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Biomedical subjects

M Okabe

Publications and source records attributed to M Okabe.

At least 271 records · Page 15Linked to original sources
PubMed1993

Characterization of capacitation inhibitory protein from rabbit seminal plasma: homology with human annexins.

A protein was purified from rabbit seminal plasma using preparative acrylamide disc electrophoresis, ammonium sulfate precipitation and gel filtration. The protein inhibited the in vitro fertilization of mouse ova inseminated with epididymal sperm and with capacitated sperm. The inhibition was not observed, however, when only ova were exposed to the protein prior to mixing with sperm. The partial protein sequence analysis revealed the strong homology of the rabbit fertilization inhibitory protein to human annexin V.

Amino Acid Sequence↗
PubMed1993

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats.

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.

Adrenergic alpha-Antagonists↗
PubMed1993

Pathological extent of interventricular septal infarction in patients with acute anteroseptal myocardial infarction with and without right bundle branch block.

The purpose of the present study is to elucidate the difference in extent of myocardial infarction (MI) between those cases with and those without right bundle branch block (RBBB) occurring during the course of acute MI. We examined postmortem hearts from 20 patients with acute anteroseptal MI; 10 with (group A) and 10 without RBBB (group B). The extent of MI was studied pathologically in the interventricular septum (IVS) and reconstructed. The longitudinal extent of MI did not distinctly differ between groups A and B. In 5 hearts of group B, the anterior limit of the MI extended as high, or as close to the cardiac base, as in group A hearts. Transmural MI was relatively common and seen more frequently in group A than in group B. However, the MI did not always extend evenly to the left and right ventricular sides in the IVS. Left-sided predominance in extent of the MI was more frequently observed in group B than in group A. Right-sided predominance in the extent of septal MI was relatively rare and was seen in 5 cases at the portion where the right bundle branch came down. Four of these were group A patients. Thus, involvement of the right bundle branch might partly depend on the unevenness of the mural extent of the MI as well as the height of extension of the MI in the IVS.

Aged↗
PubMed1993

Effects of mitomycin-C and etoposide in cell culture and in nude mice: the role of G-CSF mutein.

The combination of mitomycin-C and etoposide showed synergistic cell kill effects in vitro against HEp-2 laryngeal squamous carcinoma cells both in monolayer and in multicellular tumor spheroid systems. This combination was also synergistic in inhibiting HEp-2 tumors growing in nude mice. One course of this combination produced no complete regression of this tumor. When these two agents were combined with recombinant human granulocyte colony-stimulating factor (G-CSF) mutein, the doses of the drugs could be escalated approximately 1.5-fold higher than the doses that were tolerated without G-CSF support. With this modest dose intensification, apparent cure was observed. High-dose mitomycin-C plus etoposide with G-CSF support may be useful for the treatment of patients with inoperable squamous cell carcinoma of the head and neck.

Animals↗
PubMed1993

New insight into oncoprotein-targeted antitumor effect: herbimycin A as an antagonist of protein tyrosine kinase against Ph1-positive leukemia cells.

Herbimycin A, a benzoquinonoid anasamycin antibiotic, has been shown to reserve the oncogenic phenotypes of p60v-src transformed cells by the virtue of the inhibition of src protein tyrosine kinase. Furthermore, we previously demonstrated that herbimycin A displayed the antitumor activity on Ph1-positive leukemia cells and bcr/abl oncoprotein-associated transformed murine hematopoietic cells with the transfection of a retroviral vector expressing bcr/abl. Herbimycin A showed preferential inhibition on the in vitro growth of Ph1-positive leukemia cells and bcr/abl oncoprotein-associated murine hematopoietic cells through the inhibition of bcr/abl tyrosine kinase activity and the reduction of subsequent phosphotyrosyl proteins. Recently, from the view of investigating the oncogenic significance or of developing a future clinical application in malignancies, several developing agents targeted against oncoprotein have been tried. We reviewed the present progress in the mechanism of oncoprotein-targeted antitumor effects and focused on herbimycin A-induced antitumor activity on Ph1-positive leukemia cells.

Animals↗
PubMed1993

BCR/ABL oncoprotein-targeted antitumor activity of antisense oligodeoxynucleotides complementary to bcr/abl mRNA and herbimycin A, an antagonist of protein tyrosine kinase: inhibitory effects on in vitro growth of Ph1-positive leukemia cells and BCR/ABL oncoprotein-associated transformed cells.

We investigated whether antisense oligodeoxynucleotides complementary to bcr/abl mRNA or protein kinase antagonists display antitumor activity on Ph1-positive leukemia cell lines. bcr/abl antisense oligomers showed inhibitory effects on the in vitro growth of Ph1-positive leukemia cell lines in liquid culture, and further displayed an inhibitory effect on transformed murine hematopoietic cells using transfection with a retroviral vector expressing P210bcr/abl oncoprotein. However, in vitro treatment with a bcr/abl antisense oligomer did not completely abolish the expression of bcr/abl mRNA and did not display the desired "killing effect" on Ph1-positive leukemia cells. On the other hand, investigation of the effect on Ph1-positive leukemia cells by various types of protein kinase antagonists revealed that herbimycin A, a protein tyrosine kinase antagonist, displays preferential and remarkable suppression of the growth of Ph1-positive leukemia cells and P210bcr/abl associated transformed cells by virtue of suppressing bcr/abl protein tyrosine kinase activity. These results may provide important future insights in developing a new category of antitumor therapy by targeting oncogene products.

