Clinicopathological features of narrow-band imaging endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms.

To reveal clinicopathological features of narrow-band imaging (NBI) endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms. If a lesion diameter was smaller or same compared with a width of closed biopsy forceps, a lesion was defined to be an ultraminute lesion. Twenty-five consecutive patients with 33 ultraminute esophageal lesions that were removed by endoscopic mucosal resection were included in the present study. We conducted two questionnaire surveys of six endoscopists by their retrospective review of endoscopic still images. The six endoscopists evaluated the endoscopic findings of the ultraminute lesions on still images taken by conventional white-light imaging endoscopy and non-magnified NBI endoscopy in the first questionnaire, and taken by magnified NBI endoscopy in the second questionnaire. An experienced pathologist who was unaware of any endoscopic findings made histological diagnosis and evaluated immunoexpression of p53 and Ki67. The 33 ultraminute lesions were all determined to be either 11 high-grade intraepithelial neoplasias (HGIENs) or 22 low-grade intraepithelial neoplasias (LGIENs). The tumor diameters were histologically confirmed to be <3 mm. All of the ultraminute tumors were visualized as unstained areas and brownish areas by real-time endoscopy with Lugol dye staining and non-magnified NBI endoscopy, respectively. All of the ultraminute IENs were visualized as brownish areas by real-time non-magnified NBI endoscopy. Three of the 25 patients with the ultraminute IENs (12%) had multiple brownish areas (more than several areas) in the esophagus on real-time non-magnified NBI endoscopy. All of the ultraminute IENs were visualized as unstained areas by real-time Lugol chromoendoscopy. Twenty of the 25 patients (80%) had multiple unstained areas (more than several areas) in the esophagus on real-time Lugol chromoendoscopy. The first questionnaire survey revealed that a significantly higher detection rate of the ultraminute IENs on non-magnified NBI endoscopy images compared with conventional white-light imaging endoscopy ones (100% vs. 72%, respectively: P < 0.0001). The second questionnaire survey revealed that presence rates of any magnified NBI endoscopy findings were not significantly different between HGIENs and LGIENs. Proliferation, dilation, and various shapes of intrapapillary capillary loops indicated remarkably high presence rates of more than 90% in both HGIENs and LGIENs. Six of 22 LGIENs (27%) and 3 of 11 HGIENs (27%) show a positive expression for p53. None of peri-IEN epithelia was positive for p53. A mean of Ki67 labeling index of LGIENs was 33% and that of HGIENs 36%. Ki67 labeling index was significantly greater in the LGIENs and HGIENs compared with that in the peri-IEN epithelia. There were no significant differences in p53 expression and Ki67 labeling index between the HGIENs and LGIENs. Non-magnified/magnified NBI endoscopy could facilitate visualization and characterization of ultraminute esophageal squamous IENs. The ultraminute HGIENs and LGIENs might have comparable features of magnified NBI endoscopy and immunohistochemistry.

Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.

Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Granular flow experiment using artificial gravity generator at International Space Station.

Studying the gravity-dependent characteristics of regolith, fine-grained granular media covering extra-terrestrial bodies is essential for the reliable design and analysis of landers and rovers for space exploration. In this study, we propose an experimental approach to examine a granular flow under stable artificial gravity conditions for a long duration generated by a centrifuge at the International Space Station. We also perform a discrete element simulation of the granular flow in both artificial and natural gravity environments. The simulation results verify that the granular flows in artificial and natural gravity are consistent. Further, regression analysis of the experimental results reveals that the mass flow rate of granular flow quantitatively follows a well-known physics-based law with some deviations under low-gravity conditions, implying that the bulk density of the granular media decreases with gravity. This insight also indicates that the bulk density considered in simulation studies of space probes under low-gravity conditions needs to be tuned for their reliable design and analysis.

Risk factor analysis for low blood pressure and hyponatremia in acutely and subacutely spinal cord injured patients.

