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)

Specific mutations in the ras gene impair the guanosine triphophatase (GTPase) activity of Ras proteins, which play a fundamental role in the signaling cascade, leading to uninterrupted growth signals and to the transformation of normal cells into malignant phenotypes. It has been shown that normal cells transfected with mutant ras gene become cancerous and that unfarnesylated, cytosolic mutant Ras protein does not anchor onto cell membranes and cannot induce this transformation. Posttranslational modification and plasma membrane association of mutant Ras is necessary for this transforming activity. Since its identification, the enzyme protein farnesyltransferase (FTase) that catalyzes the first and essential step of the three Ras-processing steps has emerged as the most promising target for therapeutic intervention. FTase has been implicated as a potential target in inhibiting the prenylation of a variety of proteins, thus in controlling varied disease states (e.g. cancer, neurofibromatosis, restenosis, viral hepatitis, bone resorption, parasitic infections, corneal inflammations, and diabetes) associated with prenyl modifications of Ras and other proteins. Furthermore, it has been suggested that FTase inhibitors indirectly help in inhibiting tumors via suppression of angiogenesis and induction of apoptosis. Major milestones have been achieved with small-molecule FTase inhibitors that show efficacy without toxicity in vitro, as well as in mouse models bearing ras-dependent tumors. With the determination of the crystal structure of mammalian FTase, existent leads have been fine-tuned and new potent molecules of diverse structural classes have been designed. A few of these molecules are currently in the clinic, with at least three drug candidates in Phase II studies and one in Phase III. This article will review the progress that has been reported with FTase inhibitors in drug discovery and in the clinic.
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PMID:Protein farnesyltransferase inhibitors. 1273 81

Diabetes mellitus is a common endocrine disorder that is becoming a major public health problem. Viral hepatitis infection is one of the most common causes of chronic liver disease. Several reports from different parts of the world found an association between these two common disorders. In this review we highlight some of the epidemiological aspects of these two disorders, discussed some of the possible mechanisms and questions to be answered to understand this link and be able to solve this mystery.
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PMID:Diabetes mellitus and viral hepatitis: the unsolved mystery. 1286 4

The morbidity of insulin-dependent diabetes mellitus (IDDM) in children develops not evenly. Epidemiological leaps are periodically registered. This character of dynamics suggests the existence of environmental factors having the influence on the IDDM morbidity. One of these environmental factors is viral infection. We have set ourselves as an object to analyze the relationship between the primary morbidity of IDDM and some infectious diseases in children, to build up the prognostic models for the dynamics of IDDM morbidity and to evaluate their quality. Statistic analysis of the relationship between the primary morbidity of chicken pox, scarlet fever, measles, mumps, viral hepatitis, acute intestinal infectious diseases (AIID), acute upper respiratory infections (AURI) and insulin-dependent diabetes mellitus in children of Grodno region covering the period from 1980 to 2001 years has been performed. It has been established, that morbidity rate of IDDM reliably positively correlated with morbidity of AURJ and AIID (accordingly r=0.62; and p=0.02 and r=0.46; p=0.04) and negatively with the scarlet fever and mumps morbidity (accordingly r=-0.55; p=0.008 and r=-0.53; p=0.01). But cluster analysis has shown, that really only indices of AURI and AIID morbidity were connected and formed one cluster. Morbidity rate of IDDM in children in the current year is most closely connected with AURI and AIID frequency in the previous year, but frequency of the above-mentioned infections registered in the same year influences less on diabetes morbidity, not mentioning the infections of 2-years standing which practically have no influence. If the increase in AURI morbidity accounts for 10% as compared to the previous year one may prognosticate with high reliability an increase of primary morbidity of IDDM by 7.7% on the average during the same year, and by 8.3% in the following year. For AIID these indices account for 3.5% and 4.4% correspondingly. In the increase of the morbidity rate of AIID the morbidity rate of IDDM reduces.
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PMID:[The relationship between insulin-dependent diabetes mellitus and acute infections in children]. 1457 15

