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Biomedical subjects

H Mitsui

Publications and source records attributed to H Mitsui.

At least 127 records · Page 7Linked to original sources
PubMed1990

The high affinity receptor for omega-conotoxin represents calcium channels different from those sensitive to dihydropyridines in mammalian brain.

A monoclonal antibody recognizing the alpha 2 delta complex of the dihydropyridine (DHP)-sensitive calcium channel of skeletal muscle immunoprecipitated most of the DHP receptor solubilized from bovine and rabbit brains, and bovine cardiac muscle. However, it did not significantly immunoprecipitate the high affinity omega-conotoxin receptor solubilized from these brains. These results indicate that the DHP receptor and the high affinity omega-conotoxin receptor are different molecules in mammalian brain.

Animals↗
PubMed1990

Synthesis and antitumor activities of platinum complexes of unsymmetrical alicyclic diamines as carrier ligands.

The synthesis and biological activities of the platinum complexes of 2-aminomethylaziridine, 2-aminomethylazetidine, 2-aminomethylpyrrolidine, 2-aminomethylpiperidine as carrier ligands are described. The platinum complexes of 2-aminomethylazetidine and 2-aminomethylpyrrolidine are significantly effective against murine tumors. In particular, 2-aminomethylazetidine (1,1-cyclobutanedicarboxylato)platinum II (13) and 2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platin um II (16) exhibited potent antitumor activity and were soluble in water, and their antitumor activities against Colon 26 carcinoma (sc-ip system) were superior to CBDCA and comparable to CDDP.

Animals↗
PubMed1990

Aberrant expression of immunoglobulin light chain isotype in B lymphocytes from patients with monoclonal gammopathies: isotypic discordance and clonal B-cell excess.

A study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B-cell differentiation, namely, circulating surface Ig positive (SIg+) cells, Ig-secreting cells (plaque forming cells, PFC) and mitogen-induced PFC. By using kappa-lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B-cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen-induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B-cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P less than 0.02). ID and CE can therefore be considered as useful markers for discriminating between MGUS and myeloma, evaluating the clinical stability and predicting the clinical course.

Antibody-Producing Cells↗
PubMed1990

Effect of recombinant human erythropoietin on anticancer drug-induced anaemia.

Anaemia was induced in rats with fluorouracil (5-FU) or cisplatin (CDDP) and the mechanisms of anaemia induction were analysed. Furthermore, the therapeutic effects of recombinant human erythropoietin (rHu Epo) on these anticancer drug-induced anaemias were investigated. In 5-FU-induced anaemia, marked serum erythropoietin (Epo) elevation was observed in inverse correlation to blood Hb concentration and Hb concentration rapidly recovered to normal levels. On the other hand, in CDDP-induced anaemia, serum Epo elevation was modest and the lowered Hb concentration persisted longer. Treatment with rHu Epo significantly improved both anticancer drug-induced anaemias but rHu Epo was more effective on CDDP-induced anaemia. These results suggest that rHu Epo might be useful for the therapy of anaemia associated with anticancer chemotherapy.

Anemia↗
PubMed1990

Synthesis of platinum complexes of 2-aminomethylpyrrolidine derivatives for use as carrier ligands and their antitumor activities.

In order to study a new antitumor platinum complex, various platinum complexes were prepared from 2-amino-methylpyrrolidine derivatives synthesized to serve as carrier ligands and tested for their antitumor activity against Colon 26 carcinoma (s.c.-i.p. system) and P388 leukemia (i.p.-i.p. system) in mice. 2-Aminomethylpyrrolidine proved to be the most effective carrier ligand in its amine derivatives. The structure-activity relationships of the carrier ligands in the platinum complexes with dichloro, oxalato, 1,1-cyclobutanedicarboxylato and dichlorodihydroxo as leaving group were clearly shown on the Colon 26 carcinoma screen and were as follows: the antitumor activity of the platinum complexes with any leaving groups was considerably decreased by the substitution of hydrogen by alkyl group (Me, Et) on nitrogen of aminomethyl and the effects of 1,1-cyclobutanedicarboxylato Pt(II) complexes completely disappeared with the same substitution on nitrogen of pyrrolidine. In all the tested platinum complexes 2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platin um(II) (15) exhibited the most potent antitumor activity. 15 was superior to 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (CBDCA) and similar to cis-diamminedichloroplatinum(II) (CDDP) on the Colon 26 carcinoma screen but it was inferior to CBDCA and CDDP on the P388 leukemia screen. Furthermore, 15 showed more potent antitumor activity than CBDCA against Colon 38 carcinoma (s.c.-i.p. system).

