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H Kitano

Publications and source records attributed to H Kitano.

At least 91 records · Page 5Linked to original sources
PubMed1998

Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging.

The mechanism of cellular aging has been suggested to play an important role in organismic aging, but the molecular linkage between them is not still understood. The recent progress in the studies of telomere and telomerase demonstrates their substantial roles in the mechanism of cellular aging. On the other hand, these studies also raise controversial issues about the generality of the telomere hypothesis. The heterochronic, polymorphic, and probabilistic features of cellular aging should be reconsidered critically. In this review, we attempt to develop a general scheme for the driving force of cellular aging, based on our molecular and computational studies. Our molecular analyses suggest that global transcriptional repressive structures are essentially involved in cellular aging-associated transcriptional regulation. From our theoretical studies, systematic reorganization of these repressive structures are suggested to be a fundamental driving force of cellular aging. The heterochromatin island hypothesis is proposed to give a rational explanation for the three distinctive features of cellular aging. The importance of a dynamic equilibrium in heterochromatin islands is also discussed for cellular and organismic aging.

Animals↗
PubMed1998

Evaluation of [1-11C]octanoate as a new radiopharmaceutical for assessing liver function using positron emission tomography.

[1-11C]Octanoate was evaluated as a new radiopharmaceutical for the evaluation of liver function using positron emission tomography (PET). In biodistribution studies with normal mice, [1-11C]octanoate was rapidly taken up by the liver. [1-11C]Octanoate in the liver was present in the parenchymal cells and was predominantly metabolized via beta-oxidation followed by its rapid clearance. In the CCl4-treated mice, [1-11C]octanoate showed significantly slower hepatic clearance than that in the controls. In PET studies using rats, the time-radioactivity curves in the liver showed a two-phase decrease, and compared with the normal rat, the CCl4-treated rat showed a slower hepatic half-clearance time for the first phase, which is related to beta-oxidation metabolism. A preliminary PET study of [1-11C]octanoate metabolism in a normal volunteer was consistent with these animal studies. The present study showed that metabolism of [1-11C]octanoate in the liver was influenced by beta-oxidation, and it is advantageous to use [1-11C]octanoate clinically as a regional liver-function diagnostic agent in conjunction with PET.

Acetates↗
PubMed1998

Association between asthma and an intragenic variant of CC16 on chromosome 11q13.

The beta subunit of high affinity immunoglobulin E (IgE) receptor (FcepsilonRIbeta) and the Clara cell derived inflammatory molecule, CC16 have been cited as candidate genes for atopic asthma on chromosome 11q13. A genetic association study was performed with an intragenic microsatellite repeat of CC16 gene on chromosome 11q12-13 in relation to atopic and non-atopic asthma. Whereas variants of FcepsilonRIbeta at chromosome 11q13 show association with atopy and asthma, no significant association was found between asthma and CC16 genotypes irrespective of atopic status. These data support the candidacy of FcepsilonRIbeta rather than CC16 for the atopic asthma locus on chromosome 11q.

Adult↗
PubMed1998

Differences between cochlear blood flow and endolymphatic sac blood flow in guinea-pigs.

Cochlear blood flow (CoBF) and endolymphatic sac (ES) blood flow (ESBF) were measured in different groups of guinea-pigs by laser-Doppler flowmetry after the intravenous administration of various drugs through the jugular vein for 60 sec. These drugs included 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium bicarbonate and 1% diphenidol. For CoBF measurements, a probe was positioned on the basal turn of the right cochlea via a ventral approach. For ESBF measurements, it was placed on the right ES through the posterior cranial fossa via a dorsal approach. The average initial measured value of ESBF (8.31 +/- 2.97 ml/min/100 g) was significantly greater (p < 0.0001) than that of CoBF (4.33 +/- 1.15 ml/min/100 g). Following administration of most drugs except for diphenidol, both CoBF and ESBF increased immediately after administration; however, following diphenidol administration both CoBF and ESBF decreased. The magnitude of the CoBF response tended to be greater than that of the ESBF response (p = 0.006-0.112). It seems likely that this reflects anatomical differences in the vascular supplies, i.e. CoBF from the vertebrobasilar artery and ESBF from the external carotid artery. In addition, the presence of micropores or fenestrations in the ES vasculature may contribute to the differences between CoBF and ESBF.

