The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

Background  Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.
Methods  Female subjects ( N = 9265) aged 16–24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.
Results  Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8–100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4–100.0).
Conclusion  These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.
NCT0009252, NCT00092534, NCT00092495     

Motor unit number index (MUNIX) in the orbicularis oculi muscle of healthy subjects

Introduction: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo‐facial muscles have not been reported. Methods: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. Results: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. Conclusions: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis. Muscle Nerve 51 : 197–200, 2015     

Attention deficit hyperactivity disorder and sensory modulation disorder: a comparison of behavior and physiology

Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these disorders in children, clinical ADHD, SMD, and dual diagnoses were assessed. All groups had significantly more sensory, attention, activity, impulsivity, and emotional difficulties than typical children, but with distinct profiles. Inattention was greater in ADHD compared to SMD. Dual diagnoses had more sensory-related behaviors than ADHD and more attentional difficulties than SMD. SMD had more sensory issues, somatic complaints, anxiety/depression, and difficulty adapting than ADHD. SMD had greater physiological/electrodermal reactivity to sensory stimuli than ADHD and typical controls. Parent-report measures identifying sensory, attentional, hyperactive, and impulsive difficulties varied in agreement with clinician's diagnoses. Evidence suggests ADHD and SMD are distinct diagnoses.     

Nuclear matrix protein alterations associated with colon cancer metastasis to the liver.

PURPOSE: The development of colon cancer markers that can detect liver metastases early and predict which patients are at risk to develop liver metastases would have a major impact on this disease. We have previously identified G. Brunagel, et al., Cancer Research, 62:2437-2442, 2002, nuclear matrix proteins (NMPs), which are associated with colon cancer. The objective of this study is to identify the existence of a specific NMP "fingerprint" for human liver metastasis from colon cancer. Experimental Design: Using high-resolution two-dimensional gel electrophoresis, we analyzed the NMP expression of 12 matched liver metastases and adjacent normal samples and three normal donor liver samples. These were compared with colon cancer NMP patterns, along with several primary cell systems and lines. RESULTS: Analysis of multiple gels for each sample revealed three proteins present in all liver metastases, which are not present in normal liver tissue and normal hepatocytes. These three proteins were also present in colon cancer samples. CONCLUSION: Data provided here demonstrate that the NMP composition is able to differentiate liver metastases from normal liver tissue and normal hepatocytes and that these proteins are also expressed in colon cancer. These results further show that the adjacent normal liver tissue changes its NMP pattern of expression. Development of an assay to detect these specific NMPs in tissue and/or serum specimens is a promising modality for early detection of liver metastases from colon cancer or potentially as a prognostic tool. In addition the functional characterization of these proteins will significantly enhance our understanding of the development of liver metastases of this disease.     

Induction of chromosome-specific aneuploidy and micronuclei in human lymphocytes by metabolites of 1,3-butadiene

1,3-Butadiene is a carcinogen in rodents, but its potential carcinogenicity to humans remains controversial. Numerous studies have shown that butadiene and its metabolites cause sister chromatid exchanges in vitro and in vivo. To test for other types of genotoxicity, the micronucleus assay and fluorescence in situ hybridization (FISH) have been used to detect chromosome damage in human lymphocytes caused by two reactive metabolites of butadiene, diepoxybutane (DEB) and monoepoxybutene (MEB). DEB (0.5-5.0 microM) significantly increased micronucleus formation 4- to 6-fold (P <0.01) and MEB (1-500 microM) by 2- to 4-fold (P <0.01) over control levels. The ability of DEB and MEB to induce aneuploidy of chromosomes 7, 8, 12, and X was examined using dual-color FISH in both interphase and metaphase cells. These chromosomes were chosen because of their involvement in leukemogenesis. Both DEB and MEB caused dose-dependent increases in hyperdiploidy of chromosomes 12 and X, but had no discernible effect on chromosomes 7 and 8. These results suggest that DEB and MEB cause chromosome-specific aneuploidy in human cells. If formed in sufficient amounts, DEB and MEB may produce chromosome damage of the type found in leukemia following exposure to butadiene.      

Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1— 29)-NH2 in children with GH deficiency

Six children presenting with partial growth hormone (GH) deficiency (mean GH peak in two different tests, 8.0 k1.3 μ g/l ) aged 8–10.3 years (mean, 2.7 ± 0.9 years) were treated for 6 months by continuous subcutaneous infusion of GH-releasing hormone(1–29)-NH, (GHRH(1–29)-NH₂); 24-hour GH profiles and height velocity were measured. A biphasic effect of GHRH(1–29)-NH₂ infusion was observed. After an early substantial increase in the 24-hour integrated concentration of GH, from 1.6 ± 0.1 to 3.5 ± 0.7 μg/l/minute, a subsequent consistent decrease occurred by 3 months, which was more pronounced after 6 months (mean 24-hour integrated concentration of GH, 1.9± 0.9 μg/l/minute). This effect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 μg/1 during a 24-hour period. No correlation was found between these changes and height velocity. Three children did not grow significantly; the other three children who had a growth response to GHRH(1–29)-NH₂ were those with the lowest 24-hour integrated GH concentration at the end of the study. The possible mechanisms involved in this biphasic effect, including GHRH antibodies, changes in somatostatin levels and/or desensitization of pituitary GHRH receptors, have been investigated.