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Biomedical subjects

S Ohki

Publications and source records attributed to S Ohki.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Application of alpha-hANP for the management following open-heart surgery: report of two cases].

Alpha-human atrial natriuretic peptide (alpha-hANP) has a vasodilating and diuretic action. Intravenous continuous administration of alpha hANP (0.05 microgram/kg/min) was attempted for two patients with low urine output despite good hemodynamics following open-heart surgery. Following the administration of alpha-hANP, urine volume increased markedly, and central venous and pulmonary capillary wedge pressures immediately decreased. Intravenous continuous administration of alpha-hANP is useful for the management of patients associated with the volume overload following open-heart surgery.

Aged↗
PubMed1997

Availability of nasal mask BiPAP systems for the treatment of respiratory failure after cardiovascular surgery.

BACKGROUND: The availability of nasal mask bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery was studied. MATERIALS AND METHODS: BiPAP support was used for eight patients requiring postoperative prolonged respiratory support of 72 hours or longer. Their mean age was 65 years of age and the mean periods of postoperative endotracheal intubation was 12+/-5 days. BiPAP support was removed within 48 hours in six out of eight patients. Reintubation of an endotracheal tube was not necessary in all eight patients after the BiPAP treatment. RESULTS: The respiratory rates during the BiPAP management remained unchanged. The values of the respiratory index significantly (p<0.01) improved after BiPAP management (1.5+/-0.2 --> 0.9+/-0.2). A-aDO2 and Qs/Qt decreased (p<0.1) after the BiPAP management. There were no significant differences in central venous pressure and circulatory states during BiPAP support. CONCLUSIONS: In conclusions, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.

Aged↗
PubMed1996

The Dual Role of Fibrinogen as Inhibitor and Nucleator of Calcium Phosphate Phases: The Importance of Structure.

Constant composition and free drift methods have been used to investigate the abilities of human serum albumin (HSA) and fibrinogen to influence calcium phosphate precipitation. Both molecules inhibit hydroxyapatite (HAP) crystal growth when present in the solution phase. Fibrinogen, when immobilized at hydrophobicized germanium or silica surfaces, is able to nucleate calcium phosphate phases; at clean germanium or silica surfaces, it appears to be inactive. The apparent configuration of fibrinogen molecules at germanium or silica surfaces on which octadecyltrichlorosilane (OTS) was deposited probably exposes more negative sites for participation in nucleation.

Journal Article↗
PubMed1996

Inhibition of HTLV-I induction and virus-induced syncytia formation by oligodeoxynucleotides.

HTLV-I is an exogenous human retrovirus that is a causative agent of adult T cell leukemia (ATL). In addition to the structural genes (gag, pol and env), a gene termed pX is postulated to be associated with leukemogenesis in ATL. Since no effective chemotherapy is currently available, it is important to find suitable therapeutic means against ATL. Here, we tested the inhibitory effect of antisense oligodeoxynucleotides (ODNs) on HTLV-I infection in different systems. ODNs were synthesized with the phosphorothioate backbone targeted to either structural genes or transactivator genes. The phosphorothioate ODNs were found to have two distinct target sites to exert their effect on HTLV-I infection: 1) Several ODNs, including sense ODNs and random oligomers, blocked syncytium formation induced by HTLV-I at a concentration of 0.1 microM. Their inhibitory effect on syncytium formation seemed to be exerted in a nonantisense manner, most probably due to their interaction with the cell membrane. 2) Efficient suppression by ODNs of gag gene expression after chemical induction was observed in HTLV-I-transformed T cells in an antisense manner. In this suppression, tax-antisense ODN showed virtually complete inhibition of gag protein expression, but not RNA expression, at the concentration of 0.1 microM, whereas tax-sense ODN displayed a weak inhibitory effect. Our results suggest that the influence of the phosphorothioate compound should be considered from the aspect of two separated mechanisms of antiviral activity, the effects on early (viral adsorption) and late (translation) phase infection.

