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Biomedical subjects

K Saitoh

Publications and source records attributed to K Saitoh.

At least 253 records · Page 14Linked to original sources

Biosynthesis of the pradimicin family of antibiotics. II. Fermentation, isolation and structure determination of metabolites associated with the pradimicins biosynthesis.

Ten metabolites produced by 4 mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40, a high pradimicins producer, were isolated and their structures were determined. Strain JN-219 produced 3 novel analogs of the pradimicin A aglycone, i.e. 11-O-demethyl-7-methoxypradinone II and 11-O-demethylpradinones I and II together with a known aglycone analog, pradinone I, while the metabolites from strain JN-47 were determined to be 2 new aglycone analogs, 11-O-demethylpradimicinone I and 11-O-demethyl-7-methoxypradimicinone II and a known aglycone analog, 11-O-demethylpradimicinone II (11dM-PMN II). Products of strain JN-207 were identified as 11-O-demethyl-6-deoxypradinone I and 11dM-PMN II. Interestingly, a new pradimicin analog, 7-hydroxypradimicin A was isolated from strain JN-58 together with a new aglycone analog, pradimicinone II and 11dM-PMN II. None of these metabolites showed antifungal activity.

Actinomycetaceae↗

Biosynthesis of the pradimicin family of antibiotics. III. Biosynthetic pathway of both pradimicins and benanomicins.

The biosynthetic pathway of the pradimicin-benanomicin family of antibiotics was investigated by using sinefungin and blocked mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40 (a high pradimicin producer) or Actinomadura sp. AB1236 (a benanomicin producer). Addition of sinefungin to strain E-40, pradimicin A aglycone-producing mutant or strain AB1236 inhibited the formation of 11-O-demethyl-7-methoxypradinone II (11dM-7M-PN II), resulting in the accumulation of 11-O-demethylpradimicinone II and pradimicinone II. By feeding pradimicin A aglycone and its analogs to mutants blocked early in pradimicin or benanomicin biosynthesis, the following results were obtained: 11-O-demethylpradinone II, 11dM-7M-PN II 11-O-demethylpradinone I, 11-O-demethylpradimicinone I and pradimicinone I were converted to pradimicin A or benanomicin A; the remaining 6 aglycone analogs were not incorporated into the antibiotics. Pradimicin B, dexylosylpradimicin C and dexylosylbenanomicin A were converted to pradimicin A, pradimicin C and benanomicin A, respectively. A biosynthetic pathway for the antibiotics is proposed.

Actinomycetales↗

Pradimicin S, a new pradimicin analog. I. Taxonomy, fermentation and biological activities.

A directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of HeLa-T4 cells expressing CD4 antigen and BSC-1 cells expressing gp-120 led to the isolation of pradimicin S, a new member of the pradimicin family. The producing strain (AA0851) was characterized as a new species of Actinomadura for which the name Actinomadura spinosa sp. nov. is proposed. Production of pradimicin S by strain AA0851 was significantly improved by addition of ferrous sulfate (0.1-0.4%) to the production medium. Pradimicin S showed potent activity against human immunodeficiency virus (HIV) LAVBRU strain in a CPE assay, and moderate activity against influenza virus type A. The antibiotic was active against a wide variety of fungi and yeasts in vitro and demonstrated in vivo efficacy against a systemic Candida albicans infection in mice.

Actinomycetaceae↗

Inhibition of ATPase activity in pea plasma membranes by fungal suppressors from Mycosphaerella pinodes and their peptide moieties.

The effects of two suppressors of the defense reactions of host plants, which had been purified from the pea pathogen Mycosphaerella pinodes, as well as the effects of peptide moieties, on the ATPase activity in pea plasma membranes were examined in vitro. One of the suppressors, Supprescin B, inhibited the ATPase activity in a non-competitive manner, but the other suppressor, Supprescin A, did not. Supprescin A was observed to reduce the inhibitory effect of Supprescin B. A tripeptide, Ser-Ser-Gly, and a hexapeptide, Ser-Ser-Gly-Asp-Glu-Thr, which were the respective peptide moieties of Supprescin A and B, inhibited the ATPase activity in a competitive manner. Supprescin B and fragments of the hexapeptide, such as Asp-Glu-Thr and Gly-Asp-Glu, inhibited not only the ATPase activity but also the acid phosphatase activity of plasma membranes in vitro. These results indicate that the acidic amino-acid residues of the "Asp-Glu" moiety seem to act as inhibitors of the phosphatase activity. Thus, the peptide moiety of Supprescin B consists of at least two functional elements.

