University of Fukui

Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension. In addition, they dose-dependently destabilized preformed fAbetas. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC(50)) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAbetas were in the order of 0.1-1 microM. Although the mechanism by which Cur and RA inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD.

BACKGROUND: -mutated AML. METHODS: -mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission with full or partial hematologic recovery. Secondary end points included event-free survival (freedom from treatment failure [i.e., relapse or lack of remission] or death) and the percentage of patients who had complete remission. RESULTS: Of 371 eligible patients, 247 were randomly assigned to the gilteritinib group and 124 to the salvage chemotherapy group. The median overall survival in the gilteritinib group was significantly longer than that in the chemotherapy group (9.3 months vs. 5.6 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P<0.001). The median event-free survival was 2.8 months in the gilteritinib group and 0.7 months in the chemotherapy group (hazard ratio for treatment failure or death, 0.79; 95% CI, 0.58 to 1.09). The percentage of patients who had complete remission with full or partial hematologic recovery was 34.0% in the gilteritinib group and 15.3% in the chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4); the percentages with complete remission were 21.1% and 10.5%, respectively (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4). In an analysis that was adjusted for therapy duration, adverse events of grade 3 or higher and serious adverse events occurred less frequently in the gilteritinib group than in the chemotherapy group; the most common adverse events of grade 3 or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%). CONCLUSIONS: -mutated AML. (Funded by Astellas Pharma; ADMIRAL ClinicalTrials.gov number, NCT02421939.).

Imbalanced learning problems contain an unequal distribution of data samples among different classes and pose a challenge to any classifier as it becomes hard to learn the minority class samples. Synthetic oversampling methods address this problem by generating the synthetic minority class samples to balance the distribution between the samples of the majority and minority classes. This paper identifies that most of the existing oversampling methods may generate the wrong synthetic minority samples in some scenarios and make learning tasks harder. To this end, a new method, called Majority Weighted Minority Oversampling TEchnique (MWMOTE), is presented for efficiently handling imbalanced learning problems. MWMOTE first identifies the hard-to-learn informative minority class samples and assigns them weights according to their euclidean distance from the nearest majority class samples. It then generates the synthetic samples from the weighted informative minority class samples using a clustering approach. This is done in such a way that all the generated samples lie inside some minority class cluster. MWMOTE has been evaluated extensively on four artificial and 20 real-world data sets. The simulation results show that our method is better than or comparable with some other existing methods in terms of various assessment metrics, such as geometric mean (G-mean) and area under the receiver operating curve (ROC), usually known as area under curve (AUC).

Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. CagA is injected from the attached Helicobacter pylori into host cells and undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant CagA induced a growth factor-like response in gastric epithelial cells. Furthermore, CagA formed a physical complex with the SRC homology 2 domain (SH2)-containing tyrosine phosphatase SHP-2 in a phosphorylation-dependent manner and stimulated the phosphatase activity. Disruption of the CagA-SHP-2 complex abolished the CagA-dependent cellular response. Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on cancer cell membranes and activates the zymogen of MMP-2 (gelatinase A). We have recently isolated MT1-MMP complexed with tissue inhibitor of metalloproteinases 2 (TIMP-2) and demonstrated that MT1-MMP exhibits gelatinolytic activity by gelatin zymography (Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H., Seiki, M., and Okada, Y. (1996) Cancer Res. 56, 2707-2710). In the present study, we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast carcinoma cell line (MDA-MB-231 cells) and examined their substrate specificities. Both proteinases are active, without any treatment for activation, and digest type I (guinea pig), II (bovine), and III (human) collagens into characteristic 3/4 and 1/4 fragments. The cleavage sites of type I collagen are the Gly775-Ile776 bond for alpha1(I) chains and the Gly775-Leu776 and Gly781-Ile782 bonds for alpha2(I) chains. DeltaMT1 hydrolyzes type I collagen 6.5- or 4-fold more preferentially than type II or III collagen, whereas MMP-1 (tissue collagenase) digests type III collagen more efficiently than the other two collagens. Quantitative analyses of the activity of DeltaMT1 and MMP-1 indicate that DeltaMT1 is 5-7.1-fold less efficient at cleaving type I collagen. On the other hand, gelatinolytic activity of DeltaMT1 is 8-fold higher than that of MMP-1. DeltaMT1 also digests cartilage proteoglycan, fibronectin, vitronectin and laminin-1 as well as alpha1-proteinase inhibitor and alpha2-macroglobulin. The activity of DeltaMT1 on type I collagen is synergistically increased with co-incubation with MMP-2. These results indicate that MT1-MMP is an extracellular matrix-degrading enzyme sharing the substrate specificity with interstitial collagenases, and suggest that MT1-MMP plays a dual role in pathophysiological digestion of extracellular matrix through direct cleavage of the substrates and activation of proMMP-2.

