Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. III. New anthracycline metabolites produced by blocked mutants 4L-660 and YDK-18.
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Animals↗
Biomedical subjects
R Okamoto
Publications and source records attributed to R Okamoto.
Mer-WF3010, a new member of the papulacandin family. I. Fermentation, isolation and characterization.
Mer-WF3010, a new member of the papulacandin family, was isolated from the mycelia of Phialophora cyclaminis Mer-WF3010 (FERM P-11475). The molecular formula of Mer-WF3010 was determined as C45H60O16.
Aminoglycosides↗
Mer-WF3010, a new member of the papulacandin family. II. Structure determination.
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Aminoglycosides↗
Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. II. New anthracycline metabolites produced by a blocked mutant strain RPM-5.
A daunorubicin-blocked mutant strain RPM-5 derived from a new baumycin-producing Streptomyces sp. D788 accumulated a major precursor metabolite D788-1 (10-carboxyl-13-deoxocarminomycin) and nine minor metabolites in the culture broth. Five among them were new with a substituent at C-10 or the altered side chains at C-9. Isolation, purification and identification of all anthracycline metabolites produced by strain RPM-5 are described with their antitumor activities against L1210 cells.
Animals↗
Development of a cyclodextrin production process using specific adsorbents.
Novel adsorbents that are composed of ligand, spacer, and support were chemically synthesized, and the two consecutive screenings made it possible to determine the adsorbents that were most suitable for alpha- and beta-CD production, respectively. Stearic acid was the most effective ligand for alpha-CD, whereas cyclohexanepropanamide-n-caproic acid was best for beta-CD. The adsorption selectivity of adsorbents derived from carboxylic acids (stearic or palmitic acid) and Chitosan beads was almost 100%, and their adsorption capacities were large enough to meet the demand for economical production and purification of CDs on an industrial scale. Next we discussed a novel process of alpha-CD production using the newly synthesized adsorbent characterized by the exceedingly powerful selectivity of alpha-CD from other CDs. alpha-CD production was carried out in the closed system converted to CDs by CGTase, and the column was packed with the adsorbent selective for alpha-CD. The yield of alpha-CD was 22.3%, and alpha-CD occupied a fraction of 57.4% in the overall CD reaction mixture. In the batch system without adsorbent, the yields of alpha-CD and its fraction were 10.8 and 24%, respectively. This novel process is particularly useful for the large-scale production of alpha-CD, in which the use of organic solvent is not preferable. We will now develop a novel process for the industrial production of CDs other than alpha-CD, such as gamma-CD, by using specific adsorbents.
Adsorption↗
Shortening of patellar ligament and patella baja with improvement of quadriceps muscle strength after high tibial osteotomy.
One hundred and eight osteoarthritic knees that had high tibial osteotomy were examined, in the length of the patellar ligament, patellar height, and the strength of the quadriceps muscle. Patellar ligament shortening occurred until one year after surgery. Subsequently, shortening was not observed to be significant over a 10 year followup period. Using Insall-Salvati ratio, a majority of knees seemed to have lower patellae, because of the shortening of the patellar ligament. However, using patellotibial distance, 68 percent of patellae maintained the same height as preoperatively and 26 percent became patella baja. The strength of the quadriceps muscle increased postoperatively, reached the maximum at 2 years, and preserved the same strength over 10 years. Patellar ligament shortening and patella baja were probably thought to be caused by the biological adaptation of the extensor mechanism and the shrinking of the scar tissue in and around the postoperative patellar ligament.
Adaptation, Physiological↗
Patella baja after displacement of tibial tuberosity for patellofemoral disorders.
The change of patellar height after the displacement of tibial tuberosity and its effect on the improvement of clinical signs of knees was studied. The anterior displacement of tibial tuberosity was performed on fourteen knees and the anteromedial displacement on twenty knees with patellofemoral arthrosis of twenty-nine patients, four men and twenty-five women with the age at operation ranging from 47 to 79 years (average: 58.3). The anteromedial displacement of tibial tuberosity was performed on ten knees and medial displacement on fifteen knees with recurrent patellar dislocation (eleven knees) or patellar subluxation (fourteen knees) of twenty-four patients, two men and women with the an age range from 14 to 37, (average: 22.4). Patellar height was measured on lateral view by the Insall-Salvati method using Ligament/Patella ratio (Lt/Lp ratio). Ligament/Patella ratio of the older group with patellofemoral arthrosis was decreased significantly (p < 0.01) after surgery, from 1.10 to 0.94. The ratio of the younger group with patellar dislocation or subluxation showed no significant changes, but of seven knees with high riding patella, which ratio revealed more than 1.2 before operation, decreased significantly (p < 0.001) from 1.47 to 1.31. The postoperative patella baja had no poor effect on the improvement of clinical signs.
