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Biomedical subjects

N Matsuoka

Publications and source records attributed to N Matsuoka.

At least 19 recordsLinked to original sources

Tacrolimus (FK506) attenuates biphasic cytochrome c release and Bad phosphorylation following transient cerebral ischemia in mice.

Tacrolimus (FK506) has a neuroprotective action on cerebral infarction produced by cerebral ischemia, however, detailed mechanisms underlying this action have not been fully elucidated. We examined temporal profiles of survival-and death-related signals, Bad phosphorylation, release of cytochrome c (cyt.c), activation of caspase 3 and DNA fragmentation in the brain during and after middle cerebral artery occlusion (MCAo) in mice, and then examined the effect of tacrolimus on these signals. C57BL/6J mice were subjected to transient MCAo by intraluminal suture insertion for 60 min. Tacrolimus (1 mg/kg, i.p.) was administered immediately after MCAo. There were biphasic increases in the release of cyt.c in the ischemic core and penumbra; with the first increase toward the end of the occlusion period and the second increase 3-12 h after reperfusion. Tacrolimus significantly inhibited the increase of cytosolic cyt.c during ischemia and reperfusion. Phosphorylated Bad, Ser-136 (P-Bad(136)) and Ser-155 (P-Bad(155)) were detected 30 min after MCAo and after reperfusion in the ischemic cortex, respectively. Tacrolimus increased P-Bad(136) during ischemia and prolonged P-Bad(155) expression after reperfusion. Tacrolimus also decreased caspase-3 and terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling-positive cells, and reduced the size of infarct 24 h after reperfusion. Our study provided the first evidence that the neuroprotective action of tacrolimus involved inhibition of biphasic cyt.c release from mitochondria, possibly via up-regulation of Bad phosphorylation at different sites after focal cerebral ischemia and reperfusion.

Analysis of Variance↗

Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma- reaction at E gamma = 1.5-2.4 GeV.

Differential cross sections and photon-beam asymmetries have been measured for the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using liquid deuterium and hydrogen targets with incident linearly polarized photon beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin 1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large positive asymmetries are observed, indicating the dominance of K* exchange. The large difference between the asymmetries for the K+ Sigma- and K+ Sigma0 reactions cannot be explained by simple theoretical considerations based on Regge model calculations.

Journal Article↗

Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults.

OBJECTIVE: To test for association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q polymorphism with body mass index (BMI) and diabetes in a large sample of Caucasians and African-Americans by selectively genotyping individuals at the extremes of the phenotypic distribution. SUBJECTS: Subsets comprising the extremes of the BMI distribution (10th-20th and above the 90th BMI percentile for Caucasians and between the 10th-30th and above the 80th percentile for African-Americans) from a group of 10,260 Caucasian and 2268 African-American adults participating in New York Cancer Project were studied. METHODS: Subjects were genotyped for the ENPP1 K121Q polymorphism by pyrosequencing and tested for association with BMI and diabetes by regression analysis. RESULTS: Regression analysis with BMI as the dependent variable demonstrated a significant association (P = 0.02) of genotype at K121Q with BMI, with no significant race-by-genotype interaction (P = 0.30). Compared with Q/Q or Q/K individuals, the K/K individuals had a BMI approximately 1.3 kg/m2 higher, without effects of age, gender or race. By logistic regression analysis, the K121Q alleles had no significant effect on diabetes status (P = 0.37) in obese subjects. CONCLUSION: In both Caucasians and African-Americans, the K121 polymorphism in ENPP1 was associated with increased BMI, but not with diabetes.

Adult↗

Near-threshold diffractive psi-meson photoproduction from the proton.

Photoproduction of a phi meson on protons was studied by means of linearly polarized photons at forward angles in the low-energy region from threshold to Egamma = 2.37 GeV. The differential cross sections at t = -|t|min do not increase smoothly as Egamma increases but show a local maximum at around 2.0 GeV. The angular distributions demonstrate that phi mesons are photoproduced predominantly by helicity-conserving processes, and the local maximum is not likely due to unnatural-parity processes.

Journal Article↗

Adolescents' attachment style and early experiences: a gender difference.

