Cellular‐FLIP,Raji isoform (c‐FLIPR) modulates cell death induction upon T‐cell activation and infection

Dysregulation of apoptosis caused by an imbalance of pro‐ and anti‐apoptotic protein expression can lead to cancer, neurodegenerative, and autoimmune diseases. Cellular‐FLIP (c‐FLIP) proteins inhibit apoptosis directly at the death‐inducing signaling complex of death receptors, such as CD95, and have been linked to apoptosis regulation during immune responses. While the isoforms c‐FLIP_L and c‐FLIP_S are well characterized, the function of c‐FLIP_R remains poorly understood. Here, we demonstrate the induction of endogenous murine c‐FLIP_R in activated lymphocytes for the first time. To analyze c‐FLIP_R function in vivo, we generated transgenic mice expressing murine c‐FLIP_R specifically in hematopoietic cells. As expected, lymphocytes from c‐FLIP_R transgenic mice were protected against CD95‐induced apoptosis in vitro. In the steady state, transgenic mice had normal cell numbers and unaltered frequencies of B cells and T‐cell subsets in lymphoid organs. However, when challenged with Listeria monocytogenes, c‐FLIP_R transgenic mice showed less liver necrosis and better bacterial clearance compared with infected wild‐type mice. We conclude that c‐FLIP_R expression in hematopoietic cells supports an efficient immune response against bacterial infections.     

Empfehlungen zu Ernährung und Bewegung von Kleinkindern

Monatsschrift Kinderheilkunde -     

Isolated polyarteritis nodosa of the male reproductive system associated with a germ cell tumor of the testis: a case report

Polyarteritis nodosa (PAN) presents mostly as a systemic disease with poor prognosis, rarely in an isolated form with a usually favorable outcome. Both forms may affect the male reproductive system and both forms have been associated with malignancies. We describe for the first time the occurrence of isolated PAN in the reproductive system combined with a mixed germ cell tumor of the testis in a 21-year-old man presenting with symptoms of chronic epididymitis. Two years after surgery he is without evidence of recurrence of either the tumor or PAN.     

Involvement of Toll-like receptor 4 in the embryogenesis of the rodent filaria <Emphasis Type="Italic">Litomosoides sigmodontis</Emphasis>

To examine the role that lipopolysaccharide (LPS)-like molecules from the filarial intracellular endobacteria Wolbachia might play in the development of filarial infections, a natural infection in the LPS-nonresponsive C3H/HeJ mouse strain was compared to that of the LPS-responsive C3H/HeN mouse strain. C3H/HeN mice have been shown to be susceptible to the rodent filarial nematode Litomosoides sigmodontis, with the development of adult worms including females containing mature microfilariae (first stage larvae) in the uterine tubes. However, free microfilariae are not detected. In this study the worm burden and worm length were not significantly different between the C3H/HeN and C3H/HeJ mice. However, the fertility of worms from CeH/HeJ mice was found to be higher than those from C3H/HeN mice. Significantly, mature microfilariae were found at the site of infection only in C3H/HeJ mice. These results indicate a role for TLR4 signaling in the immune response that inhibits worm embryogenesis and prevents the release of microfilariae or directly kills released microfilariae.     

Transcriptional oscillation of lunatic fringe is essential for somitogenesis

A molecular oscillator that controls the expression of cyclic genes such as lunatic fringe (Lfng) in the presomitic mesoderm has been shown to be coupled with somite formation in vertebrate embryos. To address the functional significance of oscillating Lfng expression, we have generated transgenic mice expressing Lfng constitutively in the presomitic mesoderm in addition to the intrinsic cyclic Lfng activity. These transgenic lines displayed defects of somite patterning and vertebral organization that were very similar to those of Lfng null mutants. Furthermore, constitutive expression of exogenous Lfng did not compensate for the complete loss of cyclic endogenous Lfng activity. Noncyclic exogenous Lfng expression did not abolish cyclic expression of endogenous Lfng in the posterior presomitic mesoderm (psm) but affected its expression pattern in the anterior psm. Similarly, dynamic expression of Hes7 was not abolished but abnormal expression patterns were obtained. Our data are consistent with a model in which alternations of Lfng activity between ON and OFF states in the presomitic mesoderm prior to somite segmentation are critical for proper somite patterning, and suggest that Notch signaling might not be the only determinant of cyclic gene expression in the presomitic mesoderm of mouse embryos.     

