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Biomedical subjects

M Yoshikawa

Publications and source records attributed to M Yoshikawa.

At least 199 records · Page 11Linked to original sources
PubMed1999

Development of a totally implantable biventricular bypass centrifugal blood pump system.

BACKGROUND: During the past 2 years, the development of a totally implantable biventricular bypass rotary blood pump system has been made. METHODS: An extracorporeal gyro centrifugal pump, the CIE3, was miniaturized and developed into the PI601, a totally implantable plastic pump. Two-day anatomic and hemodynamic feasibility studies demonstrated that these two pump systems were easily implantable inside a calf's abdominal wall, directly under the diaphragm. The priming volume of the pump was 20 mL, with sufficient cardiac outputs at approximately 2,000 rpm and requiring less than 10 W of power. Two-week antithrombogenic screening tests also revealed these pump systems to be quite antithrombogenic. In addition, 1-month system reliability studies demonstrated fail-safe reliable performances. RESULTS AND CONCLUSIONS: Encouraged by these preliminary studies, the PI601 model was converted to the permanently implantable titanium gyro pump PI702 model. The long-term implantations were initiated approximately 3 months ago, and two such long-term LVAD studies are currently underway with no sign of difficulty (October 10, 1997). They were followed 283 days and 72 days, respectively. Both terminated due to functional inflow obstruction. There were no blood clots or emboli at autopsy.

Animals↗
PubMed1999

Long-term effects of prostaglandin E2 on the mineralization of a clonal osteoblastic cell line (MC3T3-E1).

Prostaglandin (PG) E2 is thought to be a mediator of the effect of mechanical stress on bone formation, but its effects on osteoblasts have not yet been fully described. Here, the effects of the continuous application of PGE2 and indomethacin, an inhibitor of prostaglandin G/H synthase (cyclo-oxygenase), on the proliferation, differentiation and mineralization of a clonal osteoblastic cell line, MC3T3-E1, were investigated. The cells were cultured in media with either a high (1 microg/ml) or a low (1 ng/ml) concentration of PGE2, with indomethacin (1 microg/ml) and, as a control, with neither agent. The effects of PGE2 and indomethacin were assessed quantitatively. Indomethacin and a high concentration of PGE2 increased the total protein compared to the control and low-PGE2 cultures. 7 days after confluence, alkaline phosphatase (ALP) activity within the cells and extracellular matrices increased. This increase was highest with indomethacin and lowest with a high concentration of PGE2. ALP activity also increased in the medium, but only 21 days after confluence; the effects of the agents were similar to those on the cells and matrices. The accumulation of calcium, inorganic phosphate and hydroxyproline was highest with indomethacin. PGE2 production was at its maximum when the cells were at confluence and was inhibited by indomethacin. Specific [3H]PGE2 binding to the microsomal fraction of the cell was also measured to examine the expression of the PGE2 receptor. The amount of [3H]PGE2 binding per mg of protein was highest at confluence, then decreased and again increased in the mineralizing stage. These results suggest that indomethacin increases ALP activity and the accumulation of mineralized tissue in MC3T3-E1 cells, presumably by inhibiting the production of PGE2. PGE2 could signal the suppression of mineralization as early as confluence.

3T3 Cells↗
PubMed1999

Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulfhydryls, and prostaglandins in gastroprotection by momordin Ic, an oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesions in rats.

The roles of capsaicin-sensitive sensory nerves (CPSN), endogenous nitric oxide (NO), sulfhydryls (SHs), prostaglandins (PGs) in the gastroprotection by momordin Ic, an oleanolic acid oligoglycoside isolated from the fruit of Kochia scoparia (L.) SCHRAD., on ethanol-induced gastric mucosal lesions were investigated in rats. Momordin Ic (10 mg/kg, p.o.) potentially inhibited ethanol-induced gastric mucosal lesions. The effect of momordin Ic was markedly attenuated by the pretreatment with capsaicin (125 mg/kg in total, s.c., an ablater of CPSN), N(G)-nitro-L-arginine methyl ester (L-NAME, 70 mg/kg, i.p., an inhibitor of NO synthase), N-ethylmaleimide (NEM, 10 mg/kg, s.c., a blocker of SHs), or indomethacin (10 mg/kg, s.c., an inhibitor of PGs biosynthesis). The attenuation of L-NAME was abolished by L-arginine (300 mg/kg, i.v., a substrate of NO synthase), but not by D-arginine (300 mg/kg, i.v., the enatiomer of L-arginine). The effect of the combination of capsaicin with indomethacin, NEM, or L-NAME was not more potent than that of capsaicin alone. The combination of indomethacin and NEM, indomethacin and L-NAME, or indomethacin and NEM and L-NAME increased the attenuation of each alone. These results suggest that CPSN play an important role in the gastroprotection by momordin Ic on ethanol-induced gastric mucosal lesions, and endogenous PGs, NO, and SHs interactively participate, in rats.

