Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients

Proinsulin is a key autoantigen in type 1 diabetes. Evidence in the mouse has underscored the importance of the insulin B chain region in autoimmunity to pancreatic beta cells. In man, a majority of proteasome cleavage sites are predicted by proteasome cleavage algorithms within this region. To study CD8+ T cell responses to the insulin B chain and adjacent C peptide, we selected 8- to 11-mer peptides according to proteasome cleavage patterns obtained by digestion of two peptides covering proinsulin residues 28 to 64. We studied their binding to purified HLA class I molecules and their recognition by T cells from diabetic patients. Peripheral blood mononuclear cells from 17 of 19 recent-onset and 12 of 13 long-standing type 1 diabetic patients produced IFN-gamma in response to proinsulin peptides as shown by using an ELISPOT assay. In most patients, the response was against several class I-restricted peptides. Nine peptides were recognized within the proinsulin region covering residues 34 to 61. Four yielded a high frequency of recognition in HLA-A1 and -B8 patients. Three peptides located in the proinsulin region 41-51 were shown to bind several HLA molecules and to be recognized in a high percentage of diabetic patients.     

A2 gene of Old World cutaneous <Emphasis Type="Italic">Leishmania</Emphasis> is a single highly conserved functional gene

Background  

Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates.     

No evidence of maternal cell colonization in reverted liver nodules of tyrosinemia type I patients

BACKGROUND AND AIMS: Hereditary tyrosinemia type I (HTI) is a recessively inherited disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH), the last enzyme of the tyrosine catabolic pathway. The mosaic pattern of FAH expression observed in the livers of >85% of studied patients was shown to result from the correction of the mutation in one of the FAH alleles. Bilateral cell trafficking can occur between mother and fetus and such an event could be responsible for the chimerism observed in some diseases. It also has been reported that the liver repopulation observed in a HTI murine model by serial transplantation of bone marrow-derived cells was caused by a fusion of these cells to host hepatocytes. These observations led us to test the possibility that the transfer of nucleated heterozygous maternal cells in the fetal circulation could be responsible for the mosaic liver expression of FAH in HTI patients. METHODS: We used polymorphic markers of short cytosine-adenine DNA repeats to compare DNA from corrected liver sections of 4 HTI patients with DNA from their parents' blood. RESULTS: Genotyping showed that only one maternal allele is present in DNA isolated from FAH-expressing liver nodules of each proband for at least 1 marker. CONCLUSIONS: The corrected liver nodules in HTI patients are not of maternal origin and do not support cell trafficking and cell fusion as mechanisms of correction of the gene defect in hepatocytes of tyrosinemia patients.     

Correlates of hepatitis B among patients with mental illness in Brazil

Objective

To assess correlates of hepatitis B among adults with mental illness under care in Brazil.

Method

Cross-sectional national multicenter study of 2206 patients with mental illnesses randomly selected from 26 public mental health services. Sociodemographic and behavioral data were obtained from face-to-face interviews and psychiatric diagnoses from medical charts. Serology testing was conducted, and prevalence rate ratios were estimated by log-binomial regression.

Results

The weighted prevalence rates of current hepatitis B virus (HBV) infection (HBsAg +) and previous HBV exposure (anti-HBc +) were 2.0% [95% confidence interval (CI): 1.5%–2.7%] and 17.1% (95% CI: 16.0%–19.0%), respectively. Correlates of HBsAg + included male gender, younger age (18–29 years), unstable place of residence, intellectual disability, main psychiatric diagnosis of dementia, presence of other medical comorbitidy, use of alcohol/drugs during sex, more than one sexual partner and use of cocaine. Correlates of anti-HBc + included male gender, older age (≥ 30 years), black skin color, lower education, unstable place of residence, currently hospitalized, intellectual disability, history of any sexually transmitted disease or syphilis, poor HIV knowledge, history of imprisonment and sexual violence.

Conclusions

Hepatitis B is an important comorbidity among psychiatric patients in Brazil. Screening for HBV, effective prevention and intervention strategies, including universal HBV immunization, should be routine practices in these mental health services.     

Patterns of attendances to the hospital emergency eye care service: a multicentre study in England

Background/ObjectivesTo characterise the patterns of presentation and diagnostic frequencies in Hospital Emergency Eye Care Services (HEECS) across 13 hospitals in England.MethodsRetrospective, cross-sectional, observational multi-centre (n = 13) study to assess HEECS attendances over a 28-day study period. Data derived included: number of consecutive attendances, patient demographics and diagnoses. Age and gender variations, the impact of day of the week on attendance patterns, diagnostic frequencies and estimates of the annual incidence and attendance rates were evaluated.ResultsA total of 17,667 patient (mean ± standard deviation age = 49.6 ± 21.8 years) attendances were identified with an estimated HEECS annual new attendance rate of 31.0 per 1,000 population. Significantly more females (53%) than males (47%) attended HEECS (p < 0.001). Female attendances were 13% higher in those ≥50 years of age. Weekends were associated with a significant reduction in attendances compared to weekdays (χ² = 6.94, p < 0.001). Among weekdays, Mondays and Fridays were associated with significantly higher attendances compared with midweek (χ² = 2.20, p = 0.032). Presenting pathologies involving the external eye, cornea and conjunctiva accounted for 28.6% of the caseload.ConclusionThis is the largest multicentre study assessing attendance patterns in HEECS in England. We have, for the first time, observed a “weekend effect” in relation to attendance to HEECS. Differences in health-seeking behaviour and lack of awareness of HEECS weekend services may be partly attributed to the differences observed. Our findings, along with the type of presentations, have the potential to guide commissioners with future planning of HEECS.Subject terms: Epidemiology, Epidemiology     

Low dietary adherence after a positive food challenge in food allergic adults

BackgroundAfter a positive food challenge (FC), patients receive dietary advice regarding avoidance of the culprit food. We examined the frequency and variables associated with dietary adherence after a positive FC in adults.MethodsIn this prospective daily practice study, adults with a positive FC were included. After every FC, dietary advice was given consisting of three options: (1) strict avoidance, (2) avoidance but products with precautionary allergen labelling (PAL) allowed and (3) (small) amounts allowed. Questionnaires about dietary adherence and associated variables were completed prior to and 6 months after the FC(s).Results41 patients (with 58 positive FCs) were included. Overall, patients adhered to the advised diet after 31% of the FCs. After 33 FCs, the advice was strict avoidance, whereof 82% followed a less strict diet. After 16 FCs, the advice was avoidance but products with PAL allowed, whereof 19% followed a less strict and 25% a stricter diet. In 9 FCs with the least strict advice, “(small) amounts allowed’’, 67% followed a stricter diet. Three variables were associated with adherence: misremembering dietary advice, impaired health‐related quality of life (HRQL) on domain “Emotional impact’’ and the need for dietary change after the FC.ConclusionAfter one third of the positive FCs, patients adhered to the dietary advice. Variables associated with adherence were misremembering dietary advice, impaired HRQL on domain “Emotional impact’’ and the need for dietary change after the FC. It seems important that healthcare professionals should more frequently apply adherence‐enhancing strategies to improve dietary adherence.