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Biomedical subjects

M Ohkubo

Publications and source records attributed to M Ohkubo.

At least 91 records · Page 5Linked to original sources
PubMed1994

Studies on cerebral protective agents. VI. Synthesis of novel 4-(4-nitrobenzoyl)pyrimidine and related compounds with anti-anoxic activity.

Novel pyrimidine derivatives, possessing linkages between the aryl group and the pyrimidine nucleus at the C-4 position, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-ylcarbonyl)-4-(4-nitrobenzoyl)-2-p henylpyrimidine (2f, FR76659) possessed significant AA activity (10-100 mg/kg, i.p.) with low acute toxicity (LD50 > 1000 mg/kg, i.p.). Structure-activity relationships in regard to AA activity of this series of compounds were examined.

Animals↗
PubMed1994

[Quantifying regional cerebral blood flow with N-isopropyl-p-[123I]iodoamphetamine and SPECT by one-point sampling method].

We developed a new non-invasive technique; one-point sampling method, for quantitative measurement of regional cerebral blood flow (rCBF) with N-isopropyl-p-[123I]iodoamphetamine and SPECT. Although the continuous withdrawal of arterial blood and octanol treatment of the blood are required in the conventional microsphere method, the new technique does not require these two procedures. The total activity of 123I-IMP obtained by the continuous withdrawal of arterial blood is inferred by the activity of 123I-IMP obtained by the one point arterial sample using a regression line. To determine when one point sampling time was optimum for inferring integral input function of the continuous withdrawal and whether the treatment of sampled blood for octanol fraction was required, we examined a correlation between the total activity of arterial blood withdrawn from 0 to 5 min after the injection and the activity of one point sample obtained at time t, and calculated a regression line. As the results, the minimum % error for the inference using the regression line was obtained at 6 min after the 123I-IMP injection, moreover, the octanol treatment was not required. Then examining an effect on the values of rCBF when the sampling time was deviated from 6 min, we could correct the values in approximately 3% error when the sample was obtained at 6 +/- 1 min after the injection. The one-point sampling method provides accurate and relatively non-invasive measurement of rCBF without octanol extraction of arterial blood.

Adolescent↗
PubMed1994

[Elevation of cerebral lactate detected by localized 1H magnetic resonance spectroscopy in a patient with migraine].

Localized 1H magnetic resonance spectroscopy was performed in a 45-year-old woman with migraine. She developed throbbing headache attacks without aura since thirteen years ago and the attack was accompanied with right hemiplegia since seven years ago. Brain MRI showed no abnormalities and 123I-IMP SPECT revealed mild frontal dominant decrease of cerebral blood flow. It seemed that her condition was positioned between migraine with prolonged aura and migrainous infarction of complicated migraine in the classification of International Headache Society. Spectra obtained from bilateral frontal lobe interictally showed elevation of lactate at left side. Choline, creatine, and N-acetyl-aspartate were almost equal on both side. The above results suggest that slight ischemia which is not detected by MRI is present or there is a disturbance of oxidative glycolysis, which is induced by mitochondrial dysfunction.

Brain↗
PubMed1994

[A study on evaluation of CBF measurement based on microsphere model with N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT--its correction with the value of PaCO2].

To evaluate the regional cerebral blood flow measurement with N-isopropyl-p-[123I]iodoamphetamine (IMP), we performed 123I-IMP SPECT and 133Xe inhalation method on 9 patients with mild cerebrovascular diseases and so on. A tracer dose of 123I-IMP (111 MBq) was injected i.v. and the data were obtained 15 min later. Regional CBF was measured by the microsphere model and arterial blood sampling method. However, mean cerebral blood flow values was not in agreement with both methods. We supposed the reason of the disagreement was due to the difference of PaCO2 when the studies were performed. Hence, CBF measurement with 123I-IMP was performed on the other patient's population with loading of hyperventilation before the IMP injection. Comparing with the control state with normal breathing, we calculated the rate of change of mean CBF between the state with normal breathing and the state with hyperventilation that was 1.02 ml/100 g/min/mmHg PaCO2. After the correction with the rate, we observed a much significant relation between the mean CBF measured with 123I-IMP SPECT and 133Xe inhalation method. When compared CBF values with loading studies or certain therapies, the correction of CBF with the rate of change of PaCO2 is one of the very important factors to be considered. Moreover, 133Xe inhalation method without the correction of PaCO2 can not be a golden standard method for rCBF measurement.

