Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice.

Similar to pancreatic islets, submandibular glands are more rapidly infiltrated in female NOD mice than in males. The present comparative analysis of cellular infiltrations in lacrimal glands, however, revealed the opposite finding. At 12 wk of age, approximately 25% of male lacrimal tissue area is infiltrated, whereas age-matched female NOD mice still lack major signs of inflammation. T cells predominate in early stages of invasion, but B cells accumulate promptly in more advanced stages, and ultimately dominate over T cells. Dacryoadenitis is promoted by sex hormones, as suggested by the reduced infiltrations seen in orchidectomized NOD males (P < 0.01). It is also controlled by the local environment provided by the lacrimal tissue. Splenocytes from 4- and 20-wk-old female NOD mice cause massive lesions upon adoptive transfer into NOD male recipients while, conversely, female recipients develop barely any histological sign of infiltration, even after transfer of splenocytes from 20-wk-old donor males. These observations provide strong evidence for a dacryoadenitis-promoting role of male gonadal hormones in NOD mice, a finding that contrasts the known androgen-mediated protective effects on insulitis and submandibulitis in the same strain and on dacryoadenitis in other animal models of Sjögren's syndrome.     

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.     

Production of a monoclonal antibody for evaluation of hard red winter wheat cultivars to wheat streak mosaic virus

The monoclonal antibody technology has provided a means to produce a supply of highly specific uniform antibody which is useful in the detection of plant viruses and which facilitates disease resistance screening. Because of the specificity of a monoclonal antibody to an epitope, a monoclonal antibody may not react to a partially degraded protein. Wheat streak mosaic virus (WSMV) is a member of the potyvirus group and is transmitted by the wheat curl mite Eriophyes tulipae Keifer. The capsid protein of WSMV, like many potyviruses, is degraded in planta. Monoclonal antibodies produced to WSMV reacted to native as well as trypsin treated virions. The antibodies were also useful for evaluation of hard red winter wheat cultivars inoculated with WSMV in the fall or in the spring under field conditions.     

Elevated levels of the antimicrobial peptide LL‐37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response

Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL‐37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL‐37 in HS lesions, and therefore, the aim of this study was to compare levels of LL‐37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL‐37 in HS. We confirm an upregulation of the LL‐37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL‐37 in HS with the presence of T cells, macrophages, neutrophils, IFN‐γ, IL‐17, IL‐23, TNF‐α, IL‐32 and IL‐1β. Mechanistically, LL‐37 boosts the proliferation of unspecifically activated CD4⁺ T cells via an increased calcium signalling independent of antigen‐presenting cells. Targeting LL‐37 may therefore represent a new therapeutic option for the treatment of this recalcitrant disease, but it has to be kept in mind that LL‐37 also has an antimicrobial function.     

Estimation of the relationship between body mass index and EQ-5D health utilities in individuals with type 2 diabetes: Evidence from the population-based KORA studies

ObjectivesObesity is known to be an important risk factor for type 2 diabetes and its related comorbid conditions; however, its specific impact on generic health-related quality of life (HRQL) is less clear. The objective of this study was to estimate the association between body mass index (BMI) and HRQL in individuals with type 2 diabetes.MethodsThe EQ-5D quality of life questionnaire was administered in a follow-up of 10,385 participants aged 33–94 of the population-based German MONICA/KORA surveys. 1033 participants with type 2 diabetes were identified by self-report combined with validated physician diagnoses. Semiparametric additive regression models were used to estimate the effect of BMI on EQ-5D health utilities adjusted for age, sex, education and comorbidities.ResultsBMI was significantly associated with EQ-5D health utilities even after adjustment for macro- and microvascular complications. The functional relationship between BMI and utilities was nonlinear, reflecting optimal health around 26 kg/m² and significantly decreasing health utilities with increasing levels of overweight and obesity (? 0.09 points between BMI values 26 and 40). Among the diabetic complications, the history of a stroke (? 0.13) and neuropathy (? 0.10) were the strongest predictors of reduced health utility scores.ConclusionsBMI is strongly associated with health utilities in persons with type 2 diabetes. This suggests that lifestyle measures to reduce obesity can markedly improve patients' health-related quality of life and that the negative effect of potential weight gain should be taken into account when determining patient preferences for different type 2 diabetes treatment options.     

Nimmt die gesundheitliche Ungleichheit zu?

The analyses focused on time trends in health inequalities in the 25 to 64-year-old population of Augsburg. The analyses are based on four independent cross-sectional surveys from the MONICA/KORA study covering 15 years: 1984/1985 (n?=?4,022), 1989/1990 (n?=?3,966), 1994/1995 (n?=?3,916) and 1999/2000 (n?=?3,492). Socioeconomic status (SES) was assessed by educational level and per capita household income with separate analyses for each of these two variables. Both absolute and relative health inequalities were calculated. The results showed that inequalities in self-rated health did not change very much (with some indications for increasing inequalities). However, concerning smoking the results clearly pointed towards increasing health inequalities (for example concerning relative inequalities among women by educational level: significant increase from survey to survey of about 20?%). The prevalence of obesity was increased in all SES groups but the inequalities did not change very much. These time trends show that the efforts aimed at reducing health inequalities should be intensified.