The main objective of this review was to assess the role of dairy cattle and their products in human infections with Shiga toxin-producing Escherichia coli (STEC). A large number of STEC strains ...(e.g., members of the serogroups O26, O91, O103, O111, O118, O145, and O166) have caused major outbreaks and sporadic cases of human illnesses that have ranged from mild diarrhea to the life-threatening hemolytic uremic syndrome. These illnesses were traced to O157 and non-O157 STEC. In most cases, STEC infection was attributed to consumption of ground beef or dairy products that were contaminated with cattle feces. Thus, dairy cattle are considered reservoirs of STEC and can impose a significant health risk to humans. The global nature of food supply suggests that safety concerns with beef and dairy foods will continue and the challenges facing the dairy industry will increase at the production and processing levels. In this review, published reports on STEC in dairy cattle and their products were evaluated to achieve the following specific objectives: 1) to assemble a database on human infections with STEC from dairy cattle, 2) to assess prevalence of STEC in dairy cattle, and 3) to determine the health risks associated with STEC strains from dairy cattle. The latter objective is critically important, as many dairy STEC isolates are known to be of high virulence. Fecal testing of dairy cattle worldwide showed wide ranges of prevalence rates for O157 (0.2 to 48.8%) and non-O157 STEC (0.4 to 74.0%). Of the 193 STEC serotypes of dairy cattle origin, 24 have been isolated from patients with hemolytic uremic syndrome. Such risks emphasize the importance and the need to develop long-term strategies to assure safety of foods from dairy cattle.
Summary The purpose of this study was to investigate the relationship between the ease of swallowing and the deglutition‐related muscle activity in various body and head postures by surface ...electromyography (EMG). Bipolar surface electrodes were placed on the right suprahyoid and infrahyoid muscles of nine healthy adults (19–28 years) while swallowing jelly. Ten postures per subject were examined: five body angulations (0° supine, 30°, 60°, 90° upright and 120° from the horizontal) and two head positions (chin‐up and chin‐down). The duration and amplitude of suprahyoid and infrahyoid muscle activity were measured by an electromyograph, and the ease of swallowing was subjectively determined by using a rating scale (0 = difficult to swallow, 10 = easy to swallow). The group‐average duration and amplitude of muscle activity and the group‐average rating scales mostly showed insignificant changes with the body angulations independent of the head positions. Interestingly, the duration and amplitude of muscle activity during swallowing were negatively correlated with the rating scales, indicating that a shorter duration and smaller activity of muscle activity corresponds to easier swallowing. Consequently, the duration and amplitude of suprahyoid and infrahyoid muscle activity measured by surface EMG would be a useful indicator of the easy‐to‐swallow performance.
Protection of β cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 ...molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here we employed β-cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to overexpress an artificial PDL1-CTLA4Ig polyprotein or interleukin 10 (IL10). β-Cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved β-cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received major histocompatibility complex (MHC)-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus the present study demonstrates the potent immuno-suppressive effects of β-cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity.
Nuclear reprogramming of somatic tissue enables derivation of induced pluripotent stem (iPS) cells from an autologous, non-embryonic origin. The purpose of this study was to establish efficient ...protocols for lineage specification of human iPS cells into functional glucose-responsive, insulin-producing progeny. We generated human iPS cells, which were then guided with recombinant growth factors that mimic the essential signaling for pancreatic development. Reprogrammed with four stemness factors, human fibroblasts were here converted into authentic iPS cells. Under feeder-free conditions, fate specification was initiated with activin A and Wnt3a that triggered engagement into definitive endoderm, followed by priming with fibroblast growth factor 10 (FGF10) and KAAD-cyclopamine. Addition of retinoic acid, boosted by the pancreatic endoderm inducer indolactam V (ILV), yielded pancreatic progenitors expressing pancreatic and duodenal homeobox 1 (PDX1), neurogenin 3 (NGN3) and neurogenic differentiation 1 (NEUROD1) markers. Further guidance, under insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and N-N-(3,5-Difluorophenacetyl)-L-alanyl-S-phenylglycine t-butyl ester (DAPT), was enhanced by glucagon-like peptide-1 (GLP-1) to generate islet-like cells that expressed pancreas-specific markers including insulin and glucagon. Derived progeny demonstrated sustained expression of PDX1, and functional responsiveness to glucose challenge secreting up to 230 pM of C-peptide. A pancreatogenic cocktail enriched with ILV/GLP-1 offers a proficient means to specify human iPS cells into glucose-responsive hormone-producing progeny, refining the development of a personalized platform for islet-like cell generation.
