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Biomedical subjects

H Tanaka

Publications and source records attributed to H Tanaka.

At least 271 records · Page 15Linked to original sources

Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells.

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.

Animals↗

Transparent nematic phase in a liquid-crystal-based microemulsion.

Complex fluids are usually produced by mixing together several distinct components, the interactions between which can give rise to unusual optical and rheological properties of the system as a whole. For example, the properties of microemulsions (composed of water, oil and surfactants) are determined by the microscopic structural organization of the fluid that occurs owing to phase separation of the component elements. Here we investigate the effect of introducing an additional organizing factor into such a fluid system, by replacing the oil component of a conventional water-in-oil microemulsion with an intrinsically anisotropic fluid--a nematic liquid crystal. As with the conventional case, the fluid phase-separates into an emulsion of water microdroplets (stabilized by the surfactant as inverse micelles) dispersed in the 'oil' phase. But the properties are further influenced by a significant directional coupling between the liquid-crystal molecules and the surfactant tails that emerge (essentially radially) from the micelles. The result is a modified bulk-liquid crystal that is an ordered nematic at the mesoscopic level, but which does not exhibit the strong light scattering generally associated with bulk nematic order: the bulk material here is essentially isotropic and thus transparent.

Journal Article↗

Effects of stimulus presentation rate on the activity of primary somatosensory cortex: a functional magnetic resonance imaging study in humans.

To investigate the effect of stimulus presentation rate on the activity of primary somatosensory cortex, we performed echo-planar functional magnetic resonance imaging using a 1.5-tesla magnetic resonance system. Eight right-handed normal volunteers underwent functional magnetic resonance imaging during somatosensory stimulation with a 0.2 ms electrical square wave to the left index finger at 1, 4, 8, 16, and 32 Hz at constant intensity. Activated areas were located mainly around 'the hand area' of the right postcentral gyrus. Between 4 and 16 Hz, almost all subjects showed significant activation, but at 1 Hz and 32 Hz, five of eight subjects showed no activation. The average number of activated pixels in this area between 4 and 16 Hz were significantly greater than those at 1 Hz and 32 Hz, and the average percent signal increase had its activation peak at 8 Hz. Our results suggest that the existence of the optimal stimulation rate range may be a common phenomenon to a variety of sensory modalities. The electrical somatosensory stimulation rates from 4 Hz to 16 Hz are advisable to investigate the activation of the primary somatosensory cortex in human subjects.

Adult↗

Autonomic consequences of brainstem infarction.

OBJECTIVE: It is well known that patients with brainstem infarctions sometimes experience dizziness, vertigo and falls, although the exact mechanism is not clear. Therefore, we designed a study to quantify autonomic function in patients with brainstem infarction. PATIENTS AND METHODS: We examined autonomic function in 15 patients with brainstem infarctions, who had a history of vertigo, nausea, floating sensation and/or general fatigue during standing, and 31 age-matched controls using the composite autonomic scoring scale (CASS), which was used to grade autonomic function. The patients underwent initial autonomic assessment and then were subjected to aniracetam therapy. The drug was given orally (dose of 600 mg/day) for a duration of 56 days. Upon completion of aniracetam administration, the CASS was again tested. RESULTS: Upon initial assessment, the patients had mild reductions in mean blood pressure (MBP) and lack of an increasing heart rate (HR) within 5 min of head up-tilt, an impairment in BP correction during late phase II and reduced phase IV beat-to-beat BP response to the Valsalva maneuver, and reduced heart rate response to deep breathing (HRdb). CASS indicated mild autonomic dysfunction. After 8 weeks of treatment with aniracetam, the patients' symptoms improved and the autonomic tests showed improvement in autonomic function. CONCLUSION: Part of the pathogenesis of recurrent vertigo or dizziness with brainstem infarction might be due to mild autonomic dysfunction. Aniracetam, which activates the cholinergic system in brain, might correct the cardiovagal system in these patients. The CASS may be a sensitive tool for assessing mild autonomic dysfunction in patients with brainstem infarction.

