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Biomedical subjects

T Hatta

Publications and source records attributed to T Hatta.

At least 55 records · Page 3Linked to original sources

Are nonproper chopstick holders clumsier than proper chopstick holders in their manual movements?

To examine the working hypothesis that a lack of childhood training in the fine-detailed finger movements illustrated by learning to use chopsticks properly as a child has later rendered such individuals clumsier in the execution of other more adult-like motor movements, four experiments were conducted. Groups of proper and nonproper users (both males and females) performed a task of picking up rice grains (Exp. 1), a pin-down task (Exp. 2), a task of unfastening nuts from bolts (Exp. 3), and a knot-tying task (Exp. 4). Only on the rice-grain transfer task and the knot-tying task, proper chopstick users showed better performance than nonproper users. On the pin-down task and the nuts-and-bolts task, no difference was found between groups. These results suggest that there is no clear evidence to support the hypothesis that a lack of early training for proper chopstick use makes such individuals more clumsy as adults in at least some motor movements.

Adult↗

Renal expression of insulin-like growth factor-l in acute renal failure: a preliminary report.

Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.

Acute Kidney Injury↗

Hemisphere specialization of Go experts in visuospatial processing.

To investigate hemisphere function of experts, Go experts and novices were given two Salthouse-type visuospatial tasks. In Experiment 1, stimuli of 4 digits in 6 cells were projected to the left (LVF) or right visual field (RVF). There was no prominent group difference in identification of digits and locations. In Experiment 2, stimuli of 4 digits in 16 cells were projected to the LVF or RVF. Go experts showed more accurate performance than novices. Both groups showed the same laterality, an RVF advantage, in the number identification. However, in the location identification, Go experts showed no visual field difference, whereas novices showed an RVF advantage. Based on these findings, the relationship between task demand and hemisphere function of experts is discussed.

Adult↗

Inhibition of influenza virus RNA polymerase by 5'-capped short RNA fragments.

We have demonstrated that 5'-capped short RNA fragments inhibit the expression of chloramphenicol acetyltransferase (CAT) in the murine 76 cell line, derived which expresses the genes for the RNA polymerases (PB1, PB2, and PA) and the nucleoprotein (NP) of influenza virus in response to treatment with dexamethasone. We have synthesized 5'-capped short RNA fragments (8-13 ntds long) with a 5'-capped structure (m7GpppGm) using T7 RNA polymerase. The 5'-capped short RNA fragments (8-13 ntds long) were encapsulated in liposomes and were tested for their inhibitory effect by a CAT-ELISA assay using the clone 76 cells. The RNA fragments that were 9-12 ntds long showed inhibitory effects. In particular, the 9 ntds long RNA fragment, was highly inhibitory. On the other hand, the inhibitory effect of the 13 ntds long RNA fragment was considerably decreased in comparison with the other short RNA fragments. The minimal RNA chain length required for priming activity was found to be 12 ntds long. Furthermore, the 5'-capped RNA fragments exhibited higher inhibitory activities than the antisense phosphorothioate oligonucleotide (PB2-AUG-as, 20 ntds long) complementary to the site of the PB2-AUG initiation codon. Liposome encapsulation protected the RNA fragments in serum-containing medium and substantially improved their cellular accumulation.

DNA-Directed RNA Polymerases↗

Analysis of changes in congener selectivity during PCB degradation by Burkholderia sp. strain TSN101 with increasing concentrations of PCB and characterization of the bphBCD genes and gene products.

We isolated and characterized a gram-negative bacterium, Burkholderia sp. strain TSN101, that can degrade polychlorinated biphenyls (PCBs) at concentrations as high as 150 microg Kaneclor 300/ml, a PCB mixture equivalent to Aroclor 1242. Growing cells of strain TSN101 degraded most of the tri- and tetrachlorobiphenyls in medium containing 25 microg Kaneclor 300/ml. Using PCB concentrations of 50-150 microg of Kaneclor 300/ml, the congener selectivity pattern was different and the pattern of chlorine substitution strongly affected degradation of some congeners. At 25 microg Kaneclor 300/ml, strain TSN101 degraded di- and trichlorinated congeners with chlorine substitutions at both the ortho and the para positions. At higher concentrations of Kaneclor 300, di- and trichlorobiphenyls with ortho substituents in both phenyl rings were not degraded well. Trichlorobiphenyls with para and meta substitutents were degraded equally well at all concentrations studied. The ability of strain TSN101 to degrade ortho and para-substituted congeners was confirmed using a defined PCB mixture with chlorine substituents at 2'- and 4'-positions. A 5-kb DNA fragment containing the bphBCD genes was cloned and sequenced. Comparison of the deduced amino acid sequences of these genes with related proteins indicated 99 and 98% sequence similarity to the BphB and BphD of Comamonas testosteroni strain B-356, respectively. The bphC gene product showed 74% sequence similarity to the BphC of Burkholderia cepacia strain LB400 and exhibited a narrow substrate specificity with strong affinity for 2, 3-dihydroxybiphenyl. A bphC-disrupted mutant of Burkholderia sp. strain TSN101, constructed by gene replacement, lost the ability to utilize biphenyl, thus supporting the role of the cloned bph gene in biphenyl metabolism.

