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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 343 records · Page 19Linked to original sources

Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging.

(beta-Hydroxyethyl)tri([11C]methyl)ammonium ([11C]choline) is a tracer very effective in imaging various human tumors using positron emission tomography (PET). We have constructed a computer-controlled [11C]choline synthetic apparatus which carries out the whole process of synthesis and product purification automatically. The setup is simple and the process quick. In 20 min, 11 GBq of [11C]choline (chloride) is obtainable from 26 GBq of [11C]CO2. The final product is a sterile and pyrogen-free [11C]choline "injection".

Carbon Radioisotopes↗

Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region.

Recent studies with avian embryos and murine embryonic stem cells have suggested that hematopoietic cells are derived from hemangioblasts, the common precursors of hematopoietic and endothelial cells. We molecularly cloned podocalyxin-like protein 1 (PCLP1) as a novel surface marker for endothelial-like cells in the aorta-gonad-mesonephros (AGM) region of mouse embryos, where long-term repopulating hematopoietic stem cells (LTR-HSCs) are known to arise. PCLP1+ CD45 cells in the AGM region incorporated acetylated low-density lipoprotein and produced both hematopoietic and endothelial cells when cocultured with OP9 stromal cells. Moreover, multiple lineages of hematopoietic cells were generated in vivo when PCLP1 +CD45-cells were injected into neonatal liver of busulfan-treated mice. Thus, PCLP1 can be used to separate hemangioblasts that give rise to LTR-HSCs.

Amino Acid Sequence↗

Three-dimensional microstructural analysis of human trabecular bone in relation to its mechanical properties.

The purpose of this preliminary study is to explore the relationship between elastic modulus, bone mineral density (BMD), and trabecular microstructure in three dimensions. Twenty cubes of trabecular bone were processed from two lumbar vertebrae obtained from one individual. The BMD of each cube was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Each cube was serially scanned by microcomputed tomography to produce three-dimensional data sets. By analyzing these data sets, three-dimensional trabecular microstructural indices of connectivity density and fractal dimension were calculated as well as histomorphometric parameters. The cubes were tested mechanically in a nondestructive manner for measurement of their elastic modulus. This preliminary study showed that: (1) bone mass index is correlated with mechanical properties, with coefficients of correlation ranging from 0.552 to 0.601; and (2) when controlling for BMD, no association could be detected between measures of structural complexity (connectivity density and fractal dimension) and elastic modulus in the craniocaudal direction of human vertebral bodies.

Biomechanical Phenomena↗

The laminin-derived peptide YIGSR (Tyr-Ile-Gly-Ser-Arg) inhibits human pre-B leukaemic cell growth and dissemination to organs in SCID mice.

The YIGSR (Tyr-Ile-Gly-Ser-Arg) laminin beta1 chain sequence has an inhibitory effect on tumour growth and the metastasis of melanoma and fibrosarcoma cells. In the present study, we investigated whether the multimeric YIGSR peptide (Ac-Y16) has an antiproliferative effect and/or prevents the metastasis of human pre-B acute lymphoblastic leukaemia cells (NALM6) in severe combined immune deficient (SCID) mice. In in vitro studies, Ac-Y16 significantly inhibited leukaemic cell colony formation and the invasion of NALM6 cells in a Matrigel-based assay. The tumour growth and leukaemic infiltration in peripheral tissues were also analysed in SCID mice 9 weeks after NALM6, Matrigel and Ac-Y16 were subcutaneously co-injected. The weight of the subcutaneous tumours was significantly suppressed by Ac-Y16 in a dose-dependent manner. Flow cytometry analysis showed that the leukaemic infiltration was significantly inhibited in all organs with 1.5-2.0 mg of Ac-Y16. Leukaemic infiltrations in the brain were inhibited with 0.5 mg of Ac-Y16, and those in brain and bone marrow were also inhibited with 1.0 mg of Ac-Y16. With Ac-S16, a control-scrambled peptide, the only significant inhibition of the leukaemic infiltration was observed in bone marrow at a much higher dose. These data suggest that the multimeric YIGSR peptide can inhibit the tumour growth and metastasis of leukaemic cells and may be useful as a potential therapeutic reagent for leukaemic infiltrations.

