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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 1,117 records · Page 62Linked to original sources
PubMed1988

[Anti-tumor effect of human recombinant TNF].

In this article, the clinical effects of rH-TNF on various cancer patients and the mechanism of self-induction of defense against rH-TNF cytotoxicity in tumor cells and the counter measures against this are reviewed. 1) Clinical effects of rH-TNF Intratumoral administration of rH-TNF was performed in 7 patients and clinical efficacy (PR + MR) was observed in 3/7 (42.9%). Also a reduction of leukemia cells in peripheral blood was observed in all 4 leukemia patients following intravenous (i.v.) administration of rH-TNF. Furthermore, in 2 multiple myeloma patients, the myeloma protein and plasma cells in bone marrow were reduced by i.v. administration of rH-TNF. 2) Self-induction of defense against rH-TNF cytotoxicity Investigation of the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed that their synthesis in tumor cells was increased at 12 h and peaked at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells, upon addition of Act D or CHI increased the cytotoxic effect of TNF, thus suggesting that the elevated RNA and protein synthesis is related not to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubation of HEL cells with TNF in the presence of either inhibitor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor cells. 3) Combination therapy of rH-TNF with various anticancer drugs. A synergistic increase in the cytotoxic effects of rH-TNF and anti-cancer drugs was demonstrated in vitro The cytotoxicity of rH-TNF against L-M cells in combination with MMC, ADM, Ara-C, ACD, DM, CDDP, VCR and 5-FU was 4 to 347 times as high as that of rH-TNF alone. These results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.

Antineoplastic Agents↗
PubMed1988

Effects of irradiation on cortical bone and their time-related changes. A biomechanical and histomorphological study.

The effects of high-dose irradiation on the biomechanical and morphological properties of cortical bone and their time-related changes were studied in male Sprague-Dawley rats. A single fraction of 3500 rads was applied to the middle part of the right thigh. Age and sex-matched control rats that did not receive radiation were used for comparison. Two weeks after irradiation, the animals had lost weight and disappearance of bone cells, shrunken osteocytes, and significantly decreased bone-turnover activities were noted. The bone marrow showed reduced hematopoietic elements and sinusoids with increased fat. No change in the torsional strength and geometric properties of bone was noted at this time. Six to ten weeks after irradiation, histopathological abnormalities of the bone persisted, and there was an accelerated resorption process. However, significant increases in the strength and cortical area of bone appeared only in the non-irradiated, contralateral femur. On the irradiated side, decreased cortical area and increased porosity of bone were found at fourteen to eighteen weeks when compared with the control rats. Other histomorphological properties, such as bone porosity, osteocyte count, and periosteal new-bone formation, appeared to recover eighteen weeks after irradiation, as they became similar to the values for the age-matched normal control rats.

Animals↗
PubMed1988

[A case of advanced gastric cancer responsive to intratumoral OK-432 injection].

An 83-year-old patient with advanced gastric cancer was given repeated endoscopic administration of OK-432 combined with systemic immunochemotherapy. The cancerous lesion gradually regressed following the treatment, and remarkable degeneration was observed in many tumor cells. Detailed immunohistochemical examination revealed that Leu 7-positive cells had markedly infiltrated the cancerous tissue. This finding suggests that NK cells may play an important role in tumor regression induced by intratumoral OK-432 therapy.

Adenocarcinoma↗
PubMed1988

[Basic and clinical study of anticancer effect of etoposide on choriocarcinoma].

To establish a new method for treating choriocarcinoma, basic and clinical studies were made on Etoposide, a newly developed anticancer drug. I. Basic study 1) The crystal violet uptake sensitivity tests for anticancer drugs were examined with 5 human choriocarcinoma cell lines, BeWo, SCH, HCCM-5, JEG and SMT-CCl. 2) A drug concentration which could reduce the survival rate of SMT-CCl cells to 50% was regarded as the standard concentration. 3) Etoposide showed the same strong anticancer activity on all the choriocarcinoma cell lines as Act-D and CPA. II. Clinical study 1) In the treatment of trophoblastic diseases (choriocarcinoma 15 cases and invasive mole 14 cases), Etoposide therapy manifested a much higher effective rate (93.3%) than conventional Act-D therapy (50.0%) and MTX therapy (21.0%). But side effects of Etoposide therapy were milder than those of the other drugs. 2) Especially in the high risk choriocarcinoma group, the remission rate was 50% (PR 3, NC 2 and PD 1) for the conventional MAC protocol and 100% (CR 3 and PR 2) for the MECA protocol. In conclusion, it was demonstrated basically and clinically that Etoposide was very effective in the treatment of choriocarcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[The surgical treatment for the site of metastases of choriocarcinoma].