Aroclors↗

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Animals↗

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗

Two nearly identical aromatic compound hydrolase genes in a strong polychlorinated biphenyl degrader, Rhodococcus sp. strain RHA1.

The two 2-hydroxy-6-oxohepta-2,4-dienoate (HOHD) hydrolase genes, etbD1 and etbD2, were cloned from a strong polychlorinated biphenyl (PCB) degrader, Rhodococcus sp. strain RHA1, and their nucleotide sequences were determined. The etbD2 gene was located in the vicinity of bphA gene homologs and encoded an enzyme whose amino-terminal sequence was very similar to the amino-terminal sequence of the HOHD hydrolase which was purified from RHA1. Using the etbD2 gene fragment as a probe, we cloned the etbD1 gene encoding the purified HOHD hydrolase by colony hybridization. Both genes encode a product having 274 amino acid residues and containing the nucleophile motif conserved in alpha/beta hydrolase fold enzymes. The deduced amino acid sequences were quite similar to the amino acid sequences of the products of the single-ring aromatic hydrolase genes, such as dmpD, cumD, todF, and xylF, and not very similar to the amino acid sequences of the products of bphD genes from PCB degraders, including RHA1. The two HOHD hydrolase genes and the RHA1 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HPDA) hydrolase gene, bphD, were expressed in Escherichia coli, and their relative enzymatic activities were examined. The product of bphD was very specific to HPDA, and the products of etbD1 and etbD2 were specific to HOHD. All of the gene products exhibited poor activities against the meta-cleavage product of catechol. These results agreed with the results obtained for BphD and EtbD1 hydrolases purified from RHA1. The three hydrolase genes exhibited similar induction patterns both in an RNA slot blot hybridization analysis and in a reporter gene assay when a promoter probe vector was used. They were induced by biphenyl, ethylbenzene, benzene, toluene, and ortho-xylene. Strain RCD1, an RHA1 mutant strain lacking both the bphD gene and the etbD2 gene, grew well on ethylbenzene. This result suggested that the etbD1 gene product is involved in the meta-cleavage metabolic pathway of ethylbenzene.

Amino Acid Sequence↗

Specific inhibition of influenza virus RNA polymerase and nucleoprotein gene expression by liposomally encapsulated antisense phosphorothioate oligonucleotides in MDCK cells.

We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza A virus replication in MDCK cells. Liposomally encapsulated and free antisense S-ODNs with four target sites (PB1, PB2, PA and NP genes) were tested for their abilities to inhibit virus-induced cytopathogenic effects in a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the site around the PB2 AUG initiation codon showed highly inhibitory effects. In contrast, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with that directed to the PB2 target site. The liposomally encapsulated antisense S-ODNs exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas free antisense S-ODNs were observed to inhibit viral adsorption to MDCK cells. Liposomal preparations of oligonucleotides facilitated their release from endocytic vesicles, and thus cytoplasmic and nuclear localization was observed. The activities of the antisense S-ODNs were effectively enhanced by using the liposomal carrier. Interestingly, the liposomally encapsulated FITC-S-ODN-PB2-as accumulated in the nuclear region of MDCK cells. However, weak fluorescence was observed within the endosomes and the cytoplasm of MDCK cells treated with the free antisense S-ODNs. The cationic lipid particles may thus be a potentially useful delivery vehicle for oligonucleotide-based therapeutics and transgenes, appropriate for use in vitro or in vivo.

Antiviral Agents↗

Induction of ectopic corticotropic tumor in mouse embryos by exo utero cell transplantation and its effects on the fetal adrenal gland.