Animals↗
PubMed1998

Involvement of round and oval windows in the vestibular response to pressure changes in the middle ear of guinea pigs.

Changes in ambient pressure can elicit the vertigo and bodily disequilibrium known clinically as alternobaric vertigo. Our previous studies showed that changes in middle ear pressure altered the activity of the primary vestibular neuron, and the finding suggests that the pressure-induced vestibular response causes alternobaric vertigo. To investigate the roles played by the round window (RW) and the oval window (OW) in the vestibular response induced by pressure, we measured the change in perilymphatic pressure and the firing rates of primary vestibular neurons after the application of positive or negative pressure to the middle ear. We found an increase in the pressure-induced vestibular response in the group with a closed OW, and a decrease in the group with a closed RW. Measurements showed that the amplitude of the change in perilymphatic pressure in the group with a closed OW did not differ from that in the control group, whereas the amplitude of the perilymphatic pressure change in the group with a closed RW was significantly reduced. A discrepancy between the number of neurons responding and the amplitude of the perilymphatic pressure change in the closed OW group suggests that the vestibular response induced by the change in middle ear pressure was not related solely to the magnitude of the pressure change in the inner ear, but also involved the oval and round windows.

Animals↗
PubMed1998

A recessive heterochronic mutation, plastochron1, shortens the plastochron and elongates the vegetative phase in rice

We describe two recessive alleles of a rice heterochronic gene, plastochron1-1 (pla1-1) and pla1-2, that reduce the length of the plastochron to approximately half that of the wild type. Because the onset of the reproductive phase in pla1 was not temporally affected, the number of leaves produced in the vegetative phase was nearly twice that produced in the wild type. Panicle development was severely disturbed in pla1 mutants. In pla1-1, many primordia of primary rachis branches were converted into vegetative shoots. These ectopic shoots repeated the initiation of panicle development and the conversion of primary rachis branches into shoots. In the weak allele pla1-2, however, only the basal one or two primordia developed as vegetative shoots, and the remaining primordia developed to produce a truncated panicle. These results indicate that both vegetative and reproductive programs are expressed simultaneously during the reproductive phase of pla1; however, the degree varied depending on the strength of the allele. Accordingly, pla1 is a heterochronic mutation that extends the vegetative period. The shoot apical meristem of pla1 was larger than that of the wild type, although the shape was not modified. An in situ hybridization experiment using the histone H4 gene as a probe revealed that cell divisions are accelerated in the pla1 meristem. The PLA1 gene is considered to regulate the duration of the vegetative phase by controlling the rate of leaf production in the meristem.

Journal Article↗
PubMed1998

The perfect C. elegans project: an initial report.

The soil nematode Caenorhabditis Elegans (C. elegans) is the most investigated of all multicellular organisms. Since the proposal to use it as a model organism, a series of research projects have been undertaken, investigating various aspects of this organism. As a result, the complete cell lineage, neural circuitry, and various genes and their functions have been identified. The complete C. elegans DNA sequencing and gene expression mapping for each cell at different times during embryogenesis will be identified in a few years. Given the abundance of collected data, we believe that the time is ripe to introduce synthetic models of C. elegans to further enhance our understanding of the underlying principles of its development and behavior. For this reason, we have started the Perfect C. elegans Project, which aims to produce ultimately a complete synthetic model of C. elegans' cellular structure and function. This article describes the goal, the approach, and the initial results of the project.

Animals↗
PubMed1998

Immunohistochemical detection of vasoactive intestinal polypeptide (VIP) and the VIP receptor in the rat inner ear.

