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Biomedical subjects

T Inada

Publications and source records attributed to T Inada.

At least 37 records · Page 2Linked to original sources

The yeast nuclear cap binding complex can interact with translation factor eIF4G and mediate translation initiation.

The mRNA cap structure is bound by either the nuclear (CBC) or the cytoplasmic (eIF4F) cap binding complex. Following mRNA export, CBC must be exchanged for eIF4F in the cytoplasm. It is not known how this exchange occurs or how this RNP remodeling event is integrated with mRNA function. Here we report genetic and biochemical evidence that the yeast translation initiation factor eIF4G associates with CBC, and that eIF4E, the eIF4F component that binds both the cap and eIF4G, antagonizes this interaction. Furthermore, we find that CBC can stimulate translation in extracts containing an eIF4G protein deficient for eIF4E binding. These data suggest that eIF4E binding to the eIF4G-CBC complex on newly exported mRNA displaces CBC, and that the first round of translation on mRNA may occur via a different mechanism than subsequent rounds.

Cell Nucleus↗

[A patient with gastric cancer with para-aortic lymph node metastases surviving for 9 years after effective preoperative chemotherapy and radical operation].

A 63-year-old male patient with type 3 advanced gastric cancer was referred to our hospital. Preoperative examination by CT-scan revealed swollen para-aortic lymph nodes and cancer invasion to the pancreas. The patient was treated pre-operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1 week. Immediately after the chemotherapy, the patient underwent total gastrectomy, splenctomy, left-adrenectomy and resection of the body and tail of the pancreas, along with para-aortic lymph node dissection. Microscopic examination revealed that the tumor was a moderately differentiated tubular adenocarcinoma, which displayed invasion to the pancreas with lymph node metastasis up to the level 3 lymph node. Histologically, the effect of preoperative chemotherapy showed a grade 2 effect on the main tumor, but a grade 3 chemotherapeutic effect was observed at the para-aortic lymph nodes. The patient has subsequently remained disease free for 9 years. In this case, it is considered that the preoperative chemotherapy by 5-FU and potentially curative radical operation yielded a good outcome.

Adenocarcinoma↗

Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor kappaB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms(+)RANK(-)) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms(+)RANK(+)) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK-RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

Animals↗

Protective effect of histidine on MPP+-induced hydroxyl radical generation in rat striatum.

We investigated the efficacy of histidine on MPP+-induced hydroxyl radical (.OH) formation in extracellular fluid of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol microl-1 min-1) was infused through a microdialysis probe to detect the generation of.OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP+ (5 mM) clearly produced an increase in.OH formation. However, histidine (25 mM) reduced the.OH formation by the action of MPP+. These results indicate that histidine protects MPP+-induced.OH formation in rat striatum.

1-Methyl-4-phenylpyridinium↗

Anesthesia for insertion of a Dumon stent in a patient with a large tracheo-esophageal fistula.

PURPOSE: To present the anesthetic management for the insertion of a Dumon silicon stent to the trachea of a patient with a large tracheo-esophageal fistula. The aim of the stent insertion was to seal the fistula in order to prevent aspiration of esophageal content and subsequent pneumonitis. CLINICAL FEATURES: A 45-yr-old man with a large tracheo-esophageal fistula was scheduled for the insertion of the Dumon stent. Since placement of the stent necessitates the insertion of a rigid bronchoscope, under general anesthesia, with its tip just proximal to the fistula, controlled ventilation was expected to be difficult to achieve because of the diversion of oxygen through the large fistula to the esophagus. We successfully ventilated the lungs, after the fistula was sealed using a large balloon which was inserted in the esophagus, and the stent insertion was completed uneventfully. CONCLUSION: Anesthesia for procedures involving the central airway is challenging. This report describes a simple and practical method to facilitate ventilation by temporary seal of a tracheo-esophageal fistula using a modified esophageal balloon.

Anesthesia, General↗

Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters.

OBJECTIVES: The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio). BACKGROUND: While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous ET-1 in cardiac growth in primary myocardial disease is unknown. METHODS: We measured left ventricular ET-1 levels by a specific sandwich enzyme-linked immunosorbent assay. Furthermore, we examined the chronic effect of T0201, an ET type A receptor-specific antagonist. RESULTS: The ET-1 levels in the left ventricles were 1.8-fold higher (p < 0.0005) at 20 weeks and 6.4-fold higher (p < 0.0001) at 35 weeks in the Bio compared to age-matched control F1B hamsters (F1B). The Bio ET-1 levels in the lungs exhibited an only 1.3-fold elevation at 35 weeks. Immunohistochemistry demonstrated the localization of ET-1 mainly in the cardiac myocytes. The treatment with T0201 significantly reduced the heart weight/body weight ratio in the Bio, but did not affect the heart weight/body weight ratio in the F1B. Histologically, T0201 reduced the myocyte diameter of Bio to a level similar with that of F1B. However, T0201 did not affect the extent of fibrosis in Bio or F1B. CONCLUSIONS: The ET-1 level in the heart of cardiomyopathic hamsters increases in stage-dependent and organ-specific manners. Though myocyte degeneration and subsequent replacement fibrosis do not require an ET-1 pathway, the accelerated synthesis of ET-1 in the heart may contribute to the pathological growth of remaining myocytes in this animal model.

Animals↗

Molecular and serological characterization of adenovirus genome type 7h isolated in Japan.

In 1996, three adenovirus type 7 (Ad7) strains were isolated from children with fever and upper respiratory diseases in Japan. Restriction endonucleases (REs) analysis and PCR amplification of the E3 7.7 kDa ORF revealed that these strains were genotype Ad7h and closely related to an Argentine Ad7h strain, which has been reported to be highly virulent and so far predominant only in South America. These strains showed weak cross-neutralizing activity and specific haemagglutination-inhibition activity to Ad3 antiserum. The present findings suggest that Ad7h in South America has spread to other parts of the world. Since the seroprevalence to Ad7 in the current Japanese population is very low due to the absence of Ad7 circulation in Japan for decades, Ad7 outbreak as a typical case of re-emerging infectious diseases is a cause for serious concern.

Adenovirus Infections, Human↗

Effects of nitrous oxide on haemodynamic and electroencephalographic responses induced by tetanic electrical stimulation during propofol anaesthesia.

We studied the effect of nitrous oxide on haemodynamic and electroencephalographic responses caused by noxious stimulation during propofol anaesthesia. Thirty-four patients (ASA I-II) were anaesthetised with propofol 3 mg x kg(-1) and were randomly allocated to receive either 60% nitrous oxide in oxygen or 40% oxygen in air. Anaesthesia was maintained using propofol infusion of 10 mg x kg(-1) x h(-1) for the first 10 min, 8 mg x kg(-1) x h(-1) for the next 10 min and 6 mg x kg(-1) x h(-1) thereafter. Thirty minutes after the induction of anaesthesia, tetanic electrical stimulation (80 mA, 100 Hz) was applied to the ulnar nerve. Tetanic stimulation significantly increased blood pressure and heart rate in both groups (p < 0.005 or less), but did not induce any arousal pattern on the electroencephalograph. Nitrous oxide significantly attenuated the tetanic stimulation-induced increase in blood pressure (p < 0.05 or less), but not the heart rate.

Adult↗

Electroencephalographic arousal response during tracheal intubation and laryngeal mask airway insertion after induction of anaesthesia with propofol.

Laryngoscopy and tracheal intubation, or insertion of a laryngeal mask airway may lead to an arousal response on the electroencephalogram. We studied whether more intense stimulation (laryngoscopy and tracheal intubation) causes a greater arousal response than less intense stimulation (laryngeal mask airway insertion). Thirty-four patients (ASA I-II) were anaesthetised with propofol 3 mg.kg-1, followed by vecuronium 0.15 mg.kg-1 and a propofol infusion of 10 mg.kg-1.h-1. Three minutes after induction of anaesthesia, either laryngoscopy and tracheal intubation (n = 18), or laryngeal mask airway insertion (n = 16) was performed. Laryngoscopy and tracheal intubation caused a significantly greater increase in blood pressure (but not heart rate) than laryngeal mask airway insertion (p < 0.05). Electroencephalogram responses were not different. More intense stimulation does not cause a greater arousal response during propofol anaesthesia.

Adult↗

Negative regulation of the pts operon by Mlc: mechanism underlying glucose induction in Escherichia coli.

BACKGROUND: The pts operon of Escherichia coli consists of three genes ptsH, ptsI and crr, each encoding for central components of the phosphoenolpyruvate: carbohydrate phosphotransferase system, HPr, enzyme I and IIAGlc, respectively. Transcription of the pts operon is stimulated when glucose is present in the culture medium. One of the two major promoters, P0, is responsible for this glucose induction. However, no regulatory protein responsible for the glucose induction of the pts operon has been identified yet and molecular mechanism by which glucose stimulates the pts transcription is not known. RESULTS: We found by Northern blotting that the pts mRNA levels in cells lacking Mlc, a new global repressor of carbohydrate metabolism, were increased without external glucose and that the addition of glucose had no effect on the pts mRNA levels in the mutant cells. Western blotting revealed that the enzyme I level in the mlc- cells was also elevated without glucose and no further increase in the enzyme I level was observed in the presence of glucose. S1 analysis revealed that transcription of the glucose-sensitive promoter, P0, occurs constitutively in the mlc- cells independently from the external glucose. In vitro transcription studies indicated that Mlc strongly inhibited P0 transcription. DNase I footprinting experiment revealed that Mlc bound to P0 promoter region to prevent RNA polymerase binding at P0. CONCLUSION: We conclude that Mlc is a repressor for the pts transcription acting as a major regulatory protein involved in the glucose induction of pts operon. We propose that glucose induces the pts transcription by modulating the Mlc activity. The mechanism by which glucose modulates the Mlc action remains to be studied.

