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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 253 records · Page 14Linked to original sources

Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies.

Using the vesicular stomatitis virus (VSV) pseudotype system, we studied the functional properties of the Ebola virus glycoprotein (GP). Amino acid substitutions at the GP cleavage site, which reduce glycoprotein cleavability and viral infectivity in some viruses, did not appreciably change the infectivity of VSV pseudotyped with GP. Likewise, removal of two acylated cysteine residues in the transmembrane region of GP showed no discernible effects on infectivity. Although most filoviruses are believed to target endothelial cells and hepatocytes preferentially, the GP-carrying VSV showed greater affinity for epithelial cells than for either of these cell types, indicating that Ebola virus GP does not necessarily have strong tropism toward endothelial cells and hepatocytes. Finally, when it was used to screen for neutralizing antibodies against Ebola virus GP, the VSV pseudotype system allowed us to detect strain-specific neutralizing activity that was inhibited by secretory GP (SGP). This finding provides evidence of shared neutralizing epitopes on GP and SGP molecules and indicates the potential of SGP to serve as a decoy for neutralizing antibodies.

Acylation↗

Postgastrectomy polyneuropathy with thiamine deficiency.

OBJECTIVE: Polyneuropathy has been reported after gastrectomy performed to treat various lesions. Although thiamine deficiency is a possible cause of this neuropathy, the pathogenesis still remains to be clarified. Seventeen patients with peripheral neuropathy with thiamine deficiency after gastrectomy are described. METHODS: Seventeen patients with polyneuropathy after gastrectomy accompanied by thiamine deficiency were selected. Patients were restricted to those with total or subtotal gastric resection to treat ulcer or neoplasm. Patients who had undergone operations to treat morbid obesity were excluded. RESULTS: Intervals between the operation and onset of neuropathy varied from 2 months to 39 years. Most patients did not seem malnourished. Serum concentrations of B vitamins other than thiamine were nearly normal. Symmetric motor-sensory polyneuropathy, predominantly involving the lower limbs, had progressed over intervals varying from 3 days to 8 years. Relative degrees of motor and sensory impairment also varied extensively. Some cases that progressed rapidly mimicked Guillain-Barré syndrome. Electrophysiological and pathological findings were those of axonal neuropathy. Substantial functional recovery from polyneuropathy was seen in most patients by 3 to 6 months after initiating thiamine supplementation. Motor recovery was better than sensory recovery. CONCLUSIONS: Various symptoms were seen in patients with postgastrectomy neuropathy. Thiamine deficiency should be considered in the differential diagnosis of motor-sensory polyneuropathy after gastrectomy.

Activities of Daily Living↗

Encoding of different aspects of afferent activities by two types of cells in the corpus glomerulosum of a teleost brain.

The corpus glomerulosum (CG) is an expansive nucleus in acanthopterigian teleosts that has been suggested to be involved in vision-related information processing and the control of the hypothalamic function. The CG has only two types of constituent cells, the large cell and the small cell, and well-defined afferent/efferent fiber connections. One of the three types of teleostean CG, type III has additional outstanding morphological characters: clearly laminated organization and giant (>50 microm in diameter) tips of postsynaptic dendrites. Although such histological architecture is potentially advantageous for the study of information processing in a brain nucleus based on the physiological properties of identified cells and synapses, previous studies on the CG have been limited to anatomy. In this study, we developed a slice preparation of the type III CG in a teleost, Stephanoplepis cirrhifer, and studied the morphology and physiology of individual cells and synaptic transmission by means of dendritic intracellular and somatic whole cell recordings. The characteristic morphology of the two types of cells was revealed by intracellular staining. While both of them received similar glutamatergic and GABAergic projections from the nucleus corticalis mediated by AMPA, N-methyl-D-aspartate, and GABA(A) receptors, they showed quite distinctive firing properties and postsynaptic responses with current injection and synaptic inputs: the large cell fired a single spike, and the small cell fired a spike train whose frequency was dependent on the stimulus intensity. Furthermore, the large cell showed low-pass temporal filtering properties with paired stimuli. These results suggest that the large cell and the small cell may encode different aspects of the corticalis activities.

