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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 199 records · Page 11Linked to original sources

Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis.

Transgenic flies were established in which ectopic expression of boundary element-associated factor (BEAF) 32A was targeted to the Drosophila eye imaginal disc. The eyes of the adult fly displayed a severe rough eye phenotype. When these eyes were sectioned, most ommatidia were found to be fused and irregularly shaped rhabdomeres were observed. In the developing eye imaginal disc, expression of BEAF32A inhibited differentiation of photoreceptor cells. Expression of BEAF32A also induced extensive apoptosis of eye imaginal disc cells and, consistent with this, co-expression of baculovirus P35 in the eye imaginal disc suppressed the BEAF32A-induced rough eye phenotype. To investigate the effects of BEAF32A on regulation of chromatin structure, genetic crosses of the BEAF32A-overexpressing flies with loss-of-function mutants for genes encoding other boundary element-binding factors or regulators of chromatin structure were conducted. Interestingly, half-dose reduction of the su(Hw) gene strongly enhanced the rough eye phenotype induced by BEAF32A. Furthermore, genetic crosses of the transgenic flies with loss-of-function mutants for genes interacting with Polycomb revealed specific links between BEAF32A and genes such as Distalless and kohtalo, suggesting a relation to the chromatin insulator function of BEAF. In addition, genetic crosses of transgenic flies expressing BEAF32A with a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or suppression of the BEAF32A-induced rough eye phenotype. The transgenic flies established in this study should be useful to identify targets of BEAF32A and its positive or negative regulators in Drosophila.

Animals↗

Strangulated umbilical hernia in a child: report of a case.

Most umbilical hernias in children close spontaneously. Complications associated with umbilical hernias are rarely observed during follow-up. We report herein a 5-month-old girl with a strangulated umbilical hernia. Her umbilicus was hard, reddish, and irreducible. Plain radiography of the abdomen showed signs of mechanical ileus. The patient was thus diagnosed to have a strangulated umbilical hernia. A 5-cm section of the ascending colon and a 5-cm section of the terminal ileum, as well as the cecum and appendix, were congested, edematous, and erythematous, and together were enclosed by a firm hernial ring. A closure of the fascial defect and umbilicoplasty were performed. The postoperative course was uneventful. In patients with infantile umbilical hernias, strangulation may occur as the fascial defect decreases in size.

Constriction, Pathologic↗

Effects of dietary defatted squid on cholesterol metabolism and hepatic lipogenesis in rats.

Male Sprague-Dawley rats were fed a cholesterol-free (Exp. 1) or cholesterol-supplemented (Exp. 2) diet containing 20% casein (control group) or 15% defatted squid and 5% casein (defatted squid group), as protein, for 14 d. Serum and hepatic cholesterol concentrations were lower in rats fed defatted squid than in those fed casein in both cholesterol-free (-20%, P < 0.05 and -15%, P < 0.05, respectively) and cholesterol-supplemented (-25%, P < 0.05 and -15%, P < 0.05, respectively) diets. Hepatic triglyceride concentration was lower in the defatted squid than in the control groups in both cholesterol-free (-51%, P< 0.05) and cholesterol-supplemented diets (-38%, P < 0.01). The activities of cytosolic fatty acid synthase and the NADPH-generating enzymes, malic enzyme and glucose-6-phosphate dehydrogenase, in the liver were lower in the defatted squid than in the control groups in both cholesterol-free (-21%, P< 0.01, -33%, P < 0.05, and -33%, P < 0.01, respectively) and cholesterol-supplemented diets (-34%, P < 0.05, -57%, P < 0.05, and -67%, P < 0.05, respectively). The activity of mitochondrial carnitine palmitoyltransferase in the liver was comparable between the control and defatted squid groups. The activity of Mg2+-dependent phosphatidate phosphohydrolase in the liver cytosol was lower in the defatted squid (-9%, P < 0.05) than in the control groups only in the cholesterol-free diet. Fecal excretion of total steroids was stimulated by the feeding of defatted squid in both cholesterol-free (+77%, P < 0.005) and cholesterol-supplemented diets (+29%, P < 0.01). These results suggest that the nonlipid fraction of squid exerts a hypocholesterolemic effect by increasing the excretion of total steroids in feces. The fraction also induces a triglyceride-lowering activity in the liver by decreasing hepatic lipogenesis.

