mammalian species: a new species of whiskered bat (Myotis alcathoe n. sp.) in Europe.

The analysis of morphological, behavioural and genetic characters of whiskered bats revealed a new European bat species within the family Vespertilionidae. We describe the morphology, karyology, genetic similarity, ecology and distribution of Myotis alcathoe n. sp. It closely resembles Myotis mystacinus, Myotis brandtii and Myotis ikonnikovi in morphology, but all four species show clear genetic differences in two mitochondrial genes (ND1 and 12S rRNA). Myotis alcathoe n. sp. is the smallest species among the European whiskered bats and uses the highest-frequency echolocation calls of all the European Myotis species. It prefers to hunt in small valleys with deciduous trees and flowing water, which is an endangered habitat. Records from Greece and Hungary indicate a distribution range in south-eastern Europe.

Animals↗
PubMed2001

Clinical aspects on neonatal cholestasis based on observations at a Swedish tertiary referral centre.

UNLABELLED: The aim of the study was to investigate the clinical aspects of neonatal cholestasis. The medical records of 85 cholestatic infants were retrospectively reviewed. A majority of the patients were referred from other parts of the country. The most common diagnoses were extrahepatic biliary atresia (n = 30 patients), alpha1-antitrypsin deficiency (n = 11) and progressive familial intrahepatic cholestasis (n = 11). On presentation, the biliary atresia group had higher mean serum values of bilirubin, G-GT and cholesterol than the patients with intrahepatic cholestasis, with no significant differences noticed for any other biochemical parameter. A lack of excretion on hepatobiliary scintigraphy was noticed in all investigated patients with biliary atresia, but also in 9 of 34 patients with intrahepatic neonatal cholestasis. There was no statistical correlation between the age at portoenterostomy and the outcome in patients with biliary atresia. However, both the detection of a partial flow on perioperative cholangiogram and the establishment of a non-icteric phase within 6 mo after the portoenterostomy correlated to a good outcome. Eight of 11 patients with progressive familial intrahepatic cholestasis were treated with a biliary diversion procedure, five of eight experienced a sustained cholestatic remission. CONCLUSIONS: Progressive familial intrahepatic cholestasis may be a more common cause of neonatal cholestasis in Sweden than reported elsewhere and that the experience with biliary diversion is positive. While early referral in patients with extrahepatic biliary atresia remains important, a portoenterostomy should be attempted also in patients referred after 3 mo of age.

Blood Chemical Analysis↗
PubMed2001

Aetiological factors in neonatal cholestasis.

UNLABELLED: The aim of the study was to investigate factors of possible importance for the aetiology of neonatal cholestasis. The medical records of 85 cholestatic infants were retrospectively reviewed. The most common diagnoses were extrahepatic biliary atresia (n = 30 patients), alpha1-antitrypsin deficiency (n = 11) and progressive familial intrahepatic cholestasis (n = 11). The mothers of the patients with biliary atresia had a higher mean age and were more commonly treated for gestational diabetes than the mothers of patients with intrahepatic neonatal cholestasis. The morbidity and mortality in the siblings of patients with biliary atresia were also greater than expected. There was a seasonal variation of the birth months in the biliary atresia group. possibly indicating an association to viral infections. Signs of ongoing cytomegalovirus infection were more common in both the extrahepatic and the intrahepatic group. CONCLUSIONS: Progressive familial intrahepatic cholestasis may be a more common cause of neonatal cholestasis in Sweden than reported elsewhere. A maternal vulnerability, of genetic or other origin, is suggested in the aetiology of biliary atresia. The true pathogenetic importance of cytomegalovirus infection in patients with neonatal cholestasis of different origins remains to be established.

Adult↗
PubMed2001

Increased risk for cancer in multiple myeloma patients and their first-degree relatives.

Analyzing data of 125 multiple myeloma patients, the authors found a 40-fold increased tumor incidence among the patients and their first-degree relatives as compared to the average population. These tumors were the same as those usually found among Hungarians. There was no difference as to the patient's blood group antigens in the families of myeloma patients with or without other tumor. IgA-type disease was found to be relatively more frequent in the group of patients who had tumor besides myeloma. In a prospective study, authors could not find mutation of suppressor gene p53 in 14 patients and their 16 healthy first-degree relatives. This may indicate that there is no p53 suppressor gene alteration responsible for the high-risk condition for tumorgenesis in this population.