Action Potentials↗

Brain structures of a medaka mutant, el (eyeless), in which eye vesicles do not evaginate.

Eye development and brain structures of a mutant teleost fish were investigated. The el (eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.

Animals↗

Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa.

OBJECTIVE: We examined cell cycle and cell death biomarker trends with the normal-dysplasia-carcinoma sequence of the oral epithelia analyzing the pathological significance of a new biomarker, minichromosome maintenance 2 (MCM2). METHODS: This study analyzed 12 patients with normal oral epithelia, 69 with dysplasia, and 35 with squamous cell carcinoma (SCC); in 13 patients, SCCs were preceded by dysplasia. The sections were immunostained for MCM2, Ki-67, P53, P27(Kip1) and P21(CIP1/WAF1), and conducted by TUNEL methods. Western blot analysis of MCM2 was performed in the 4 human cultured oral SCCs, all of which showed the expression. RESULTS: Significantly higher labeling indices (LI; %) of MCM2, Ki-67, and P53, as well as lower LI of TUNEL indices (TI; %), P27, and P21 were noted in the SCCs than in the dysplasias. The 13 dysplasias developed SCC with significantly higher LI of MCM2 and P53, and lower LI of P21 than the other dysplasias (each p < 0.05). The LI of MCM2, P21 and the TI were not correlated with P53 expression. CONCLUSIONS: Oral dysplasia was characterized by lower cell proliferation and a higher frequency of cell death compared to SCCs. The higher LI of MCM2 and P53 and the lower LI of P21 might predict malignant transformation of oral dysplasia. MCM2 is regulated via a P53-independent pathway, and a useful biomarker of proliferating cells.

Apoptosis↗

Transurethral holmium: YAG laser prostatectomy using a side-firing fiber for bladder outlet obstruction due to benign prostatic enlargement: urodynamic evaluation of surgical outcome.

OBJECTIVES: To prospectively assess the efficacy of transurethral holmium (Ho):YAG laser prostatectomy using a side-firing fiber in patients with bladder outlet obstruction due to benign prostatic enlargement (BPE) from the standpoint of urodynamics. METHODS: 32 male patients with BPE aged 53-83 (mean 69.4) years were operated on. All patients, excluding 3 with urinary retention, were evaluated with the International Prostatic Symptom Score (IPSS), Quality of Life (QOL) score and uroflowmetry up to 12 months postoperatively, and a pressure/flow study was performed before and 3 months after the operation. RESULTS: The total IPSS score, QOL score, average and maximum flow rates improved significantly (p<0.0001) at 12 months postoperatively. In the pressure/flow study, detrusor opening pressure, maximum detrusor pressure, detrusor pressure at maximum flow, minimum urethral opening pressure, and Abrams-Griffiths number decreased significantly (p<0.0001, p = 0.0001, p<0.0001, p = 0.0019 and p<0.0001, respectively) 3 months postoperatively. Detrusor instability disappeared in 12 of 17 patients and remained in 2. CONCLUSIONS: Transurethral Ho:YAG laser prostatectomy was found to be effective for the treatment of bladder outlet obstruction due to BPE.

Aged↗

Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no correlation with p53 expression and apoptosis.

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.

Acid Anhydride Hydrolases↗

Isolation, characterization, and chromosome mapping of a human A-C1 Ha-Ras suppressor gene (HRASLS).

Recently, we cloned a cDNA encoding a novel mouse protein, named A-C1, by differential display between two mouse cell lines, embryonic fibroblast C3H10T1/2 and chondrogenic ATDC5. Mouse A-C1 has homology with a ras-responsive gene, rat Ha-rev107 (Hrasls), and modulates a Ha-ras-mediated signaling pathway. Here, we report a cDNA encoding a human homolog of mouse A-C1. The deduced amino acid sequence of human A-C1 consists of 168 amino acids, and shows 83% identity with that of mouse A-C1. Human A-C1 mRNA was expressed in skeletal muscle, testis, heart, brain, and thyroid in vivo. Moreover, expression of human A-C1 mRNA was detected at a high level in human osteosarcoma-derived U2OS cells in vitro. By FISH analysis the human A-C1 gene (HRASLS) was mapped to human chromosome 3q28--> q29.