Animals↗
PubMed1996

Changes in diastolic regional stiffness of the left ventricle before and after coronary artery bypass grafting.

To evaluate the effect of coronary artery bypass grafting (CABG) on regional diastolic function of the left ventricular wall, we applied the concept of the stiffness constant to the diastolic sigma-ln (1/H) relation, where sigma is the mean wall stress, and H is the wall thickness of the region of concern, and ln (1/H) is the natural logarithm of the reciprocal of wall thickness. We assessed 12 cardiac regions in six patients with coronary artery disease who underwent CABG at the Cardiovascular Hospital of Central Japan between May 1994 and January 1995. Left ventricular pressure and regional wall thickness were measured simultaneously, with a micromanometer-tipped catheter and by two-dimensional echocardiography, respectively, before and after CABG. The stiffness constant (K) was obtained by fitting the diastolic sigma-ln (1/H) data points to an exponential curve with zero asymptote: sigma = Cexp[Kln (1/H)]. Preoperatively, the stiffness constant in the affected region (CABG region) was greater than that in the unaffected region (non-CABG region) (4.79 +/- 2.56 vs 2.95 +/- 0.72). Postoperatively, the stiffness constant in the CABG region was significantly decreased, to 3.21 +/- 1.22. The stiffness constant, which is derived from the sigma-ln (1/H) relation, is useful for the assessment of LV regional diastolic function.

Aged↗
PubMed1996

Secondary structure and Ca(2+)-binding property of the N-terminal half domain of calmodulin from yeast Saccharomyces cerevisiae as studied by NMR.

Using two- and three-dimensional NMR techniques, 1H and main-chain 15N resonances of the N-terminal half domain of yeast calmodulin (YCM0-N) in the presence of Mg2+ and Ca2+ (Mg(2+)-and Ca(2+)-forms) were assigned. The secondary structures of YCM0-N in both forms were determined. The NOESY and 15N-edited NOESY spectra of YCM0-N in each form indicate that there is a hydrophobic core and that two Ca(2+)-binding loops are connected by a short antiparallel beta-sheet. There are four helices (A, B, C, and D named from the N-terminus) for YCM0-N in the Mg(2+)-form. The B-helix is, however, not formed in the Ca(2+)-form. The Ca(2+)-binding of YCM0-N was monitored by (1H,15N)-HSQC at various Ca2+ concentrations. The observed spectral changes as a function of Ca(2+)-concentration can not readily be grouped into a small number of classes; each residue shows individual spectral change. There is no apparent relationship between the spectral change and the type or location of the amino acid concerned.

Amino Acid Sequence↗
PubMed1996

Preoperative intra-arterial infusion chemotherapy for invasive thymoma: a case report.

A 24-year-old man was diagnosed as having mixed-type thymoma by preoperative percutaneous needle biopsy. A chest computed tomogram showed a tumor measuring 12x9 cm. Selective intra-arterial infusion chemotherapy was first selected because invasion to the superior vena cava was suspected. Bolus injection of 50 mg/m2 cisplatin and 20 mg/m2 adriamycin was performed once into the right internal thoracic artery. The resulting decrease in tumor size was 81%. Neither complications due to the infusion procedure nor side effects due to the anticancer drugs were encountered. An extended thymectomy with partial resection of the mediastinal pleura was safely performed. The histological diagnosis of the resected tumor was thymic hyperplasia. The patient was transferred to a radiologist for additional radiotherapy. Selective intra-arterial infusion chemotherapy for invasive thymoma is an effective therapy, producing no significant side effects and allowing safe resection.

Adult↗
PubMed1996

[Prognostic factors of colorectal cancer concerning metastases].

