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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

196 records · Page 11Linked to original sources

Radioreceptor assay for insulin.

A sensitive and simple radioreceptor assay (RRA) capable of detecting 10 muU/ml of serum insulin has been developed using the crude membrane fraction of guinea pig kidney and 125I-porcine insulin. Using this assay system, serum insulin during 100 g oral glucose tolerance tests in six males including one obese man was measured. The mean concentration of serum insulin increased from 19 muU/ml during fasting to maximum of 90 muU/ml after 60 min of glucose load and then gradually declined to 38 muU/ml by 180 min. The values obtained by the present RRA agreed well with immunoreactive insulin (IRI).

Glucose Tolerance Test↗

Enzymatic radioiodination of succinyl cyclic AMP tyrosine methyl ester by lactoperoxidase and radioimmunoassay for cyclic AMP.

A highly specific and simple radioimmunoassay for cyclic AMP with a sensitivity of 0.04 picomoles/tube has been developed according to the method of Steiner et al., using 125I-succinyl cyclic AMP tyrosine methyl ester as a tracer. The tracer with higher immunoactivities could be simply and constantly prepared by an enzymatic iodination procedure utilizing lactoperoxidase, radioactive iodide and hydrogen peroxide generated by glucose-glucose oxidase system, rather than by chloramine-T procedure.

Adipose Tissue↗

Chemiluminescence sandwich enzyme immunoassay for determination of human granulocyte colony stimulating factor (G-CSF).

A chemiluminescence sandwich enzyme immunoassay, using a glucose oxidase (GO) label, was developed for detecting attomole amounts of human granulocyte colony stimulating factor (G-CSF). Purified goat (F(ab')2 immobilized on a bead and purified goat Fab' labelled with GO were selected in combination with a chemiluminescent detection system comprising luminol and ferricyanide. The detection limits for G-CSF were 4amol/assay (1 pg/mL) in buffer solution and 10 amol/assay (2.5pg/mL) in human serum. Coefficients of variation within assay and between assay ranged from 5.5% to 7.8% and from 3.4% to 16.0%, respectively. The C-CSF content of serum from normal healthy individuals was measurable using this method. G-CSF in 24 normal human sera showed a mean value of 19.3pg/mL and ranged from 3.6 to 83.0pg/mL.

Animals↗

Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.

Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

Acarbose↗

Lignified materials as potential medicinal resources. II. Prevention of pathogenic bacterial infections in mice.

Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E. coli or P. aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi. Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection.

Animals↗

Antimicrobial spectrum of lignin-related pine cone extracts of Pinus parviflora Sieb. et Zucc.

Pine cones of Pinus parviflora Sieb., et Zucc, were extracted successively with 5% NaHCO3, 3% NH4OH, 1% NaOH and 4% NaOH, and the extracts were tested for ability to induce antimicrobial activity in mice infected with Staphylococcal aureus. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, or Salmonella enteritidis. These alkaline extracts were potent against the first 5 of these strains of microorganisms, and the activity was recovered mostly from their acid-precipitates at pH 5. After further fractionation on a Sephadex LH-60 column, the highest molecular weight fraction was most potent. Chemical structures in these bioactive fractions were assumed to be lignin-related structures, based on spectral data from UV, NMR and IR spectroscopy.

Anti-Bacterial Agents↗

Chemical modification potentiates paramylon induction of antimicrobial activity.

Induction of antimicrobial activity by two water-insoluble polysaccharides, paramylon and TAK, was significantly potentiated by introduction of positively charged groups (such as N,N-dimethylaminoethyl; N,N-diethylaminoethyl; and 2-hydroxy-3-trimethylammoniopropyl), but not by introduction of negatively charged groups (such as carboxymethyl or sulfate). Cross-linking of these derivatives with epichlorohydrin did not increase their potentiating activity. The effects of these derivatives did not always correlate with their ability to accumulate polymorphonuclear cells and to stimulate the generation of luminol-dependent chemiluminescence by peritoneal exudate cells.

Animals↗

Deterministic chaos in the hemodynamics of an artificial heart.