Ten percent of patients who undergo resection for hepatocellular carcinoma (HCC) associated with chronic liver disease have no detectable cause for this underlying liver disease. Recent studies have shown that patients with cryptogenic chronic liver disease frequently have risk factors for nonalcoholic fatty liver disease (NAFLD). This study examines the incidence of risk factors for NAFLD in patients with chronic liver disease who underwent resection for HCC. Among 210 patients with chronic liver disease who underwent resection for HCC, 18 (8.6%) had no identifiable cause for the underlying liver disease. These patients were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma. Comparisons were made with matched patients with alcohol- and chronic-viral-hepatitis-related HCC. The prevalence of obesity (50% vs. 17% vs. 14%), diabetes (56% vs. 17% vs. 11%), aspartate aminotransferase/alanine aminotransferase ratio<1 (50% vs. 19% vs. 17%), and steatosis>20% (61% vs. 17% vs. 19%) was significantly higher in patients with cryptogenic liver disease than in patients with alcohol abuse and chronic viral hepatitis (P<0.0001 for each). Well-differentiated tumors were significantly more common in patients with cryptogenic liver disease (89% vs. 64% in patients with alcohol-related HCC vs. 55% in patients with chronic viral hepatitis-related HCC, P<0.0001). In conclusion, the hypothesis that obesity and diabetes mellitus may be important risk factors for cryptogenic chronic liver disease in patients with HCC is supported by the analysis of surgically treated patients. Whether HCC is primarily related to obesity and diabetes mellitus or secondarily to a NAFLD-like parenchymal lesions remains to be clarified.
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PMID:Obesity and diabetes as a risk factor for hepatocellular carcinoma. 1476 43

The present study was performed to investigate the relationship between diabetes mellitus (DM) and primary hepatocellular carcinoma (HCC). Incident HCC cases were recruited in Kyushu, Japan. Ethnicity-, age-, gender-, residence-matched hospital controls and community controls were collected. Information on viral hepatitis B (HBsAg) or viral hepatitis C infection, history of blood transfusion, past histories including DM, amount of drinking or smoking, and genotypes of alcohol metabolizing enzymes was collected. Associations between these items and HCC were analyzed multivariately by conditional logistic regression analysis. Two hundred and twenty two (177 males and 45 females) case-control sets were completed between July 1995 and June 2000. Since hospital controls turned out to be a biased one or those sampled from a DM-prone population, a multivariate analysis was performed for the HCC-community controls sets, and it yielded significantly elevated odds ratio (OR)s due to past histories of DM (2.522; 95% Confidence Interval (CI) = 1.267-5.020), blood transfusion (1.747; 1.136-2.689), and unit increment of alcohol consumption (1.358; 1.096-1.684) for males. The same analyses of the HCC-community-controls sets for females, revealed an elevated but not statistically significant OR due to past histories of DM (4.195; 0.808-21.805). A multivariate analysis revealed that DM might be a risk factor for HCC.
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PMID:Association between diabetes mellitus and hepatocellular carcinoma: results of a hospital- and community-based case-control study. 1476 71

Clinicians in both the developed and also the newer industrial economies in the Asia-Pacific region will encounter non-alcoholic fatty liver disease (NAFLD) with increasing frequency. Although the region has been a significant contributor to the current state of knowledge, the spectrum of NAFLD, its severity and the potential for significant future morbidity and health costs are not widely recognized. Lifestyle changes, the epidemic of childhood and adult obesity and type 2 diabetes sweeping the Asia-Pacific represent the key substrates for the rising prevalence of NAFLD. Physicians in all disciplines need to be aware of clinical clues to the presence of NAFLD in the absence of other liver disease and in those with chronic viral hepatitis and they should be able to identify subsets at risk for liver-related morbidity. Given the scope of the problem, efforts should focus primarily on preventing or ameliorating the impact of risk factors; the key one is insulin resistance and its associates of diabetes and central obesity. Pharmacotherapy may play a role in selected individuals. A regional agenda for case definition, future study and public health initiatives is urgently required.
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PMID:Non-alcoholic steatohepatitis in the Asia-Pacific region: future shock? 1501 72

