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Biomedical subjects

T Inubushi

Publications and source records attributed to T Inubushi.

At least 73 records · Page 4Linked to original sources

Genetic susceptibility to herpetic encephalitis of inbred rabbits of B/Jas strain.

Inbred rabbits of B/Jas strain were found to be highly susceptible to herpes simplex virus type 1 encephalitis, following i.v. injection of the virus, while Chbb:HM strain rabbits were not susceptible. The susceptibility trait seemed to be inherited recessively, involving multiple genes, because (B/Jas x Chbb:HM)F1 hybrids were as resistant as Chbb:HM rabbits, and because more than 90% of backcrosses of (B/Jas x Chbb:HM)F1 to B/Jas were resistant to viral inoculation. The encephalitis in B/Jas rabbits resembled human herpes simplex encephalitis, in that the temporal lobe as well as the brain stem were affected preferentially, leading to the development of various types of seizures, such as circling, loss of balance leading to a fall, and tonic and clonic convulsions. The disease could be diagnosed by magnetic resonance imaging (MRI) analysis before onset of seizures, and diseased rabbits showed a marked lymphopenia at onset of seizures.

Animals↗

Evaluation of protective effects of prostaglandin E1 on ischemic liver damage with in vivo 31P-MR spectroscopy.

The cytoprotective effect of prostaglandins (PG) was evaluated by in vivo 31P MR spectroscopy. Twenty rabbits were divided into two groups; the control group given physiological saline, and the PG group given prostaglandin E1 (0.5 microgram/kg/min). Each solution was infused for 8 min, after which complete hepatic ischemia was induced for 20 min, followed by reperfusion for 40 min. During ischemia, beta-ATP decreased to 23.6% and 42.3%, phosphomonoester increased to 260% and 200% of their initial values in the control and the PG groups, respectively. Inorganic phosphate also increased. After reperfusion, beta-ATP recovered to 65.2% and 96.5%, phosphomonoester to 130% and 110%, inorganic phosphate to 140% and 120% in the control and PG groups, respectively. The changes during ischemia were significantly smaller and the recoveries during reperfusion were more complete in the PG group. These results may confirm the cytoprotective effect of prostaglandins by in vivo 31P-MR spectroscopy.

Adenosine Triphosphate↗

Long-term observation of in vivo 31P NMR spectra in carbon tetrachloride-intoxicated rabbit liver using implanted wireless surface coil.

Phosphorus-31 NMR spectra in rabbit liver were successively observed for more than 5 months in a chronic CCl4 intoxication model using implanted wireless surface coils. The quality of the obtained NMR spectra was satisfactory and there was sufficient time resolution to follow the dynamic changes that occurred during a fructose tolerance test. The implanted coil did not lead to any serious adverse effects such as infection or liver dysfunction. During an 18-week administration of CCl4, the area of the phosphodiester peak significantly decreased. The ratio of P(i)/beta-ATP was transiently elevated and gradually returned to the control level. In the fructose tolerance test, the increase in phosphomonoester and the decrease in P(i) and beta-ATP after i.v. fructose loading were apparent, but the degrees in these changes became smaller during the CCl4 intoxication. This wireless surface coil was useful for consecutive and non-invasive 31P NMR observations of the liver to follow chronically treated animal models over a period of several months.

Animals↗

Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS.

High energy phosphate metabolites were measured using phase-encoded in vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in both the left and right frontal lobes of 25 patients with bipolar disorder. Eleven patients were examined in the depressive state, 12 in the manic state, and 21 in the euthymic state. Twenty-one age-matched normal volunteers were also examined. The phosphocreatine (PCr) peak area percentage in the left frontal lobe in the patients in the depressive state was decreased compared with that in the normal controls. It was significantly negatively correlated with the Hamilton Rating Scale for Depression score evaluated at the time of 31P-MRS examination. The PCr peak area percentage in the right frontal lobe in the patients in the manic and the euthymic states was decreased compared with that in the controls. These results are compatible with previous reports describing reduction of glucose metabolism in the left frontal lobe in depressive patients with bipolar disorder and trait-dependent right hemisphere dysfunction in bipolar disorder.

