Biomedical subjects

M Nagy

Publications and source records attributed to M Nagy.

At least 37 records · Page 2Linked to original sources

PubMed2000

Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome, as revealed by direct observation in father/son pairs.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

Adolescent↗

PubMed2000

Antibacterial activity of plant extracts from the families Fabaceae, Oleaceae, Philadelphaceae, Rosaceae and Staphyleaceae.

The selected plant extracts exhibited antibacterial activity. The strongest effect was manifested by extracts prepared from Gymnocladus dioicus, Amelanchier ovalis, Exochorda racemosa, Holodiscus discolor, Philadelphus microphyllus, Philadelphus coronarius and Pelargonium tabulare. The percentage inhibition of bacterial growth was 0-41.8%. In addition it was found that extracts isolated from Amelanchier ovalis, Exochorda racemosa and Pelargonium tabulare were specifically effective only against the bacterial strains tested.

Anti-Bacterial Agents↗

PubMed2000

Somatic mutation of the 5' noncoding region of the BCL-6 gene is associated with intraclonal diversity and clonal selection in histological transformation of follicular lymphoma.

Follicular lymphoma (FL) is a B cell non-Hodgkin's lymphoma (NHL) that frequently displays a t(14;18) translocation. Clonal evolution and histological transformation of FL is frequently associated with the accumulation of secondary genetic alterations. It has been demonstrated that the BCL-6 gene can be altered by chromosomal rearrangements and by mutations clustering in its 5' noncoding region in a significant fraction of FL and diffuse large cell lymphoma (DLCL). To elucidate the role of the BCL-6 gene alterations in the histological transformation and clonal progression of FL, we analyzed serial biopsy specimens from 12 patients with FL. Two cases of FL showed no histological alteration in the second biopsy, and 10 cases of FL showed morphological transformation to DLCL in the second biopsy. Southern blot analysis was used to detect rearrangement of the BCL-6 gene, polymerase chain reaction-single strand conformation polymorphism and sequence analysis were performed for identification of mutations in the 5' noncoding region of the BCL-6 gene, and immunohistochemical analysis was applied to reveal the BCL-6 protein expression. No BCL-6 gene rearrangement was detected in any of the samples, but a total of 58 mutations were found in the 5' noncoding region of the BCL-6 gene in seven cases. In five cases, both the FL and the clonally related FL or DLCL, and in two cases only the DLCL samples were mutated. The mutations were identical in multiple biopsy specimens of FL that did not show morphological transformation. In six patients where FL cells underwent morphological transformation, considerable intraclonal sequence heterogeneity was observed, indicating an ongoing type of somatic mutation. Based on the pattern of shared and nonshared mutations, the genealogical relationship of neoplastic clones could be established. In all of these cases, the histological transformation of FL was associated with the emergence of a subpopulation marked by new sites of mutations in the BCL-6 5' noncoding sequences. In three of these six cases, the histological transformation is also associated with the reduced expression of the BCL-6 protein. These findings demonstrate that mutation of the 5' noncoding region of the BCL-6 gene developed in the clonal evolution of FL, and at different time points in the lymphoma evolution different clonotypes dominate.

5' Untranslated Regions↗

PubMed2000

Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation.

To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

Amino Acid Sequence↗

PubMed2000

Pattern of noncompliance with dialysis exchanges in peritoneal dialysis patients.

The purpose of the study is to evaluate the pattern of noncompliance in peritoneal dialysis (PD) patients using home visit supply inventories. Ninety-two patients were enrolled at the start of dialysis. Noncompliance, defined as performance of less than 90% of prescribed exchanges, was found in 30% of patients during the first 6 months of PD. Patients who were noncompliant with prescribed exchanges at the start of PD had greater rates of death (P = 0.03), transfer to hemodialysis secondary to uremia (P < 0.05), hospitalization (P < 0.001), and days hospitalized (P < 0.001) compared with compliant patients. Delivered Kt/V was 18% less in noncompliant compared with compliant patients (2.1 versus 2.57; P = 0.007). Serial evaluations of compliance in 53 patients showed that 72% were consistently compliant, 2% were consistently noncompliant, 15% were noncompliant at the beginning of PD but became compliant at follow-up, and 11% were intermittently noncompliant. The likelihood of future compliance in a patient compliant at the first home visit was 88%. Patients who were independent with their dialysis exchanges were more likely to be noncompliant (27%) than patients dependent on someone else to perform their dialysis (8%; P = 0.05). Serial 24 hour creatinine excretion was not a useful method to determine compliance. We recommend a home visit during the first 6 months of PD to determine compliance. Those found compliant probably do not need repeated evaluations, whereas noncompliant patients should be reevaluated in a few months. Involving another person in the dialysis might relieve some of the burden on patients who may be initially unable to cope with home dialysis. Identification of noncompliant patients and awareness of risk factors should reduce noncompliance and improve patient outcomes.