To establish an in vivo experimental system for developmental endocrinology research, AtT-20 cells, a corticotropic tumor cell line, were transplanted by exo utero manipulation into mouse embryos on embryonic day 14. The induced tumor secreted ACTH in situ, and the circulating ACTH level was elevated. This was the first model for studying the regulation of ACTH in the mouse fetal adrenal in vivo and the first continuous ACTH treatment model in rodent fetuses. The changes in the adrenal gland from the tumor-induced embryos were analyzed by light microscopic morphometry, immunohistochemistry for steroidogenic enzymes, and electron microscopy. In the treated adrenal, the volume of the inner cortical zone was significantly larger than that in controls. In the inner zone, cell density was decreased, and average cell size was increased, whereas bromodeoxyuridine-incorporation was not increased. The enlarged inner zone cells expressed an enhanced level of cytochrome P45011beta, the corticosterone-synthesizing enzyme, and the serum corticosterone level was increased. Electron microscopy showed an active form of the organelles involved in steroidogenesis. These findings indicate that ACTH stimulates both adrenocortical hypertrophy and steroidogenesis in fetal mice. Potential perspectives of the novel paradigm in this research for molecular developmental endocrine study are discussed.

Adrenal Glands↗

Semantic priming of Kanji words in the cerebral hemispheres.

Two experiments were conducted to investigate how the spreading activation arose in hemispheres using single and 2-letter Kanji words. Results suggested that single- and 2-letter Kanji words were processed differentially and the semantic activation mechanisms seemed to be different from that of English words.

Brain↗

[Lung laceration caused by penetrating chest wall injury in Hanshin & Awaji earthquake: a case report].

A 36-year-old man having a left lower lobe laceration caused by penetrating chest wall injury was operated on 5 hours after Hanshin & Awaji Earthquake. At thoracotomy, significant destruction of the left lower lobe was observed. Therefore, we gave up repairing a lung, and performed left lower lobectomy, with a satisfactory outcome. Our hospital is located on 30 km south of seismic center, but the function of our hospital was not completely paralyzed. In Awaji island, emergent treatments were done satisfactorily.

Adult↗

K-ras is essential for the development of the mouse embryo.

ras genes encode members of the small GTP-binding proteins. Ras protein in highly conserved in various species from yeast to humans and plays a key role in signal transduction. Ras is related to cell proliferation and differentiation. While, in addition, mutations in the ras genes are implicated in a variety of tumors. However, the physiological functions and specific roles of each ras gene, H-ras, K-ras and N-ras, are still not fully understood. To clarify the role of the K-Ras in vivo, we generated K-ras mutant mice by gene targeting. In contrast to the findings that H-Ras-deficient mice and N-Ras-deficient mice are born and grow normally, the K-Ras-deficient embryos die progressively between embryonic day 12.5 and term. At embryonic day 15.5, their ventricular walls are extremely thin. Besides, at embryonic day 11.5, they demonstrate increased cell death of motoneurons in the medulla and the cervical spinal cord. Our results thus indicate K-Ras to be essential for normal development in mice and residual Ras composed of H-Ras and N-Ras cannot compensate for the loss of K-Ras function in the mutant mice.

Animals↗

Specific inhibition of influenza virus RNA polymerase and nucleoprotein genes expression by liposomally endocapsulated antisense phosphorothioate oligonucleotides: penetration and localization of oligonucleotides in clone 76 cells.

Liposomally encapsulated phosphorothioate oligonucleotides with four target sites (PB1, PB2, PA, and NP) were synthesized and tested for inhibitory effects by a CAT-ELISA assay using the clone 76 cell line. The liposomally encapsulated phosphorothioate oligonucleotides (S-ODNs) complementary to the sites of the PB2-AUG and PA-AUG initiation codons showed highly inhibitory effects. Displacement of the target AUG initiation codon sequence to the 3'-end, 5'-end, and/or center sites on the antisense phosphorothioate oligonucleotides was studied with regard to the inhibition of influenza virus RNA polymerases and NP. The antisense phosphorothioate oligonucleotide containing the AUG initiation codon at the center site of the oligonucleotide had the highest inhibitory effects. The liposomally encapsulated phosphorothioate oligonucleotides exhibited higher inhibitory activity than the free oligonucleotides. Observation of clone 76 cells treated with the endocapsulated antisense phosphodiester oligonucleotide, FITC-ODNs-PB2-T3, by a confocal laser scanning microscope, revealed diffuse fluorescence, apparently within the cytoplasm. Interestingly, the endocapsulated antisense phosphorothioate oligonucleotide, FITC-S-ODNs-PB2-T3 accumulated in the nuclear region of clone 76 cells. However, weak fluorescence was observed in the endosomes and in the cytoplasms of the clone 76 cells treated with the free antisense phosphorothioate oligonucleotides.

