Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif

Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island-1 protein SipB whereas delayed cell death is independent of SipB and occurs 18-24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB-independent cell death through Toll-like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram(-/-) and Trif(-/-) BMDM proliferate in response to Salmonella infection.     

The effect of posterior-neck-muscle vibration on apparent straight-ahead and visual localization of targets

We examined the time course of apparent motion and apparent displacement of a visual target, and also the horizontal deviation of apparent straight-ahead related to left-posterior neck-muscle vibration. In Experiment 1, eight observers verbally judged the apparent motion and displacement of a visual target for 60 s from prior to the vibration to after its offset. We found that rightward apparent motion was an almost identical in magnitude during the vibration and disappeared within 20 s after the vibration offset. In contrast, rightward apparent displacement gradually increased during the vibration, and was sustained over 40 s after the vibration offset. In Experiment 2, five observers manually pointed to the position of a visual point in the median plane; the mean pointed position in the vibration condition was found to deviate maximally 3 degrees to the right of the mean pointed position in the control condition. In Experiment 3, the same observers closed their eyes and pointed to the apparent straight-ahead; the mean pointed positions did not differ between the vibration and control conditions.     

Malignant solitary fibrous tumor of the soft tissue: a cytogenetic study

We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX,+X[4],+1[2],add(1)(p36)[4],add(1)[2],+2[4],-3[4],+6[4],add(6)(p11)x2[4],+7[4],+9[3],-11[4],-12[4],-13[4],add(13)(p11)x2[4],-14[4],+15[4],-16[3],-17[4],-19[4],+20,[4],+21[4],+22[2],+mar1x2[4][cp4].     

Cloning and characterization of cathepsin L-like peptidases of Echinococcus multilocularis metacestodes

Cysteine peptidases have potent activities in the pathogenesis of various parasitic infections. Two cDNA clones encoding cysteine peptidases were isolated from Echinococcus multilocularis metacestode (EmCLP1 and EmCLP2). EmCLP1 and EmCLP2 shared high similarity to the cathepsin L-like peptidases. Immunoblot analyses demonstrated that native EmCLP1 and EmCLP2 were present in excretory/secretory products and extracts of E. multilocularis metacestodes. By immunohistochemistry, native EmCLP1 and EmCLP2 were shown to localize to the germinal layer, the brood capsule and the protoscolex. Recombinant EmCLP1 and EmCLP2 expressed in Saccharomyces cerevisiae exhibited substrate specificity against synthetic peptidyl substrates, Z-Leu-Arg-MCA and Z-Phe-Arg-MCA. Furthermore, recombinant enzymes degraded IgG, albumin, type I and IV collagens, and fibronectin, which suggested those key roles in parasite-host interactions. This is the first report of cysteine peptidases from E. multilocularis, and would contribute to control E. multilocularis infections by chemotherapeutic drugs and/or immunoprophylaxis.     

Rapid determination of viral RNA sequences in mosquitoes collected in the field

A method for rapid determination of viral RNA sequences (RDV) was applied to homogenates of Aedes aegypti collected in Thailand in an area in which dengue fever (dengue hemorrhagic fever) is endemic, using the mosquito cell line C6/36. Nucleic acid sequences of dengue virus type 4 and cell fusing agent virus were detected. This RDV method has the potential to become a standard method for detection of both known and newly emerging, unknown mosquito-borne viruses.     

An acute dysfunction of the glutamate transport activity has been shown to generate free radicals and suppress the anti-oxidant ability in the hippocampus of rats

In this study, we attempted to elucidate whether or not an acute inhibition of glutamate transports activity with l-trans-pyrrolidine-2,4-dicarboxylic acid (l-trans PDC) would cause neuroexcitoxicity in the hippocampus. We used in vivo microdialysis and X-band electron spin resonance (ESR) spectroscopy to measure the changes in the redox state during the perfusion of l-trans PDC. ESR signals from rats using l-trans PDC were characteristically a six-line spectra, for which the hfc was a(N)=1.57mT and a(H)=0.25mT; these hfc's were obtained from the lipoxygenase/linoleic acid system that was used for the generation of lipid radicals. The antioxidant effect was measured using an ESR analysis to monitor sequential changes in the signal amplitude of nitroxide radical in the dialysate of both l-trans PDC and control animals. The pattern showed exponential decay with median half-life of the nitroxide radical took significantly longer in the l-trans PDC group. Acute changes in the glutamate transport resulted in the generation of a lipid radical and a depletion in the anti-oxidant effect in the hippocampus. Our data indicate that a dysfunction of a glutamate transport resulted in the collapse of the redox state, which thus eventually led to neuronal necrosis in the hippocampus. This study provides clear evidence for the mechanisms associated with neuronal disorder in relation to glutamate.     

