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The development of new materials with reduced noise and vibration levels is an active area of research due to concerns in various aspects of environmental noise pollution and its effects on health. Excessive vibrations also reduce the service live of the structures and limit the fields of their utilization. In oscillations, the viscoelastic moduli of a material are complex and it is their loss part – the product of the stiffness part and loss tangent – that is commonly viewed as a figure of merit in noise and vibration damping applications. The stiffness modulus and loss tangent are usually mutually exclusive properties so it is a technological challenge to develop materials that simultaneously combine high stiffness and high loss. Here we achieve this rare balance of properties by filling a solid polymer matrix with rigid inorganic spheres coated by a sub-micron layer of a viscoelastic material with a high level of internal friction. We demonstrate that this combination can be experimentally realised and that the analytically predicted behaviour is closely reproduced, thereby escaping the often termed ‘Ashby’ limit for mechanical stiffness/damping trade-off and offering a new route for manufacturing advanced composite structures with markedly reduced noise and vibration levels., Scientific Reports, 8, ISSN:2045-2322

We have investigated the structural changes and the microstructures of Ba1-x Sr x Al2O4 for 0 directions in the hexagonal structure. In addition, real-space images of Ba1-x Sr x Al2O4 for 0 directions and on the other hand, Ba1-x Sr x Al2O4 for 0.1 < x < 0.4 be characterized as an intermediate (precursor) state with a rigid unit mode due to structural instability. These experimental results implied that the partial substitution of Sr2+ for Ba2+ should suppress a structural instability due to the AlO4 tetrahedral network and decrease the structural phase transition temperature.

We report a measurement of the branching fraction in the τ−→π−π+π−π0ντ decay using a data sample accumulated with the Belle detector at the KEKB asymmetric-energy e+e− collider. The branching fraction is measured to be B(τ−→π−π+π−π0ντ)=(4.38±0.02±0.12)% where the first uncertainty is statistical and the second is systematic. This is an initial step of the high-statistics measurement of the spectral function in the τ−→π−π+π−π0ντ decay.

We have investigated structural phase transition and changes of microstrucrtures in BaAl2O4 with the tridymite tetrahedral framework structure by transmission electron microscopy experiments in the temperature range between 100 K and 298 K. In our polycrystalline samples the transition from the paraelectric phase with the P6322 space group to the ferroelectric (FE) phase took place around 250 K, which accompanies with the appearance of the modulated structure with the three equivalent modulation wave vectors, q = 1/2 . Real-space images revealed that the FE phase should consist of nanodomains with the 10 ∼ 20 nm size. In addition, it is revealed that partial substitution of Fe3+ for Al3+ in BaAl2O4 induced structural phase transition to the modulated structure with q = 1/3 around x ∼ 0.50 in Ba(Al1-xFex)2O4.

A Bursaphelenchus species was isolated from a Japanese native wood-boring weevil, Niphades variegatus, and dead Pinaceae trees. The nematode is associated with the weevils as dauer (dispersal third stage) juveniles and the dauers enter the weevil tracheal system forming an abnormal expansion on the weevil trachea (atrium). Thus, the nematode is hypothesised to be an amensal/phoretic associate of the weevil because the abnormal expansion appeared to inhibit weevil respiration. The propagative stages of the nematode are associated with dead trees (wood and bark materials) and are thought to feed there on naturally propagated fungi. Morphologically, the new species is considered an undescribed species close to B. antoniae, B. chengi and B. hylobianum. Within these four species, the new species, which is described herein as B. niphades n. sp., is closest to B. chengi, i.e., the typological character of these two species are almost identical to each other and is distinguished by some minor characters (structure of the male P4 genital papillae and spicule length). The molecular phylogenetic analysis supported the morphological observations. Bursaphelenchus niphades n. sp. formed a well supported subclade with the four species and is intermediate between B. hylobianum and B. chengi; however, it is distinguished by the molecular sequences of some ribosomal RNA genes. Because three of these four species are associated with weevil species, the subclade is considered a ‘weevil-associated’ species group.

