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Biomedical subjects

M Ohkubo

Publications and source records attributed to M Ohkubo.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Validation study in quantitative measurement of regional cerebral blood flow using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT].

We validated following five methods to quantitate regional cerebral blood flow (rCBF) using 123I-IMP and SPECT; 1) microsphere method, which is based on a microsphere model using the SPECT image at five minutes after 123I-IMP injection with continuous withdrawal of arterial blood, 2) microsphere+ one-point sampling method, which is the same as the microsphere method except for using one-point sampling instead of continuous withdrawal, 3) conventional microsphere + one-point sampling method, which is the same as the microsphere + one-point sampling method except for using a later SPECT image corrected with the ratio of alteration of measured entire brain activity, 4) Table look-up method, which is based on a two-compartment model (influx; K1 and outflux; k2) using one arterial blood sample taken at 10 min and two SPECT images at 30 min and 180 min post-injection, and 5) functional IMP SPECT, which is based on the two-compartment model using one arterial blood sample taken at 5 min and two SPECT images at 30 min and 60 min post-injection. Those methods were applied to six patients with cerebral infarction and degenerative diseases, and rCBF results were compared with those estimated by non-linear least squares fitting (NLLSF) analysis based on the two-compartment model. The rCBF values obtained by the microsphere method was best correlated with those by NLLSF analysis (r = 0.940), followed by the microsphere+one-point sampling method (r = 0.885) and the functional IMP SPECT (r = 0.882). The table look-up method underestimated rCBF especially at the high flow level, however showed good correlation (r = 0.859). The conventional microsphere + one-point sampling method overestimated rCBF, however showed good correlation (r = 0.849). Distribution volume (Vd = K1/k2) was also estimated by both the table look-up method and the functional IMP SPECT. While values of Vd by the functional IMP SPECT were significantly correlated with those by NLLSF analysis (r = 0.785), the table look-up method overestimated Vd (43.4 +/- 6.6 ml/g) and showed not good correlation (r = 0.287).

Brain↗
PubMed1995

Behavioral studies on FR115427, a novel selective N-methyl-D-aspartate antagonist.

Behavioral and in vitro receptor binding methods were used to evaluate and compare the effects of FR115427 ((+)-l-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride) with those of MK801, a non-competitive NMDA antagonist. FR115427 inhibited NMDA-induced convulsions in mice by intracerebroventrical(ICV) and systematic injection. FR115427 was found to be about ten times less potent than MK801. Furthermore, the inhibitory effect of FR115427 and MK801 on NMDA-induced convulsions was evaluated in time course studies in mice. MK801 exhibited a more sustained anticonvulsive activity than FR115427. In addition, PCP-like behaviors were examined in mice after ICV injection of these compounds. At the lowest dose FR115427 significantly increased locomotor activity, although the effect of this compound was about hundred times less potent than that of MK801. At higher dose a more complex pattern of behavior, e.g. head-movement and eventually ataxia was observed. In binding assays with rat brain membranes, FR115427 inhibited the binding of (3H)TCP (IC50 = 0.249 microM) and (3H)MK801 (IC50 = 0.312 microM) but did not inhibit the binding of (3H)CPP or (3H)glycine. These results suggest that FR115427 is a novel non-competitive NMDA antagonist that acts on a binding site located within the NMDA receptor associated ion channel.

Animals↗
PubMed1995

Evaluation of cerebral blood flow in patients with idiopathic orthostatic hypotension using Tc-99m HMPAO brain SPECT during postural testing.

To determine whether regional cerebral blood flow (rCBF) would change on standing in patients with idiopathic orthostatic hypotension (IOH), Tc-99m HMPAO SPECT studies were performed during postural testing in five patients with IOH. After 10 minutes of quiet rest on a bed, the patients arose quickly and, at the same time, the radiotracer was injected intravenously. SPECT data were obtained with a ring-type SPECT scanner. Another dose of Tc-99m HMPAO was injected with the subjects in the supine position, and SPECT was performed again. Image subtraction was used to evaluate the change in rCBF caused by postural testing. In all patients, the authors observed a decrease of rCBF ni the frontal cortex and basal ganglia. This preliminary study suggests that changes in rCBF occur in patients with IOH on standing, and Tc-99m HMPAO SPECT performed during postural testing may have an important role in evaluating these changes.

Brain↗
PubMed1995

Can the microsphere model by applied to cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine with SPET regardless of washout from brain tissue?