STUDY DESIGN: Case control. OBJECTIVE: To clarify the predictors of low blood pressure (BP) and hyponatremia after spinal cord injury (SCI) and to discuss their pathophysiology. SETTING: A SCI center in Japan. METHODS: Age, gender, initial ASIA impairment scale (AIS) score, BP, blood electrolytes (sodium, K and Cl) and biochemical markers were evaluated at 1 month after injury. Risk factors of low BP and hyponatremia were analyzed using uni- and multivariate logistic regression models. RESULTS: This study comprised of 172 SCI patients. Initial AIS score (Odds ratio (OR): 1.24, 95% confidence intervals (CI) 1.13-1.49, P-value <0.01) and hyponatremia (OR: 3.71, 95%CI 1.27-6.96, P<0.01) were the most important risk factors of low BP. As a second step, risk factors of hyponatremia were initial AIS score (OR: 1.36, 95%CI 1.08-2.78, P<0.01) and age (OR: 1.55, 95%CI 1.17-2.93, P<0.01). CONCLUSIONS: In acute and subacute period, the more severe SCI and lower AIS score patients have the more frequently low BP and/or hyponatremia do appear.

Identification of Sc-type ILV6 as a target to reduce diacetyl formation in lager brewers' yeast.

Diacetyl causes an unwanted buttery off-flavor in lager beer. It is spontaneously generated from α-acetolactate, an intermediate of yeast's valine biosynthesis released during the main beer fermentation. Green lager beer has to undergo a maturation process lasting two to three weeks in order to reduce the diacetyl level below its taste-threshold. Therefore, a reduction of yeast's α-acetolactate/diacetyl formation without negatively affecting other brewing relevant traits has been a long-term demand of brewing industry. Previous attempts to reduce diacetyl production by either traditional approaches or rational genetic engineering had different shortcomings. Here, three lager yeast strains with marked differences in diacetyl production were studied with regard to gene copy numbers as well as mRNA abundances under conditions relevant to industrial brewing. Evaluation of data for the genes directly involved in the valine biosynthetic pathway revealed a low expression level of Sc-ILV6 as a potential molecular determinant for low diacetyl formation. This hypothesis was verified by disrupting the two copies of Sc-ILV6 in a commercially used lager brewers' yeast strain, which resulted in 65% reduction of diacetyl concentration in green beer. The Sc-ILV6 deletions did not have any perceptible impact on beer taste. To our knowledge, this has been the first study exploiting natural diversity of lager brewers' yeast strains for strain optimization.

Individualized pterional keyhole clipping surgery based on a preoperative three-dimensional virtual osteotomy technique for unruptured middle cerebral artery aneurysm.

OBJECTIVE: Individualized surgical simulation using three-dimensional (3D) imaging to allow safe performance of clipping surgery for unruptured middle cerebral artery (MCA) aneurysm via pterional keyhole mini-craniotomy was performed in 100 consecutive patients. METHODS: 3D images were reconstructed of the skin, skull, cerebral arteries and veins, and aneurysm. The size, shape, and location of the scheduled keyhole and the patient's head position were individually optimized using this preoperative simulation system. The site of opening of the sylvian fissure was also preoperatively determined according to the spatial relationships between the aneurysm and sylvian veins. 110 pterional keyhole clipping surgeries were consecutively performed in 100 patients. RESULTS: The mean diameter of the pterional keyhole was 25±2 mm. Magnetic resonance imaging detected lacunar infarction in 4 cases (3.6%) but no other abnormalities. 1 patient suffered a reversible ischemic neurological deficit and 1 patient (79 years old) showed mild dementia. The modified Rankin scale at 3 months after the operation was grade 0 in all cases except 1 patient with mild dementia (grade 1). Mini-mental state examination, Hamilton rating scale for depression, and Beck depression inventory were all significantly improved (p<0.01) after the operations. CONCLUSION: Pterional keyhole clipping surgery based on careful surgical simulation with 3D images is a safe and less invasive means to treat relatively small unruptured MCA aneurysms.

[Graft replacement for surgical repair of coarctation of the aorta in adults].

We report the graft replacement for surgical repair of coarctation of the aorta (CoA) in 2 men, aged 19 and 30 years old, respectively. In both patients, the pressure gradients were higher than 20 mmHg across the coarctaion by cathetherization, and higher than 30 mmHg between the upper and lower limbs. The graft replacement of the coarctated aorta was performed under cardiopulmonary bypass. Postoperatively, the pressure gradients between the upper and lower limbs dropped below 20 mmHg in both cases. Since about 50% of surgically untreated patients with this disease may be expected to die before 30 years of age, repair of CoA in adults should be performed as soon as possible.

Clonal character of F1 hybrid lymphocyte subset recognition of parental cells in one-way mixed lymphocyte cultures.

Proliferation of F(1) hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F(1) hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F(1) hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F(1) cells, and not the blocked parental cells, enter mitosis. Stimulation of F(1) cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F(1) recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F(1) spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes.

