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Biomedical subjects

H Morishima

Publications and source records attributed to H Morishima.

At least 55 records · Page 3Linked to original sources
PubMed1999

In vivo anti-tumor activity of a novel indolocarbazole compound, J-107088, on murine and human tumors transplanted into mice.

J-107088 (6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo [3,4-c]carbazole-5,7(6H)-dione) is a derivative of NB-506, an indolocarbazole compound previously reported as an anti-tumor agent targeting topoisomerase I. The optimal administration schedule of J-107088 was found to be intermittent injections. The GID75 (75% growth inhibiting total dose) values of J-107088 against LX-1 lung cancer and PC-3 prostate cancer when given by intermittent injection (twice a week for 2 consecutive weeks) were 200 and 15 mg/m2, respectively, whereas the 10% lethal dose (LD10) values of J-107088 against LX-1- and PC-3-bearing mice were 578 and 1200 mg/m2. The ratio of LD10/GID75 indicates the therapeutic window of an anti-tumor agent. Although the ratios of doxorubicin, paclitaxel and cisplatin against PC-3 were <0.3, <0.5 and <0.2, J-107088 showed the widest therapeutic window among the anti-tumor drugs tested. J-107088 was also effective on cells that had acquired resistance related to P-glycoprotein. Furthermore, J-107088 was found to be highly effective in inhibiting proliferation of micro-metastases of tumors to the liver in mice. Therefore, J-107088 is considered to be a promising candidate as an anti-tumor drug for treatment of solid tumors in humans.

Animals↗
PubMed1999

Carbapenem derivatives as potential inhibitors of various beta-lactamases, including class B metallo-beta-lactamases.

A variety of 1beta-methylcarbapenem derivatives were screened to identify inhibitors of IMP-1 metallo-beta-lactamase, a class B beta-lactamase, in an automated microassay system using nitrocefin as a substrate. The structure-inhibitory-activity relationship study revealed that three types of 1beta-methylcarbapenems having benzothienylthio, dithiocarbamate, or pyrrolidinylthio moieties at the C-2 position showed good inhibitory activity. Among the compounds screened, J-110,441, having a benzothienylthio moiety at the C-2 position of 1beta-methylcarbapenem, was the most potent inhibitor of class B metallo-beta-lactamases with K(i) values of 0. 0037, 0.23, 1.00, and 0.83 microM for IMP-1 encoded by the bla(IMP) gene, CcrA from Bacteroides fragilis, L1 from Stenotrophomonas maltophilia, and type II from Bacillus cereus, respectively. In a further characterization study, J-110,441 also showed inhibitory activity against TEM-type class A serine beta-lactamase and chromosomal class C serine beta-lactamase from Enterobacter cloacae with K(i) values of 2.54 and 0.037 microM, respectively. Combining imipenem or ceftazidime with J-110,441 had a synergistic effect on the antimicrobial activity against beta-lactamase-producing bacteria. Against the isolates of IMP-1-producing Serratia marcescens, the MICs of imipenem decreased to levels ranging from 1/64 to 1/4 in the presence of one-fourth of the MIC of J-110,441. Against E. cloacae producing high levels of class C beta-lactamase, the MIC of ceftazidime decreased from 64 to 4 microg/ml in the presence of 4 microg of J-110,441 per ml. This is the first report to describe a new class of inhibitor of class B and class C beta-lactamases including transferable IMP-1 metallo-beta-lactamases.

Bacterial Proteins↗
PubMed1999

[Mediastinoscopic resection combined with a sternum lift technique in a case of thymic cyst].

We report on a case of thymic cyst which was successfully treated with mediastinoscopic resection combined with a sternum lift technique. A 62-year-old man was admitted to our hospital with a thymic cyst, which was causing chest discomfort and was increasing in size. The tumor was located above the pulmonary artery in the anterior mediastinum. He underwent mediastinoscopic resection while lifting the inferior portion of the sternum with a Laparolift. The cyst was resected sharply and bluntly with the Harmonic Scalpel without rupture. The patient was discharged on the 6th postoperative day in a good condition. Mediastinoscopic resection of a thymic cyst through a xiphoid approach is a useful surgical approach because of the absence of postoperative pain and because it allows early discharge from the hospital.