We examined gender differences in perceived rearing and adult attachment style in adolescents. A total of 3,912 senior college students (1,149 men and 2,763 women) ages 18-23 (men's M = 20.1 years, women's M = 20.0 years) were administered a set of questionnaires including Relationship Questionnaire (to measure adult attachment), the Parental Bonding Instrument (perceived rearing), and a list of early life events. In the men, positive adult total attachment style was predicted by the scores of paternal care and low scores on maternal overprotection in a hierarchical regression analysis. On the other hand, in the women, positive adult total attachment style was predicted by the scores of paternal and maternal care, and low score on maternal overprotection. Adult attachment was also predicted by fewer Peer Victimization experience as a child in both men and women. However, while men's adult attachment was predicted by Self Disease experiences, women's adult attachment was predicted by Top Star experiences and fewer Relocation experiences. The adult attachment style was predictable from early experiences but there existed some gender differences.

Adolescent↗

Beam-polarization asymmetries for the p(gamma-->, K+)Lambda and p(gamma-->, K+)Sigma(0) reactions for E(gamma)=1.5-2.4 GeV.

Beam polarization asymmetries for the p(gamma-->,K+)Lambda and p(gamma-->,K+)Sigma(0) reactions are measured for the first time for E(gamma)=1.5-2.4 GeV and 0.6<cos((theta(c.m.)(K+))<1.0 by using linearly polarized photons at the Laser-Electron-Photon facility at SPring-8 (LEPS). The observed asymmetries are positive and gradually increase with rising photon energy. The data are not consistent with theoretical predictions based on tree-level effective-Lagrangian approaches. Including the new results in the development of the models is, therefore, crucial for understanding the reaction mechanism and to test the presence of baryon resonances which are predicted in quark models but are thus far undiscovered.

Journal Article↗

Evidence for a narrow S = +1 baryon resonance in photoproduction from the neutron.

The gamman-->K(+)K(-)n reaction on 12C has been studied by measuring both K+ and K- at forward angles. A sharp baryon resonance peak was observed at 1.54+/-0.01 GeV/c(2) with a width smaller than 25 MeV/c(2) and a Gaussian significance of 4.6sigma. The strangeness quantum number (S) of the baryon resonance is +1. It can be interpreted as a molecular meson-baryon resonance or alternatively as an exotic five-quark state (uuddsmacr;) that decays into a K+ and a neutron. The resonance is consistent with the lowest member of an antidecuplet of baryons predicted by the chiral soliton model.

Journal Article↗

Dopamine stabilizes milrinone-induced changes in heart rate and arterial pressure during anaesthesia with isoflurane.

BACKGROUND AND OBJECTIVE: Phosphodiesterase-III inhibitors and dobutamine effectively improve cardiac function in patients with cardiac failure, but they are limited by possible hypotensive effects. We tested the hypothesis that dopamine contributes to stabilizing milrinone-induced haemodynamic changes. METHODS: Nine patients undergoing major surgery were anaesthetized using nitrous oxide and oxygen supplemented with isoflurane 1-2%. After baseline haemodynamics were recorded, milrinone (25 or 50 microg kg(-1)) was administered over 10min, followed by a continuous infusion (0.5 microg kg(-1) min(-1). The second set of haemodynamic values was measured 50 min after beginning the continuous infusion of milrinone. Dopamine (4 microg kg(-1) min(-1)) was then administered with milrinone. RESULTS: Milrinone significantly increased the heart rate from 81 +/- 8 to 102 +/- 16beats min(-1), but it decreased the mean arterial pressure from 83 +/- 10 to 66 +/- 10 mmHg and systemic vascular resistance (P < 0.05 for each). The pulmonary capillary wedge pressure, cardiac index and pulmonary vascular resistance did not change significantly. The addition of dopamine to the milrinone infusion significantly decreased the heart rate (94 +/- 12 beats min(-1)) and increased the mean arterial pressure (82 +/- 11 mmHg). Dopamine and milrinone, but not milrinone alone, significantly increased the cardiac index and the rate-pressure product. CONCLUSIONS: The combination regimen of milrinone and dopamine improved cardiac function, and changes in heart rate and mean arterial pressure induced by milrinone were attenuated by dopamine. The results suggest that a combination regimen of milrinone and dopamine rather than milrinone alone should be used to maintain arterial pressure.

Analysis of Variance↗

FK960, a novel potential anti-dementia drug, enhances high K(+)-evoked release of somatostatin from rat hippocampal slices.