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide that was originally isolated from porcine duodenum. The presence of VIP has been demonstrated in the central nervous system and peripheral tissues. However, there have been few reports on VIP as a neurotransmitter, especially in the inner ear. To investigate the function of VIP in the rat inner ear, we examined the expression of VIP and the VIP receptor by immunohistochemistry. Using the anti-VIP and VIP receptor antibodies, scattered fibres in the cochlear nerve trunk demonstrating VIP-like immunoreactivity were found, and the spiral ganglion cells demonstrated ring-shaped VIP-like immunoreactivity. Immunoreactivity for the VIP receptor was predominantly found in the spiral ganglion cells. Our results suggest that VIP may play an important role as a possible neurotransmitter not only in the local control of cochlear blood flow, but also in the auditory system.

Animals↗
PubMed1998

Surgical observations on the endolymphatic sac in Meniere's disease.

OBJECTIVE: This study aimed to clarify the pathoanatomic characteristics of the endolymphatic sac in Meniere's disease by surgical observations. STUDY DESIGN: The study design was a retrospective case study conducted in the setting of University Hospital at Shiga University of Medical Science. PATIENTS: Studied were 101 patients with Meniere's disease who underwent endolymphatic sac drainage surgery at the university hospital by the same surgical team between 1984 and 1995. Control group consisted of 23 patients with non-Meniere's disease. MAIN OUTCOME MEASURES: Photographs were taken of the sac in 101 patients with Meniere's disease during endolymphatic sac drainage surgery, and the pathoanatomic findings of the sacs were classified into three grades regarding position (types I, II, III), size (large, intermediate, small), color (red, intermediate, white), and vascularity (fair, intermediate, poor). Statistical difference was studied between Meniere's group and non-Meniere's group by chi-square test. RESULTS: The patients with Meniere's disease were found to have endolymphatic sacs located inferiorly to the posterior semicircular canal, very close to the jugular bulb (type III) (p < 0.001). The sacs also were smaller in size (p = 0.068), whiter in surface color (p = 0.0036, 0.01), and of less vascularity (p = 0.051) than those of the patients with non-Meniere's disease. The comparisons showed significant differences only in position and color. CONCLUSION: The patients with Meniere's disease were found to have endolymphatic sacs located inferiorly to the posterior semicircular canal, very close to the jugular bulb. The sacs also were whiter in surface color.

Endolymphatic Sac↗
PubMed1998

First-pass radionuclide angiography using iodine-123 myocardial tracers and a multicrystal gamma camera.

UNLABELLED: The purpose of this study was to validate the accuracy of the assessment of ventricular function by first-pass radionuclide angiography (FPRNA) with 123I myocardial tracers and a multicrystal gamma camera. METHODS: Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction were measured in 69 patients by FPRNA using 123I myocardial tracers (126 +/- 7 MBq) and 99mTc tracers (541 +/- 141 MBq) on a multicrystal gamma camera with a high-sensitivity collimator. For 44 patients, ejection fraction values measured by 123I-FPRNA were compared to those estimated by equilibrium radionuclide angiography (ERNA). Visual wall-motion analysis was also performed to judge clinical acceptability of 123I-FPRNA images for identification of wall-motion abnormality. RESULTS: Mean LVEFs (%) estimated by 123I-FPRNA and by 99mTc-FPRNA were 49.6 +/- 13.6 and 49.1 +/- 14.1, respectively (nonsignificant p value). An excellent correlation was found between LVEFs estimated by 123I-FPRNA and 99mTc-FPRNA (r = 0.96, s.e.e. = 1.9%). Values of LVEF measured by 123I-FPRNA also demonstrated excellent correlation with those measured by ERNA (r = 0.95, s.e.e. = 2.2%). A good correlation was also noted between right ventricular ejection fractions measured by 123I-FPRNA and 99mTc-FPRNA (r = 0.72, s.e.e. = 4.0%). The Spearman rank correlation coefficient between 123I-FPRNA and ERNA wall-motion scores was 0.87 (n = 135, p < 0.001). CONCLUSION: Resting ventricular function can be reliably measured with 123I-FPRNA in combination with a multicrystal gamma camera. This indicates that the assessment of ventricular function is feasible in conjunction with 123I myocardial imaging without an increase in cost or radiation dose to patients.

Adult↗
PubMed1998

[A case of osteolytic metastases from breast cancer effectively treated with pamidronate].

