Biomedical subjects

X Pan

Publications and source records attributed to X Pan.

At least 127 records · Page 7Linked to original sources

PubMed1998

The prognostic role of p53, metallothionein, P-glycoprotein, and MIB-1 in muscle-invasive urothelial transitional cell carcinoma.

Tissue from primary tumors was analyzed for 118 patients with urothelial cancer who subsequently received cisplatin-based chemotherapy. Immunohistochemical staining was performed for nuclear p53 reactivity; for two proposed mediators of drug resistance, metallothionein (MT) and P-glycoprotein; and for the cell proliferation marker MIB-1. For each marker, immunoreactivity was expressed as a percentage of positively staining cells, and overall intensity of staining was graded on a scale from 0 to 3. The product of these two measurements was calculated to generate a percentage-intensity index. Clinical data were obtained independently via retrospective chart review. Chemotherapy regimens containing cisplatin (cisplatin, methotrexate, and vinblastine or methotrexate, vinblastine, doxorubicin, and cisplatin) were administered for metastatic disease (n = 64), for locally advanced disease (n = 45), or as an adjuvant treatment (n = 9). The overall response rate was 56% among 99 evaluable patients, and median survival was 12.7 months. By univariate analysis, Eastern Cooperative Oncology Group performance status (P = 0.0025), tumor grade (P = 0.03), percentage of MT staining (P = 0.01), and percentage-intensity index of MT staining (P = 0.04) were significant predictors of response to chemotherapy. The first three of these were significant in a multivariate model (P = 0.05, 0.04, and 0.04, respectively). By subgroup analysis, the percentage of MT staining predicted for response in metastatic disease (P = 0.03), but not in locally advanced disease (P = 0.28). Only performance status was significantly related to overall survival (P = 0.0001, log-rank test) in the whole cohort. Overexpression of MT in the 64 patients with metastatic disease was associated with a shorter survival (P = 0.04). Expression of p53, P-glycoprotein, and MIB-1 did not predict for survival. In conclusion, overexpression of MT is associated with a poorer outcome from chemotherapy, possibly due to cisplatin resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

[Detection of presymptomatic patients and heterozygotes with Wilson's disease by using haplotypes of microsatellites].

OBJECTIVE: To develop a rapid, exact and effective technique of gene diagnosis for the early diagnosis of patients with wilson's disease(WD) and detection of WD heterozygotes. METHODS: Five microsatellite (or short tandem repeat, STR) loci at D13S301, D13S316, D13S296, AFM238vc3 and AFM184xc5 were amplified by polymerase chain reaction(PCR). D13S301 was a locus within WD gene, the others were in the flank of WD gene. After detection of amplified fragment length polymorphism of the five STR loci with denaturing polyacrylamide gel electrophoresis(AFLP-PAGE), the STR haplotypes analyses were performed on 120 members in 23 WD families. RESULTS: The five STR loci had high polymorphism information content(PIC). PICs of D13S301, D13S316, D13S296, AFM084xc5 and AFM238vc3 were 0.89, 0.93, 0.91, 0.91 and 0.94 respectively. The STR haplotypes analyses confirmed that the two patients previously diagnosed doubtfully were WD patients definitely. Among 31 sibs without any clinical symptoms, 4 were diagnosed as presymptomatic patients, 8 as WD heterozygotes, 17 as normal homozygotes and 2 as doubtful presymptomatic patients. CONCLUSION: Haplotypes analysis of the five STR loci can provide high genetic information. It provides a new important technique in gene diagnosis of WD.

Adult↗

PubMed1997

Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination.

One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacterial pathogens. The lack of neutral mutations in structural genes indicates that M. tuberculosis is evolutionarily young and has recently spread globally. Species diversity is largely caused by rapidly evolving insertion sequences, which means that mobile element movement is a fundamental process generating genomic variation in this pathogen. Three genetic groups of M. tuberculosis were identified based on two polymorphisms that occur at high frequency in the genes encoding catalase-peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old and allied with M. bovis, the cause of bovine tuberculosis. A subset of several distinct insertion sequence IS6110 subtypes of this genetic group have IS6110 integrated at the identical chromosomal insertion site, located between dnaA and dnaN in the region containing the origin of replication. Remarkably, study of approximately 6,000 isolates from patients in Houston and the New York City area discovered that 47 of 48 relatively large case clusters were caused by genotypic group 1 and 2 but not group 3 organisms. The observation that the newly emergent group 3 organisms are associated with sporadic rather than clustered cases suggests that the pathogen is evolving toward a state of reduced transmissability or virulence.