Animals↗

The bphDEF meta-cleavage pathway genes involved in biphenyl/polychlorinated biphenyl degradation are located on a linear plasmid and separated from the initial bphACB genes in Rhodococcus sp. strain RHA1.

The bphACB genes responsible for the initial oxidation of the aromatic ring of biphenyl/polychlorinated biphenyls (PCB) to meta-cleavage product in Rhodococcus sp. RHA1 have been characterized. We cloned the 6.1 kb EcoRI fragment containing another extradiol dioxygenase gene (etbC) which was induced during the growth on ethylbenzene. The bphD, bphE and bphF encoding 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HOPD) hydrolase, 2-hydroxypenta-2,4-dienoate hydratase and 4-hydroxy-2-oxovalerate aldolase, respectively, were found downstream of etbC. The deduced amino acid (aa) sequence of RHA1 bphD and bphE had 27-33% and 32-38% identity, respectively, with those of the corresponding genes in Pseudomonas. BphE and BphF are closely related to the corresponding homoprotocatechuate meta-cleavage pathway enzymes of Escherichia coli C. The bphD and bphF were expressed in E. coli and the BphD activity was detected. The etbCphDEF genes were transcribed in biphenyl and ethylbenzene growing cells. Pulsed field gel electrophoresis (PFGE) analysis indicated that RHA1 contains three large linear plasmids. Southern blot analysis indicated that the meta-cleavage pathway for biphenyl/PCB catabolism in RHA1 is directed by the 390 kb plasmid borne bphDEF genes located separately from bphACB gene cluster on the 1100 kb plasmid.

Benzene Derivatives↗

Apoptosis in the development of the temporomandibular joint.

Apoptosis has been shown to be involved in remodeling of organs during development, and derangement of the apoptotic process may result in temporomandibular joint (TMJ) dysfunction or congenital malformation. To investigate the relationship between the development of the TMJ and apoptosis, rat fetuses at 17.5-20.5 days of gestation (E17.5-20.5, vaginal plug=E0) and rats at postnatal days 1, 2, 3, 5, and 10 (P1, 2, 3, 5, and 10) were examined by light (LM) and transmission electron microscopy (TEM) and electrophoretic analysis of DNA fragmentation. At E17.5 and 18.5, a few layers of slender mesenchymal cells which eventually develop into the TMJ disk were observed, although TEM or electrophoresis did not reveal apoptotic cells at these stages. At E19.5 and 20.5, all structures of the TMJ except the lower joint cavity could be distinguished, but at these stages apoptotic cells were not observed. In P1 condyles, apoptotic cells were observed by TEM both at the subsurface of the condyle and in the region at which the lateral pterygoid muscle attaches to the condyle. These apoptotic cells showed irregular chromatin condensation, convolution of the cell membrane, and fragmentation and disintegration of the cytoplasm. Electrophoretic analysis of the P1 condyle further confirmed DNA fragmentation. Apoptosis was not observed in all specimens at the P1 stage. It was confirmed in 8 out of 20 animals (10 out of 27 joints) by TEM and/or electrophoretic analysis. The shape of the upper portion of the condyle flattened progressively from E20.5 to P2. At this stage, the lower joint cavity was developing, as observed by LM. These findings suggest that the morphological changes of the mandibular condyle effected by apoptosis, together with development of the lower joint cavity, play important roles in the postnatal functional adaptation to external stimuli such as mechanical strain.

Animals↗

Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR.

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.

Animals↗

Image generation and handedness: is the hemi-imagery method valid for studying the hemisphere imagery generation process?

The validity of the proposal by Shuren et al. (Neuropsychologia, 1996, 34, 491-492) that there is some relation between handedness and hemi-imagers was investigated by means of the hemi-imagery test. Two-hundred and two subjects were asked to image one-half of an object and to report which half (left or right) they saw. The analyses, based on criteria identical to those of Shuren et al., did not replicate their findings that subjects were more likely to image the right half of objects than the left, and that right handers are right hemi-imagers. Rather, our subjects were more inclined to image the left half than the right, and no relation between handedness score and right hemi-imagers was found. It is suggested that the reading habits of the different cultures of the groups of subjects may account for this discrepancy.

Adolescent↗