Adult↗
PubMed1994

[A problem of quantitative measurement of regional cerebral blood flow using microsphere model and N-isopropyl-p-[123I]iodoamphetamine (IMP): comparison with 133Xe SPECT and sequential dynamic 123I-IMP SPECT].

Regional cerebral blood flow (rCBF) was measured in 13 patients with various cerebral disease by N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT with the microsphere model (rCBF (CbST)), which was compared with 133Xe inhalation SPECT (rCBFXe). Continuous withdrawal of arterial blood was performed for 5 minutes and SPECT image was obtained from 25 min to 55 min after the tracer injection. The reconstructed counts at 5 min was corrected using entire cerebral counts collected at 5 min, 20 min, and 60 min after the tracer injection. As compared with rCBFXe, rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. Regional CBF was also measured using one minute short time SPECT images at 5 min (rCBF (Cb5)), 20 min (rCBF (Cb20)), and 60 min (rCBF (Cb60)) after the injection. Regional CBF tended to be underestimated with time from the tracer injection due to the wash-out from brain tissue to blood. In comparison with rCBF (Cb5), rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. This error was considered to be due to the correction of reconstruct counts using entire cerebral counts, because of the kinetic behavior of 123I-IMP was different in each region of the brain.

Adult↗
PubMed1993

Neurochemical and electrophysiological studies on FR115427, a novel non-competitive NMDA receptor antagonist.

The pharmacological profile of FR115427 has been examined using ligand binding and electrophysiological techniques. Binding of [3H]dizocilpine in the presence of L-glutamate was inhibited by the (+) isomers of dizocilpine and FR115427. The corresponding (-) isomers were less active, and stereoselectivity was particularly marked in the case of FR115427. In contrast to dizocilpine, the affinity of FR115427 for [3H]dizocilpine binding sites was little affected by addition of either L-glutamate and/or glycine. In a cortical wedge preparation, FR115427 inhibited N-methyl-D-aspartate (NMDA)-induced responses in a non-competitive, use-dependent manner. Intracellularly recorded excitatory synaptic responses in hippocampal neurones were only partially inhibited by FR115427 thereby confirming a selective effect on the NMDA-mediated component of neuronal excitation induced by the endogenous neurotransmitter. The data suggest that FR115427 is a non-competitive, use-dependent NMDA receptor antagonist with more pronounced stereoselectivity and less marked use dependence than dizocilpine.

Action Potentials↗
PubMed1993

Studies on cerebral protective agents. III. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities. (3).

Novel 4-arylpyrimidine derivatives, bearing an amino moiety in the C-5 or C-6 position of the pyrimidine ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6,7-dihydro-6-[2-(dimethylamino)-ethyl]-4-(3-nitrophenyl)-2-phenyl-5H- pyrrolo[3,4-d]pyrimidine-5-one (2a, FR 75469) and 6-methyl-5-(4-methyl-piperazin-1-ylmethyl)-4-(3-nitrophenyl) - 2-phenylpyrimidine (4c, FR 72707) had comparable potency 10-100 mg/kg, i.p. and p.o.) to that of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidine (FK 360). These were also effective on anti-lipid peroxidation (ALP) assay and arachidonate-induced cerebral edema in rats. Structure-activity relationship in regard to AA activity of this series of compounds are discussed. Three-dimensional molecular electrostatic potentials (3D-MEP) around the nitrogenous basic moiety of FK 360 and 5-acetyl-6-(2-dimethylaminoethyl)-4-(3-nitrophenyl)-2- phenylpyrimidine (5f) were compared, and both electrostatic potential maps were similar.

Animals↗
PubMed1993

Studies on cerebral protective agents. V. Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives with anti-anoxic activity.

Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives, possessing three-atom linkages between basic nitrogen and at the C-5 (or C-3) position of the pyrimidine (or pyridine) ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-(pyrrolidinomethylcarbonylamino )pyrimidin e (10f) had the most potent AA activity (3.2 mg/kg, i.p.). Three-dimensional molecular electrostatic potentials (3D-MEP0 around the nitrogenous basic moiety of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidin e (FK 360) and 10f were compared. The negative zone of 10f is broader and deeper and positioned somewhat differently to that of FK 360, although there is a co-occupied spacial area in part.

Animals↗
PubMed1993

Changes of 31P-MR spectroscopy in experimental tumors following radiotherapy combined with 5-fluorouracil compound (UFT).