Aged↗
PubMed1999

The Drosophila poly(A)-binding protein II is ubiquitous throughout Drosophila development and has the same function in mRNA polyadenylation as its bovine homolog in vitro.

The poly(A)-binding protein II (PABP2) is one of the polyadenylation factors required for proper 3'-end formation of mammalian mRNAs. We have cloned Pabp2, the gene encoding the Drosophila homolog of mammalian PABP2, by using a molecular screen to identify new Drosophila proteins with RNP-type RNA-binding domains. Sequence comparison of PABP2 from Drosophila and mammals indicates that the most conserved domains are the RNA-binding domain and a coiled-coil like domain which could be involved in protein-protein interactions. Pabp2 produces four mRNAs which result from utilization of alternative poly(A) sites and encode the same protein. Using an antibody raised against Drosophila PABP2, we show that the protein accumulates in nuclei of all transcriptionally active cells throughout Drosophila development. This is consistent with a general role of PABP2 in mRNA polyadenylation. Analysis of Drosophila PABP2 function in a reconstituted mammalian polyadenylation system shows that the protein has the same functions as its bovine homolog in vitro : it stimulates poly(A) polymerase and is able to control poly(A) tail length.

Amino Acid Sequence↗
PubMed1999

Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3.

Arginine methylation is a post-translational modification found mostly in RNA-binding proteins. Poly(A)-binding protein II from calf thymus was shown by mass spectrometry and sequencing to contain NG, NG-dimethylarginine at 13 positions in its amino acid sequence. Two additional arginine residues were partially methylated. Almost all of the modified residues were found in Arg-Xaa-Arg clusters in the C terminus of the protein. These motifs are distinct from Arg-Gly-Gly motifs that have been previously described as sites and specificity determinants for asymmetric arginine dimethylation. Poly(A)-binding protein II and deletion mutants expressed in Escherichia coli were in vitro substrates for two mammalian protein arginine methyltransferases, PRMT1 and PRMT3, with S-adenosyl-L-methionine as the methyl group donor. Both PRMT1 and PRMT3 specifically methylated arginines in the C-terminal domain corresponding to the naturally modified sites.

Amino Acid Sequence↗
PubMed1999

A high prevalence of serum GB virus C/hepatitis G virus RNA in children with and without liver disease.

The role of GB virus C/hepatitis G virus (GBV-C/HGV) in adult and pediatric liver disease is unclear. We detected serum GBV-C/HGV RNA by reverse transcriptase polymerase chain reaction in 1 (3%) of 38 cholestatic infants, in 4 (4%) of 95 children without liver disease, and in none of 30 children with autoimmune hepatitis. One cholestatic infant had antibodies, presumably maternal, to GBV-C/HGV. Sequence analysis of a nonstructural 3 region fragment suggested that mother-to-infant transmission was the route of infection for the cholestatic infant. The four infected children without liver disease had normal liver function test results and lacked risk factors for bloodborne infections. Thus, the detection of GBV-C/HGV RNA among children with and without liver disease suggests that chronic GBV-C/ HGV infections may be established early in life, possibly by mother-to-infant transmission. This may explain in part the high prevalence of serum GBV-C/HGV RNA and antibodies in healthy adults.

Adolescent↗
PubMed1999

Analysis of GB virus C markers in families over three generations.

GB virus C (GBV-C) markers were analyzed in two to three generations in three families with documented vertical transmission of GBV-C. None of the maternal grandparents had GBV-C markers, whereas the male spouses had GBV-C envelope 2 antibodies. Evidence was found for intrafamilial transmission but not for GBV-C transmission over three generations.

Adult↗
PubMed1999

Cytomegalovirus DNA detection on Guthrie cards in patients with neonatal cholestasis.

