Antiviral resistance during pandemic influenza: implications for stockpiling and drug use

Background  

The anticipated extent of antiviral use during an influenza pandemic can have adverse consequences for the development of drug resistance and rationing of limited stockpiles. The strategic use of drugs is therefore a major public health concern in planning for effective pandemic responses.     

Polypectomy of a large juvenile polyp in the ascending colon

A large juvenile polyp in the ascending colon of a 5-year-old boy was successfully polypectomized . The boy often had rectal bleeding, and anemia was known. Transection was necessary to prevent bleeding and anemia.     

NAD+ ameliorates inflammation-induced epithelial barrier dysfunction in cultured enterocytes and mouse ileal mucosa

In the course of other experiments, we serendipitously observed that extracellular nicotinamide adenine dinucleotide (NAD+) ameliorated the development of epithelial hyperpermeability when monolayers of Caco-2 enterocyte-like cells were incubated with cytomix, a mixture containing interferon-gamma, interleukin-1beta, and tumor necrosis factor-alpha. We sought to characterize the effects of NAD+ on inflammation-induced epithelial barrier dysfunction using Caco-2 monolayers that were exposed to cytomix in the absence or presence of NAD+ or other purine-containing molecules. Paracellular barrier function measured as the apical-to-basolateral passage of fluorescein isothiocyanate-conjugated dextran (mol. wt. approximately 4000) was preserved in a concentration-dependent manner when immunostimulated Caco-2 cells were exposed to extracellular NAD+. Incubation with NAD+ prevented cytomix-induced derangements in the expression and localization of the tight junction proteins occludin and zonula occludens-1 in Caco-2 cells. Treatment of cytomix-stimulated cells with NAD+ also blocked nuclear factor-kappaB (NF-kappaB) activation, inducible nitric-oxide synthase induction, and increased production of nitric oxide (NO.). Ileal mucosal permeability to fluorescein isothiocyanate-dextran mol. wt. approximately 4000 was increased in mice 18 h after lipopolysaccharide (endotoxin) injection, but treatment of endotoxemic mice with NAD+ ameliorated the development of gut mucosal hyperpermeability. Thus, extracellular NAD+ seems to ameliorate inflammation-induced intestinal epithelial barrier dysfunction by inhibiting NF-kappaB activation and increased NO. production.     

The basic study on kappa-lambda imaging by delta-curve for the detection of a monoclonal B-cell population in the peripheral blood

Recently, kappa-lambda analysis with the "D" value was developed by Ault to detect a minor population of malignant B cells in peripheral blood. This analysis is based on the Kolmogorov-Smirnov test, and the D value is calculated by a flowcytometer and a computer. We have recently devised a more sensitive parameter for the kappa-lambda analysis than the D value called the delta-curve (delta c); the delta c applies the same principle as that of the D value. Mixing experiments with kappa- type and lambda-type chronic lymphocytic leukemia cells revealed that the delta c could not only detect a minor population of malignant kappa- B cells, but also that of malignant lambda-B cells using more sensitivity than the D value. A total of 49 blood samples obtained from 27 patients with various B-cell malignancies were investigated. D values were abnormal in 37% of all samples, while abnormal patterns of the delta c were recognized in 71%. On the other hand, 59% of samples obtained from the patients with B-cell lymphoma in aleukemic phase showed abnormal delta c, whereas D values exceeded the upper limit of the normal value in only 15% of the samples. It was suggested that the delta c could detect 3% to 7% of malignant B cells that were mixed with a population of normal lymphocytes.     

Fibroblast growth factor (FGF) gene expression in the developing cerebellum suggests multiple roles for FGF signaling during cerebellar morphogenesis and development

The cerebellum is derived from the anterior‐most segment of the embryonic hindbrain, rhombomere 1 (r1). Previous studies have shown that the early development and patterning of r1 requires fibroblast growth factor (FGF) signaling. However, many of the developmental processes that shape cerebellar morphogenesis take place later in embryonic development and during the first 2 weeks of postnatal life in the mouse. Here, we present a more comprehensive analysis of the expression patterns of genes encoding FGF receptors and secreted FGF ligands during these later stages of cerebellar development. We show that these genes are expressed in multiple cell types in the developing cerebellum, in an astonishing array of distinct patterns. These data suggest that FGF signaling functions throughout cerebellar development to regulate many processes that shape the formation of a functional cerebellum. Developmental Dynamics, 2009. © 2009 Wiley‐Liss, Inc.     