Bacterial Proteins↗

Mutation induction and RBE of low energy neutrons in V79 cells.

We have examined the neutron energy dependency of cell killing and mutation induction at the hprt locus in Chinese hamster V79 cells. Monoenergetic neutrons at 0.32, 0.57, and 1.2 MeV were generated at the Hiroshima University Radiobiological Research Accelerator (HIRRAC) Facility, and were used to irradiate cells. The variation in RBE with neutron energy for the end points of cell survival and hprt mutation induction was observed. When compared to 137Cs gamma-rays, all neutron energies were more effective at both cell killing and induction of mutation. Over the range of the neutron energies examined, we found that cytotoxicity increased as the energy decreased from 1.2 to 0.32 MeV. In comparison to gamma-rays, RBEs for cell lethality at 10% survival were 5.7, 6.7, and 7.6 for 1.2, 0.57, and 0.32 MeV, respectively. Mutation induction, on the other hand, was highest at 0.57 MeV with a gradual decrease at 1.2 and 0.32 MeV. RBEs for mutation induction were 9.7, 19.4, and 13.9 for 1.2, 0.57, and 0.32 MeV neutrons. We isolated independent V79 cell mutants at the hprt locus from untreated and neutron-exposed cells and determined the genetic changes underlying the mutation by multiplex polymerase chain reaction (PCR)-based exon deletion analysis. Preliminary results are suggestive of a specific relationship between deletion pattern and neutron energy.

Animals↗

Increased hyperkinesis in noninfarcted areas during short-term follow-up in patients with first anterior acute myocardial infarction treated by direct percutaneous transluminal coronary angioplasty.

The time course and clinical significance of hyperkinetic wall motion (HWM) in a noninfarcted area in direct percutaneous transluminal coronary angioplasty (PTCA) has not been clearly demonstrated in patients with acute myocardial infarction (AMI). The objectives of this study were to examine the change in HWM during one-month follow-up after direct PTCA and determine its impact on the recovery of global left ventricular function. A total of 61 patients with first anteroseptal AMI and one vessel disease were evaluated. The paired left ventriculograms in the 30 degrees right anterior oblique view taken both at baseline and follow-up were analyzed by the centerline and area length methods. The severity of hypokinesis was expressed by mean regional wall motion (standard deviation/chord) in most hypocontractile 50% of chords respondable to left anterior descending coronary artery area and HWM by mean regional wall motion in most hypercontractile 50% of chords of noninfarcted area. HWM increased from 0.18 +/- 1.07 to 0.48 +/- 1.30 (p = 0.0608). The delta global ejection fraction (global ejection fraction at follow-up minus global ejection fraction at baseline) was correlated with both delta infarcted wall motion (infarcted wall motion at follow-up minus infarcted wall motion at baseline) and delta HWM (HWM at follow-up minus HWM at baseline) (r = 0.576, p < 0.0001, r= 0.383, p = 0.0036, respectively) during follow-up. Further, the delta global ejection fraction showed better correlation with delta (HWM + infarcted wall motion) [(HWM plus infarcted wall motion at follow-up) minus (HWM plus infarcted wall motion at baseline)] (r= 0.593, p < 0.0001). Direct PTCA resulted in the enhancement of HWVM, which contributed to the increase in the global ejection fraction with the recovery of infarcted wall motion.

Aged↗

[Preliminary evaluation of adjuvant chemotherapy against stage Ib or II gastric cancer].

The prognostic influence of post-operative adjuvant chemotherapy on stage I b or II gastric cancer was studied retrospectively. The immunohistochemical expressions of p53 protein and thymidine phosphorylase (TP) were also examined; the relations between these protein expressions and clinicopathological features along with the effect of adjuvant chemotherapy were also investigated. The 5-year survival rate of the patients who received adjuvant chemotherapy was 95.5%, which was better than that (89.8%) of those who did not, although the difference did not reach significance (p = 0.09). The venous invasion of tumor was slight frequently observed in p53 or TP positive cases than negative cases, respectively (p < 0.1), but no significant associations were found between the t-, n- or ly-factor, and p53 or TP expression. Moreover p53 and TP expression had no significant influence on post-operative survival. But, among the patients with p53- or TP-positive tumor, adjuvant chemotherapy conferred survival benefits, although the difference did not reach significance. The 5-year survival rate was 100% with adjuvant chemotherapy, 84.3% without chemotherapy in p53-positive patients (p = 0.137), 97.0% with adjuvant chemotherapy, and 90.8% without chemotherapy in TP-positive tumors (p = 0.326).

