Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice

Autoimmune diabetes is characterized by an early mononuclear infiltration of pancreatic islets and later selective autoimmune destruction of insulin-producing beta cells. Lymphocyte homing receptors have been considered candidate targets to prevent autoimmune diabetes. L-selectin (CD62L) is an adhesion molecule highly expressed in naive T and B cells. It has been reported that blocking L-selectin in vivo with a specific antibody (Mel-14) partially impairs insulitis and diabetes in autoimmune diabetes-prone non-obese diabetic (NOD) mice. In the present study we aimed to elucidate whether genetic blockade of leukocyte homing into peripheral lymph nodes would prevent the development of diabetes. We backcrossed L-selectin-deficient mice onto the NOD genetic background. Surprisingly NOD/L-selectin-deficient mice exhibited unaltered islet mononuclear infiltration, timing of diabetes onset and cumulative incidence of spontaneous diabetes when compared to L-selectin-sufficient animals. CD4, CD8 T cells and B cells were present in islet infiltrates from 9-week-old L-selectin-sufficient and -deficient littermates. Moreover, total splenocytes from wild-type, heterozygous or NOD/L-selectin-deficient donor mice showed similar capability to adoptively transfer diabetes into NOD/SCID recipients. On the other hand, homing of activated, cloned insulin-specific autoaggressive CD8 T cells (TGNFC8 clone) is not affected in NOD/L-selectin-deficient recipients. We conclude that L-selectin plays a small role in the homing of autoreactive lymphocytes to regional (pancreatic) lymph nodes in NOD mice.     

Evaluación de la validez de las funciones SCORE de bajo riesgo y calibrada para población española en las cohortes FRESCO

Introduction and objectives

To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population.

Progress in the control of HIV infection and AIDS in Navarre, 1985-2003

The epidemiological situation of HIV infection and AIDS in Navarre in 2003 is reviewed. Up until December 2003, 1,610 HIV infections had been diagnosed in residents of Navarre, of whom 41% had died. The new diagnoses of HIV fell by some 81% between 1993 and 2003, a year in which 28 cases were diagnosed (4.8 per 100,000 inhabitants). The fall basically occurred in infections in injection drug users, since the cases due to sexual transmission had remained stable. Over half of the infections diagnosed in the period 2000-2003 (58%) were attributable to heterosexual transmission, 18% occurred in parenteral drug users and 12% in homosexual men. Thirty-three percent were persons originally from other countries. The incidence of AIDS fell from 75 cases in 1996 to 20 in 2003, and mortality from 65 to 8 cases, respectively. In the 2000-2003 period, the average annual incidence of AIDS was 4.2 per 100,000 inhabitants and the average annual rate of mortality was 1.6 per 100,000 inhabitants. At the end of 2003, there were 902 living persons with a diagnosis of HIV monitored by the health system (1.6 known infections per 1,000 inhabitants). In 2003, 65% of the youths aged between 15 and 29 referred to coital sexual relations, a higher percentage than in previous years, but their level of information on the prevention of AIDS was acceptable. It is necessary to insist on prevention and to adapt this to the new situation.     

A Reg family protein is overexpressed in islets from a patient with new-onset type 1 diabetes and acts as T-cell autoantigen in NOD mice.

Genes overexpressed in pancreatic islets of patients with new-onset type 1 diabetes are potential candidates for novel disease-related autoantigens. RT-PCR-based subtractive hybridization was used on islets from a patient who died at the onset of type 1 diabetes, and it identified a type 1 diabetes-related cDNA encoding hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP). This protein belongs to the family of Reg proteins implicated in islet regeneration; its gene contains a putative interleukin-6 (IL-6) response element. Islets from healthy cadaveric human donors released HIP/PAP protein into the culture medium, and this release was enhanced by the addition of IL-6. The expression pattern of mouse homologues of HIP/PAP was determined in pancreata of prediabetic and diabetic NOD mice. Both groups showed positive immunostaining for HIP/PAP in islets and ductal epithelium. To test whether HIP/PAP is a target of islet-directed autoimmunity, we measured splenic T-cell responses against HIP/PAP in NOD mice. Spontaneous proliferation was detected after 4 weeks. Lymphocytes from islet infiltrates and pancreatic lymph nodes from 7- to 10-week-old NOD mice were used to establish an HIP/PAP-specific I-A(g7)-restricted T-cell line, termed WY1, that also responded to mouse islets. WY1 cells homed to islets of NOD-SCID mice and adoptively transferred disease when coinjected with purified CD8(+) cells from diabetic NOD mice. Our conclusion was that differential cloning of Reg from islets of a type 1 diabetic patient and the response of Reg to the cytokine IL-6 suggests that HIP/PAP becomes overexpressed in human diabetic islets because of the local inflammatory response. HIP/PAP acts as a T-cell autoantigen in NOD mice. Therefore, autoimmunity to HIP/PAP might create a vicious cycle, accelerating the immune process leading to diabetes.     

Evaluation of the surveillance system for human immunodeficiency virus infections of Navarra, Spain, 1985-2003

BACKGROUND: Navarra has an information system of HIV diagnoses working since the beginning of the epidemic up to the present day. This study aims at describing and evaluating this system, focusing on its sensitivity. METHODS: The updated guidelines for evaluating public health surveillance systems from the CDC were used to describe the purpose and operation of the system and to analyse its attributes for the period 1985-2003. For the evaluation of the sensitivity the regional database of antiretrovirals distribution was used. RESULTS: The HIV surveillance system of Navarra is confidential and name-based, and includes all HIV-infection cases diagnosed each year. The information sources of the system are: (a) all the laboratories in the public health system that perform the western blot test, and (b) hospital discharge registries. The system covers the entire population of Navarre (584,734 inhabitants). It uses the HIV case definition proposed by the European Centre for the Epidemiological Monitoring of AIDS. The system is well-accepted by the community and by all the stakeholders, including those providing data. By the end of 2003 it included 2302 HIV cases, and 98.8% of all patients who had ever received antiretrovirals in Navarra. CONCLUSIONS: The HIV information system of Navarra is simple, useful, well-accepted and highly sensitive. The information about antiretroviral distribution was useful for this evaluation.     

Adherence to the Mediterranean diet reduces mortality in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain)

Epidemiological studies show that adherence to a Mediterranean diet (MD) increases longevity; however, few studies are restricted to Mediterranean populations or explore the effect of a MD pattern that directly incorporates olive oil. Therefore the relationship between adherence to the MD and mortality was studied within the the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain analysis included 40 622 participants (37·7?% males) aged 29-69 years who were recruited from five Spanish regions in 1992-1996. During a mean follow-up of 13·4 years, 1855 deaths were documented: 913 from cancer, 399 from CVD, 425 from other causes and 118 from unknown causes of death. Risk of all-cause and cause-specific mortality was assessed according to the level of adherence to a relative MD (rMED) score, measured using an 18-unit scale incorporating nine selected dietary components. A high compared with a low rMED score was associated with a significant reduction in mortality from all causes (hazard ratio (HR) 0·79; 95?% CI 0·69, 0·91), from CVD (HR 0·66; 95?% CI 0·49, 0·89), but not from overall cancer (HR 0·92; 95?% CI 0·75, 1·12). A 2-unit increase in rMED score was associated with a 6?% (P?相似文献