Animals↗
PubMed1999

Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein.

Conditions for the release of beta-casomorphin-7 from bovine beta-casein by gastrointestinal proteases in vitro were investigated. beta-Casomorphin-7 was released only from a genetic variant of beta-casein containing a His residue at the 67th position of the peptide chain. Elastase cleaved the peptide bond between Ile66 and His67, releasing the carboxyl terminus of beta-casomorphin-7. Pepsin and leucine aminopeptidase were required to release the amino terminus of this peptide. beta-Casomorphin-9, -13, and -21 also were isolated, and their opioid activities were measured. In this study, we also isolated a novel opioid peptide neocasomorphin-6 (Tyr-Pro-Val-Glu-Pro-Phe), which was released by action of trypsin or pepsin and chymotrypsin.

Amino Acid Sequence↗
PubMed1999

Determination of TA-0201, a novel orally active non-peptide endothelin antagonist, in rat plasma and tissues by a liquid chromatography--electrospray ionization--tandem mass spectrometry system.

N-[6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-5-(4-methylphenyl)-4-pyrimid inyl]-4-(2-hydroxy-1, 1-dimethylethyl) benzenesulfonamide sodium salt (TA-0201) is a novel orally active non-peptide antagonist for endothelin (ET) receptors. A sensitive and simultaneous determination method of TA-0201 and its major metabolites by liquid chromatography tandem mass spectrometry (LC--MS/MS) in a selected reaction monitoring mode using [2H6]TA-0201 as the internal standard was developed, and the plasma and tissue concentrations of TA-0201 and its major metabolites were determined in a pharmacokinetic study. The lower limit of determination of plasma TA-0201 concentrations by this method was 0.1 ng/0.5 ml, and the between- and within-run accuracy and precision were both less than 5.1%, in the calibration curve range of 0.1-50 ng/0.5 ml. This method was applied to determine the concentrations of TA-0201 and its metabolites in plasma and various target tissues, i.e. the heart, lung and kidney, after oral administration of TA-0201 (0.1 mg/kg(-1)) to male rats. TA-0201 and its major metabolite of a carboxylic acid form were detected in plasma and all the tissues 24 h after administration, their tissue concentrations being higher than those in plasma and still detectable at 72 h. Thus, this method could successfully be applied to study pharmacokinetic properties of TA-0201 in rats.

Administration, Oral↗
PubMed1999

Structure-related inhibitory activity of oleanolic acid glycosides on gastric emptying in mice.

We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on gastric emptying in non-nutrient meal- or nutrient meal-loaded mice. Test samples were given orally to fasted mice 0.5 h before loading of test meals. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (3, 12.5-50 mg/kg), momordin Ic (4, 25 and 50 mg/kg), momordin I (6, 12.5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (8, 12.5-50 mg/kg) and V (10, 50 mg/kg)] were found to show inhibitory effects on gastric emptying in 1.5% CMC-Na test meal-loaded mice. 4, 6, and 8 also inhibited gastric emptying in mice given 40% glucose test meal, milk test meal, and 60% ethanol test meal. 3 inhibited gastric emptying in mice given milk test meal or 60% ethanol test meal, but lacked significant inhibition in 40% glucose test meal-loaded mice. 10 (50 mg/kg) also slightly inhibited gastric emptying in milk test meal-loaded mice, but lacked the significant inhibition in mice given 40% glucose or 60% ethanol test meal. Whereas oleanolic acid 3,28-0-bisdesmosides [momordin IIc (5), chikusetsusaponins IV (7) and V (9)], oleanolic acid 28-O-monodesmoside [compound O (2)], and their common aglycon [oleanolic acid (1)] showed no such effects at dose of 50 mg/kg. 28-O-Deglucosyl-chikusetsusaponin V (10) showed a little inhibition in these experiments. These results indicate that both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 28-ester glucoside moiety and 2'-O-beta-D-glucopyranoside moiety reduce the activity.

Animals↗
PubMed1999

Effects of oleanolic acid glycosides on gastrointestinal transit and ileus in mice.

