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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 1,027 records · Page 57Linked to original sources

Subcapsular phacoemulsification and aspiration.

To protect the corneal endothelium from ultrasound damage, we performed phacoemulsification under the anterior capsule on 26 eyes of 21 patients between January 7, 1980, and September 1, 1980. Patients were followed for at least three years. In 20 eyes, various intraocular lenses were implanted. The average corneal endothelial cell loss in all eyes was 12.0 +/- 7.4% (M.S.D.), range 1.3% to 36.2%. In six eyes without intraocular lens implantation, the average cell loss was 6.9 +/- 3.0% (M.S.D.), range 1.3% to 10.0%. The best postoperative visual acuity was 20/40 or better in all patients. Intraoperative and postoperative complications occurred in 11 eyes (42.3%), including three (11.5%) posterior capsule ruptures. All complications were managed satisfactorily.

Aged↗

A novel method of conjugation of daunomycin with antibody with a poly-L-glutamic acid derivative as intermediate drug carrier. An anti-alpha-fetoprotein antibody-daunomycin conjugate.

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunomycin (DM) was first linked to a poly-L-glutamic acid (PLGA) derivative having a single masked thiol group. At the thiol group, DM-linked PLGA was bound to horse anti-rat alpha-fetoprotein (AFP) antibody. The anti-AFP antibody-PLGA-DM conjugate (anti-AFP conjugate, DM/PLGA/Ig molar binding ratio, 7.5/1.2/1.0) retained most of the antigen-binding activity of the parent antibody and was more potent than either unconjugated DM, a conjugate similarity prepared with normal horse immunoglobulin (normal conjugate), or an unconjugated mixture of anti-AFP antibody and DM in an in vitro cytotoxicity assay against the AFP-producing rat ascites hepatoma cell line AH66. Anti-AFP conjugate tended to be less cytotoxic than DM against the AFP-nonproducing rat ascites hepatoma AH272 cells, and in this case there was no difference between the cytotoxicities of anti-AFP conjugate and of normal conjugate.

Animals↗

Central nervous system complications in childhood leukemia. Correlation between clinical and computed tomographic findings.

We used cranial computed tomography (CT) to evaluate 51 leukemic patients with or without central nervous system (CNS) symptoms. Among 17 symptomatic patients, nine had gross abnormalities on CT scans; leukemic infiltrations, infections (CNS aspergillosis), hemorrhages, and therapy-related complications were all evident. One with a leukemic infiltration showed a periventricular low density on the CT scans. The differential diagnosis of CT findings and the correlation between clinical and CT findings is described. The significance of a low-density area observed in an asymptomatic patient on long-term intrathecal methotrexate therapy for CNS leukemia is also discussed.

Brain↗

In vitro and in vivo antibacterial activities of MT-141, a new semisynthetic cephamycin, compared with those of five cephalosporins.

The in vitro and in vivo antibacterial activities of MT-141 were compared with those of cefoxitin, cefmetazole, moxalactam, cefotaxime, and cefoperazone. The MICs of MT-141 for 90% of bacterial isolates were lower than the reference drugs against clinical isolates of Campylobacter jejuni, Clostridium difficile, and Bacteroides fragilis, whereas against clinical isolates of other gram-positive, gram-negative, and anaerobic bacteria, the MICs of MT-141 were similar to or higher than those of the reference drugs. In contrast, the bactericidal activity of MT-141 after 6- and 24-h exposures was superior to all of the reference drugs against 9 to 10 of the 12 bacterial strains studied, including Escherichia coli, Klebsiella pneumoniae, Salmonella enteritidis, indol-positive Proteus species, Serratia marcescens, Yersinia enterocolitica, Pseudomonas cepacia, and Clostridium perfringens. In the treatment of systemic infections in mice, MT-141 was again superior against 9 of the 12 strains tested, showing a good correlation with the bactericidal activity. It was found that the 50% effective doses of the six cephalosporins studied correlated better with the MBCs than with the MICs. As the serum levels of MT-141 in mice after subcutaneous administration were similar to those of the reference drugs, it was concluded that the bactericidal activity of MT-141 was a dominant factor in its in vivo activity.

Animals↗

High-dose 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitro sou rea hydrochloride (ACNU) with autologous bone marrow rescue for patients with brain stem tumors.

4 patients with brain stem tumors were treated with high-dose ACNU with autologous bone marrow rescue. Hematologic and nonhematologic toxicities were not profound. There was objective evidence of response in 2 out of the 4. All were alive for 11-21 months from onset. Safe administration of high-dose ACNU with marrow rescue will warrant further control studies to determine its superiority over conventional doses.

Astrocytoma↗

Effects of ovine corticotrophin-releasing factor and hydrocortisone on growth hormone secretion by pituitary adenoma cells of acromegaly in culture.