Age-dependent changes in the hippocampal antioxidant ability of EL mice

Electron spin resonance (ESR) spectroscopy combined with in vivo microdialysis was used to analyze the antioxidant ability in the hippocampus of mice in an interictal state of EL mice utilizing decay ratio of an exogenously applied nitroxide radical (3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM)). In EL mice with a history of frequent seizures, the half-life of the electron paramagnetism of PCAM in the hippocampus was prolonged. These results revealed decreased antioxidant ability, suggesting vulnerability against oxidative stress. Our data suggest that epileptogenesis in EL mice with chronic seizures is associated with functional failure due to the oxidized redox state and revealed that the decreased hippocampal antioxidant ability is related to the regional vulnerability to oxidative stress in the limbic system of EL mice during epileptogenesis.     

The effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of depressive mood

We examined the effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of different mood states. Fifty-five healthy men and women (mean age 23.4 +/- 3 years) were recruited. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale (CES-D) and participants were classified into high depressive (CES-D*16) or low depressive symptoms (CES-D < 16) groups. Following a baseline period, participants were required to complete two separate speech tasks where they were asked to recall life events that made them feel angry or depressed. The tasks were separated by a 30-min recovery period and the order was randomised between participants using a counterbalanced design. Cardiovascular function was monitored continuously using a Finometer device and saliva was collected for the assessment of 3-methoxy-phenylglycol (MHPG, the major metabolite of norephinephrine). Blood pressure (BP), heart rate, and total peripheral resistance (TPR) were significantly increased in response to both tasks (p = .001). Averaged over conditions, higher diastolic BP and higher MHPG levels were observed in high depressive symptoms participants. MHPG levels did not change in response to mood induction in the low depressive symptoms group. However, the high depression symptoms group showed significantly higher levels of MHPG during recovery from the depressed mood induction task and increased levels immediately after the anger induction task. These findings suggest depressive symptoms are associated with heightened central adrenergic activation during negative mood induction, but that the time course of responses is dependent on the type of emotion elicited.     

Unusual abscesses associated with colon cancer: report of three cases

Three cases of colon cancer accompanied by unusual abscess formation are reported. Case I : A 77-year-old man was diagnosed with a paracolic abscess formation behind the cecum and a swollen appendix by computed tomography (CT) scan. Case II : An 85-year-old woman was diagnosed with an abscess formation of the right iliopsoas muscle, a swollen appendix, and a thickened right colon wall by CT scan. After antibiotic therapy failed, both patients underwent ileocecal resection urgently under suspicion of appendicitis, but cecal cancer around the entrance to the appendix caused secondary appendicitis in both cases. Case III : A 50-year-old woman was diagnosed with sigmoid colon cancer with an abscess formation in the pelvic cavity concomitant with ovarian tumor. A Hartmann procedure was performed, and a pathological examination revealed that a subserosal abscess behind the sigmoid colon cancer perforated the rectum with abscess formation. All cases were definitively diagnosed intraoperatively. The cancer recurred in cases I and III. We emphasize that precise surgical evaluation has an important role in the diagnosis of these complicated diseases. In addition, surgery affords the patient the best chance of recovery, and in these advanced cases radical treatment is recommended as early as possible.     

Laughter up-regulates the genes related to NK cell activity in diabetes

To elucidate the sustainable effects of laughter on gene expression, we recruited type 2 diabetic patients who were in-patient for receiving self-management education and examined time-dependent regulation for gene expression by laughter. Two-day experiment was performed. On one day, the patients watched comic video and laughed together with hospital staffs. On the other day, they participated in an inpatient diabetes educational program. Blood samples were collected before and 1.5, 4 h after watching comic video or spending lecture time, and changes in gene expression were comprehensively analyzed by microarray technique. Of the 41,000 genes analyzed, the laughter relatively up-regulated 39 genes, among which, 27 genes were relatively increased in the expression for all the observation period after watching comic video. By functional classification of these genes, 14 genes were found to be related to natural killer cell activity. No genes were included that are directly involved in blood glucose regulation, though successive suppression of postprandial blood glucose levels was observed. These results suggest that the laughter influences the expression of many genes classified into immune responses, and may contribute to amelioration of postprandial blood glucose elevation through a modulation of NK cell activity caused by up-regulation of relating genes.