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Biomedical subjects

H Yu

Publications and source records attributed to H Yu.

819 records · Page 46Linked to original sources

Mutations in the first intron of the SHR renin gene disrupt putative regulatory elements.

1. Four single base mutations unique to the spontaneously hypertensive rat (SHR) were identified in the first 1100 base pairs of its renin gene first intron when compared to that of Wistar-Kyoto and Sprague-Dawley normotensive rats. 2. These mutations were found to fall within the consensus sequences for a number of transcription factors and thus may alter the affinity of these putative transcription factor binding sites. 3. The reported overexpression of the renin gene in the SHR may therefore result from these structural abnormalities and, in turn, result in a tissue angiotensin-dependent hypertension in this strain.

Angiotensin II↗

Rapid diagnosis of Campylobacter pylori infection by urea test paper.

Antral biopsy specimens from 106 patients were examined by culture, Gram stain and silver stain for Campylobacter pylori. Biopsies were also examined by a urea test paper test (UTPT). Of 106 patients studied C. pylori was detected in 68 (64.2%) by Gram stain, silver stain and culture. The UTPT was positive in 63 (59.4%) specimens. Five had false negative results using the UTPT with no false positive subjects. Thus, UTPT has a sensitivity of 92.6% (63/68) and a specificity of 100%. Of the 63 specimens that were UTPT positive, 45 were positive within 1 min, 58 were positive within 5 min. The remainder became positive between 5 and 15 min. There was a negative correlation between the time required for positive UTPT and the number of C. pylori per pit as seen on silver stained sections (P less than 0.05). UTPT is a rapid and sensitive method for detecting C. pylori in gastric mucosa. This enables early therapy, if indicated, before discharge from hospital. Moreover, the urea test paper method is cheap and easily stored.

Adult↗

Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer.

Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family, which regulates the mitogenic and antiapoptotic effects of insulin-like growth factors. Hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of 235 consecutively selected epithelial ovarian cancer patients in association with IGFBP-3 promoter methylation and IGFBP-3 expression in tumor tissue. IGFBP-3 promoter methylation was analyzed using methylation-specific polymerase chain reaction. Cytosol protein was extracted and measured using a bicinchoninic acid assay; IGFBP-3 was measured by enzyme linked immunosorbent assay. Promoter methylation of the IGFBP-3 gene was detected in 44% (104/235) of patients. IGFBP-3 promoter methylation was associated with disease progression and death after adjusting for clinical and pathologic variables. The association was more evident in patients with early-stage disease: RR = 2.87 (95% CI: 0.78-10.63) for disease progression and RR = 3.94 (95% CI: 0.91-15.78) for death. Tissue levels of IGFBP-3 did not differ by methylation status but were inversely associated with disease stage and residual tumor size. These results suggest that IGFBP-3 promoter methylation may be a useful prognostic marker for disease progression and death in early-stage ovarian cancer.

Biomarkers, Tumor↗

Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest China.

It is just in recent years that mitochondrial DNA (mtDNA) mutations have been found in solid tumors. Although a direct link between the presence of mtDNA mutations and the development of tumors has not been made, mtDNA mutations might prove significant in the detection of tumor recurrence and possibly in the detection of genotoxic damage. To investigate the relationship between mtDNA variation and endometrial cancer, we collected blood samples from subjects with Han native background in Yunnan province in China, 49 of them with pathologically conformed endometrial cancer and 31 as controls with no cancer disease and sequenced two hypervariable segments of control region, part of 16sRNA gene, tRNA(leu) (tRNA is transfer RNA) gene and ND1 gene of mtDNA and identified some diagnostic polymorphisms by restriction fragment length polymorphism of coding region of mtDNA. We could not identify the suspected mutations that are related to diabetes and obesity from our endometrial cancer patients. However, our data showed that patients with endometrial cancers clustered in haplogroup D in a significantly higher frequency when compared with controls, implicating a possible association of haplogroup D to endometrial cancer. We concluded that mitochondrial polymorphisms in haplogroup D might play a genetic role in predisposing to endometrial cancer.

Case-Control Studies↗

Evolutionary origins of the mammalian apolipoproteinB RNA editing enzyme, apobec-1: structural homology inferred from analysis of a cloned chicken small intestinal cytidine deaminase.

