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BACKGROUND Traditional moyamoya disease (MMD) classification relies on morphological digital subtraction angiography (DSA) assessment, which do not reflect hemodynamic status, clinical symptoms, or surgical treatment outcome. OBJECTIVE To (1) validate the new Berlin MMD preoperative symptomatology grading system and (2) determine the clinical application of the grading system in predicting radiological and clinical outcomes after surgical revascularization. METHODS Ninety-six MMD patients (192 hemispheres) with all 3 investigations (DSA, magnetic resonance imaging [MRI], Xenon-CT) performed preoperatively at our institution (2007-2013) were included. Two clinicians independently graded the imaging findings according to the proposed criteria. Patients' modified Rankin Score (mRS) scores (preoperative, postoperative, last follow-up), postoperative infarct (radiological, clinical) were collected and statistical correlations performed. RESULTS One hundred fifty-seven direct superficial temporal artery-middle cerebral artery bypasses were performed on 96 patients (66 female, mean age 41 yr, mean follow-up 4.3 yr). DSA, MRI, and cerebrovascular reserve capacity were independent factors associated hemispheric symptomatology (when analyzed individually or in the combined grading system). Mild (grade I), moderate (grade II), severe (grade III) were graded in 45, 71, and 76 hemispheres respectively; of which, clinical symptoms were found in 33% of grade I, 92% of grade II, 100% of grade III hemispheres (P

We sought to assess the feasibility and reproducibility of 3-dimensional ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression in tumor angiogenesis using a clinical matrix array transducer and a clinical grade VEGFR2-targeted contrast agent in a murine model of human colon cancer.Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice with human colon cancer xenografts (n = 33) were imaged with a clinical ultrasound system and transducer (Philips iU22; X6-1) after intravenous injection of either clinical grade VEGFR2-targeted microbubbles or nontargeted control microbubbles. Nineteen mice were scanned twice to assess imaging reproducibility. Fourteen mice were scanned both before and 24 hours after treatment with either bevacizumab (n = 7) or saline only (n = 7). Three-dimensional USMI data sets were retrospectively reconstructed into multiple consecutive 1-mm-thick USMI data sets to simulate 2-dimensional imaging. Vascular VEGFR2 expression was assessed ex vivo using immunofluorescence.Three-dimensional USMI was highly reproducible using both VEGFR2-targeted microbubbles and nontargeted control microbubbles (intraclass correlation coefficient, 0.83). The VEGFR2-targeted USMI signal significantly (P = 0.02) decreased by 57% after antiangiogenic treatment compared with the control group, which correlated well with ex vivo VEGFR2 expression on immunofluorescence (ρ = 0.93, P = 0.003). If only central 1-mm tumor planes were analyzed to assess antiangiogenic treatment response, the USMI signal change was significantly (P = 0.006) overestimated by an average of 27% (range, 2%-73%) compared with 3-dimensional USMI.Three-dimensional USMI is feasible and highly reproducible and allows accurate assessment and monitoring of VEGFR2 expression in tumor angiogenesis in a murine model of human colon cancer.

Background Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. Materials and methods Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2·5 years by fluorescence single-strand conformation polymorphism and sequence analysis. Results There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. Conclusion Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

Background: Helicobacter pylori resistance to clarithromycin, probably due to the frequent use of this antibiotic for the treatment of other diseases, is the greatest obstacle against its eradication. Aim: To clarify the prevalence of clarithromycin-resistant H. pylori in patients with non-tuberculous mycobacterial lung disease receiving multiple antibiotic treatment, including clarithromycin. Methods: We enrolled 88 patients with non-tuberculous mycobacterial lung disease; 29 underwent upper gastrointestinal endoscopy for the diagnosis of H. pylori infection prior to treatment, and 60 underwent it during treatment. The diagnosis of H. pylori infection was confirmed by histological examination, urease test and microaerobic bacterial culture. The minimum inhibitory concentration of clarithromycin was determined and the DNA was analysed for each of the isolated H. pylori strains. Results: Patients during the treatment had a high prevalence rate of clarithromycin-resistant H. pylori (100%). Analysis of DNA of the clarithromycin-resistant H. pylori isolates revealed point mutations at A2142G or A2143G. Moreover, a linear correlation was found between the total cumulative dose of clarithromycin and the minimum inhibitory concentration. Conclusion: All patients with non-tuberculous mycobacterial lung disease being treated long-term with multiple antibiotics, including clarithromycin, harboured clarithromycin-resistant H. pylori in the stomach. Therefore, eradication of H. pylori before commencement of long-term therapy including clarithromycin should be recommended.

