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Biomedical subjects

H Ohtaki

Publications and source records attributed to H Ohtaki.

34 records · Page 2Linked to original sources

In vitro effects of sho-saiko-to on production of granulocyte colony-stimulating factor by mononuclear cells from patients with chronic hepatitis C.

During the past 2 years, drug-induced interstitial pneumonia was reported in 66 Japanese patients, mainly among chronic hepatitis C patients, undergoing treatment with the Japanese herbal medicine "Sho-saiko-to" (TJ-9). As interstitial pneumonia is also induced by granulocyte colony-stimulating factor (G-CSF), we examined the effects of TJ-9 on G-CSF production in peripheral blood mononuclear cells. In patients with hepatitis B or C, G-CSF production in the absence of any stimulation was significantly lower than healthy controls (p < 0.01). G-CSF production increased along with the increase of TJ-9 levels, and this could induce excessive production of G-CSF in hepatitis C patients, and this may be a cause of interstitial pneumonia.

Anti-Inflammatory Agents, Non-Steroidal↗

[A comparative study of the quality of SPECT images obtained by 123I-IMP, 99mTc-HMPAO and 99mTc-ECD].

The purpose of this study was to comparatively evaluate the quality of SPECT images for the mapping of rCBF using three tracers, 123I-IMP, 99mTc-HMPAO and 99mTc-ECD. We performed three SPECT studies on seven patients with various cerebral diseases under the same conditions. An effect of Lassen's correction on SPECT images obtained by HMPAO was also evaluated. The same irregular regions of interest were placed on the four transaxial SPECT images. To quantitatively evaluate the pattern of tracer uptake and image contrast, the uptake ratio, regional count/mean count of the cerebrum, and its coefficient variations (CV) were defined, respectively. The order of the value of CV was HMPAO with correction > IMP > ECD > HMPAO without correction. HMPAO with correction showed the best image contrast, but HMPAO without correction was the worst. Uptake ratios of ECD and HMPAO with correction were decreased in the brain stem and thalamus in comparison with those of IMP. Both uptake ratios of ECD and HMPAO without correction were increased in the occipital cortex. IMP provides high quality SPECT images. Images obtained by HMPAO should be modified by Lassen's correction to increase image contrast. ECD or HMPAO should not be used to evaluate patients with spinocerebellar degeneration.

Aged↗

[A limitation of the split-dose method for evaluating rCBF changes using 99mTc-ECD and SPECT].

The purpose of the study is to validate the split-dose method corrected with dose ratio of 99mTc-ECD for brain perfusion scan. A dose of 600 MBq of 99mTc-ECD was divided into two with various dose ratios from 1:1 to 1:4, and injected to eleven patients with various cerebral diseases. A lesser dose of 99mTc-ECD was injected under a control state for the first SPECT scan, and 15 min SPECT scan was performed 10 min after injection with a triple-head high resolution gamma camera. After the scan, the other dose of 99mTc-ECD was injected under the same control state and the second SPECT scan was performed as same as above. A ratio of the activity of the first scan to the net activity of the second scan corrected by dose ratio, defined as K, was measured in brain regions of each subject. Expected value of K was 1, but the value was distributed with large variations in each subject. The mean % error of the K value was 10.4 +/- 4.9%. Hence it is considered that activity changes by more than 20% from the control values should be required to detect a significant rCBF change in an activation SPECT study. Then, we proposed a new method in which the activity of both two SPECT scans was normalized by cerebellar or occipital activity and compared. The ratio obtained by the proposed method came closer to 1 with less variations and with less mean % error in comparison with those of K value obtained by the dose-correction method. Although the proposed method has a limitation in the use of an activation study loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the study such as postural testing or finger-moving test.

Brain↗

A rapid typing system at three STR loci from bloodstains using a simple DNA extraction kit and capillary electrophoresis.

A rapid typing method for STR analysis from bloodstains was devised. DNA from three-year-old bloodstains of six individuals was extracted with a cationic detergent in a newly-released kit. Amounts of DNA extracted by the kit were 16.2 +/- 1.8 ng from 10 microliters of fresh blood samples. DNA was also extracted from bloodstains of three months and three years left at room temperature, and amounts of extracted DNA were estimated at 2.2 +/- 1.0 ng and 0.1 +/- 0.1 ng, respectively. The PCR mixture supplied with the kit, plus three sets of fluorescently labeled primers, were directly added to the tube used for DNA extraction. The amplified products were then analyzed by capillary electrophoresis, and the obtained data were automatically sized and typed using computer software. Three genotypes of all bloodstains except one sample at a single locus were determined correctly as those of freshly collected blood from the same individuals although some stains contained no more than 0.1 ng. Using this typing system, we were able to type three STR loci, HUMTH01, HUMF13A1 and HUMFES/FPS, from a single bloodstain within five hours. This typing is particularly useful for forensic practice.

Blood Stains↗

[Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample].

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.

Adult↗

Effects of ebelactone B, a lipase inhibitor, on intestinal fat absorption in the rat.

