Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta.

The destruction of beta cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-beta in beta cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-beta mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-beta transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of beta cell-specific autoimmunity mediated by NK cells.

Nager anomaly with severe facial involvement, microcephaly, and mental retardation.

A girl is reported who has severe facial abnormalities with preaxial anomalies of upper and lower limbs indicative of Nager syndrome. Additional findings include marked microcephaly, mental retardation, and normal hearing.

The shadow uniform resource locator: standardizing citations of electronically published materials.

Citation of scientific materials published on the Internet is often cumbersome because of unwieldy uniform resource locators (URLs). The authors describe a format for URLs that simplifies citation of scholarly materials. Its use depends on a simple HTML device, the "refresh page." Uniform citation would follow this format: [Author I. Title of article. http:// domain/year/month-day(e#).html]. The HTML code for such a page is: (HTML) (head) (meta HTTP-EQUIV="Refresh" CONTENT="0; URL= http://Actual-URL/ for-article/ referred-to/ incitation.html") (/head) (/HTML). The code instructs the browser to suppress the content of the refresh page and bring up the title page of the cited article instead. Citations would be succinct and predictable. An electronic journal would not need to alter its existing file hierarchy but would need to establish a distinct domain name and maintain a file of refresh pages. Utilization of the "shadow" URL would bring us one step closer to truly universal resource locators.

Uncommon serious complications in Stevens-Johnson syndrome: a clinical case.

We present an extremely serious clinical case of Stevens-Johnson syndrome, the evolution of which has been followed for 3 years. The etiology was unknown, although it was related with the administration of amoxicillin. We found a type III immunity mechanism involving immune complexes. The serious complications affected the skin, mucosae and internal organs. The present sequelae are: esophageal stenosis, pneumopathy with a 50% deficit of pulmonary perfusion and bilateral trichiasis.

[Cardiopulmonary resuscitation in hospitalized patients in conventional units. Prospective study of 356 consecutive cases. Commission for Care of Cardiorespiratory Arrest]. / Reanimación cardiopulmonar en enfermos hospitalizados en unidades convencionales. Estudio prospectivo de 356 casos consecutivos. Comisión de Atención al Paro Cardiorrespiratorio.

BACKGROUND: Information regarding to the system functioning and to the outcome of patients in whom cardiopulmonary resuscitation (CPR) was performed during their in hospital period in non intensive care units are essentially lacking in Spain. The objectives of the present work were: 1) to define clinical and demographic characteristics of the patients who develop cardiopulmonary arrest in general hospitalization wards; 2) to analyze immediate and late (at discharge) survival rates as well as the frequency of severe sequelae in final survivors; 3) to identify prognostic factors in relationship to survival, and 4) to detect possible internal deficiencies in the organized system of CPR. PATIENTS AND METHODS: All patients who develop cardiac and pulmonary arrest through their hospitalization in general wards during a three year period, were prospectively included. Clinical and demographic data from all the patients as well as data related to the internal functioning of the system were recorded. RESULTS: From 356 included cases, 196 (55%) were initially recovered and 128 (36%) were discharged from the hospital. Among the latter group, 12.5% remained with severely disabling neurologic damage. Age under 80 years, resuscitation maneuvers for less than 20 minutes and respiratory arrest as the ultimate event leading to cardiopulmonary arrest were associated with better prognosis. The internal deficiencies most commonly recorded in the system were false calling to the emergency team, the wrong identification of the location in the hospitalization unit and several abnormalities in the content of CPR sets. CONCLUSIONS: With the currently available organized system directed towards CPR for patients admitted in general hospitalization wards, our rates of success are good and similar to those achieved in some intensive care units. Thus, a similar policy may be encouraged in large hospitals. Since most of the detected deficiencies in internal functioning are easy to rectify, a close monitoring is warranted in order to optimize the results.

Is the incidence of optic neuritis rising? Evidence from an epidemiological study in Barcelona (Spain), 2008-2012.

It is currently believed that the incidence rate of optic neuritis (ON) ranges between 0.56 and 5.1 cases per 100,000 person-years. However, since these figures were generated, they have not been updated and there are suggestions that the incidence of ON is on the rise. When designing new therapies and clinical trials for ON, and to improve the management this disease, it is important to have accurate epidemiological data. Thus, we set out to obtain the prevalence and incidence rates of ON in Barcelona (Spain) from 2008 to 2012, by a retrospective evaluation of electronic hospital records at the Hospital Clinic of Barcelona (population of 300,000 in the catchment area) matching the following ICD-9-CM codes as search terms: 377.3-optic neuritis; 377.30-optic neuritis, unspecific; 377.31-optic papillitis; 377.32-retrobulbar neuritis, acute; 377.39-other optic neuritis and "optic neuropathy". Demographic and clinical data were collected from records with a confirmed diagnosis of ON, including cases of idiopathic ON, multiple sclerosis, neuromyelitis optica and CRION. The prevalence of acute ON on 31 December 2012 was 2.75 cases per 100,000 people. The mean annual prevalence of acute ON during the 2008-2012 period was 7.87 cases per 100,000 person-year and the mean annual incidence rate was 5.36 cases per 100,000 person-years. The incidence of ON in Barcelona during 2008-2012 was higher than previously reported. This increase may reflect the evolution of diagnostic criteria, the use of a referral-center approach instead of a population-based approach, increased awareness of demyelinating diseases, latitude-related factors and possibly a true increase in its incidence.

Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta.

AIMS/HYPOTHESIS: The expression of IFNbeta in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNbeta on Reg expression, and the implications of this in terms of autoimmunity. METHODS: Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNbeta mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNbeta on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. RESULTS: Reg2 was upregulated in islets from the NOD RIP-HuIFNbeta mice at the onset of the autoimmune attack. IFNbeta upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNbeta. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. CONCLUSIONS/INTERPRETATION: Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNbeta-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes.