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Biomedical subjects

J Ishii

Publications and source records attributed to J Ishii.

At least 19 recordsLinked to original sources

Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription.

Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.

Base Sequence↗

A comparison of brachytherapy and surgery for the treatment of stage I-II squamous cell carcinoma of the tongue.

The treatment method for early stage tongue cancer is still controversial in Japan. The aim of this study is to compare the prognosis for patients with early tongue cancer treated with brachytherapy and surgery. A retrospective study was conducted to compare the efficacy of low-dose-rate brachytherapy (LDR), high-dose-rate brachytherapy (HDR), and surgery for early tongue cancer. A total of 180 patients with stage I-II tongue cancer were divided into three treatment groups: LDR (78), HDR (26), and surgery (71). Local recurrence was seen in thirteen patients (17%) of the LDR, nine (35%) of the HDR, and four (6%) of the surgery group. After salvage therapy, final local cure was obtained for 71 patients (91%) of the LDR, 22 (85%) of the HDR, and 71 (100%) of the surgery group. Neck failure was recorded for eight patients in the LDR, six in the HDR, and three in the surgery group. The respective 5-year overall survival rates for the LDR, HDR and surgery groups were 84.0%, 72.9%, 95.4% for stage I, and 72.2%, 51.5%, 93.8% for stage II. These findings show that surgery is the optimal treatment method for patients with stage I-II tongue cancer.

Adolescent↗

Experimental study on the morphological and functional recovery following partial glossectomy in rabbits: a comparison between CO2 laser and electrocautery.

OBJECTIVE: The aim of the present study was to evaluate and compare the morphological and functional recovery following partial glossectomy in rabbits with the CO(2) laser and electrocautery. METHODS: Partial glossectomy with the CO(2) laser or electrocautery in rabbits was performed to investigate changes in the body weight and tongue width after surgery. The study models were classified into three groups. In group 1, the excised edges of the wound were left unsutured after partial glossectomy with the CO(2) laser. In group 2, the wound was closed after CO(2) laser surgery. In group 3, as a control group, the wound was closed after partial glossectomy with electrocautery. The specimens of the tongues obtained from the rabbit were microscopically assessed. RESULTS: No significant differences were found in the percent change in the body weight among the three groups. There was a significant difference in the tongue width between groups 1 and 3 at each time point: 2 weeks (p < 0.05), 4 weeks (p < 0.01), and 8 weeks (p < 0.001) postoperatively. Furthermore, there was a significant difference in the tongue width between groups 2 and 3 at 8 weeks (p < 0.02) postoperatively. Histologically, the scar tissue of the wound was extensive in the control group, although it was localized in the laser group. CONCLUSION: Postoperative dysfunction was reduced when excised edges were left unsutured after partial glossectomy with the CO(2) laser.

Animals↗

Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.

Adolescent↗

Laser surgery as a treatment for oral leukoplakia.

Various treatment procedures for oral leukoplakia have been reported. However, after some treatments, oral leukoplakia show recurrence and/or malignant transformation, even following complete resection. Furthermore, patients with oral leukoplakia may develop new lesions in other oral cavity locations. Laser surgery for oral mucosal lesions has been reported to have many advantages, and it is widely used in the treatment of oral leukoplakia. In previous studies, recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery. We reviewed the records of oral leukoplakia patients treated with laser surgery to assess its clinical usefulness. It has been reported that the rate of recurrence was 7.7-38.1%, while malignant transformation was 2.6-9% for oral leukoplakia treated with laser surgery. In the present study, there was 29.3% recurrence and 1.2% malignant transformation after laser surgery. This was similar to previous findings. This suggests that non-homogeneous leukoplakia on nonkeratinized epithelia, i.e. the tongue mucosa has a high risk for malignant transformation, so lesions should be excised after detecting abnormal epithelia using vital tissue staining. The wound healing process after laser surgery was satisfactory and no significant complications were observed. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction: laser surgery is an excellent procedure that is able to overcome these problems.

Adult↗

Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis.

BACKGROUND: It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS: We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS: The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION: cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

Adult↗

Infection of human lung fibroblasts with Epstein-Barr virus causes increased IL-1beta and bFGF production.

An association between Epstein-Barr virus (EBV) infection and fibroblast proliferation in the interstitial spaces of the lung has been suggested in idiopathic interstitial pneumonia. In this study we show that EBV can infect human lung fibroblasts in vitro. A primary-cultured human lung fibroblast cell line, designated CCD-32Lu, expressed EBV nuclear antigen 1 after coculture with lethally irradiated EBV producing cells. The infection further induced CCD-32Lu cells to produce the fibrogenic cytokines basic fibroblast growth factor (bFGF) and interleukin-1beta. These findings indicate that lung fibroblasts may be a target for EBV infection and suggest that EBV may play a role in increased production of these cytokines and induce fibroblast proliferation in idiopathic interstitial pneumonia.

Antibodies, Blocking↗

Theoretical and experimental dissection of gravity-dependent mechanical orientation in gravitactic microorganisms.