Creatinine↗

PubMed2000

Characterization of early region 4 of porcine adenovirus serotype 5.

To locate the E4 region on the genome of the HNF-70 prototype strain of the porcine adenovirus serotype 5 (PAdV-5), 4.5 kb at the extreme right end was sequenced. This area had 11 open reading frames (ORFs) on the left strand encoding more than 50 amino acids (aa). A Genbank homology search indicated that 8 of these ORFs were unique to PAdV-5. ORF5:253 aa, ORF6:245 aa and ORF11:146 aa showed similarities to known mammalian and avian adenovirus E4 ORFs. The putative E4 promoter sequences were also identified. Two TATA boxes, several GC boxes and two typical CCAAT boxes were located within this region. The presence of several potential poly-adenylation signals and the number of E4 transcripts detected by Northern blot analysis suggested the possibility of a complex mRNA transcription.

Adenoviridae↗

PubMed2000

Genetic instability is associated with histological transformation of follicle center lymphoma.

Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histological transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal levels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair defects in this procedure, we have performed microsatellite analysis, comparative genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to diffuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients were analyzed for microsatellite instability and structural alterations for hMLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated with histological transformation of two cases of FCL, but no mutations of the hMLH1 and hMSH2 genes were detected in any of the lymphoma samples. In the five cases subjected to CGH analysis, the histological transformation of FCLs was associated with genomic imbalances at 21 chromosomal regions. The genomic abnormalities found were rather heterogeneous and none of the genetic changes were overrepresented in the transformed DLCLs. These data suggest that histological transformation of FCLs to DLCL is frequently associated with genome wide instability at both nucleic acid and chromosomal levels, although mutations of the hMSH1 and hMLH2 genes are not involved in this process.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Correlation of findings on direct laryngoscopy and bronchoscopy with presence of extraesophageal reflux disease.

OBJECTIVE: To determine the correlation between findings at direct laryngoscopy and bronchoscopy and presence of extraesophageal reflux disease (EERD). STUDY DESIGN: Retrospective chart review METHODS: Operative notes of 155 children undergoing direct laryngoscopy and bronchoscopy between 1996 and 1999 for airway symptoms for whom there was a suspicion of EERD were examined. Gastroesophageal reflux disease (GERD) was considered present if at least one test was positive (including upper GI series, pH probe, gastric scintiscan, or esophageal biopsy). RESULTS: A total of 130 (84%) patients had GERD diagnosed. Ninety percent had at least one laryngotracheal abnormality: 83% had an abnormal larynx and 66% had an abnormal trachea. Laryngeal abnormalities in GERD included postglottic edema, 69%; arytenoid edema, 30%; large lingual tonsil, 16%; vocal fold edema, 12%; vocal fold nodule, 12%; ventricular obliteration, 5%; and hypopharyngeal cobblestoning, 3%. Tracheobronchial abnormalities in GERD included tracheal cobblestoning, 33%; blunting of carina, 12.5%; subglottic stenosis, 11%; increased secretions, 11%; and generalized edema or erythema, 5%. The best sensitivity or specificity was obtained by combining postglottic edema, arytenoid edema, and vocal fold edema, resulting in a sensitivity of 75% and a specificity of 67%. Positive predictive value was 100% for the combination of postglottic edema and any vocal fold or ventricular abnormality. CONCLUSION: Laryngoscopy and bronchoscopy can reveal findings with a high positive predictive value for the presence of GERD. Endoscopy of the upper airway in children with clinical signs and symptoms of EERD is a promising tool for diagnosis.

Bronchi↗

PubMed2000

Porcine adenoviruses: an update on genome analysis and vector development.

Although porcine adenoviruses (PAdV) are present in the swine populations worldwide, they usually do not cause any disease, or the infection is only manifested in a mild diarrhoea or respiratory signs. The importance of adenoviruses, however, is constantly growing as there is a possibility of developing them into viral vector vaccines against more significant swine pathogens. A short summary of the well-established facts of porcine adenoviruses is given and recent developments of the genetic analysis of these viruses are discussed in detail. The possibilities of vector development and examples of vector vaccines already reported in the literature are mentioned.

Animals↗

PubMed2000

[Apigenin-7-methylglucuronide from Cynara cardunculus L].