Acid Phosphatase↗

Synthesis and biological activity of 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethylarabinofuranosyl)-cytosines.

We newly synthesized 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethyl-arabinofuranosyl)cytosines and evaluated their biological activities. The syntheses of these compounds were achieved by radical deoxygenation of tert-alcohol of 2'-position of the corresponding fluorohydrine and acetoxymethyl derivative. 1-(2-Deoxy-2-C-fluoromethylarabinofuranosyl)cytosine (5) showed potent antileukemic and anticytomegalovirus activities.

Antineoplastic Agents↗

[Comparison of the severity of postoperative pain in patients after thoracic, upper abdominal or lower abdominal surgery].

Different factors influence the severity of postoperative pain. Personality and cultural factors as well as anxiety and fear modify the degree of postoperative pain. The site of surgery is also a major determinant. We evaluated the severity of postoperative pain in patients after three different surgeries, thoracic, upper abdominal and lower abdominal surgeries, from 24 h to 72 h postoperatively. Thirty patients were divided into three groups: thoracic, upper abdominal and lower abdominal groups (n = 10, respectively). All patients received continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) and buprenorphine (0.2 mg x 24 h-1). Additional analgesics were given when the patient complained of pain. Analgesia was evaluated by 100 mm visual analog scale and demands of analgesics. Pain scores at rest were not different among three groups. Pain after lower abdominal surgery tended to be less severe compared with that after thoracic surgery. Demands of analgesics were not different among three groups at any evaluated point. Pain after thoracic surgery was consistent during 72 postoperative hs, but in the upper and lower abdominal surgery groups pain at 72 hs was significantly weaker than that at 24 hs. We conclude that postoperative pain was not different among the three surgery groups, but pain after upper and lower abdominal surgery decreased more rapidly compared with that after thoracic surgery.

Abdomen↗

[Continuous epidural buprenorphine for postoperative pain relief in patients after lower abdominal surgery].

Postoperative analgesia with epidurally injected buprenorphine and its side effects were investigated in 100 patients who had received lower abdominal surgery. All patients received initially 8 ml of bupivacaine and 0.1 mg of buprenorphine. Following bolus epidural injection, five different groups of 20 patients each received either bupivacaine alone (group A), 5 micrograms.ml-1 buprenorphine.bupivacaine mixture (group B), 8 micrograms.ml-1 buprenorphine.bupivacaine mixture (group C), 12 micrograms.ml-1 buprenorphine.bupivacaine mixture (group D), or 15 micrograms.ml-1 buprenorphine.bupivacaine mixture (group E) by a portable disposable device at a rate of 1 ml.h-1 for 48 h. The analgesic efficacy in group E was superior to those in groups A, B, C or D. No significant difference in the incidence of side-effect was found among groups C, D, E. We conclude that a dose of a approximately 15 micrograms.h-1 might be optimal for postoperative pain relief after lower abdominal surgery.

Abdomen↗

[Patient-controlled analgesia with epidural pethidine or buprenorphine plus bupivacaine for postoperative analgesia].

We evaluated the efficacy of epidural patient-controlled analgesia (PCA) with pethidine or buprenorphine plus 0.25% bupivacaine for postoperative analgesia after laparotomy with a midline incision under general anesthesia. Twenty patients were randomly allocated to two groups. In one group (PCEA-P group; n = 10), epidural pethidine plus 0.25% bupivacaine by PCA with 5 mg of pethidine and 2.5 ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to a continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) plus pethidine (100 mg.24h-1) for 72 h. In the other group (PCEA-B group; n = 10), epidural buprenorphine plus 0.25% bupivacaine by PCA with 0.03 mg of buprenorphine and 2.5 ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to a continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) and buprenorphine (0.6 mg.24 h-1) for 72 h. Analgesia was evaluated by 100 mm visual analog scale and verbal descriptor scale. In PCEA-B group, 90% of the patients did not complain of pain at rest, and in PCEA-P group, all the patients did not complain of pain at rest for 72 h. There were no significantly different analgesic effects between PCEA-P and PCEA-B for 48 h. The average doses of epidural PCA were 1.9 mg.kg-1.24 h-1 of pethidine, and 0.012 mg.kg-1.24 h-1 of buprenorphine, respectively. We conclude that PCEA-P and PCEA-B were effective for postoperative pain to the same degree for the first 48 h, but PCEA-P was superior to PCEA-B for the last 24 h.

