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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 163 records · Page 9Linked to original sources

[Cerebral blood flow and event-related potential in patients with cerebral infarction].

Cerebral blood flow (CBF) and P 300, a long-latency positive component of the scalp-recorded event-related potential (ERP) associated with cognitive processing were investigated in patients with cerebral infarction to elucidate the relationship between CBF and cognitive function. Twenty-five patients with cerebral infarction with a mean age of 66.8 years were studied. ERP was recorded during auditory discrimination tasks. The latency of the P 300 from Pz region was recorded. The regional CBF was measured by the 133Xe inhalation method. The F1 (cortical gray matter flow) values were calculated using the Obrist's method. The mean F1 values in patients with cerebral infarction were significantly lower compared to the values obtained for the 15 control subjects (mean age, 68.4 years) (p less than 0.01). Patients with cerebral infarction showed significant prolongation of the P 300 latency compared to the 20 control subjects (mean age, 64.4 years) (p less than 0.02). There was a significant correlation between the P 300 latency and the mean F1 values in patients with cerebral infarction (p less than 0.01). Present results suggest that the cognitive impairment with respect to ERP may be related to the reduction of cortical blood flow in patients with cerebral infarction.

Aged↗

[Therapeutic values of prostaglandin D2 in nude mice bearing human ovarian carcinoma].

In vitro and in vivo effects of prostaglandin D2 on human ovarian cancer growth were examined by using a cell line, designated HR, derived from ascites of patient with serous cystadenocarcinoma of the ovary. The HR cell proliferation in vitro was dose-dependently inhibited at prostaglandin D2 concentrations between 0.1 and 4.0 micrograms per ml. The results of a 51Cr-release assay seemed to indicate that the inhibition resulted from a direct cytotoxic effect exerted by prostaglandin D2. All DNA, RNA, and protein synthesis by the HR cells was also inhibited in a dose-dependent manner with 48 hr exposure to prostaglandin D2. When nude mice were inoculated with 5 X 10(5) HR cells, the 50% survival time in the untreated group was 52 days. The 50% survival time of nude mice treated with 12 mg (but not 4 mg) of prostaglandin D2 per kg was significantly prolonged to 67 days, in addition to a significant inhibition of the tumor growth. Adjuvant effects of prostaglandin D2 on cisplatin in relation to tumor growth were also studied. Combinations of 0.2 or 0.4 microgram cisplatin per ml and 0.05 or 0.1 microgram prostaglandin D2 per ml, which did not affect the HR cell proliferation alone, resulted in a significant inhibition of cell proliferation. In addition, the tumor take of HR cells by nude mice in groups treated with a combination of cisplatin and prostaglandin D2 was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Involvement of central nervous system in patients with diabetes mellitus detected by evoked potentials].

Somatosensory (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded for 44 patients with diabetes mellitus (age, 63.0 +/- 9.3 years, mean +/- SD) and 20 age-matched healthy controls (age, 67.3 +/- 9.1 years) to elucidate the involvement of the central nervous system (CNS) in diabetes mellitus. Furthermore, relationships between SSEP or BAEP and clinical variables such as autonomic nervous function, peripheral nerve conduction velocity, duration of diabetes, metabolic control (fasting blood sugar level, HbA1 and HbA1c levels) and therapeutic method, were studied. The central conduction time (CCT), which represents the peak latency between N13 and N20, in patients with diabetes mellitus was significantly longer than that of the healthy controls (p less than 0.005). Likewise, diabetic patients showed significant prolongation of interpeak latency between waves I and V (I-V IPL) compared to the healthy controls (p less than 0.005). Significant correlations between CCT and motor conduction velocity of median nerve (p less than 0.05) were observed although the correlation between CCT and sensory nerve conduction velocity was not found to be significant (p less than 0.1). Furthermore, I-V IPL was significantly correlated with the duration of illness (p less than 0.05). There were no significant correlations between CCT or I-V IPL and autonomic nervous dysfunction as determined by orthostatic hypotension and the coefficient variation of the R-R interval or metabolic control or therapeutic method. From the present results, it would appear that there is CNS involvement even in diabetic patients not manifesting overt CNS signs and symptoms and that it is correlated somewhat with impairment of the peripheral nervous system and duration of illness.

Aged↗

Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells.

The effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined using nude mice as a model, with malignant ascites produced by intraperitoneal inoculation of human ovarian cancer cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. Twenty-eight days after tumor inoculation, all nude mice in the untreated group and in the group treated with spleen cells alone formed ascites. Two of ten nude mice treated with IL-2 alone after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells alone had formed ascites 14 days after tumor inoculation. When LAK cells and IL-2 were combined, five of ten mice survived without forming ascites during the experimental period. The survival time of the group treated with IL-2 alone was significantly prolonged compared to the groups that received medium alone, spleen cells alone and LAK cells alone. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.