Four prognostics factors were investigated for colorectal cancer metastases. 1) There were statistically more venous invasions using Victoria blue elastic staining in patients with liver or lymph node metastasis than in those without metastasis. 2) The immunohistochemical expression rate of c-erbB-2 in liver metastasis cases was 27%, which was significantly higher than 3% in no metastasis cases. 3) Sialyl Lewis x (SLex) is related with cell adhesion. SLex positive rates in vessel invasion cancer cells were 71.4% with metastasis and 31.0% without metastasis. 4) Matrilysin is one of MMPs and it was significantly increased with Dukes stage by fluorescence intensity.

Colorectal Neoplasms↗
PubMed1996

[K-ras gene mutations in adenomas from familial adenomatous polyposis].

A 18-year-old woman underwent total colectomy for familial adenomatous polyposis. In order to clarify the significance of K-ras mutations in early colorectal carcinogenesis, K-ras mutations were analyzed in multiple adenomas by PCR-SSCP method. A total of 256 adenomas were found throughout the entire colon and rectum, and the distribution was a sparse type. The correlation between K-ras gene and clinicopathological factors was examined in 90 adenomas. There was no correlation among K-ras mutations and anatomical distribution, or morphological classification, but K-ras mutation was more frequent in severe compared with slight atypia. We investigated the correlation between the size of adenoma in the horizontal and vertical directions and K-ras mutation. K-ras mutation was more frequent in the horizontal size greater than 6 mm in diameter, and also more frequent in vertical size greater than 20 mm in height. It was concluded that the adenomas detecting K-ras mutations might have proliferating potential, and would be applied to determine polypectomy.

Adenoma↗
PubMed1996

[Surgical treatment for acute dissection associated with thoracic aneurysm--a case report and a review of Japanese literatures].

DeBakey IIIa acute dissection associated with thoracic aneurysm was successfully operated upon in 62-year-old man. The patient was referred to our hospital complaining of sudden severe back pain, and diagnosed as having acute dissection associated with thoracic aneurysm. An emergency operation was carried out, using partial cardiopulmonary bypass support with the cannulation into the right atrium via left femoral vein and left femoral artery. There was an entry in a true aneurysm of the descending aorta, which was replaced with a 22 mm Hemashield prosthetic graft. His postoperative course was uneventful. Acute dissection associated with a true thoracic aneurysm is rare and belongs to high risk groups for rupture. An urgent operation is often the treatment of choice.

Acute Disease↗
PubMed1995

The C-terminal region, Arg201-Gln209, of glutathione S-transferase P contributes to stability of the active-site conformation.

The C-terminal region of rat glutathione S-transferase P (GST-P) was deleted by either carboxypeptidase (CPase) A and B or site-specific truncation to evaluate the role of the region in the catalytic mechanism. The C-terminal sequence from the 201st to 209th amino-acid residues is Arg-Pro-Ile-Asn-Gly-Asn-Gly-Lys-Gln. When seven of the C-terminal amino-acid residues from the C-terminus were removed by the CPases, the catalytic activity decreased in parallel with the amino-acid removal, amounting to less than 5% of that of the wild-type GST-P. On the other hand, a decrease of the catalytic activity was observed in a different manner when the C-terminal sequence was site-specifically truncated. The VmaxGSH/KmGSH values of the mutants withthree (GSTd207-209), four (GSTd206-209) and seven (GSTd203-209) C-terminal amino-acid residues deleted, were comparable or similar to that of the wild-type GST-P, whereas those of five (GSTd205-209), six (GSTd204-209), and eight (GSTd202-209) amino-acid residue-truncated mutants decreased to 43%, 40%, and 19% of that of the wild-type GST-P, respectively. Similar results were obtained as for VmaxCDNB/KmCDNB. The nine amino-acid residue-truncated mutant showed no catalytic activity. Heat treatment at 50 degrees C for 5 min had little effect on the catalytic activities of the wild-type GST-P and GSTd204-209, whereas those of GSTd207-209, GSTd206-209, GSTd203-209 and GSTd202-209 decreased to 22%, 27%, 18% and 10%, respectively, compared to the catalytic activity of the non-treated enzymes. Considering these results, it is concluded that the C-terminal region, Arg201-Gln209, has an important role in stabilizing the active-site conformation.