Animals↗

Experimental analysis of a new flexible neck model for low-speed rear-end collisions.

Whiplash injuries occur frequently in rear-end automobile accidents even at low-speed. The hybrid III dummy has been used for various tests in order to investigate the mechanism of whiplash injuries. However, since this dummy neck is too rigid for low-speed collisions, we developed a new flexible neck model for low-speed rear-end collisions. Each component of this new flexible neck model is made of polymers with material properties close to those of the human body. Sled tests were conducted to measure the displacements of cervical vertebrae of the new flexible neck model at 11 km/h. The figures of s-shape and shear displacement in the plane of the intervertebral disks were observed, and it was recognized that shear displacement resulted from the inconsistency of motion between the head and neck. The regions of shear displacement agreed well with the statistics of the critical regions where whiplash injuries have frequently occurred. It is assumed that shear displacement is one of the causes of the mechanism of whiplash injuries.

Accidents, Traffic↗

Presenilin binding protein is associated with neurofibrillary alterations in Alzheimer's disease and stimulates tau phosphorylation.

A novel presenilin binding protein, PBP, has recently been identified. PBP is localized to the particulate fraction of extracts of Alzheimer's disease brain but is found in the soluble fractions of brain from age matched normal controls. It is shown here that PBP is associated with neurofibrillary tangles in Alzheimer's disease brain. In addition, the expression of PBP increases the phosphorylation of tau in cultured cells. Therefore PBP may have a regulatory role in tau phosphorylation and in the genesis of neurofibrillary tangles.

Aged↗

Characterization of cardiac myocyte and tissue beta-adrenergic signal transduction in rats with heart failure.

OBJECTIVE: The cellular basis of alterations in beta-adrenergic signal transduction in rats with chronic heart failure (CHF) remains unclear. The aim of the present study was to examine this signal transduction system in isolated ventricular cardiomyocytes of rats with CHF. We focused on changes in the levels of stimulatory (Gs) and inhibitory G-proteins (Gi). METHODS: CHF was induced in male Wistar rats by coronary artery ligation (CAL). Hemodynamic and biochemical parameters were measured 8 weeks after CAL. Alterations in contractile function and Ca(2+) transients via beta-adrenergic receptor signaling of cardiomyocytes isolated from rats with CHF were characterized by simultaneous measurements of cell shortening and fura-2 fluorescence intensity. RESULTS: Coronary artery-ligated rats showed symptoms of CHF, such as decreased contractile function, increased left ventricular volume, decreased chamber stiffness, and about 40% infarct formation of the left ventricle, by 8 weeks after surgery. The contractile function and Ca(2+) dynamics of cardiomyocytes from the rats with CHF remained normal under basal conditions. Only cardiac cell length was increased. The responses of peak shortening, fura-2 fluorescence ratio amplitude, and cAMP content to beta-adrenoceptor stimulation were reduced in cardiomyocytes of the rats with CHF, whereas direct stimulation of adenylate cyclase did not affect the response of these variables. Cardiomyocyte Gsalpha protein was decreased, whereas no changes in Gialpha proteins were seen in these cells. Increases in tissue Gsalpha and Gialpha proteins in the scar zone were detected. The results on tissue levels of collagen and G-proteins in the viable left ventricle appeared to depend on the presence of nonmyocytes. CONCLUSIONS: The results suggest that impaired contractile function of cardiomyocytes is unlikely to account for global LV contractile dysfunction, and that down-regulation of beta-adrenoceptors occurs in cardiomyocytes per se. The difference in changes of G-protein between the cardiomyocyte and myocardial tissue suggests an appreciable contribution of nonmyocytes to myocardial G-protein levels.

Animals↗

Dystrophin-deficient myocardium is vulnerable to pressure overload in vivo.