We have demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel putative anti-dementia drug of piperazine derivative, ameliorates memory deficits in a variety of animal models of dementia in rats and monkeys, and also augments long-term potentiation (LTP) in the mossy fiber-CA3 pathway in guinea-pig hippocampal slices. Our recent studies have further suggested that somatostatin activation could be a primary mechanism of the pharmacological action of FK960. To clarify the mode of action of FK960 on somatostatinergic neurotransmission, FK960 was examined for its effects on somatostatin release from rat hippocampal slices. FK960 significantly enhanced high K(+)-evoked release, but not basal release, of somatostatin with similar concentration-dependency to its LTP augmenting action. On the other hands, FK960 had no effects on the release of neurotransmitters such as acetylcholine, 5-HT, D-aspartate or GABA from hippocampal slices. Our results provide compelling evidence that FK960 exerts specific and facilitatory actions on neural mechanisms involved in the activity-dependent release of somatostatin from nerve terminals of the hippocampus. These results also strengthen the view that FK960 regulates cognitive functions and augments LTP through an activation of the somatostatinergic nervous system in the hippocampus.

Acetylcholine↗

Novel immunosuppressive effect of FK506 by augmentation of T cell apoptosis.

We have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.

Animals↗

Long-term outcome of urinary function after extended lymphadenectomy in patients with distal rectal cancer.

AIMS: Extended lymphadenectomy for rectal cancer has been superseded by autonomic nerve-sparing surgery, but it still has historical significance. It is useful to document the long-term outcome of urinary function in cases who had resection of the inferior hypogastric nerve plexus (pelvic nerve plexus). METHODS: The long-term urinary function following extended lymphadenectomy was studied retrospectively through the medical records of 83 patients who had been followed-up for more than 5 years after surgery. RESULTS: Forty-four per cent of the male patients and 17% of the female patients had to perform clean intermittent self-catheterization (CIC) for more than 1 year; these rates were almost the same at 3 years after the procedure. Urinary incontinence was reported in 34% of the male patients and 45% of the female patients. Complicated cystitis (eight patients), complicated pyelonephritis (two patients), bladder stones (five patients) that required surgical treatment, and chronic renal failure (two patients) were considered as adverse outcomes of extended surgery. In particular, one case needed to undergo urinary diversion. CONCLUSIONS: A surprisingly large proportion of patients suffered various urinary tract problems due to extended lymphadenectomy. The findings demonstrate the importance of selection of well-balanced operations that can encompass both radicality and quality of life. The extent of resection should be decided by the extent of the cancer and routine excision of the inferior hypogastric nerve plexus should not be performed.

Adult↗

Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin.

Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may modulate glucose and lipid metabolism. In the present study, we examined lipid metabolism in transgenic skinny mice with elevated plasma leptin concentrations. The plasma concentrations of triglycerides and free fatty acids in transgenic skinny mice were 71.5 (P < 0.01) and 89.1% (P < 0.05) of those in their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density lipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estimated by a fat-loading test was enhanced in transgenic skinny mice; the triglyceride concentration in transgenic skinny mice 3 h after fat loading was 39.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin plasma lipoprotein lipase activity increased 1.4-fold (P < 0.05) in transgenic skinny mice. Our data demonstrated a significant reduction in plasma triglyceride concentrations, accompanied by increased lipoprotein lipase activity in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.

Animals↗

[Trial manufacture of a plunger to reduce finger exposure].

According to the results of to a survey conducted by the Japanese Society of Nuclear Medicine Technology in 1995, the mean monthly exposure dose to the trunk of nuclear medicine technicians was less than 0.2 mSv at more than 75% of the institutions, whereas the exposure dose to the fingers exceeded 0.5 mSv at 30% of the institutions. Many recent radiopharmaceuticals are being supplied as the syringe type, and while the syringe is surrounded by a tungsten or lead-glass shield, there is no shielding of the syringe needle or the plungers. The plastic plunger provides little shielding effect, and even when a tungsten plunger is used, calculating back from the leakage rate, the shielding effect for 99mTc is approximately 75%. We therefore trial-manufactured a plunger devised in such a manner as to considerably reduce exposure of the fingers and evaluated its shielding effect from leakage rate obtained with a dual-detector scintillation camera when the radionuclides 99mTc, 67Ga, 201Tl, and 123I were used. Its performance was satisfactory, with shielding effects (99mTc, 99%; 67Ga, 95%, 201Tl, 95%; 123I, 73%) about the same or better than back-calculated from the leakage rates.