From an ethanolic extract of the flower buds of Cynara cardunculus L. (Asteraceae), apigenin-7-methylglucuronide and chlorogenic acid were isolated. The isolated compounds were identified by spectroscopic means, by comparison with authentic samples and literature data.

Apigenin↗

PubMed1999

[Analysis of T-cell receptor gamma-gene rearrangement in lymphoproliferative disorders using polymerase chain reaction].

T-cell non-Hodgkin's lymphomas (NHL) exhibit a clonal T-cell receptor (TCR) gamma gene rearrangement as a result of sequential assembly of their variable (V gamma) and joining (J gamma) region segments. The analysis of the TCR gamma gene rearrangements may help to differentiate reactive lymphoproliferations from T-cell NHLs. The aim of this study was to reveal the usefulness of polymerase chain reaction (PCR) analysis of the TCR gamma gene rearrangement in the diagnosis of T-cell NHLs using native and formol-paraffin embedded tissues. The PCR amplification of the TCR gamma gene was performed by the V gamma specific sense and J gamma specific antisense primer pairs. The PCR products were evaluated by polyacrilamide gel electrophoresis containing ethidium bromide. The PCR analysis of the TCR gamma gene rearrangements has been performed in 95 lymphoproliferative disorders. The PCR analysis of the TCR gamma gene showed clonal gene rearrangement in 22 cases out of the 39 T-cell NHLs and in one case out of the 12 O-cell anaplastic large cell lymphoma but no clonal rearrangements were detected in any of the 15 reactive lymphoproliferations or 13 B-cell NHLs. Thus, clonal TCR gamma gene rearrangements was detected by PCR in 58.2% of T-cell NHLs but no clonal TCR gamma gene rearrangements were shown in any of reactive lymphoproliferations of B-cell NHLs. These studied showed that the PCR amplification of the TCR gamma gene can be a powerful tool in the diagnosis of T-cell NHLs.

Gene Rearrangement, T-Lymphocyte↗

PubMed1999

Molecular genetic evidence for the human settlement of the Pacific: analysis of mitochondrial DNA, Y chromosome and HLA markers.

Present-day Pacific islanders are thought to be the descendants of Neolithic agriculturalists who expanded from island South-east Asia several thousand years ago. They speak languages belonging to the Austronesian language family, spoken today in an area spanning half of the circumference of the world, from Madagascar to Easter Island, and from Taiwan to New Zealand. To investigate the genetic affinities of the Austronesian-speaking peoples, we analysed mitochondrial DNA, HLA and Y-chromosome polymorphisms in individuals from eight geographical locations in Asia and the Pacific (China, Taiwan, Java, New Guinea highlands, New Guinea coast, Trobriand Islands, New Britain and Western Samoa). Our results show that the demographic expansion of the Austronesians has left a genetic footprint. However, there is no simple correlation between languages and genes in the Pacific.

Base Sequence↗

PubMed1999

Changes in immunomodulatory activity of human mononuclear cells after cultivation with leaf decoctions from the genus Ligustrum L.

Leaf decoctions from Ligustrum vulgare (LV) and Ligustrum delavayanum (LD) were studied for candidacidal activity, phagocytic activity studied on human mononuclear cells (MO) and complement activated by the classical pathway. Candidacidal activity was studied on Candida albicans SC 1539 incubated with MO. The decoction of LD increased the candidacidal activity of MO, whereas LV did not show any effect. The phagocytic activity of MO was decreased by the decoction of LV, whereas LD did not change the activity. The phagocytic index of MO incubated with LD decoction was increased, but use of the LV decoction did not show significant changes. Decoctions from LD and LV significantly decreased the haemolytic activity of complement activated by the classical pathway (conc. 0.78 mg/mL).

Adjuvants, Immunologic↗

PubMed1999

Mhc-DQ-DRB haplotype analysis in the rhesus macaque: evidence for a number of different haplotypes displaying a low allelic polymorphism.

In the HLA-DRB subregion of man, five major groups of haplotypes, often displaying a remarkable polymorphism, are distinguishable. The polymorphism is thought to be generated by point mutation, microgene conversion and gene rearrangement by recombination. In order to gain insight into the organization of the rhesus macaque major histocompatibility complex (MHC) class II region, DRB genes from monkeys of different origins previously typed for their DQ genes were analyzed. At first DRB haplotypes were deduced from DQ-homozygous monkeys. The stability of these haplotypes was then examined in DQ-heterozygous monkeys by sequence-based typing for the presence of members of the DRB1*03 and DRB1*04 lineage, and for seven single alleles detected on the haplotypes. Six DRB haplotypes linked to the five most frequent and three haplotypes linked to less frequent DQ haplotypes were identified. Six novel DRB alleles were detected. The number of DRB genes per haplotype varied between two and four. The results altogether suggest that in rhesus macaques, in comparison to man, the DQ haplotypes are linked to only a small number of DRB haplotypes, the number and diversity of DRB haplotypes is larger, and the allelic polymorphism of a given haplotype is smaller. The diversity of the DRB haplotypes was partly due to the varying number and identity of genes linked to DRB1*03 and DRB1*04. Furthermore, the number of DRB1 genes themselves varied from zero to two.