Animals↗
PubMed1990

[Comparison of the effects of various immunosuppressive drugs on subrenal capsule assay (SRC assay)].

We evaluated the effect of various immunosuppressive drugs in the SRC assay. We chose the most appropriate day to obtain the results of the SRC assay using the MBT-2 tumor. MBT-2 tumor-bearing mice of homogenic and heterogenic strains were separately given one of the three: cyclophosphamide, azathioprine or mizoribine. These drugs were evaluated on the 6th and the 11th day for the immunosuppressive effects expected from a host versus graft reaction. Concerning the homogenic mice that were injected with drugs, on the 11th day, the growth of the tumor was favorably suppressed in comparison with the growth of the control group (A-1) due to the anti-tumor effect of immunosuppressive drugs. We concluded that the 6th day was the most, appropriate day to obtain the results of this assay. Concerning the heterogenic mice, similar results were observed. In the mizoribine-group, we subcutaneously injected 200 mg/kg on alternate days. Yet the implanted tumor grew almost at the same rate as that of the A-1 group. In this group, a histological study showed reduction of the tumor cells and few inflammatory cells. We concluded that this drug was more useful than the others in the SRC assay and the suitable day for judgement was the 6th day.

Animals↗
PubMed1990

[Subrenal capsule assay for chemosensitivity test of urological malignancy].

We evaluated the subrenal capsule assay with a chemosensitivity test using 47 fresh surgical explants, including 16 renal cell carcinomas and 10 uroepithelial cancers. Forty-one explants were evaluable and 166 drug tests were performed. Forty-seven tests (28.3%) were found to be sensitive. Ten of 16 renal cell carcinomas involved a sensitive drug, 3 involved more than 2 sensitive drugs. VP-16, ADM, BLM and 5-FU were the most sensitive compared with the others. Concerning the uroepithelial cancers, 8 of 10 involved a sensitive drug, 5 involved more than 2 sensitive drugs. CDDP and VP-16 were more effective than the other drugs. This result showed a good correlation with the clinical therapeutic efficacy using CDDP. In the future, we hope to evaluate the clinical correlation between clinical efficacy and this assay.

Adenocarcinoma↗
PubMed1990

[Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II), against cisdiamminedichloroplatinum (II)-resistant murine leukemia cell line].

Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) (DWA 2114 R) against cisdiamminedichloroplatinum (II) (CDDP)-resistant tumor was examined in in vitro and in vivo experiments. CDDP-resistant line was established from L 1210 mouse leukemia cells by continuous exposure to CDDP in dose-escalation manner. Six clones were isolated from parental resistant line and one of these clones, clone f, which was found to be highly resistant (30-40 fold) to CDDP, was used in the following experiments. Clone f showed 4-7 fold cross-resistance to DWA 2114 R and 11-19 fold to cisdiammine-1, 1-cyclobutanedicarboxylatoplatinum (II) (CBDCA) in in vitro growth inhibition assay. DWA 2114 R showed the most effective antitumor activity against mice transplanted with the resistant cells in the increase of life span (ILS%). About 100% of ILS and cured mice were observed in the treatment with DWA 2114 R. On the other hand, CDDP or CBDCA showed a little increase in the survival time (less than 40% of ILS) and all mice died. These results suggest that DWA 2114 R seemed to be more effective against CDDP-resistant tumors clinically than CDDP and CBDCA.

Animals↗
PubMed1989

[Study of flow cytometric BrdU/DNA assay].

To investigate the possibility of flow cytometric BrdU/DNA assay as a rapid chemosensitivity test, preliminary studies were performed utilizing CDDP-sensitive and CDDP-resistant mouse leukemic L1210 cell lines. The results indicated that the anticancer effects of CDDP to these cells could be rapidly determined by analyzing the effects on cell kinetics and the effects on BrdU uptake with this method. Also, this method could detect CDDP-resistant cells at proportion approaching 0.1% in a predominantly CDDP-sensitive population. In the near future, this flow cytometric method could be utilized not only as a useful screening test for anticancer drugs for initial cancer chemotherapy but also as a monitoring test to rapidly detect drug-resistant cells and thereby aid in the selection of a more effective anticancer therapy.

Animals↗
PubMed1989

cDNA cloning and nucleotide sequence of rat muscle-specific enolase (beta beta enolase).