OBJECTIVE: Dystrophin provides mechanical reinforcement to the membranes of myocytes. Dystrophin abnormalities are known to cause cardiomyopathy and skeletal muscle disorders; however, the pathogenesis of these abnormalities remains unclear. Dystrophin-deficient skeletal muscle is vulnerable to stresses such as stretch and hypo-osmotic shock. We investigated whether the myocardium of dystrophin-deficient (mdx) mice shows increased vulnerability to acute pressure overload in vivo. METHODS AND RESULTS: Abdominal aortic banding was performed in 12-week-old mdx and control mice. The aortic pressure was measured by cannulation of the right carotid artery at the time of sacrifice. Systolic pressures in mdx mice at 0, 1, 2, 7 and 14 days after aortic banding were 100 +/- 11, 119 +/- 7, 123 +/- 4, 134 +/- 11 and 130 +/- 10 mmHg, respectively. Microscopic analysis revealed focal lesions in the left ventricular wall in banded mdx mice. These lesions consisted of damaged myocytes and inflammatory cells, and also of fibrosis at a late stage. Similar lesions were not observed in non-banded or banded control mice. The proportion of areas of lesions to total left ventricular area increased over time: 1.0 +/- 0.6% in mdx mice without aortic banding (sham, n = 6), and 1.7+/-1.4% 1 day (n = 6, vs. sham, NS), 2.6 +/- 1.9% 2 days (n = 7, vs. sham, P < 0.05), 6.3+ /- 6.5% 7 days (n = 13, vs. sham, P < 0.05) and 9.9 +/- 8.3% 14 days after aortic banding (n=15, vs. sham, P < 0.01). Furthermore, linear regression analysis revealed a significant correlation between percentage of lesion area and systolic pressure in mdx mice (P < 0.05). CONCLUSION: Dystrophin-deficient myocardium is more vulnerable than normal myocardium to pressure overload in vivo. This result has two clinical implications: (1) the patients with dystrophynopathy, such as the Duchenne and the Becker types of muscular dystrophy and X-linked type of dilated cardiomyopathy, who develop arterial hypertension should be treated aggressively, and (2) they should avoid stresses that elevate blood pressure.

Animals↗

Early noun lexicons in English and Japanese.

Previous research suggests that children learning a variety of languages acquire similar early noun vocabularies and do so by similar and universal processes. We report here results from two studies that show differences in the early noun learning of English- and Japanese-speaking children. Experiment 1 examined the relative numbers of animal names and object names in vocabularies of English-speaking and Japanese-speaking children. English-speaking children's vocabularies were heavily lopsided with many more object than animal names whereas Japanese-speaking children's vocabularies were more evenly balanced. Experiment 2 used a novel noun extension task to examine what young children know about the different organizations of animal and artifact categories. The results suggest that early learners of English but not Japanese over-generalize what they know about object categories to animal categories. The role of culture, input and linguistic structure in early noun acquisitions is discussed.

Analysis of Variance↗

Power Doppler signals after percutaneous ethanol injection therapy for hepatocellular carcinoma predict local recurrence of tumors: a prospective study using 199 consecutive patients.

BACKGROUND/AIMS: This study was prospectively conducted to elucidate the relationship between pre-/post-treatment power Doppler signals of hepatocellular carcinoma (HCC) and local recurrence. METHODS: One hundred ninety-nine consecutive patients with 359 HCC lesions receiving percutaneous ethanol injection therapy (PEIT) as a first-line option were enrolled. Arterial power Doppler signals in the tumor were found in 130 nodules, but not detected in 229. After confirmation of complete tumor necrosis on dynamic CT, Doppler signals in nodules were re-evaluated. Patients received periodical examinations to detect HCC recurrence. RESULTS: Local HCC recurrence was observed in 36 lesions; 22%(28/130) of the pretreatment signal positive lesions, in contrast to 3.5% (8/229) of the pretreatment signal negative lesions (P < 0.01). Out of 130 signal positive nodules, signals disappeared in 120 (92%) after PEIT, but were present in ten (8%). During the 25-month follow up, local recurrence was detected in 19 (16%) from the former, in contrast to nine (90%) from the latter (P < 0.001). Uni- and multivariate Cox analysis revealed that the presence of pre-/post-treatment power Doppler signals, histological differentiation and tumor number were independent factors for local recurrence. However, 3-year recurrence rate of new lesions was 51%, but no predictors were identified. CONCLUSIONS: Residual Doppler signals in tumor after PEIT were related to the local HCC recurrence.