Actins↗

Oversecretion of IL-18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity.

We investigated the significance of interleukin (IL)-18 levels in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). IL-18 levels were significantly elevated in all nine patients with active HLH compared with those of healthy controls. Serial determination of IL-18 levels in three cases, showed a gradual decrease compared with those of IL-12, interferon (IFN)-gamma or soluble Fas ligand (sFasL) in the course of clinical improvement, and seemed to be elevated until complete disappearance of disease activity. IL-18 and IFN-gamma (CC 0.711, P = 0.018), and IFN-gamma and sFasL (CC 0.849, P = 0.0049) levels were significantly correlated. On the other hand, correlation between IL-12 and IFN-gamma, IL-18 and sFasL, or IL-18 and IL-12 was not observed. IL-18, IFN-gamma and sFasL levels significantly correlated with disease activity such as fever and alanine transaminase (ALT) levels. IL-18 mRNA expression was enhanced in spleen, but not in peripheral blood mononuclear cells (MNC), bone marrow MNC, liver from patients of active HLH, or the tumour from a patient with lymphoma-associated haemophagocytic syndrome (LAHS). These results suggest that IL-18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. IL-18 measurement may be useful for the diagnosis and for the detection of smouldering disease activity.

Cell Communication↗

Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients.

The effects of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function were studied in 28 patients undergoing spinal fusion surgery. Patients were randomly divided into three groups to receive TMP (group A, n = 10), TNG (group B, n = 10) or PGE1 (group C, n = 8). Anaesthesia was maintained with N2O and sevoflurane. The mean arterial blood pressure was maintained at 60 mmHg for 90 min. Measurements included arterial ketone body ratio (AKBR-acetoacetate/3-hydroxybutyrate), SGOT, SGPT, LDH, blood glucose and blood gases were made. Measurements were taken before hypotension, 60 min and 90 min after starting hypotension, 60 min after recovery from hypotension and on the post-operative day. AKBR showed no significant change. SGOT, SGPT and LDH were within normal limits. Controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia in surgical patients did not cause hepatocellular damage.

Adult↗

Splanchnic perfusion during controlled hypotension with haemodilution under isoflurane anaesthesia in elderly patients.

We investigated the effects of controlled hypotension with haemodilution under isoflurane anaesthesia on splanchnic perfusion in elderly patients. We determined the intramucosal pH using gastric tonometry in 28 patients scheduled for hip surgery. Patients without cardiac disease were assigned to two groups according to age. Group A (adult patients, n = 14) included patients aged less than 60 years (range 29-58 years, 47 +/- 11 years, mean +/- SD) and group B (elderly patients, n = 14) more than 65 years (68-78 years, 72 +/- 5 years). Anaesthesia was maintained with N2O-O2-isoflurane. After induction of anaesthesia, haemodilution was produced by drawing 800-1000 mL of blood and replacing it with the same amount of hydroxyethyl starch. Final haematocrit values were 23-24% in all groups. Controlled hypotension was induced with prostaglandin E1 (PGE1) and mean blood pressure was maintained at approximately 60 mmHg for approximately 80 min. Measurements, including gastric intramucosal pH (pHi), arterial blood pH (pHa) and serum lactate were measured before haemodilution (T0), after haemodilution (T1), 80 min after starting hypotension (T2), 60 min after recovery from hypotension (T3) and on the 1st post-operative day (T4). The values of pHa and lactate showed no change in the groups throughout the time course. The gastric pHi values showed significant decreases from 7.418 +/- 0.035 to 7.334 +/- 0.024 (P < 0.05) in group A and from 7.428 +/- 0.029 to 7.320 +/- 0.039 (P < 0.05) in group B after haemodilution, while no further decreases were found at 80 min after starting the hypotension (7.329 +/- 0.038 in group A and 7.322 +/- 0.031 in group B) and 60 min after recovery from hypotension (7.331 +/- 0.029 in group A and 7.328 +/- 0.034 in group B). It can be concluded that moderate haemodilution under isoflurane anaesthesia might impair splanchnic perfusion in adult and elderly patients. The addition of controlled hypotension with PGE1 or an increase in age did not further impair splanchnic perfusion nor the splanchnic oxygen supply.