A number of large noncoding RNAs (ncRNAs) epigenetically silence genes through unknown mechanisms. The Air ncRNA is imprinted--monoallelically expressed from the paternal allele. Air is required for allele-specific silencing of the cis-linked Slc22a3, Slc22a2, and Igf2r genes in mouse placenta. We show that Air interacts with the Slc22a3 promoter chromatin and the H3K9 histone methyltransferase G9a in placenta. Air accumulates at the Slc22a3 promoter in correlation with localized H3K9 methylation and transcriptional repression. Genetic ablation of G9a results in nonimprinted, biallelic transcription of Slc22a3. Truncated Air fails to accumulate at the Slc22a3 promoter, which results in reduced G9a recruitment and biallelic transcription. Our results suggest that Air, and potentially other large ncRNAs, target repressive histone-modifying activities through molecular interaction with specific chromatin domains to epigenetically silence transcription.

This collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

During the last few years the interest in the indium nitride (InN) semiconductor has been remarkable. There have been significant improvements in the growth of InN films. High quality single crystalline InN film with two-dimensional growth and high growth rate are now routinely obtained. The background carrier concentration and Hall mobility have also improved. Observation of strong photoluminescence near the band edge is reported very recently, leading to conflicts concerning the exact band gap of InN. Attempts have also been made on the deposition of InN based heterostructures for the fabrication of InN based electronic devices. Preliminary evidence of two-dimensional electron gas accumulation in the InN and studies on InN-based field-effect transistor structure are reported. In this article, the work accomplished in the InN research, from its evolution to till now, is reviewed. The In containing alloys or other nitrides (AlGaInN, GaN, AlN) are not discussed here. We mainly concentrate on the growth, characterization, and recent developments in InN research. The most popular growth techniques, metalorganic vapor phase epitaxy and molecular beam epitaxy, are discussed in detail with their recent progress. Important phenomena in the epitaxial growth of InN as well as the problems remaining for future study are also discussed.

Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Mice lacking the gene encoding the receptor for prostaglandin F2alpha (FP) developed normally but were unable to deliver normal fetuses at term. Although these FP-deficient mice showed no abnormality in the estrous cycle, ovulation, fertilization, or implantation, they did not respond to exogenous oxytocin because of the lack of induction of oxytocin receptor (a proposed triggering event in parturition), and they did not show the normal decline of serum progesterone concentrations that precedes parturition. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and permitted successful delivery in the FP-deficient mice. These results indicate that parturition is initiated when prostaglandin F2alpha interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis.