Abdomen↗

[Spread of spinal anesthesia with 0.5% isobaric bupivacaine].

The effects of age, weight, height, weight.height ratio, and body mass index on the spread of spinal anesthesia with 3.0 ml of 0.5% isobaric bupivacaine was examined in 185 patients. No significant correlation was found between the spread of analgesia and the age, weight, height, weight.height ratio, or body mass index. A significant correlation was found between the decrease in mean arterial pressure and the height of sensory analgesia (rho = -0.21, P < 0.05) as well as the aging (rho = -0.35, P < 0.001).

Adolescent↗

[Rapid induction of anesthesia with inhalation of sevoflurane].

Induction of anesthesia with inhalation of sevoflurane was evaluated in 45 patients. Inhalation anesthesia was induced by a single vital capacity breath followed by spontaneous breathing. The compositions of anesthetic gases were as follows: 5% sevoflurane in oxygen, 5% sevoflurane in 67% nitrous oxide and oxygen, and 7% sevoflurane in 67% nitrous oxide and oxygen. The time (mean +/- SEM) necessary for the loss of consciousness was 85 +/- 6, 56 +/- 4, and 42 +/- 3 seconds, and breathing frequency was 8 +/- 1, 5 +/- 0.6, 1.4 +/- 0.2, in each composition of anesthetic gasses, respectively. Changes in blood pressure and heart rate were relatively small. The technique was found to be acceptable to all of the patients studied. We conclude that the technique of single breath induction with sevoflurane is a safe and acceptable alternative to intravenous induction in cooperative adult patients.

Adult↗

[Postoperative pain therapy: a survey of patient attitudes to postoperative pain relief].

We surveyed the attitudes of general surgical patients to the management of their postoperative pain relief. Elective surgical patients (n = 232) were asked postoperatively about their experienced pain which was expressed according to verbal pain scale, the duration of experienced pain, satisfaction with pain relief and medication, and expectations of pain on the 5th to 7th postoperative day. Thirteen percent of the patients had no pain, 47% of whom had no rest pain but pain on moving or coughing, 32% of whom had rest and moving pain, and 0.4% of whom experienced horrible and excruciating pain. Duration of postoperative pain was 2.5 +/- 1.9 days, and 76% of the patients experienced pain only for 3 postoperative days. Results of the interviews indicated that 80% of these patients were satisfied with their postoperative pain relief. Although 80% expressed satisfaction, 39% of whom did have rest pain. In the patients with continuous epidural infusion of buprenorphine and 0.25% bupivacaine, incidence of complained rest pain was significantly low compared with those with intermittent i.v. and/or im injection of analgesics on demands of patients. Lag between patient's demand and nurse's response concerning medication correlated significantly to the satisfaction. There was no relation between satisfaction and age, the nature of operation or sex. Fifty-two percent of the patients reported that degree of experienced pain had been less than expected preoperatively. In conclusion, 80% of the patients were satisfied, but our postoperative pain therapy was still insufficient because 39% of them had rest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Serum nitroglycerin concentrations during extracorporeal circulation with a membrane oxygenator incorporated with a cardiopulmonary bypass circuit].

The effect of a cardiopulmonary bypass circuit (CPB) on serum nitroglycerin (TNG) concentrations was studied in eight patients scheduled for cardiac surgery. The CPB consisted of polyvinyl chloride tubes and polypropyrene membrane oxygenator. TNG was administered intravenously at a rate of 1 microgram.kg-1.min-1 after induction of anesthesia. Blood samples were obtained from the radial artery, central vein, venous inlet of the CPB, and arterial outlet of the CPB. No significant difference in serum TNG concentration was found between the venous inlet of the CPB and arterial outlet of the CPB. Serum TNG concentration tended to increase during complete extracorporeal circulation. This suggests that the hypothermic inhibition of TNG metabolism may be greater than the adsorption of TNG by the CPB.

Adolescent↗

[Effect of age on dose requirement for lumbar epidural anesthesia].