Endoscopy↗
PubMed1998

The value of long-term clinical follow-up for cases of spontaneous carotid cavernous fistula.

To clarify the value of clinical long-term follow-up with radiological examination, ranging from 12 to 63 months (average: 35 months), 18 consecutive patients suffering from spontaneous carotid cavernous fistula (CCF), were studied prospectively. Five aged patients without aggressive symptoms were treated conservatively, and the other 13 underwent transarterial embolization. The radiological follow-up was primarily by magnetic resonance angiography (MRA), performed from 2 to 6 times (average: 4.1 times) during the follow-up period. In three cases, CCFs persisted, but the other fifteen (83%) demonstrated complete cure as defined by long-term follow-up MRA. The three patients with persistent CCFs were comparatively young, less than 60 years old, had no atherosclerotic factors and demonstrated multiple venous drainage routes with cortical venous drainage on angiography. In two of them, the symptoms completely disappeared, and the other had only mild chemosis. However, surprisingly, in two, MRA revealed residual CCF with drainage into only cortical veins through the sphenoparietal sinus, this radiological finding being well known to signify danger. During the follow-up period, central retinal vein thrombosis occurred in two cases. The common point in these cases was that the superior ophthalmic vein was the only venous drainage route. This is also a point requiring care. We therefore emphasize the importance of careful long-term radiological follow-up for spontaneous CCF patients even when their symptoms improve or disappear. MRA is particularly suitable for this purpose and applicable in the out-patient clinic because of its non-invasive nature.

Adult↗
PubMed1998

Efficacy of the stump pressure ratio as a guide to the safety of permanent occlusion of the internal carotid artery.

To determine whether the absolute value for the stump pressure might be a useful index of symmetrical cerebral blood flow (CBF), and to examine correlations with the stump pressure ratio (initial mean stump pressure/preocclusion mean arterial pressure), fifty candidates for ICA injury or permanent occlusion were evaluated preoperatively. Each was continuously monitored for mean stump pressure and arterial pressure before, during (for a total of 20 min), and after balloon test occlusion. During the occlusion, CBF was measured by 99 m Tc-hexamethyl-propyleneamine oxime (99 m Tc-HMPAO) single photon emission computed tomography (SPECT). The stump pressure and the stump pressure ratio were then compared with the results of 99 m Tc-HMPAO SPECT. Patients who failed to tolerate even brief periods of carotid occlusion and showed asymmetric decreases in CBF on SPECT were divided into high and moderate risk groups. Those with no significant changes in CBF on the occluded site formed the minimum risk group. Mean stump pressure was over 50 mmHg in 10 of a total of 25 patients in the high and moderate risk groups, and below 50 mmHg in 5 of the 25 patients in the minimum risk group. The stump pressure ratio did not exceed 56% in any but two patients in the high and moderate risk groups, and values were at least 60% in all patients of the minimum risk group. Decrease of CBF in two moderate risk group cases was localized in the posterior circulation. Difference in symmetrical CBF between the stump pressure ratio vs. the absolute value of mean stump pressure were statistically significant (p < 0.01, Fisher's Exact Test). Maintenance of a stump pressure ratio of 60% or more during test occlusion may be a more useful index for a good collateral circulation than any absolute value for mean stump pressure.

Blood Pressure↗
PubMed1998

Mortality and cancer incidence in Misasa, Japan, a spa area with elevated radon levels.