Helicobacter pylori is a causative agent of gastritis and peptic ulcer. cagA(+) H. pylori strains are more virulent than cagA(-) strains and are associated with gastric carcinoma. The cagA gene product, CagA, is injected by the bacterium into gastric epithelial cells and subsequently undergoes tyrosine phosphorylation. The phosphorylated CagA specifically binds SHP-2 phosphatase, activates the phosphatase activity, and thereby induces morphological transformation of cells. CagA proteins of most Western H. pylori isolates have a 34-amino acid sequence that variably repeats among different strains. Here, we show that the repeat sequence contains a tyrosine phosphorylation site. CagA proteins having more repeats were found to undergo greater tyrosine phosphorylation, to exhibit increased SHP-2 binding, and to induce greater morphological changes. In contrast, predominant CagA proteins specified by H. pylori strains isolated in East Asia, where gastric carcinoma is prevalent, had a distinct tyrosine phosphorylation sequence at the region corresponding to the repeat sequence of Western CagA. This East Asian-specific sequence conferred stronger SHP-2 binding and morphologically transforming activities to Western CagA. Finally, a critical amino acid residue that determines SHP-2 binding activity among different CagA proteins was identified. Our results indicate that the potential of individual CagA to perturb host-cell functions is determined by the degree of SHP-2 binding activity, which depends in turn on the number and sequences of tyrosine phosphorylation sites. The presence of distinctly structured CagA proteins in Western and East Asian H. pylori isolates may underlie the strikingly different incidences of gastric carcinoma in these two geographic areas.

STUDY DESIGN: The study of seven patients with primary malignant or benign aggressive tumors who underwent a new aggressive surgical technique termed "total en bloc spondylectomy" is reported. OBJECTIVES: To report a new surgical technique of total en bloc spondylectomy for complete, resection of primary spinal malignancy and for oncologic curability. SUMMARY OF BACKGROUND DATA: The conventional approach for primary spinal malignancy is via intralesional piecemeal resection, and very few reports have described en bloc extralesional resectioning with histopathologically wide or marginal surgical margins. METHODS: Total en bloc spondylectomy, consisting of en bloc laminectomy and en bloc corpectomy followed by anterior instrumentation with spacer grafting and posterior spinal instrumentation, was performed in five patients with primary malignant tumors and two patients with giant cell tumors. Patients were observed for 2 years to 6.5 years, except for one patient who died 7 months after surgery because of a mediastinal metastasis. RESULTS: All patients, except one, attained significant clinical improvement after surgery with no major complications. Histologically, the margins were wide or marginal except for the pedicles, and occasionally the spinal canal and the posterior, where they were accepted to be intralesional. One patient died of metastasis that was not directly related to surgery itself. There was no local recurrence. CONCLUSIONS: The advantages of total en bloc spondylectomy include resection of the involved vertebra(e) in two major blocs, rather than in a piecemeal pattern, and completion of the procedure during one surgical session posteriorly. The "total en bloc spondylectomy" offers one of the most aggressive modes of therapy for primary spinal malignancy.

BACKGROUND: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications. METHODS: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points. RESULTS: Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts. CONCLUSIONS: PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04198701.

BACKGROUND: Development of emergency department (ED) triage systems that accurately differentiate and prioritize critically ill from stable patients remains challenging. We used machine learning models to predict clinical outcomes, and then compared their performance with that of a conventional approach-the Emergency Severity Index (ESI). METHODS: Using National Hospital and Ambulatory Medical Care Survey (NHAMCS) ED data, from 2007 through 2015, we identified all adult patients (aged ≥ 18 years). In the randomly sampled training set (70%), using routinely available triage data as predictors (e.g., demographics, triage vital signs, chief complaints, comorbidities), we developed four machine learning models: Lasso regression, random forest, gradient boosted decision tree, and deep neural network. As the reference model, we constructed a logistic regression model using the five-level ESI data. The clinical outcomes were critical care (admission to intensive care unit or in-hospital death) and hospitalization (direct hospital admission or transfer). In the test set (the remaining 30%), we measured the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and net benefit (decision curves) for each model. RESULTS: Of 135,470 eligible ED visits, 2.1% had critical care outcome and 16.2% had hospitalization outcome. In the critical care outcome prediction, all four machine learning models outperformed the reference model (e.g., AUC, 0.86 [95%CI 0.85-0.87] in the deep neural network vs 0.74 [95%CI 0.72-0.75] in the reference model), with less under-triaged patients in ESI triage levels 3 to 5 (urgent to non-urgent). Likewise, in the hospitalization outcome prediction, all machine learning models outperformed the reference model (e.g., AUC, 0.82 [95%CI 0.82-0.83] in the deep neural network vs 0.69 [95%CI 0.68-0.69] in the reference model) with less over-triages in ESI triage levels 1 to 3 (immediate to urgent). In the decision curve analysis, all machine learning models consistently achieved a greater net benefit-a larger number of appropriate triages considering a trade-off with over-triages-across the range of clinical thresholds. CONCLUSIONS: Compared to the conventional approach, the machine learning models demonstrated a superior performance to predict critical care and hospitalization outcomes. The application of modern machine learning models may enhance clinicians' triage decision making, thereby achieving better clinical care and optimal resource utilization.

