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Biomedical subjects

K Ohkubo

Publications and source records attributed to K Ohkubo.

At least 91 records · Page 5Linked to original sources
PubMed1992

Effect of glycyrrhizinate on dissolution behavior and rectal absorption of amphotericin B in rabbits.

The effects of dipotassium glycyrrhizinate (GLYK) on the dissolution behavior and bioavailability of amphotericin B (AMB) were investigated. The mixtures of AMB and GLYK were prepared at different molar ratios by lyophilization. Lyophilization resulted in amorphous AMB either alone or in the mixture. Dissolution rates of AMB of the mixtures were markedly faster than that of lyophilized AMB alone, which was followed by a decrease of dissolution. The initially-enhanced dissolution rate was likely to be due to the improvement of surface wettability of drug particles with GLYK rather than the amorphous state of AMB. A phase solubility study of AMB with GLYK indicated that the increasing solubility was caused by micellar solubilization. The in vitro release rate of AMB from suppositories containing the lyophilized mixtures was significantly accelerated by increasing the amount of GLYK. The rectal absorption of AMB from suppositories containing either the drug alone, a physical mixture or a lyophilized mixture was studied using rabbits. The absorption of the mixture (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum concentration-time curve (0-24 h) than that of lyophilized AMB alone. These results suggest that GLYK is useful for improving the dissolution property of AMB and the bioavailability of the drug incorporated in suppositories.

Amphotericin B↗
PubMed1992

[Growth rate of hepatocellular carcinoma and nutritional state].

To clarify the relationship between the growth rate of hepatocellular carcinoma (HCC) and nutritional state or liver function 32 HCC patients with a tumor volume less than 100 ml at the beginning of the study were investigated. These patients all had been treated by serial transcatheter arterial embolization (TAE). Tumor volume was measured by integrating the CT images of the liver before each TAE. The tumor at the TAE just before significant enlargement occurred was defined as the stage I tumor and it was designated stage II at the next TAE. The growth rate of the HCC was then calculated from the tumor volume at stage II minus that at stage I. Caloric intake, protein intake, liver function, and serum amino acid were determined in the patients at each stage. The results were as follows: 1) The tumor growth rate was greater in patients whose caloric intake and protein intake were more than 35 kcal/kg/day and 1.5 g/kg/day, respectively. 2) In patients with the greater tumor growth rate, the plasma BCAA/AAA ratio was the lower. However, after tumor growth, the ratio became higher, indicating that the growth of HCC decreased the requirement of BCAA. 3) The tumor growth rate correlated to the change of plasma arginine level (r = -0.76, p less than 0.05).

Amino Acids↗
PubMed1992

[A case report of radiation osteomyelitis 9 years after irradiation for thymoma].

Radiation osteomyelitis of the sternum is rare and usually difficult to cure. A 75-year-old man, who had undergone an exploratory sternotomy for a mediastinal tumor, not resected after all, 9 years earlier and received radiation therapy successively for the histological diagnosis of malignant thymoma, was admitted to our hospital with the chief complaint of fever and pus discharge of the anterior chest wall. He also suffered from diabetes mellitus. The skin around the fistula was dark-red and atrophic due to irradiation dermatitis and the manubrium was fissured in the midline. Open drainage and two-stage operation of direct closure was tried in vain. This case was treated successfully by resection of necrosed portion of sternum and pectoral muscle flap closure.

Aged↗
PubMed1992

Functional electrical stimulation (FES) systems for restoration of motor function of paralyzed muscles--versatile systems and a portable system.

Multichannel functional electrical stimulation (FES) systems were developed to restore the motor functions of the paralyzed muscles, i.e. two kinds of versatile systems for laboratory use and a practical portable system were developed. The first microcomputer-based FES system was composed of an 8 bit microcomputer (PC-8801mkII) with a voice recognition board and 30 stimulation outputs, in which the voice commands were used for selecting a motion pattern, and for executing (start), (hold), (restart) and (stop) commands. In combination with the voice commands, a proportional control command detected from a head angle sensor was used for volitional control of motion. The second microcomputer-based FES system was composed of a 16 bit microcomputer (PC-9801 UV or compatible) with flexible control capabilities (e.g. respiratory sensors) for volitional control and with 64 stimulation outputs. An originally designed practical portable FES system was 89 x 145 x 31 mm in dimension and 380 g in weight. This paper describes the system configurations, the control methods of these FES systems and three examples of the clinical applications of the FES systems.