Arousal↗

Evaluation of water molecules in the cold-preserved rat liver by proton magnetic resonance imaging.

Hypothermically preserved rat livers were studied with proton magnetic resonance imaging (1H-MRI) under proton density-, spin-lattice relaxation time-, spin-spin relaxation time- and diffusion-weighted (P-W, T1-W, T2-W and D-W) conditions. Relative signal intensities (RSI) of the liver to distilled water in terms of P-W, T1-W, T2-W and D-W increased time-dependently during 12 h hypothermic (4 degrees C) preservation with saline, while these parameters did not increase during preservation with University of Wisconsin (UW) solution. One-hour Wiggers' hypotensive treatment before the harvesting increased the RSIs of P-W, T2-W and D-W, and the subsequent 12-hour preservation with UW solution did not improve the increased RSIs. These results suggest that 1H-MRI has potential application in evaluating the biophysical changes of water molecules in the liver graft, which were measured by placing the harvested liver in a plastic bag under a magnetic field at a low temperature.

Adenosine↗

Biochemical and biophysical alterations of lipoprotein after liver transplantation from a living related donor. A biochemical and proton NMR study.

Changes in lipoprotein metabolism after liver transplantation from living related donors were investigated in nine pediatric patients by means of biochemical and proton nuclear magnetic resonance (NMR) analyses of lipoprotein. NMR offers rapid and nondestructive measurement of lipoprotein. The ratio of esterified cholesterol to total cholesterol, expected to be a prognostic indicator after liver transplantation, was low before the operation (0.44) and recovered to over 0.6 at 3 weeks. The half line width of the methylene peak of lipoprotein, as measured by proton NMR, was correlated with the ratio of esterified cholesterol to total cholesterol. It is suggested that proton NMR analysis can provide information about the biophysical changes in lipoprotein associated with liver transplantation.

Biochemical Phenomena↗

Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy.

Brain phosphorus metabolism was measured by 31P-MRS in 15 patients with bipolar II disorder (BP II) and 14 patients with bipolar I disorder (BP I). Phosphocreatine (PCr)levels were significantly lower in patients with BP II in all three psychiatric states compared to 59 normal controls (PCr (%) was 13.5 +/- 1.5 (mean +/- SD) for controls, and 12.2 +/- 1.7, 12.1 +/- 1.3, 12.0 +/- 1.9 for hypomanic, euthymic and depressed bipolar II patients respectively). High values of phosphomonoester (PME) were found in BP II patients in the hypomanic and depressive states, but PME values in the euthymic state did not differ significantly from controls. Intracellular pH of BP II patients in all three psychiatric phases was similar to control values, whereas euthymic BP I patients had lower pH values. These results suggest that brain high energy phosphate metabolism may be impaired in BP II and that there may be pathophysiological differences between BP I and BP II.

Adenosine Triphosphate↗

Correlations of phosphomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia.

Frontal lobe dysfunction has been linked to negative symptoms of schizophrenia. We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to examine phosphorous metabolism in frontal brain regions in 26 schizophrenic patients compared with 26 sex- and age-matched control subjects. The relative signal intensities of phosphorous metabolites in frontal regions did not differ significantly between schizophrenic patients and control subjects. However, phosphomonoester levels were significantly decreased in frontal regions of 12 schizophrenic patients who had high scores on negative symptom subscales from the Brief Psychiatric Rating Scale (i.e., emotional withdrawal, motor retardation, and blunted affect) compared with 14 patients with low negative symptom scores on the same subscales and control subjects. The correlations between negative symptoms and phosphorous metabolism in the frontal lobes support the "hypofrontality hypothesis" in schizophrenia.

Adenosine Triphosphate↗

Imaging of phosphoenergetic state and intracellular pH in human calf muscles after exercise by 31P NMR spectroscopy.