Adult↗

A surgical simulation system of skin sutures using a three-dimensional finite element method.

OBJECTIVE: To establish a surgical simulation system of skin sutures using a three-dimensional finite element method. DESIGN: Three-dimensional finite element models were developed from point data obtained with a rapid three-dimensional surface-measuring device and postoperative profiles were evaluated using these models. BACKGROUND: Since suturing a wound may result in undesirable skin extrusion, it is important to make the extrusion as inconspicuous as possible. We have investigated a means of determining appropriate suture methods to decrease the extrusion. METHODS: Affected body parts were measured non-invasively with a rapid three-dimensional surface-measuring device. Finite element models were prepared, and an appropriate method for reducing skin extrusion was evaluated by attempting various suturing methods. RESULTS: Two kinds of finite element models were prepared: a conventional spindle model and a modified S-shape model. The height of the extrusion of the modified S-shape model was decreased by 40% in comparison with that of the spindle model. These results agreed with clinical findings. CONCLUSIONS: Due to this surgical simulation system of skin sutures, with a rapid three-dimensional surface-measuring device and three-dimensional finite element analysis, it was possible to design an appropriate suturing method and to evaluate the postoperative skin profiles. The modified S-shape suture method would be a recommendable method. RELEVANCE: Using this surgical simulation system of skin sutures, a surgeon can evaluate an appropriate suturing method before operation. It is expected that this system will reduce a surgeon's labor.

Computer Simulation↗

Vascular endothelial growth factor levels in pleural and peritoneal fluid in Meigs' syndrome.

We report that we found differences in changes in vascular endothelial growth factor (VEGF) levels in pleural effusion and ascites after removal of ovarian tumor complicated by Meigs' syndrome. Postoperative VEGF levels decreased in the patient's pleural fluid but not in the peritoneal fluid. The mechanism of the development of the pleural effusion and ascites in Meigs' syndrome may differ.

Ascitic Fluid↗

WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection.

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors. The physiological role of WSX-1, which is expressed mainly in T cells, was investigated in gene-targeted WSX-1-deficient mice. IFN-gamma production was reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation in vitro to induce Th1 differentiation but was normal in fully differentiated and activated WSX-1(-/-) Th1 cells that had received secondary stimulation. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infection, showing impaired IFN-gamma production early in the infection. However, IFN-gamma production during the later phases of the infection was not impaired in the knockout. WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus, WSX-1 is essential for the initial mounting of Th1 responses but dispensable for their maintenance.

Animals↗

Effect of a mutant form of IkappaB-alpha on 5-fluorouracil-induced apoptosis in transformed human salivary gland cells.

Increasing evidence indicates that transcription factor NF-kappaB may play a role in cell survival, and that some chemotherapeutic agents activate NF-kappaB, while inhibition of NF-kappaB renders cells sensitive to these drugs. 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. However, it still remains uncertain whether 5-FU treatment in combination with the inhibition of NF-kappaB largely exerts an anti-proliferative effect on the growth of neoplastic human salivary gland cells. Thus, we investigated whether NF-kappaB suppression in transformed human salivary gland (NS-SV-AC) cells leads to a marked reduction in cell growth in response to 5-FU treatment. Our results demonstrated that under unstimulated conditions, the ability of cell growth in the super-repressor form of IkappaB-alpha (srIkappaB-alpha) cDNA-transfected cell clones (ACMT-6 and -7) was significantly lower than that in the empty vector-transfected cell clone (ACpRc-1). In addition, the growth inhibition caused by 5-FU was greatly enhanced in ACMT-6 and -7 as compared to ACpRc-1. Based on fractional inhibition analysis, this growth inhibition was due to an additive effect of both inhibitors. Electrophoretic mobility shift assay revealed that NF-kappaB activity in these cell clones was not affected by treatment with 5-FU. Accordingly, our data provide evidence that the combination of 5-FU and NF-kappaB suppression cooperatively functions in the growth inhibition of NS-SV-AC cells.