Amino Acid Sequence↗
PubMed1995

The structure and physicochemical properties of rat liver macrophage migration inhibitory factor.

We expressed rat macrophage migration inhibitory factor (rMIF) in E. coli using the cDNA isolated from a rat liver cDNA library. rMIF specifically bound glutathione (dissociation constant = 500 microM). We purified rMIF homogeneously on SDS-PAGE by S-hexylglutathione Sepharose affinity column chromatography and Sephadex G-100 column chromatography. The amino-acid sequence of rMIF was highly homologous to that of human MIF from a T-cell line; only a single amino-acid residue was substituted if conservative amino-acid substitutions were involved. The molecular weight of rMIF was calculated to be 12.4 kDa and 23.6 kDa by SDS-PAGE and analytical ultracentrifugation, respectively. Thus, it was concluded that the native rMIF formed a homodimeric structure. Proton nuclear magnetic resonance (1H-NMR) study revealed that rMIF was less thermostable (the denaturing temperature was from 50-60 degrees C) than human MIF (the denaturing temperature is about 80 degrees C (Nishihira et al. (1993) Biochem. Mol. Biol. Int. 31, 841-850). The secondary structure of rMIF evaluated by 1H-NMR experiments revealed that the contents of alpha-helix, beta-strand, and coil were 13.8%, 55.6%, and 30.6%, respectively.

Animals↗
PubMed1994

Interaction of melittin with lipid membranes.

Interaction of melittin with lipid membranes was studied systematically with respect to its adsorption onto membranes, its effect on membrane leakage and fusion, and micellization at various melittin/lipid ratios. It was found that melittin has a strong affinity for adsorption onto lipid membranes. The analysis of the measured electrophoretic mobilities by use of a Gouy-Chapman double layer theory, shows that melittin is adsorbed onto the phosphatidylserine membrane several times more than the phosphatidylcholine membrane. However, it was observed that the phosphatidylcholine membrane is more susceptible to membrane leakage, vesicle fusion and micellization at a lower level of melittin adsorbed than the phosphatidylserine membrane. For small unilamellar phosphatidylcholine vesicles in 0.1 M NaCl, membrane leakage started at melittin to lipid ratio of 1:2000, a large increase in the rate of membrane leakage occurred at a ratio of about 1:500 or higher, membrane fusion occurred at a ratio of 1:200, and membrane micellization at a ratio of 1:10. On the other hand, for small unilamellar phosphatidylserine vesicles, the respective concentrations of melittin to result in membrane leakage, vesicle fusion, and membrane micellization were several times higher. Surface pressure measurements of lipid monolayers showed that the increase in surface pressure of the phosphatidylcholine monolayer due to the presence of melittin in the subphase solution was greater than that for the phosphatidylserine monolayer at any melittin concentration in the subphase solution. These experimental results indicate that melittin tends to be adsorbed on the surface of the negatively charged phosphatidylserine membrane due to the electrostatic binding so that the melittin molecule can stay out more on the surface of the membrane, while melittin appears to be adsorbed more into the hydrophobic membrane core for the electrically neutral phosphatidylcholine membrane.

Adsorption↗
PubMed1994

[Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase].

