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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 19 recordsLinked to original sources

Total vascular exclusion for hepatic resection in cirrhotic patients. Application of venovenous bypass.

Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes.

Adult

A prolongation of hepatic vascular exclusion by in situ hypothermic perfusion in dogs.

In situ hypothermic hepatic perfusion was performed in dogs to explore whether the time limit of hepatic vascular exclusion could be prolonged. During hepatic vascular exclusion, hepatic hypothermic perfusion was performed via portal vein using various perfusates under active bypass from the portal vein and infrahepatic inferior vena cava area to the superior vena cava system. Dogs receiving hepatic hypothermic perfusion for 1 hour died when given Ringer's solution but survived more than 7 days when given Euro-Collins' and University of Wisconsin solutions. Although dogs tolerated 2 hours of hepatic hypothermic perfusion when give University of Wisconsin solution, all dogs died by 2 hours of hepatic hypothermic perfusion when given Euro-Collins' solution. The hepatic energy charge and arterial ketone body ratio of dogs that died were significantly lower than for those that survived. This suggests that the regimen of hepatic hypothermic perfusion with University of Wisconsin solution is able to maintain the energy metabolism of the liver under hepatic vascular exclusion for prolonged periods, hence, its possible clinical application.

Adenosine

Effect of beta-endorphin on cAMP accumulation in rat luteal cells.

The effect of beta-endorphin on cAMP levels in 4-day-old rat luteal cells was investigated. In both the presence and absence of low doses of human chorionic gonadotropin (hCG, 0.001 IU/ml), beta-endorphin inhibited cAMP accumulation, whereas in the presence of high doses of hCG (0.01 IU/ml) it did not. This inhibitory effect was abolished by pre-treatment with islet-activating protein (IAP). Moreover, treatment with IAP resulted in an overall enhancement of hCG-stimulated cAMP accumulation when compared with untreated controls. These results suggest that beta-endorphin suppresses adenylate cyclase activity via Gi, which may be coupled to the LH receptor.

Adenylate Cyclase Toxin

Comparative in-vitro activity of RP 59500 against clinical bacterial isolates.

The activity of RP 59500 against Gram-positive cocci was determined by an agar dilution method and compared with that of erythromycin, cefotaxime and ampicillin. Of the 344 clinical isolates tested, none was resistant to RP 59500; this compound was active both against methicillin-resistant Staphylococcus aureus and against macrolide-resistant Gram-positive cocci. The bactericidal activity of RP 59500 was confirmed by killing curve determinations.

Ampicillin

Maintenance of liver graft viability in the state of brain death. Synergistic effects of vasopressin and epinephrine on hepatic energy metabolism in brain-dead dogs.

The influence of vasopressin and epinephrine on hepatic energy metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) and hepatic energy charge (EC) in brain-dead dogs. Mean arterial blood pressure (MABP) was significantly decreased from 125.5 +/- 5.5 to 53.4 +/- 1.7 mmHg after complete brain death (P less than 0.01). In the control group AKBR and EC were maintained at near the normal values thereafter, despite marked hypotension. Combined administration of vasopressin and epinephrine sustained AKBR normally and improved MABP above 90 mmHg (P less than 0.01). EC was also maintained within the normal range at 5 hr after initiation of administration of the drugs. By contrast, vasopressin or epinephrine alone maintained AKBR and EC at near the normal values, but improved MABP just slightly to around 60 mmHg (P less than 0.01). As for the volume control, the urinary output was significantly smaller in the vasopressin and epinephrine-treated group than in the control group (P less than 0.05). It is suggested that combined administration of vasopressin and epinephrine has a synergistic effect in improving the hemodynamics and maintenance of the energy status of the liver. This regimen is recommended as a good one for maintaining potential liver donors in the state of brain death.

Adenine Nucleotides

Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death.

The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.

Animals

Acquisition of a sucrose utilization system in Escherichia coli K-12 derivatives and its application to industry.

