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Biomedical subjects

V Lin

Publications and source records attributed to V Lin.

12 recordsLinked to original sources

Elastin gene expression in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.

Aged↗

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). METHODS: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. RESULTS: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (p < 0.001), BP4 (p < 0.01), and BP1 (p < 0.05) were significantly associated with risk of breast cancer. The level of BP3 was the most significant factor predictive of breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066 ng/ml was 0.18 (95% CI, 0.05-0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07-0.68) for breast cancer. When considering only cancer patients (n = 63), decreasing levels of BP4 (p < 0.01) and increasing levels of BP1 (p < 0.02) were significantly associated with progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5-37.4). Better grade of tumor (well and moderately differentiated) was observed in patients with higher levels of BP3 (p < 0.03). CONCLUSIONS: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.

Age Factors↗

Decreased elastin gene expression in noncompliant human bladder tissue: a competitive reverse transcriptase-polymerase chain reaction analysis.

PURPOSE: In low capacity noncompliant fibrotic bladders, as seen in patients with myelomeningocele, elevated storage pressures ultimately can lead to renal damage. Earlier studies have described an increased deposition of extracellular matrix protein, especially type III collagen, in the detrusor muscle. We analyzed elastin gene expression and quantified elastin gene alteration in the obstructed bladder, correlating urodynamically measured compliance with elastin messenger ribonucleic acid (mRNA) concentration. MATERIALS AND METHODS: Using a reverse transcriptase-polymerase chain reaction quantitative technique elastin mRNA can be reliably measured in 5 to 8 mg. samples of bladder tissue. We compared tissue samples from patients with urodynamically demonstrated noncompliant bladders (less than 10 cc/cm. water) to a control group with normal bladder compliance (greater than 20 cc/cm. water). Tissue samples were homogenized and sonicated, and complementary deoxyribonucleic acid (cDNA) was synthetized from mRNA using reverse transcriptase. Wild type and mutant elastin cDNA were synthetized, and target elastin cDNA with unknown concentration was competitively co-amplified with known serial dilutions of the mutant template (competitive polymerase chain reaction). Computerized densitometry allowing cDNA concentration measurement was performed and competitive reverse transcriptase-polymerase chain reaction was repeated at least twice for every sample. RESULTS: Elastin mRNA concentration ranged from 27.6 to 63.2 attomole per mg. in noncompliant bladders compared to 62 to 190 attomole per mg. in controls. The variation within the same sample was less than 10%. There was a statistically significant difference between mean plus or minus standard deviation elastin cDNA concentration in noncompliant bladders (37.48 attomole per mg. +/- 12.06) and controls (119.63+/-41.01 attomole per mg.). CONCLUSIONS: A significant decrease in elastin mRNA matches the decreased deposition of elastic fibers noted in previous immunohistochemical studies. Our data suggest that this decrease is mainly due to a transcriptional down regulation of the elastin gene in noncompliant bladders.

Adolescent↗

Partnership in public health.

In Australia the States, Territories, Federal Government, nongovernmental organizations and the community all contribute to public health development. Efforts are being made to build a partnership between them to improve efficiency and effectiveness.

Australia↗

Loss of c-met protooncogene in primary and metastatic sites of breast cancer.

BACKGROUND: It has been proposed that clones of tumor cells acquire higher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncogene in systemic spread by comparing the loss of the c-met protooncogene between primary and metastatic breast carcinomas. METHODS: Only patients who had not received chemotherapy or radiotherapy in the preceding 6 months were included in this study. Histologically proven malignant tissue was obtained from the primary tumor, involved nodes, and distant metastatic and recurrent tumors of patients with breast carcinomas. Allelic loss of the c-met protooncogene in tumor tissue was determined by Southern blotting using a polymerase chain reaction-generated 347-bp human met-H probe. Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls. RESULTS: Of 52 patients, lymphocyte DNA from 36 patients was heterozygous for the c-met protooncogene (69% informative). Forty-six tumors from these 36 patients were analyzed. Four of 30 primary tumors (13%) showed allelic loss of c-met. Of the nine nodal metastases examined, three (33%) showed allelic loss of the c-met protooncogene. Of seven distant metastatic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall). CONCLUSIONS: Allelic loss of the c-met protooncogene was detected in both primary (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/recurrent disease, the difference when compared with the primary tumor was not statistically significant. These findings indicate a limited role of the c-met protooncogene in breast cancer metastases.

Adult↗

The sequence and structure of the 3' arm of the first stem-loop of the human immunodeficiency virus type 2 trans-activation responsive region mediate Tat-2 transactivation.

