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)

Aberrant dendritic cell (DC) development and function may contribute to autoimmune disease susceptibility. To address this hypothesis at the level of myeloid lineage-derived DC we compared the development of DC from bone marrow progenitors in vitro and DC populations in vivo in autoimmune diabetes-prone nonobese diabetic (NOD) mice, recombinant congenic nonobese diabetes-resistant (NOR) mice, and unrelated BALB/c and C57BL/6 (BL/6) mice. In GM-CSF/IL-4-supplemented bone marrow cultures, DC developed in significantly greater numbers from NOD than from NOR, BALB/c, and BL/6 mice. Likewise, DC developed in greater numbers from sorted (lineage(-)IL-7Ralpha(-)SCA-1(-)c-kit(+)) NOD myeloid progenitors in either GM-CSF/IL-4 or GM-CSF/stem cell factor (SCF)/TNF-alpha. [(3)H]TdR incorporation indicated that the increased generation of NOD DC was due to higher levels of myeloid progenitor proliferation. Generation of DC with the early-acting hematopoietic growth factor, flt3 ligand, revealed that while the increased DC-generative capacity of myeloid-committed progenitors was restricted to NOD cells, early lineage-uncommitted progenitors from both NOD and NOR had increased DC-generative capacity relative to BALB/c and BL/6. Consistent with these findings, NOD and NOR mice had increased numbers of DC in blood and thymus and NOD had an increased proportion of the putative myeloid DC (CD11c(+)CD11b(+)) subset within spleen. These findings demonstrate that diabetes-prone NOD mice exhibit a myeloid lineage-specific increase in DC generative capacity relative to diabetes-resistant recombinant congenic NOR mice. We propose that an imbalance favoring development of DC from myeloid-committed progenitors predisposes to autoimmune disease in NOD mice.
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PMID:Increased generation of dendritic cells from myeloid progenitors in autoimmune-prone nonobese diabetic mice. 1199 55

A case of Pulmonary Alveolar Proteinosis (PAP), in association with tuberculosis, is described in a 35-year-old diabetic patient. Lung biopsy showed an intra-alveolar accumulation of PAS-positive material, and multifocal granulomas compatible with tuberculosis. The bronchoalveolar culture was positive for Mycobacterium tuberculosis. PAP results from an imbalance of the mechanisms that regulate the homeostasis of the surfactant, where specific proteins are involved, especially SP-A and SP-D, the cytokines, IL-10 and GM-CSF, in addition to alveolar macrophages and type-II pneumocytes. Chemotaxis and phagocytic capacity are reduced. PAP and diabetes share several immunological disfunctions that may increase the risk for tuberculosis. Although there are no controlled studies, the diagnosis of PAP in diabetic patients with tuberculosis must be considered.
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PMID:Pulmonary alveolar proteinosis and tuberculosis in a diabetic patient: a rare or a seldom diagnosed association? 1220 86

Airway smooth muscle is actively involved in the inflammatory process in diseases such as chronic obstructive pulmonary disease and asthma by 1) contributing to airway narrowing through hyperplasia and hypertrophy and 2) the release of GM-CSF and G-CSF, which promotes the survival and activation of infiltrating leukocytes. Thus, the identification of novel anti-inflammatory pathways in airway smooth muscle will have important implications for the treatment of inflammatory airway disease. This study identifies such a pathway in the activation of peroxisome proliferator-activated receptors (PPARs). PPAR ligands are known therapeutic agents in the treatment of diabetes; however, their role in human airway disease is unknown. We demonstrate, for the first time, that human airway smooth muscle cells express PPAR alpha and -gamma subtypes. Activation of PPAR gamma by natural and synthetic ligands inhibits serum-induced cell growth more effectively than does the steroid dexamethasone, and induces apoptosis. Moreover, PPAR gamma activation, like dexamethasone, inhibits the release of GM-CSF. However, PPAR gamma ligands, but not dexamethasone, similarly inhibits G-CSF release. These results reveal a novel anti-inflammatory pathway in human airway smooth muscle, where PPAR gamma activation has additional anti-inflammatory effects to those of steroids. Hence, PPAR ligands might act as potential treatments in human respiratory diseases.
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PMID:Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. 1259 95