Phosphoenergetic and pH images in human calf muscles before and after ischemic exercise were generated by 31P NMR chemical shift imaging (CSI) with a 1.5 T standard clinical MR machine using a home-built volume coil. Acquisition of data was repeated four times with 8 x 8 phase-encoding steps and 1 s repetition time. The total acquisition time was 4 min 16 s. After 3-dimensional (3D) Fourier transformation with zero-filling, 2-dimensional (2D) images with 32 x 32 matrices of phosphocreatine (PCr), inorganic phosphate (Pi), PCr/(PCr + Pi) and pH were constructed. These metabolic images were overlaid with concurrently observed 1H MRI to locate the areas showing metabolic response. After 3 min exercise consisting of repeated plantarflexion of the foot under ischemic conditions, decreases in phosphoenergetic levels and acidosis were the most severe in the peroneus muscles, moderate in the tibialis anterior muscle, and slight in the triceps muscle of the calf. Under maintained ischemic conditions, phosphoenergetic level further decreased, but the acidosis in each muscle did not progress further. Heterogeneous metabolic and pH changes throughout the entire calf muscle were clearly demonstrated in detail by these images.

Acidosis↗

Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder.

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was used to examine whether reduced levels of phosphomonoesters (PME) were correlated with ventricular enlargement in 40 patients with bipolar disorder and 60 age-matched normal control subjects. Ventricular enlargement was assessed by magnetic resonance imaging (1H-MRI) using the following three methods: Evans ratio (ER), Huckman number (HN), and minimum distance of caudate nuclei (MDCN). Although MDCN and ER were significantly larger in the patient group, no significant correlations were found between 31P-MRS and 1H-MRI. PME was negatively correlated with age in bipolar disorder. Decreased levels of PME were found only in bipolar I disorder. Intracellular pH was positively correlated with duration of lithium treatment. These results suggest that the observed PME reduction was not related to ventricular enlargement, but the issue should be further studied with volumetric MRI analysis.

Adult↗

Specific assay method for the activities of cathepsin L-type cysteine proteinases.

We have established a new differential assay method for cathepsin L-type proteinases using specific inhibitors, E-64 for all cysteine proteinases, CA-074 for cathepsin B, and PLCPI for cathepsin L-type proteinases with Z-Phe-Arg-MCA as the substrate. The value of cathepsin B calculated by this method did not coincide with value assayed directly in terms of the hydrolysis of Z-Arg-Arg-MCA, a specific substrate for cathepsin B. The activities of cathepsin L-type proteinases, cathepsins B and J in rat liver and kidney were assayed at the same time using this new assay method as a representative example.

Amino Acid Sequence↗

Lactate and pH mapping in calf muscles of rats during ischemia/reperfusion assessed by in vivo proton and phosphorus magnetic resonance chemical shift imaging.

RATIONALE AND OBJECTIVES: Metabolic images of phosphocreatine, inorganic phosphate (Pi), and pH formed by phosphorus 31 (31P) nuclear magnetic resonance (NMR) spectroscopy, that of lactate by proton (1H) NMR spectroscopy and 1H magnetic resonance imaging (MRI) were concurrently observed using the same ischemia/reperfusion model in the calf muscles of rats. From the multidimensional analyses, the correlation between tissue pH and lactate formation was examined. METHODS: Six rats were used in the study. For the selective detection of lactate by 1H NMR, a multiple quantum coherence filter was used. The localization of the metabolites and pH was achieved by three-dimensional chemical shift imaging technique. These observations were repeated in 1-hour cycles during 6 hours of ischemia and after reperfusion. RESULTS: The tibialis anterior and gastrocnemius muscles, which are mainly composed of fast-twitch muscle fibers, showed severe tissue edema and irreversible phosphoenergetic change. These muscles became more acidic than other portions of the calf. In contrast, the central part of the calf including soleus muscle (slow-twitch muscle) showed reversible phosphoenergetic changes. Lactate accumulated mainly between the muscles showing reversible and irreversible phospho-energetic changes. CONCLUSION: Discrepancy between acidosis and lactate accumulation in calf muscles was observed in this ischemia/reperfusion model, although the exact reasons for this phenomenon could not be explained by this study.