Adult↗

The effect of diabetes mellitus on histopathological changes in the denture-supporting tissues under continuous mechanical pressure in rat.

The histopathological changes in denture-supporting tissues of streptozotocin-induced diabetes mellitus rat were studied in relation to continuous mechanical pressure exerted through an experimental denture base. The experimental dentures were designed to load continuous mechanical pressures (3.4, 1.5 or 0.5 kPa) to the hard palate of the molar region of a rat. From the results of this study, the following conclusions were drawn: the streptozotocin-induced diabetic condition (1) tended to prolong the appearance period of a shortened epithelial ridge, and weakened the phenomenon, (2) reduced the appearance period and severity of the compression of epithelium, (3) delayed the time of manifestation of the proliferative change in the recovery process of the shortened epithelial ridge, and weakened the phenomenon, (4) prolonged the appearance period of the compressed lamina propria mucosae, and enhanced the phenomenon, (5) reduced the number of osteoclasts, (6) lowered the threshold for induction of the osteoclastic bone resorption to between 1.5 and 0.5 kPa, (7) inhibited the appearance of osteoblast which follows the disappearance of osteoclasts, (8) did not induce any inflammatory change, and (9) tended to enhance the longitudinal change of the continuous mechanical pressure. The histopathological changes in the denture-supporting tissues of the streptozotocin-induced diabetes mellitus rat related highly to the longitudinal change of the continuous mechanical pressure exerted through the denture base. From the results of this study, it was suggested that the streptozotocin-induced diabetic condition lowers the tolerance of the denture-supporting tissues to continuous mechanical pressure.

Animals↗

The effect of diabetes mellitus on histopathological changes in the tissues under denture base bearing masticatory pressure.

The effect of streptozotocin-induced diabetes mellitus on histopathological changes in tissues bearing masticatory pressure exerted through an experimental denture base has been studied in animal specimens. Experimental dentures, which prescribed the masticatory pressure by the amount of subsidence of the denture base (100, 50 or 13 microm), were constructed for the hard palate of the molar regions of rats. It was revealed that streptozotocin-induced diabetes mellitus (1) weakened the intercellular junctions in the epithelium and gradually enhanced this state with time, (2) lessened the atrophic and proliferative reactions in the epithelial ridge and prolonged their appearance period, (3) enhanced the compression of lamina propria mucosae and prolonged the appearance period of this reaction, (4) enhanced the inflammatory change and extended its appearance period, (5) lowered the threshold for the inflammatory reaction induced by the masticatory pressure, (6) increased the number of osteoclasts and prolonged the period of their presence, (7) lowered the threshold for osteoclastic bone resorption induced by the masticatory pressure, (8) inhibited the appearance of osteoblasts following the disappearance of osteoclasts and (9) accelerated the decline rate of masticatory pressure exerted to the denture supporting tissues. Therefore, it can be concluded that the streptozotocin-induced diabetes mellitus in the animals tested deteriorated the tolerance of the denture supporting tissues to masticatory pressure.

Alveolar Bone Loss↗

Relationship between anterior guidance and mesiodistal inclination of lower incisor in human subject with or without TMJ noise.

The relationship between anterior guidance and the mesiodistal inclination of the lower incisors relative to the existence of temporomandibular joint (TMJ) noise was investigated. One hundred and thirty-four individuals, 21 to 40 years of age (mean age 23.8; 104 men and 30 women), were examined. A highly significant correlation was observed between the mean lower-incisor inclination and the difference in steepness between the right and left anterior guidances in the subject group showing TMJ noise (P<0.001), whereas no significant correlation was observed in the group without TMJ noise.