The microsphere model and the continuous withdrawal of arterial blood have commonly been used in clinical studies when measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission tomography. The method is considered to underestimate rCBF because of the washout of tracer from brain tissue; however, the extent of this underestimation is not known. To assess whether this underestimation can be determined quantitatively, we performed simulation analysis based on the microsphere model and the two-compartment model [influx, K1(rCBF); and outflux, k2(washout)] using the time-activity curves of 123I-IMP in arterial blood [Ca(t)] of 10 subjects. With the microsphere method, rCBF values fell as time post-injection increased. The extent of underestimation of rCBF was 4.7 +/- 0.28% (mean +/- S.D.) at 5 min, 10.2 +/- 0.42% at 10 min and 15.2 +/- 0.55% at 15 min. There was little variation in the extent of underestimation and it was not dependent on the Ca(t) of the subjects. We therefore considered the results to be generally applicable to various studies of the microsphere model. As 4.7% is considered to be negligible in clinical studies, we conclude that the microsphere model can be applied to obtain accurate measurement of rCBF up to 5 min regardless of washout.

Amphetamines↗
PubMed1995

Therapy and imaging of pancreatic carcinoma xenografts with radioiodine-labeled chimeric monoclonal antibody A10 and its Fab fragment.

Recombinant mouse/human chimeric monoclonal antibody A10 (ch-A10) and its Fab fragment (ch-Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I-labeled ch-A10 and ch-Fab in an antigen-positive human pancreatic carcinoma (BxPC-3) xenograft model. We also evaluated the anti-tumor effect of 131I-labeled ch-A10, and studied the detection of BxPC-3 xenografts with 123I-labeled ch-Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I-labeled ch-A10 was significantly greater than that of 125I-labeled ch-Fab 24 h post-injection. However, the tumor-to-blood ratio was 46.8 for ch-Fab at 24 h post-injection, while it was only 1.4 for ch-A10. Microautoradiography studies showed that ch-Fab penetrated more uniformly into the tumor nodules than did ch-A10. In mice given a therapeutic dose of 131I-labeled ch-A10, a significant inhibition of tumor growth was seen, while control 131-I-labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I-labeled ch-A10, but leukocyte counts recovered to normal levels at 8 weeks post-injection. In whole-body scintigraphy, clear and rapid tumor imaging was obtained with 200 microCi of 123I-labeled ch-Fab 24 h post-injection. These results suggest that radioiodine-labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radioimmunodetection of pancreatic carcinomas.

Adult↗
PubMed1995

Studies on cerebral protective agents. VIII. Synthesis of 2-aminothiazoles and 2-thiazolecarboxamides with anti-anoxic activity.

Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h), possessing a nitrogenous basic moiety at the C-2 position of the thiazole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, N-[2-(4-morpholinyl)ethyl]-4-(3-trifluoromethylphenyl)-2- thiazolecarboxamide hydrochloride (4e, FR108143) (minimum effective doses of 3.2 mg/kg i.p. and 10 mg/kg p.o., respectively) exhibited more potent AA activity than either FK360 or compound 1, each of which has a nitrogenous basic moiety at the C-5 position. The structure-activity relationships with regard to AA activity of this series of compounds are discussed, and the three-dimensional electrostatic potentials (3D-MEP) around the basic nitrogen atom of FK360 and the thiazole derivative (4e) are compared.

Animals↗
PubMed1995

Studies on cerebral protective agents. VII. Synthesis of novel 4-arylazole derivatives with anti-anoxic activity.

Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing an amino moiety at the C-5 position of the azole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-yl)methyl-4-(3-nitrophenyl)-2-phenylthia zole (3b, FR75094) possessed significant AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate-induced cerebral edema in rats. Structure-activity relationships in regard to AA activity of this series of compounds are discussed.

Animals↗
PubMed1995

[A study on accuracy of rCBF measurements using the conventional microsphere method with N-isopropyl-p-[123I]iodoamphetamine and SPECT].

To evaluate the accuracy of conventional microsphere method for the measurement of regional cerebral blood flow (rCBF) based on the microsphere model with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT, we performed simulation analysis and clinical studies. Although the microsphere method requires early SPECT scan at a few minutes after injection of the tracer for the accurate measurement of rCBF, the conventional microsphere method, which is generally used, requires more delayed SPECT scan with long scan-duration. In the conventional microsphere method, the delayed SPECT image is corrected to the image at a few minutes after injection of the tracer by using the monitored entire brain activity. By the simulation analysis based on the 2-compartment model (influx; K1 and outflux; k2) using the input function and the entire brain activity obtained from eight subjects respectively, it was found that the conventional microsphere method overestimated the rCBF in the practical range of rCBF and Vd (= K1/k2) given in the 2-compartment model. When the values of rCBF and Vd in the 2-compartment model were given at 0.5 (ml/g/min) and 30 (ml/g) respectively, the rate of overestimation of rCBF by the conventional microsphere method was determined to be 17.3 +/- 0.7% (mean +/- S.D.). Also in clinical studies for eight subjects, the conventional microsphere method overestimated the rCBF compared with those evaluated by non-linear least squares fitting (NLLSF) analysis based on the 2-compartment model. Those results agreed well with the simulation analysis, suggesting the validity of the simulation. The rCBF values clinically estimated by the conventional method were, however, significantly correlated with those calculated by NLLSF analysis, and there were not so much difference between the two quantitative rCBF images obtained by the conventional microsphere method and the microsphere method. Therefore, we conclude that the conventional microsphere method is clinically useful in spite of the overestimation of rCBF.