AIM: To time the onset of cytomegalovirus (CMV) infection in patients (n = 39) with CMV associated neonatal cholestasis by analysing CMV DNA on Guthrie cards sampled at 3 days of age. METHODS: CMV infection was diagnosed by serology/urine isolation or by CMV DNA detection (polymerase chain reaction) in liver biopsy specimens. In order to time the infection dry blood filter paper discs were punched out from stored Guthrie cards. After phenol-choloroform extraction CMV DNA was detected by nested polymerase chain reaction. RESULTS: All cards from control children (n = 8) with congenital CMV tested positive; none of the negative controls (n = 4) did so. Two of 39 cholestatic infants were CMV DNA positive; their mothers had serological signs compatible with infection during the second half of the pregnancy. All other cholestatic infants tested negative. CONCLUSIONS: CMV DNA was not detected in most of the children using Guthrie cards, suggesting that infection developed at or soon after birth.

Blood Specimen Collection↗
PubMed1999

Relation between GB virus C/hepatitis G virus and fulminant hepatic failure may be secondary to treatment with contaminated blood and/or blood products.

BACKGROUND: The role of the recently discovered GB virus C (GBV-C)/hepatitis G virus in fulminant hepatic failure (FHF) has been debated. Although GBV-C RNA has been detected in many cases of FHF, recent data suggest that the relation between GBV-C and FHF may be accidental. AIMS: To retrospectively investigate the possible relation between the presence of GBV-C markers (RNA or antibodies to the GBV-C envelope 2 (E2) glycoprotein) and FHF. METHODS: The presence of GBV-C RNA was determined in serum samples from 58 patients diagnosed with FHF using a reverse transcriptase polymerase chain reaction. Amplified genetic fragments were directly sequenced by the dideoxy chain termination method. Antibodies to GBV-C in serum samples were detected by enzyme immunoassay based on a recombinant GBV-C E2 protein. RESULTS: Nine (16%) patients with FHF had GBV-C RNA and 13 (22%) [corrected] had GBV-C E2 antibodies, which are higher frequencies than in healthy subjects (p<0.01 and p<0.05 respectively). Six of nine [corrected] patients with GBV-C markers during FHF tested negative for these markers before therapy with blood and/or blood products. Sequence analysis of the GBV-C NS3 region fragments of six FHF patients showed no common sequence pattern or motif. CONCLUSIONS: The frequencies of both GBV-C RNA and antibodies are higher in patients with FHF than in healthy subjects. However, these increased frequencies may in many cases be explained by the use of contaminated blood and/or blood products given as therapy.

Adolescent↗
PubMed1998

The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia.

BACKGROUND: In addition to earlier reports on the association between viral infections and intrahepatic neonatal cholestasis, in recent studies, investigators have suggested a similar link to extrahepatic biliary atresia. METHODS: Fifty-nine cholestatic infants (mean age 8 weeks) were investigated for signs of infection with a large spectrum of viruses. Twenty-one infants had extrahepatic biliary atresia, 38 had intrahepatic cholestasis. The virologic methods included serologic investigation in 59 infants and 54 mothers, virus isolation from stools (49 infants), urine (58 infants) and liver biopsies (40 infants). Polymerase chain reaction was used to detect cytomegalovirus DNA in 25 of the liver biopsy specimens. Two control groups, one with 35 noncholestatic infants and one with 111 healthy, pregnant women were checked for serologic signs of cytomegalovirus. RESULTS: Nineteen of 59 (32%) cholestatic infants, including 8 of 21 (38%) with extrahepatic biliary atresia, compared with 2 of 35 (6%) control infants had cytomegalovirus-immunoglobulin (Ig) M detected in serum (p < 0.01). Fifty-one of 54 (94%) tested mothers of cholestatic infants were seropositive for cytomegalovirus, compared with 83 of 111 (75%) control mothers (p < 0.01). Cytomegalovirus DNA in liver specimens was detected by polymerase chain reaction in 9 of 18 (50%) analyzed patients with biliary atresia and in specimens from 3 of 7 patients with intrahepatic cholestasis. CONCLUSIONS: Cytomegalovirus infection may play a role, not only in intrahepatic neonatal cholestasis, as was suggested earlier, but also in extrahepatic biliary atresia. The pathogenetic mechanism for this link remains to be established.

Antibodies, Viral↗