Background and purpose The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA). Methods Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of

This journal suppl. entitled: Special Issue: The 64th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2013

We assessed somatic alleles of six receptor tyrosine kinase genes mutated in lung adenocarcinoma for oncogenic activity. Five of these genes failed to score in transformation assays; however, novel recurring extracellular domain mutations of the receptor tyrosine kinase gene ERBB2 were potently oncogenic. These ERBB2 extracellular domain mutants were activated by two distinct mechanisms, characterized by elevated C-terminal tail phosphorylation or by covalent dimerization mediated by intermolecular disulfide bond formation. These distinct mechanisms of receptor activation converged upon tyrosine phosphorylation of cellular proteins, impacting cell motility. Survival of Ba/F3 cells transformed to IL-3 independence by the ERBB2 extracellular domain mutants was abrogated by treatment with small-molecule inhibitors of ERBB2, raising the possibility that patients harboring such mutations could benefit from ERBB2-directed therapy.

Purpose To identify novel genetic markers predictive of clinical benefit from epidermal growth factor receptor–directed antibody therapy in patients with metastatic colorectal cancer. Patients and Methods Seventy-six consecutive patients who received cetuximab or panitumumab, either alone or in combination with chemotherapy and with available tumor tissue were included. Tumor tissue was tested by pyrosequencing for mutations at known hot spots in the KRAS, BRAF, PIK3CA, PIK3R1, AKT1, and PTEN genes. PTEN promoter methylation status was analyzed by methylation-specific polymerase chain reaction, and expression was determined by immunohistochemistry (IHC). Forty-four patients had 4 weeks of therapy and were considered for clinical correlates. Results Consistent with previous studies, KRAS gene mutations were associated with a shorter progression-free survival (PFS) and overall survival (OS). Among the patients with wild-type KRAS, preservation of PTEN expression and PIK3CA wild-type status was associated with improved OS (median OS, 80.4 vs. 32.5 weeks; hazard ratio, 0.33; P = .0008) and a trend toward improved PFS (median PFS, 24.8 vs. 15.2 weeks; hazard ratio, 0.51; P = .06), compared with PTEN-negative or PIK3CA-mutant tumors. PTEN methylation was more common in the metastatic samples than in the primary samples ( P = .02). The simultaneous presence of methylation and mutation in the PTEN gene was associated with IHC negativity ( P = .026). Conclusion In addition to KRAS mutation, loss of PTEN expression (by IHC) and PIK3CA mutation is likely to be predictive of a lack of benefit to anti-EGFR therapy in metastatic colorectal cancer. PTEN promoter methylation and mutation status was predictive of PTEN expression and may be used as an alternative means of predicting response to EGFR-targeted therapy.

Rare blood is generally defined as one that occurs at a frequency of 1:100~1000 individuals or less, and it is sometimes difficult to provide such blood types to patients because of their rarities. The Japanese Red Cross (JRC) Society lists 46 rare blood phenotypes that are divided into two categories. The rare blood types listed in Category I occur much less frequently than those listed in Category II. We screen for rare blood cells using monoclonal antibodies (MoAbs). Since 1987, our blood centre has established 93 MoAbs (32 human and 61 murine) and has provided them to the other blood centres. Many of IgG MoAbs are available on the machine by saline or bromelin method by cross-linking with anti-human or anti-mouse IgG. Thus, more than 10 000 donors with rare blood phenotypes (Category I, 748; Category II, 9314) are registered in Japan. We freeze rare blood, particularly Category I types. Since 1977, a total of 576 units of rare blood with phenotypes Di(b−), D−−, Jr(a−), Ko and Lan-, etc. have been supplied to 23 international countries. Thus, the JRC contributes to the International Panel of Donors of Rare Blood Type (IDP) which is maintained by the International Blood Group Reference Laboratory (IBGRL) in Bristol, UK. The IDP provides information on the location of rare blood donors when they cannot be found in their respective countries. We also joined the ISBT Working Party on Rare Donors which handles all matters related to rare blood. Our rare blood donor programme is successful because of international co-operation.

The purpose of this study is to develop a constitutive model of skeletal muscle that describes material anisotropy, viscoelasticity and damage of muscle tissue. A free energy function is described as the sum of volumetric elastic, isochoric elastic and isochoric viscoelastic parts. The isochoric elastic part is divided into two types of shear response and the response in the fiber direction. To represent the dependence of the mechanical properties on muscle activity, we incorporate a contractile element into the model. The viscoelasticity of muscle is modeled as a three-dimensional model constructed by extending the one-dimensional generalized Maxwell model. Based on the framework of continuum damage mechanics, the anisotropic damage of muscle tissue is expressed by a second-order damage tensor. The evolution of the damage is assumed to depend on the current strain and damage. The evolution equation is formulated using the representation theorem of tensor functions. The proposed model is applied to the experimental data on tensile mechanical properties in the fiber direction and the compression properties in the fiber and cross-fiber directions in literature. The model can predict non-linear mechanical properties and breaking points.