Human immunodeficiency virus type 2 (HIV-2) causes AIDS, but generally after a much longer asymptomatic period than that which follows infection with HIV-1. At the molecular level, HIV-2 is much more closely related to the simian immunodeficiency viruses than to HIV-1 and our previous studies have demonstrated that HIV-2 and HIV-1 enhancer stimulation is mediated by different sets of cellular proteins following T-cell activation. Similar to HIV-1, HIV-2 encodes a transactivating protein, Tat, which appears to be necessary for viral replication and stimulates viral transcriptional initiation and/or elongation. While Tat-1 binds to the RNA of the trans-activation responsive (TAR) region of HIV-1 and HIV-2, cellular factors that bind to the RNA transcript are also necessary for Tat to function in vivo. Since almost all previous investigations of cellular cofactors for Tat had focused on HIV-1, we undertook studies aimed at understanding the interaction between the TAR RNA region of the HIV-2 promoter (TAR-2) and cellular proteins. By using extension inhibition analysis (toeprinting) and RNA electrophoretic mobility shift assays, we demonstrated binding of a nuclear factor(s) in T cells to the base of the promoter-proximal stem-loop structure. Mutational analysis of this region revealed that both the sequence of the 3' arm and the stem structure itself are important for activation of the promoter by Tat-2. In contrast, the structure is necessary for activation of TAR-2 by Tat-1 but the sequence is less important. These results suggest that a cellular factor interacts with the 3' arm of the proximal stem-loop structure of TAR-2 and mediates Tat-2-induced increases in the level of HIV-2 transcripts.

Base Sequence↗

Health status differentials in the People's Republic of China.

OBJECTIVES: This study sought to demonstrate that health status varies markedly in different parts of China. METHODS: The main source of data was statistics compiled by the Chinese Ministry for Public Health for 1978 to 1990 regarding causes of death. However, because mortality statistics in China are based on localities that have the capacity to provide data, they are not entirely representative. The international classification of disease categories was also used, together with anatomically based disease descriptions. Rates were calculated using the 1982 and 1990 population censuses. RESULTS: Death rates differ markedly between urban and rural areas. Deaths due to infectious diseases, respiratory diseases, pregnancy and childbirth, and injuries and poisoning are much higher in rural areas; those due to pertussis, dysentery, typhoid, hepatitis, rabies, and anthrax are much more common in the apparently poorer provinces. Schistosomiasis remains a major problem in some provinces. Goiter and cretinism are still major diseases in many parts of China, especially those areas with iodine deficiency. CONCLUSIONS: Cause-of-death patterns in Chinese cities are similar to those of industrially developed countries such as Australia, Japan, and the United States. Such patterns in the poorer rural areas are much more typical of those of developing countries.

Cause of Death↗

Health policy reform in the People's Republic of China.

With very limited resources, China has developed perhaps the world's largest network of health care services. The health status of its peoples has risen dramatically during the past 40 years. The reasons for these achievements are complex and include an ideology of equity for all citizens, the near universal availability of adequate food, education, housing, jobs, and transport, and the universal availability of accessible and affordable treatment and preventive health services. Despite these achievements China is facing new problems. These include the aging of the population, continued growth of the population leading to ever increasing demands on all sectors of the economy including health services, urban-rural inequalities, low productivity in the health services, lack of legal safeguards for health protection, a continued burden of infectious and endemic diseases, weak infrastructure for prevention and primary health care, and an increasing burden of chronic diseases associated with tobacco smoking and atherosclerotic circulatory diseases and trauma due to traffic accidents and occupational hazards. Decentralized management, financial incentives for health workers, privatization of medical practitioners, health legislation, and changes to health insurance arrangements have been introduced as a means of addressing the issues. The outcomes have been uneven, with little or no improvements in some problems and good progress in others. Changes in the health system appear to be reflecting not only health reform measures but also general economic reforms.

Aged↗

Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis.

MyoD1 and myogenin are muscle-specific proteins which can convert non-myogenic cells in culture to differentiated muscle fibres, implicating them in myogenic determination. The pattern of expression of MyoD1 and myogenin during the early stages of muscle formation in the mouse embryo in vivo and in limb-bud explants cultured in vitro, indicates that they may have different functions in different types of muscle during development.

Animals↗

Automated sensory nerve conduction testing using fuzzy logic.

Nerve conduction studies continue to be an important tool in the evaluation of peripheral nerve disorders but have come under increased scrutiny because of heightened cost control in health care service delivery. In selected clinical settings, automated nerve conduction studies may be a useful clinical tool replacing conventional testing, but existing instruments are limited and have not generally been accepted into clinical practice. Further advancements in nerve conduction automation may be possible by incorporating expert system approaches into nerve conduction measurement and control algorithms. Using fuzzy logic techniques to duplicate the reasoning strategies of experienced electrodiagnostic clinicians, a software controller was developed to automatically perform sensory nerve conduction studies. The fuzzy logic system successfully performed 88% of 97 sensory studies in a mixed group of normal and patient populations. Sensory nerve action potential latency and amplitude measures obtained with automated testing were the same as determined by clinicians. Failures were related to design limitations of the controller, noise, and artifact. The high negative predictive value and sensitivity of fuzzy logic based testing suggest that its utility is in minimizing the need for unnecessary conventional electrodiagnostic studies in patients with normal nerve function. Fuzzy logic appears to be a useful approach to nerve conduction automation that can model expert reasoning and judgment.

Action Potentials↗