Electric Stimulation Therapy↗
PubMed1992

Nicardipine infusion improved hepatic function but failed to reduce hepatic venous pressure gradient in patients with cirrhosis.

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.

Adult↗
PubMed1991

Cloning, structure and expression of cDNA for mouse contrapsin and a related protein.

A cDNA clone (lambda MC-2) for contrapsin, a serine-proteinase inhibitor, was isolated from a lambda ZAP mouse liver cDNA library. The 1.6 kb cDNA insert of lambda MC-2 contained an open reading frame that encodes a 418-residue polypeptide (46,970 Da), in which a signal peptide of 21 residues was identified by comparison with the N-terminal sequence of the purified protein. The predicted structure (MC-2) also contained other peptide sequences determined by Edman degradation. Four potential sites for N-linked glycosylation were found in the molecule, accounting for the difference in molecular mass between the predicted form and the purified protein (63 kDa). Further screening of the cDNA library with an EcoRI-EcoRI fragment (510 bp) of lambda MC-2 as a probe yielded another cDNA clone (lambda MC-7), which encodes a 418-residue polypeptide (MC-7) with a calculated mass of 47,010 Da. MC-2 showed 83% similarity at the amino acid level to MC-7, in contrast with 44% similarity to alpha 1-proteinase inhibitor. The possible reactive site (P1-P'1) for serine proteinase is suggested to be Lys-Ala for MC-2 and Ser-Arg for MC-7. Northern-blot analysis revealed that both MC-2 and MC-7 mRNAs have the same size of 1.8 kb and are markedly induced in response to acute inflammation. Construction of the expression plasmids pSVMC-2 and pSVMC-7 and their transfection into COS-1 cells demonstrated that pSVMC-2 directs the synthesis of a 63 kDa form whereas pSVMC-7 expresses a 56 kDa form. The difference in molecular mass between the two may be explained by the fact that the MC-7 sequence contains three potential sites for N-glycosylation, one site less than that of MC-2.

Amino Acid Sequence↗
PubMed1991

Effect of intraportal nitroglycerin on portosystemic hemodynamics in patients with cirrhosis: comparison with i.v. route.

We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus -25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension.

Administration, Oral↗
PubMed1991

Molecular cloning and characterization of rat contrapsin-like protease inhibitor and related proteins.

A glycoprotein with Mr 63,000 purified from rat serum was found to inhibit trypsin activity but not chymotrypsin or elastase activity, resembling contrapsin purified from mouse serum. To obtain further information on the molecular structure, a cDNA clone (lambda CPi-21) for this contrapsin-like protease inhibitor was isolated from a rat liver cDNA library. The 1.6-kb cDNA insert contained an open reading frame that encodes a 416-residue polypeptide (CPi-21), in which the first 29 residues were suggested to comprise a signal peptide by comparison with the NH2-terminal sequence of the purified protein. The predicted structure also contained other peptide sequences determined by Edman degradation. Four potential N-linked glycosylation sites were found in the molecule, presumably accounting for the larger molecular mass of the mature form. Further screening of the cDNA library with a Pst-XbaI fragment (302 bp) of lambda CPi-21 as a probe yielded two other cDNA clones (lambda CPi-23 and lambda CPi-26), which encode 413-residue and 418-residue polypeptides, respectively. A comparison of their amino acid sequences revealed that CPi-21 has 89 and 71% homology with CPi-23 and CPi-26, respectively. The primary structure of each of the three proteins has about 70% homology with that of mouse contrapsin, in contrast to 43-46% homology with that of rat alpha 1-protease inhibitor. These results indicate that all the CPi proteins presented here belong to a subfamily of "serpins" of which mouse contrapsin was the first member to be identified.

Acute Disease↗
PubMed1991

Hemodynamic study during transdermal application of nitroglycerin tape in patients with cirrhosis.