Animals↗

Detection of myocardial ischemia by 31P magnetic resonance spectroscopy during handgrip exercise.

BACKGROUND: The metabolic changes of myocardial ischemia in patients with coronary artery disease assessed by 31P magnetic resonance spectroscopy (MRS) have been reported previously. A significant decrease in the ratio of phosphocreatine (PCr) to ATP during handgrip exercise in a group of patients with severe coronary artery disease has been demonstrated. However, there are no reports at present that directly compare cardiac 31P MRS data with exercise 201Tl myocardial scintigraphy, now established as one of the most important clinical methods to assess myocardial ischemia. The purpose of this study was to investigate whether 31P MRS with handgrip exercise testing is able to detect myocardial ischemia, demonstrated by exercise 201Tl scintigraphy. METHODS AND RESULTS: Twenty-seven patients with severe stenosis of the left anterior descending coronary artery (> or = 75%) and 11 normal control subjects composed the present study. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+]) who demonstrated redistribution at the late image and a fixed 201Tl defect group (RD[-]). While lying supine within the magnet, subjects performed handgrip exercise at 30% of maximal force once in every two cardiac cycles. 31P MR spectra were collected before and during handgrip exercise. Data were corrected for the saturation factor. ANOVA revealed significant differences among the three groups with respect to the mean +/- SD PCr/ATP ratio at rest (control, 1.85 +/- 0.28 > RD(+), 1.60 +/- 0.19 > RD(-), 1.24 +/- 0.30; P < .05). The PCr/ATP ratio decreased significantly from 1.60 +/- 0.19 at rest to 0.96 +/- 0.28 during exercise (P < .001) in the RD(+) group (n = 15). However, in the RD(-) group (n = 12), the ratio did not change significantly during handgrip exercise (1.24 +/- 0.30 at rest versus 1.19 +/- 0.28 during exercise). Similarly, the ratio did not change in the control group (n = 11) (1.85 +/- 0.28 at rest versus 1.90 +/- 0.23 during exercise). CONCLUSIONS: Contrary to normal subjects or patients with fixed thallium defects, the PCr/ATP ratio was significantly altered by exercise in patients with reversible thallium defects. These results suggest that 31P MRS with handgrip exercise testing is a sensitive method for detecting myocardial ischemia.

Adenosine Triphosphate↗

Relationship of lithium concentrations in the brain measured by lithium-7 magnetic resonance spectroscopy to treatment response in mania.

Lithium concentrations in the brain were measured in 14 manic patients with bipolar disorder (12 with bipolar disorder, manic, and 2 with bipolar disorder, not otherwise specified, by DSM-III-R) by the use of lithium-7 magnetic resonance spectroscopy ([7Li]MRS). The reduction of Petterson Mania Rating Scale 4 weeks after the initiation of lithium treatment was not significantly correlated with concentrations in serum (r = 0.33), but was correlated with concentrations in the brain (r = 0.64; p < 0.05). These results suggest that the treatment response to lithium in manic patients with bipolar disorder is more closely related to the lithium concentration in the brain as measured by [7Li]MRS than to the concentration in serum.

Adult↗

1H-detected in vivo 13C NMR spectroscopy and imaging at 2T magnetic field: efficient monitoring of 13C-labeled metabolites in the rat brain derived from 1-13C-glucose.

Gradient-select hetero-nuclear multiple quantum coherence in nuclear magnetic resonance (NMR) an indirect method of detecting nuclei in low sensitivity by 1H NMR, was used to observe 13C-enriched metabolites in the rat brain in vivo, with a 2 T NMR system. We detected the accumulation of 13C-labeled glucose and its metabolites, glutamine and/or glutamate, in less than 5 min. The extension of this technique to chemical shift imaging permitted the localization of these chemicals in the rat brain. This approach may have various applications for non-invasive monitoring of 13C-labeled compounds in humans and other animals.

Animals↗