In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFRalpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRalpha/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFRalpha/KIT inhibitors.

The hepatocellular mechanisms underlying the development of steatosis and the progression to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) remain unclear.1 A critical factor in the pathogenesis of this disease is thought to be the existence of insulin resistance, and NAFLD can be considered a component of the metabolic syndrome whose manifestations also include obesity and diabetes.2,3 Recent investigations have suggested that activation of the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) is a central mechanism for the development of obesity and insulin resistance as well as for steatohepatitis.4-7 JNK may therefore represent a unique common target for the therapy of a variety of diseases that comprise the metabolic syndrome, but whether an inhibition of JNK function will decrease or prevent further progression of established steatohepatitis is currently unknown. Most cells including hepatocytes express two JNK genes, jnk1 and jnk2, which are alternatively spliced to yield α and β forms of both a p54 and p46 protein.8 Recent studies have demonstrated that the JNK isoforms differ in function as exemplified by the ability of JNK1 to phosphorylate and activate the transcription factor c-Jun, whereas JNK2 lacks this activity and may even oppose this action of JNK1.9 Our prior studies have implicated JNK signaling in the development of steatohepatitis. First, it was demonstrated that hepatocyte overexpression of the prooxidant enzyme cytochrome P450 2E1 as occurs in human NAFLD induced sustained JNK activation and insulin resistance.10 Second, the development of murine steatohepatitis induced by a methionine- and choline-deficient diet was associated with increased JNK activation.6 The development of steatosis and liver injury was prevented in jnk1 but not jnk2 null mice, indicating that JNK1 specifically functions in the development of this disease.6 JNK1 has also been demonstrated to mediate the development of obesity and insulin resistance in both high fat diet (HFD)-fed and genetically obese mouse models.4 JNK2 was reportedly not involved in these processes, but subsequent studies in mice haploinsufficient for jnk1 and null for jnk2 suggested that JNK2 may also promote the development of obesity and insulin resistance.7 These mice and jnk1-/- mice also failed to develop steatosis from a HFD.7 Thus, JNK1 function is clearly linked to the development of steatohepatitis, obesity and insulin resistance whereas the function of JNK2 in these conditions is less clear. To more clearly establish the function of JNK1 and JNK2 in steatohepatitis occurring in the setting of obesity and insulin resistance, the effect of JNK1 or JNK2 ablation on the development of steatohepatitis was examined in HFD-fed mice. Although such studies are important to our understanding of the pathophysiology of NAFLD, findings derived from investigations of developing disease do not define JNK function in the progression or perpetuation of established steatohepatitis. Studies to examine the role of JNK in existing steatohepatitis have not been performed and are critical to determine whether JNK is a viable therapeutic target in this disease. The development of antisense oligonucleotides (ASO) that are effective in inhibiting JNK1 or JNK2 expression in the liver,11 led us to examine the effects of JNK inhibition in established as well as developing steatohepatitis in HFD-fed mice. The studies demonstrate that JNK1 mediates insulin resistance and both the development and progression of steatohepatitis. In contrast, although JNK2 promoted insulin resistance, this JNK isoform did not mediate the development or progression of steatohepatitis. These findings indicate that the JNK isoforms have distinct functions that differ among the various manifestations of the metabolic syndrome and have important implications for JNK as a therapeutic target in this disorder.

Dengue infections are caused by a single-stranded RNA virus, which has four serotypes (DEN 1-4); mosquitoes of the genus Aedes serve as vectors of transmission. Risk factors for dengue infection are related to both the host and virus. Age, gender, immune status, and genetic background of the host all contribute to the severity of dengue infection. Recently, international travel to endemic areas has also been identified as a major risk factor for both primary and secondary dengue infection. Dengue remains a diagnostic challenge, given its protean nature, ranging from mild febrile illness to profound shock. The most severe manifestation of dengue infection is dengue shock syndrome, which has an estimated mortality rate close to 50%. Dengue shock syndrome typically presents with increased anion gap metabolic acidosis, disseminated intravascular coagulation, severe hypotension, and jaundice. Liver involvement appears to occur more frequently when infections involve DEN-3 and DEN-4 serotypes. While hepatocellular damage has been reported previously in dengue infection, acute liver failure is an extremely rare occurrence in adults. We report a patient with dengue shock syndrome who presented with acute liver failure and hepatic encephalopathy after recent travel to an endemic area.