Animals↗

Inhibition of human ovarian cancer cell proliferation by calmodulin inhibitors and the possible mechanism.

Direct inhibitory effects of calmodulin inhibitors on human ovarian cancer cell proliferation in vitro were examined. All calmodulin inhibitors used in this study inhibited proliferation of HR cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition by melittin and W-5 was most marked and was followed by that of W-7, R24571, and bepridil. HR cell proliferation was dose-dependently stimulated by epidermal growth factor (EGF). The stimulatory effects seemed to be a result of the binding of EGF to HR cells. Binding of EGF was significantly inhibited by W-5, R24571, and melittin. These results suggest that inhibition by calmodulin inhibitors of cancer cell proliferation may result in part from the interference in the binding of EGF to the cells.

Biomechanical Phenomena↗

Adjuvant effects of calmodulin antagonists on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur) and a mixture of ftorafur and uracil (UFT) in nude mice bearing human ovarian carcinomas.

Effects of N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur, FT) and a mixture of FT and uracil (UFT) were determined in nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed palpable tumor 17 days after KF cell inoculation unless treated. A combination of UFT and calmodulin antagonists (W-5 and W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volumes in groups treated with the combinations of UFT and calmodulin antagonists were significantly smaller than those in the untreated group after 31 days of tumor inoculation. In addition, tumor volumes in a group treated with UFT plus W-7 were significantly smaller than not only those in the untreated group but also those in groups treated with UFT alone, FT alone, W-5 alone, or W-7 alone. The longest median survival time was also observed in the group treated with UFT plus W-7. 5-Fluorouracil (5-FU) content of the tumors of groups treated with FT plus W-5 or W-7 was similar to that of the group treated with FT alone. On the other hand, 5-FU content of a group treated with UFT plus W-7 was about twofold higher than that of a group treated with UFT alone. These results suggest that a synergistic effect of W-7 and UFT on inhibition of tumor growth and prolongation of survival time may result from accumulation of 5-FU in the tumor.

Animals↗

Inhibition of human ovarian cancer cell proliferation in vitro by neuroendocrine hormones.

Direct inhibitory effects of neuroendocrine hormones on human ovarian cancer cell proliferation in vitro were examined. Except for melatonin, all neuroendocrine hormones used in this study inhibited proliferation of KF cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition of prostaglandin D2 was most marked being comparable to that of 5-fluorouracil and followed by beta-endorphin, alpha-endorphin, and Met-enkephalin. More than 200 microM melatonin stimulated the cell proliferation. The inhibitory effects by endorphins were partially reversible by 20 microM naloxone. From analyses of uptakes of radiolabeled precursors by the KF cell, endorphins were considered to inhibit protein and RNA syntheses but not DNA synthesis. These results suggest that neuroendocrine hormones may play an important role in regulation of tumor growth.

Cell Division↗

Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6-8) were investigated. The degradation of the starting delta 3 cephalosporin ester proceeded mainly via isomerization to the delta 2 ester and subsequent hydrolysis to the delta 2 acid. Hydrolysis to the delta 3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the delta 3 ester kdeg, and slower than the hydrolysis rate of the delta 2 ester k24. The isomerization process to the delta 2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentration and added protein.

Administration, Oral↗

Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of delta 3 cephalosporin in phosphate buffer solution (pH 6-8) was investigated. In the degradation, the isomerization process to the delta 2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the delta 2 ester (log k12) correlated with the carbon-13 nuclear magnetic resonance chemical shift difference value at C-3 and C-4 of the delta 3 ester (delta delta (4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the delta 3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the delta 3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated pi-bond system (C3 = C4 - C4 = O) and consequently affects the feasibility of isomerization to the delta 2 ester, i.e., the stability to degradation.

Administration, Oral↗

Studies on orally active cephalosporin esters. IV. Effect of the C-3 substituent of cephalosporin on the gastrointestinal absorption in mice.

The effect of the C-3 substituent on the oral absorbability of pivaloyloxymethyl (POM) ester of cephalosporin in mice is described. The C-3 substituent affects the physicochemical and biochemical properties of POM ester, such as lipophilicity, water solubility, chemical stability and enzymatic stability. Quantitative analyses of the relationships between these properties and the oral bioavailability have been attempted. Lipophilicity made a parabolic contribution to the absorption. The optimum log P octanol/water value was estimated to be around 2.22. The chemical isomerization of the cephem double bond from delta 3 to delta 2 in the intestinal lumen prior to absorption contributed linearly to decrease of absorption. In the case of POM ester having a larger isomerization rate, more delta 2 isomer was detected in feces and urine. Enzymatic hydrolysis of POM ester to the parent acid in intestinal tissue was faster for a more lipophilic ester. Hydrolytic activity, which was detected in the content of the intestinal lumen, would lower the absorption. The effect of the C-3 substituent on water solubility was not important for the absorption of cephalosporin employed in the present study. Isomerization of the double bond, which was found to be characteristic for cephalosporin ester, presented a problem in the prodrug approach for oral use.