Hypertension is proposed as a risk factor among others (high age, diabetes mellitus, and pre- and intraoperative bleeding) for adverse outcomes, such as severe infections, leading to sepsis and to multiple organ failure as the most deleterious complication. Hypertension was modeled with spontaneous hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats and the infective complication by polymicrobial, peritoneal contamination, and infection (PCI). The concept of clinic modeling randomized trials was used to simulate clinical complexity, including a relevant antibiotic prophylaxis in combination with granulocyte-colony stimulating factor (G-CSF) and clinical trial conditions. Outcome parameters were: survival, systemic cytokines (protein), and organ-specific cytokine levels (mRNA). With low complexity (no prophylaxis), 28% of the animals in the Wistar and 50% in the SHR group survived (P=0.17). Tumor necrosis factor-alpha levels were lower in the liver of SHR vs. Wistar rats with PCI (P<0.01). The anti-inflammatory cytokine interleukin (IL)-10 was expressed on a higher level in SHR with PCI compared with Wistar rats (P<0.01). With increased complexity (antibiotic and G-CSF prophylaxis) the survival rate was increased from 50% in Wistar rats to 89% in SHR (P<0.01) and the mRNA expression of IL-6 was decreased in the kidney of SHR (P<0.05). Survival rate was 44% in the DS rats vs. 67% of the Wistar rats (P=0.18). The mRNA expression of tumor necrosis factor-alpha and IL-10 was reduced (P<0.01) by pretreatment in the liver of DS rats with PCI. The hypertensive, genetically distinct SHR and DS rats express different patterns of pro- and anti-inflammatory cytokine levels after PCI. G-CSF and antibiotic prophylaxis increases only in SHR survival and decreases IL-6 mRNA expression in the kidney significantly.
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PMID:The genetic background of hypertensive, septic rats determines outcome improvement with antibiotic and G-CSF prophylaxis. 1450 46

Endogenous Aspergillus endophthalmitis (AE) is a rare complication of invasive aspergillosis (IA) in transplant patients. In this report, we describe two patients with polycystic kidney disease, who developed AE with cerebral involvement after renal transplantation. Both patients received intense immunosuppression with methyl prednisolone and mycophenolate mofitil (MMF) because of persistent rejection, which rendered them diabetic and vulnerable to opportunistic infections. Endophthalmitis developed within six months of transplantation and was confirmed by microscopy and culture of the vitreous fluid. Patients were treated with combinations of different anti-fungal agents including liposomal amphotericin B, 5-flucytosine, itraconazole, voriconazole and terbinafine. In an electronic MEDLINE review, we found eight further cases of AE in renal transplant patients between 1959 and September 2002. Based on this review, we identified possible risk factors including CMV infection, diabetes mellitus and treatment for rejection with agents such as methyl prednisolone and MMF. In 70% of cases the histology, microscopy or culture of vitreous fluid confirmed the diagnosis. The outcome of AE in renal transplant patients was poor with 70-100% mortality. The review of reported cases and current practice guidelines suggests that vitrectomy and intravitreal amphoterecin B is the treatment of choice. In addition, new antifungal agents with good CSF and ocular penetration such as voriconalzole should be considered for the treatment of invasive cerebral/ocular aspergillosis.
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PMID:Aspergillus endophthalmitis: an unusual complication of disseminated infection in renal transplant patients. 1455 60

The advances in endoscopic instruments have eased the approach to the sellar region through the nasal cavity. We carry out an analysis of the surgical results on 20 patients that underwent surgery for sellar tumours through a transeptal-transphenoidal approach in the last 2 years in our hospital. The average was 45.6 years old, and 75% were females. 30% of cases were pituitary adenomas and another 30% acromegaly, 25% Cushing's disease and 10% prolactinomas. No complications were encountered during surgery being the most common postoperative complications, diabetes insipida in two cases (10%) and CSF leak in one case. At present 2 patients are having hormonal treatment for panhypopituitarism. No patients developed a septal perforation, nasal deformity, epistaxis, meningitis, lip numbness or oronasal fistula. The rest did have good results noith no recurrence and hormonal values back to normal.
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PMID:[Trans-septal endoscopic approach of pituitary tumors]. 1475 17

Type 1 diabetes is an autoimmune disease that results from the destruction of the insulin-producing pancreatic beta islet cells, probably via the influence of cytokines. However, direct correlation between the expression of selected cytokines by various immune cells at different time points during the progression of the disease has not yet been clearly demonstrated. In this study, we showed that the mRNA expression of the pro-inflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, and GM-CSF, were increased while the anti-inflammatory cytokine, TGF-beta, decreased in the peritoneal macrophages of nonobese diabetic (NOD) mice. IL-6 expression however decreased when the mice became diabetic. Surprisingly the expression of IFN-gamma and IL-2 by splenic CD4+ cells were lower in 5-week-old NOD mice as compared to the nonobese diabetic resistant (NOR) control mice, but their expression was higher in older NOD mice. The expression of IL-4 and IL-10 decreased in splenic CD4-positive lymphocytes. Splenic CD8-positive lymphocytes expressed increased levels of IFN-gamma and IL-10 but the latter decreased sharply when diabetes occurred. The relevance of these findings to the pathogenesis of type 1 diabetes is discussed.
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PMID:The expression of cytokine genes in the peritoneal macrophages and splenic CD4- and CD8-positive lymphocytes of the nonobese diabetic mice. 1502 85