In an attempt to test the hypothesis that pituitary adenomas of acromegaly may possess altered cellular membrane receptors, the response of growth hormone (GH) secretion to ovine corticotrophin-releasing factor (CRF) in cultured adenoma cells of acromegaly was studied. In three out of seven experiments using different pituitary adenoma cells in culture, nanomolar concentrations of CRF caused a significant increase in GH release. The CRF-induced GH release was reproducible and a dose-response relationship was observed between the CRF concentrations and the amounts of GH released into the incubation media. Hydrocortisone, at a concentration of 1 microM, on the other hand, resulted in a significant decrease in GH secretion in four out of five experiments. When adenoma cells were co-incubated with CRF and 1 microM hydrocortisone, CRF-induced GH release was partially overcome. In one experiment, the inhibitory effect of hydrocortisone was reversed by co-incubation with CRF, although CRF alone was ineffective in the stimulation of GH. These results suggest that CRF may stimulate GH release in some, though not all, patients with acromegaly, and that glucocorticoids may block this effect of CRF acting directly on the pituitary adenoma cells of acromegaly.

Acromegaly↗

Susceptibility of Kintoki bean lectin to digestive enzymes in vitro and its behavior in the digestive organs of mouse in vivo.

The enzymatic digestion of a Kintoki bean lectin in vitro resulted in neither the extensive hydrolysis nor complete inactivation of the lectin. The majority of [3H]lectin administered to mice by stomach-intubation was found in the digestive tract at levels of 88.7%, 99.4%, 99.5% and 78.6%, after 0.5, 2, 5 and 24h of intubation, respectively. Twenty to forty percent of the administered radioactivity was found combined with the mucosa of the small intestine. After 24 h of intubation, part of the radioactivity was found in the feces. The recovery test of hemagglutinating activity and the molecular weight determination of the lectin administered to and recovered from mice revealed that more than 70% of the radioactivity detected in the digestive tract represented intact lectin. Therefore, it was concluded that most of the Kintoki bean lectin survived its passage through the gastrointestinal tract. The lectin-binding sites in the intestinal mucosa were traced with fluorescence microscopy using the lectin conjugated with fluorescein isothiocyanate. The fluorescent sites were found located at the top and upper sites of the villi, but not at the crypt.

Animals↗

[Cerebral metastasis of choriocarcinoma].

One hundred and eighty-two cases of choriocarcinoma were treated in our clinic during the 26 years period from 1957 to 1982. Forty-one patients among them (2.3%) had cerebral metastases. Analysis on the autopsy findings of patients with cerebral metastases of choriocarcinoma proved neurosurgical resectability in most cases. Craniotomy and removal of cerebral metastatic lesion has been adopted since 1972, and a significant difference was noted in the surviving time between surgically treated group and the group without surgery. The risk factors for developing brain metastases were analyzed. Patients whose uterine lesion showed immature type of histopathology (p less than 0.01), patients without uterine lesion (p less than 0.05) and patients with pulmonary metastasis (p less than 0.01) had higher risk of developing cerebral metastasis.

Adolescent↗

Decreased serum levels of various hydrolytic enzymes in patients with rheumatoid arthritis.

It is known that the serum level of glycylproline aminopeptidase (Gly-Pro-AP) is decreased in the patients with rheumatoid arthritis. In the present study, the serum levels of various hydrolytic enzymes were tested in such patients. In comparison to the controls, many enzymes, including Ala-AP, Ser-AP, Phe-AP, Gly-Pro-AP, Gly-Pro-Leu-AP, dipeptidyl carboxypeptidase (angiotensin converting enzyme), and esterase, showed significantly decreased activities in the patients' sera. Only the activity of Trp-AP was significantly increased. Of these enzymatic activities in serum, several ones including those of Gly-Pro-AP, Ala-AP, Phe-AP, trypsin-like enzyme, and esterase, were significantly correlated with the severity of the disease. Although a part of these findings are compatible with previous observations, they suggest rather more extensive disorders of peptide metabolism in this immunological disease.

Acetylcholinesterase↗

Different tendencies of changes in hydrolytic enzyme activities in sera from prostatic cancer patients with or without bone metastasis.

Serum levels of various hydrolytic enzymes in prostatic cancer patients with or without bone metastasis were compared with those in patients with prostatic hypertrophy and in the control subjects. The enzymes tested included 11 aminopeptidases, 2 endopeptidases, dipeptidyl carboxypeptidase, esterase, acetyl cholinesterase, and RNase. Although most of the enzymatic levels tended to be decreased in the cancer patients without bone metastasis, they tended to be increased in those with metastasis as well as in the patients with prostatic hypertrophy. Thus, bone metastasis is an important factor affecting the serum levels of hydrolytic enzymes in cancer patients. Of the enzymes tested, RNase was unique in that its serum levels were significantly increased regardless of the existence of bone metastasis. This enzyme may become a marker of malignancy.