An rf ion guide for mass separation of fission fragments has been developed as a new type of the ion-source of an ion guide isotope separator on-line (IGISOL). Fission fragments from an uranium target are thermalized in a large helium gas cell and extracted by a combination of dc and inhomogeneous rf electric fields. They are subsequently mass separated by an electromagnetic mass separator. Test experiments with a radioactive α-source and with fission fragments produced in the proton-induced fission of 238 U reveal that the yields of mass-separated radioactive ion beams are enhanced, due to the dc and rf electric fields in the gas cell.

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.

Recent evidence that excessive lipid accumulation can decrease cellular levels of autophagy and that autophagy regulates immune responsiveness suggested that impaired macrophage autophagy may promote the increased innate immune activation that underlies obesity. Primary bone marrow-derived macrophages (BMDM) and peritoneal macrophages from high-fat diet (HFD)-fed mice had decreased levels of autophagic flux indicating a generalized impairment of macrophage autophagy in obese mice. To assess the effects of decreased macrophage autophagy on inflammation, mice with a Lyz2-Cre-mediated knockout of Atg5 in macrophages were fed a HFD and treated with low-dose lipopolysaccharide (LPS). Knockout mice developed systemic and hepatic inflammation with HFD feeding and LPS. This effect was liver specific as knockout mice did not have increased adipose tissue inflammation. The mechanism by which the loss of autophagy promoted inflammation was through the regulation of macrophage polarization. BMDM and Kupffer cells from knockout mice exhibited abnormalities in polarization with both increased proinflammatory M1 and decreased anti-inflammatory M2 polarization as determined by measures of genes and proteins. The heightened hepatic inflammatory response in HFD-fed, LPS-treated knockout mice led to liver injury without affecting steatosis. These findings demonstrate that autophagy has a critical regulatory function in macrophage polarization that downregulates inflammation. Defects in macrophage autophagy may underlie inflammatory disease states such as the decrease in macrophage autophagy with obesity that leads to hepatic inflammation and the progression to liver injury.

Approximately one-third of the human population is latently infected withMycobacterium tuberculosis, comprising a critical reservoir for disease reactivation. Despite the importance of latency in maintainingM. tuberculosisin the human population, little is known about the mycobacterial factors that regulate persistence and reactivation. Previous in vitro studies have implicated a family of five relatedM. tuberculosisproteins, called resuscitation promoting factors (Rpfs), in regulating mycobacterial growth. We studied the in vivo role ofM. tuberculosis rpfgenes in an established mouse model ofM. tuberculosispersistence and reactivation. After an aerosol infection with theM. tuberculosisErdman wild type (Erdman) or single-deletionrpfmutants to establish chronic infections in mice, reactivation was induced by administration of the nitric oxide (NO) synthase inhibitor aminoguanidine. Of the fiverpfdeletion mutants tested, one (ΔRv1009) exhibited a delayed reactivation phenotype, manifested by delayed postreactivation growth kinetics and prolonged median survival times among infected animals. Immunophenotypic analysis suggested differences in pulmonary B-cell responses between Erdman- and ΔRv1009-infected mice at advanced stages of reactivation. Analysis ofrpfgene expression in the lungs of Erdman-infected mice revealed that relative expression of four of the fiverpf-like genes was diminished at late times following reactivation, when bacterial numbers had increased substantially, suggesting thatrpfgene expression may be regulated in a growth phase-dependent manner. To our knowledge, ΔRv1009 is the firstM. tuberculosismutant to have a specific defect in reactivation without accompanying growth defects in vitro or during acute infection in vivo.