Mammalian apolipoproteinB (apoB) RNA editing is a site-specific deamination reaction that mediates the C to U conversion responsible for apoB48 production in the mammalian small intestine. This process is not detected in chicken apoB RNA. Mammalian apoB RNA editing is mediated by a multicomponent enzyme complex that includes a single catalytic subunit, apobec-1. In order to examine the evolution of apobec-1, we have cloned and characterized an orthologous cytidine deaminase cDNA isolated from chicken small intestine. Northern blot analysis revealed expression restricted to the small intestine, colon and lung but not the liver or other tissues. The cDNA encodes a single 31 kDa protein with features reminiscent of other cytidine deaminases and with approximately 39% overall homology to rat apobec-1. The recombinant protein is a cytidine deaminase with activity on a monomeric substrate that was found to be zinc-dependent. However, no RNA editing activity was detectable towards cytidine nucleotides presented in the context of an optimally configured mammalian apoB RNA template. These studies provide information concerning the evolution of the apoB RNA editing machinery and indicate that a chicken small intestinal cytidine deaminase with homology to apobec-1 demonstrates no activity on an RNA substrate.

APOBEC-1 Deaminase↗

Immunofluorometric assay of p53 protein versus sequencing of p53 exons 5 to 9 for the detection of p53 abnormalities in ovarian carcinoma.

p53 alteration, detected as mutation of the p53 gene or as accumulation of mutant p53 protein, is a common feature of most malignancies, including ovarian carcinoma, and may identify patients with unfavorable prognosis and resistance to chemotherapy. Tumor tissues from 55 patients with well or poorly differentiated (grades 1 or 3) primary epithelial ovarian carcinoma were assessed both for p53 protein overexpression by a sensitive time-resolved immunofluorometric assay employing DO-1 and CM-1 antibodies, and for genetic p53 abnormalities by direct sequencing of PCR-amplified exons 5 to 9. Sixteen p53 mutations (29%), including 3 deletions causing frameshifts as well as one nonsense and 12 missense point mutations were found in all exons except exon 9. Overexpression of p53 protein, defined as a concentration exceeding the 75th percentile, was found in 15 cases (27%), 10 of which had missense mutations (P < 0.01). Tumors with nonsense and frameshift mutations were p53-negative by immunoassay. Both p53 mutation (P = 0.04) and p53 protein accumulation (P < 0.01) were associated with stage III-IV disease, while p53 mutation was more closely related to grade 3 lesions (P = 0.04) and serous histotype (P = 0.01). These results indicate that p53 protein accumulation correlates well with missense point mutation in carcinoma of the ovary and, together with other evidence that p53 abnormality may be prognostic of outcome in this disease, suggest that the immunoassay of p53 protein may have clinical value.

Adult↗

Clinical implications of prostate-specific antigen in men and women.

Prostate-specific antigen (PSA) is a valuable tumor marker for prostate cancer. Although it is indeed produced at an extremely high level by the prostate, PSA is also expressed in many female tissues, especially those regulated by sex steroid hormones. PSA is detected in both normal and abnormal breast tissue, as well as in various breast fluids, including milk, nipple aspirate, and cyst fluid. Clinical studies suggest that the presence of PSA in breast tissue may indicate a favorable prognosis for breast cancer patients. Levels of PSA in nipple aspirate fluid, however, may be indicative of breast cancer risk. Concentrations of PSA in serum are elevated in pregnant women as well as in women who have excess androgens. More studies are necessary to determine the clinical implications of the presence of PSA in amniotic fluid and female serum.

Body Fluids↗

Vitrification of encapsulated hepatocytes with reduced cooling and warming rates.

We have used microencapsulated hepatocytes as model to develop a method of vitreous cryopreservation of large quantities of cell-containing constructs. The method included a pre-equilibration procedure in which the amount of penetrating cryoprotectant was gradually increased by 15% in each step. The optimal vitrification solution consists of 40% ethylene glycol and 0.6M sucrose. The concentration of 1M sucrose used for the first dilution solution with subsequent decrease of sucrose concentration to 0.7 M sucrose and by 0.2-0.15M for each subsequent step. This sucrose dilution procedure had no adverse effect on cell functions. Three cooling rates (400 degrees C/min and above) and three warming rates (650 degrees C/min and above), in combination with the proposed vitrification solution, were equally effective. The optimization of the procedure and solutions allow microencapsulated hepatocytes to be preserved with almost 100% retention of cell functions and no detectable damage to the fragile microcapsules. The de-linking of the cooling/warming rates with the effectiveness of vitrification potentially paves the way for large scale cryopreservation of complex tissue engineered constructs.

Animals↗