A historical cohort study was conducted in Misasa town, Tottori prefecture, Japan, where radon spas have been operating for a long time. Misasa town was divided into an elevated radon level area and a control area, with mean indoor radon levels of about 60 and 20 Bq/m3, respectively. In total, 3,083 subjects in the elevated radon level area and 1,248 in the control area, all aged 40 or older on January 1, 1976, were followed up until December 31, 1993, for a mean period of 14 years. The mortality rates from all causes exhibited no difference between the elevated radon level area and the control area for both sexes. No difference was observed in the incidence of all-site cancers (age, period-adjusted rate ratios by Poisson regression, RR = 1.06, 95% confidence interval (CI) 0.79-1.42 for males, RR = 0.90, 95% CI 0.65-1.24 for females), while stomach cancer incidence seemed to decrease for both sexes (RR = 0.70, 95% CI 0.44-1.11 for male, RR = 0.58, 95% CI 0.34-1.00 for female) and lung cancer incidence for males only seemed to increase (RR = 1.65, 95% CI 0.83-3.30 for male, RR = 1.07, 95% CI 0.28-4.14 for female) in the elevated radon level area. Caution is needed in the interpretation of these findings, however, since the individual exposure level was not measured and major confounding factors, such as smoking and diet, could not be controlled in this study.

Adult↗
PubMed1994

Renin inhibitors. III. Synthesis and structure-activity relationships of transition-state inhibitors containing dihydroxyethylene isostere at the P1-P1 site.

The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3-pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.

Animals↗
PubMed1994

BE-23372M, a novel protein tyrosine kinase inhibitor. III. Synthesis.

In a preceding paper, the physico-chemical properties and structural elucidation of BE-23372M, a potent novel protein tyrosine kinase inhibitor, were described. In this paper, we report the synthesis of BE-23372M from 3-(3,4-dimethoxybenzoyl)propionic acid and veratraldehyde or 3,4-diacetoxy-benzaldehyde. The structure of BE-23372M was confirmed to be (E)-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)-2(3H)-fur anone.

Furans↗
PubMed1993

Residual 152Eu and 60Co activities induced by neutrons from the Hiroshima atomic bomb.

Specific activities of 152Eu:Eu in stone samples exposed to the Hiroshima atomic bomb were determined for 70 samples up to a 1,500-m slant range from the epicenter. The specific activities of 60Co:Co were also determined for six samples near the Hiroshima hypocenter. First, the 152Eu data were investigated to find out the directional dependence of neutron activation. Directional anisotropy was not definite; however, there was an indication that the activation in the west-southwest was lower than in other directions. Second, measured 152Eu and 60Co radioactivity data were compared with activation calculations based on DS86 neutrons. It is clearly shown that the measured data are lower than the calculation near the hypocenter and vice versa at long distances beyond 1,000 m. The calculated-to-measured ratios of 152Eu are 1.6 at the hypocenter, 1.0 at approximately 900 m, and 0.05 at a 1,500-m slant range. Present results indicate that systematic errors exist in the DS86 neutrons concerning the source-term spectrum, neutron transport calculations in air, and/or activation measurements.

Cobalt Radioisotopes↗
PubMed1992

Renin inhibitors. II. Synthesis and structure-activity relationships of N-terminus modified inhibitors containing a homostatine analogue.

The synthesis and structure-activity relationships of N-terminus modified renin inhibitors containing the homostatin analogue, (2RS,4S,5S)-5-amino-2-ethyl-4-hydroxy-7-methyloctanoic acid, are described. The compounds having a 3-alkyl (or aryl)sulfonylpropionyl residue at the N-terminus are found to be potent inhibitors which contain two amino acids. (2RS,4S,5S)-N-Isobutyl-5-[N-[(2S)-3-ethylsulfonyl-2-(1- naphthylmethyl)propionyl]-L-norleucyl]-amino-2-ethyl-4-hydroxy-7- methyloctanamide (20) has an IC50 of 0.5 nM against human plasma renin and the oral bioavailability of 20 is 0.73% in rats. Interaction between renin and the N-terminus of 1 and 20 is discussed in molecular modeling studies.

Amino Acids↗
PubMed1992

Renin inhibitors. I. Synthesis and structure-activity relationships of transition-state inhibitors containing homostatine analogues at the scissile bond.

The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result suggests that S1, S3 and S4 form a huge hydrophobic core together in renin.

Humans↗
PubMed1992

Specific activities of 60Co and 152Eu in samples collected from the Atomic-Bomb Dome in Hiroshima.

