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161.
Hon YY; Fessing MY; Pui CH; Relling MV; Krynetski EY; Evans WE 《Human molecular genetics》1999,8(2):371-376
The molecular basis for the genetic polymorphism of thiopurine S -
methyltransferase (TPMT) has been estab-lished for Caucasians, but it
remains to be elucidated in African populations. In the current study, we
determined TPMT genotypes in a population of 248 African-Americans and
compared it with allele frequencies in 282 Caucasian Americans. TPMT
genotype was determined in all individuals with TPMT activity indicative of
a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n
= 21 Caucasians) and a control group with TPMT activity indicative of a
homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23
African-Americans, n = 21 Caucasians). No mutant alleles were found in the
high activity control groups. The overall mutant allele frequencies were
similar in African-Americans and Caucasians (4.6 and 3.7% of alleles,
respectively). However, while TPMT*3C was the most prevalent mutant allele
in African-Americans (52.2% of mutant alleles), it represented only 4.8% of
mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and
TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant
alleles), whereas TPMT*3A was the most prevalent mutant allele in
Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing
a single nucleotide transition (G644A), leading to an amino acid change at
codon 215 (Arg-->His), was found in one African-American with
intermediate activity. These data indicate that the same TPMT mutant
alleles are found in American black and white populations, but that the
predominant mutant alleles differ in these two ethnic groups.
相似文献
162.
Genome sequence analysis of HIV-1 subtype C viruses from India shows monophyletic lineage and relatively limited genetic diversity. To understand its immunological implication, cross-reactivity of neutralizing antibody response was investigated. In primary screening, neutralizing antibody response to single heterologous primary HIV-1 subtype C isolate was assessed in plasma samples from 235 HIV-1 infected, anti-retroviral treatment naive individuals from Pune, India. Plasma samples that showed > or =90% neutralization and two randomly selected plasma samples that showed 50-60% neutralization were tested against a panel of primary HIV-1 subtype C isolates obtained from epidemiologically unlinked individuals from India. The neutralizing antibody response showed extensive cross-neutralization, suggesting presence of shared neutralization determinants among circulating HIV-1 subtype C viruses in India. 相似文献
163.
Kimberly I. Mills Jacqueline Anderson Philip T. Levy F. Sessions Cole Jennifer N.A. Silva Shashikant Kulkarni Marwan Shinawi 《American journal of medical genetics. Part A》2013,161(1):137-144
Wolff–Parkinson–White (WPW) syndrome is caused by preexcitation of the ventricular myocardium via an accessory pathway which increases the risk for paroxysmal supraventricular tachycardia. The condition is often sporadic and of unknown etiology in the majority of cases. Autosomal dominant inheritance and association with congenital heart defects or ventricular hypertrophy were described. Microdeletions of 20p12.3 have been associated with WPW syndrome with either cognitive dysfunction or Alagille syndrome. Here, we describe the association of 20p12.3 duplication with WPW syndrome in a patient who presented with non‐immune hydrops. Her paternal uncle carries the duplication and has attention‐deficit hyperactivity disorder and electrocardiographic findings consistent with WPW. The 769 kb duplication was detected by the Affymetrix Whole Genome‐Human SNP Array 6.0 and encompasses two genes and the first two exons of a third gene. We discuss the potential role of the genes in the duplicated region in the pathogenesis of WPW and possible neurobehavioral abnormalities. Our data provide additional support for a significant role of 20p12.3 chromosomal rearrangements in the etiology of WPW syndrome. © 2012 Wiley Periodicals, Inc. 相似文献
164.