It has been proposed that T helper (Th) 2 cells play a key role in the pathogenesis of atopic dermatitis (AD) because of clinical and experimental findings including hyper IgE, eosinophilia and Th2 type cytokine overexpression, etc. In contrast, several observations such as Th1 type cytokine detection in chronic lesions and histological features resembling allergic contact dermatitis suggest that Th1 rather than Th2 cells are important for the pathogenesis of skin lesions. In order to clarify this paradox, we investigated the function of T cell clones established from AD patients. Most T cell clones induced by house dust mite antigen and interleukin (IL)-2 from peripheral blood mononuclear cells of two AD patients exhibited CD4+/ CD8-, CD45RO+/ CD45RA-, and produced high levels of IL-4 and low levels of interferon-gamma (IFN-gamma) after phytohemagglutinin (PHA) (1 microg/ml) stimulation, suggesting a Th2 subtype. When stimulated with a high dose of concanavalin A (conA) (10 microg/ml), however, these clones produced high amounts of IFN-gamma. IL-4 production reached a peak 24 hours after conA (10 ,g/ml) stimulation, whereas IFN-gamma production was increased up to 48 hours after stimulation. The findings of T cell receptor (TCR) stimulation with immobilized anti-CD3 monoclonal antibody (mAb) showed that the suitable strength of TCR stimulation for IFN-y production was higher than for IL-4. Also, in the TCR stimulated condition, the peak of IFN-gamma production was later than that of IL-4. These results indicate that T cell clones which exhibited a Th2 profile under weak stimulation can produce IFN-y in the late phase of stimulation when strong stimuli are used. The results are consistent with the previous observation that IFN-gamma production prominently appears in the chronic and late phase lesions of AD.

This report discusses the effectiveness of conservative treatment of burns using applications of prostaglandin E 1 (PGE 1 ) containing ointment (PGE 1 ointment) to the wound site. Fourteen patients with superficial dermal burns (SDB), deep dermal burns (DDB) and full-thickness dermal burns (DB), who were treated with repeated applications of this ointment, showed rapid epithelialization of the affected tissue. Hypertrophic scarring after epithelialization was less than that expected after other therapies. The degree of scarring was graded as ‘none’, ‘mild’, ‘moderate’ or ‘severe’. The results of this therapy revealed no scarring in two sites (8.7 per cent), mild scarring in 16 sites (69.6 per cent), moderate scarring in one site (4.3 per cent) and severe scarring in four sites (17.4 per cent) out of 23 sites distributed among the patients. The application of PGE 1 ointment in combination with skin grafting surgery was found to improve functional and aesthetic results in the patients with DDB and DB, by minimizing the area of the donor site; it was especially useful for children with extensive burns because of the shortage of available tissue as donor site material for skin grafting.

