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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,063 records · Page 59Linked to original sources

[Combination chemotherapy with vincristin, actinomycin D, cyclophosphamide and adriamycin in soft-part sarcoma].

Fifteen patients with soft-part sarcoma were treated with combination chemotherapy consisting of vincristin, actinomycin D, cyclophosphamide and adriamycin (VACA therapy). The cumulative five-year survival rate by the Kaplan-Meier method was about 73%. This VACA therapy was effective for malignant fibrous histiocytoma and synovial sarcoma as well as rhabdomyosarcoma. Side effects such as anemia, leucocytopenia, nausea and alopecia were observed, but could be managed. VACA therapy is considered to be useful as a combination chemotherapy for patients with soft-part sarcoma.

Adolescent↗

[Pharmacokinetics of cefixime in patients with impaired renal function].

Cefixime (CFIX) was given orally in a single dose of 100 mg to 7 patients with varying degrees of impaired renal function (Ccr 12.0-56.7 ml/min) and serum concentrations and urinary excretion rates were measured with time for the first 24 hours by the bioassay method to investigate in vivo pharmacokinetics of the drug. The results obtained are summarized as follows. The mean peak serum concentration of CFIX in 3 patients with moderately impaired renal function (group I: Ccr greater than or equal to 30-less than 60 ml/min) was 2.04 micrograms/ml at 6 hours after dosing and gradually declined to 0.10 microgram/ml at 24 hours after dosing. The half-life was 4.15 hours. The mean peak serum concentration of CFIX achieved was 2.27 micrograms/ml at 8 hours after dosing in 4 patients with severely impaired renal function (group II: Ccr greater than or equal to 10-less than 30 ml/min) and the concentration of CFIX was 0.99 microgram/ml even after 24 hours. The half-life was prolonged to 11.05 hours. There was no great difference between groups I and II in the first 24-hour urinary excretion rates. However, the first 4-hour urinary excretion accounted for 2.14% of the administered dose of CFIX in group I but only 0.47% in group II. Urinary concentrations of CFIX peaked at 4-6 hours after dosing in both groups, and thereafter gradually decreased in group I. Whereas, they did not decline much in group II until 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Induction of IgG1 and IgE responses to protein-conjugated and unconjugated beta-lactam antibiotics in the mouse--efficacy of Freund's complete adjuvant.

One or two injections two weeks apart of protein-conjugated penicillin G, cephalothin or cefmetazole emulsified with Freund's complete adjuvant were quite effective in producing anti-antibiotic antibodies of the IgE as well as of the IgG1 class in mice. Long-lasting and boostable production of both antibody classes was also obtained against unconjugated cephalothin or cefmetazole, though the positivity depended on the mouse strain.

Animals↗

Depth of side-chain pocket in the S2 subsite of dipeptidyl peptidase IV.

Kinetic studies of pig kidney dipeptidyl peptidase IV (dipeptidyl-peptide hydrolase, EC 3.4.14.5) were carried out using substrates possessing a side-chain of different length at the P2 position (or amino-terminal position in this case) such as Lys-, Arg-, Phe-, Met-, Ser-, His-, Glu- and Gly-Pro-pNA. The hydrolytic coefficient (Kcat/Km) has determined in the order Met- greater than Glu- greater than Ser- greater than His- greater than Phe- greater than Lys- greater than Gly- greater than Arg-, indicating a gradual increase with elongation of the side-chain from 0.03 to 0.60 nm followed by a decline when side-chain length approached 0.70 nm. Thus, the most probable depth of the side-chain pocket at the S2 subsite of the enzyme is proposed to be 0.50-0.60nm.

Animals↗

A sensitive and specific assay for dipeptidyl-aminopeptidase II in serum and tissues by liquid chromatography-fluorometry.

A highly sensitive and specific method for the assay of dipeptidyl-aminopeptidase II (DAP II) in crude enzyme preparations such as serum and tissue homogenates has been established by using a newly synthesized fluorogenic substrate, 7-Lys-Ala-4-methylcoumarinamide. The enzymatically formed 7-amino-4-methylcoumarin was determined by high-performance liquid chromatography with fluorescence detection. The activities of other aminopeptidases in human serum and rat brain homogenates were completely inhibited by o-phenanthroline without any effect on DAP II activity to permit specific determination of DAP II. The limit of sensitivity for DAP II activity was about 300 fmol/30 min. DAP II activity was found to be increased in sera from cancer patients, in contrast to the decrease in serum DAP IV activity. DAP II activity was found to be unequally distributed in rat brain regions, and the highest activity was found in the hypothalamus.

Animals↗

Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats.