In order to understand the rheological and transport properties of a suspension of swimming micro-organisms, it is necessary to analyse the fluid-dynamical interaction of pairs of such swimming cells. In this paper, a swimming micro-organism is modelled as a squirming sphere with prescribed tangential surface velocity, referred to as a squirmer. The centre of mass of the sphere may be displaced from the geometric centre (bottom-heaviness). The effects of inertia and Brownian motion are neglected, because real micro-organisms swim at very low Reynolds numbers but are too large for Brownian effects to be important. The interaction of two squirmers is calculated analytically for the limits of small and large separations and is also calculated numerically using a boundary-element method. The analytical and the numerical results for the translational–rotational velocities and for the stresslet of two squirmers correspond very well. We sought to generate a database for an interacting pair of squirmers from which one can easily predict the motion of a collection of squirmers. The behaviour of two interacting squirmers is discussed phenomenologically, too. The results for the trajectories of two squirmers show that first the squirmers attract each other, then they change their orientation dramatically when they are in near contact and finally they separate from each other. The effect of bottom-heaviness is considerable. Restricting the trajectories to two dimensions is shown to give misleading results. Some movies of interacting squirmers are available with the online version of the paper.

UNLABELLED: An ideal hypoxia imaging agent should have high membrane permeability for easy access to intracellular mitochondria and low redox potential to confer stability in normal tissue, but it should be able to be reduced by mitochondria with abnormally high electron concentrations in hypoxic cells. In this context, nitroimidazole residues are not considered to be essential. In this study, Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM), a 62Cu-bisthiosemicarbazone complex, with high membrane permeability and low redox potential, was evaluated as a possible hypoxia imaging agent, using electron spin resonance spectrometry and the Langendorff isolated perfused rat heart model as well as rat heart left anterior descending occlusion model. METHODS: Nonradioactive Cu-ATSM was incubated with rat mitochondria, after which reduction of Cu(II) to Cu(I) was measured with electron spin resonance. As a model of hypoxic mitochondria, rotenone (Complex I inhibitor)-treated mitochondria were used. RESULTS: In this study, Cu-ATSM was reduced by hypoxic but not by normal mitochondria. CONCLUSION: Thus, retention of 62Cu-ATSM was studied serially in perfused rat hearts under conditions of normoxia (95% O2 + 5% CO2), hypoxia (95% N2 + 5% CO2) and reoxygenation (95% O2 + 5% CO2). In normoxia and reoxygenation, 62Cu-ATSM injected as a single bolus showed low retention (23.77% and 22.80%, respectively) 15 min after injection, but retention was increased markedly under hypoxic conditions (81.10%). Also, in the in vivo left anterior descending occluded rat heart model, 62Cu-ATSM retention was inversely correlated with accumulation of 201Tl, a relative myocardial blood flow marker.

