[Genital reassignment surgery in male-to-female transsexuals: do we have guidelines or standards?]. / Operative Genitalangleichung bei Mann-zu-Frau-Transsexualität: Gibt es Leitlinien oder Standards?

BACKGROUND: In 2011 the WPATH (World Professional Association for Transgender Health) published the 7th version of their "Standards of Care" for diagnosis and treatment of transsexual people. In face of further recent peer-reviewed reports of experienced centres on surgical sex reassignment it should be examined whether or not genital sex reassignment in male-to-female transsexuals actually can be based on evidence-based guidelines or standards. RESULTS: The indication for surgery is widely standardised and evidence-based. Most critical steps of the operation are also founded on grade B recommendations. Most experienced authors rely on penoscrotal pedicled flaps for neovaginal lining. The topic of ideal reconstruction of the vulva, especially the clitoro-labial complex is still a field of debate. Due to the high frequency of further corrective surgeries which exceeds 50% in most experienced centres, some authors prefer a primary 2-step procedure for genital reassignment. CONCLUSIONS: The indication and principal operative steps in surgical genital reassignment in male-to-female patients rely on evidence-based recommendations. By respecting these recommendations subjective success rates of over 80% can be expected.

Chitinase induce the release of IL-8 in human airway epithelial cells, via Ca2+-dependent PKC and ERK pathways.

Chitinases are produced in significant quantities by hosts defending against infections with chitin-containing organisms. However, little is known about the immune response of exogenous chitinase in human epithelial cells. IL-8 has been suggested to have a role in the pathogenesis of the allergenic inflammation of bronchial asthma. We examined whether Streptomyces griseus (S. griseus) chitinase-induced IL-8 on airway epithelium and identified the involvement of intracellular signalling pathways. H292 cells were treated with S. griseus chitinase with different concentrations and times. The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction. Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to S. griseus chitinase. Cells exposed to S. griseus chitinase showed higher level of IL-8 protein production and mRNA expression. Cells stimulated by S. griseus chitinase resulted in the activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-kB) pathways. Inhibitors of Ca(2+)-dependent PKC (Ro-31-8220, calphostin C and Go6976) significantly abolished chitinase-induced expression of IL-8. However, Ca(2+)-independent PKC inhibitor (rottlerin) did not inhibit IL-8 expression. Through ERK inhibitor (U0126) and NF-kB inhibitor (caffeine acid phenethyl ester) treatment, it was proven that ERK and NF-kB regulated chitinase-induced IL-8 expression. We concluded that S. griseus chitinase-induced IL-8 expression was regulated by the activation of Ca(2+/-)-dependent PKC, ERK and NF-kB in human airway epithelial cells.

Increased serum B cell-activating factor level in children with atopic dermatitis.

BACKGROUND: B cell-activating factor (BAFF) is a tumour necrosis factor superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is seen in naïve and effector/memory T cells. AIM: To investigate the level and role of BAFF in serum of patients with atopic dermatitis (AD). METHODS: Levels of serum BAFF, a proliferation-inducing ligand (APRIL) and total serum IgE level, and total eosinophil count were measured in 245 children. RESULTS: Patients were characterized as having atopic eczema (AE) (n = 90) or non-AE (n = 77); the remainder were healthy control subjects (n = 78). Serum BAFF level in children with AE (1625.04 +/- 708.32 pg/mL) was significantly higher than in non-AE children (1194.69 +/- 448.44 pg/mL, P < 0.0001) or healthy controls (1062.89 +/- 444.74 pg/mL, P < 0.0001). Serum APRIL level was not different between the three groups. Serum BAFF level significantly correlated with total serum IgE level (gamma = 0.42, P < 0.0001) and total eosinophil count. It was also positively correlated with serum BAFF and egg-specific IgE level (gamma = 0.252, P = 0.045) in AE. CONCLUSIONS: Serum BAFF level is high in AE and might be a useful marker for AE.

Combined effect of tumour necrosis factor-alpha and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma.