To analyze the hemodynamic parameters during prosthetic circulation as an entity, non linear mathematical techniques were used. To compare natural and prosthetic circulation, two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses in chronic animal experiments using adult goats to consitute the biventricular bypass complete prosthetic circulation model with ventricular fibrillation. After implantation, these goats were placed in a cage and extubated after waking. All hemodynamic parameters with the natural circulation without biventricular bypass pumping, and the artificial circulation with biventricular bypass pumping under ventricular fibrillation were recorded under awake conditions. By the use of a non linear mathematical technique, the arterial blood pressure waveform was embedded into a four dimensional phase space and projected into three dimensional phase space. The Lyapunov numeric method is used as an adjunct to the graphic analysis of the state space. A phase portrait of the attractor showed a high dimension complex structure, with three dimensional solid torus suggesting deterministic chaos during natural circulation. However, a simple attractor, such as a limit cycle attractor, was observed during artificial circulation. Positive Lyapunov exponents during artificial circulation suggest the lower dimensional chaotic system. Thus, hemodynamic parameters during prosthetic circulation must be carefully controlled when unexpected stimuli are fed from outside.

Animals↗

A phase II multi-institutional study of estra-1,3,5(10)-triene-3,17 beta-diol, 3-benzoate, 17[[4-[4-[bis(2-chloroethyl)amino]phenyl]-1- oxobutoxy]acetate] (KM2210), a novel antitumor agent, for advanced and recurrent breast carcinoma.

In order to evaluate the efficacy of Estra-1,3,5(10)-Triene-3,17 beta-Diol, 3-Benzoate, 17[[4-[4-[Bis(2-Chloroethyl) Amino]Phenyl]-1-Oxobutoxy] Acetate] (KM2210), a multi-institutional cooperative Phase II study was performed in patients with measurable advanced and recurrent breast cancer. Two hundred miligrams of KM2210, a conjugate of chlorambucil and 17 beta-estradiol, were administered orally daily for more than 4 weeks to each patient. According to the WHO criteria of response, 103 evaluable cases were assessed. Complete response was obtained in 9 cases, partial response in 19, no change in 39 and progressive disease was observed in 36. The overall response rate was 27.2% (28/103). The response rate was higher in patients without prior treatment than in those with prior treatment. However, KM2210 was also effective against breast cancers treated previously with tamoxifen, anthracyclines and their combinations, showing response rates of 25.5%, 22.0% and 29.6% respectively, suggesting that this agent is also effective on breast carcinomas which were insensitive to tamoxifen and anthracyclines. For efficacy classified in terms of metastatic lesions, the response rate was significantly higher in soft tissues than in other involved organs, and the response rate of bone metastasis was limited. Bone marrow suppression, including leukopenia and thrombocytopenia, was thought to be the dose-limiting toxicity of KM2210. Genital bleeding due to the released estrogen was observed as a characteristic side effect. KM2210 is considered to be useful for the treatment of advanced and recurrent breast cancer when administered at a dose level of 200 mg per day for more than 4 weeks.

Adult↗

Mode of action of estra-1,3,5(10)-triene-3, 17 beta-diol, 3-benzoate, 17[4-[4-[bis(2-chloroethyl)amino]phenyl]-1-oxobutoxy] acetate] (KM2210) on MCF-7 human breast tumours transplanted into nude mice.

KM2210 is a benzoate of an estradiol-chlorambucil conjugate with three active metabolites, KM2202, estradiol (E2) and chlorambucil (CBL). The mode of action of this compound was assessed using MCF-7 human breast tumours transplanted into nude mice. The growth of MCF-7 in nude mice was inhibited by KM2210 and enhanced by E2, although the serum levels of E2 in nude mice treated with KM2210 and E2 were similar. The antitumour activity of CBL was completely blocked by extrinsic E2, while KM2210 suppressed the growth of MCF-7 in spite of the presence of E2 in the serum of tumour-bearing nude mice. KM2210 and KM2202 suppressed the expression of cytosol estrogen receptor (ER) of MCF-7 cells detected by the dextran-coated charcoal and fluorescent E2 staining method, although CBL did not affect the ER expression of MCF-7 cells. This inhibitory effect of KM2210 on ER was also corroborated by the fact that the pretreatment with KM2210 prevented the E2-stimulated growth of MCF-7 in nude mice. These results indicated that one of the effects induced by KM2210 is the blockage of ER expression in combination with the alkylating antitumour activity of CBL. KM2210 is thought to be a promising agent with unique modes of action for ER-positive breast carcinomas.

Animals↗