Summary Excessive T helper type 1 (Th1) cell activity has been reported in Behçet's disease (BD). Recently, association of Th17 cells with certain autoimmune diseases was reported, and we thus investigated circulating Th17 cells in BD. CD4+CD45RO– (naive) T cells were cultured with Th0-, Th1-, Th2- and Th17-related cytokines and antibodies, and their mRNA was studied by real-time polymerase chain reaction (PCR). When naive CD4+ T cells were cultured with Th1- and Th17-related cytokines, interferon (IFN)-γ mRNA and interleukin (IL)-17 mRNA were up-regulated, respectively, in BD patients. Naive CD4+ T cells cultured in a Th17 cell-inducing condition expressed IL-23 receptor (IL-23R) mRNA excessively. IL-17 mRNA expression was induced only when naive CD4+T cells were cultured in the presence of IL-23. CD4+ T cells cultured with Th17 cytokines expressed excessive RAR-related orphan receptor C (RORC) mRNA. Using intracellular cytokine staining, we found that CD45RO+(memory) CD4+ T cells producing IL-17 and IFN-γ simultaneously were increased significantly. Memory CD4+ T cells producing IFN-γ but not IL-17 decreased profoundly in BD patients. CD4+ T cells producing IL-17 and IFN-γ simultaneously were found in BD skin lesions. Collectively, we found excessive CD4+ T cells producing IL-17 and IFN-γ (Th1/Th17) cells in patients with BD, and possible involvement of IL-23/IL-23R pathway for the appearance of excessive Th1/Th17 cells.

A dermis slicer designed by the authors enabled us to prepare about 10 sheets of sliced dermal grafts (SDG), 300 μm thick, from the dermis harvested from the back or buttocks of adult patients during operations. Such a sliced dermal sheet was stretched with one surface stuck on the base of a culture dish. It was then incubated in Dulbecco's essential medium for tissue culture, to which epidermal growth factor had been added. By the first week only its upper side was epithelialized from epithelial components in sliced dermis. The formation of basement membrane with anchoring fibrils was confirmed by electron microscopy. The appearance of type IV collagen and laniinin was observed between epithelialized basal cells and the dermal layer. Thus, it is thought that the SDG is useful not only for immediate grafting, when epithelialization follows, but also as a substitute for free split thickness skin grafts following tissue culture.

Deep dermal burns covering 30 per cent of the total body surface area were prepared by immersing the backs of rabbits in hot water at 80 degrees C for 20 s, to determine whether platelet activating factor (PAF) was involved in the onset of oedema following burns and to evaluate the effect of TCV-309, a potent PAF antagonist. The PAF antagonist, which was infused soon after the burn, blocked oedema formation in the wound and significantly (P0.001) inhibited PAF increase (P0.05) in the damaged tissue in a dose-dependent manner. This was confirmed by immunohistochemistry. In contrast, the superoxide dismutase content in the group treated with a high dose of TCV-309 was significantly (P0.01) higher than that of the control group. These findings suggest that administration of large doses of a PAF antagonist immediately after injury prevents oedema of burn wounds and the subsequent onset of burn shock by suppressing PAF and superoxide radical formation.

Objective: To evaluate the performance of multidetector computed tomographic angiography (MDCTA) in assessing the surgical resectability of pancreatic head adenocarcinoma. Methods: With institutional review board approval, radiographic, surgical, and pathological records of 203 consecutive patients with adenocarcinoma of the pancreatic head were analyzed retrospectively. Patients were imaged with MDCT scanners using our institution's CTA pancreatic protocol. Images were compared with surgical outcomes to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCTA in determining resectability. Results: Data were analyzed twice, once with equivocal findings on MDCTA assumed as resectable and again with equivocal cases assumed as unresectable. All equivocal cases were ultimately unresectable; when this was assumed, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were determined to be 100%, 71%, 85%,100% and 89%. Twelve patients deemed resectable by preoperative MDCTA were found to be unresectable on surgical exploration owing to vascular involvement (n = 4), liver metastases (n = 4), and peritoneal involvement (n = 4). Conclusions: Multidetector CT angiography offers accurate and valuable preoperative assessment of surgical resectability of pancreatic ductal adenocarcinoma. Liver and peritoneal metastases and vascular invasion still remain important pitfalls in preoperative evaluation.