The NTPR continues to maintain an ongoing active database as a resource for health professionals counseling recipients regarding pregnancy and for recipients themselves to contact the registry and request information. This includes female transplant recipients as well as male recipients who father pregnancies. Recipients who consent are entered into a database; analyses are ongoing, including long-term follow-up of the recipient, the graft and the offspring. The safety of pregnancy for parent and child remains the goal of the registry. Guidelines for counseling recipients proposed in 1976 remain applicable. Recipients should be in general good health and graft function should be stable and ideally rejection free. Comorbid conditions should be well controlled, especially hypertension and diabetes. While these counseling guidelines were formulated for kidney recipients, they may be extrapolated for other organ recipients. Analyses this year included pregnancy outcomes of recipients on newer agents, MMF and sirolimus. It remains unclear whether these adjunctive therapies should be altered for pregnancy. The balance of immunosuppression and the prevention of rejection need to be weighed against the potential for teratogenicity when counseling these recipients inquiring about pregnancy. Although there are periodic reports of recipients with graft dysfunction, rejection or graft loss possibly related to pregnancy events throughout all the organ groups, whether transplanted as adults or as pediatric patients, the majority of pregnancy outcomes reported to the NTPR appear favorable for parent and newborn. Whether recipients should breastfeed remains controversial. Recent reports in the literature as well as NTPR data appear favorable. This represents the last report from our initial established location at Thomas Jefferson University. In January of this year, the registry moved to Temple University School of Medicine, Department of Surgery, Philadelphia, PA. The NTPR remains committed to investigating outcomes of pregnancies reported by centers or self-referrals nationwide. Some of the active issues for the upcoming year include the potential for teratogenicity with combinations of newer agents, incidence of viral hepatitis, risk assessment for pregnancy in female lung recipients, and long-term maternal and pediatric follow-up.
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PMID:Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. 1538 4

Hepatocellular carcinoma (HCC) is increasing in frequency in the United States. The age-adjusted incidence rates have doubled over the past 2 decades. Similar increases have affected the mortality and hospitalization rates. Although there has been a small recent improvement in survival, it remains generally dismal (median, 8 months). It is estimated that 8500 to 11,500 new cases of HCC occur annually in the United States. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age, 65 years) population, there has been a shift toward relatively younger age cases. Men are affected 3 times more frequently than women, Asians are affected 2 times more than blacks, and Hispanics are affected 2 times more often than whites. However, the recent increase has disproportionately affected white (and Hispanic) men between ages 45 and 65 years. The temporal changes of risk factors among HCC cases in the United States remain unclear. However, available studies indicate that hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely to continue to increase for the next decade. A variable but significant proportion of cases (15% to 50%) do not have evidence of the risk factors of viral hepatitis or heavy alcohol consumption. The insulin resistance syndrome, manifesting as obesity and diabetes, is emerging as a risk factor for HCC in the United States; however, its impact on the current trend in HCC remains unclear.
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PMID:Hepatocellular carcinoma: recent trends in the United States. 1550 94

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including China and Africa, whereas in developed countries such as the United States, HCV plays a more prominent role and is at least partially responsible for the increase in HCC incidence in this country. Humans are exposed to hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of poor storage of susceptible grains. Highly exposed populations are primarily in sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of cigarette smoke are hepatic carcinogens in animals, and there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Diabetic patients are at risk for HCC probably as a result of the hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the current epidemic of obesity and diabetes in the United States, this risk factor will be increasingly important. Increased risk for HCC is evident in young noncirrhotic users of oral contraceptives in the United States and Europe. In summary, risk factors for HCC are identifiable in most patients and primarily are associated with chronic hepatic injury.
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PMID:Environmental factors and risk for hepatocellular carcinoma. 1550 6

Hereditary hemochromatosis is a common disorder of iron metabolism that increasingly is diagnosed and treated prior to the development of cirrhosis or diabetes. The discovery of a candidate gene for hereditary hemochromatosis undoubtedly will result in improved diagnosis of hereditary hemochromatosis and to a better understanding of certain aspects of iron absorption, hepatic iron uptake and release, and whole body iron metabolism. In turn, this enhanced understanding of iron biology can be applied to the observations seen in patients with other hepatic diseases such as chronic viral hepatitis.
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PMID:Iron overload states. 1556 46


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