Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main principles of this hypothesis are very general: (i) signal-detection from background noise is one central issue in electronics; (ii) an important source of misunderstanding at different levels of communication is the fact that a given signal may have different meanings in different contexts; (iii) the unique role of chance in developmental biology is generally appreciated (37). In AIDS the basic defect would be the human specific inability to distinguish between the amino acid sequence of neuroleukin and peptides derived from the gp120 envelope protein of HIV, resulting in a slowly progressing failure of the CD4+ T cell-mediated immunity. In IDDM the postulated HLA class II-dependent hypersensitivity to immunological noise could predispose to random contacts between cells with a different signalling language. In the ensuing dialogue neuroleukin secreted by T cells would imply a continuous demand for insulin secretion to pancreatic beta cells resulting in diabetes. This hypothesis does not contradict with the provocative ideas proposed by Duesberg concerning the relationships between HIV and AIDS (24) and the known data on the genesis of IDDM.
 ...
PMID:Are syntax errors due to the amino acid sequence of neuroleukin involved in the pathogenesis of the acquired immunodeficiency syndrome (AIDS) and insulin dependent diabetes mellitus (IDDM)? 204 84

Chimpanzees (Pan Troglodytes) and humans are closely related and belong to the same subfamily, Homininae. The approximately 1.8% genetic difference that exists between humans and the chimpanzees must be responsible for observed differences between these two species. It has been shown that chimpanzees can be infected with HIV, but AIDS has not been reported. Furthermore, the prevalence of autoimmune diseases may be low in this species. For instance, type II diabetes occurs, but type I (autoimmune) diabetes (IDDM), to our knowledge, has not been reported. In humans, susceptibility genes for MG and IDDM have been localized to the region between TNF and HLA-B. This region may also influence the rate of progression to death after HIV infection. We have identified differences in this region between humans and the chimpanzees. As shown by PFGE, the TNF to Patr-B region in the chimpanzees is approximately 130-160 kb shorter than the equivalent in humans. Southern and sequence analyses indicate that the deletions in chimpanzees (insertions in humans) include one copy of CL (approximately 10 kb) and the X sequences (< 30 kb). Obviously, other deletions/insertions (approximately 120 kb) need to be identified. Since CL has been shown to be transcribed, the results imply the lack of the gene or, at least, a different gene copy number in the chimpanzees, and we propose that such differences may be relevant to the observed functional differences. We demonstrate here a strategy to identify critical genes responsible for disease development.
 ...
PMID:Differences in the central major histocompatibility complex between humans and chimpanzees. Implications for development of autoimmunity and acquired immune deficiency syndrome. 830 85

Acquired perforating dermatosis (APD) is a very rare disorder which has been described in association with systemic diseases such as diabetes mellitus, HIV infection or lymphoma. In this report we describe a patient with APD associated with sclerosing cholangitis and diabetes mellitus who was successfully treated with rifampicin. A 33-year-old Indian woman with a history of extensive pancreatic surgery, sclerosing cholangitis and insulin dependent diabetes mellitus was referred to our unit with intractable pruritus. She was treated with cholestyramine, ursodeoxycholic acid, several analgesics, UVB therapy, topical steroids, sedative antihistamines and plasmapheresis without significant improvement. Increasingly severe itching was associated with papular skin changes limited initially to the lower limbs but which later involved her entire body. Biopsy of a representative lesion showed the changes of APD. She was subsequently treated with rifampicin which produced a dramatic resolution of pruritus within 3 weeks and the skin changes progressively resolved over subsequent months. In this newly described association of APD with sclerosing cholangitis, rifampicin treatment appeared to be efficient in ameliorating pruritus and the papular skin changes typical of APD.
 ...
PMID:Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis. 1022 Jul 47

In 1978 the first report was published indicating that fusidic acid had an immunomodulatory effect. This study describing an in vitro effect on white cells was followed by an in vivo study showing improved survival in heart transplanted mice. In 1990 these immunomodulatory effects were shown to be related to suppression of cytokine production in animal models of septic shock and insulin dependent diabetes. Disease modulation has been investigated in a number of immunologically mediated diseases, HIV infection, Behcet's disease, Crohn's disease, uveitis and scleroderma. However whether fusidic acid has any useful function as an immunomodulating agent has yet to be fully explored.
 ...
PMID:Fusidic acid non-antibacterial activity. 1052 89