Administration, Oral↗

[Detection size dependence of field factor for narrow beam].

An absorbed dose in the narrow beam is calculated based on the depth dose distribution and a field factor. The field factor has to be measured with especially high accuracy because it is highly variable. The field factor was calculated when detection size was changed, by using Monte Carlo simulation, which had no energy dependency or geometrical error. Then the relation between field factor and detection size in the narrow beam was investigated. An absorbed dose in peak depth and reference depth according to detection size was calculated for each field size. Detection size dependency was recognized in the case of measuring a field factor, because the absorbed dose tended to decrease as detection size increased. The absorbed dose in the narrow beam has to be calculated within a change of +/- 2%. The change in peak depth according to detection size was eliminated, and then the relation between an absorbed dose at the ideal detection size of 0 mm phi by extrapolation and detection size which has a deference of 2% from it, were acquired. In addition, the maximum usable detection size was estimated in the case of measuring the field factor.

Models, Theoretical↗

[CD5 positive B cell leukemic lymphoma associated with BCL6 rearrangement].

A 59-year-old man was admitted in December 1995 because of general fatigue without lymphadenopathy. Increased abnormal lymphocytes (70%) were observed in peripheral blood. Bone marrow aspiration was a dry tap. Biopsy specimens revealed hypercellularity with infiltration of abnormal lymphocytes. Surface marker analysis of tumor cells was positive for CD5, CD19, CD20, HLA -DR, kappa, and sIgM and negative for CD10. Cytogenetic analysis disclosed a complex abnormal karyotype including t(3;22) and rearrangement of the BCL6 gene. The patient was given a diagnosis of CD5 positive B-cell lymphoma, but died in January 1997 despite repeated chemotherapy. This case was unique because BCL6 rearrangement has been reported in various types of B-cell lymphoma but rarely associated with leukemic types without lymphadenopathy.

CD5 Antigens↗

The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes quiescent but not proliferating MG-63 human osteosarcoma cells to radiation.

Recent genetic and biochemical studies indicate that DNA-dependent protein kinase (DNA-PK) plays an important role in DNA double-strand break (dsb) repair and V(D)J recombination. Since the catalytic subunit of DNA-PK (DNA-PKcs) has high sequence homology with phosphatidylinositol 3-kinase (PI 3-kinase), we examined the effect of wortmannin, a specific inhibitor of PI 3-kinase, on the survival of human tumor cells after X-irradiation. The present study demonstrates that wortmannin at 20 microM is an effective radiosensitizer of quiescent (Q), but not proliferating (P) cells. In addition, the rejoining of DNA dsb is significantly inhibited in Q, but not in P cells. Finally, we found that Q cell extracts have approximately five-fold less DNA-PK activity than those of P cells. After a 2 h exposure to wortmannin, the DNA-PK activity of Q cell extracts was considerably lower than that of P cells. This can explain why wortmannin sensitizes Q, but not P cells to radiation.

Androstadienes↗

CRP down-regulates adenylate cyclase activity by reducing the level of phosphorylated IIA(Glc), the glucose-specific phosphotransferase protein, in Escherichia coli.

The cellular cAMP level is markedly down-regulated by cAMP receptor protein (CRP) in Escherichia coli. CRP regulates adenylate cyclase both at the level of transcription of its structural gene cya and at the level of enzyme activity. We established a method to determine the phosphorylation state of IIA(Glc), the glucose-specific phosphotransferase protein, in intact cells. We found that IIA(Glc) exists predominantly in the unphosphorylated form in wild-type cells growing in LB medium, while it is largely phosphorylated in crp or cya cells. Disruption of the ptsG gene that codes for the membrane component of the major glucose transporter (IICB(Glc)), and/or the fruF gene coding for FPr (fructose-specific hybrid phosphotransferase protein), did not affect the phosphorylation state of IIA(Glc). When IICB(Glc) was overproduced in the presence of glucose, the levels of both cAMP and phosphorylated IIA(Glc) in crp cells were concomitantly decreased to wild-type levels. In addition, when His-90 in IIA(Glc) was replaced by glutamine, both phosphorylation of IIA(Glc) and the overproduction of cAMP in crp cells were eliminated. We also found that extracts of crp+ cells markedly stimulate dephosphorylation of IIA(Glc)-P in vitro. We conclude that CRP-cAMP down-regulates adenylate cyclase primarily by reducing the level of phosphorylated IIA(Glc). The data suggest that unspecified proteins whose expression is under the control of CRP-cAMP are responsible for this regulation.

Adenylyl Cyclases↗