The granulomatous reaction is the hallmark of the host response to infection with Mycobacterium tuberculosis. Despite its apparent importance to host defence against the tubercle bacillus, the granulomatous response remains to be completely defined. The present study used histological, immunohistochemical and flow-cytometric analyses to characterize pulmonic granulomatous tissues of tuberculous mice and humans. The kinetics of recruitment of neutrophils, macrophages, dendritic cells, and T and B lymphocytes into the lungs of mice infected aerogenically with the virulent Erdman strain of M. tuberculosis was evaluated in detail in both the acute and persistent phase of infection. A hypoxia-sensing compound based on the 2-nitroimidazole structure (EF5), together with immunohistochemical studies targeting endothelial cells were used to examine the relative oxygen tension in tuberculous granulomatous tissues in mice. The results have provided evidence that: (i) the granulomatous tissues are a highly organized structure whose formation is regulated by orderly recruitment of specific immune cells exhibiting distinct spatial relationship with one another; (ii) the granulomatous reaction, at least in the mouse, may represent an exaggerated response to the tubercle bacillus that can play a role in the development of immunopathology; (iii) B lymphoid aggregates are a prominent feature in both murine and human granulomatous tissues, although the immune cells that are most prominently associated with these clusters vary among the two species; (iv) murine tuberculous granulomatous tissues are relatively aerobic, suggesting that mouse models of persistent tuberculosis may not be suitable for the study of any hypoxic response of M. tuberculosis.

症例は72歳,女性.主訴は左側腹部痛,左側腹部腫瘤であり,左側腹部に可動性のない鶏卵大の庄痛をともなう弾性硬の腫瘤を触知した.腹部CT検査,および腹部超音波検査にて魚骨による横行結腸穿通による腹腔内膿瘍と診断した.腹痛が左側腹部に限局していたこと,vital signが安定していたこと,および既往歴が何も存在せず心,肺,肝,腎,などの機能が問題ないと考え,保存的治療(絶食,抗生剤投与)を行った.炎症所見の改善した第13病日より食事を開始し特に問題なく,第30病日に退院となった.退院後4カ月経過した現在,腹部症状を認めず,問題なく経過している.魚骨による消化管穿孔,穿通例の報告は本邦でも多数報告されているが,本例のように外科的な処置,または内視鏡による魚骨の除去を行わずに,保存的治療にて改善した報告例はなく,稀な1例である.

The g-factor of the 27− isomer state of 152Dy has been measured using the Time- Integral Perturbed Angular Distribution (TIPAD) method. The high-spin states of 152Dy have been populated by 141Pr(16O,p4n)152Dy reaction at E = 115 MeV from the AVF cyclotron at CYRIC. The paramagnetic correction factor of Dy ions in Pr has been determined to be 4.2(5) by the Time- Differential Perturbed Angular Distribution (TDPAD) measurement of the 21− state of 152Dy. As a result, the g-factor of the 27− isomer state of 152Dy has been obtained to be +0.09(5). This shows the smaller value than the expected one of +0.39 deduced from a fully aligned configuration of π(h 11 2/2 ) ⊗ v(f 7 2/2 h 9/2 i 13/2).

Three patients with atopic dermatitis, one boy and two girls, aged between 6 and 17 years, presented eczematous skin, pruritus, scarifications, lichenification and a family history of atopy. During exacerbations, the patients sought emergency care and were prescribed oral corticosteroids for a period of approximately 15 days. Initially, the patients improved but after cessation of therapy or dose reduction, marked worsening occurred with the development of lesions with extreme pruritus, several confluent lesions, scarification and intense exudates, as well as fever and dehydration. The patients' condition was so severe that two were admitted to the allergy unit. The medication was withdrawn and intravenous hydration was administered, together with hydrating skin creams and antihistamine therapy. In addition, weak topical corticosteroids were applied on the most severely affected areas. All three patients progressively improved. We conclude that the patients with atopic dermatitis described herein presented a rebound phenomenon after the use of corticosteroids. We believe that systemic corticosteroids may exacerbate the acute phase of atopic dermatitis, mediated by IgE, accentuating the Th2 pattern in these patients.

The outcome of treatment with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients is considerably variable and is also unpredictable. It would be useful clinically if physicians were able to predict responses to DMARDs prior to their administration. One possible cause of differences in efficacy and adverse drug reactions is genetic variation in how individuals metabolize drugs. Based on pharmacogenetics, tailor-made drug therapy, also called personalized drug therapy or individual drug therapy, will be possible with analysis of genetic polymorphism, such as single nucleotide polymorphism (SNP), and analysis of haplotype and diplotype configuration. Several studies of the correlation between the genetic polymorphism of enzymes metabolizing several DMARDs and efficacy or adverse drug reactions have already been reported, suggesting that pharmacogenetics will be applicable to the treatment of RA in the near future.