16 cases with gestational choriocarcinoma treated at our clinic from 1978 to 1987 were reviewed in connection with the surgical treatment for metastases in the brain and lung. 9 patients were classified as high risk, 5 patients as medium risk and 2 patients as low risk according to Bagshawe's prognostic score. An overall remission rate of 87.5% was achieved. 10 patients underwent surgical treatment with chemotherapy in 14 of 16 patients in whom metastases were identified, followed by complete remission. Pulmonary metastases were noted in 14 of 16 patients and lobectomy was performed in 10 of 14 patients, resulting in complete remission. Brain metastasis also was noted in 3 of 16 patients and the tumorectomy for the site of metastasis with irradiation was performed in 2 of the 3 patients, resulting in complete remission. One of 3 patients treated with chemotherapy alone, died. Our satisfactory results suggest the aggressive surgical therapy for the site of metastases in selected patients as indicated is apparently effective with vigorous systemic chemotherapy and radiotherapy.

Adult↗
PubMed1988

Internal mammary artery grafting in patients with smaller body structure.

The results of internal mammary artery grafting in 50 patients with a body surface area less than 1.6 m2 were compared with those in 54 patients with a larger body surface area. Age (58.8 +/- 8.2 versus 54.9 +/- 10.3 years old) and prevalence of female gender (28% versus 4%) were significantly different between the group of patients with a small body surface area and the group with a large body surface area, respectively. However, the prevalence of unstable angina, previous myocardial infarction, extent of coronary artery disease, and preoperative ejection fraction was not significantly different between the two groups. The mean number of distal anastomoses was 3.0 and 2.8, and the mean duration of aortic occlusion was 65.6 +/- 23.0 minutes and 59.5 +/- 21.7 minutes in the small and large body surface area groups, respectively (not significant). The mean free flow rate of the internal mammary artery was 65.6 +/- 16.8 ml/min in the small body surface area group and 78.0 +/- 21.6 ml/min in the large body surface area group (p less than 0.05). The diameters of the anterior descending and the circumflex arteries were significantly smaller in the small body surface area group. Two patients (4%) died within 30 days of operation and one patient died later in the small body surface area group, whereas no death was noted in the large body surface area group (not significant). No significant differences were found in the incidence of aortic balloon pumping, perioperative myocardial infarction, and serious postoperative complications between the two groups. Symptomatic relief was equally good in both groups (92% and 96%). The patency rate of the internal mammary artery was 95% (42/44) in the small body surface area group and 100% (48/48) in the large body surface area group within 1 year, mean 2.3 +/- 2.4 months. In conclusion, internal mammary artery grafting can be performed safely and effectively even in patients with small body structure. Though the blood flow of the internal mammary artery and the size of the coronary arteries were smaller in patients with small body structure, excellent patency of the internal mammary artery graft and satisfactory symptomatic relief can be expected.

Blood Flow Velocity↗
PubMed1987

Escherichia coli H+-ATPase. Glutamic acid 185 in beta subunit is essential for its structure and assembly.

The uncD gene for the beta subunit of Escherichia coli H+-ATPase was cloned downstream of the lac promoter and mutagenized (Glu-185----Gln or Lys) by an oligonucleotide-directed procedure. The recombinant plasmid was introduced into a strain in which the unc operon for subunits of H+-ATPase was deleted. The wild-type or mutant beta subunit synthesized amounted to about 10% total cell protein and was mainly found in the cytoplasmic fraction. These subunits could be purified to almost homogeneity by conventional procedures. The wild-type and two mutant beta subunits had essentially the same Kd values for 8-anilinonaphthalene-1-sulfonate, aurovertin, and ATP, although the fluorescence intensities of 8-anilinonaphthalene-1-sulfonate and aurovertin were significantly less when bound to the two mutant beta subunits than when bound to the wild-type subunit. The three beta subunits showed essentially the same circular dichroism spectra, indicating alpha-helical contents of about 16-18%. Thus, the mutations did not cause marked change of the secondary structure of the subunit. However, measurements of theta 208 during linear increase in temperature suggested that replacement of Glu-185 by Gln or Lys slightly changed the stability of the secondary structure. Only trace amounts of alpha beta gamma complexes could be reconstituted using the two mutant beta subunits. These results suggest that Glu-185 or the region in its vicinity may be essential for subunit assembly. The methods developed in this study should be useful for further studies on the beta subunit.