Aged↗

[Antibacterial activity of MT-141 against anaerobic bacteria].

In vitro and in vivo antibacterial activities of MT-141, a new cephamycin, against anaerobic bacteria were compared with those of cefmetazole (CMZ), cefoxitin, cefotaxime, ceftizoxime, latamoxef and cefazolin to obtain the following results. MT-141 showed high activity against a wide variety of anaerobic bacteria including B. fragilis and C. difficile except for Eubacterium lentum, E. aerofaciens and B. furcosus. Antibacterial activity of MT-141 against anaerobic bacteria was almost independent of inoculum size, medium, pH and serum addition. In vitro development of resistance of MT-141 against P. variabilis and B. fragilis was comparable to that of CMZ. Successive parenteral administration of MT-141 into mice did not cause abnormal proliferation of C. difficile. MT-141 showed excellent therapeutic effect against experimental subcutaneous abscess in mice caused by B. fragilis.

Animals↗

Antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugated with polyglutamic acid and its derivative.

Four types of 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates with poly-L-glutamic acid (PLGA) or poly-N5-(2-hydroxyethyl)-L-glutamine (PHEG) were prepared in an attempt to enhance the efficacy of the drug in simple dosage schedules. The conjugates were made by linking ara-C to the carboxyl groups of PLGA directly at N-4 of ara-C (ara-C:PLGA) or indirectly through the 2-aminoethylphosphoryl or 6-aminohexylphosphoryl side chain which had been introduced to C-5' of ara-C, 1-[5'-(2-aminoethylphosphoryl)-beta-D-arabinofuranosyl]cytosine: PLGA [araCMP(C2):PLGA and 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PLGA, respectively, or made by converting the remaining carboxyl groups in the PLGA conjugates to the 2-hydroxyethylamide groups [ara-C:PHEG, ara-CMP(C2):PHEG, 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PHEG]. Studies in vitro showed that the conjugates had decreased cytotoxicity against L1210 cells when compared with that of ara-C. Studies in vivo showed that all of the conjugates, except ara-CMP(C2):PLGA, had a greater antitumor activity than did ara-C in L1210 tumor-bearing BALB/c X DBA/2 F, (hereafter called CD2F1) mice (inoculum, 1 X 10(5) cells i.p. on Day 0) which were treated by a single i.p. injection of either the conjugates or the control ara-C on Day 1. The largest antitumor activity [increased life span (ILS) 170%] was observed with a dosage of 50 mg (equivalent ara-C per kg) of ara-C:PHEG. When CD2F1 mice which had been inoculated i.p. with 1 X 10(5) L1210 cells were treated with an i.p. injection of 12.5 or 25 mg (equivalent ara-C per kg) of ara-C:PHEG daily for 5 days starting from Day 1, 2 of 5 mice survived more than 42 days, and the ILS of the remaining mice was 153 and 184%. The injections of 3.2 mg (equivalent ara-C per kg) of ara-C:PHEG showed a moderate antitumor activity with an ILS of 113% which was similar to the ILS (119%) found when unconjugated ara-C (400 mg/kg) was used to treat tumor-bearing mice. In in vitro release experiments, ara-C was released slowly from ara-C:PLGA at pH 7.4, and ara-CMP(C2):PLGA was chemically stable but cleaved by phosphodiesterase, acid phosphatase, and alkaline phosphatase to give mainly 1-beta-D-arabinofuranosylcytosine 5'-monophosphate.

Animals↗

An anti-alpha-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier.

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunorubicin [(DM) daunomycin] was conjugated with an affinity-purified horse antibody to rat alpha-fetoprotein (AFP) with a novel derivative of poly-L-glutamic acid (PLGA) as the intermediate drug carrier. A single masked thiol group first was introduced by PLGA, and the thiol group was generated from it after the linking of DM to PLGA at the carboxyl groups of PLGA. The thiol group was used selectively for binding PLGA-DM to antibody that had been modified so as to have the maleimide groups. The conjugates (DM:PLGA:immunoglobulin molar ratio, 19.6:2.8:1 or 11.8:1.1:1) were more potent than DM in in vitro cytotoxicity against the AFP-producing rat ascites hepatoma cell line AH66. In therapeutic experiments, the conjugates were more efficacious in prolonging the lives of AH66 hepatoma-bearing DONRYU rats than DM, antibody, a mixture of DM and antibody, or a conjugate similarly prepared with normal horse immunoglobulin.

Animals↗