Amino Acid Sequence↗

Fiber connections of the nucleus isthmi in the carp (Cyprinus carpio) and tilapia (Oreochromis niloticus).

The nucleus pretectalis (NP) is a prominent nucleus in the percomorph pretectum and has been shown to project to the nucleus isthmi in the filefish by an HRP tract-tracing method [Ito et al., 1981], but a homologous nucleus to the NP is apparently lacking in ostariophysans. The present study examined fiber connections of the nucleus isthmi in an ostariophysan teleost, the carp (Cyprinidae, Cyprinus carpio), to identify a nucleus homologous to the percomorph nucleus pretectalis. Identical studies in a percomorph tilapia (Cichlidae, Oreochromis niloticus) were also performed. Injections of biotinylated dextran amine (BDA) or biocytin to the carp nucleus isthmi labeled cells in the ipsilateral optic tectum and nucleus ruber of Goldstein [1905]. Labeled tectal neurons were located in the stratum periventriculare (SPV) and the stratum fibrosum et griseum superficiale (SFGS). The somata in the SPV were pyriform and those in the SFGS were fusiform. No labeled cells were found in the pretectum. Labeled terminals were seen in the ipsilateral nucleus pretectalis superficialis pars parvocellularis (PSp), optic tectum, and bilateral nucleus ruber. Terminals in the nucleus ruber appear to come from tectal neurons in the SFGS labeled by isthmic injections. Thus the nucleus isthmi has reciprocal fiber connections with the ipsilateral optic tectum, receives projections from the ipsilateral nucleus ruber, and projects to the ipsilateral PSp. The nucleus pretectalis homologue is apparently absent in the carp. Studies in tilapia showed that the nucleus isthmi receives bilateral projections from the NP and optic tectum. In addition, the present study revealed a previously unknown afferent from the nucleus ruber to the percomorph nucleus isthmi. The tilapia nucleus isthmi projects to the same targets as in the carp. Isthmic projection neurons in the tilapia optic tectum were located in the SPV and pyriform with a similar shape to the carp SPV neurons that project to the nucleus isthmi. No labeled cells were found in the SFGS of tilapia optic tectum. The fusiform neurons in the SFGS of the carp optic tectum possess various hodological similarities with the NP and may correspond to the NP neurons of percomorphs.

Animals↗

Factors affecting psychiatric nurses' intention to leave their current job.

Using the National Institute for Occupational Safety and Health job stress questionnaire, the authors examined psychiatric nurses' intention to leave their job in relation to their perceived risk of assault, their job satisfaction, and their supervisory support. Respondents were 1,494 nurses (response rate, 76.5 percent) employed in 27 psychiatric hospitals in Japan. Forty-four percent reported intention to leave their job, and 89 percent of those perceived a risk of assault. Younger age, fewer previous job changes, less supervisory support, lower job satisfaction, and more perceived risk of assault were significant predictors of intention to leave. Organizational efforts are necessary to retain frontline professional staff.

Adult↗

Immunodominant region of Actinobacillus actinomycetemcomitans 40-kilodalton heat shock protein in patients with rheumatoid arthritis.

Bacterial heat shock proteins have been implicated in the pathogenesis of several diseases, and the immunological relationship between rheumatoid arthritis (RA) and Escherichia coli DnaJ has been reported. Since there are similarities in the tissue destruction process of RA and periodontitis, we examined the reactivities of antibodies in sera from RA patients to the DnaJ protein from Actinobacillus actinomycetemcomitans. An enzyme-linked immunosorbent assay showed that IgG titers to the N-terminal conservative region of the DnaJ are significantly higher in RA patients compared with the healthy controls (p < 0.05). Furthermore, we examined IgG titers of disease controls to determine the specificity of the immune responses to this region in RA patients. The difference between RA and infectious disease patients was also significant (p < 0.05). These results suggest that the N-terminal region of DnaJ from A. actinomycetemcomitans may contribute to the etiologic analysis of RA.

Adult↗

Testicular germ cell apoptosis in Bcl6-deficient mice.