Alleles↗

PubMed1997

The "proper" binormal model: parametric receiver operating characteristic curve estimation with degenerate data.

RATIONALE AND OBJECTIVES: The authors assessed the use of a "proper" binormal model and a new algorithm for maximum-likelihood estimation of receiver operating characteristic (ROC) curves from degenerate data. METHODS: The proper binormal ROC model uses as its decision variable a monotonic transformation of the likelihood ratio that is associated with a pair of normal distributions, thereby ensuring fitted ROC curves with monotonic slope but maintaining a relationship with the conventional binormal model. A computer program entitled PROPROC was used to fit proper ROC curves to data obtained from computer-simulated and real observer studies. RESULTS: ROC indexes such as total area were estimated with PROPROC and compared with the corresponding values obtained from the conventional procedures. CONCLUSION: The proper binormal ROC model overcomes the problem of degeneracy in ROC curve fitting. PROPROC is highly robust and yields ROC estimates with less bias and greater precision than those obtained with the conventional binormal model.

Algorithms↗

PubMed1997

Subspecific differentiation of Mycobacterium avium complex strains by automated sequencing of a region of the gene (hsp65) encoding a 65-kilodalton heat shock protein.

To develop a strategy for rapid species assignment and strain differentiation of Mycobacterium avium complex (MAC) organisms, the sequence of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat shock protein was determined for 56 isolates, including 21 patient isolates and 35 reference strains. Eleven hsp65 alleles were identified, and there was no sharing of alleles between strains classified as M. avium and Mycobacterium intracellulare based on serovar and species-specific DNA hybridization probes. Phylogenetic analysis showed that 30 strains had one of two hsp65 alleles which were found in known M. avium organisms, 23 strains had one of six alleles allied with known M. intracellulare organisms, and three MAC isolates had one of three hsp65 alleles that differed substantially from the consensus M. avium and M. intracellulare hsp65 sequences. Estimates of strain relationships based on the sequences of hsp65 and the 16S-23S ribosomal DNA internal transcribed spacer were similar. Automated DNA sequencing of a 360-bp region of the hsp65 gene from MAC organisms provides a rapid and unambiguous marker system for strain differentiation and permits specific assignment of these acid-fast organisms for diagnostic purposes.

Alleles↗

PubMed1997

Analysis of the oxyR-ahpC region in isoniazid-resistant and -susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities.

Automated DNA sequencing was used to analyze the oxyR-ahpC region in 229 Mycobacterium tuberculosis complex isolates recently recovered from diseased humans and animals. The entire 1,221-bp region was studied in 118 isolates, and 111 other isolates were sequenced for oxyR, ahpC, or the 105-bp oxyR-ahpC intergenic region. The sample included isoniazid (INH)-susceptible and -resistant organisms in which the katG gene and inhA locus had previously been sequenced in their entirety to identify polymorphisms. A total of 16 polymorphic sites was identified, including 5 located in oxyR, 2 in ahpC, and 9 in the 105-bp intergenic region. All polymorphic sites located in the intergenic region, and the two missense substitutions identified in ahpC, occurred in INH-resistant organisms. In contrast, there was no preferential association of polymorphisms in oxyR, a pseudogene, with INH-resistant organisms. Surprisingly, most INH-resistant strains with KatG codon 315 substitutions that substantially reduce catalase-peroxidase activity and confer high MICs of INH lacked alterations in the ahpC gene or oxyR-ahpC intervening region. Taken together, the data are consistent with the hypothesis that some polymorphisms located in the ahpC-oxyR intergenic region are selected for after reduction in catalase or peroxidase activity attributable to katG alterations arising with INH therapy. These mutations are uncommon in recently recovered clinically significant organisms, and hence, there is no strict association with INH-resistant patient isolates. The ahpC compensatory mutations are apparently uncommon because strains with a KatG null phenotype are relatively rare among epidemiologically independent INH-resistant organisms.

Animals↗

PubMed1997

Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms.

A gene (pncA) with mutations associated with pyrazinamide resistance in Mycobacterium tuberculosis complex members was characterized in 67 pyrazinamide-resistant and 51 pyrazinamide-susceptible isolates recovered from diverse geographic localities and anatomic sites and typed by IS6110 profiling. All pyrazinamide-susceptible organisms had identical pncA alleles. In striking contrast, 72% of the 67 resistant organisms had pncA mutations that altered the primary amino acid sequence of pyrazinamidase. A total of 17 previously undescribed mutations were found, including upstream mutations, missense changes, nucleotide insertions and deletions, and termination mutations. The mutations were arrayed along virtually the entire length of the gene. These data are further evidence that most drug resistance in M. tuberculosis is due to simple mutations occurring in chromosomally encoded genes rather than to acquisition of resistance genes by horizontal transfer events.

