Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear factor-kappaB (NF-kappaB) is a ubiquitous redox-sensitive transcription factor involved in the pro-inflammatory response to several factors, including cytokines and oxidative stress. Upon activation, NF-kappaB translocates into the nucleus and binds to specific nucleotide sequences. The cellular responses to inflammatory and stress signals have been implicated in disease conditions, such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. The conventional method for detection of NF-kappaB -DNA binding activity is the electrophoretic mobility shift assay (EMSA), which is time-consuming and non-quantitative. Here, we report (a) development of a rapid, sensitive and quantitative chemiluminescent immunoassay (QCI) for analysis of NF-kappaB DNA-binding activity, and (b) validation of the QCI with the EMSA using nuclear and cytosolic extracts from cultured prostate cancer cells (PC3), rat liver homogenates and human lymphocytes. The QCI for analysis of NF-kappaB DNA binding activity has advantages over the EMSA: (1) Higher speed: 3-5h post sample preparation, (2) Greater sensitivity: 10pg NF-kappaB/well, (3) Quantitative: linear range: 10-1000pg NF-kappaB; r2 = 0.999 (4) High throughput adaptability: 96-well plate format can analyze up to 40 samples in duplicate, (5) SAFETY: No radioactive isotopes, (6) Simplicity, and (7) Capability of measurement of both activated (free) NF-KB which is translocated into the nucleus and total (bound + unbound) NF-kappaB present in the cytosol/cell.
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PMID:Quantitative chemiluminescent immunoassay for NF-kappaB-DNA binding activity. 1579 22

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

The relationship between lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia and sexual health in men participating in a national multicenter screening program was studied. A total of 12 679 men were screened for prostate cancer in the year 2003. Of these, 6641 men had completed both the American Urological Association Symptom Score (AUA-SS) and the Sexual Health Inventory for Men (SHIM) questionnaires. We assessed the apparent effect of comorbidities (ischemic heart disease, hypertension, hypercholesteremia and diabetes), smoking habits and testosterone level on the overall sexual health. Age and race were also assessed as factors affecting the SHIM score. We used a general linear multivariable regression analysis to express the effect of these variables on the sexual health in these men adjusting for the apparent effect of LUTS. The mean and median age of the population was 58.4 +/- 9.8 and 58 y, respectively. The median AUA-SS was 4/25 (mean=5.7 +/- 5.3) and SHIM score was 19/25 (mean=16.3 +/- 5.9). Of the men, 4948 (75%) were Caucasian and 1154 (17%) were from African-American racial origin. A high AUA-SS appears to have a negative effect on the overall sexual health (P<0.05) after adjusting for all other confounding factors. As expected, age showed a significant inverse correlation with SHIM score (P<0.05). Caucasian men on average appear to have a significantly higher SHIM score by 6.5 points when compared to African-American men after adjusting for age, comorbidities, smoking habits, and AUA-SS (P<0.05). However, with increasing age, the difference in SHIM score diminishes between the two groups. Further, smoking and comorbidities were strong predictors of poor sexual health performance. Interestingly, hypogonadism (testosterone <300 ng/dl) was not a significant risk factor (P=0.104) when adjusting for all other variables. Nonetheless, in a univariate analysis, testosterone levels significantly correlated with reported SHIM scores (P<0.05). The overall sexual health in aging men is substantially affected not only by age, but by the severity of their urinary symptoms after adjusting for the most common known risk factors, suggesting perhaps a common underlying pathophysiology. Moreover, race appears to constitute another neglected potential risk factor, which should be investigated further in future studies.
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PMID:Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the Prostate Cancer Awareness Week (PCAW). 1588 21

Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.
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PMID:Factors associated with the lumbar spine and proximal femur bone mineral density in older men. 1588 16