The effects of various oleanolic acid glycosides obtained from medicinal herbs on gastrointestinal transit (GIT) and ileus were investigated in fasted mice. Ileus was induced by the peritoneal-irritation or by the laparotomy with manipulation. One hour after the oral administration, three oleanolic acid 3-O-monodesmosides (oleanolic acid 3-O-glucuronide (3, 50 mg/kg), momordin Ic (4, 25 and 50 mg/kg), and momordin I (6, 25 mg/kg)) significantly accelerated GIT, but two oleanolic acid 3-O-monodesmosides (28-deglucosyl-chikusetsusaponins IV (8) and V (10)), oleanolic acid 3,28-O-bisdesmosides (momordin IIc (5), chikusetsusaponins IV (7) and V (9)), and their common aglycon (oleanolic acid (1)) (50 mg/kg) showed no significant effect. On the other hand, oleanolic acid 28-O-monodesmoside (compound O (2, 50 mg/kg)) significantly inhibited GIT. 4 (5-25 mg/kg) and 6 (12.5 and 25 mg/kg) also significantly prevented the inhibition of GIT induced by the peritoneal injection of acetic acid. 2 and 9 (50 mg/kg) significantly potentiated the inhibition of GIT, whereas 1, 3, 5, 7, 8, and 10 (50 mg/kg) showed no significant effect. 3, 4, 6, and 10 (50 mg/kg) significantly prevented the inhibition of GIT induced by laparotomy with manipulation, while 1, 2, 5, 7, 8, and 9 (50 mg/kg) showed no significant effect. These results indicate that the 3-O-glycoside moiety seems to be essential to show the GIT accelerating activity, and the 28-O-glucoside moiety reduce the activity. The accelerations of GIT by 3, 4, and 6 were completely abolished by the pretreatment with streptozotocin (100 mg/kg, i.v.), but not by the pretreatment with capsaicin (75 mg/kg in total, s.c.). These results suggest that sympathetic nervous system, but not capsaicin-sensitive sensory nerves, be involved in the enhancements of GIT by 3, 4, and 6. It is worthy to study their therapeutical effect in the prevention of the inhibition of GIT, including ileus, in clinic.

Animals↗
PubMed1999

Structure-requirements of isocoumarins, phthalides, and stilbenes from Hydrangeae Dulcis Folium for inhibitory activity on histamine release from rat peritoneal mast cells.

We examined the structure-activity relationships of isocoumarins, phthalides and stilbenes isolated from Hydrangeae Dulcis Folium and related compounds for the inhibition of histamine release in rat peritoneal mast cells. The activities of isocoumarins such as thunberginols A and B were more potent than those of dihydroisocoumarins such as hydrangenol and thunberginol G. The double bond at the 3-position seemed to be essential to potentiate the activity. The hydroxyl groups at the 8-, 3'- and 4'-positions of isocoumarin were essential for the activity, while the hydroxyl group at the 6-position was scarcely needed. Since the activities of benzylidenephthalides such as thunberginol F were more potent than those of hydramacrophyllols A and B, the presence of a double bond at the 3-position was needed to increase the activity. Moreover, the hydroxyl group at the 8-position was essential for the activity. On the time course study, thunberginols A, B and F completely inhibited histamine release by pretreatment at 100 microM for 1 to 15 min, whereas DSCG inhibited histamine release only following 1-min pretreatment at 1000 microM. These results suggested that the mechanisms of the inhibitory effect of thunberginols are different from that of DSCG.

Animals↗
PubMed1999

Effects of escins Ia, Ib, IIa, and IIb from horse chestnuts on gastrointestinal transit and ileus in mice.

The effects of saponin fraction and its principal constituents escins Ia (1), Ib (2), IIa (3), and IIb (4) from horse chestnuts on gastrointestinal transit (GIT) and ileus were investigated in mice. Ileus was induced by acetic acid peritoneal irritation or by laparotomy with manipulation. One hour after the oral administration, the saponin fraction (12.5-100 mg/kg) and 14 (12.5-50 mg/ kg, except for 3 at 12.5 mg/kg) dose-dependently accelerated GIT. The optimal effects of the saponin fraction (25 mg/kg) occurred 5-240 min (applied intervals between the fraction and the charcoal meal) after the oral administration. The fraction (12.5-100 mg/ kg) and 1-4 (12.5-50 mg/kg, except for 1 and 2 at 12.5 mg/kg) dose-dependently prevented the inhibition of GIT induced by the acetic acid peritoneal irritation. They (12.5-100mg/kg) also dose-dependently prevented the inhibition of GIT induced by the laparotomy with manipulation. Desacylescins I (5) and II (6) (50 mg/kg) showed no such effects. These results demonstrated that the saponin fraction and 1-4 accelerated GIT and prevented the experimental ileus, and indicate that the 21, 22-acyl groups are essential for the accelerative effects of 1-4. The accelerations of GIT by 1-4 were completely abolished by the pretreatment with streptozotocin (100 mg/kg, iv), but not by the pretreatment with capsaicin (75 mg/kg in total, sc) or atropine (10 mg/kg, sc). These results imply that the sympathetic nervous system may be, but neither capsaicin-sensitive sensory nerves nor the cholinergic mechanism, involved in the accelerations of GIT by escins 1-4.