We have assessed the kinetics of host gene expression in granulomas of mice infected with virulent Mycobacterium tuberculosis, using an approach that incorporates the laser capture microdissection (LCM) and real-time PCR technology in conjunction with a newly derived mathematical equation. The results have provided evidence indicating that conventional use of whole infected lungs to study granuloma-specific gene expression can yield data that may not genuinely reflect intralesional events. Significantly, the expression of nine host genes known to regulate the inflammatory response to M. tuberculosis, as determined by real-time PCR analysis of microdissected granuloma-derived cDNAs, was downregulated (up to 27-fold) at around the time when the rapid growth phase of the bacilli in the lungs of infected mice ends. This downregulation was masked when whole infected lungs were used for the studies. The data suggest that the host immune system can adjust and respond to, or can be modulated by specific physiological states of the tubercle bacillus in vivo. The LCM/real-time PCR-based system described in this study can be applied to safely and accurately evaluate gene expression in any lesions that can be microscopically visualized, including those contained in biohazardous tissues.

The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine wilt disease. This nematode has two developmental forms in its life cycle; i.e., the propagative and dispersal forms. The former is the form that builds up its population inside the host pine. The latter is specialized for transport by the vector. This form is separated into two dispersal stages (third and fourth); the third-stage dispersal juvenile (JIII) is specialized for survival under unfavorable conditions, whereas the fourth-stage juvenile (JIV), which is induced by a chemical signal from the carrier Monochamus beetle, is transported to new host pines and invades them. Because of its importance in the disease cycle, molecular and chemical aspects of the JIV have been investigated, while the mechanism of JIII induction has not been sufficiently investigated. In an effort to clarify the JIII induction process, we established inbred lines of B. xylophilus and compared their biological features. We found that the total number of nematodes (propagation proportion) was negatively correlated with the JIII emergence proportion, likely because nematode development was arrested at JIII; i.e., they could not develop to adults via the reproductive stage. In addition, JIII induction seemed to be regulated by a small number of genes because the JIII induction proportion varied among inbred lines despite the high homozygosity of the parental line. We also demonstrated that JIII can be artificially induced by the nematode's secreted substances. This is the first report of artificial induction of JIII in B. xylophilus. The dauer (dispersal) juvenile of the model organism Caenorhabditis elegans corresponds functionally to JIII of B. xylophilus, and this stage is known to be induced by a chemical signal referred to as daumone, derived from the nematodes' secretion. The artificial induction of JIII suggests the presence of daumone-like material in B. xylophilus.

Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human immunodeficiency virus (HIV)–positive patients have been described. While these patients often have normal synthetic liver function, several reports described disease progression to liver failure. Case: We here present a 26-year-old woman with history of congenital HIV on antiretroviral therapy complicated by Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with undetectable viral load. She was referred to our Hepatology service for evaluation of splenomegaly, elevated liver tests, and thrombocytopenia. On initial presentation, she reported easy bruising and gingival bleeding, and abdominal imaging showed evidence of portal hypertension without associated cirrhosis. Upper endoscopy was significant for large esophageal varices without bleeding stigmata. Liver biopsy showed minimal fibrosis around the portal areas without significant inflammation. The lobules showed focal zones of thin hepatocyte plates on reticulin stain with adjacent areas showing mild regenerative changes. The diagnosis of NRH was made and patient was placed on propranolol for variceal bleeding prophylaxis. Two years later, the patient presented with bleeding gastric varices warranting transjugular intrahepatic portosystemic shunt. Postprocedure course was complicated by mild encephalopathy. Subsequent magnetic resonance imaging showed a 1.7 × 1.3 cm lesion suggestive of hepatocellular carcinoma (HCC). The patient was deemed to be a candidate for liver transplantation, and she is now delisted due to ongoing pregnancy. Conclusion: This report describes the first case of HCC in an HIV patient with NRH. The possible association of NRH with HCC warrants further investigation.