Animals↗

Novel cytocidal antibiotics, glucopiericidinols A1 and A2. Taxonomy, fermentation, isolation, structure elucidation and biological characteristics.

Two novel antibiotics, glucopiericidinols A1 (1) and A2 (2) were isolated from the cultured broth of Streptomyces sp. OM-5689. The structures of these two compounds were deduced employing spectroscopic analyses. These antibiotics showed potent cytocidal activities against HeLa S3 cells in vitro (MIC 1: 0.39 microgram/ml, 2: 0.10 microgram/ml) when the cells were exposed to the antibiotics for 3 days. Although 1 and 2 showed no activity at 1,000 micrograms/ml against various Gram-positive and Gram-negative bacteria, yeast or fungi, they did have inhibitory activity against Piricularia oryzae (MIC of 1: 125 micrograms/ml, of 2: 31 micrograms/ml).

Aminoglycosides↗

[The mechanism of resistance and its circumvention of cisplatin-resistant human ovarian cancer cells].

In this study, we attempted to elucidate the mechanisms of cisplatin resistance and circumvent the resistance with calmodulin antagonists using a cisplatin-resistant human ovarian cancer cell line (KFr). It was assumed that the cisplatin resistance resulted from impairment of cisplatin transport systems. In particular, we considered that a reduced cisplatin transport function caused by some amino acids had an effect on the resistance mechanism. Reduced uptake of cisplatin as well as cisplatin analogues to KFr cells was observed. Four cisplatin analogues used in this study had cross-resistance to cisplatin. However, the concentration of drugs incorporated into cells was not always correlated with the degree of resistance. Therefore, it is possible that, in addition to the reduced influx function, an other mechanism is involved in the resistance. Combined treatment with cisplatin and calmodulin antagonists significantly increased the uptake of cisplatin by KFr cells and maintained the cellular level. Thus, a combination therapy of cisplatin and calmodulin antagonists seemed to be of clinical use.

Animals↗

[Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells].

Effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined by using a nude mice model with malignant ascites by intraperitoneal inoculation of human ovarian cancer cells (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. On 28 days after tumor inoculation, all nude mice in both untreated and spleen cells only treated groups formed ascites. Two of 10 nude mice treated with IL-2 only after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells only formed ascites by 14 days after tumor inoculation. When LAK cells and IL-2 were combined 5 of 10 mice survived without forming ascites during the experimental period. The survival time of the IL-2 only treated group was significantly prolonged, compared to that of medium only, spleen cells only and LAK cells only treated groups. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.

Animals↗

[Repairing the thoracic and abdominal aortic aneurysms at the same time].

A 61-year-old man with the descending thoracic aneurysm associated with the infra-renal abdominal aneurysm was operated at the same time using the temporary bypass from right subclavian artery to right femoral artery safely. In order to observe the spinal cord function, SEP and ESP were recorded. Anastomosis of the prosthetic graft to the temporary bypass was prepared beforehand to preserve the spinal cord function during aortic cross clamping, if needed. If both aneurysms are present in the thoracic and abdominal cavity, special considerations are required, at one or two-staged operation and what adjuncts will be used to perform the repairs safely. In this case, the repair of thoracic lesion underwent well, and the repair of the abdominal one followed it. His postoperative course was uneventful.

Aorta, Abdominal↗

[Indication of femorotibial and femoroperoneal bypass for Buerger's disease].

Infrapopliteal bypass with autogenous vein graft was performed in twenty-three patients of thromboangiitis obliterans (Buerger's Disease) during the past 8 years. The outflow vessel of the graft had the direct connection with the pedal arch in 3 cases. In 20 cases the graft was anastomosed to the solitary tibial or peroneal segment, in which the occlusive lesion existed between the outflow vessel and pedal arch, or otherwise, the pedal arch was not opacified in the arteriogram. The length of the solitary tibial or peroneal segment of the successful cases ranged from 11.5 cm to 29.0 cm. The cumulative patency rates of the 23 bypass grafts at 3 months, 1 year, 3 years and 5 years were 86.7%, 77.3%, 77.3%, 77.3% respectively. This result is comparable to those of other authors. When the solitary tibial or peroneal artery is found out and is longer than 12 cm in the arteriogram of Buerger's Disease, we are going to perform bypass surgery to the vessel. If the foot is already necrotic, the amputation should be carried out several days or several weeks after the successful reconstructive surgery.

Adult↗