This article has discussed the increased incidence and disproportionately increased mortality of prostate cancer among African American men.Although the exact reasons are unknown, genetics may play a role, in addition to health care practices. Morbidity from other disease states, such as diabetes, obesity, or hypertension, may influence the overall survival of patients with prostate cancer. Current research tools will continue to explore biologic differences between the races; however, socioeconomic status and access to health care must not be overlooked. Several studies have demonstrated that similar disease stages and equal access to health care will result in similar outcomes. It is recognized that screening for prostate cancer will remain a controversial topic. Several influential professional societies recommend against screening and other professional societies endorse screening. Large-scale trials are currently underway hoping to answer this critical question. Since the advent of current screening tools, however, it seems that the overall mortality for prostate cancer has decreased and this cannot be ignored. Certainly, screening programs and clinical trials have traditionally had difficulty in recruiting minority participants, although more recent trials seem to be finding success. A primary care physician who is viewed as competent by their patients can certainly have a positive impact on their African American patients' willingness to participate in studies and screening programs. Most importantly, on the individual level, primary care physicians can provide a great service to their minority patients by offering educational materials on prostate cancer and by offering screening to qualified patients. The current American Urologic Association and National Cancer Institute guidelines recommend offering screening to all men age 50 and above. African American men or men with a first-degree relative with prostate cancer should be offered screening beginning at age 40. Proper screening consists of both a digital rectal examination to assess for asymmetry or nodules of the prostate and a serum PSA. Current recommendations are that individuals with a serum PSA greater than 4 ng/mL ora prostate nodule or asymmetric prostate should be referred to an urologist,where a biopsy can be performed easily in the office setting.The PSA cutoff of 4 has recently been questioned. A study by Thompson et al [31] evaluated 2950 men with a PSA of 4 or less with prostate biopsy.They found that the risk of prostate cancer in men with a PSA between 3.1 and 4 was 26.9% and that 25% of these men with prostate cancer had high-grade disease. All men found to have cancer had T1 disease. The clinical relevance of this surprisingly high rate of prostate cancer in men with a normal PSA is yet to be determined and is pending in studies on the ultimate effect of screening on mortality from prostate cancer. This information is not intended to confuse the issue, but intended to provide the most up-to-date information and allow for the best clinical decision making by the primary care physician. What can currently be recommended is if a patient is concerned about his possibility of having prostate cancer despite a normal PSA, a referral to an urologist to at least further discuss the issue may be in order. This may be especially true if the patient is African American or has a family history of prostate cancer at an early age.
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PMID:Minority issues in prostate disease. 1592 51

Erectile dysfunction (ED) is a frequent disorder affecting the man's sexual and relational quality of life. French epidemiological studies estimate that the prevalence of ED is between 11% and 44% and prevalence surveys show a correlation between ED and age: the relative risk of erectile dysfunction increases by a factor of 2 to 4 between the ages of 40 and 70 years. Few patients consult their doctor and only a small proportion of them receive treatment and few doctors take the initiative to discuss the question of their patients' sex life. Doctors should now have a good understanding of erectile dysfunction and must be aware of the importance of detecting or at least investigating any erectile dysfunction, which can be the first symptom of an underlying disease such as cardiovascular disease, diabetes, depression, benign prostatic hyperplasia, prostate cancer, androgen deficiency or a drug-induced effect. Demonstration of erectile disorders therefore represents an excellent opportunity to conduct a general work-up, as more than one-third of patients with ED ignore their underlying health problem and management of ED is therefore an integral part of preventive medicine.
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PMID:[Erectile dysfunction: a sentinel symptom?]. 1599 93