Ebelactones A and B, natural products from Streptomyces aburaviensis are potent inhibitors of pancreatic lipase. Lipase is the key enzyme required for the absorption of dietary triglycerides (TG). Ebelactone B inhibited, in a dose-dependent manner, the intestinal absorption of fat after fat-feeding in the rat. The most effective inhibition was observed when the inhibitor was administered at 60 min prior to fat-feeding. When ebelactone B (10 mg/kg) was administered, the serum levels of TG (58%) and cholesterol (36%) were decreased. Since ebelactone B effectively inhibitors absorption of dietary fat, if may provide a promising means for prophylaxis or therapeutics of hyperlipidemia and obesity.

Animals↗

[A new method for measurement of both regional cerebral blood flow and distribution volume using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT].

We developed a new method (functional IMP SPECT) to quantitate both regional cerebral blood flow (rCBF) and distribution volume (Vd) using 123I-IMP and SPECT based on a 2- compartment model (influx; K1 =rCBF and outflux; k2). This method requires one arterial blood sampling at 5 min after injection of the tracer and two SPECT scans at 30 min and 60 min. It takes approximately 60 min for total measurements. The integration of arterial input function is estimated by one blood sample taken at 5 min after injection of the tracer without octanol treatment, by using the correlation between one blood sample and the integration, which was obtained from studies on 25 subjects. With the value of integration, K1 and Vd are calculated from the data of two SPECT scans by using the mathematical functions based on the 2-compartment model, which were obtained from studies on 12 subjects. In the practical range of K1 (0.3-0.7 ml/g/min) and Vd (15-35 ml/g) given in the 2-compartment model, statistical errors of K1 and Vd obtained by the functional IMP SPECT were evaluated at approximately 14.0% and 17.2%, respectively. In clinical studies for eight subjects including two healthy volunteers, three patients with cerebral infarction and three patients with degenerative disease, K1 and Vd values estimated by the functional IMP SPECT were significantly correlated with those estimated by non-linear least squares fitting analysis based on the 2-compartment model, and the mean errors of K1 and Vd estimated by the functional IMP SPECT were approximately 8.0% and 11.2% respectively, suggesting the validity of the new method. We conclude that the functional IMP SPECT is clinically useful because of the accuracy, less-invasiveness and convenience.

Amphetamines↗

[A functional diagnostic method by measuring of distribution volume of 123I-IMP with SPECT].

To measure distribution volume of 123I-IMP with one-point sampling of arterial blood and 2 times SPECT scans using the Magic square method (Rate constant square method), we introduced a program on a SPECT computer system. In this program four functional images; distribution volume, CBF (K1), k2 and delayed/early ratio, and absolute values with S.D. are obtained on the computer. We have been using the program on daily SPECT studies. In this study we discussed the usefulness of the method. Redistribution phenomenon of 123I-IMP, which is not exactly enough investigated, can be transformed into a functional parameter, distribution volume. Since distribution volume represents an extent of retention of 123I-IMP in brain tissue, it can play an important role to evaluate functional activity in the brain and to diagnose cerebral diseases.

Adult↗

[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↗

[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↗

[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↗

[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↗

[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↗

Rat hepatocytes generate peptide leukotrienes from leukotriene A4.

The biosynthetic mechanism of peptide leukotrienes was studied in rat liver. A catalytic activity to synthesize leukotriene (LT) C4 from LTA4 (LTC4 synthesis activity) was shown to be associated mainly with the microsomal fraction of hepatocytes, but also to a small extent with nonparenchymal cells including Kupffer cells, suggesting that the hepatocytes have an ability to generate peptide LTs. Stimulation of the isolated hepatocytes with calcium ionophore (A23187) did not cause any significant production of peptide LTs, whereas addition of LTA4 induced a remarkable generation of peptide LTs in a dose-dependent manner. Addition of LTA4 also augmented the peptide LT production by Kupffer cells, but its amount was much smaller than that by the hepatocytes under the same culture conditions. Coincubation of the hepatocytes and Kupffer cells, following A23187 stimulation, elicited a markedly enhanced production of peptide LTs even without any addition of LTA4, whereas the LT production in the coincubation system was suppressed almost completely by treating the Kupffer cells with a specific inhibitor of 5-lipoxygenase, AA861 (10 microM). An enzymatic cooperation between the hepatocytes and Kupffer cells may play an important role in generating peptide LTs in the liver.

Animals↗

[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↗

A case of lymphoma-type alpha-chain disease.

A 69-year-old man with a rare case of lymphoma-type alpha-chain disease was admitted to the hospital with marked cervical and inguinal lymph node swelling. Lymph node biopsy showed marked infiltration of plasma cells, plasmacytoid cells and immunoblastoid cells, alone or in combination. Immunoelectrophoresis and immunoselection identified alpha-chain in the serum and urine. The site of alpha-chain synthesis was extensively studied in the whole body, and the immunoperoxidase technique eventually demonstrated the presence of alpha-chains in the cytoplasm of infiltrating malignant cells in the lymph nodes. No infiltrating malignant cells were found in other organs or tissues, including those of the digestive and respiratory tracts.

Aged↗