Highly selective inhibitors of thromboxane (TX) A2 synthase were noted as a therapeutic agent for ischemic heart diseases, thromboembolic disorders, cerebral circulatory disorders, and asthma. The 1-substituted imidazoles and beta-substituted pyridines showed high inhibitory potency on TXA2 synthase. The structure-activity relationships of the imidazole and pyridine derivatives as inhibitors of TXA2 synthase were investigated. Introduction of various substituents into the carboxy-bearing side chain of 1-(7-carboxyheptyl) imidazole and beta-(7-carboxyheptyl) pyridine was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum in the region of 8.5 to 10 A for the inhibitory potency on TXA2 synthase. Among the tested imidazole and pyridine derivatives, (E)-4-(1-imidazolylmethyl)cinnamic acid (44) and (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid (56) showed the highest potency (IC50 = 1.1 x 10(-8) and 3 x 10(-9) M). The inhibition by these derivatives was highly selective for TXA2 synthase, since other enzymes which are involved in the arachidonic acid cascade, such as fatty acid cyclooxygenase, 5-lipoxygenase, prostacyclin (PGI2) synthase, and PGE2 isomerase were not affected. On the basis of the results obtained from the pharmacological, physicochemical and toxicological studies on the two compounds (44 and 56), (E)-4-(1-imidazolylmethyl) cinnamic acid (44; OKY-046, ozagrel) was selected as the best compound of highly selective inhibitors of TXA2 synthase. The pharmacological properties of ozagrel are as follows. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase. Such an increase in PGI2 production by ozagrel was also observed in various experimental animals. We obtained the suggestion that, by the reduction of TXA2 production and increment of PGI2 production, ozagrel inhibits the spasms of basilar artery and the decreases in regional cerebral blood flow in dogs which received autologous blood into cisterna magna, and inhibits the decreases in motor function and regional cerebral blood flow, and the formation of infarcted area in the animals of cerebral ischemic treatment. It was also suggested that ozagrel inhibits leukotriene-, platelet-activating factor-, and antigen-induced bronchoconstriction in guinea-pigs and inhibits the induction of airway hyperresponsiveness by various stimuli in several species of animals by both mechanisms. The summarized results of ADME, toxicological, and clinical studies were also described.

Animals↗
PubMed1994

Involvement of beta 3-adrenoceptor in the relaxation response in guinea pig taenia caecum.

beta-Adrenoceptors in the guinea pig taenia caecum were investigated by measuring relaxation responses to agonists and by a radioligand binding assay using [3H]CGP 12177. The rightward shift of the isoprenaline concentration-response curve was observed by butoxamine, a beta 2-selective antagonist, and the pA2 value for butoxamine was 6.46. In control preparations, catecholamines caused relaxation with the following rank order of potency: isoprenaline > adrenaline > noradrenaline. However, in the presence of 10(-6) M phentolamine, 3 x 10(-4) M atenolol and 10(-4) M butoxamine, the rank order of potency of the agonists was: isoprenaline > noradrenaline > adrenaline. CGP 12177 caused graded relaxation of the guinea pig taenia caecum, and this response was not influenced by 10(-6) M phentolamine, 3 x 10(-4) M atenolol, 10(-4) M butoxamine or 10(-6) M propranolol. The Scatchard plot of the specific [3H]CGP 12177 binding to microsomal fractions from the guinea pig taenia caecum showed two affinity sites of the receptor: high affinity (KD = 0.64 nM) and low affinity (KD = 142.21 nM) sites. The pKD value of the high affinity site of [3H]CGP 12177 was in agreement with its pA2 value, and that of the low affinity site was in agreement with its pD2 value. These results suggest that isoprenaline-, noradrenaline- and adrenaline-induced relaxations of the guinea pig taenia caecum predominantly involve beta 2- and beta 3-adrenoceptors, whereas CGP 12177-induced relaxation is mediated solely through beta 3-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1994

[A study of regional chemotherapy: hepatic arterial infusion for metastatic liver tumors].

This study was designed to evaluate whether intraarterial and intra-portal infusion chemotherapy was effective in 57 patients with liver metastases from colorectal cancer and 10 from gastric cancer. Arterial infusion was effective to prevent recurrence in the remnant liver after resection of liver metastases from colorectal cancer. On the other hand, intra-portal infusion was not effective to prevent recurrence. In the patients with unresectable metastases, arterial infusion was also effective for the response rate, which was 75% (with intra-portal infusion) and 27 % (arterial infusion only), respectively. However, arterial infusion had no effect in patients with metastases from gastric cancer. As a result, arterial infusion was effective to prevent recurrence after resection of metastases, and to increase the survival rate in patients with unresectable metastases from colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