In 161 patients, aged 19-75 yr and subjected to epidural anesthesia for extracorporeal shock wave lithotripsy, the relationships between the spread of lumbar epidural analgesia with 10 ml of 2% mepivacaine and age, height, weight, weight/height ratio, and body mass index were studied. The highest correlation was found between the age and the spread (r = 0.67, P < 0.001). The next higher correlation was found between the height and the spread (r = -0.32, P < 0.001). The lowest but a statistically significant correlation was found between the body mass index and the spread (r = 0.16, P < 0.05). A strong inverse linear relationship was found between the age and the epidural dose requirement (r = -0.59, P < 0.001).

Adult↗

[Evaluation of the efficacy of a leukocyte depletion filter].

We evaluated the efficacy of a leukocyte depletion filter (Pall RC 100) during operation. Clinically necessary blood was transfused to replace blood loss during the operation. Kinds of transfused blood and speed of transfusion were selected by clinical need. One leukocyte depletion filter was used at most for 4 units of transfused pack (200 ml). Blood samples were taken before and after the filtration to measure white blood cell (WBC), red blood cell (RBC), platelet and hematocrit. Blood samples before filtration and after filtration with white blood cell excluded, were examined by automated hematology analyzer (Coulter counter). White blood cell after filtration was counted by the hemacytometer method using Hauser chamber. The method of multiple linear regression was applied in order to estimate the removal rate of WBC and recovery rate of RBC. The independent variables were categorized in the following 3 sets: the age of transfused blood (day), duration of transfusion (min) and transfused volume (ml). Removal rates of WBC when 1, 2, 3 or 4 units were passed per filter, were 99.99% +/- 0.028%, 99.89% +/- 0.224%, 99.12% +/- 1.519% and 97.81% +/- 2. 866%, respectively. Removal rate of WBC when 4 units were passed per filter, was significantly lower compared with the rate when fewer units were passed. Recovery rates of RBC when 1, 2, 3, or 4 units were passed per filter, were over 99.5%, and there were no significant differences among 4 examined points. Only three variables, the age of transfused blood, duration of transfusion and transfused volume, showed a significant correlation with the removal rate of WBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

An infant with both autoimmune neutropenia and idiopathic thrombocytopenia with IgG2/IgA deficiency.

We report an infant with autoimmune neutropenia (AIN), idiopathic thrombocytopenia (ITP), and IgG2/IgA deficiency. The patient was referred to our hospital at 5 months of age because of epistaxis and generalized petechiae. Physical examination revealed moderate hepatosplenomegaly. A complete blood count revealed a platelet count of 2.0 x 10(3) cells/microliters, and a white cell count of 3,600 cells/microliters, with severe neutropenia (less than 1% bands and segmented cells). Neutrophils and platelets adhering to megakaryocytes were decreased in the bone marrow. Tests for serum neutrophil-binding IgG (NB-IgG) and platelet-associated IgG (PA-IgG) were positive. A diagnosis of both AIN and ITP was made and therapy with intact-type gamma-globulin and prednisolone was initiated. Improvement occurred, but was temporary. A lack of serum IgA and IgG2 was noted during the clinical course. The patient has not been susceptible to bacterial infections but has had a severe clinical course with rubella and chickenpox.

Autoimmune Diseases↗

[Sevoflurane anesthesia in a patient following renal transplantation].

A 29-year-old male after renal transplantation with aseptic necrosis of the head of the left femur was anesthetized with sevoflurane-nitrous oxide-oxygen for replacement surgery. Anesthesia was induced with N2O 4 l.min-1, O2 2 l.min-1, plus sevoflurane and maintained with N2O4 l.min-1, O2 2 l.min-1 and sevoflurane. Sevoflurane concentrations ranged from 1% to 4%. The serum inorganic fluoride showed the peak level of 38.4 microM.l-1 about 60 minutes after discontinuation of sevoflurane a decrease in serum inorganic fluoride was delayed. Urinary N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP) and beta 2-microglobulin (beta 2-m) increased over five postoperative days. NAG and gamma-GTP returned to the preanesthetic level on the 6th postoperative day, but beta 2-m higher than the preanesthetic level lasted for 14 postoperative days. In conclusion, sevoflurane brought about little effect on the transplanted kidney in this patient.

Adult↗