Shrikant R Mulay Dana Thomasova Mi Ryu Onkar P Kulkarni Adriana Migliorini Hauke Bruns Regina Gröbmayr Elena Lazzeri Laura Lasagni Helen Liapis Paola Romagnani Hans‐Joachim Anders 《The Journal of pathology》2013,230(3):322-335
Podocyte apoptosis as a pathway of podocyte loss is often suspected but rarely detected. To study podocyte apoptosis versus inflammatory forms of podocyte death in vivo, we targeted murine double minute (MDM)‐2 for three reasons. First, MDM2 inhibits p53‐dependent apoptosis; second, MDM2 facilitates NF‐κB signalling; and third, podocytes show strong MDM2 expression. We hypothesized that blocking MDM2 during glomerular injury may trigger p53‐mediated podocyte apoptosis, proteinuria, and glomerulosclerosis. Unexpectedly, MDM2 blockade in early adriamycin nephropathy of Balb/c mice had the opposite effect and reduced intra‐renal cytokine and chemokine expression, glomerular macrophage and T‐cell counts, and plasma creatinine and blood urea nitrogen levels. In cultured podocytes exposed to adriamycin, MDM2 blockade did not trigger podocyte death but induced G2/M arrest to prevent aberrant nuclear divisions and detachment of dying aneuploid podocytes, a feature of mitotic catastrophe in vitro and in vivo. Consistent with these observations, 12 of 164 consecutive human renal biopsies revealed features of podocyte mitotic catastrophe but only in glomerular disorders with proteinuria. Furthermore, delayed MDM2 blockade reduced plasma creatinine levels, blood urea nitrogen, tubular atrophy, interstitial leukocyte numbers, and cytokine expression as well as interstitial fibrosis. Together, MDM2‐mediated mitotic catastrophe is a previously unrecognized variant of podocyte loss where MDM2 forces podocytes to complete the cell cycle, which in the absence of cytokinesis leads to podocyte aneuploidy, mitotic catastrophe, and loss by detachment. MDM2 blockade with nutlin‐3a could be a novel therapeutic strategy to prevent renal inflammation, podocyte loss, glomerulosclerosis, proteinuria, and progressive kidney disease. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
165.
Bhushan B. Kulkarni Shivaprakash V. Hiremath Suyamindra S. Kulkarni Umesh R. Hallikeri Basavaraj R. Patil Pramod B. Gai 《Journal of virological methods》2013
The identification of the etiology of breast cancer is a crucial research issue for the development of an effective preventive and treatment strategies. Researchers are exploring the possible involvement of Mouse Mammary Tumor Virus (MMTV) in causing human breast cancer. Hence, it becomes very important to use a consistent positive control agent in PCR amplification based detection of MMTV-Like Sequence (MMTV-LS) in human breast cancer for accurate and reproducible results. This study was done to investigate the feasibility of using genomic DNA of MCF-7 breast cancer cells to detect MMTV-LS using PCR amplification based detection. MMTV env and SAG gene located at the 3′ long terminal repeat (LTR) sequences were targeted for the PCR based detection. No amplification was observed in case of the genomic DNA of MCF-7 breast cancer cells. However, the 2.7 kb DNA fragment comprising MMTV env and SAG LTR sequences yielded the products of desired size. From these results it can be concluded that Genomic DNA of MCF-7 cell is not a suitable choice as positive control for PCR or RT-PCR based detection of MMTV-LS. It is also suggested that plasmids containing the cloned genes or sequences of MMTV be used as positive control for detection of MMTV-LS. 相似文献
166.
167.
168.
Girish Baburao Kulkarni S Roopa N Madhu Jitender Saini Ravi Yadav M Veerendrakumar D Nagaraja 《Annals of Indian Academy of Neurology》2013,16(2):272-275
Recurrent bacterial meningitis (RBM) in many instances is associated with identifiable anatomical defects. Presence of congenital deafness with recurrent meningitis should alert clinician for presence of middle and inner ear malformation. These defects can be demonstrated by various neuro imaging techniques and can be surgically corrected. In this case report we describe a child seen at our institute with congenital deafness and recurrent meningitis, discuss the approach to RBM and briefly describe inner ear malformation associated with the same and how to differentiate them. 相似文献
169.
1.5-T MR imaging of pituitary microadenomas: technical considerations and CT correlation 总被引:3,自引:0,他引:3
M V Kulkarni K F Lee C B McArdle J W Yeakley F L Haar 《AJNR. American journal of neuroradiology》1988,9(1):5-11
Thirty-seven patients with suspected pituitary tumors were evaluated prospectively with MR imaging at 1.5 T. MR detected a microadenoma at its correct location in all eight patients who underwent transsphenoidal surgery, while CT showed a focal abnormality in the correct location in only four of the eight patients. In patients who were clinically and endocrinologically considered to harbor a microadenoma, MR detected a focal pituitary signal abnormality in 83% and CT demonstrated a focal density abnormality in 42%. Infundibular displacement, focal gland convexity, and sellar-floor abnormality were seen equally well with CT and MR. MR imaging protocol included sagittal T1-weighted spin-echo, coronal inversion-recovery, and coronal spin-echo or cardiac-gated spin-echo images. Although inversion-recovery images were superior in detecting focal pituitary lesions, some microadenomas were better seen on T2-weighted images. Cardiac-gated spin-echo images showed focal pituitary lesions better than ungated images did. Our technique demonstrates MR's superior sensitivity to CT in detecting a pituitary microadenoma. 相似文献
170.