Immunologic properties of mouse thymus cells. Identification of T cell functions within a minor, low-density subpopulation.

The functional attributes of minor subpopulations of mouse thymus cells derived by bovine serum albumin density gradient centrifugation, cortisone treatment, or selective depletion by anti-TL or anti-theta treatment have been examined. A subpopulation derived in each fashion contains the cells required to evoke graft-versus-host reactions in neonatal F(1) hybrid recipients and to be stimulated by alloantigens in vitro in one-way mixed lymphocyte cultures and by phytohemagglutinin. The functions of this subpopulation are abrogated by treatment with anti-H-2 plus complement and by high concentrations of anti-theta. A tentative ordering of the various thymus cell subpopulations, on the basis of these and other data, is described.

Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.

Cell-type-independent expression of inwardly rectifying potassium currents in mouse fungiform taste bud cells.

Inwardly rectifying potassium (Kir) channels play key roles in functions, including maintaining the resting membrane potential and regulating the action potential duration in excitable cells. Using in situ whole-cell recordings, we investigated Kir currents in mouse fungiform taste bud cells (TBCs) and immunologically identified the cell types (type I-III) expressing these currents. We demonstrated that Kir currents occur in a cell-type-independent manner. The activation potentials we measured were -80 to -90 mV, and the magnitude of the currents increased as the membrane potentials decreased, irrespective of the cell types. The maximum current densities at -120 mV showed no significant differences among cell types (p>0.05, one-way ANOVA). The density of Kir currents was not correlated with the density of either transient inward currents or outwardly rectifying currents, although there was significant correlation between transient inward and outwardly rectifying current densities (p<0.05, test for no correlation). RT-PCR studies employing total RNA extracted from peeled lingual epithelia detected mRNAs for Kir1, Kir2, Kir4, Kir6, and Kir7 families. These findings indicate that TBCs express several types of Kir channels functionally, which may contribute to regulation of the resting membrane potential and signal transduction of taste.

External hip protectors are effective for the elderly with higher-than-average risk factors for hip fractures.

UNLABELLED: In our cluster randomised controlled trial for efficacy of hip protector with 672 ambulatory elderly women, a hip protector was more effective for prevention of hip fractures in residents with fall history (n = 202; hazard ratio (HR), 0.375; 95%CI, 0.14-0.98; p = 0.05) and body-mass index (BMI) < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04) by a Cox proportional hazards regression model. INTRODUCTION: Hip fractures result from both osteoporosis and falling. A potentially cost-effective method of preventing hip fractures involves the use of hip protectors but recent studies have revealed the uncertain effectiveness of hip protectors even in institutional settings. METHODS: This study was a cluster randomised controlled trial with nursing homes. We randomly assigned 76 homes with 672 ambulatory but frail elderly women. Several risk factors were assessed at baseline and incorporated into a Cox proportional hazards regression model. UMIN Clinical Trials Registry number is UMIN000000467. Research period was between January 2004 and March 2006. RESULTS: In the intervention group, 19 hip fractures occurred (54.0/1,000 person-years), whereas 39 hip fractures occurred in the control group (78.8/1,000 person-years). Hazard ratio of hip fracture in the intervention group was 0.56 (95%CI, 0.31-1.03; p = 0.06) after adjusting for risk factors. In subgroup analysis, hip protectors were more effective for prevention of hip fractures in residents with fall history (n = 202; HR, 0.375; 95%CI, 0.14-0.98; p = 0.05) and BMI < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04). Overall compliance with use of hip protectors was 79.7%. CONCLUSION: Risk of hip fracture can be reduced by hip protectors among elderly women with fall history and low BMI.

Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia.

Human T cell lymphoma leukemia virus (HTLV) is a human retrovirus (RNA tumor virus) that was originally isolated from a few patients with leukemias or lymphomas involving mature T lymphocytes. Here we report that the serum of Japanese patients with adult T cell leukemia, but not the serum of tested normal donors, contains high titers of antibodies to HTLV. These observations, together with data from Japan showing that adult T cell leukemia is endemic in southwest Japan, suggest that HTLV is involved in a subtype of human T cell malignancy, including Japanese adult T cell leukemia.

Diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess.

OBJECTIVE: To assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess. METHODS: Mean platelet volume and other laboratory data were retrospectively investigated. RESULTS: Mean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively. CONCLUSION: Our results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis.