Impact of Postoperative Infection on Long-Term Survival After Potentially Curative Resection for Gastric Cancer

We focused on the impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Postoperative surgical and medical complications have been implicated as a negative predictor of long-term outcome in various malignancies. However, there have been no published reports assessing the impact of complications arising from postoperative infection on survival in gastric cancer. We studied a population of 1,332 patients who underwent curative resection for gastric cancer. These patients were divided into two groups based on the occurrence (141 patients, 10.6%) or absence (1,191 patients, 89.4%) of postoperative complications due to infection. We investigated the demographic and clinicopathological features of each patient with and without postoperative complications from infection, and thereby the impact of postoperative infection on long-term survival. Patients with postoperative infection had significantly higher frequency of males, upper side tumor location, and total gastrectomy as a surgical procedure, more advanced stage of gastric cancer, and greater age compared with those without postoperative infection. Patients with complications due to postoperative infection had significantly more unfavorable outcome compared with those patients without postoperative infection. Multivariate analysis demonstrated that age, preoperative comorbidity, blood transfusion, tumor depth, nodal involvement, and postoperative infection correlated with overall survival. We conclude that postoperative complications from infection are a predictor of adverse clinical outcome in patients with gastric cancer. However, further immunological study and prospective trials are necessary to confirm the biological significance of these findings.     

Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo

ZSTK474 is a novel orally applicable phosphoinositide 3‐kinase‐specific inhibitor that strongly inhibits cancer cell proliferation. To further explore the antitumor effect of ZSTK474 for future clinical usage, we studied its combined effects with radiation. The proliferation of HeLa cells was inhibited by treatment with X‐rays alone or ZSTK474 alone. Combination treatment using X‐rays then ZSTK474 given orally for 8 days, starting 24 h post‐irradiation, significantly enhanced cell growth inhibition. The combined effect was also observed for clonogenic survival with continuous ZSTK474 treatment. Western blot analysis showed enhanced phosphorylation of Akt and GSK‐3β by X‐irradiation, whereas phosphorylation was inhibited by ZSTK474 treatment alone. Treatment with ZSTK474 after X‐irradiation also inhibited phosphorylation, and remarkably inhibited xenograft tumor growth. Combined treatment with X‐rays and ZSTK474 has greater therapeutic potential than radiation or drug therapy alone, both in vitro and in vivo. (Cancer Sci 2011; 102: 1176–1180)     

Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration

We have previously reported that the transplantation of dendritic cells (DCs) brings about functional recovery after spinal cord injury in mice through the activation of endogenous microglia/macrophages and neural stem/progenitor cells. In this study, the effect of interleukin-12 (IL-12), which is secreted from DCs, was evaluated for the treatment of spinal cord injury in mice. Administration of IL-12 into the injured site significantly increased the number of activated microglia/macrophages and DCs as well as the expression of brain-derived neurotrophic factor surrounding the lesion site. Immunohistochemical analyses showed that de novo neurogenesis and remyelination were induced by IL-12 treatment. Furthermore, an open field test using Basso-Beattie-Brenham scoring revealed a significant improvement of locomotor function in mice treated with IL-12. These results suggest that IL-12 administration into the injured spinal cord results in a functional recovery through the activation of microglia/macrophages and DCs.     

Parameter Predicting the Recurrence of Adhesive Small Bowel Obstruction in Patients Managed with a Long Tube

Introduction Some of our patients showed a recurrence of adhesive small bowel obstruction (ASBO) with nonoperative management. The aim of this study was to evaluate the parameters predicting the recurrence of ASBO in patients managed with a long tube. Methods Of 234 patients with ASBO admitted from April 1998 to September 2002, a total of 91 who recovered with nonoperative management after long tube placement were enrolled in this retrospective clinical study. We divided them into two groups for follow-up: the recurrence group and the no-recurrence group. We compared baseline characteristics, the number of previous ASBO admissions, the number of abdominal operations, the interval from the onset of symptoms to long-tube insertion, the duration of long-tube placement, the type of the contrasted intestine through the long tube, the location of the long-tube tip, and the drainage volume through the long tube between the two groups. We then examined the cumulative recurrence rate. Results A significant difference was found in the number of previous ASBO admissions, the duration of long-tube placement (77 hours vs. 43 hours), the contrasted intestine through the long tube, and the location of the long-tube tip. By multivariate analysis, the duration of long-tube placement was an independent parameter predicting the recurrence of ASBO. Conclusions These results suggest that the duration of long-tube placement might serve as a parameter for predicting recurrence of ASBO in patients managed with a long tube.