Alleles↗

PubMed1999

Towards understanding the origin and dispersal of Austronesians in the Solomon Sea: HLA class II polymorphism in eight distinct populations of Asia-Oceania.

HLA class II nucleotide sequence polymorphisms were examined in eight ethnic groups of Asia-Oceania using DNA typing methods. Allele frequencies and characteristic DR/DQ haplotypes were determined and compared with those of other populations of Asia-Oceania. Genetic distances were measured to show the genetic relationship within the studied populations as well as between the studied populations and previously published populations. Phylogenetic trees were constructed based on HLA allele frequencies using the neighbour-joining method. The populations, mainly Trobriand Islanders, Roro, Tolai, Western Samoans and Taiwanese Aborigines, are characterized by a reduced diversity at the HLA loci examined, especially for DPB1. The high frequency of the 'Asian'-specific DPB1*0501 allele in Trobrianders and Roro, but also in Western Samoans and Taiwanese Aborigines, was the most striking result. The prevalence of DPB1*0501 and the short genetic distance from Trobriander and Roro to Taiwanese Aborigines provide evidence that the origin of the Austronesian odyssey is south-east Asia, and Taiwan could be an important part of it. The relatedness of Trobrianders to the Polynesian population from Western Samoa indicates a probable recent common ancestor. The observed lack of diversity may reflect bottleneck(s) and/or limited diversity of the founding population. Analysis of HLA class I antigens, together with mt-DNA and Y-chromosomal studies, will give us further information about the settlement of the Trobriand and other islands during the colonization of the Pacific.

Alleles↗

PubMed1999

Distinct clonal origin of low-grade MALT-type and high-grade lesions of a multifocal gastric lymphoma.

AIMS: Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma and high-grade B-cell non-Hodgkin's lymphoma (NHL) of the stomach may occur simultaneously. To determine the clonal relationship between these tumours, we compared the immunoglobulin heavy chain gene (IgH) rearrangements of low and high-grade components of a multifocal gastric NHL. METHODS AND RESULTS: The complementary determining region 3 (CDR3) of the IgH gene rearrangements were polymerase chain reaction (PCR) amplified, cloned and sequenced. The analysis of the CDR3 sequences rearranged by tumour cells of low-grade MALT and the high-grade NHL revealed different nucleic acid sequences. CONCLUSION: These findings suggest that low-grade MALT and high-grade B-cell components of multifocal gastric NHL may represent unrelated clones.

Amino Acid Sequence↗

PubMed1999

Comparison of the sensitivity of lateral neck radiographs and computed tomography scanning in pediatric deep-neck infections.

OBJECTIVE: To compare the sensitivity of lateral neck films and computed tomography (CT) scanning with contrast in evaluating children with a high index of suspicion for a deep-neck infection, either retropharyngeal, parapharyngeal, or combined based in clinical presentation. STUDY DESIGN: A retrospective chart review of children presenting to the Children's Hospital of Buffalo, New York, with the diagnosis of a deep-neck infection between January 1991 and November 1997 was conducted. In total, 57 children were included in the study, ranging in age from 12 to 119 months (1-10 y). METHODS: Charts were reviewed for presenting signs, symptoms, and laboratory values and included only those children with the presence of fever, limited neck range of motion, a lateral neck mass, dysphagia, and a leukocyte count greater than 15,000 cells/mm3. Results of lateral neck radiographs and CT scanning with contrast were evaluated and compared when available. RESULTS: Lateral neck radiographs were found to have a sensitivity of 83% for determining the presence of a pediatric deep-neck infection, whereas CT scanning with contrast had a sensitivity of 100. CONCLUSION: Lateral neck radiographs were found to offer no benefit in the workup of children strongly suspected of having a deep-neck infection based on clinical presentation. Despite the higher cost, CT scanning with contrast is the recommended radiologic test in such cases. This single study allows the determination of size, type, and location of the infectious process and is invaluable in treatment planning for pediatric patients with infection in deep-neck spaces.

Cellulitis↗

PubMed1999

PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat.

This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.

Analysis of Variance↗