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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 1,081 records · Page 60Linked to original sources
PubMed1983

[Safety evaluation of micronomicin VIII. Teratogenicity studies in rabbits after intravenous injection].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rabbits were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 70 mg/kg). The results of studies are as follows. Fetal malformation attributable to MCR was not observed at any dose. There was no adverse effect on new borns at any dose.

Abnormalities, Drug-Induced↗
PubMed1983

[Safety evaluation of micronomicin IX. Perinatal and postnatal study by intravenous injection in rats].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Perinatal and postnatal studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. There was no adverse effect on delivery and nursing ability in dams at any dose. There was no adverse effect at any dose on postnatal development of offspring, such as weight gain, postnatal differentiation, spontaneous motor activity, learning, sexual maturation and reproductive performance. Renal toxicity was observed at dose of 75 mg/kg in autopsy of dams after treatment.

Aminoglycosides↗
PubMed1983

[Pharmacokinetic studies on micronomicin in dogs. Comparison of intramuscular and drip intravenous administration models].

The pharmacokinetics of micronomicin (MCR) were studied in dogs after intramuscular (i.m.) and drip intravenous (d.i.v., 0.5, 1 and 2 hours) administration (10 mg/kg). After i.m. administration, the plasma levels of MCR followed a one-compartment open model, and after d.i.v. administration it followed a two-compartment open model. The peak plasma levels of MCR after i.m., 0.5, 1 and 2 hours d.i.v. administration were 28.7 +/- 6.5, 36.7 +/- 3.6, 30.2 +/- 5.1 and 20.3 +/- 2.3 mcg/ml, respectively. The pharmacokinetic parameters (T1/2, AUC, Kel, Vd and Cl) of MCR except Cmax and Tmax were not differentiated by the route of administration. Urinary recovery of MCR after d.i.v. administration was equal to that of MCR after i.m. administration.

Aminoglycosides↗
PubMed1983

[Pulmonary metastasis of choriocarcinoma].

One hundred and sixty-five patients of choriocarcinoma were treated during the period from 1957 to 1979. Pulmonary metastases were found in 111 of the 165 patients. The authors found that surgical intervention for pulmonary metastasis was an extremely effective means for the patients who were not cured by chemotherapy and satisfied the criteria that we newly established for surgery. All patients satisfied the criteria achieved primary complete remission and their three years survival rate was 80%. The timing for surgery was also discussed and it was concluded that pulmonary surgery should be adopted when patient's urinary hCG values persisted at the level below 1000 iu/l for 70-80 days period.

Adult↗
PubMed1983

[Safety evaluation of micronomicin. I. Subacute and chronic toxicity in dogs].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR in dogs were carried out by intravenous injection for safety evaluation. 1. Study on subacute toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 4, 10, 25, 63 mg/kg and 100 mg/kg for 30 days. 2. Study on chronic toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 1.6, 4 mg/kg and 10 mg/kg for 180 days. The results of the studies are as follows: 1. In the subacute toxicity study, animals died at the dose level of 100g/kg (3 out of 6 animals). Main changes observed were renal disorders and ataxia which showed a close similarity to those seen during intramuscular toxicity studies in dogs. The renal histological disorders occurred at the dose levels of 10 mg/kg and over, but they were slight at the dose levels of 10 mg/kg and 25 mg/kg. Ataxia was observed at the dose levels of 63 mg/kg and over, but its grade was slight at the dose level of 63 mg/kg. 2. In the chronic toxicity study, animals did not die at any dose. Renal disorders occurred; they were almost similar to those observed in the subacute toxicity study and were slight at the dose level of 10 mg/kg. Ataxia was not observed at any dose. 3. The maximum safety dose was equal to in the subacute toxicity and chronic toxicity study (4 mg/kg). Therefore, cumulative toxicity by intravenous injection seemed very slight.

Aminoglycosides↗
PubMed1983

[Safety evaluation of micronomicin. II. Irritation by repeated intravenous injection in dogs].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. A study on the irritation by repeated intravenous injection in dogs was carried out for safety evaluation (Doses: 4, 10, 25, 63 mg/kg and 100 mg/kg). Bleeding, edema, vasculitis and perivasculitis were observed at injection sites both in physiological saline-treated controls and MCR-treated groups. But irritation attributable to MCR was not observed at any dose.

Aminoglycosides↗
PubMed1983

[Safety evaluation of micronomicin. III. Teratogenicity studies in rats].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. 1. Fetal malformation attributable to MCR was not observed at any dose. 2. Suppression of maternal weight gain was observed at the dose levels of 50 mg/kg and over. 3. There was no adverse effect on new borns at any dose.

Abnormalities, Drug-Induced↗
PubMed1983

[Effect of intravenous administration of micronomicin on the inner ear of guinea pigs].