The energy metabolism of FM3A tumors in C3H mice following radiotherapy (20 Gy or 40 Gy), 5-fluorouracil compound (UFT) chemotherapy or radiotherapy (20 Gy) combined with UFT was investigated by in vivo 31P-MR spectroscopy on day 2 after treatment. The effects were compared with the growth curves of the tumors and with the cytokinetic and histological changes in the tumors on day 5 after treatment. The combined group (20 Gy+UFT) showed growth curves similar to the 40 Gy group. Cytokinetic and histological changes of the combined group were also similar to those of the 40 Gy group, suggesting supra-additive effect of UFT. 31P-MR spectra of the combined group were similar to those of the 40 Gy group which were characterized by increase of intracellular pH(pHi), decrease of Pi/beta-NTP and of PME/total phosphorus-signal ratios. Spectra of the UFT group and the 20 Gy group, on the contrary, showed decrease of pHi, increase of Pi/beta-NTP and of PME/total phosphorus-signal ratios. Changes detected by 31P-MR spectroscopy on day 2 were considered to reflect early metabolic events which were correlated to the growth curve, cytokinetic and histological alterations observed on day 5 after treatment.

Adenocarcinoma↗
PubMed1993

[A new graphic method for evaluation of distribution volume on N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT].

We developed a new graphic method using N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT of the brain, the graph on which all three parameters, cerebral blood flow, distribution volume (Vd) and delayed count to early count ratio (Delayed/Early ratio), were able to be evaluated simultaneously. The kinetics of 123I-IMP in the brain was analyzed by a 2-compartment model, and a standard input function was prepared by averaging the time activity curves of 123I-IMP in arterial blood on 6 patients with small cerebral infarction etc. including 2 normal controls. Being applied this method to the differential diagnosis between Parkinson's disease and progressive supranuclear palsy, we were able to differentiate both with a glance, because the distribution volume of the frontal lobe significantly decreased in Parkinson's disease (Mean +/- SD; 26 +/- 6 ml/g). This method was clinically useful. We think that the distribution volume of 123I-IMP may reflect its retention mechanism in the brain, and the values are related to amine, especially to dopamine receptors and its metabolism.

Aged↗
PubMed1993

[Visualization of brain function using MRI-MR functional brain imaging].

The effects of photic stimulation on the visual cortex of human brain were studied by means of gradient-echo magnetic resonance imaging (MRI). Fast low-angle shot (FLASH) MRI was used to monitor changes in brain oxygenation in the human visual cortex during photic stimulation (PS). Whole-body 1.5 T clinical MR system was used. Elevation of image intensity up to 2% was observed in primary and associative visual cortex, corresponding to an increase of blood oxygenation in regions of increased neural activity. After the PS was switched off, the MR signal fell below the pre-PS baseline level, which may be understood as an displacement of the oxygen-hemoglobin dissociation curve (the Bohre effect).

Adult↗
PubMed1993

[Distribution and three-dimensional reconstruction of lymphatic vessels of the elbow joint capsule of rabbits].

Lymphatic vessels are believed to be distributed in the the depth of synovial membrane, but the details of this distribution remain to be fully elucidated. The synovial membrane is classified in part on the basis of histological characteristics, even in the same joint capsule, into three fundamental types: adipose type, areolar type, and fibrous type. In addition, the adipose and areolar types are involved in the absorption of synovial fluid. In this study, the distribution of lymphatic vessels was investigated with special reference to histological structure of the synovial membrane. The materials were prepared from 11 elbow joint capsules of male 8 rabbits weighting 2-3 kg. Five specimens were stained with silver nitrate, and the remainder were stained with trichrome. All of the materials were serially sectioned and observed by light microscopy. Three-dimensional reconstructions of lymphatic vessels were performed using Cosmozone 2SA software (Nikon Co.) with a PC-9800 series microcomputer (NEC Co.) When the joint capsule is divided into synovial and fibrous layers in accordance with the Nomina Histologica Japonica, the fibrous layer is frequently connected with the epimysium of neighboring muscles. The synovial and fibrous layers are occasionally continuous with each other, without a distinct boundary. The number of lymphatic vessels in the synovial layer is small, and they originate in the vicinity of the border of the fibrous layer and pass over into the lymphatic vessels of the fibrous layer. Many lymphatic vessels were found in the fibrous layer, the majority of which come from the epimysium or perimysium close to the outer surface of the fibrous layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Efficacy and safety of long-term erythropoietin therapy in chronic hemodialysis patients with renal anemia].