A full description of the ontogeny of the beta cell would guide efforts to generate beta cells from embryonic stem cells (ESCs). The first step requires an understanding of definitive endoderm: the genes and signals responsible for its specification, proliferation, and patterning. This report describes a global marker of definitive endoderm, Claudin-6 (Cldn6). We report its expression in early development with particular attention to definitive endoderm derivatives. To create a genetic system to drive gene expression throughout the definitive endoderm with both spatial and temporal control, we target the endogenous locus with an inducible Cre recombinase (Cre-ER(T2)) cassette. Cldn6 null mice are viable and fertile with no obvious phenotypic abnormalities. We also report a lineage analysis of the fate of Cldn6-expressing embryonic cells, which is relevant to the development of the pancreas, lung, and liver.

Static electrification of polypropylene polybutene-1 copolymer was investigated by means of a corona discharge. The charging characteristic of the photodegraded film was compared with that of the original film. The initial surface potential of the degraded film was smaller and decayed faster than that of the original film. The chemical change of the films was measured by means of Fourier transform infrared absorption spectrum analysis. It was confirmed that the carbonyl group and the hydro-peroxide had increased due to the irradiation of ultraviolet rays applied to the specimens. The activation energy of the electrical conduction was measured by the thermally stimulated current method. It was surmised that the activation energy of the electrical conduction of the degraded film became small because the physical trap in the crystalline part had increased due to the cutting of the molecular chain. The decrease of the activation energy affected the charging characteristic of the polymer. >

This report indicates that retention fluid from blisters of partial skin thickness burns, which contains relatively large amounts of cytokines and growth factors, stimulates the wound healing process. Although epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) levels were low, relatively large amounts of cytokines including platelet derived growth factor (PDGF), interleukin (IL-6) and transforming growth factor (TGF) alpha were present and these exercised stimulatory effects on wound healing. TGF beta, which plays an important role in collagen metabolism and in scar formation, was also detected. Contrary to our expectations, IL-1 alpha and beta, both of which initiate inflammation, were detected at relatively low levels whereas IL-8 levels were rather high. Various cytokines were shown to coexist in a balanced state in the retention fluids, suggesting that epithelialization might be regulated via a cytokine network operating on the wound surface. The growth of keratinocytes in culture significantly increased with the addition of 1 per cent or more of blister fluid to the medium.

Summary Epidermal desmogleins with molecular weights of 130/140kDa (Dsg3 or PVA) and 150/160 kDa (Dsg1 or DGI) are recognized by autoantibodies from patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. In order to understand the histogenesis of both types of pemphigus, we studied the expression patterns of Dsgl and Dsg3 during stratification of cultured keratinocytes. Monolayers of cultured normal human keratinocytes demonstrated uniform inter cellular staining with PV sera. The staining pattern was distinct from the focal staining with PF sera observed only in the stratified areas. Both Dsgl and Dsg3 proteins and their mRNA were expressed by the monolayers, whereas no production of Dsg2 (HDGC) mRNA was found. The relative ratio of Dsg3 to the total desmogleins, as determined by density on immunoblotting, decreased as the cultured keratinocytes stratified. In the completely stratified keratinocytes cultured on collagen membrane, Dsgl became predominant, with subsequent reduction of PV antigen expression. The relative decrease of Dsg3 (PVA) during epidermal differentiation might be responsible for the induction of suprabasal acantholysis in PV.

Patients with Behcet's disease (BD) are highly associated with HLA-B51 immunogenetically and tend to be involved with chronic infectious foci, such as tonsillitis and dental caries, by nonpathogenic streptococci in the oral cavity. BD patients were suggested to be hypersensitive to streptococci and we immunohistologically demonstrated the deposits of streptococcal related antigen at infiltrated cells which were adhering to the vascular walls in erythema nodosum (EN)-like lesions. The Japanese Research Group for BD also demonstrated that BD patients showed greater hypersensitivity against streptococcal antigens than normal healthy controls and that the BD symptoms were frequently induced by the skin tests using these antigens and the treatment of the dental caries. Streptococcus sanguis was dominantly isolated from the infectious foci and the strain strongly adhered to the epithelial cells of the oral membrane, which might be correlated with chemotactic activity of neutrophils in the BD lesions. An attempt at cloning and sequencing the bes-1 gene of S. sanguis isolated from BD patients was made and it has been found that the amino acid sequence of the bes-1 gene has more than 60% of homology with the human intraocular peptide brn-3b, which is a POU domain expressed in the retinal ganglion cells. On the other hand, heat shock protein-65 kDa (HSP-65) derived from microbial organisms which had homology with human HSP-60 was shown to be cross-reactive to the serotype of S. sanguis found in BD patients. Recently we recognized the antibody cross-reactivity against human HSP-60 peptide (336–351), which might stimulate T-lymphocytes of BD patients. In order to explain more precisely the relationship between S. sanguis and BD symptoms, we attempted to find bes-1 gene in the various lesions and to detect the antibodies against both bes-1 synthetic peptides and recombinant HSP-60/65 of S. sanguis in sera of BD patients.