Mechanisms of gravitactic behaviors of aquatic microorganisms were investigated in terms of their mechanical basis of gravity-dependent orientation. Two mechanical mechanisms have been considered as possible sources of the orientation torque generated on the inert body. One results from the differential density within an organism (the gravity-buoyancy model) and the other from the geometrical asymmetry of an organism (the drag-gravity model). We first introduced a simple theory that distinguishes between these models by measuring sedimentation of immobilized organisms in a medium of higher density than that of the organisms. Ni2+-immobilized cells of Paramecium caudatum oriented downwards while floating upwards in the Percoll-containing hyper-density medium but oriented upwards while sinking in the hypo-density control medium. This means that the orientation of Paramecium is mechanically biased by the torque generated mainly due to the anterior location of the reaction center of hydrodynamic stress relative to those of buoyancy and gravity; thus the torque results from the geometrical fore-aft asymmetry and is described by the drag-gravity model. The same mechanical property was demonstrated in gastrula larvae of the sea urchin by observing the orientation during sedimentation of the KCN-immobilized larvae in media of different density: like the paramecia, the gastrulae oriented upwards in hypo-density medium and downwards in hyper-density medium. Immobilized pluteus larvae, however, oriented upwards regardless of the density of the medium. This indicates that the orientation of the pluteus is biased by the torque generated mainly due to the posterior location of the reaction center of gravity relative to those of buoyancy and hydrodynamic stress; thus the torque results from the fore-aft asymmetry of the density distribution and is described by the gravity-buoyancy model. These observations indicate that, during development, sea urchin larvae change the mechanical mechanism for the gravitactic orientation. Evidence presented in the present paper demonstrates a definite relationship between the morphology and the gravitactic behavior of microorganisms.

Animals↗

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. RESULTS: Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Aldehyde Reductase↗

F-wave latency serves as the most reproducible measure in nerve conduction studies of diabetic polyneuropathy: multicentre analysis in healthy subjects and patients with diabetic polyneuropathy.

AIMS/HYPOTHESIS: For use in future drug development for diabetic polyneuropathy, we conducted multicentre trials to assess the reproducibility of nerve conduction studies. METHODS: All measurements were repeated twice at a time interval of 1-4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic polyneuropathy. Using a standardised method, 32 centres participated in the study of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and recording the compound action potential from abductor policis and adductor hallucis for measuring amplitude, terminal latency and minimal F-wave latency. For sensory conduction studies, sensory nerve action potentials were recorded antidromically from the second digit and the posterior aspect of the lateral malleous after distal stimulation of the left median and sural nerves. We also calculated motor conduction velocity, F-wave conduction velocity and sensory conduction velocity. The relative intertrial variation and intraclass correlation coefficient were used as an index of reproducibility. RESULTS: Of all the measurements, F-wave latency yielded the highest intraclass correlation coefficient with the smallest relative intertrial variation for both median and tibial nerves in both groups. CONCLUSION/INTERPRETATION: Median and tibial F-wave latency provide the most reproducible measures for a nerve conduction study, serving as one of the best measures in multicentre drug trials for diabetic polyneuropathies.

Adult↗

Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease.

The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0. 85, P<0.0001), and showed a weak linear correlation with cardiac output (r=-0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO(2) to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.

Aged↗

A case of false median cleft of upper lip with IV-A holoprosencephaly that underwent cheiloplasty at 2.5 years of age.

Holoprosencephaly results from the incomplete development of midline structures within the cerebrum and encompasses a series of abnormalities of mid-facial development. Here, we report a case of male holoprosencephaly associated with false median cleft of upper lip. This patient belonged clinically to the DeMyer's group IV holoprosencephaly, semilobar type. An infant with this type of holoprosencephaly has been thought to die generally within 1 to 2 years after birth and to rarely benefit from an operation. In this case, the patient had cheiloplasty at the age of 2.5 years at the request of his parents and he lives currently, being 3 years and 2 months old.

Child, Preschool↗

[An electron microscopic study of the relation between epithelial cell damage and eosinophilia in the nasal mucosa of patients with nasal allergy].

To determine the relationship between epithelial damage and eosinophilia in the nasal mucosa of patients with nasal allergy, we examined the nasal mucosa (obtained by surgery) from 74 patients with allergic rhinitis, using light and electron microscopy. The extent of eosinophilia correlated significantly to grades of epithelial damage and torn tight junctions of the epithelial cells. No significant relationships were found between the severity of nasal symptoms and the extents of eosinophilia or grades of torn tight junctions of the epithelial cells. More than 50% specific granules in eosinophils in the allergic nasal mucosa showed normal findings. There were no significant relationships between the extent of eosinophil degranulation and grades of epithelial damage. Based on our results, the release of tubular vesicular structures from the eosinophil granule may be one form of eosinophil degranulation in the nasal mucosa of patients with nasal allergy.