Amidohydrolases↗

PubMed1997

Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations.

Ethambutol [(S,S')-2,2'-(ethylenediimino)di-1-butanol; EMB], is a first-line drug used to treat tuberculosis. To gain insight into the molecular basis of EMB resistance, we characterized the 10-kb embCAB locus in 16 EMB-resistant and 3 EMB-susceptible genetically distinct Mycobacterium tuberculosis strains from diverse localities by automated DNA sequencing and single-stranded conformation polymorphism analysis. All 19 organisms had virtually identical sequences for the entire 10-kb region. Eight EMB-resistant organisms had mutations located in codon 306 of embB that resulted in the replacement of the wild-type Met residue with Ile or Val. Automated sequence analysis of the 5' region (1,892 bp) of embB in an additional 69 EMB-resistant and 30 EMB-susceptible M. tuberculosis isolates from diverse geographic localities and representing 70 distinct IS6110 fingerprints confirmed the unique association of substitutions in amino acid residue 306 of EmbB with EMB resistance. Six other embB nucleotide substitutions resulting in four amino acid replacements were uniquely found in resistant strains. Sixty-nine percent of epidemiologically unassociated EMB-resistant organisms had an amino acid substitution not found in susceptible strains, and most (89%) replacements occurred at amino acid residue 306 of EmbB. For strains with the Met306Leu or Met306Val replacements EMB MICs were generally higher (40 microg/ml) than those for organisms with Met306Ile substitutions (20 microg/ml). The data are consistent with the idea that amino acid substitutions in EmbB alter the drug-protein interaction and thereby cause EMB resistance.

Antitubercular Agents↗

PubMed1997

Characterization of group A Streptococcus strains recovered from Mexican children with pharyngitis by automated DNA sequencing of virulence-related genes: unexpectedly large variation in the gene (sic) encoding a complement-inhibiting protein.

Sequence variation was studied in several target genes in 54 strains of group A Streptococcus (GAS) cultured from children with pharyngitis in Mexico City. Although 16 distinct emm alleles were identified, only 4 had not been previously described. Virtually all bacteria (31 of 33 [94%] with the streptococcal pyrogenic exotoxin gene (speA) had emm1-related, emm3, or emm6 alleles. The gene (sic) encoding an extracellular GAS protein that inhibits complement function was unusually variable among isolates with the emm1 family of alleles, with a total of seven variants identified. The data suggest that many GAS strains infecting Mexican children are genetically similar to organisms commonly encountered in the United States and western Europe. Sequence variation in the sic gene is useful for rapid differentiation among GAS isolates with the emm1 family of alleles.

Amino Acid Sequence↗

PubMed1997

[Prevalence of diabetes and its risk factors in China 1994. National Diabetes Prevention and Control Cooperative Group].

We studied the prevalence of diabetes and impaired glucose tolerance (IGT) and their risk factors in the population of China. It was a population-based, cross-sectional study of 224,251 residents aged 25 years and over in 19 provinces and areas, including cities and rural areas of the North, South, East, West and central China. Using 1985 WHO criteria, We found the prevalence of diabetes and IGT were 2.51% and 3.20% respectively in 213,515 subjects aged 25 to 64 years. 70.33% of the subjects had newly recognised diabetes. The prevalence of diabetes in China is about 3 times higher than it was ten years ago, and the rate is increasing faster in the countryside than in cities. On average, subjects with diabetes are older, have higher personal annual incomes, and have more frequently a family history of diabetes. They also have higher mean body mass index (BMI), ratio of circumference of the waist to hip, systolic blood pressure, diastolic blood pressure and a greater prevalence of hypertension. They perform less physical activity and receive less education than persons with normal OGTT. Multiple logistic, stepwise regression analysis shows that age, BMI (or WHR), family history of diabetes, hypertension, less physical activity and higher annual income are independent risk factors of NIDDM, and that low education is also an independent risk factor of NIDDM in people with higher personal annual income.

Adult↗

PubMed1997

[Clinical characteristics and main diagnostic points of latent autoimmune diabetes mellitus in adults].