Aged↗

A three-dimensional synthetic metallic crystal composed of single-component molecules.

Molecular metals normally require charge transfer between two different chemical species. We prepared crystals of [Ni(tmdt)2] (tmdt, trimethylenetetrathiafulvalenedithiolate) and carried out crystal structure analyses and resistivity measurements. The analyses and measurements revealed that these single-component molecular crystals are metallic from room temperature down to 0.6 kelvin. Ab initio molecular orbital calculations suggested that pi molecular orbitals form conduction bands. The compact molecular arrangement, intermolecular overlap integrals of the highest occupied and lowest unoccupied molecular orbitals, and tight-binding electronic band structure calculation revealed that [Ni(tmdt)2] is a three-dimensional synthetic metal composed of planar molecules.

Journal Article↗

Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas.

HER2 / neu is a potential antigen candidate for immunotherapy because of its correlation to a poor prognosis and high expressions in many kinds of epithelial tumours. Especially in the colorectal carcinomas, the higher expression of HER2 / neu is recognized in metastatic regions as well as in primary sites. Several CTL epitopes restricted by HLA-A2.1 and -A3 were identified so far, however epitopes restricted by HLA-A24, that is one of the most common allele in Japanese and Caucasians, have not been identified. In this paper, we showed identification of a CTL epitope peptide of HER2 / neu restricted by HLA-A24. HLA-A24 binding peptides selected by an analysis based on HLA-A24 binding motifs were determined for their binding affinities to HLA-A24 molecules. The peptide with a sequence of RWGLLLALL (position 8-16) named HE1 showed the highest affinity. We induced CTLs from CD8(+)cells of HLA-A24 healthy donors by stimulation with HE1-pulsed autologous dendritic cells. The CTLs showed cytotoxic activity against not only the peptide-pulsed target cells but also HLA-A24 colorectal tumour cell lines that endogenously overexpressed HER2 / neu. The antigen-specificity was confirmed by cold target inhibition assay using HE1-pulsed target cells. In summary, HER2 / neu peptide, RWGLLLALL, may contribute to the induction of antitumour immunity with the peptide-based immunotherapy for the colorectal carcinomas.

Colorectal Neoplasms↗

Prevention of postoperative nausea and vomiting with antiemetics in patients undergoing middle ear surgery: comparison of a small dose of propofol with droperidol or metoclopramide.

OBJECTIVE: To compare the efficacy and safety of a small dose of propofol with other commonly used antiemetics, droperidol and metoclopramide, for the prevention of postoperative nausea and vomiting in patients undergoing middle ear surgery. DESIGN: Prospective, randomized, double-blind study. SETTING: University-affiliated teaching hospital. PATIENTS: Ninety patients (48 females, 42 males) scheduled for middle ear surgery. INTERVENTION: Patients received propofol, 0.5 mg/kg, droperidol, 20 microg/kg, or metoclopramide hydrochloride, 0.2 mg/kg, intravenously at the end of the surgical procedure. A standardized general anesthetic technique was employed throughout the surgical procedure. MAIN OUTCOME MEASURE: Emetic episodes and safety assessment were performed during 2 periods-0 to 3 hours in the postanesthetic care unit and 3 to 24 hours in the ward-after receiving anesthesia. RESULTS: The incidence of patients who were emesis free during the 0- to 3-hour period after receiving anesthesia was 93% for those who received propofol, 73% for those who received droperidol, and 70% for those who received metoclopramide, respectively; the respective corresponding incidence during the 3- to 24-hour period after receiving anesthesia was 90%, 67%, and 60% (P<.05, overall Fisher exact probability test). No clinically adverse events were observed in any of the groups. CONCLUSION: A small dose of propofol is a better antiemetic than droperidol or metoclopramide for the prevention of postoperative nausea and vomiting after middle ear surgery.

Adult↗

Prophylaxis with oral granisetron for the prevention of nausea and vomiting after laparoscopic cholecystectomy: a prospective randomized study.