An Escherichia coli strain, B-62, that was isolated from a clinical source and was epidemiologically unrelated to E. coli K-12 was the source of chromosomal DNA for a sucrose utilization system (Scr+) in the construction of a plasmid, pST621. The cloned insert of a gene encoding Scr+ in pST621 conferred a sucrose-positive phenotype onto transformed cells of E. coli K-12 derivatives. Sucrase activity of the transformants was as high as that which would correspond to a "gene dosage effect" of a vector plasmid pBR322, whereas the transformants' sucrose uptake activity was always lower than that of E. coli B-62. A region within an XhoI-SacI fragment (3.2 kb) of pBR322-glyA was replaced in the construction of another plasmid, pST5R7, by a fragment (about 2.6 kb) of pST622 containing the gene encoding Scr+. A genetically stable Scr+ derivative of E. coli K-12 was obtained by introducing the gene encoding Scr+ onto E. coli chromosome via homologous recombination between pST5R7 and the chromosome and subsequent plasmid segregation. The use of low-copy-number plasmid RP4 as a cloning vector was also effective for enhancing the stability of Scr+. Tryptophan producers E. coli SGIII1032S, in which the gene encoding Scr+ was cloned onto the chromosome, and E. coli SGIII1032, which carried Scr+ plasmid RP4.5R7, produced from 6% sucrose in shake flasks (33 degrees C, 96 h) 2.3 and 5.7 g of tryptophan per liter, respectively.

Biological Transport, Active

Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas.

Kuei-chih-fu-ling-wan (Keishi-bukuryo-gan; KBG), a traditional Chinese herbal remedy contains five components: bark of Cinnamomum cassia Bl. (Lauraceae), root of Paeonia lactiflora Pall. (Paeoniaceae), seed of Prunus persica Batsch. or P. persiba Batsch.var.davidiana Maxim. (Rosaceae), carpophores of Poria cocos Wolf. (Polyporaceae), and root bark of Paeonia suffruticosa Andr. (Paeoniaceae). This prescription has been frequently used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and sterility. We previously reported that KBG might act as a LH-RH antagonist and a weak anti-estrogen on the uterine DNA synthesis in immature rats. In the present study, we investigated the effects of KBG on 110 premenopausal patients with uterine myomas. Clinical symptoms of hypermenorrhea and dysmenorrhea were improved in more than 90% of the cases with shrinking of uterine myomas in roughly 60% of the cases.

Adult

Antigonadotropic activity of hop extract.

Biological activity of water soluble fractions F-1 and F-2, which were extracted from hop, was studied and its action mechanism was speculated using the immature female SD rats. Administration of the substance significantly inhibited the effects of pregnant mare serum gonadotropin (PMSG) on 22-day-old female rats. Thus, PMSG-induced increases in ovarian weight, estrogen secretion, number of ovulated egg, progesterone production, uterine thymidine kinase activity, and plasma LH level were suppressed significantly. Furthermore, addition of the substance to incubated ovarian cells of the second day after PMSG injection resulted in suppression of FSH-induced estradiol secretion in vitro, probably via cAMP-dependent mechanism. But addition of the substance to incubated pituitary cells from ovariectomized rats did not change in LH secretion.

Animals

A novel steroidogenic role of suramin-blocked luteal cell growth factors.

Growth factors synthesized in the ovarian corpus luteum (CL) have been implicated in the development of the CL. One of these growth factors is basic fibroblast growth factor which acts on luteal cells in an autocrine manner (Tamura et al. 1991; Asakai et al. 1992). To elucidate effects of these growth factors in the development of the CL, we cultured immature luteal cells with defined medium for a week in the presence or absence of a growth factor inhibitor, and measured progesterone in the medium as an indicator of cell differentiation. Culture of luteal cells showed an increased amount of progesterone for three days and continued to synthesize progesterone for at least another four days without serum and pituitary hormones. The addition of suramin, previously reported to inhibit autocrine growth stimulation, accelerate the daily progesterone production of luteal cells apparently by switching on the early onset of differentiation. Suramin also induced apoptosis of the cells after the 3rd day of culture. These data suggest that an autostimulation mechanism by growth factors plays a physiological role on normal cell differentiation, and it is not limited to neoplastic transformation.

Animals

Thymidine kinase activity in familial adenomatous polyposis.

Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of normal colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of normal; this increase seems attributable mainly to increased activity of cytosolic TK isozyme activity; the colorectal TK isozymes were separated into two types, i.e., fetal type and adult type isozymes predominantly in, respectively, cytosolic and mitochondrial fractions, by DEAE-cellulose column chromatography. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over normal. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity being elevated in some cases (8 of 15) and remaining low in others. Thus FAP polyps seem to be a heterogenous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.

Adenomatous Polyposis Coli

Family of a patient with serum cholinesterase deficiency.