A 55-year-old woman complained of neck pain ten years after the mastectomy. She was diagnosed as multiple bone metastases and received chemoendocrine therapy with 5'-DFUR and tamoxifen. Bone scintigram showed progressive disease, so we attempted biweekly administration of fadrozole and pamidronate (30 mg). After four months, pamidronate administration relieved her neck pain. CT revealed that all lytic lesions of cervical and thoracic vertebra showed sclerosis 11 months after pamidronate infusion. New lytic lesions are not defined, and the sclerosis has continued thus far. Pamidronate therapy is promising as an effective treatment in patients with osteolytic metastasis from breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Abnormality of myocardial oxidative metabolism in noninsulin-dependent diabetes mellitus.

UNLABELLED: The purpose of this study was to evaluate oxidative metabolism and its response by dobutamine in patients with noninsulin-dependent diabetes mellitus (NIDDM) using 11C-acetate PET. METHODS: We studied 16 patients with NIDDM (9 men, 7 women; mean age 53.7 +/- 12.8 yr) and 6 healthy male control subjects (mean age 41.8 +/- 17.2 yr). None of them had an abnormality on stress-perfusion SPECT. The 11C-acetate clearances (Kmono) were compared regionally for five myocardial segments in all subjects at rest and during low-dose dobutamine stress in 13 patients (8 patients with NIDDM, age 51.9 +/- 13.6 yr; 5 healthy male control subjects, age 45.6 +/- 16.3 yr). Correlation between regional Kmono and rate-pressure product (RPP) was also studied. RESULTS: At rest, the clearance of 11C-acetate was slightly heterogeneous for both patients with NIDDM and healthy control subjects, with smaller values in the apex and inferior wall in both groups. The difference became significant during dobutamine stress in the patients. The RPP-to-Kmono (average for five segments) ratio at rest was slightly smaller in the patients (1042.7 +/- 559.1 x 0.01) than in the healthy control subjects (1391.4 +/- 209.6 x 0.01, not significant), and those during dobutamine stress were almost the same in the two groups (1457.3 +/- 737.4 x 0.01 and 1486.0 +/- 211.8 x 0.01, respectively). A significant correlation was seen between regional Kmono and RPP in every segment in the healthy control subjects (average; r = 0.89; p < 0.01), whereas more scattered correlation with greater regional variation was observed in the patients (average; r = 0.31; p value was not significant). CONCLUSION: Patients with NIDDM showed slight regional heterogeneity in myocardial oxidative metabolism. They also had more scattered correlation between myocardial oxidative metabolism and cardiac work (RPP) than healthy control subjects, with the smallest correlation coefficient observed in the inferior wall. These findings may help the understanding of dynamics in myocardial oxidative metabolism of NIDDM hearts.

Acetates↗
PubMed1997

Vasopressin and oxytocin receptor mRNAs are expressed in the rat inner ear.

The cause of endolymphatic hydrops, a characteristic finding in Menière's disease, is not known. To study the possible involvement of the neurohormones vasopressin and oxytocin in this condition, we investigated whether transcripts of the genes encoding the arginine vasopressin (AVP) and oxytocin receptors are expressed in the rat inner ear. Utilizing the reverse transcription-polymerase chain reaction (RT-PCR) method, primers specific for each receptor showed a single message band of the expected size in the rat inner ear. When the PCR products were cloned, the sequences were identical to those of the real-type (V2) AVP receptor and oxytocin receptor transcripts. The finding of vasopressin and oxytocin receptor mRNAs in the inner ear suggests that these neurohypophyseal hormones may have roles in the regulation of inner ear fluid. In particular, the presence of vasopressin receptor mRNA in the inner ear supports the hypothesis of a relationship between high plasma vasopressin levels and endolymphatic hydrops.

Animals↗
PubMed1997

Detection of C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP-B) receptor mRNAs in rat inner ear.