Circular Dichroism↗
PubMed1987

Beta-subunit of Escherichia coli F1-ATPase. An amino acid replacement within a conserved sequence (G-X-X-X-X-G-K-T/S) of nucleotide-binding proteins.

A mutant strain KF87 of E. coli with a defective beta-subunit (Ala-151----Val) of F1-ATPase was isolated. The mutation is within the conserved sequence (G-X-X-X-X-G-K-T/S) of nucleotide-binding proteins. The mutant F1-ATPase had a much higher rate of uni-site hydrolysis of ATP than the wild type, and about 6% of the wild-type multi-site activity. The mutant enzyme showed defective transmission of conformational change(s) between the ligand- and aurovertin-binding sites.

Adenosine Triphosphate↗
PubMed1987

Loss of unisite and multisite catalyses by Escherichia coli F1 through modification with adenosine tri- or tetraphosphopyridoxal.

Pyridoxal phosphate (PLP) and adenosine diphospho (AP2-PL)-, triphospho (AP3-PL)-, and tetraphospho (AP4-PL)-pyridoxals (Tagaya, M., and Fukui, T. (1986) Biochemistry 25, 2958-2964) were tested as potential affinity probes for F1 ATPase of Escherichia coli. Both AP3-PL and AP4-PL bound and inhibited F1 ATPase, whereas PLP and AP2-PL were weak inhibitors. The concentrations of AP3-PL and AP4-PL for half-maximal inactivations of the multisite (steady state) ATPase activity were both 18 microM. The binding of these reagents to a reactive lysyl residue(s) was confirmed from the difference absorption spectra, and the stoichiometry of binding of [3H]AP3-PL to F1 at the saturating level was about 1 mol/mol F1. The analogue bound to both the alpha subunit (about two-thirds of the radioactivity) and the beta subunit (about one-third of the radioactivity). No inactivation of multisite ATPase activity or binding of AP3-PL was observed in the presence of ATP. F1 modified with about one mol of AP3-PL had essentially no uni- and multisite hydrolysis of ATP. The rate of binding of ATP decreased to 10(-2) of that of unmodified F1, and the rate of release of ATP was about two times faster. The equilibrium F1 X ATP in equilibrium F1 X ADP X Pi was shifted toward F1 X ATP, and no promotion of ATP hydrolysis at unisite was observed with excess ATP. These results suggest that the AP3-PL or AP4-PL bound to an active site, and catalysis by the two remaining sites was completely abolished.

Adenine Nucleotides↗
PubMed1987

Mode of inhibition of sodium azide on H+-ATPase of Escherichia coli.

Sodium azide inhibited multi-site (steady-state) ATPase activity of E. coli F1 more than 90%, but did not affect uni-site (single-site) ATPase activity. Thus azide inhibited multi-site ATPase activity by lowering catalytic cooperativity. Consistent with this observation, azide changed the ligand-induced fluorescence response of aurovertin bound to F1.

Adenosine Diphosphate↗
PubMed1987

Separation and quantitation of plasma free fatty acids as phenacyl esters by HPLC.

We have developed a rapid method for the separation of plasma free fatty acids as their phenacyl esters by high-performance liquid chromatography (HPLC) using a reversed-phase (C18) column. The derivatives of series of both saturated and unsaturated fatty acids (C12:0-C22:6) are simultaneously separated within 45 min and detected with ultraviolet at 241 nm. The limit of detection of fatty acids was approximately 0.5 nmol in 20 microL injected volume of extracts, and the coefficient of variation of the present method did not exceed 3.0%. Comparison of the results of the present HPLC method with those of gas chromatography, gave very good correlations for all fatty acids in human plasma.

Chromatography, High Pressure Liquid↗