Bcl6 protein has been detected in testicular germ cells, mainly spermatocytes, of normal mice, but its physiological role is largely unknown. The number of spermatozoa in the cauda epididymis of adult Bcl6-deficient (Bcl6-/-) mice is lower than that of Bcl6+/+ mice. We have found numerous apoptotic spermatocytes at the metaphase I stage with induction of Bax protein in adult Bcl6-/- testes. Developmentally, the incidence of germ cell apoptosis of Bcl6-/- mice was similar to that of Bcl6+/+ mice until six weeks of age and increased after eight weeks of age. The incidence of apoptosis in heterozygous Bcl6+/- mice was also higher than that of Bcl6+/+ mice. Since the activated form of p38 MAP kinase was detected in spermatocytes of adult Bcl6-/- mice, the germ cell apoptosis may be induced by stressors. Treatment of testes of adult Bcl6+/+ mice with a mild hyperthermia resulted in germ cell apoptosis predominantly in metaphase I spermatocytes with induction of Bax protein and activation of p38 MAP kinase and this apoptosis mimics that in adult Bcl6-/- mice. Thus, Bcl6 may play a role as a stabilizer in protecting spermatocytes from apoptosis induced by stressors.

Animals↗

Proanthocyanidins and related compounds: antileishmanial activity and modulatory effects on nitric oxide and tumor necrosis factor-alpha-release in the murine macrophage-like cell line RAW 264.7.

A series of 17 proanthocyanidins and structurally related compounds was tested for activity against Leishmania donovani amastigotes and promastigotes in vitro. Most of the polyphenols significantly inhibited the intracellular survival of L. donovani amastigotes (EC50 0.8-10.6 nM) when compared with the antileishmanial drug Pentostam (EC50 10.6 nM), but all were inactive against the extracellular form (EC50 7.8 to >86 nM). Noteworthy is that all compounds exhibited only moderate or no cytotoxicity against the murine host cells (EC50 7.8 to >56 nM; >25 microg/ml). These polyphenols were further evaluated for immunomodulatory effects on macrophage functions, including release of nitric oxide (NO), tumor necrosis factor-alpha (TNF) and interferon (IFN)-like properties using several functional assays. The results showed that all compounds induced murine RAW 264.7 cells only moderately to release NO (7-26 microM) relative to the reference stimulus IFN-gamma/LPS (119 microM). The TNF-inducing potential of the polyphenols producing 50% lysis in murine L929 cells ranged from absent to 138 U/ml at the host cell subtoxic concentration of 50 microg/ml. The highest TNF-inducing activity was associated with those flavan-3-ols with galloyl groups (98-127 U/ml). For proanthocyanidins, it appeared that an increase in the flavanyl chain length did not enhance the induction of TNF-release (32-86 U/ml and below detection limits for oligomers and polymers, respectively). With interferon-like activities, phylloflavan and a prodelphinidin polymer showed appreciable cytoprotective effects, as reflected by the inhibition of the cytopathic effect of encephalomyocarditis virus on L929 fibroblast cells (38 and 36 U/ml, respectively). All remaining compounds displayed only negligible or moderate protective effects at subtoxic concentrations up to 25 microg/ml (<5 to 12 U/ml). These results indicate that proanthocyanidins and related compounds have favorable antileishmanial activity in vitro and might be considered as beneficial immunological response modifiers provided there are no bioavailability problems.

Adjuvants, Immunologic↗

Effect of calpain on hereditary cataractous rat, ICR/f.

The crystallins in the lenses of ICR/f mutation rat, a known hereditary cataract model, were analyzed during cataractogenesis. Opacification of the mutant lenses was found to be accompanied by changes in crystallin structure and composition, including several deletions of the N-terminals of beta-crystallins and low molecular weight alpha- crystallins. Because similar deletions were observed when the soluble fraction of normal lens protein was incubated with calpain, we considered that calpain could be related to the deletions in mutant lenses. Although measurement of the content of calpain protein by the ELISA method revealed no significant difference between mutant and normal lenses, it was found that the concentrations of Ca2+ and K+ were different between the two lenses and that calpain activity was dependent on both ion concentrations. Endogenous m-calpain in the soluble fraction from normal lenses was activated by addition of 1 mm calcium chloride in the presence of 50 mm KCl (the same concentration as in mutant lenses), and insoluble protein was found in the fraction 1 d after calpain activation. On the other hand, the presence of 120 mm KCl (the concentration in normal lenses) inhibited calpain activity and prevented this insolubilization. These results suggest that calpain in mutant lenses is involved in the proteolysis of crystallins and the progression of cataract formation.