Water droplets on rugged hydrophobic surfaces typically exhibit one of the following two states: (i) the Wenzel state [Wenzel RN (1936) Ind Eng Chem 28:988-994] in which water droplets are in full contact with the rugged surface (referred as the wetted contact) or (ii) the Cassie state [Cassie, ABD, Baxter S (1944) Trans Faraday Soc 40:546-551] in which water droplets are in contact with peaks of the rugged surface as well as the "air pockets" trapped between surface grooves (the composite contact). Here, we show large-scale molecular dynamics simulation of transition between Wenzel state and Cassie state of water droplets on a periodic nanopillared hydrophobic surface. Physical conditions that can strongly affect the transition include the height of nanopillars, the spacing between pillars, the intrinsic contact angle, and the impinging velocity of water nanodroplet ("raining" simulation). There exists a critical pillar height beyond which water droplets on the pillared surface can be either in the Wenzel state or in the Cassie state, depending on their initial location. The free-energy barrier separating the Wenzel and Cassie state was computed on the basis of a statistical-mechanics method and kinetic raining simulation. The barrier ranges from a few tenths of k(B)T(0) (where k(B) is the Boltzmann constant, and T(0) is the ambient temperature) for a rugged surface at the critical pillar height to approximately 8 k(B)T(0) for the surface with pillar height greater than the length scale of water droplets. For a highly rugged surface, the barrier from the Wenzel-to-Cassie state is much higher than from Cassie-to-Wenzel state. Hence, once a droplet is trapped deeply inside the grooves, it would be much harder to relocate on top of high pillars.

Attachment of Helicobacter pylori to gastric epithelial cells induces various cellular responses, including the tyrosine phosphorylation of an unknown 145-kD protein and interleukin 8 production. Here we show that this 145-kD protein is the cagA product of H. pylori, an immunodominant, cytotoxin-associated antigen. Epithelial cells infected with various H. pylori clinical isolates resulted in generation of tyrosine-phosphorylated proteins ranging from 130 to 145 kD in size that were also induced in vitro by mixing host cell lysate with bacterial lysate. When epithelial cells were infected with [(35)S]methionine-labeled H. pylori, a radioactive 145-kD protein was detected in the immunoprecipitates with antiphosphotyrosine antibody or anti-CagA (cytotoxin-associated gene A) antibody. Consistently, the 145-kD protein recognized by the anti-CagA and antiphosphotyrosine antibodies was induced in epithelial cells after infection of wild-type H. pylori but not the cagA::Km mutant. Furthermore, the amino acid sequence of the phosphorylated 145-kD protein induced by H. pylori infection was identical to the H. pylori CagA sequence. These results reveal that the tyrosine-phosphorylated 145-kD protein is H. pylori CagA protein, which may be delivered from attached bacteria into the host cytoplasm. The identification of the tyrosine-phosphorylated protein will thus provide further insights into understanding the precise roles of CagA protein in H. pylori pathogenesis.

Organophilic montmorillonite was obtained by the reaction of montmorillonite (MON) and distearyldimethylammonium chloride (DSAC). The modified clay and poly(l-lactide), (PLLA), were solvent-cast blended using chloroform as cosolvent. The structure and properties of the PLLA-clay blends were investigated. Thermal measurements revealed that cold crystallization took place in the as-cast PLLA, and that the clay served as a nucleating agent. From small and wide-angle x-ray scattering measurements, it was found that silicate layers forming the clay could not be individually well dispersed in the PLLA-clay blends prepared by the solvent-cast method. In other words, the clay existed in the form of tactoids, which consist of several stacked silicate monolayers. However, these tactoids formed a remarkable geometrical structure in the blend films. That is, their surfaces lay almost parallel to the film surface, and were stacked with the insertion of PLLA crystalline lamellae in the thickness direction of the film. During the blend drawing process, fibrillation took place with the formation of plane-like voids developed on the plane parallel to the film surface. Furthermore, delamination of the silicate layers did not occur even under the application of a shearing force. Finally, Young's modulus of the blend increased with the addition of a small amount of the clay. © 1997 John Wiley & Sons, Inc.