Adolescent↗
[A comparative study of VEPA and ACOMEP-BD regimen for the patients with non-Hodgkin's lymphoma].
Between 1981 and 1990, ACOMEP-BD regimen (adriamycin, cyclophosphamide, vincristine, methotrexate, etoposide, prednisolone, bleomycin, dacarbazine) was compared with VEPA regimen (vincristine, cyclophosphamide, prednisolone, adriamycin) in 66 newly diagnosed patients younger than 65 of age, with non-Hodgkin's lymphoma (NHL). The median age of the patients was 47.5 years (range 22-64 years), 43 males and 23 females. One patients were in stage I, 6 were in II, 27 were in III, 32 were in IV. Twenty-seven patients received VEPA and 39 received ACOMEP-BD. The therapeutic results of 66 patients with ACOMEP-BD or VEPA were as follows: complete remission (CR) rate of 54% and 48%; relapse rate of 29% and 77%; CR duration of 2-34 months (mean: 22 months) and 2-74 months (16 months); freedom-from-relapse survival (at 3 years) of 71% and 38%; and overall survival (at 4 years) of 62% and 26%, respectively. In these results, only relapse rate was significant and the others were not. Prognostic factors were performance status (PS) and lactate dehydrogenase level for ACOMEP-BD, and PS and marrow involvement for VEPA. Received dose intensity was 0.85 in ACOMP-BD and 0.41 in VEPA. It was expected that outcome of patients with NHL can be improved by increasing dose intensity.
Adult↗
[Neutrophilic myelofibrosis; a case report].
A 53-year-old male was admitted to our hospital with abdominal pain. Physical examination revealed marked splenomegaly. The white blood cell count increased to 5.8 x 10(4)/microliters. Bone marrow biopsy showed hypercellularity with a moderate increase in reticulin fiber. Chromosomal analysis showed 47, XY, +9q-, -9q- without Ph1 chromosome and bcr-abl rearrangement. MCNU therapy was successful in reducing the white blood cell count and splenomegaly. It is likely that the diagnosis of our patient is compatible with the neutrophilic myelofibrosis described by Stewart, et al.
Blood Cell Count↗
Effects of triiodothyronine on canine hepatic ischemia caused by Pringle's maneuver.
BACKGROUND: A significant reduction in the serum concentration of triiodothyronine is frequently observed in surgical stress and may influence the severity and prognosis of the underlying disease. METHODS: Alterations of thyroid hormone levels and effects of triiodothyronine were evaluated in the shock state after Pringle's maneuver for 60 minutes in dogs. Triiodothyronine (1 micrograms/kg/hr) was infused intravenously for 3 hours after declamping in the triiodothyronine-treated group. The effect of triiodothyronine on hepatic mitochondrial function was investigated by measuring the arterial ketone body ratio (AKBR). RESULTS: In the control group (n = 6) the low triiodothyronine syndrome was observed and progressive deterioration of AKBR and standard liver functions represented by aspartate aminotransferase, glutamic-pyruvic transaminase, and lactic dehydrogenase were noted after declamping. All dogs went into shock and died within 24 hours. By contrast, in the triiodothyronine-treated group (n = 6), hemodynamics were stabilized and standard liver functions were maintained favorably (p < 0.01). AKBR was fully restored to the preischemic liver within 30 minutes after declamping, with a decrease in serum lactate levels (p < 0.05). All dogs survived at least 7 days after operation (p < 0.01). CONCLUSIONS: These results indicate that triiodothyronine has beneficial effects on cytoprotection, hemodynamics, and hepatic energy metabolism in the ischemic liver injury. Furthermore, it improves survival in the shock state after Pringle's maneuver.
Animals↗
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↗