Objective: To compare single-dose antibiotic prophylaxis (cefotetan 1 g vs cefoxitin 2 g) in various subpopulations based upon risk factors for postsurgical infection following cesarean section.Methods: Patients undergoing cesarean section from April 1993 through March 1994 were included in a retrospective analysis if either of the above antibiotics were administered, surgery was non-emergent, gestational age was less than 32 weeks, absence of fever or prior antibiotics therapy within 72 hours, and no history of organ transplantation or HIV. Cases classified as high risk for infection: IDDM, obesity, autoimmune disease, sickle cell disease, or corticosteroid use. Cases classified as high risk for endometritis (any 2 factors): labor >12 hours, >4 vaginal examinations, ruptured membranes >9 hours, and internal fetal monitor. Cases were separated into 4 groups: elective vs non-elective, low vs high surgical risk. A chi(2) analysis was used to test for differences in infection rates between groups (P <.05).Results: Of 1383 cesarean sections, 385 met criteria for inclusion. Non-elective cases accounted for 77% of cases. Postsurgical infection rate was greater in non-elective cases, 7.4%, vs elective cases, 3.0% (P =.056) as was the rate of endometritis (3.2% vs 1.2%, P =.185). No differences were noted based on antibiotic regimen. Postsurgical infection rate was greater for 28 cases at high risk for both surgical infection and endometritis (17.9%) when compared to all 357 other cases (4.5%), P =.003. No difference was noted for endometritis. Of the 28 cases 28.6% of patients treated with cefoxitin and 7.1% of cases treated with cefotetan developed postsurgical infection (P =.13).Conclusion: Overall cefoxitin and cefotetan provided equivalent clinical outcome. A small subset of patients with multiple risk factors for infection may benefit from cefotetan.
 ...
PMID:Single-dose antibiotic prophylaxis during cesarean section. 1083 70

Diabetes is an important cause of morbidity and mortality in Africa. Although a dramatic increase in disease burden is projected, it remains to be seen what effect the ongoing devastation of HIV disease will have on the epidemiology of such chronic diseases as diabetes. Recent data on type 2 diabetes prevalence indicate low rates in some rural populations, moderate rates similar to those in developed areas in some countries, and alarmingly high rates in others. The frequent observation of moderate to high prevalence of impaired glucose tolerance, particularly in populations with a low prevalence of diabetes, may indicate the early stage of a diabetes epidemic. Risk factors include urbanization, age, and family history of disease, as well as such modifiable risk factors as adiposity and physical inactivity. For type 1 diabetes, limited data indicate that the prevalence is low in sub-Saharan Africa and that onset occurs later in life there than in other parts of the world. Mortality associated with diabetes is unacceptably high and is disproportionately due to preventable acute metabolic and infective causes. With long duration of disease, there is a high frequency of hypertension and microvascular complications. The apparent low frequency of chronic macrovascular complications needs fuller documentation - as does the apparent high frequency of hypertension even in the non-diabetic population. Efforts to prevent this disease and its complications in Africa are impeded by inadequate health care infrastructure, inadequate supply of medications, absence of educational programs, and lack of available health care facilities and providers.
 ...
PMID:Diabetes trends in Africa. 1232 80

Until recently, there was a paucity of data on the epidemiology of diabetes mellitus in Africa. Over the past decade, information on the prevalence of type 2 diabetes has increased, albeit still limited, but there is still a lack of adequate data on type 1 diabetes in sub-Saharan Africa (SSA). For type 2 diabetes, although the prevalence is low in some rural populations, moderate and even high rates have been reported from other countries. In low diabetes prevalence populations, the moderate to high rates of impaired glucose tolerance is a possible indicator of the early stage of a diabetes epidemic. Diabetes prevalence is higher in urban, migrant and African-origin populations living abroad. There is evidence for a significant association with preventable and modifiable risk factors viz. adiposity, known diabetes, physical activity; but a dearth of data on the impact of dietary and genetic factors. For type 1 diabetes, the limited available data suggest that in SSA the frequency is low and that age of onset occurs later than in the western world. There is evidence for the role of genetic and immunological factors in its pathogenesis. The impact of HIV/AIDS on projected estimates for diabetes prevalence in Africa needs to be established.
 ...
PMID:Diabetes in Africa. Epidemiology of type 1 and type 2 diabetes in Africa. 1266 4