HYPOTHESIS: Laparoscopic cholecystectomy is associated with a relatively high incidence of postoperative nausea and vomiting when no prophylactic antiemetic is given. This study assesses the efficacy and safety of oral granisetron hydrochloride for the prevention of nausea and vomiting after laparoscopic cholecystectomy. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: University teaching hospital. PATIENTS: The study comprised 120 patients, 92 women and 28 men, undergoing laparoscopic cholecystectomy. INTERVENTIONS: Patients received orally either placebo or granisetron at 3 different doses (1 mg, 2 mg, and 4 mg; n = 30 of each) 60 minutes before surgery. A standard general anesthetic technique and postoperative analgesia were used. MAIN OUTCOME MEASURES: Emetic episodes were recorded during the first 24 hours after anesthesia. RESULTS: The incidence of patients who were emesis-free 24 hours after anesthesia was 60% with 1 mg of granisetron (P =.40), 83% with 2 mg of granisetron (P =.01), and 83% with 4 mg of granisetron (P =.01), compared with placebo (53%). No clinically important adverse effects were observed in any of the groups. CONCLUSION: Preoperative oral granisetron in doses higher than 2 mg is effective for the prevention of nausea and vomiting after laparoscopic cholecystectomy.

Administration, Oral↗

Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthritis synovial fluid: expression on human T cells with transendothelial migratory activity.

OBJECTIVE: We have previously reported that the anti-6C2 monoclonal antibody (mAb) defines a subset of human CD4+ memory T cells. The present study sought to determine the nature of the 6C2 molecule and the function associated with 6C2+ T cells, and to examine whether this T cell subset is involved in the pathophysiology of rheumatoid arthritis (RA). METHODS: Cytofluorographic analysis was performed for identification of T cell surface molecules displaying a distribution similar to that of the 6C2 molecule. T cells in the synovial fluid of RA patients were examined for expression of the 6C2 molecule. Transendothelial migratory activity was assessed by assay using monolayers of human endothelial cells. Specific reactivity of the anti-6C2 mAb was determined by immunoblotting on gangliosides separated by thin-layer chromatography, and flow cytometric analysis of the cells transfected with complementary DNA (cDNA) was performed for determination of the glycosyltransferases involved in biosynthesis of the gangliosides. RESULTS: On human peripheral T cells, the 6C2 molecule was distributed, by and large, in a pattern similar to that of CDw60, or O-acetyl-GD3. The majority (>70%) of synovial fluid T cells from patients with RA were found to be 6C2 positive, and those 6C2+ T cells exhibited a transendothelial migratory capacity that was inhibited by pretreatment of T cells with anti-6C2 mAb. Moreover, treatment of T cells with neuraminidase resulted in a loss of 6C2 expression as well as a reduction in the transendothelial migratory activity. Anti-6C2 mAb reacted specifically with GD3, but not with O-acetyl-GD3. The reactivity of anti-6C2 mAb was induced on the cell surface only by transfection with cDNA for GD3 synthase. CONCLUSION: The 6C2 molecule is a disialoganglioside, GD3, and is present on a subset of T cells with transendothelial migratory capacity. The 6C2/GD3 molecules, as well as 6C2/GD3+ T cells, appear to play a role in T cell migration and in the inflammation of RA.

Antibodies, Monoclonal↗

Compensating for central nervous system dysmyelination: females with a proteolipid protein gene duplication and sustained clinical improvement.