Amphetamines↗
PubMed1994

Levels of serum colony-stimulating factors (CSFs) in patients on long-term haemodialysis.

We measured the levels of colony-stimulating factors (G-CSF, M-CSF and GM-CSF) and several cytokines in paired sera obtained from 51 patients (33 males and 18 females; mean age: 53 years) on long-term haemodialysis (HD). The mean pre-HD G-CSF level was 22.7 +/- 21.7 pg/ml and the post-HD level was 40.3 +/- 54.4 pg/ml. The mean pre-HD M-CSF level was 2.4 times higher than normal at 1287 +/- 380 U/ml, and it increased to 1644 +/- 456 U/ml after HD (r = 0.83). GM-CSF was not detectable in any of the serum samples. IL-1 beta was detectable in 38 pre-HD sera at a mean level of 57.1 +/- 21.8 pg/ml, but was rarely detected after HD. TNF-alpha was not usually detected. When the CSF levels were divided by the product of the serum total protein concentration and body weight, the post-HD value for G-CSF was almost always greater than the pre-HD value and there was an improved pre-post correlation (r = 0.69). In the transformed pairs of M-CSF level, the post-HD value did not differ much from the pre-HD value, and a strong pre-post correlation was noted (r = 0.94). These results suggest that the serum G-CSF level is not affected by chronic renal failure, although HD may induce an increase of G-CSF. In the case of M-CSF, however, impaired renal metabolism and/or excretion may increase the serum concentration, but it is not modulated by haemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A new method of regional cerebral blood flow measurement using one-point arterial sampling based on the microsphere model with N-isopropyl-p-[123I]-iodoamphetamine SPECT.

We developed a new method for quantitative measurement of regional cerebral blood flow (rCBF) using one-point arterial sampling with N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) and single photon emission computed tomography (SPECT) based on the microsphere model. Although the conventional microsphere method requires both the continuous withdrawal of arterial blood (integral of Ca(t)) and treatment of the blood with octanol to obtain the fraction of true tracer activity in the integral of Ca(t) (N), the new method does not require these two procedures. We examined 14 patients to analyse the correlation between the integral of Ca(t)N and a small arterial sample obtained at one time point [one-point Ca(t)] after the injection of 123I-IMP without octanol treatment. The integral of Ca(t)N was calculated from one point Ca(t) using the regression line of the correlation. An error of 8.1% in the calculated value compared to the actual value of the integral of Ca(t)N, could be inferred from one-point Ca(t) obtained at 6 min after the injection. Then regional cerebral blood flow was measured by the method and a significant correlation was obtained with rCBF measured using the 133Xe inhalation method (r = 0.773). The one-point Ca(t) method provides fast, easy, accurate and non-invasive measurement of rCBF without inserting catheters and without treatment of arterial blood with octanol.

Adolescent↗
PubMed1994

Different effects between antihypertensive drugs on nephrotic-range proteinuria in renovascular hypertension.

A 61-year-old man developed renovascular hypertension characterized by nephrotic-range proteinuria. When he was treated with a calcium channel blocker, glomerular filtration fraction was 0.26 and massive proteinuria ranging from 10 to 15 g/day persisted. An angiotensin-converting enzyme inhibitor markedly reduced the proteinuria to 1-2 g/day with a filtration fraction of 0.20. After the antihypertensive drug was switched to a beta-blocker, the filtration fraction was 0.23 and urinary protein excretion was 3-4 g/day. Blood pressure control was comparable by each drug. These findings suggest a role of intraglomerular hydraulic mechanism in the etiology of massive proteinuria in renovascular hypertension.

Adrenergic beta-Antagonists↗
PubMed1994

Mitochondrial encephalomyopathy: elevated visual cortex lactate unresponsive to photic stimulation--a localized 1H-MRS study.

We used localized H-magnetic resonance spectroscopy (MRS) to study the metabolic changes in the visual cortex of patients with mitochondrial encephalomyopathy. Measurement of metabolite levels in the occipital visual cortex obtained in the dark with seven normal subjects and with four patients (all four of whom had Kearns-Sayre syndrome [KSS]) showed high lactate levels in the patients. Photic stimulation (PS) in four normal volunteers showed that lactate increased immediately after the start of PS and that it decreased to the baseline level with continued PS. Lactate in the resting state was higher in the KSS patients than in the controls, and, unlike the controls, the KSS patients showed no significant elevation of lactate with PS.

Humans↗