C-Type natriuretic peptide (CNP) is the third member of the natriuretic peptide family which plays an important role in body fluid homeostasis. To determine a possible role of CNP in regulation of an inner ear fluid, we investigated the expression of CNP and atrial natriuretic peptide B receptor (ANP-B receptor) mRNAs in rat inner ear using a reverse transcription polymerase chain reaction (RT-PCR) method. Amplification products with sizes expected for CNP and ANP-B were detected in the inner ear. After cloning and analysis, the sequences for PCR products were identical to those of CNP or ANP-B receptor in the brain. These results indicate that both CNP and ANP-B receptor are expressed in the inner ear of the rat and suggest that CNP may play a role in inner ear function (such as regulation of inner ear fluid) in an autocrine and/or paracrine manner.

Animals↗
PubMed1997

[Differences in temporal bone development in various ear diseases].

To investigate the differences in temporal bone development in various ear diseases--bilateral Meniere's disease (n = 13), unilateral Meniere's disease (n = 41), unilateral chronic otitis media (COM) (n = 25), temporal bone fracture (n = 9) and otosclerosis (n = 12)--the following 4 distances on a temporal bone CT slice encompassing the lateral semicircular canal (LSC) were measured by using the NIH Image program. These distances included the minimal distance between the posterior semicircular canal (PSC) and the posterior petrous surface (PPS) (P-P distance), the minimal distance between the PSC and the LSC (P-L distance), the minimal distance between the vestibule and the PPS (V-P distance) and the minimal distance between the PSC and the anterior margin of the sigmoid sinus (P-S distance). Both the P-P and V-P distances showed significant differences among the ear diseases, but the P-L and P-S distance did not. Meniere's disease showed significantly shorter P-P and V-P distance especially in bilateral Meniere's disease than those in COM and otosclerosis (p < 0.05). Affected ears in unilateral Meniere's disease showed a shorter P-P distance than non-affected ears (p < 0.01). In contrast, both ears with otosclerosis showed significantly longer P-P and V-P distances than those in Meniere's disease, COM (p < 0.01) and temporal bone fracture (p < 0.05). COM and temporal bone fracture showed intermediate P-P and V-P distances, without a difference between the affected and non-affected ears. In conclusion, the development of the posterior part of the temporal bone is reduced in Meniere's disease and greatly increased in otosclerosis. These findings by CT may be useful for diagnosing ear diseases.

Ear Diseases↗
PubMed1996

Evidence for the involvement of ecto-5'-nucleotidase (CD73) in drug resistance.

Increased ecto-5'-nucleotidase (ecto-5'NT) protein expression in several multidrug-resistant (MDR) cell lines, documented previously by our group, suggests that this enzyme is involved in drug resistance. Here, Northern blot analysis of selected cell lines and their MDR variants positively correlated ecto-5'NT protein with its mRNA expression. An inhibitor of ecto-5'NT enzymatic activity, alpha,beta-methyleneadenosine 5'-diphosphate (AMP-CP), was used to determine if functionally active enzyme had a role in drug resistance. AMP-CP (0.3 mM) reversed the resistance of ecto-5'NT-positive MDR cells (MCF7/A6, L1210/A) to doxorubicin, whereas it did not affect the doxorubicin sensitivity of the ecto-5'NT-negative parental cell lines or that of 2 ecto-5'NT-negative MDR cell lines (HL60/VCR and A2780/DX5). Furthermore, AMP-CP increased rhodamine uptake and inhibited rhodamine efflux from ecto-5'NT-positive MDR cells without affecting ecto-5'NT-negative MDR cells. The presence of exogenous adenosine (0.5 microM) circumvented AMP-CP-induced inhibition of rhodamine efflux from EL4/ADM cells. AMP-CP inhibited the growth of the ecto-5'NT-positive L1210/A MDR cells but had no effect on the growth of the parental cell line. Determination of intracellular ATP levels indicated that MDR cells which had increased ecto-5'NT expression also had a lower intracellular ATP level than their parental cells. Our results suggest that, in certain MDR cell lines, ecto-5'NT serves as a required accessory molecule in resistance mediated by ATP-dependent mechanisms and that growth-sustaining nucleosides are provided by this salvage pathway.

5'-Nucleotidase↗