To understand latent autoimmune diabetes mellitus in adults (LADA), we compared the clinical characteristics, fasting plasma glucose and C-peptide level, genetic frequency of HLA-DQA1, -DQB1 chain in 25 patients with LADA, 57 patients with insulin-dependent diabetes mellitus (IDDM, 21 patients with children-onset IDDM, 36 patients with adult-onset IDDM with ketosis), 38 patients with NIDDM (mild and moderate 30 patients and severe 8) and 42 normal persons. The onset of age was 20-48 years old associated with obvious polyphagia, and weight loss. Body mass index (BMI) was < or = 25 and fasting plasma glucose was > or = 16.5 mmol/L (297 mg/dl). Fasting and 1, 2 hour post prandial C-peptide level showed low and flatter curve (0.4, 0.8 and 0.8 nmol/L respectively). Glutamate decarboxylase (GAD) antibody was positive. HLA-DQ beta chain substitution of aspartate molecule was at position 57 (susceptic gene). LADA could be diagnosed if a patient has the first point and any point of the second to the fourth point. Patients with LADA should take diet, exercises, especially insulin as early as possible in order to control fasting and post prandial plasma glucose, and prevent from further destroy of residue islet B cells and reduce diabetic complications of eye, kidney and nerve.

Adult↗

PubMed1997

[Immunohistochemical study of type IV collagen chain distribution within basement membrane in patients with Alport syndrome].

To observe the distribution of type IV collagen chains within basement membrane in patients with Alport syndrome (AS), discuss the pathogenesis of AS and assess the diagnostic value of indirect immunofluorescent study of type IV collagen chains. By using indirect immunofluorescence technique, the distribution of different chains of type IV collagen in specimen of renal (6 specimens) and skin (5 specimens) basement membrane of 8 AS patients belonging to 7 kindreds were investigated. In 4 male patients with X-linked dominant (XD) AS, the specific monoclonal antibodies against NC1 domains of the alpha 3, alpha 4 and alpha 5 chains of type IV collagen failed to localize on glomerular basement membrane (GBM) and the alpha 5 chain of type IV collagen were also absent in the epidermal basement membrane (EBM). The results of immunofluorescent study were positive in 3 autosomal dominant and 1 autosomal recessive AS patients as same as that in control. AS presents a biochemical abnormality of type IV collagen. The pathogenesis of XD-AS may associate with the abnormal products of alpha 5 chain. The immunofluorescent study of type IV collagen chains distribution within GBM and EBM by using monoclonal antibodies is useful in confirming the diagnosis of AS, especially XD-AS.

Adolescent↗

PubMed1997

[The effect of the expression of BHRF1 gene of EB virus on the proliferation of the cells of nasopharyngeal carcinoma].

In order to learn the effect of the expression of BHRF1 of Epstein-Barr virus on the growth of the cell of nasopharyngeal carcinoma, high BHRF1 expressive vector was set up and transfected in low grade cell line of nasopharyngeal carcinoma, CNE2. Then the cells were cultivated under the condition of insufficient nutrition. The results show that the BHRF1 expression can prohibit the expression of PCNA, and enhance the survival of tumor cells under conditions of nutrition deprivation. So, it suggests that BHRF1 of EB virus could be involved in the development of nasopharyngeal carcinoma.

Cell Division↗

PubMed1997

[Pharmacognostical identification of Anoectochilus roxburghii].

This paper reported the pharmacognostical identification on characters, microscopic characteristics and TLC of the Anoectochilus roxburghii (Wall.) Lindl., and compared with different resouce samples. The results may provide reference for its identification.

Chromatography, Thin Layer↗

PubMed1997

[The changes and relation among platelet function, plasma heparin and anti-coagulation-III: activity in patients with hemorrhagic fever with renal syndrome].

Blood platelet count (BPC), platelet adhesive rate (PAdT), platelet aggregate rate (PAgT), plasma heparin and anti-coagulation-III: activity (AT-III: alpha) were determined in 55 cases with hemorrhagic fever with renal syndrome (HFRS). In these patients, decreased BPC, defect PAdT, PAgT, increased plasma heparin as well as decreased AT-III: a were found, moreover, these changes were much notable in patients with severe type. A positive correlation existed between plasma heparin and BPC, PAdT, PAgT in cases with 80% AT-III: alpha or above (r values were -0.4344, -.7157 and -0.5547 respectly, p<0.01). The results suggested that plasma heparin may be one of factors resulting in decreased BPC and defect platelet function in HFRS patients with 80% AT-III: alpha or above.

Adolescent↗

PubMed1997

[Study on prethrombotic state in patients with paroxysmal nocturnal hemoglobinuria].