Animals↗
PubMed1999

Parenchymal echo patterns of cirrhotic liver analysed with a neural network for risk of hepatocellular carcinoma.

BACKGROUND: To objectively evaluate the parenchymal echo patterns of the liver in cirrhosis, an image analysing system in which a neural network is used has been found capable of numerically calculating coarse score (CS). Using this system, we analysed whether or not CS can serve as a predictive factor for the development of hepatocellular carcinoma (HCC). METHODS: The risk factors for HCC were evaluated in 95 patients with liver cirrhosis with an average follow-up period of 2041 +/- 823 days. We used a three-layer feed-forward neural network and a back-propagation algorithm to calculate CS. RESULTS: There were strong correlations between CS, alanine aminotransferase (ALT) and alpha-fetoprotein (AFP) and the average cumulative incidence rate of HCC evaluated by the Cox's proportional hazards model. The adjusted rate ratios were estimated to be 3.00, 2.80 and 2.01, respectively. The cumulative risks of HCC were significantly higher with an initial CS > or = 1.5 than with an initial CS < 1.5, with ALT > or = 80 IU/L than with initial ALT < 80 IU/L and with AFP > or = 20 ng/mL than with initial AFP < 20 ng/mL, all analysed by the log-rank test. CONCLUSIONS: Coarse score is a useful predictor for development of HCC.

Adult↗
PubMed1999

Long-term in vivo left ventricular assist device study for 284 days with Gyro PI pump.

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, the Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart (TAH), 2 week screening tests for anti-thrombogenecity, and a 1 month system feasibility study. Based upon these results, a metallic prototype, the Gyro PI 700 series, was subjected to long-term in vivo left ventricular assist device (LVAD) studies of over 1 month. The Gyro PI 700 series has the same inner dimension and same characteristics of the Gyro PI 601 such as an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI metallic pump is also driven with the Vienna DC brushless motor actuator like the PI 601. The pump-actuator package was implanted in 3 calves in the preperitoneal space, bypassing from the left ventricular (LV) apex to the descending aorta. Case 1 achieved a 284 day survival. Case 2 was euthanized early at 72 postoperative days as a result of the functional obstruction of the inlet port due to the excessive growth of the calf. There was no blood clot inside the pumps of either case. Case 3 is on-going (22 days on July 24, 1998). During these periods, all cases showed no physiological abnormalities. In conclusion, the PI 700 series pump has excellent results as a long-term implantable LVAD.

Animals↗
PubMed1999

A new control method that estimates the backflow in a centrifugal pump.

The rotary blood pump will be widely used in the near future as an implantable left ventricular assist device (LVAD). However, one obstacle for the centrifugal pump is a control method that can maintain an optimum flow rate in a physiological condition. Thus, the object of this study is to develop this optimum control system for the centrifugal pump. If the heart function and pump efficiency are stable, the ratio of the systole current to the the diastole current (S/D) will be a fixed value. However, if the heart function and pump efficiency are unstable, S/D will not be a fixed value. This control system was investigated with a calf that was subjected to an ex vivo LVAD study. The LVAD was a Gyro C1E3 centrifugal pump. The pump flow rate was changed to 1.5, 3.5, 5.2, and 6.2 L/min. According to the changes of the pump flow rates, the S/D values were 1.01 +/- 0.01, 1.06 +/- 0.05, 1.03 +/- 0.01, and 1.03 +/- 0.01, respectively. There was no statistical difference among the 3 groups. In a separate experiment, the backflow condition S/D was 1.88 +/- 0.6, and the normal condition S/D was 1.35 +/- 0.5. There was a statistical difference between the 2 groups. The results of this study suggest that S/D is not influenced by the pump flow rate. However, the S/D was changed when the pump was in a backflow condition. This method will be useful in controlling a centrifugal pump requiring only electrical current information.

Analysis of Variance↗
PubMed1999

An emergency balloon occlusion system for a rotary blood pump left ventricular assist system.