Antibiotics, Antineoplastic↗
PubMed1993

Development of a cyclodextrin production process using specific adsorbents.

Novel adsorbents that are composed of ligand, spacer, and support were chemically synthesized, and the two consecutive screenings made it possible to determine the adsorbents that were most suitable for alpha- and beta-CD production, respectively. Stearic acid was the most effective ligand for alpha-CD, whereas cyclohexanepropanamide-n-caproic acid was best for beta-CD. The adsorption selectivity of adsorbents derived from carboxylic acids (stearic or palmitic acid) and Chitosan beads was almost 100%, and their adsorption capacities were large enough to meet the demand for economical production and purification of CDs on an industrial scale. Next we discussed a novel process of alpha-CD production using the newly synthesized adsorbent characterized by the exceedingly powerful selectivity of alpha-CD from other CDs. alpha-CD production was carried out in the closed system converted to CDs by CGTase, and the column was packed with the adsorbent selective for alpha-CD. The yield of alpha-CD was 22.3%, and alpha-CD occupied a fraction of 57.4% in the overall CD reaction mixture. In the batch system without adsorbent, the yields of alpha-CD and its fraction were 10.8 and 24%, respectively. This novel process is particularly useful for the large-scale production of alpha-CD, in which the use of organic solvent is not preferable. We will now develop a novel process for the industrial production of CDs other than alpha-CD, such as gamma-CD, by using specific adsorbents.

Adsorption↗
PubMed1993

[Coronary artery bypass surgery in patients older than 75 years of age].

There is controversy whether the short-term and long-term results of coronary artery bypass surgery in elderly patients justify the commencement of the procedure. Between February 1988 and July 1992, 113 patients underwent CABG in our hospital, of whom 15 (13.3%) patients were 75 years old or older (mean 76 years). They consisted of 5 men and 10 women, and all were in New York Heart Association class III or IV. Unstable angina was observed in 13, left main trunk stenosis was in 4, and left ventricular dysfunction, ejection fraction of less than 0.30 was in 2 of 15 patients. The mean number of bypass grafts was 2.7 per a patient, and only autologous greater saphenous vein was used. In seven (47%) cases, CABG was performed urgently or emergently. There was neither operative nor hospital death, although some complications occurred in 11 (73%) patients. Post-operatively, 13 patients were in NYHA class I and 2 in class II. Only one patient died of pneumonia one year after operation. Although high risks of operative mortality and morbidity with coronary artery bypass surgery for elderly patients, particularly in urgent or emergent cases, had been reported, the long-term survival rate and freedom from angina were excellent, justifying continuous commencement of coronary bypass surgery in the selected patients over 75 years of age.

Aged↗
PubMed1993

[Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog].

The antitumor activity of navelbine (vinorelbine ditartrate, KW-2307) against murine and human transplantable tumors was compared with those of other vinca alkaloids, vindesine (VDS), vincristine (VCR) or vinblastine (VLB). KW-2307 and VDS increased the life span of mice bearing ascitic tumors (P 388 leukemia, L 1210 leukemia, EL-4 lymphoma, Colon 26, FM 3 A mammary carcinoma and M 5076 sarcoma) slightly more than VCR or VLB. A significant difference was not found in the antitumor activities against 6 murine solid tumors (B 16 melanoma, Colon 26, FM 3 A mammary carcinoma, Lewis lung carcinoma, M 5076 sarcoma and Sarcoma 180). However, a remarkable difference was observed in the antitumor activities against 11 human tumors inoculated into nude mice. The activity of KW-2307 was more than those of other 3 drugs against 4 human non-small cell lung carcinomas (Lu-65, Lu-99, LC-6 and L-27) and 2 stomach carcinomas (St-4 and St-40). KW-2307 and VDS were also effective in inhibiting the growth of 2 human breast carcinomas (MX-1 and Br-10).

Animals↗
PubMed1993

[Effect of medroxyprogesterone acetate on the anticellular activity of 5-fluorouracil against human breast and stomach cancer cells].

As 5-fluorouracil (5-FU) has been known to show clinically antitumor effects against both breast and stomach carcinomas. We compared the combined effects of medroxyprogesterone acetate (MPA) with 5-FU on the growth of cultured human breast and stomach carcinoma cells. MPA inhibited the growth of estrogen-dependent human breast carcinoma MCF-7 cells at the low concentrations and exhibited an additive effect in combination with 5-FU. MPA also inhibited the growth of human stomach carcinoma MKN-45 cells at relatively high concentrations and exhibited an additive effect in combination with 5-FU. Human stomach carcinoma MKN-28 cells were rather insensitive to MPA, but, an additive combination effect of MPA and 5-FU was observed. These three cell lines were found to have MPA-binding proteins which may be distinct from the nuclear progesterone receptor, suggesting the correlation with growth-inhibitory activity of MPA.