Ibaraki prefecture, the local government of the area for J-PARC site, was decided to build a versatile neutron diffractometer (IBARAKI Materials Design Diffractometer, iMATERIA) to promote an ...industrial application for neutron beam in J-PARC. iMATERIA is planned to be a high throughput diffractometer so that materials engineers and scientists can use it like the chemical analytical instruments in their materials development process. It covers in
d range 0.18<
d (Å)<5 with Δ
d/
d=0.16% at high resolution bank, and covers 5<
d (Å)<800 with gradually changing resolution at three detector bank (90°, low angle and small angle). Typical measuring time to obtain a ‘Rietveld-quality’ data is several minutes with the sample size of laboratory X-ray diffractometer. To promote industrial application, a utilization system for this diffractometer is required. We will establish a support system for both academic and industrial users who are willing to use neutron but have not been familiar with neutron diffraction. The analysis software is also very important for powder diffraction, we will also prepare a software package consisting of combination of several powder-diffraction software, structural databases and visualization. The construction of iMATERIA will be completed in the end of April 2008, as one of day-one instruments for J-PARC.
Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established.
The copy number of ...the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung.
Amplification (an increase in the copy number by ≥2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I–IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10-5, Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients.
Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.
Fatigue lives of Ti–Ni and Ti–Ni–10Cu alloys were measured using a rotary bending fatigue tester. The fatigue tests were carried out at 308, 323, 338, 368, and 398 K, respectively, under a constant ...strain amplitude condition. The
A
f points of Ti–Ni and Ti–Ni–10Cu alloys, which were annealed at 673 K for 3.6 ks, were 351 and 331 K, respectively. Two types of strain amplitude vs fatigue life curves were observed, one composed of two straight lines with one turning point whereas the other composed of three straight lines with two turning points. The upper turning point coincided with the elastic limit strain and the lower one with the proportional limit strain. The single turning point was observed in a fatigue test condition under which both the limit strains are almost the same. The fatigue life decreased with increasing test temperature in general. However, it became less sensitive to test temperature both in higher and lower temperature regions. Deformation mode and applied stress during fatigue testing are factors affecting fatigue life. However, the fatigue life of the Ti–50.0 at.% Ni is always longer than that of the Ti–40Ni–10Cu (at.%) if the fatigue life is plotted as a function of temperature difference between test temperature and
M
s.
In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 ...pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.
The activating transcription factor, ATF-2, is a target of p38 and JNK that are involved in stress-induced apoptosis. Heterozygous Atf-2 mutant (Atf-2+/-) mice are highly prone to mammary tumors. The ...apoptosis-regulated gene GADD45alpha and the breast cancer suppressor gene Maspin, both of which are known to be p53 target genes, are downregulated in the mammary tumors arisen in Atf-2+/- mice. Here, we have analysed how ATF-2 controls the transcription of GADD45alpha and Maspin. ATF-2 and p53 independently activate the GADD45alpha transcription. ATF-2 does not directly bind to the GADD45alpha promoter; instead, it is recruited via Oct-1 and NF-I. ATF-2 simultaneously binds to Oct-1, NF-I and breast cancer suppressor BRCA1 to activate transcription. With regard to Maspin, ATF-2 and p53 directly bind to different sites in the Maspin promoter to independently activate its transcription. Consistent with the observation that ATF-2 and p53 independently activate the transcription of Maspin and GADD45alpha is that the loss of one copy of p53 shortened the period required for mammary tumor development in Atf-2+/- mice. These studies suggest the functional link between the ATF-2 and the two tumor suppressors BRCA1 and p53.
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