The present experiment was made to clarify the effect of intravenous administration of micronomicin (sagamicin, MCR) on the inner ear of guinea pigs (300--350 g). MCR was given to the animals intravenously at dose of 25, 50 mg/kg and 100 mg/kg, respectively for 28 days. Pinna reflex test in frequency range from 20 kHz to 0.5 kHz was performed before, during and after the administration. The temporal bones were removed after intravital perfusion of the inner ears with neutral formation after the end of the administration. Histopathological examination was performed on the serial celloidin sections of the inner ears which had been stained with hematoxylin eosin. The following results were obtained. 1. MCR had a mild corti toxicity, which did not show remarkable dose dependent increase. 2. MCR had more affinity for the vestibular organs than for the organ of corti. The affinity for the vestibular organ increased with increase in dose. 3. MCR showed less increase in corti toxicity in intravenous administration than in intramuscular injection. However, the affinity of MCR for the vestibular organ showed little more increase in the intravenous administration than in the intramuscular injection.

Aminoglycosides↗
PubMed1983

[In vitro and in vivo antitumor activity of monoclonal anti-MM46 antibody-ricin A chain conjugate].

In an approach to antitumor agents with improved tumor specificity, the ricin toxic subunit A chain was covalently coupled with a monoclonal IgG2b antibody directed against MM antigen, a tumor-specific antigen on syngeneic mouse mammary tumor MM46 cells (anti-MM46 IgG), using N-succinimidyl-3-(2-pyridyldithio) propionate as cross-linking agent. The conjugate thus prepared (anti-MM46 conjugate) showed potent dose-dependent cytotoxicity against MM antigen-positive MM46 cells in vitro and inhibited the cell growth at concentrations above 1 micrograms/ml. The immunological specificity was verified by the observation that anti-MM46 conjugate did not show cytotoxicity against MM antigen-negative MM48 cells. In Winn-type tumor-neutralizing assay in which C3H/He mice were inoculated i.p. or s. c. with MM46 cells preincubated with a test material, anti-MM46 conjugate showed greater activity than did anti-MM46 IgG. When a group of five C3H/He mice inoculated i.p. with 5 X 10(4) MM46 cells were treated with an i.p. injection of 1 micrograms of anti-MM46 conjugate on days 1, 3, and 5, all five mice survived tumor free, although those treated with 1 micrograms of anti-MM46 IgG died before day 20 with a life span similar to those of mice treated with non-immune conjugate or phosphate-buffered saline (the control). Anti-MM46 conjugate also showed antitumor effects when injected i.v. to C3H/He mice bearing s. c. inoculated MM46 (inoculum, 4 X 10(6)) on day 1 at doses of 5 to 50 micrograms. Thus, the results demonstrated that in vivo efficacy of anti-MM46 conjugate over anti-MM46 IgG alone by therapeutic experiments as well as by tumor-neutralizing assay and suggested the potential use of monoclonal antibody-cytotoxic agent conjugates in cancer therapy.

Animals↗
PubMed1982

Polyamines alter the substrate preference of nuclear protein kinase NII.

When investigating the effects of polyamines on substrate specificity of adenosine cyclic 3', 5'-monophosphate (cAMP) independent nuclear protein kinase NII, we found that the substrate preference of NII was drastically altered in the presence of polyamines. When casein was used as a substrate, spermine stimulated the enzyme activity 7.3-fold at 2 mM, and a 6.5-fold stimulation was observed with 6 mM spermidine. Putrescine was also slightly effective at higher concentrations. With phosvitin as the substrate, however, 2 mM spermine and 4 mM spermidine strongly inhibited the activity by 93% and 80%, respectively, while putrescine showed a weak stimulatory effect. Steady-state kinetics and binding studies suggested that both stimulatory and inhibitory effects of polyamines on NII enzyme activity are probably due to substrate protein-polyamine interactions. The circular dichroism spectrum of phosvitin was apparently altered by spermine, whereas no significant change was observed with casein.

Animals↗
PubMed1982

Investigation of brachial plexus injuries by intraoperative cortical somatosensory evoked potentials.

With the intention of estimating the extent and site of damage in brachial plexus injuries which involve close to the root outlet and also the distal portion, cortical somatosensory evoked potentials (SEP) were recorded in 21 patients by directly stimulating the exposed brachial plexus. In 38 avulsed nerve roots which showed positive sensory action potentials (SNAP)/nerve action potentials (NAP) in their peripheral part, 15 roots (nine patients) were apparently in continuity and confirmed as root avulsion injury by the absence of cortical SEP. However, 11 roots (ten patients) which showed neither SNAP nor SEP would suggest either extensive lesions involving root and more distal segment or a combination of root avulsion and postganglionic injury. Fourteen patients who showed a positive Tinel's sign had at least one root with a postganglionic type lesion, but cortical SEP evoked by stimulation of the most proximal root zone sometimes revealed a reduced amplitude and prolonged latency. This would indicate the retrograde extension of damage. To confirm the extent and degree of the nerve lesions in brachial plexus injuries, an intraoperative SEP and NAP recording is very useful, practical, and also indispensable.

Adolescent↗
PubMed1982

A new stapling technique in esophageal mucosal transection.

Transabdominal esophageal mucosal transection for control of bleeding esophageal varices has been used in our clinic since 1972. The most difficult part in this procedure is the reanastomosis of the transected mucosal tube. To facilitate this procedure, end-to-end anastomosis (EEA) stapling instrument has been in use since July, 1980. Thirteen patients have so far undergone this procedure and there have been no complications. The technique of anastomosis of the mucosal tube is described herein.

Esophageal and Gastric Varices↗