We studied 14 patients with portal hypertension and cirrhosis using portal and hepatic vein catheterizations to determine the effects of transdermal application of nitroglycerin tape (containing 10 mg of nitroglycerin and capable of releasing 6 to 7 mg of nitroglycerin in 12 hr) on splanchnic hemodynamics. Patients randomly received nitroglycerin (n = 7) or a placebo (n = 7). No significant changes were observed after the administration of the placebo. In contrast, transdermal nitroglycerin caused a significant reduction in portal pressure, as evaluated by measurements of the portal venous pressure gradient (-22%, p less than 0.01). The reduction of portal pressure was due to a decrease in the portal venous pressure, with no changes in the free hepatic venous pressure. Despite the fall in portal pressure, the hepatic blood flow was maintained. These findings suggest that transdermal nitroglycerin could be potentially useful in the treatment of portal hypertension associated with cirrhosis.

Administration, Cutaneous↗
PubMed1991

Pancreatic pseudocyst in the left hepatic lobe: a report of two cases.

The ultrasound and computed tomographic imaging features in a rare pancreatic pseudocyst of the liver are described in two patients. The pseudocysts occurred in the left lobe in both cases, one after a traumatic injury and the other after alcoholic pancreatitis. The possible topographical sequences with which pancreatic secretions entered the left hepatic lobe to form a cyst are discussed.

Adult↗
PubMed1990

Intracellular processing of complement pro-C3 and proalbumin is inhibited by rat alpha 1-protease inhibitor variant (Met352----Arg) in transfected cells.

Complement C3, when its cDNA was transfected into COS-1 cells, was synthesized as a precursor, pro-C3, which was intracellularly processed into the alpha and beta subunits, although not completely. A cDNA for rat alpha 1-protease inhibitor (alpha 1-PI) was mutated in vitro to encode its variant with the modified active site (Met352----Arg). In cells co-transfected with the mutant alpha 1-PI cDNA and the C3 cDNA, pro-C3 expressed was secreted without being processed into the subunits. Co-transfection of the mutant alpha 1-PI cDNA and the albumin cDNA also resulted in the inhibition of intracellular conversion of proalbumin into serum-type albumin. No inhibition of the processing of each preform was observed in cells co-transfected with the normal alpha 1-PI cDNA. Taken together, the results indicate that the alpha 1-PI variant (Met352----Arg) expressed inhibits specifically an intracellular enzyme which is involved in the proteolytic processing of both pro-C3 and proalbumin.

Amino Acid Sequence↗
PubMed1990

Primary structure of human placental 5'-nucleotidase and identification of the glycolipid anchor in the mature form.

A cDNA was cloned coding for human placental 5'-nucleotidase. The 3547-bp cDNA contains an open reading frame that encodes a 574-residue polypeptide with calculated size of 63 375 Da. The NH2-terminal 26 residues comprise a signal peptide, which is followed by the NH2-terminal sequence of the purified protein. four potential N-linked glycosylation sites are found in the molecule, accounting for a larger mass of the mature form (71 kDa). The predicted structure contains a hydrophobic amino acid sequence at the COOH terminus, a possible signal for the post-translational modification by glycophospholipid. To confirm this possibility, we tried to isolate and characterize the membrane-anchoring domain of 5'-nucleotidase. BrCN-cleaved fragments of the protein were extracted with hexane and subjected to HPLC, resulting in purification of a single component of 2.3 kDa. Chemical analyses revealed that the purified fragment contains the tetradecapeptide Lys-Val-Ile-Tyr-Pro-Ala-Val-Glu-Gly-Arg-Ile-Lys-Phe-Ser, ethanolamine, glucosamine, mannose, inositol, palmitic acid, and stearic acid. The peptide sequence determined is identified at positions 510-523 in the primary structure deduced from the cDNA sequence, which predicts a further extension to position 548, containing the hydrophobic amino acid sequence. Thus, it is concluded that the mature 5'-nucleotidase lacks the predicted COOH-terminal peptide extension (524-548), which has been replaced by the glycophospholipid functioning as the membrane anchor of 5'-nucleotidase.