C-KIT expression in ductal carcinoma in situ of the breast: co-expression with HER-2/neu

The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT gene was performed to analyze the hot spot mutational regions in representative cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth pattern (P = .001). Furthermore, c-KIT expression was strongly associated with HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive cases (P = .001 and P = .006, respectively). C-KIT expression alone or co-expression with HER-2 in pure DCIS did not differ significantly from DCIS with invasive component (P = .09). Mutational analysis in 6 c-KIT-positive DCIS revealed no activating mutations in exons 9 or 11. Our findings suggest that the expression of c-KIT protein might define a subset of poorly differentiated, HER-2-positive DCIS with decreased expression of steroid hormone receptors, comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2 co-expression for breast carcinogenesis should be further evaluated.     

Differential display of genes expressed in the filarial nematode Litomosoides sigmodontis reveals a putative phosphate permease up-regulated after depletion of Wolbachia endobacteria

Mutualist symbiotic Wolbachia endobacteria are found in most filarial nematodes. Wolbachia are essential for embryogenesis and for larval development into adults, and thus represent a new target for anti-filarial drug development. Tetracycline antibiotics deplete Wolbachia in animal model filaria Litomosoides sigmodontis and Brugia pahangi, as well as in the human parasites Brugia malayi, Onchocerca volvulus and Wuchereria bancrofti. Very little is known about the molecular details of the symbiotic interaction between Wolbachia and filarial nematodes. Nematode genes that respond to anti-Wolbachia antibiotic treatment may play important roles in the symbiosis. Differential display PCR was used to detect several candidate genes that are up-regulated after 3, 6, 15, 30 and 36 days of tetracycline treatment. One of these genes, Ls-ppe-1, was similar to a family of phosphate permeases, and had putative orthologues in O. volvulus and B. malayi. Ls-ppe-1 steady-state mRNA levels were elevated by day 3-6 of treatment, and remained elevated through to 70 days post-treatment. In Caenorhabditis elegans, the knockdown of a homologous phosphate permease results in embryonic lethality, with the production of degenerating embryos, a phenotype also seen in filarial nematodes after depletion of Wolbachia with tetracycline. The potential role of Ls-ppe-1 in the nematode-bacterial symbiosis is discussed.     

The impact of the body mass index (BMI) on laparoscopic hysterectomy for benign disease

Purpose

To investigate the influence of the body mass index (BMI) on laparoscopic hysterectomy, including all intra- and postoperative findings and complications.

Methods

We reviewed and analyzed the medical records of 200 patients who underwent laparoscopic hysterectomy for benign disease at the Saarland University Hospital. The patient collective was subdivided into four weight groups on the basis of the current WHO BMI classification. Data analysis was carried out by a professional statistician.

Results

Over half of the women screened were overweight or obese. The operating times increased together with the BMI (p = 0.017). Blood losses differed significantly between the weight groups (p = 0.027), but ranged to a maximum of only 300 ml. One laparoconversion had to be performed. No other intraoperative complications occurred. During our follow-up time of 13.2 ± 5.4 months, the overall rate of postoperative complications differed significantly between the weight groups (p = 0.008). The group of overweight women had the highest rate of complications and the group of obese women had the lowest. However, the rate of women who required readmission and reoperation was not elevated in the overweight group.

Conclusion

Laparoscopic hysterectomy is a safe and feasible method even in obese and morbidly obese patients. Overweight and obesity increase the time needed to perform laparoscopic hysterectomy but do not seem to relevantly influence the rate of major intra- or postoperative complications.     

Selective pair recognition memory impairment with no response bias in schizophrenia

Memory is one of the cognitive functions most affected in schizophrenia, but the severity of deficits varies from one task to another. In particular, greater impairments have been reported for pair recognition than item recognition. However, decision biases and how they could affect memory dysfunction in schizophrenia have received scant attention. In this study, 26 people with schizophrenia and 28 healthy controls were administrated an association item recognition task. During encoding, participants studied pairs of visual objects, and they had to memorise objects and their pairing. In a subsequent retrieval task, participants performed an item recognition test (old/new items) and a pair recognition test (intact/rearranged pairs). Results showed that both groups were better at recognizing items than pairs, with lower performance for pair recognition, but not for item recognition, in people with schizophrenia. Analyses of response biases revealed that patients had a conservative response bias for items but not for pairs. The study also provides evidence that associative impairment may not result from decisional bias but rather from impairments in mnesic processes.