BACKGROUND: TNF-alpha and IL-13, two pivotal pro-inflammatory cytokines, are increased in asthmatic airways and may be linked to asthma susceptibility and/or bronchial hyperresponsiveness (BHR). OBJECTIVE: We investigated the association between the TNF-alpha-308G/A polymorphism and asthma susceptibility or asthma-related phenotypes in Korean children with asthma, and tested for a combined effect with IL-13 polymorphisms. METHODS: Asthmatic children (n=719) and non-atopic healthy control children (n=243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-restriction fragment length polymorphism analysis. RESULTS: The allele frequency of TNF-alpha-308A in asthmatics (14.1%) was higher than that in control children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05-2.82]. Significantly lower PC(20) values were found in asthmatic children carrying one or two copies of the TNF-alpha risk allele (-308A) vs. those homozygous for the common allele (P=0.026). Combined analysis revealed that atopic asthmatic children co-inherited the risk alleles of TNF-alpha-308G/A and IL-13 +2044G/A more frequently than control children (aOR 1.91, 95% CI 1.00-3.65), and asthmatic children co-inheriting both risk alleles had significantly lower PC(20) values vs. asthmatic children homozygous for the common alleles (P=0.024). CONCLUSION: The TNF-alpha promoter polymorphism (-308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, there appears to be a synergistic effect between the TNF-alpha promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.

Regulation of German cockroach extract-induced IL-8 expression in human airway epithelial cells.

BACKGROUND: Cockroaches have been known as a cause of respiratory allergies such as asthma. IL-8 plays an integral role in the coordination and persistence of the inflammatory process in the chronic inflammation of the airways in asthma. OBJECTIVE: We investigated the mechanism by which German cockroach extract (GCE) triggers IL-8 release from human airway epithelial cells. METHODS: Chemical inhibitors were pretreated before addition of GCE for promoter activity and protein synthesis of IL-8. The Transcriptional activity of IL-8 promoter was analysed by mutational, deletional anaylsis and electrophoretic mobility shift assay (EMSA). RESULTS: Stimulation of H292 cells with GCE resulted in a time- and concentration-dependent induction of IL-8 transcription and protein synthesis. IL-8 promoter deletion analysis indicated that position -132 to +41 was essential for GCE-induced IL-8 transcription, and mutants with substitutions in activator protein (AP)-1, nuclear factor (NF)-IL6 and NF-kappaB-binding sites revealed a requirement for NF-kappaB and NF-IL6, but not AP-1, in GCE-induced activation of the IL-8 promoter. The DNA-binding activities of NF-kappaB and NF-IL6 were induced by GCE, as determined by EMSA. The chemical inhibition of extracellular signal-regulated kinase (ERK) attenuated GCE-induced transcriptional activity and protein synthesis. In addition, through aprotinin treatment and PAR2 small interfering RNA transfection, it was proven that protease of GCE is consistent with the regulation of GCE-induced IL-8. CONCLUSION: We conclude that GCE with protease activity-induced IL-8 expression is regulated by transcriptional activation of NF-kappaB and NF-IL6 coordinating with the ERK pathway in human airway epithelial cells.

Basement membrane thickening and clinical features of children with asthma.

BACKGROUND: Asthma is a chronic inflammatory disease, characterized by airway inflammation, bronchial hyper-responsiveness, and airway obstruction. Although asthma induces partially reversible airway obstruction, obstruction can sometimes become irreversible. This may be a consequence of airway remodeling, which includes a number of structural changes, such as epithelial detachment, basement membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation. This study evaluated children with asthma for the presence of BM thickening. METHODS: Eighteen children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM thickness in paraffin-embedded biopsy sections. The association between BM thickening and age, sex, duration of asthma, asthma severity, FEV(1), FEV(1)/FVC, FEF(25-75%), methacholine PC(20), eosinophil count, and presence of atopy was examined. RESULTS: Basement membrane thickness was greater in subjects with asthma (8.3 +/- 1.4 microM) than in control subjects (6.8 +/- 1.3 microM, P = 0.0008). Multiple regression analysis revealed that sex, FEV(1)/FVC, total IgE, and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant predictive factors for BM thickness. There was no significant association between BM thickness and age, duration of asthma, FEV(1), FEF(25-75%), methacholine PC(20), eosinophil count, or asthma severity. CONCLUSIONS: Basement membrane thickening has been known to be present in children with asthma. In addition, we report an association between BM thickness and sex, FEV(1)/FVC, total IgE, and the presence of IgE specific to D. pteronyssinus.

Hepatocellular carcinoma with metastasis to the spleen in a Holstein cow.