A fatal outcome is expected in a left ventricular assist system (LVAS) utilizing a rotary blood pump if there is no mechanism to prevent the backflow from the aorta to the heart in the case of acute pump failure. To solve this problem, a passive mechanical clamping system at the outflow graft of a rotary blood pump was developed together with Fuji Systems, Inc., Yokohama, Japan. The system consisted of an emergency clamp port and an occlusion balloon. The balloon was fixed around the outlet graft of the LVAS. In an in vitro study, a fail-safe clamping operation with 2 ml saline injection under 7 L/min flow against 140 mm Hg pressure reduced the flow to 0.5 L/min while the pressure in the system increased to 190 mm Hg. The systems were also applied to 2 in vivo LVAD studies. When the pumps were stopped, there were approximately 3.0 L/min regurgitant flows. The balloon occluder prevented this regurgitant flow effectively against a 100/80 mm Hg arterial pressure. In conclusion, this emergency balloon occlusion system is relatively easy to operate and will work efficiently in all possible clinically encountered malfunctions of the rotary blood pump LVAS.

Animals↗
PubMed1999

Feasibility of a tiny Gyro centrifugal pump as an implantable ventricular assist device.

The Gyro pumps were developed for long-term circulatory support. The first generation Gyro pump (C1E3) achieved 1 month paracorporeal circulatory support in chronic animal experiments; the second generation (PI702) implantable ventricular assist device (VAD) was successful for over 6 months. The objective of the next generation Gyro pump is for use as a long-term totally implantable VAD and for pediatric circulatory support. This tiny Gyro pump (KP101) was fabricated with the same design concept as the other Gyro pumps. The possibility of an implantable VAD was determined after performance and hemolysis test results were compared to those of the other Gyro pumps. The pump housing and impeller were fabricated from polycarbonate with an impeller diameter of 35 mm. The diameter and height of the pump housings are 52.3 mm and 29.9 mm, respectively. At this time, a DC brushless motor drives the KP101, which is the same as that for the C1E3. The pump performance was measured in 37% glycerin water at 37 degrees C. Hemolysis tests were performed utilizing a compact mock loop filled with fresh bovine blood in a left ventricular assist device (LVAD) condition at 37 degrees C. The KP101 achieved the LVAD conditions of 5 L/min and 100 mm Hg at 2,900 rpm; generated 10 L/min against 100 mm Hg at 3,200 rpm; 3 L/min against 90 mm Hg at 2,600 rpm; and 2 L/min against 80 mm Hg at 2,400 rpm. In addition, the pump efficiency during this experiment was 12.5%. The other Gyro pumps. that is, the C1E3, PI601, and PI701, in an LVAD condition require 1,600, 2,000, and 2,000 rpm, respectively. The KP101 produced a normalized index of hemolysis (NIH) value of 0.005 g/100 L. With regard to the NIH, the other Gyro pumps, namely the C1E3, PI601, and PI701 demonstrated 0.0007, 0.0028, and 0.004 g/100 L, respectively. The KP101 produced an acceptable pressure flow curve for a VAD. The NIH value was higher than that of other Gyro pumps, but is in an acceptable range.

Equipment Design↗
PubMed1999

Dr. Kiyoshi Shiga: discoverer of the dysentery bacillus.

The clinical manifestations of dysentery have been described for centuries, and the prototypic bacterial agent, Shigella dysenteriae, was identified 100 years ago. In the English language there has been remarkably little written about Dr. Kiyoshi Shiga, discoverer of the dysentery bacillus. We submit a brief biography of Dr. Shiga and the circumstances leading to his discovery, which proved the bacterial etiology of nonamebic dysentery.

Dysentery, Bacillary↗
PubMed1999

Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma.

PURPOSE: To investigate the relationship between the metal content of hepatocellular carcinoma (HCC) and the signal intensity pattern on magnetic resonance images. MATERIALS AND METHODS: The signal intensity patterns of 59 HCCs 3 cm in diameter or smaller were correlated with histologic findings and metal content. RESULTS: HCCs with high signal intensity on T1-weighted images demonstrated more steatosis (P = .035) and higher copper content (P = .008) than did surrounding hepatic parenchyma. HCCs with high signal intensity on T2-weighted images demonstrated more clear cells (P = .001) than did surrounding hepatic parenchyma. The higher signal intensities on T1-weighted and T2-weighted images were related to a higher and a lower degree of histologic differentiation, respectively. Multivariate analysis showed that the contrast-to-noise ratio between the HCC and surrounding hepatic parenchyma was affected by intratumoral copper content (P = .0338), zinc content of surrounding hepatic parenchyma (P = .0379), and the degree of histologic differentiation on T1-weighted (P = .0031) and T2-weighted (P = .0062) images. CONCLUSION: The signal intensity of HCC on T1-weighted images is related to the degree of histologic differentiation, intratumoral copper content, and zinc content of surrounding hepatic parenchyma, whereas the signal intensity on T2-weighted images is related to the degree of histologic differentiation.

Adult↗