Animals↗

Isoflavonoids from Belamcanda chinensis.

Four new isoflavonoids were isolated along with six known related compounds from a rhizome of Belamcanda chinensis (Iridaceae), and their structures were characterized as 6''-O-p-hydroxybenzoyliridin, 6''-O-vanilloyliridin, 5,6,7,3'-tetrahydroxy-4'-methoxyisoflavone and 2,3-dihydroirigenin, respectively, on the basis of spectroscopic methods and chemical evidence.

Indicators and Reagents↗

Subthreshold stimulation in three types of reentrant supraventricular tachycardia: correlation with the results of catheter ablation.

The effects of subthreshold stimulation (STS) by direct current were investigated in 20 patients with atrioventricular nodal reentrant tachycardia (AVNRT), 27 with atrioventricular reentrant tachycardia (AVRT) and 3 with idiopathic atrial reentrant tachycardia (IART) STS was delivered to each eligible site for ablation prior to radiofrequency application. STS was defined as 'positive' if it could terminate the tachycardia or disrupt the conduction of accessory pathways without myocardial capture and defined as 'negative' if it could not. Radiofrequency ablation was performed irrespective of a positive or negative result from STS and was successful in all 50 patients. Among the 50 successful ablation sites, STS was positive at 26 sites (11 sites in AVNRT, 12 in AVRT and 3 in IART). STS was positive at 4 sites where ablation failed in 3 patients with AVRT and was negative at 8 sites where ablation was successful in 4 patients with AVNRT and 4 with AVRT. The positive and negative predictive value of STS for the detection of the optimal ablation site were, respectively, 100% and 74% in AVNRT, 73% and 72% in AVRT, and both 100% in IART STS-guided mapping is a specific method to predict the successful catheter ablation of reentrant supraventricular tachycardia.

Adolescent↗

Large thrombus in the ascending aorta successfully treated by thrombolysis--an unusual cause of acute massive myocardial infarction.

A 52-year-old woman suffered from acute massive myocardial infarction in association with a large thrombus in the ascending aorta. She was a moderate smoker and was taking hormone supplement therapy for menopausal hormone insufficiency and the contraceptive pill for endometriosis. Cardiac angiography revealed a large mobile filling defect close to the orifice of the left coronary artery, but the left coronary artery could not be visualized. Her hemodynamic condition was impaired so greatly that intraarterial counterpulsation and intravenous thrombolysis was immediately performed. The thrombus dissolved in 1 h and recanalization of the left coronary artery was achieved without serious systemic thromboembolism. She has been doing well with no cardiac events for 7 years. This is the second report of a large thrombus in ascending aorta being the cause of acute myocardial infarction in the whole territory of the left coronary artery, and the first to diagnose such a thrombus antemortem and treat it successfully.

Aorta↗

Circadian variation of the onset of acute myocardial infarction in the Osaka area, 1998-1999: characterization of morning and nighttime peaks.

The onset of acute myocardial infarction (AMI) shows characteristic circadian variations; that is, a definite morning peak related to biologic rhythms and a vague nighttime peak related to socioeconomic factors. The recent economic recession in Japan may change the circadian variation, especially the nighttime peak. This study evaluated the recent circadian variation of AMI in Osaka and specified the patient subgroups showing either a morning or nighttime peak predominantly. Of 1,609 consecutive patients with AMI registered from April 1998 to January 2000, 1,252 whose onset of AMI was definitely identified were studied. The day was divided into six 4-h periods with a morning peak between 08.01 h and 12.00h, and nighttime peak between 20.01 h and 24.00h. When subgroup analysis was performed, female patients aged 65 years or more showed a morning peak alone and male patients aged less than 65 years with an occupation and the habits of cigarette smoking and alcohol intake showed a nighttime peak alone. Thus, in Osaka nighttime socioeconomic factors may currently be more potent triggers of AMI than the morning surges in younger male workers who smoke and drink.

Adult↗