The nucleotide sequence of rat muscle-specific enolase cDNA was determined by sequencing three cDNA clones encoding this enolase isozyme. The nearly full-length cDNA consists of 13-bp 5'- and 84-bp 3'-noncoding regions and a poly(A) tail in addition to a 1302-bp coding region encoding a polypeptide composed of 434 amino acid residues. The deduced primary structure of this enolase isozyme is about 80% similar to those determined previously for rat neuron-specific and non-neuronal enolase isozymes. Southern blot analysis suggested strongly the existence of a single copy of the muscle-specific enolase gene per haploid genome. The mRNA for this enolase isozyme was detected in rat skeletal muscle on day 1 after birth and its level increased rapidly during 10-30 days after birth without any change in its size (1500 bases).

Age Factors↗
PubMed1989

Decrease in a constitutive form of cytochrome P-450 by macrolide antibiotics.

The effects of administration of macrolide antibiotics on cytochrome P-450 in liver microsomes of male rats were investigated. The macrolides tested were those with a 14-membered ring such as oleandomycin, troleandomycin, erythromycin and erythromycin estolate, and those with a 16-membered ring such as rokitamycin, leucomycin and josamycin. Cytochrome P-450-metabolite complex was detected with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, whereas no such effect was observed with rokitamycin, leucomycin and josamycin. The content of uncomplexed cytochrome P-450 in liver microsomes remained unchanged with rokitamycin, leucomycin and josamycin, decreased with troleandomycin and oleandomycin, and increased with erythromycin and erythromycin estolate, indicating that oleandomycin, troleandomycin, erythromycin and erythromycin estolate also affect the amounts of other forms of cytochrome P-450. The administration of oleandomycin, troleandomycin, erythromycin and erythromycin estolate resulted in a dramatic decrease in the activities of testosterone 2 alpha- and 16 alpha-hydroxylases in liver microsomes. Supporting these results, a marked decrease (more than 75%) in the content of P-450-male, a major constitutive form of cytochrome P-450 in male rats, was noted with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, while the decrease was rather small with rokitamycin and leucomycin. We conclude that the administration of the 14-membered ring macrolides may affect drug and steroid metabolism not only by formation of P-450-metabolite complex but also by decrease in the content of P-450-male.

Animals↗
PubMed1989

[Antitumor activity of a new platinum complex (R)-(-)-2-aminomethylpyrrolidine (1,1-cyclobutane dicarboxylato) platinum (II) (DWA2114R) by its serial administration].

Antitumor activity of a newly synthesized platinum complex, DWA2114R, by the serial administration was examined and compared with that of cis-diammine-1,1-cyclobutane dicarboxylato platinum (II) (CBDCA). In mice transplanted s.c. with tumor, the serial i.p. administration resulted in the increases of both maximal tolerated dose (MTD) and growth inhibitory ratio (GIR) of DWA2114R than single administration. Such increases in MTD and GIR were also shown by CBDCA, but the degree of these increases, such as the ratio of MTD or GIR by the serial administration compared to that at the single administration, was higher in DWA2114R than CBDCA. GIR of DWA2114R by the serial administration was higher than that of CBDCA at the doses to induce the same toxicity which was estimated by body weight loss. In addition, in the experiment using ascites tumor-bearing mice, better antitumor activity of DWA2114R was shown by the elongation of survival time. These results indicate that the cumulative toxicity of DWA2114R is lower than that of CBDCA, which causes the therapeutic advantages of DWA2114R in the serial administration.

Animals↗
PubMed1989

[Specific cardiomyopathy caused by high dose cyclophosphamide immediately after bone marrow transplantation].

An 11-year-old girl with CML in chronic phase was treated with allogeneic bone marrow transplantation (BMT). She had had no episode of heart disease, and her chest roentgenogram and electrocardiogram were within normal ranges. She had no anthracycline, but 120 mg/kg (2.01 g/m2/d x 2 days) of cyclophosphamide (CY) for conditioning of BMT. She suffered from an acute heart failure on 14 days after BMT and died 2 days later. Autopsy revealed "specific heart muscular disease" with apparent degeneration and necrosis of heart muscle cells. More than 30 fatal cases of CY cardiotoxicity after BMT have been reported, and most patients developed acute heart failure within 10 days after CY dosing. Goldberg et al. reviewed 14 cases of CY cardiotoxicity, and considered more than 1.55 g/m2/day to be the critical doses for the onset of fatal cardiomyopathy. This case was considered to be first case in Japan. CY cardiomyopathy is an early fatal complication of BMT when CY used for conditioning. The dosing schedule may be considered.

Bone Marrow Transplantation↗
PubMed1989

Ureteric obstruction after allogeneic bone marrow transplantation: an unusual complication.