Murine macrophages effect potent antimycobacterial function via the production of nitric oxide by the inducible isoform of the enzyme nitric oxide synthase (NOS2). The protective role of reactive nitrogen intermediates (RNI) againstMycobacterium tuberculosisinfection has been well established in various murine experimental tuberculosis models using laboratory strains of the tubercle bacillus to establish infection by the intravenous route. However, important questions remain about the in vivo importance of RNI in host defense againstM. tuberculosis. There is some evidence that RNI play a lesser role following aerogenic, rather than intravenous,M. tuberculosisinfection of mice. Furthermore, in vitro studies have demonstrated that different strains ofM. tuberculosis, including clinical isolates, vary widely in their susceptibility to the antimycobacterial effects of RNI. Thus, we sought to test rigorously the protective role of RNI against infection with recent clinical isolates ofM. tuberculosisfollowing both aerogenic and intravenous challenges. Three recently isolated and uniqueM. tuberculosisstrains were used to infect both wild-type (wt) C57BL/6 andNOS2gene-disrupted mice. Regardless of the route of infection, NOS2−/−mice were much more susceptible than wt mice to any of the clinical isolates or to either the Erdman or H37Rv laboratory strain ofM. tuberculosis. Mycobacteria replicated to much higher levels in the organs of NOS2−/−mice than in those of wt mice. Although the clinical isolates all exhibited enhanced virulence in NOS2−/−mice, they displayed distinct growth rates in vivo. The present study has provided results indicating that RNI are required for the control of murine tuberculous infection caused by both laboratory and clinical strains ofM. tuberculosis. This protective role of RNI is essential for the control of infection established by either intravenous or aerogenic challenge.

There are many cases where the vortex-induced oscillations estimated by wind tunnel tests are not observed in full-scale bridges. Many researchers suggest that these are caused by turbulence of natural wind. Certainly, it is true that turbulence controls the vortex-induced oscillation. However, the turbulence scale in wind tunnel test is usually too small to estimate its effects on a full-scale bridge in natural wind. In this study, the vortex-induced oscillation of a bridge model in large-scale turbulence flow was examined by using the slowly fluctuating wind generated with an active-controlled wind tunnel system. As aresult of the tests, it was made clear that the vortex-induced oscillation is controlled with large-scale turbulence flow.

Experimental studies have revealed that stent configuration influences intimal hyperplasia. The purpose of this study was to evaluate clinical outcomes for 2 stent designs in a randomized trial with quantitative coronary angiography (QCA) and intravascular ultrasonography (IVUS).We randomly assigned 100 patients with 107 lesions and symptomatic coronary artery disease to deployment of a Multilink stent (Advanced Cardiovascular Systems, Guidant, Santa Clara, Calif) or a GFX stent (Applied Vascular Engineering, Santa Rosa, Calif) with IVUS guidance. QCA and IVUS studies were performed before and after intervention and at follow-up (4.2 +/- 1.0 months).There were no significant differences in baseline characteristics and QCA and IVUS parameters before and after intervention between the 2 groups. However, minimal lumen diameter at follow-up was significantly larger in the Multilink group (2.46 +/- 0.59 vs 2.08 +/- 0.79 mm, P.05). Maximal in-stent intimal hyperplasia was significantly larger in the GFX group (2.9 +/- 1.7 vs 1.8 +/- 1.2 mm(2), P.01). The restenosis rate differed between the 2 groups (Multilink 4% vs GFX 26%, P =.003). In multiple stepwise logistic regression analysis, the only predictor that significantly correlated with restenosis was stent type (P.01). The odds ratio for the GFX stent-treated vessels was 18.65 (95% confidence interval 2.10-165.45).With deployment of the GFX stent, a thicker neointima develops within the stent. Stent configuration may affect clinical outcomes.

In this study, we have carried out an investigation to determine if chlorzoxazone (CZX) is a suitable probe drug for predicting hepatic injury in carbon tetrachloride (CCl4)-intoxicated rats. The animals received oral doses of CCl4 (0.25, 0.5 and 1 ml/kg) 24 h prior to intraperitoneal administration of CZX. The total CYP and CYP2E1 content, as well as the aniline and CZX hydroxylase activity (V max and CLint), was reduced depending on the dose of CCl4 administered. At the highest concentration (128 mM) of diethyldithiocarba mate, a specific inhibitor of CYP2E1, the production of 6-hydroxychlorzoxazone (HCZX) in microsomes from CCl4 treated rats was reduced by about 85%. The IC50value in microsomes from CCl4 treated rats was between 3 and 5 M. The production of HCZX and the activity of aniline hydroxylase in CCl4 treated rats correlated with the amount of rat CYP2E1 protein (r =0.881, P 4 treated rats was reduced and the HCXZ production in the CCl4 treated group was less than that in the olive oil-treated control group. The correlations between the intrinsic clearance (CLint:V max /Km) in vitro and the total body clearance (CLtot) of CZX hydroxylation and the elimination half-life (t1/2) of CZX in vivo in CCl4 treated rats were high (r =0.839, P int (V max / K m) in vitro (r = 0.909, P4 treatment.