Diabetes is one of the most common chronic diseases in the United States. An estimated 18.2 million people in the US (6.3%) have diabetes; among them 2.8 million are African Americans (AAs). On average, AAs are twice as likely to have diabetes as European Americans (EAs) of similar age. AAs disproportionately suffer from various diseases in the US. Many of these diseases include hypertension, cardiovascular disease (CVD), diabetes mellitus (DM-beta predominantly Type II), and cancers of the prostate and pancreas. A number of risk factors such as smoking, a high fat diet, little physical activity, stress, and meager access to health care have been the subject of numerous investigations. However, the factor of the interaction between genetics and the environment has received very little attention in the scientific community. Of note, the content of zinc in pancreatic beta gells is among the highest in the body; however, very little is known about the uptake and storage of zinc inside these cells. We hypothesize that one of the major reason AAs disproportionally suffer from DM (as well as some other illnesses like prostate cancer, CVD and hypertension) is due to their inherent inability to transport appropriate amount of zinc in the crucial cell types that require relatively higher amount of zinc than the other cell types. In this article, we will explore in detail the possible genetic and environmental link between human zinc transporters (hZIPs) and their differential expressions in the islet beta cells from AAs as compared to other racial groups, particularly EAs, in both normal healthy individuals and diabetic patients. We hypothesize that the hZIPs play an important role in the development of diabetes, and the main reason AAs disproportionately suffer from DM (as well as other illnesses like prostate and pancreatic cancers, hypertension, and CVD) as compared to EAs may be due the low degree of expressions of the critical zinc transporters in the beta cells. Understanding the molecular events in the pathogenesis of DM with regards to regulation of zinc uptake would be critical to the evaluation of the natural history of diabetes in humans and especially in various racial groups. If a direct link between zinc transport and diabetes can be established, then a special nutritional formula, medication or other intervention might be especially designed to test the ability to decrease the incidence of this disease in DM susceptible groups, particularly in AAs.
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PMID:Role of zinc and zinc transporters in the molecular pathogenesis of diabetes mellitus. 1604 3

The vitamin-D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of immune responses, and regulation of cell proliferation and differentiation. Variation in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular ailments, urolithiasis and tuberculosis. Activity of Vit-D is mediated by the vitamin D receptor (VDR), a ligand dependent receptor. VDR gene polymorphisms thus represent strong positional candidates for different diseases like prostate cancer, urolithiasis, inflammatory bowl disease and osteoporosis. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and can reveal modest and subtle but true biological effects. The abundance of polymorphisms in the human genome as well as high frequencies in human populations have made them targets to explain variation in risk of common diseases. The present study was carried out to determine the distribution of VDR gene (Fok-I, Taq-I and Apa-I) polymorphisms using a PCR-based restriction analysis in unrelated normal healthy individuals from a north Indian population. We obtained allelic frequencies of (68.5% vs 31.5%), (66% vs 34%) and (58% vs 42%) for (F vs f), (T vs t) and (A vs a) alleles, with 44%, 49% and 7%, respectively, for genotypes FF, Ff and ff , 49%, 40% and 11% for TT, Tt and tt and 36%, 44% and 20% for AA, Aa and aa. Our results suggest that the frequency and distribution of the polymorphisms in India are substantially different from in other populations and ethnic groups. Thus the data signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.
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PMID:Vitamin-D receptor (VDR) gene (Fok-I, Taq-I and Apa-I) polymorphisms in healthy individuals from north Indian population. 1610 24

A major stumbling block for research on and treatment of type 1 diabetes is the inability to directly, but noninvasively, visualize the lymphocytic/inflammatory lesions in the pancreatic islets. One potential approach to surmounting this impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes in the microvasculature that invariably accompany inflammation. MNP-MRI did indeed detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions in vivo in real time. We demonstrate, in proof-of-principle experiments, that this strategy allows one to predict, within 3 days of completing treatment with an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are responding to therapy and may eventually be cured. Importantly, an essentially identical MNP-MRI strategy has previously been used with great success to image lymph node metastases in prostate cancer patients. This success strongly argues for rapid translation of these preclinical observations to prediction and/or stratification of type 1 diabetes and treatment of individuals with the disease; this would provide a crucially needed early predictor of response to therapy.
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PMID:Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes. 1611 Mar 29

In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically important production and reproduction traits. Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans, associations have been found with overweight or (early-onset) obesity, non-insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin's lymphoma. In cattle, associations have been found with feed intake, milk yield traits, carcass traits, and reproduction-related traits, and in pigs with feed intake, average daily gain, carcass traits (backfat/leanness), and reproduction performance traits. Many of the polymorphisms were only included in a limited number of association studies, or the phenotypes studied varied largely for a given polymorphism between studies. Therefore, many of the associations found for these polymorphisms need to be confirmed in future studies before firm conclusions can be drawn.
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PMID:Leptin gene polymorphisms and their phenotypic associations. 1611 75


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