OBJECTIVE: To explore the mechanism of thrombogenesis in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: Thirteen parameters concerning endotheliocytes, platelets, blood coagulation, and fibrinolysis were measured in 21 PNH patients. RESULTS: As compared with normal controls, plasma fibrin peptide A (FPA) levels were significantly higher, but antithrombin-III (AT-III) and protein C (PC) antigen levels lower in the PNH patients. Plasma tissue plasminogen activator (t-PA) activities were significantly lower while plasminogen activator inhibitor (PAI) activities markedly higher in the patients than those in the controls. The levels of the blood coagulation and fibrinolysis parameters changed more notably during the occurrence of thrombosis and hemoglobinuria episodes in the PNH patients. Platelet adhesion rates, platelet aggregation rates, beta-thromboglobulin (beta-TG), and granule membrane protein-140 (GMP-140) were within the normal ranges. Plasma vWF:Ag and endothelin-1 (ET-1) concentrations were normal in the patients as well. CONCLUSION: Prethrombotic state is present in PNH patients, which may be caused by hypercoagulability and low fibrinolytic activity.

Adult↗

PubMed1997

Routine rapid Mycobacterium species assignment based on species-specific allelic variation in the 65-kilodalton heat shock protein gene (hsp65).

OBJECTIVE: To assess the utility of automated DNA sequencing strategies for Mycobacterium species assignment and surrogate rifampin susceptibility testing of Mycobacterium tuberculosis complex isolates in a hospital-based clinical microbiology laboratory. DESIGN: Consecutive patient specimens (n = 161) cultured in BACTEC 12B medium (growth index of 50 or greater) or on solid media (Löwenstein-Jensen) were analyzed. A 360-bp segment of a gene (hsp65) encoding a 65-kd heat shock protein was sequenced to identify species-specific allelic polymorphism. Identification of sequence variation in the rpoB gene encoding the beta subunit of RNA polymerase was used as a surrogate method to assess rifampin susceptibility in M tuberculosis complex isolates. RESULTS: The automated DNA sequencing strategies rapidly identified virtually all mycobacteria (158 [98%] of 161) to the species level and unambiguously characterized the region of rpoB that contains mutations responsible for rifampin resistance in M tuberculosis strains. With few exceptions, DNA sequence-based species assignment data agreed with diagnostic information obtained by conventional methods. All discrepancies were due to ambiguous biochemical test data or interpretation. The rifampin susceptibility phenotype was correctly predicted for all strains by rpoB sequencing. CONCLUSIONS: Rapid mycobacterial species assignment based on hsp65 sequencing can be routinely performed in a hospital diagnostic microbiology laboratory setting. The method is especially useful for identification of fastidious organisms, such as Mycobacterium genavense. Sequencing of the rifampin-resistance-determining region of rpoB provides a convenient surrogate strategy for predicting rifampin susceptibility in M tuberculosis complex isolates.

Alleles↗

PubMed1997

[Molecular evolution of MHC DQA genes. I. The maintenance of interallelic divergence and the influence of GC content on gene structure].

The analyses of the proportion of synonymous and missense nucleotide substitution (PS and PN) in different exons, antigen recognition sites (ARS) and non-ARS of EN2 (NAEN2) of 23 alleles at MHC DQA loci in 7 mammal species gave rise to the following findings. (1) PN was about twice as much as PS in ARS among the alleles at DQA1 of any given species, i.e. 7 alleles at HLA-DQA1 or 8 alleles at IaAa this accords with overdominant selection; (2) PS showed more or less the same as PN in ARS among different loci (DQA1 or DQA2 in different species, or DQA1 and DQA2 in one species) or NAEN2 of all comparative pairs, this conforms the expectation of neutral selection; (3) In exon4 and exon3, not only was the substitution proportion extremely low, but also PS was much higher than PN (the ratio PS over PN is 19.5 in alleles at IaAa of mouse and 4 among alleles at different loci), this coincides obviously with purification selection. The analysis of GC content of MHC DQA showed that its peaks were in the regions corresponding to the middle bulks of some domains, that the highest and constant level was in exon4 and that GC content in the third codon position (GC III content) associates inversely with PS. These results indicate that the specified maintenance mechanisms of interallelic diversity relevant to their functions exist in given exons corresponding to some domains of the same MHC DQA locus and GC III content is an important factor in keeping the structure and function of gene under selection constraint. The method for estimating nucleotide substitution proportion was modified.

Alleles↗