Natriuretic peptide receptor A is related to the expression of vascular endothelial growth factors A and C, and is associated with the invasion potential of tongue squamous cell carcinoma.

Natriuretic peptide receptor A (NPRA) is one of the natriuretic peptide receptors. NPRA has been reported to play a role in the carcinogenesis of various tumours, as well as functional roles in renal, cardiovascular, endocrine, and skeletal homeostasis. The clinicopathological significance of NPRA in tongue squamous cell carcinoma (TSCC) was examined in this study. The overexpression of NPRA was more frequent in TSCC (21/58, 36.2%) than in the normal oral epithelium (0/10, 0%) (P<0.05). It was also more frequently observed in cancers with higher grades according to the pattern of invasion (grades 1-2 vs. grades 3-4, P<0.01). Additionally, there was a tendency towards an association between the N classification and NPRA expression (N0 vs. N1-2, P=0.06). Significant correlations were also observed between the expression of NPRA and that of VEGF-A (P<0.001) and VEGF-C (P<0.001). The high-NPRA expression group had a significantly poorer prognosis, with a 5-year disease-specific survival rate of 39.7%, compared to 97.0% in the low-expression group (P<0.001). Multivariate analysis suggested that the overexpression of NPRA may also be an independent prognostic factor (P<0.05). In conclusion, NPRA is associated with VEGF expression levels, invasion, and metastasis, and may be a prognostic factor in TSCC patients.

Immunoglobulin G heavy-chain allotypes as possible genetic markers for human cancer.

Serum samples from 343 unrelated, healthy Japanese, 194 hepatitis B surface antigen (HBsAg)-positive healthy carriers, 96 patients with primary hepatoma, 91 patients with lung cancer, 94 patients with breast cancer, and 87 patients with gastric cancer were examined for IgG heavy-chain allotypes (Gm). The Gm phenotypes of the sera from patients with breast cancer exhibited a distribution similar to that of the normal controls. However, compared to that of normal controls, the Gm phenotype (1,2,21,13,15,16) was significantly increased in the patients with primary hepatoma(chi 2 (1) = 15.12, corrected P less than 0.01) and in the patients with lung cancer (chi 2 (1) = 10.97, corrected P less than 0.05). Compared to that of normal controls, the haplotype Gm 1,2,21 was significantly increased in the patients with primary hepatoma (chi 2 (1) = 22.34, corrected P less than 0.01). Increased frequency of Gm 1,2,21 in primary hepatoma was also significant compared to that of HBsAg-positive healthy carriers (chi 2 (1) = 9.25, corrected P less than 0.05).

Effect of 1 alpha,25-dihydroxyvitamin D3 on proliferation of activated T-cells and established human lymphotropic virus type I-positive T-cell lines.

The effects of 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] on proliferation and de novo DNA synthesis were studied in the following established human leukemia cell lines: lymphoblastic T-cell lines HPB-ALL, CCRF-HSB-2, p12/lchikawa, and HPB-MLT; adult T-cell leukemia- (ATL) and human lymphotropic virus type I (HTLV-I)-infected T-cell lines HUT102, HUT-102B2, MT-1, MT-2, MJ, C2/MJ, KH-2, KH-2Lo, HPB-CTL-1, and ATN-C1; ATL-derived B-cell lines ATL-BK9 and ATL-BK10; lymphoblastic B-cell line Daudi; and myelocytic-monocytic lineage cell lines HL-60 and U937. 1,25(OH)2D3 inhibited proliferation and de novo DNA synthesis of phytohemagglutinin-P-activated T-cells and certain established HTLV-I-positive T-cells. However, it did not inhibit immature lymphoblastic T- and B-cells or ATL-derived B-cells. The degree of inhibition depended on the dose of 1,25(OH)2D3 and the heterogeneity of the established HTLV-I-positive T-cells. KH-2 and subclone KH-2Lo were markedly inhibited, and HPB-CTL-1 was moderately inhibited. Marked inhibition of DNA synthesis in KH-2Lo cells was observed in the proliferative phase of the cell cycle. No inhibition of KH-2Lo proliferation or expression of interleukin-2 and transferrin receptor was noted after removal of 1,25(OH)2D3 from the culture medium. 1,25(OH)2D3 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced multinucleated cell formation of various HTLV-I-positive T-cell lines and TPA-induced HTLV-I p19 expression in KH-2Lo cells.