The effects of gomisin A, which is a lignan component of schizandra fruits, on liver functions in various experimental liver injuries and on bile secretion in CCl4-induced liver injury were studied. Gomisin A weakly accelerated the disappearance of plasma ICG by itself at a high dose (100 mg/kg, i.p.). All of the hepatotoxic chemicals used in this study inhibited the excretion of ICG from plasma. Gomisin A showed a tendency to prevent the delays of the disappearance of plasma ICG induced by CCl4, d-galactosamine and orotic acid, but not that by ANIT. Bile flow and biliary outputs of total bile acids and electrolytes (Na+, K+, Cl- and HCO3-) were decreased in CCl4-treated rats. Gomisin A maintained bile flow and biliary output of each electrolyte nearly to the level of the vehicle-treated group, but did not affect biliary output of total bile acids. These findings suggest that gomisin A possesses a liver function-facilitating property in normal and liver injured rats and that its preventive action on CCl4-induced cholestasis is due to maintaining the function of the bile acids-independent fraction.

1-Naphthylisothiocyanate↗

Morphology of ectopic ventricular beats and their relationship to ventricular tachycardia in acute myocardial ischemia.

The features of ventricular arrhythmia in coronary spasm induced by ergonovine were examined to elucidate the characteristics of ventricular arrhythmia in acute myocardial ischemia. The coupling intervals and configurations of the QRS wave of the premature ventricular beats (PVBs) were extremely variable, even in the same individual and at the closer time phases. The prematurity index (R-R'/QT) of PVBs with the right bundle branch block (RBBB) pattern was significantly smaller than with the left bundle branch block (LBBB) pattern. The vulnerability index (R-RX QT/R-R') of PVBs with the RBBB pattern was significantly larger than with the LBBB pattern. The incidence of PVBs with the RBBB pattern (50.4%) was slightly larger than with the LBBB pattern (40.5%). PVBs deteriorated into ventricular tachycardias (VTs) in 29 (24.8%) of 117 cases with the RBBB pattern and in 11 (11.7%) out of 94 cases with the LBBB pattern. Thus, PVBs with the RBBB pattern were more likely to progress to VT than with the LBBB pattern. But it is difficult to assess the clinical significance of PVBs from their QRS morphology alone, because 11 (27.5%) of 40 cases of VT were initiated by PVBs with the LBBB pattern.

Acute Disease↗

Incidental carcinoma of the prostate: histopathology and natural history.

We reviewed 60 cases of incidental carcinoma of the prostate treated conservatively. Subclassification of incidental carcinoma was based on histologic grade and tumor size. Stage A1 was defined as a low grade (grade I) and focal lesion, and stage A2 as a high grade (grade II, III) or diffuse lesion. The distinction between focal and diffuse was set at three chips in a transurethrally resected specimen or a diameter of 5 mm for a total lesion in an enucleated specimen. Patients with stage A1 tumors did significantly better (p less than 0.05) than those with A2, the 5-year survival rates being 88% and 70%, respectively. It is believed that patients with stage A2 should be treated aggressively. However, conservative therapy is recommended for the patients with stage A1 prostate cancer.

Aged↗

Incidental carcinoma of the prostate in Japan: histological characteristics and tumor size.

The incidence of incidental carcinoma of the prostate in Japan is reported, and a retrospective study of 60 incidental carcinoma of the prostate is presented on the basis of tumor size and histological features. As the tumor progressed in size, there was a corresponding increase in its malignant potential. The survival rate according to tumor size and histological grade showed a significant difference between A1 (less than 10 mm diameter and low grade) and A2 (greater than or equal to 10 mm diameter or moderate to high-grade tumor).

Adenocarcinoma↗

[Effect of anticancer agents on rat prostate. Evaluation of organ weight, histological finding and 5 alpha-reductase activities].

To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of activated lymphocytes on the regulation of hematopoiesis: suppression of in vitro granulopoiesis and erythropoiesis by OKT8+ Ia- T cells induced by concanavalin-A stimulation.

The effects of activated lymphocytes were studied in the regulation of in vitro hematopoiesis. Peripheral blood lymphocytes stimulated by concanavalin A (Con A) were cocultured with normal bone marrow cells in the assay system of hematopoietic stem cells. Con-A-stimulated lymphocytes and their supernatants showed significant suppression of in vitro growth of myeloid and erythroid progenitor cells (CFU-C, CFU-E, and BFU-E). Suppressive activity detected in the T-cell fraction was completely abolished by treatment with OKT3 or OKT8 monoclonal antibody and complement and 20 Gy radiation but not OKT4 or OKIa1 antibody and complement. These observations indicate that peripheral blood lymphocytes can be induced by Con-A stimulation to become suppressor T cells for myeloid and erythroid progenitor cells that are OKT8 positive, Ia negative, and radiosensitive. Together with our previous observation that CFU-C suppressor cells induced by alloantigen stimulation are radioresistant and OKT8- and Ia-positive T cells, it is suggested that in vitro hematopoiesis may be regulated by heterogeneous subpopulations of activated T-lymphocytes.

Antibodies, Monoclonal↗