Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although weight loss associated with human immunodeficiency virus (HIV) infection is multifactorial in its pathogenesis, it has been speculated that hypogonadism, a common occurrence in HIV disease, contributes to depletion of lean tissue and muscle dysfunction. We, therefore, examined the effects of testosterone replacement by means of Androderm, a permeation-enhanced, nongenital transdermal system, on lean body mass, body weight, muscle strength, health-related quality of life, and HIV-disease markers. We randomly assigned 41 HIV-infected, ambulatory men, 18-60 yr of age, with serum testosterone levels below 400 ng/dL, to 1 of 2 treatment groups: group I, two placebo patches (n = 21); or group II, two testosterone patches designed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment. Serum total and free testosterone and dihydrotestosterone levels increased, and LH and FSH levels decreased in the testosterone-treated, but not in the placebo-treated, men. Lean body mass and fat-free mass, measured by dual energy x-ray absorptiometry, increased significantly in men receiving testosterone patches [change in lean body mass, +1.345 +/- 0.533 kg (P = 0.02 compared to no change); change in fat-free mass, +1.364 +/- 0.525 kg (P = 0.02 compared to no change)], but did not change in the placebo group [change in lean body mass, 0.189 +/- 0.470 kg (P = NS compared to no change); change in fat-free mass, 0.186 +/- 0.470 kg (P = NS compared to no change)]. However, there was no significant difference between the 2 treatment groups in the change in lean body mass. The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels (r = 0.41; P = 0.02). The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches (P = 0.04). There was no significant change in body weight in either treatment group. Changes in overall quality of life scores did not correlate with testosterone treatment; however, in the subcategory of role limitation due to emotional problems, the men in the testosterone group improved an average of 43 points of a 0-100 possible score, whereas those in the placebo group did not change. Red cell count increased in the testosterone group (change in red cell count, +0.1 +/- 0.1 10(12)/L) but decreased in the placebo group (change in red cell count, -0.2 +/- 0.1 10(12)/L). CD4+ and CD8+ T cell counts and plasma HIV copy number did not significantly change during treatment. Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group. Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment, an increased red cell count, and an improvement in role limitation due to emotional problems. Further studies are needed to assess whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men.
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PMID:Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. 974 19

The prostate-specific antigen (PSA) promoter is known to be highly tissue specific. Although its tissue specificity has been confirmed, its efficiency of gene transcription is significantly lower compared to known nonspecific viral promoters. These lower levels of promoter activity therefore pose a problem when developing an efficacious gene vector for prostate cancer gene therapy. Thus, selecting an appropriate therapeutic gene and vector system to carry the gene driven by the PSA promoter (PSAP) is important. In the studies described here, a human immunodeficiency virus (HIV)-1-based lentiviral vector carrying either the enhanced green fluorescent protein (EGFP) reporter or the diphtheria toxin A (DTA) gene was constructed. The results demonstrate that the PSA promoter in a lentiviral vector drives genes in prostate cells with satisfactory efficacy and specificity. The tissue-specific expression of the DTA protein efficiently eradicates LNCaP prostate cells in culture. We also infected prostate cancer cells and control cells carried by nude mice with the EGFP lentiviral vector. Significant numbers of EGFP-positive LNCaP cells were detected in all the mice bearing these tumors, but no EGFP-positive control cells were detected in any other mouse tissue. The high levels of expression in prostate cells, compared with the low levels of background expression in other cells, show that the PSAP-lentiviral vector could be a potential useful tool for gene therapy of metastatic prostate cancer.
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PMID:Prostate-specific targeting using PSA promoter-based lentiviral vectors. 1159 31

Upon binding to androgen, androgen receptor (AR) can activate expression of target genes through its direct binding to the androgen-responsive elements (AREs), which are located within the target gene promoters and/or enhancers. A number of cellular proteins have been identified as co-regulators to regulate this transactivation process. One common structural feature among these co-regulators is the presence of the LXXLL motif (X, any amino acid), the so-called nuclear receptor (NR) box, through which binding of these regulatory proteins to AR occurs. We have recently shown that Tip110 functions to potentiate the transactivation activity of human immunodeficiency virus type I (HIV-1) Tat protein. In this study, we report that Tip110 is a potent AR-binding protein that can suppress AR activity. Tip110 bound to AR in an NR box-dependent manner and inhibited AREs-mediated reporter gene expression. The inhibitory effects were abolished by removal of the NR box. Moreover, knock-down of the constitutive Tip110 expression significantly augmented AR transcriptional activation. In agreement with these findings, Tip110 overexpression blocked the prostate-specific antigen (PSA) gene, a well characterized target gene of AR from expression in LNCaP cells. Further analysis revealed that Tip110 prevented the complex formation between AR and AREs. Taken together, these results indicate that Tip110 is a negative regulator of AR transcriptional activation, and may be directly involved in AR-related developmental, physiological, and pathological processes.
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PMID:Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation. 1503 Dec 86

Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7, a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.
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PMID:Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context. 1674 21

Study of male genital tract (MGT) pharmacology is relevant to the treatment of prostatitis, prostate cancer, infertility, and seminal human immunodeficiency virus transmission. However, the time course of drug concentrations in the MGT is largely unknown. To determine the feasibility of frequent semen sampling in assessing the pharmacokinetics of the MGT, we administered efavirenz, indinavir, and zidovudine to subjects to achieve steady-state levels and then collected semen samples at sequentially decreasing ejaculation intervals. The volume of seminal plasma decreased from 4.0 (1.2-5.1) ml (median with range) at 48 h after the baseline ejaculation to 0.72 (0.45-1.6) ml 1 h after a previous ejaculation, which was still adequate for drug concentration assessment. The seminal fructose concentration also decreased. However, the concentration of prostate-specific antigen and all three drugs did not decrease, even if the ejaculation intervals decreased to 1 h. Thus, semi-intensive semen sampling can be used to assess MGT pharmacokinetics.
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PMID:Effect of semen sampling frequency on seminal antiretroviral drug concentration. 1791 41

Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fisher's exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.
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PMID:Biomarker validation of reports of recent sexual activity: results of a randomized controlled study in Zimbabwe. 1974 Oct 42

We demonstrate a Google Glass-based rapid diagnostic test (RDT) reader platform capable of qualitative and quantitative measurements of various lateral flow immunochromatographic assays and similar biomedical diagnostics tests. Using a custom-written Glass application and without any external hardware attachments, one or more RDTs labeled with Quick Response (QR) code identifiers are simultaneously imaged using the built-in camera of the Google Glass that is based on a hands-free and voice-controlled interface and digitally transmitted to a server for digital processing. The acquired JPEG images are automatically processed to locate all the RDTs and, for each RDT, to produce a quantitative diagnostic result, which is returned to the Google Glass (i.e., the user) and also stored on a central server along with the RDT image, QR code, and other related information (e.g., demographic data). The same server also provides a dynamic spatiotemporal map and real-time statistics for uploaded RDT results accessible through Internet browsers. We tested this Google Glass-based diagnostic platform using qualitative (i.e., yes/no) human immunodeficiency virus (HIV) and quantitative prostate-specific antigen (PSA) tests. For the quantitative RDTs, we measured activated tests at various concentrations ranging from 0 to 200 ng/mL for free and total PSA. This wearable RDT reader platform running on Google Glass combines a hands-free sensing and image capture interface with powerful servers running our custom image processing codes, and it can be quite useful for real-time spatiotemporal tracking of various diseases and personal medical conditions, providing a valuable tool for epidemiology and mobile health.
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PMID:Immunochromatographic diagnostic test analysis using Google Glass. 2466 Aug 16

The adult well-male examination should provide evidence-based guidance toward the promotion of optimal health and well-being. The medical history should focus on tobacco and alcohol use, risk of human immunodeficiency virus and other sexually transmitted infections, and diet and exercise habits. The physical examination should include blood pressure screening, and height and weight measurements to calculate body mass index. Lipid screening is performed in men 40 to 75 years of age; there is insufficient evidence for screening younger men. One-time screening ultrasonography for detection of abdominal aortic aneurysm is recommended in men 65 to 75 years of age who have ever smoked. Screening for prostate cancer using prostate-specific antigen testing in men 55 to 69 years of age should be individualized using shared decision making. Screening for colorectal cancer should begin at 50 years of age for average-risk men and continue until at least 75 years of age. Screening options include fecal immunochemical testing, colonoscopy, or computed tomography colonography. Lung cancer screening using low-dose computed tomography is recommended in men 55 to 80 years of age who have at least a 30-pack-year smoking history and currently smoke or have quit within the past 15 years. Immunizations should be updated according to guidelines from the Advisory Committee on Immunization Practices.
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PMID:The Adult Well-Male Examination. 3130 52