Thymus exerts a prominent role in the establishment os central T-cell tolerance, as well as in the development of self major histocompatibility complex (MHC)-restricted T lymphocytes. Like others autoimmune diseases, type 1 diabetes emergence implies central or peripheric self tolerance breakdown. Environmental factors, especially enterovirus infections, are supposed to be involved in diabetes pathophysiology. Epidemiological studies have highlighted a frequent association between enterovirus Coxsackievirus B4 (CVB4) and type 1 diabetes. The aim of our work was to study whether a thymus infection by CVB4 could induce modifications of thymic function. In primary cultures of thymic epithelial cells (TEC), we detected viral proteins, positive- and negative- strand RNA, and infectious virus in the supernatants, meaning that TEC cultures were susceptible to CVB4 infection and that CVB4 induced a persistent infection in those cells. CVB4 also modulated TEC proliferation and cytokine, such as IL-6, GM-CSF and LIF secretions. Studies using fetal organ thymus culture (FTOC) showed that CVB4 induced a marked and progressive thymocytes depletion, in particular double positive (DP) and CD4+ cells. CVB4 replicated in those subpopulations, indeed positive- and negative-atrand RNA were detected. CVB4 also upregulated MHC class I expression on DP thymocytes. The upregulation of MHC expression required viral infection in DP cells. IL-6 and GM-CSF secretions were also involved in this phenomenom, but IFN-alpha was shown not to be involved. Taken together, our results showed the susceptibility of the human thymus to CVB4 infection, and an important thymic dysfuntion due to this infection. Our work is a novel approach in the understanding of the mechanisms of CVB4-induced type 1 diabetes.
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PMID:[Demonstration and immunologic effect of an infection of the human thymus by the diabetogenic human Coxsackievirus B4]. 1502 68

Aberrant prostaglandin synthase 2 (PGS2/COX2) expression constitutes an antigen presenting cell (APC) dysfunction seen in monocytes of humans at risk for or with Type 1 diabetes. During endotoxin activation of PGS2 expression in healthy monocytes, granulocyte-monocyte colony stimulating factor (GM-CSF) is activated and, in turn, promotes PGS2 gene activation. GM-CSF is considered a major target the action for IL10 in its suppression of PGS2. We found that the PGS2 expression in monocytes from 47% of at-risk and diabetic humans tested were highly resistant to suppression by IL10 (maintaining > or =50% of their untreated expression), and had significantly increased GM-CSF production in vitro (1043+/-SD2798 pg/10(6)cells, subject n=35, vs 29.7+/-SD91 pg/10(6)cells, control n=20; P=0.0165). The PGS2 insensitivity to IL10 of these cells was not due to a lack of IL10 functionality or its suppression of GM-CSF. In contrast to its effects on PGS2, IL10 regulation of GM-CSF and other monocyte factors (i.e., DR, IL1beta, TNFalpha, IL12, CD54, and CD64) remained intact. These findings suggest that the inability of IL10 to properly downregulate PGS2 gene expression may contribute to its dysregulation in Type 1 diabetes.
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PMID:IL10 resistant PGS2 expression in at-risk/Type 1 diabetic human monocytes. 1504 Oct 43

In vitro experiments and animal models indicate that advanced glycation end products (AGEs) may play a crucial role in the vascular dysfunctions observed in patients with diabetes mellitus. These results prompted us to study subrogate markers of inflammation or vascular dysfunction in type II diabetic patients. Monocyte count and activation are dependent upon macrophage colony stimulating factors (M-CSF). Soluble vascular cell adhesion molecule (sVCAM-1) blood levels have been proposed as a marker for endothelium activation. To explore a possible relationship between these factors in diabetic patients, we measured a chemically defined AGE, N(carboxymethyl)lysine-protein (CML-protein) in a group of normal subjects (n = 55) and of diabetic patients (n = 40) using ELISA. Simultaneously, we determined M-CSF and sVCAM-1 blood levels. We found that CML-protein blood levels were significantly higher in patients with diabetes compared to non-diabetic subjects (40.2 +/- 4.7 and 7.9 +/- 0.7 pmol/mg protein respectively, p < 0.0001). M-CSF was increased while sVCAM-1 blood levels were normal in the group of diabetics. M-CSF blood level was correlated to CML-protein blood level (p < 0.05). In addition CML-protein, M-CSF and sVCAM-1 were increased in patients with micro-angiopathy. These results suggest that AGE may contribute to vascular dysfunction including microangiopathy.
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PMID:AGEs, macrophage colony stimulating factor and vascular adhesion molecule blood levels are increased in patients with diabetic microangiopathy. 1511 47


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