Adult↗

Biochemical characterization of various catalytic complexes of the brain platelet-activating factor acetylhydrolase.

Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH) isoform I is a member of a family of complex enzymes composed of mutually homologous alpha(1) and alpha(2) subunits, both of which account for catalytic activity, and the beta subunit. We previously demonstrated that the expression of one catalytic subunit, alpha(1), is developmentally regulated, resulting in a switching of the catalytic complex from alpha(1)/alpha(2) to alpha(2)/alpha(2) during brain development (Manya, H., Aoki, J., Watanabe, M., Adachi, T., Asou, H., Inoue, Y., Arai, H., and Inoue, K. (1998) J. Biol. Chem. 273, 18567-18572). In this study, we explored the biochemical differences in three possible catalytic dimers, alpha(1)/alpha(1), alpha(1)/alpha(2), and alpha(2)/alpha(2). The alpha(2)/alpha(2) homodimer exhibited different substrate specificity from the alpha(1)/alpha(1) homodimer and the alpha(1)/alpha(2) heterodimer, both of which showed similar substrate specificity. The alpha(2)/alpha(2) homodimer hydrolyzed PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) most efficiently among 1-O-alkyl-2-acetyl-phospholipids. In contrast, both alpha(1)/alpha(1) and alpha(1)/alpha(2) hydrolyzed 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid more efficiently than PAF. AAGPE was the poorest substrate for these enzymes. The beta subunit bound to all three catalytic dimers but modulated the enzyme activity in a catalytic dimer composition-dependent manner. The beta subunit strongly accelerated the enzyme activity of the alpha(2)/alpha(2) homodimer but rather suppressed the activity of the alpha(1)/alpha(1) homodimer and had little effect on that of the alpha(1)/alpha(2) heterodimer. The (His(149) to Arg) mutant beta, which has been recently identified in isolated lissencephaly sequence patients, lost the ability to either associate with the catalytic complexes or modulate their enzyme activity. The enzyme activity of PAF-AH isoform I may be regulated in multiple ways by switching the composition of the catalytic subunit and by manipulating the beta subunit.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Small GTPase RhoD suppresses cell migration and cytokinesis.

Rho family small GTPases regulate organization of the actin cytoskeleton. Among them, RhoA plays essential roles in the formation of the actin stress fibers, the associated focal adhesions, and the contractile rings necessary for cytokinesis. Recently, RhoD, a novel member of Rho family has been identified. The amino acid sequences of its effector domain is distinct from those of the other Rho family proteins, suggesting its unique cellular functions. Introduction of the constitutively active form of RhoD(G26V) into fibroblasts by microinjection or transfection resulted in disassembly of the actin stress fibers and the focal adhesions, whereas the dominant negative form of RhoD(T31K) did not affect these structures. The degree of cell migration assessed by the phagokinetic tracks on a substrate covered with gold particles was diminished by the expression of RhoD(G26V) but not by RhoD(T31K). Thus, cytoskeletal alterations including the loss of stress fibers and focal adhesions by RhoD seems to lead to the retardation of cell migration. Transfection of RhoD(G26V) cDNA into cultured cells also induced multinucleation. Moreover, RhoD(G26V) microinjected into fertilized eggs and embryos of Xenopus laevis caused cleavage arrest only in the injected cells, and the uncleaved cells contained multiple nuclei. These results imply that RhoD does not affect nuclear division but can interfere with cytokinesis presumably by preventing the formation of the actin-based contractile ring. Enhancement of the stress fibers by RhoA or RhoA-activating lysophosphatidic acid was reversed by the transfection of RhoD cDNA. Accordingly, the cellular functions of RhoD are likely to be antagonistic to those of RhoA.

Amino Acid Sequence↗

Androgenetic complete mole coexistent with a twin live fetus.

OBJECTIVE: The aim of this study was to evaluate the clinical course and the management policy of complete mole coexistent with a twin live fetus confirmed with DNA polymorphism in a single hospital. METHODS: From 1981 to 1995, six patients with androgenetic complete hydatidiform mole coexistent with a twin live fetus were diagnosed by DNA polymorphism analysis. The clinical course of these six patients was analyzed. RESULTS: Two patients chose to terminate pregnancies and four patients desired to continue the pregnancy. However, the pregnancy had to be interrupted in two patients because of severe preeclampsia and sudden intrauterine fetal death. In two patients, fetuses were growing unremarkably and normal babies were delivered at term. The development of persistent trophoblastic tumor (PTT) in these rare pregnancies was higher (50.0%: 3/6) than that of single complete mole. In three patients, serum hCG titers during pregnancy were monitored. Although serum hCG levels progressively decreased during pregnancy in one patient without PTT, hCG levels initially decreased, but subsequently increased or showed a plateau with advancing gestational age in two patients with PTT. CONCLUSIONS: In patients with complete mole coexistent with a live fetus, the pregnancy may be allowed to continue when the fetal karyotype and development are normal and serum hCG titers are constantly falling with advancing gestational age.

Adult↗