Hepatocellular carcinoma (HCC) with metastasis to the spleen in a Holstein cow was studied by histopathologic and immunohistochemical methods. The tumor was characterized by a pseudoglandular (acinar) pattern with an associated fibrous stroma. Individual cells often had a "hepatoid" appearance but were interspersed with scattered cells exhibiting a clear, periodic acid-Schiff (PAS)-positive cytoplasm and small eccentric nuclei. This pattern was present in nodules found in both liver and spleen. Moreover, hepatoid tumor cells were positive for alpha-fetoprotein. Immunohistochemical studies suggest that myofibroblasts were responsible for the production of fibrous septa surrounding the pseudoglandular structures of bovine HCC. In summary, our histologic and immunohistochemical findings support a diagnosis of primary HCC with splenic metastasis. Furthermore, the associated stromal response appears to be of a myofibroblast origin. The primary etiology of bovine HCC and the significance of the intralesional, PAS-positive clear cells remain undetermined.

Self-reported prevalence and risk factors of asthma among Korean adolescents: 5-year follow-up study, 1995-2000.

OBJECTIVES: The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. METHODS: We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15,481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15,894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. RESULTS: The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. CONCLUSIONS: In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.

Staphylococcal enterotoxin B upregulates fas-mediated apoptosis of peripheral blood mononuclear cells in childhood atopic dermatitis.

Staphylococcal infection-producing superantigens, such as staphylococcal enterotoxin B (SEB), are presumed to play an important role of inflammatory processes in atopic dermatitis (AD). The aim of this study was to elucidate the apoptotic response of peripheral blood mononuclear cells (PBMCs) from children with AD. PBMCs from AD children were sampled and cultured with SEB stimulation. Levels of apoptosis and Fas expression were measured using flow cytometry; the soluble Fas ligand (sFasL) was also measured using the enzyme-linked immunosorbent assay method, and the expression of FasL in PBMCs was observed using reverse transcriptase-polymerase chain reaction. There was no difference in the initial levels of apoptosis and Fas expression in precultured PBMCs of AD patients and healthy donors. After culturing for 48 h under SEB stimulation, the apoptosis level and Fas expression were significantly upregulated in the PBMCs from AD children compared with that from the normal controls. In patients, the sFasL was significantly increased, and the expression of FasL was observed in messenger RNA of peripheral monocytes. These results suggest that the Fas/FasL system is involved in the apoptosis induced by SEB in AD, with simultaneous increases in sFasL and expression of FasL.

Circulating interleukin 17 is increased in the acute stage of Kawasaki disease.

OBJECTIVES: During the acute phase, patients with Kawasaki disease (KD), an acute systemic vasculitis, demonstrate a drastic increase in serum interleukin-6 (IL-6), which parallels the duration of the fever. Recently, IL-17 has been reported to induce IL-6 production. The aim of this study was to elucidate the involvement of IL-17 in the pathogenesis of KD. METHODS: Serum samples were obtained from patients with KD (n=30) and normal controls (n=20), and the concentrations of IL-17 and IL-6 measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal controls (2.08 +/- 2.14 pg/mL), serum IL-17 was markedly elevated in patients with acute KD (25.47 +/- 5.05 pg/mL): levels gradually decreased in the subacute phase (5.94 +/- 2.83 pg/mL). In the acute phase, levels of IL-6 were 83.52 +/- 19.12 pg/L, which correlated well with the serum levels of IL-17. CONCLUSION: These results suggest that IL-17 may be involved in the development of, or the effects of inflammation in KD.

Interleukin 6 gene promoter polymorphism is not associated with Kawasaki disease.

We examined the IL-6 gene promoter and detected several interesting promoter polymorphisms: GGGCTG insertion at +162 bp and G deletion at +168 bp positions (M1), A to G substitution at -594 bp (M2) of the reported IL-6 promoter sequence. Other rare variations were also observed at several positions: -583 bp (T insertion), -507 bp (C insertion), -71 bp (T deletion), +17 bp (C insertion), and +121 bp (GC insertion). Although Kawasaki disease (KD) patients demonstrate a drastic increase in serum interleukin-6 (IL-6) during the acute phase that parallels the duration of fever, there were no significant differences in the nucleotide sequence between the KD patients and normal control group. By transient transfection with IL-6 gene promoter-luciferase fusion plasmids into CV-1 cells, we tested the functional significances of the polymorphisms. Mutations at +162 bp, +168 bp and -594 bp significantly decreased luciferase expression (P < 0.05), suggesting the promoter elements flanking the mutated nucleotides are important in transcriptional activation.