Patients with unilateral varicocele, grade 3, (n=11), were analyzed to study if there are morphological or fuctional alterations in the testes. They were classified according to genital stage given GnRH (100 mcg) and hCG (50 U/kg/dose. 5 days) and underwent bilateral testicular biopsy. Testicular volume (TV) was measured and differences > 2 cm3 were considered significant Basal testoterone (T) and peak LH, FSH and T were similar to the control group. There was no difference in basal LH and FSH between groups G1, G2, G3+4. Tubular diameter (TD) and area (TA) are showed in the table. In the five cases with decreased testicular volume, there was a higher TD on the Va side. Six patients didn't have a reduction in testicular volume and only two had a difference in TD between both sides. There was a tendency for a decrease in testicular volume and an increase in TD advancing pubertal development.

Patients with Behcet's disease show an intense delayed hypersensitivity (DH) reaction to a group of streptococcal bacteria. We have attempted to detect deposits of immune complexes and to analyse cytological reactions in the aphthous ulcers and erythema nodosum (EN)-like eruptions. Deposits of IgM and positive fluorescence of anti-streptococcal group D serum were found in vessel walls and sites infiltrated by inflammatory cells. Cytological analysis has revealed that the inflammatory infiltrating cells are mainly composed of activated T-cells and macrophages in association with natural killer cells. These results suggest that DH reactions with antigen-antibody mediated cytotoxicity may play an important role in causing the lesions of Behcet's disease.

We investigated the menstruation of the telephone-operators in Japanese National Railways. A questionaire method was applied, which was repeated every month from June 1948 to May 1949. This is an interim report for 7 months.(1) 276 operators at two telephone operating offices in Tokyo were investigeted, where majority of the examinee were 16-21 years of age. They averaged 3.9 y. on service of Railway, but their experience as operator was 2.6 y. in consequence. of the redistribution after the war.(2) The average age of the first menstruation was found M±σ= 15.45±1.22 y., and in its distribution frequency by age, majority (75.8 %) concentrate in 14-16 y., having its peak at 15 y.(3) The average length of menstruation cycle was, M±σ=31.75±8.66 days (with 'dpeak of distribution at 31 days), and the average cycle transition, M±σ=17, 8±12, 01 ays.(4) If we classify the menstruation, cycle of whichis 23-40 days and transition is within 20 days, as the regular type, and otheres as irregular, the occurrence frequency of the former is 45.5 %(5) The menstrual duration is 4, 60 days on an average and its S.D. is 1.38 day.The duration, types could be classified as follows :There was found on correlation between the duration type and the cycle type.(6) The objective inference Of the menstrual blood was unsuccessful.(7) The accompanied Symptoms of Menstruation were very higt in its occurrence, i. e. reported of in 8.8 % of the whole sample. Itemi4ing them, ache of lower abdomen was 45.8 %, headache 27.6 %, huckleache 17.2 %, etc.(8) The labour in menstrual period, therefore, was more for less painful, but the grade of pain was moderate in 62.1 % of operators.(9) The operators who had to be absent from their service in the menstrual period were 32.3 % of all. In number of days, 2 day's absence amounted to 47.5 % of those operators, which is the highest percentage of absence.