Antimetabolites, Antineoplastic↗

Cisplatin inhibits the expression of X-chromosome-linked inhibitor of apoptosis protein in an oral carcinoma cell line.

Cisplatin is known to activate caspase-3 through the mitogen-activated kinase (MAPK) pathway. We found that X-chromosome-linked inhibitor of apoptosis protein (XIAP), a direct inhibitor of caspase-3, 7, and 9, is constitutively expressed in a cell line of oral squamous cell carcinoma, KOSC-2. Cisplatin treatment of the cells inhibited the expression of XIAP, and this was associated with DNA fragmentation. Overexpression of XIAP, by a transfection experiment, inhibited the cisplatin-induced apoptosis. We conclude that cisplatin induces apoptosis mediated not only by the activation of MAPK pathway but by the inhibition of XIAP.

Antineoplastic Agents↗

Characteristics of antitumour activity of cepharanthin against a human adenosquamous cell carcinoma cell line.

Cepharanthin is one of the biscoclaurine alkaloids widely used for treatment of many acute and chronic diseases; snakebite, bronchial asthma, alopecia areata, leukopenia during radiation therapy or anticancer treatment. Recently, it has been reported that cepharanthin exerts antitumour effects by increasing immunological competence of the host or apoptosis-inducing activity. In this study, we examined the antitumour effects of cepharanthin against a human adenosquamous cell carcinoma cell line (TYS). Treatment of TYS cells with cepharanthin (10 approximately 20 microg/ml) resulted in a significant suppression of cell growth. Moreover, it was found by the flow cytometry analysis, nick end labelling or agarose gel electrophoresis, that G1 arrest and DNA fragmentation occurred in cepharanthin-treated cells. In addition, it was detected that induction of p21(WAF1) protein and activation of caspase 3 protype, which is one of Interleukin-1beta converting enzyme (ICE) family proteases, were detected by Western blotting. The TYS tumour-bearing nude mice were treated with cepharanthin, which was administered subcutaneously (20 mg/kg/day). The cepharanthin treatment results in a significant suppression of tumour growth and an induction of apoptosis. These findings suggest that cepharanthin induces G1 arrest via expression of p21(WAF1) and apoptosis through caspase 3.

Alkaloids↗

Comparison of cytokine-inducing activity in a lipoteichoic acid-related molecule isolated from a penicillin-killed group A Streptococcus and from untreated bacteria.

We previously generated a monoclonal antibody, TS-2, that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432, a penicillin-killed streptococcal preparation [J. Immunother. 13 (1993) 232]. Expression of the TS-2-binding antigen was markedly higher in the cell wall of the penicillin-treated Streptococcus pyogenes (OK-432) than in the untreated bacteria (Su-BBM). We here isolated the antigens from OK-432 and Su-BBM, designated OK-PSA and Su-PSA, respectively. OK-432 markedly induced IFN-gamma and interleukin (IL)-18 as compared with Su-BBM in human peripheral blood mononuclear cells (PBMC). Furthermore, all of the Thl-type and Th1-inducing cytokines tested [IFN-gamma, tumor necrosis factor (TNF)-alpha, IL-12 and IL-18] were secreted by OK-PSA-stimulated PBMC far better than by Su-PSA-treated PBMC. In addition, the cytolytic activities of the PBMC were accelerated by the stimulation with OK-432 or OK-PSA far better than by the stimulation with Su-BBM or Su-PSA. These findings strongly suggested that OK-PSA is a highly important molecule of OK-432 and may be a useful immunotherapeutic agent for the patients with malignant diseases as a potent Th inducer. It was also shown that penicillin treatment effectively enhances OK-PSA-induced anti-cancer immunity.

Caspase 1↗