5'-Nucleotidase↗
PubMed1990

[An experimental trial for quantitative estimation of lipiodol using CT value--application to hepatic arterial infusion therapy].

An experimental trial for quantitative estimation of Lipiodol (Lp.) using CT scan was performed. Simulating the average CT value of Lp. to known iodine concentration calculated from the standard curve of KI solution/CT value, quantity of Lp. can be given by following formula; (Lp-dose/slice) = KS d/480 (K: known iodine concentration, S: area square of Lp., d: slice thickness). Satisfactory data were given, and clinical application was expected.

Embolization, Therapeutic↗
PubMed1990

Molecular cloning and sequencing of the cDNA of rat alpha 1-protease inhibitor and its expression in COS-1 cells.

A cDNA clone for alpha 1-protease inhibitor (pc alpha 1P1212) was isolated from a lambda ZAP rat liver cDNA library. The 1.4 kb cDNA insert of pc alpha 1P1212 contained an open reading frame that encodes a 411-residue polypeptide (46,125 Da), in which a signal peptide of 24 residues was identified by comparison with the NH2-terminal sequence of the purified protein. Three potential sites for N-linked glycosylation were found in the molecule, accounting for the difference in molecular mass between the predicted form and the purified protein (56 kDa). The deduced primary structure of rat alpha 1-protease inhibitor showed 68.5% homology to that of the human inhibitor. We then constructed the expression plasmid pSV2 alpha 1PI from pSV2-gpt and pc alpha 1P1212, and transfected it into COS-1 cells. The transfected cells synthesized a molecule which was precipitated with anti-(rat alpha 1-protease inhibitor)-IgG and had the same molecular size as that of the inhibitor produced by rat hepatocytes.

Amino Acid Sequence↗
PubMed1990

[Aneurysm of the diverticulum of the ductus arteriosus in the adult].

Aneurysm of the diverticulum of the ductus arteriosus is a rarely reported entry in adult. To our knowledge, only two previous patients underwent successful aneurysmectomy in Japan. Three new cases of aneurysm of the ductus arteriosus diverticulum in the adult, all diagnosed preoperatively and successfully repaired, are presented. All three patients are alive 17 to 44 months postoperatively. Our experience with these patients suggests several important features of these aneurysms: (1) CT scanning with contrast enhancement will almost invariably confirm the diagnosis of these aneurysms. (2) Exposure through a median sternotomy is generally good and carries less operative morbidity from rupture than a posterolateral thoracotomy. (3) Because of their critical location and the high incidence of rupture in reported cases, aneurysms producing symptoms, or those showing progressive enlargement should be surgically resected. (4) When a succular aneurysm of the aortic arch is demonstrated expanding toward the aortopulmonary window with adhesion to the pulmonary artery, the possibility of its origin from the ductus arteriosus must be investigated.

Age Factors↗
PubMed1990

[Left ventricular myxoma with mucocutaneous myxoid tumors--a case report].

A surgical treatment of left ventricular myxoma arising from the anterior wall of the left ventricle is reported. A 32 year old man with a history of transient syncopal attack had an echocardiographic diagnosis of left ventricular myxoma. He previously had had myxoid tumors excised from the nose and from the posterior part of the left thigh. Cardiac surgery was performed under extracorporeal circulation on December 20, 1989. A friable, gelatinous 5 cm long myxoma with a diameter of 3 cm was excised from the left ventricule. The postoperative course was uneventful. The clinical characteristics in all the reported cases of cardiac myxomas with associated myxoid tumors of the skin are reviewed. Cardiac myxomas in patients with mucocutaneous myxoid tumors have an atypical biological behavior with early development of myxomas, atypical location, multiple tumors and high rate of recurrent myxomas.

Adult↗
PubMed1990

[Three cases of alveolar soft part sarcoma and MRI findings].

Three cases of alveolar soft part sarcoma were reported with characteristic MRI findings. On MRI findings, slightly higher signal intensity than muscles on T1 weighted image and remarkably high signal intensity on T2 weighted image were thought to be characteristic of alveolar soft part sarcoma.

Adult↗