Adult↗

Hereditary angioedema with gastrointestinal involvement: endoscopic appearance.

We present the first reported case of hereditary angioedema (HAE) with gastric involvement to be successfully evaluated by endoscopy both during and after an attack. A 31-year-old man who had a family history of angioedema was admitted to our hospital with complaints of abdominal pain and swelling of extremities. Computed tomography scan and endoscopy carried out during this attack revealed transient gastrointestinal wall edema which, along with decreased levels of serum C4 and C1 inhibitor, confirmed the diagnosis of HAE with gastrointestinal involvement. During the attack, the gastric mucosa was erythematous and edematous, and parts of its surface bulged into the gastric lumen, resembling a submucosal tumor, as a result of massive submucosal edema. During the healing process, a number of small nodules and raised erosions developed over the entire gastric mucosal surface after healing of prominent gastric edema. Within 55 days, the gastric mucosa had returned to normal. The endoscopic findings for the stomach in HAE have not, to our knowledge, been previously described.

Adult↗

Factors affecting maternal anxiety about child rearing in Japanese mothers.

In order to determine the factors causing anxiety in raising young children, data were collected from questionnaires completed by 1164 mothers of 3-y-old children at a standardized baby check-up. Factors concerning demographic characteristics, delivery and child rearing practice were used in multivariate logistic regression analysis. Stepwise logistic regression analysis showed that mothers rearing first children and toddlers who were susceptible to common illnesses were likely to worry. Improvements in the child rearing environment are needed.

Anxiety↗

Long-term outcome of 51 liveborn neonates with non-immune hydrops fetalis.

To search for an efficient method of management of non-immune hydrops fetalis (NIHF), the clinical outcome of 51 newborns with NIHF was retrospectively assessed in a single centre. As the short-term outcome, the mortality rate was mainly dependent on the causes of NIHF and the presence of pleural effusion. The survival rate of the patients with pleural effusion (7/28; 25%) was significantly lower than that of those without it (14/23; 61%) (p < 0.02). All 7 survivors with pleural effusion were diagnosed antenatally after 29 weeks of gestation and were delivered after 31 weeks of gestation. With respect to the long-term outcome, 13 (68.4%) of 19 patients who survived beyond 1 y of age showed normal development, 2 mild developmental delay at 1 y of age and 1 mental retardation at 8 y of age, while 3 (15.8%) had severe psychomotor retardation with marked growth failure. Two of these three patients were born as very-low-birthweight infants. The follow-up results indicate that pleural drainage in utero and prevention of premature delivery should be proposed to improve the outcome of NIHF patients.

Female↗

Adenovirus vector expressing mouse oncostatin M induces acute-phase proteins and TIMP-1 expression in vivo in mice.

Mouse oncostatin M (MuOSM) regulates the production of acute-phase proteins by hepatocytes as well as tissue inhibitor of metalloproteinases-1 (TIMP-1) production by fibroblasts in vitro. We have generated an adenovirus (Ad) encoding MuOSM and tested the effects of administration of recombinant AdMuOSM to mice in vivo. On intramuscular injection, AdMuOSM (5 X 10(7) plaque-forming units, pfu) induced an increase in serum levels of interleukin-6 (IL-6) as well as the acute-phase proteins serum amyloid A (SAP) and alpha1-acid glycoprotein (AGP) at day 1. SAP and AGP concentrations were elevated to greater levels at day 3 and decreased to near control levels at day 7. Intratracheal treatment with AdMuOSM induced TIMP-1 mRNA levels (as assessed by Northern blots) that corresponded to the presence of transgene MuOSM mRNA levels. TIMP-1 was elevated at day 1 and day 3 and less consistently at day 7 after administration. Intraperitoneal treatment with AdMuOSM also resulted in elevation of TIMP-1 mRNA in lung tissue. These results show that AdMuOSM can induce both local and systemic effects and demonstrate in vivo effects of OSM that are consistent with in vitro studies on acute-phase protein and TIMP-1 expression.