A submicroscopic duplication that contains the entire proteolipid protein gene is the major cause of Pelizaeus-Merzbacher disease, an X-linked central nervous system dysmyelinating disorder. Previous studies have demonstrated that carrier females for the duplication are usually asymptomatic. We describe 2 unrelated female patients who present with mild Pelizaeus-Merzbacher disease or spastic paraplegia. In 1 patient, clinical features as well as cranial magnetic resonance imaging and brainstem auditory evoked potential results have improved dramatically over a 10-year period. The other patient, who presented with spastic diplegia and was initially diagnosed with cerebral palsy, has also shown clinical improvement. Interphase fluorescent in situ hybridization identified a proteolipid protein gene duplication in both patients. Interphase fluorescent in situ hybridization analyses of the family members indicated that the duplication in both patients occurred as de novo events. Neither skewing of X inactivation in the peripheral lymphocytes nor proteolipid protein gene coding alterations were identified in either patient. These findings indicate that, occasionally, females with a proteolipid protein gene duplication can manifest an early-onset neurological phenotype. We hypothesize that the remarkable clinical improvement is a result of myelin compensation by oligodendrocytes expressing one copy of proteolipid protein gene secondary to selection for a favorable X inactivation pattern. These findings indicate plasticity of oligodendrocytes in the formation of central nervous system myelin and suggest a potential role for stem cell transplantation therapies.

Brain↗

Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw.

To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype-specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3- to 4-month interval. At a median follow-up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 < or = ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw-related cirrhosis.

Adult↗

Adhesion of composite resins to enamel irradiated by the Er:YAG laser: application of the ultrasonic scaler on irradiated surface.

BACKGROUND AND OBJECTIVE: The clinical use of the Er:YAG laser in cavity preparation has become widespread. With respect to cavities prepared with the Er:YAG laser, restorations using composite resins and glass ionomer cements are common. The bond strength of current resin bonding systems to ground enamel is 14-30 MPa, whereas the strength to Er:YAG laser-irradiated enamel, regardless of the use or non-use of phosphoric acid etching is less than 10 MPa. STUDY DESIGN/MATERIALS AND METHODS: In this investigation, an ultrasonic scaler was tested as a technique to increase the bond strength of composite resins to the Er:YAG irradiated enamel surface. RESULTS: The application of the ultrasonic scaler significantly increased bond strength. CONCLUSIONS: The tensile bond strength in the groups treated with the ultrasonic scaler exhibited approximately twice the strength observed in groups treated with laser irradiation alone.

Composite Resins↗

Molecular cloning of actinohivin, a novel anti-HIV protein from an actinomycete, and its expression in Escherichia coli.

Syncytium-inducing variants of the HIV-1 virus are correlated with poor diagnosis and rapid disease progression. We have recently discovered a novel anti-HIV protein, referred to as actinohivin, that inhibits syncytium formation. Here we describe the cloning and sequencing of the gene encoding actinohivin from the actinomycete strain K97-0003, and its expression in Escherichia coli. The actinohivin gene was located on a 0.8-kb BamHI fragment of genomic DNA. The fragment contained an open reading frame of 480 bp, which encoded a protein of 160 amino acids with calculated molecular weight of 17492.7. The N-terminal region was found to be a typical signal peptide of prokaryotes, and actinohivin was located at amino acid positions 46-160. The actinohivin gene could be expressed in E. coli using a pET30Xa/LIC expression vector and the purified recombinant actinohivin was found to inhibit syncytium formation to a similar extent as actinohivin from its natural source.

Actinomycetales↗

Estradiol-17beta stimulates gonadotropin II expression and release in the protandrous male black porgy Acanthopagrus schlegeli Bleeker: a possible role in sex change.

The objective of the present study was to investigate the in vivo effects of sex steroids (estradiol-17beta, E(2); testosterone, T) and the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT) on the levels of gonadotropin II (GTH II) in plasma and pituitary and on aromatase activity in 2-year-old male black porgy, Acanthopagrus schlegeli, during the prereproductive season. Black porgy GTH II and GTH II beta subunits were purified and anti-GTH II beta serum was induced. A specific radioimmunoassay for black porgy GTH II was developed. cDNA GTH II beta was also cloned from a black porgy pituitary cDNA library for use as a probe for Northern analysis. Male fish were divided into eight groups (n = 64): control; E(2) (3 doses, 2.4 ng, 72 ng, and 2.2 microg/g body weight); T (2 doses, 72 ng and 2.2 microg/g body weight); and DHT (2 doses, 72 ng and 2.2 microg/g body weight). Fish were injected with the respective vehicle or different doses of material on days 0, 8, and 16. Plasma was collected at 4-day intervals from days 4 to 20. Plasma GTH II concentrations were significantly increased (up to 45-fold) in the E(2) group from days 4 to 20 in a dose-dependent manner. In a further experiment during the late reproductive season, plasma GTH II levels increased at 4 h and on days 1 and 2 following a single injection of 1.0 microg E(2)/g body weight (on day 0). Androgens (T or DHT) had little or no effect on plasma GTH II. Pituitary GTH II contents on day 20 were significantly lower in the 72-ng E(2) and 2.2-microg E(2) groups but not in the 2.4-ng E(2) group compared with the control group. Pituitary GTH II beta mRNA levels were significantly stimulated in the 72-ng and 2.2-microg E(2) groups on day 20. Gonadal aromatase activity was not significantly changed in any of the treated or control groups. It is concluded that GTH II secretion in black porgy is regulated by an estrogen-specific effect. Increased plasma GTH II levels or other factors in addition to E(2) might be involved in the regulation of gonadal aromatase activity and sex change in protandrous black porgy.