A patient with acute myeloid leukemia (M4) in the first complete remission received a bone marrow transplantation (BMT) from an HLA-compatible sibling. Sustained engraftment was achieved, but she developed colicky pain at the back and lower quadrant of both sides on days 19-21 post-BMT, followed by hemorrhagic cystitis 13 days later. Ultrasonogram, intravenous pyelogram and computed tomogram of the abdomen showed hydronephrosis and ureteric obstruction of both sides. There was no stone in the urinary tract or abnormality of the bladder. The cortex of the right kidney was rather hypertrophic in spite of the persistent presence of hydronephrosis. Viral culture of urine and electron microscopic examination of urine sediments revealed the presence of adenovirus type II. Infection of the urinary tract with adenovirus type II may have been the underlying cause of the hemorrhagic cystitis and possibly also of the otherwise unexplained ureteric obstruction.

Adenoviruses, Human↗
PubMed1989

[Cell kinetic study of urogenital tumors utilizing in vitro BrdU-labelling method and anti-BrdU monoclonal antibody].

With the aim to apply a rapid analytic method of cell kinetics using in vitro BrdU labelling and anti-BrdU monoclonal antibody to the clinical fields, we investigated the cell kinetics of 20 urogenital malignant tumors. The DNA synthesizing cells which take up BrdU in its nuclei can be detected so clearly, since the labelling index (LI) is easily identified. The correlations between LI and age and with histological grade and stage of 14 transitional cell cancers of urinary tract were investigated. There was no correlation between LI and age. The LI of high grade groups (G2 & G3) were significantly higher than that of the low grade group (G1) (p less than 0.05). Also between LI of pT1 group and pT3 group, there was a statistical significance (p less than 0.05) and generally LI tended to increase according to stage progression. Therefore, the cytokinetic data obtained from the before mentioned method can be utilized as a useful marker for measuring malignant potentials of each tumor.

Aged↗
PubMed1988

Solubilization of the omega-conotoxin receptor associated with voltage-sensitive calcium channels from bovine brain.

The omega-conotoxin receptor in brain membranes contains components of Mr approximately equal to 310,000, approximately equal to 230,000, and 37,000 as identified by photoaffinity labeling. The toxin specifically bound to two sites with apparent dissociation constants (Kd) of approximately 3 pM and 3.5 nM under the conditions employed. There was about 8 times more of the low affinity site than the high affinity site. Binding was not affected by dihydropyridines or verapamil. However, diltiazem stereospecifically inhibited the binding to the high affinity site. Dissociation of the toxin from the membranes was very slow and only partial. Among the detergents tested, digitonin solubilized the highest toxin-binding activity. The digitonin extract contained only a single class of binding sites with an apparent Kd of about 0.46 nM. Probably only the high affinity binding site was recovered in active form in digitonin extract. The properties of the toxin binding to digitonin extract were in good agreement with those of the binding to the high affinity site in the original membranes. Photoaffinity labeling of the digitonin extract indicated that the solubilized toxin receptor contained the two large components (Mr congruent 310,000 and approximately equal to 230,000) observed in the membranes.

Animals↗
PubMed1988

Preadipocyte differentiation in vitro: identification of a highly active adipogenic agent.

A highly active adipogenic agent was identified in an in vitro adipose conversion system. This agent, ADD 4743 (or ADD), was synthesized by Takeda Chemical Industries (Osaka) as a 3-hydroxy derivative of an oral antidiabetic agent, ciglitazone, and has been presumed to be an active metabolite of the latter substance. When ST 13 mouse preadipose cells were treated with micromolar concentrations of ADD they rapidly and uniformly converted into lipid-accumulating adipocytelike cells within 8-11 days after cell seeding. The degree of adipose conversion and lipid accumulation induced by ADD far exceeded those of the previously known inducing agents such as indomethacin plus insulin. The highly potent adipogenic activity of ADD was confirmed with two other preadipose cell lines (3T3 L1 and RMT rat preadipose cells). In addition to adipogenic activity, ADD inhibited cell proliferation of preadipose cells specifically. Activity of ADD induced lipid accumulation and growth inhibition of ST 13 cells, exhibiting very similar dose-response relationships. Cell proliferation or triacylglycerol content of nonadipocytic mesenchymal cells or epithelial cells were not affected by ADD. These observations strongly suggest that ADD-induced growth inhibition is not due to the nonspecific toxicity of the drug but is tightly associated with the adipocytic character of the treated cells. The present observation provides evidence that ADD would be a powerful agent in studies that involve preadipocyte differentiation.

Adipose Tissue↗