In order to examine the efficacy and safety of long-term erythropoietin (rHuEPO) therapy, 103 hemodialysis patients were treated with rHuEPO for their renal anemia and the effects were observed for 1 year. Within 3 or 4 months after starting the rHuEPO therapy, the hematocrit (Ht) value rose up to nearly 30% and the level was maintained thereafter by approximately 4500 IU per week of rHuEPO. Tachyphylaxis did not occur even after 1 year of rHuEPO treatment. Symptoms such as headache, dizziness or palpitation were markedly reduced with the improvement of anemia. Although blood pressure was modestly elevated (systolic by 9 mmHg, p < 0.01 and diastolic by 5 mmHg, p < 0.01 at 6-month-stage), only 1 patient was forced to stop the therapy. Moreover, the blood pressure was successfully controlled to the original level after 11 months. This blood pressure elevation was not related to the increase of Ht level nor the dose of rHuEPO. Serum protein, lipid, electrolytes and liver enzymes did not change during 1 year of rHuEPO therapy. These results indicate that rHuEPO treatment is effective and innocuous as a long-term therapy of renal anemia in hemodialysis patients.

Anemia↗
PubMed1993

Marked islet amyloid polypeptide-positive amyloid deposition: a possible cause of severely insulin-deficient diabetes mellitus with atrophied exocrine pancreas.

An insulin-deficient 51-year-old man was put on dietary therapy and sulfonylurea (SU). Although there was good glycemic control for 2 years, the fasting blood glucose (FBG) level increased gradually over the subsequent 4-year period, and there was a marked increase in body weight. Secondary failure of SU therapy 20 years after the initial diagnosis led to insulin therapy. The FBG became unstable, and the C-peptide response disappeared. The patient died of nonketotic hyperosmolar coma and pneumonia at the age of 87. At autopsy, the pancreas showed marked atrophy (32 g) with extensive fatty degeneration. Islets replaced by islet amyloid polypeptide (IAPP)-positive amyloid (IAPP-AM) amounted to 77% in the tail, 74% in the body, and 73% in the head of the pancreas. All islets were positive for IAPP-AM throughout the pancreas, except for a pancreatic polypeptide-rich lobe, where none were positive. IAPP-AM-positive islets had also undergone fatty change of the surrounding pancreatic acinar cells. beta-Cells decreased remarkably in number and were displaced to the periphery of the islets by the IAPP-AM deposits. These findings suggest that IAPP-related diabetes could have a progressive course, with secondary oral hypoglycemic agent failure and the subsequent development of severe insulin deficiency similar to that seen in insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1992

Plasma endothelin concentration: relation with vascular resistance and comparison before and after balloon dilatation procedures.

Endothelin (ET) is a potent vasoconstrictor peptide with an as yet uncertain physiological role in cardiovascular disease. We measured blood plasma ET concentrations using a recently developed radioimmunoassay and analysed the relations between ET concentration, systemic arterial pressure and systemic vascular resistance. In addition, ET levels before and after percutaneous balloon valvuloplasty and angioplasty were measured. Fifty-one patients were studied: (1) 13 patients with small left-to-right shunting or Kawasaki heart disease (age ranged from 4 to 144 months); (2) 10 patients who had undergone balloon valvuloplasty or angioplasty (age ranged from 1 to 233 months) and (3) 28 healthy infants and children (age ranged from 3 to 152 months). Systemic vascular resistance was calculated by the formula (mean aortic pressure--mean right atrial pressure) X 80/cardiac output (dyne.sec.cm-5). Plasma ET concentrations in healthy children less than 2 years were significantly higher than those over 2 years (2.48 +/- 0.62 vs 1.31 +/- 0.53 pg/ml). In eight patients in groups 1 and 2, plasma ET concentration in the pulmonary artery (2.00 +/- 0.43 pg/ml) was significantly lower than that in the femoral vein (2.39 +/- 0.69 pg/ml) and aorta (2.23 +/- 0.59 pg/ml), suggesting ET secretion derived from endothelial cells in peripheral pulmonary vessels. There was a significant positive correlation between ET concentrations in the femoral vein and systemic vascular resistance (r = 0.55, p less than 0.05). After balloon dilatation ET concentration rose from 2.15 +/- 0.82 pg/ml to 2.61 +/- 1.38 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Klinefelter's syndrome accompanied by diabetes mellitus and diabetes insipidus.

The first case of Klinefelter's syndrome accompanied by diabetes insipidus and diabetes mellitus is reported. A 41-year-old man admitted for hyperosmolar diabetic coma with a past history of diabetes insipidus was diagnosed as having Klinefelter's syndrome by endocrinological examination and sex chromosome analysis. In this case, glucose tolerance test was normalized half a year later and blood glucose was well controlled with diet therapy alone.

Adult↗