Fingers↗

[Method of evaluating the shielding effect of syringe shields and plungers].

The opportunities to use the syringe-type radiopharmaceuticals being supplied by manufacturers to conduct examinations in the ordinary clinical practice of nuclear medicine have recently increased, and the radiation doses to the fingers of those performing the examinations has been reduced. However, not much is known about the shielding effect of the syringe-type syringe shields and plungers. In order to evaluate their shielding effect, we devised a method in which leakage rates are calculated from the counts of the image data acquired with a 2-detector scintillation camera and compared with the values and graphs. The values made it possible to determine and compare single-direction leakage rates, whereas the graphs made it possible to determine and compare 360 degrees-direction leakage rates. This method is convenient, enables satisfactory result to be obtained in any institution, and appears to make it easy to understand the shielding effect. The validity of this method was confirmed in a comparative assessment with a survey-meter.

Evaluation Studies as Topic↗

Yb fiber laser pumped mid-IR source based on difference frequency generation and its application to ammonia detection.

A Yb fiber laser pumped cw narrow-linewidth tunable mid-IR source based on a difference frequency generation (DFG) in a periodically poled LiNbO3 (PPLN) crystal for trace gas detection was demonstrated. A high power Yb fiber laser and a distributed feedback (DFB) laser diode were used as DFG pump sources. This source generated mid-IR at 3 microns with a powers of ~2.5 microW and a spectral linewidth of less than 30 MHz. A frequency tuning range of 300 GHz (10 cm-1) was obtained by varying the current and temperature of the DFB laser diode. A high-resolution NH3 absorption Doppler-broadened spectrum at 3295.4 cm-1 (3.0345 microns) was obtained at a cell pressure of 27 Pa from which a detection sensitivity of 24 ppm m was estimated.

Ammonia↗

[A case of myasthenia gravis accompanied by large thymoma and anti-GAD antibody].

A 61-year-old woman had repeated episodes of muscle weakness of face, neck and limbs for 18 years. She was diagnosed as having myasthenia gravis (MG) by the positive anti-acetylcholine receptor antibody and findings of electromyogram. Simultaneously, she was noticed to have diabetes mellitus with high titers of anti-glutamic acid decarboxylase (GAD) antibody. Magnetic resonance imaging showed a large thymoma. In spite of the improvement of MG after thymectomy, the insulin secretion slowly exacerbated during next two years. The clinical course of her disease was characteristic as slowly progressive insulin dependent diabetes mellitus (SPIDDM). She continued to have positive autoantibody against beta-cell of pancreas. Recently, anti-GAD antibody is detected in patients with SPIDDM and stiffman syndrome (SS) in high rate, and it is closely associated with the cause of these syndromes. The patient did not reveal the symptoms of SS. From the clinical course, MG and SPIDDM in this patient may be caused by a common underlying autoimmune abnormality resulting from the long presence of the thymoma. MG and SPIDDM may be derived from organ-specific autoimmunopathy from the defect of self-tolerance.

Autoantibodies↗

Adenovirus-mediated gene transfer of basic fibroblast growth factor promotes the survival of primary-cultured rat neuronal cells.

We constructed two replication-deficient recombinant adenovirus vectors coding human basic fibroblast growth factor (bFGF), one with and one without the interleukin-2 (IL-2) secretory signal sequence and examined their neurotrophic effects on primary neuronal cells in vitro. The primary neuronal cells were successfully infected at a high efficiency with the adenovirus vectors. bFGF protein was detected in the culture medium of the neurons infected with both these vectors. The cells infected with the bFGF-expressing adenovirus containing the IL-2 signal sequence showed 2- to 10-fold higher levels of secretion levels than cells infected with the native bFGF-expressing adenovirus alone. Both bFGF-expressing vectors augmented the survival of primary neuronal cells in an in vitro culture, compared with a mock infection or control virus infection. Notably, the cells infected with the bFGF-expressing adenovirus containing the IL-2 signal sequence were markedly enhanced cell survival in the early phase of the culture, compared with the control cells and even those infected with the bFGF-expressing adenovirus without the IL-2 signal sequence. However, in the late phase of neuronal culture, neither viral vector could support the cell survival. In contrast the co-infection of the bFGF-expressing vector with a Bcl-xL-expressing vector was extremely effective on neuronal survival.

Adenoviridae↗