Acute-Phase Proteins↗

Tissue specific expression and chromosomal mapping of a human UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1, 4-N-acetylglucosaminyltransferase.

A human cDNA for UDP- N -acetylglucosamine:alpha1,3-d-mannoside beta1,4- N- acetylglucosaminyltransferase (GnT-IV) was isolated from a liver cDNA library using a probe based on a partial cDNA sequence of the bovine GnT-IV. The cDNA encoded a complete sequence of a type II membrane protein of 535 amino acids which is 96% identical to the bovine GnT-IV. Transient expression of the human cDNA in COS7 cells increased total cellular GnT-IV activity 25-fold, demonstrating that this cDNA encodes a functional human GnT-IV. Northern blot analysis of normal tissues indicated that at least five different sizes of mRNA (9.7, 7.6, 5.1, 3.8, and 2.4 kb) forGnT-IV are expressed in vivo. Furthermore, these mRNAs are expressed at different levels between tissues. Large amounts of mRNA were detected in tissues harboring T lineage cells. Also, the promyelocytic leukemia cell line HL-60 and the lymphoblastic leukemia cell line MOLT-4 revealed abundant mRNA. Lastly, the gene was mapped at the locus on human chromosome 2, band q12 by fluorescent in situ hybridization.

Amino Acid Sequence↗

Over expression of mitochondrial citrate synthase gene improves the growth of carrot cells in Al-phosphate medium.

A mitochondrial citrate synthase (CS) of Arabidopsis thaliana was introduced into carrot (Daucus carota L. cv. MS Yonsun) cells by Agrobacterium tumefaciens-mediated transformation. Transgenic cell lines had high CS activity, the highest value observed was 0.24 mumol (mg protein)-1 min-1 which was 1.9-fold of that in wild-type cells. Transcript levels of DcCS were similar between transgenic lines, but those of AtCS were increased as the CS activity of cells was increased. Isoelectric focussing revealed that the CS polypeptide of the transgenic lines had a pI value different from that of the wild-type cells, although the molecular mass was the same. These results indicate that the CS polypeptides of A. thaliana were expressed and processed to the mature form in carrot cells. The growth rate and excretion was 2.2-2.8 and 2.8-4.0 fold greater in the transgenic cells than in the wild type cells, respectively. Phosphate uptake from Al-phosphate also increased in transgenic cells. It appears, the overexpression of mitochondrial citrate synthase in carrot cells improves the growth rate in Al-phosphate medium possibly as a result of increased citrate excretion.

Agrobacterium tumefaciens↗

Comparative analysis of systemic and coronary hemodynamics during sevoflurane- and isoflurane-induced hypotension in dogs.

We studied the effects of sevoflurane on myocardial contractility and systemic and coronary hemodynamics, as compared with the effects of isoflurane in dogs under the same cardiac work conditions. Sixteen mongrel dogs were anesthetized with alpha-chloralose. Heart was paced at 100 beats/min after producing a complete atrioventricular (A-V) block. Controlled hypotension to a mean arterial pressure (MAP) of 60 mm Hg was induced and maintained by inhalation of either anesthetic, lasting for 60 min. Measurements were made at baseline, 15 min (T1), and 60 min (T2) after starting hypotension, and 30 min after discontinuing equihypotension (T3). Although left ventricular systolic segment shortening (%SS) decreased approximately 20% in both groups, cardiac output (CO) decreased only in sevoflurane during equihypotension (-27.6% at T2). Sevoflurane decreased the coronary blood flow (CBF; -34.8% at T2) with no significant change of coronary vascular resistance (CVR), whereas isoflurane produced a significant decrease in CVR resulting in no change of CBF despite of decreased coronary perfusion pressure (-37.4% at T2). These systemic and coronary vascular effects were continued even at T3. In conclusion, myocardial depressant effects were comparable between sevoflurane and isoflurane. Both systemic and coronary vasodilatory effects of isoflurane are greater than those of sevoflurane.

Anesthetics, Inhalation↗