A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.

Adult

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. I. Isolation of antibiotic-blocked mutants and their characterization.

Biosynthetically blocked mutants were obtained from a baumycin-producing Streptomyces sp. D788 newly isolated from soil. The first mutant isolated was a baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'-substitution activity, from which all other blocked mutants were successively derived. These included a known 11-deoxydaunorubicin-producing mutant and several new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10-methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor aglycone, respectively. In this paper, all the anthracycline components produced by the parent strain and its two known blocked mutants, a daunorubicin producer and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new components are isolated. Cytotoxicities in vitro of all the components against L1210 cell culture are also described.

Animals

Production of new anthracycline antibiotics 1-hydroxy-oxaunomycin and 6-deoxyoxaunomycin by limited biosynthetic conversion using a daunorubicin-negative mutant.

A limited biosynthetic conversion of some known anthracyclinones using a specific daunorubicin-nonproducing mutant provided four new anthracycline antibiotics: 1-Hydroxy-10-methoxycarbonyl-13-deoxocarminomycin; 1-hydroxy-13-deoxocarminomycin; 1-hydroxyoxaunomycin and 6-deoxyoxaunomycin. Their isolation and purification from bioconversion broth, structural determination and antitumor activities against leukemic L1210 cells are described.

Animals

Photochemically obtained N-demethyl derivatives of anthracyclines.

New N-monodemethyl and N-didemethyl derivatives were obtained from seven N-dimethylamino sugar (rhodosamine)-containing anthracyclines by photochemical reaction and their in vitro bioactivities against L1210 cell culture were compared with those of their N-dimethyl parent compounds. N-Demethyl derivatives obtained from betaclamycin T (7-O-rhodosaminyl-beta-rhodomycinone) were much more cytotoxic while those from the other six antibiotics were rather less active as compared with their parent compounds. The N-demethylation also gave a considerably greater decrease in the inhibitory activity on RNA synthesis as compared to DNA synthesis, so that the N-demethyl derivatives showed smaller IC50 ratios on DNA/RNA than their parent compounds.

Animals

Production of new anthracycline antibiotics by microbial 4-O-methylation using a specific daunorubicin-negative mutant.

Microbial 4-O-methylation using a specific daunorubicin-blocked, nonproducing mutant provided the new anthracycline antibiotics 4-O-methylbetaclamycin T, 4-O-methylyellamycin A and 4-O-methyl-13-hydroxyoxaunomycin, from which 4-O-methyloxaunomycin and 4-O-methyl-6-deoxyoxaunomycin were then prepared by further photochemical N-demethylation. Antitumor activities in vitro and in vivo against L1210 cells were compared with those of their 4-O-demethyl derivatives. It was found that all the 4-O-methyl derivatives had a markedly reduced cytotoxicity in vitro as compared with the 4-O-demethyl compounds. However, some of them were endowed with a significantly improved antitumor activity in vivo.

Animals

[Aminoglycosides resistance of methicillin-resistant Staphylococcus aureus].

In the last decade, there has been a dramatic increase in the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) in Japan. Especially, a high incidence of multiple resistant MRSA strains has been reported. These strains are resistant not only to beta-lactams but to aminoglycosides and macrolides. About 90% of MRSA strains were resistant to gentamicin (GM) and/or tobramycin (TOB), producing an aminoglycoside modifying enzyme, mainly, APH (2")/AAC (6) and/or AAD (4',4"). Based on these modifying enzymes produced, MRSA strains were classified into three groups; group 1 produced APH (2")/AAC (6), belonging to phage group I and coagulase IV, group 2 produced AAD (4',4"), belonging to phage group III and coagulase II, and group 3 produced APH (2")/AAC (6) and AAD (4',4"), belonging to phage group III and coagulase II. The epidemiological results suggest that MRSA strains changed from group 1 to group 2, and then to group 3. Recently, arbekacin (ABK), a new anti-MRSA aminoglycoside, has been introduced into clinical practice. ABK shows a potent activity to GM-resistant strains, due to poorly modification by APH (2")/AAC (6'). However, there were few ABK- and GM-resistant strains in clinical isolates. These strains produced a higher amount of the enzyme than ABK-susceptible and GM-resistant strains. This observation suggests that ABK-resistant strains might be derived from GM-resistant strains by mutation of the gene coding APH (2")/AAC (6').

Acetyltransferases