Neutron-induced activities 60Co and 152Eu have been measured for samples collected from the Atomic-Bomb Dome locating at 161 m from the hypocenter of the Hiroshima Bomb. Specific activities 60Co/Co and 152Eu/Eu at the time of the detonation have been determined as 10.0 +/- 1.0 Bq mg-1 (steel sample S4) and 80 +/- 9 Bq mg-1 (granite sample G1), respectively. Detailed measurements of 60Co and 152Eu activities for samples collected from various locations of the Dome show almost no directional dependence whether the sample faced to the epicenter or not, nor vertical height dependence between 17 m height and the ground level. In addition, 152Eu was not detected in the sample collected from the basement. It has been shown that the present 60Co activity value, the nearest steel one to the hypocenter, as well as other short distance data are systematically lower than the calculated values based on the neutron fluence of the DS86.

Cobalt Radioisotopes↗
PubMed1991

Tritium precipitation in European cities and in Osaka, Japan owing to the Chernobyl nuclear accident.

Tritium precipitations in European cities and in Osaka, Japan were analyzed before and after the Chernobyl nuclear plant accident by the time series analysis code Census IIX11 developed by US Department of Commerce Bureau of the Census. Results of this analysis showed no significant tritium precipitation was produced by the accident although marked amounts of other radioactive nuclides were detected in Europe and Japan immediately after the accident.

Accidents↗
PubMed1990

Spontaneous lesions in beagle dogs used in toxicity studies.

Spontaneous histopathologic lesions were examined in 276 young beagle dogs (8 to 15 months old) used in toxicity studies. Mononuclear cell infiltration in the liver was observed with the highest incidence (more than 95%). Calcium deposition in the kidney, mononuclear cell infiltration in the salivary glands, pigmentation in the spleen, and cortical atrophy in the thymus were seen with relatively high incidences (more than 30%). The incidence of mononuclear cell infiltration in the gallbladder, vacuolization of the tubular epithelium in the kidney, and vacuolization of the zona glomerulosa cell in the adrenal gland showed differences between the sexes. No abnormalities were seen in the spinal cord, sternum, and femur. Although most lesions observed are considered to be age-related, several were considered to be due to congenital anomalies observed in some organs.

Animals↗
PubMed1989

A novel nonpeptidic, orally active renin inhibitor.

BW-175 is a newly synthesized renin inhibitor which is a nonpeptidic, norleucine analog. Its IC50 values for renin activity in human, squirrel monkey, marmoset, dog, hog, rabbit and rat plasma were 3.3, 6.6, 2.4, 42, 110, 86 and 3500 nM, respectively, and 26 microM for cathepsin D. Pepsin and angiotensin converting enzyme were hardly inhibited at 10(-4) M. BW-175 showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. In normotensive, furosemide-treated high-renin marmosets, BW-175 (30 mg/kg p.o.) caused an intensive reduction in plasma renin activity and plasma angiotensin I formation, associated with a reduction in systolic blood pressure of 10-20 mm Hg for 2 hours.

Aminocaproates↗
PubMed1989

Relationship among iodine, bromine and chlorine concentrations in cow's milk in Japan.

In order to know the relationship among some elements in biological materials, iodine, bromine and chlorine concentrations in cow's milk samples in Japan were determined by the thermal neutron activation analysis using a low power research reactor and a Van de Graaff accelerator. The iodine contents in cow's milk samples ranged from 0.041 to 0.316 ppm with an average of 0.096 ppm. The bromine and chlorine in these samples ranged from 2.3 to 11.1 ppm and from 475 to 1650 ppm, respectively. The average concentration of the bromine was calculated to be 5.6 ppm and that of the chlorine was 853 ppm. The relationship among iodine, bromine and chlorine concentrations in cow's milk samples in Japan was studied with a regression analysis. It was suggested that the correlation has a power function as follows; Y = K(Z)-A where, Y is elemental concentration in ppm, Z is atomic weight [corrected] of element, A (= 7.4) is exponent and K (= 14.7) is a constant.

Animals↗