There is growing evidence that genetic variation plays an important role in the determination of individual susceptibility to complex disease traits. In contrast to coding sequence polymorphisms, where the consequences of non-synonymous variation may be resolved at the level of the protein phenotype, defining specific functional regulatory polymorphisms has proved problematic. This has arisen for a number of reasons, including difficulties with fine mapping due to linkage disequilibrium, together with a paucity of experimental tools to resolve the effects of non-coding sequence variation on gene expression. Recent studies have shown that variation in gene expression is heritable and can be mapped as a quantitative trait. Allele-specific effects on gene expression appear relatively common, typically of modest magnitude and context specific. The role of regulatory polymorphisms in determining susceptibility to a number of complex disease traits is discussed, including variation at the VNTR of INS, encoding insulin, in type 1 diabetes and polymorphism of CTLA4, encoding cytotoxic T lymphocyte antigen, in autoimmune disease. Examples where regulatory polymorphisms have been found to play a role in mongenic traits such as factor VII deficiency are discussed, and contrasted with those polymorphisms associated with ischaemic heart disease at the same gene locus. Molecular mechanisms operating in an allele-specific manner at the level of transcription are illustrated, with examples including the role of Duffy binding protein in malaria. The difficulty of resolving specific functional regulatory variants arising from linkage disequilibrium is demonstrated using a number of examples including polymorphism of CCR5, encoding CC chemokine receptor 5, and HIV-1 infection. The importance of understanding haplotypic structure to the design and interpretation of functional assays of putative regulatory variation is highlighted, together with discussion of the strategic use of experimental tools to resolve regulatory polymorphisms at a transcriptional level. A number of examples are discussed including work on the TNF locus which demonstrate biological and experimental context specificity. Regulatory variation may also operate at other levels of control of gene expression and the modulation of splicing at PTPRC, encoding protein tyrosine phosphatase receptor-type C, and of translational efficiency at F12, encoding factor XII, are discussed.
 ...
PMID:Regulatory polymorphisms underlying complex disease traits. 1559 5

Stem cell technologies hold great potential for the treatment of type 1 diabetes, provided that functional transplantable beta-cells can be selectively generated in an efficient manner. Such a process should recapitulate, at least to a certain extent, the embryonic development of beta-cells in vitro. However, progress at identifying the transcription factors involved in beta-cell development has not been accompanied by a parallel success at unraveling the pattern of their instructive extracellular signals. Here we present proof of principle of a novel approach to circumvent this problem, based on the use of the HIV/TAT protein transduction domain. Neurogenin 3 (ngn3), a factor whose expression is essential for pancreatic endocrine differentiation, was fused to the TAT domain. Administration of TAT/ngn3 to cultured pancreatic explants results in efficient uptake, nuclear translocation, and stimulation of downstream reporter and endogenous genes. Consistent with the predicted activity of the protein, e9.5 and e13.5 mouse pancreatic explants cultured in the presence of TAT/ngn3 show an increased level of endocrine differentiation compared with control samples. Our results raise the possibility of sequentially specifying stem/progenitor cells toward the beta-cell lineage, by using the appropriate sequence and combination of TAT-fused transcription factors.
 ...
PMID:TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro. 1573 48

Islet transplantation has become an accepted method to treat type 1 diabetes. To succeed and achieve normal levels of glucose in transplant recipients, the quality of the transplanted islets is of the utmost importance. Lack of oxygen during organ procurement, islet isolation, and subsequent culture triggers apoptosis or necrosis and loss of islet function, causing the yield and quality to diminish. A promising candidate for cytoprotection against oxygen deprivation is neuroglobin (Ngb). Ngb is a recently described member of globin family and is expressed in neurons, retina, and pancreatic islets. To overexpress this protein in the islets and study its ability to protect them, we utilized protein transduction. Protein transduction is achieved by fusing Ngb to the TAT/PTD transduction domain, a peptide originated from the HIV transcriptional transactivator protein. Our study proved that TAT-Ngb is an efficient fusion protein capable of protecting the human islets in culture from loss of cell mass and function, thus increasing the quality of transplantable islets. If the islets could be cultured for a longer period of time without suffering harmful effects, it would be possible to precondition the recipient and there would be more time to assess their quality and function before transplantation.
 ...
PMID:Protection of islets in culture by delivery of oxygen binding neuroglobin via protein transduction. 1580 6


1 2 3 4 Next >>