Amino Acid Sequence↗

Overexpression of cdk Inhibitor p16INK4a by adenovirus vector inhibits cardiac hypertrophy in vitro and in vivo: a novel strategy for the gene therapy of cardiac hypertrophy.

Cardiac hypertrophy is one of the serious complications which increase mortality due to cardiovascular diseases. However, only a partial reduction of cardiac hypertrophy has been successful using current drug therapy. We demonstrate here reduction of cardiac hypertrophy in vitro and in vivo using an adenovirus vector encoding cyclin-dependent kinase (cdk) inhibitor p16INK4a. Adenovirus-mediated overexpression of cdk inhibitor p16INK4a completely inhibited cardiac myocyte hypertrophy induced by endothelin (ET)-1, as evaluated by [3H]leucine incorporation into the cells and mRNA levels of skeletal alpha -actin (SK-A) or atrial natriuretic peptide (ANP) as well as by morphometric analyses. We then evaluated whether p16INK4a can suppress left-ventricular (LV) hypertrophy induced by aortic banding (AOB) in rats. Catheter-mediated gene transfer of AxCAp16 was performed according to the method reported by Hajjar et al. LV overload was produced by coarctation of the ascending aorta immediately after inoculation of the heart with adenovirus. Two weeks after the procedure, the left ventricular weight/body weight ratio (LVW/BW) increased in the AOB+LacZ group in comparison to that in controls. However, LVW/BW was identical in the AOB+p16 group and controls. Histologic analysis revealed that p16INK4a inhibited hypertrophy of cardiac myocytes. These results suggest that G1 cell cycle regulators may restrict cardiac hypertrophy, and offer a novel strategy for the gene therapy of cardiac hypertrophy.

Actins↗

Mitral regurgitation after myocardial infarction. Coronary artery bypass grafting and mitral valve replacement with chordae preservation.

A patient with acute ischemic mitral regurgitation after acute myocardial infarction required emergency coronary artery bypass grafting and mitral valve replacement with chordae preservation. For severe mitral regurgitation and heart failure due to myocardial infarction and ischemic papillary muscle dysfunction, mitral valve replacement with chordae preservation was effective. Here, we discuss the etiology of ischemic mitral regurgitation and the operative method for valve repair or replacement.

Aged↗

Mediastinal liposarcoma appearing as a tumor arising in the esophageal wall.

We report a case of mediastinal liposarcoma, a relatively uncommon neoplasm, in which the mass also appeared as a tumor arising in the esophageal wall. A 76-year-old man diagnosed with a posterior mediastinal mass had the tumor extirpated in local esophageal myectomy due to its unclear margin on the esophageal wall. The resected specimen was diagnosed as well-differentiated liposarcoma. Preoperative angiography showed the tumor received its blood supply from a branch of the left gastric artery, suggesting it arose in the lower esophageal segment close to the hiatus and extended to the mediastinum. Since this tumor's growth pattern differed completely from esophageal liposarcoma described in previous case reports, we concluded that it was mediastinal liposarcoma.

Aged↗