Breast Neoplasms↗
PubMed1993

[Effect of medroxyprogesterone acetate on antitumor efficacies and side effect of 5-fluorouracil].

Effect of medroxyprogesterone acetate (MPA) on the lethal toxicity, bone marrow toxicity and antitumor efficacies of 5-fluorouracil (5-FU) was examined. The following results were obtained. In aged female ddY mice, the lethal toxicity and body weight loss caused by 5-FU were reduced by MPA. MPA also reduced the bone marrow toxicity of 5-FU in aged female ddY mice. These effects of MPA were not observed in young male ddY mice. Moreover, MPA did not affect the antitumor activity of 5-FU against MPA-insensitive mouse breast carcinoma FM3A, or rather augmented its antitumor activity against MPA-sensitive human breast carcinoma MCF-7. These results indicate that MPA reduces the side effects of 5-FU and augments the antitumor activity of 5-FU in female mice.

Animals↗
PubMed1993

[Molecular analysis of transformation into blast crisis in chronic myelogenous leukemia].

Molecular events associated with the transformation into blast crisis phase in Ph1-positive CML were analyzed in the present study. The 9;22 chromosomal translocation in CML generates the bcr/abl fused gene coding P210bcr/abl that has enhanced tyrosine kinase activity. In 55 CML cases, Southern and RT-PCR analysis revealed that breakpoints of the bcr gene on chromosome 22q11 were clustered in M-bcr, except for one case and no obvious difference was observed between chronic and crisis phases. However, blast crisis cells displayed enhanced the expression of bcr/abl mRNA, when compared with those in chronic phase cells. By DNA transfection and PCR analysis, the point-mutational activation of N-ras oncogene was rarely identified, and no point-mutational activation of fms gene was found in the crisis phase cases. On the other hand, 2 out of 13 crisis cases contained gross alteration of p53 anti-oncogene. Furthermore, all 4 myeloid crisis cases and K562 cells showed disappearance of the P53 transcript, and MC3 cells derived from a myeloid crisis case showed an aberrant transcript, whereas chronic phase cases, Ph1-positive ALL cell lines and lymphoid crisis cases including NALM-1 cells showed normal expression of the P53 gene. At present, the precise mechanism associated with the blastic trans-formation in CML remain to be determined. The present study suggested one possibility that a selective and progressive process of Ph1 clone with high expression of the bcr/abl gene may be involved with the transformation into non-lymphoid crisis phases from chronic phases. In addition, this progression may be accelerated by the alteration of p53 anti-oncogene, or/and rarely by the point-mutational activation of ras oncogene family.

Base Sequence↗
PubMed1992

Induction of mammalian DNA topoisomerase I mediated DNA cleavage by antitumor indolocarbazole derivatives.

DNA topoisomerases have been shown to be important therapeutic targets in cancer chemotherapy. We found that KT6006 and KT6528, synthetic antitumor derivatives of indolocarbazole antibiotic K252a, were potent inducers of a cleavable complex with topoisomerase I. In DNA cleavage assay using purified calf thymus DNA topoisomerase I and supercoiled pBR322 DNA, KT6006 induced topoisomerase I mediated DNA cleavage in a dose-dependent manner at drug concentrations up to 50 microM, while DNA cleavage induced by KT6528 was saturated at 5 microM. The maximal amount of nicked DNA produced by KT6006 was more than 50% of substrate DNA, which was comparable to that of camptothecin. Heat treatment (65 degrees C) of the reaction mixture containing these compounds and topoisomerase I resulted in a substantial reduction in DNA cleavage, suggesting that topoisomerase I mediated DNA cleavage induced by KT6006 and KT6528 is through the mechanism of stabilizing the reversible enzyme-DNA "cleavable complex". Both KT6006 and KT6528 did not induce topoisomerase II mediated DNA cleavage in vitro. KT6006 and KT6528 were found to induce nearly identical topoisomerase I mediated DNA cleavage patterns, which was distinctly different from that with camptothecin. In contrast to the similarity between KT6006 and KT6528 in their structures and the nature of their cleavable complex with topoisomerase I, these drugs have different properties with respect to their interaction with DNA: KT6006 is a very weak intercalator whereas KT6528 is a strong intercalator with potentials comparable to that of adriamycin. These results indicate that KT6006 and KT6528 represent a new distinct class of mammalian DNA topoisomerase I active antitumor drugs.

Animals↗
PubMed1992

Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein-associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth.

Herbimycin A, a benzoquinoid ansamycin antibiotic, was demonstrated to decrease intracellular phosphorylation by protein tyrosine kinase (PTK). In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis. However, the same dose of herbimycin A did not inhibit in vitro growth of a broad spectrum of Ph1-negative human leukemia cells, and several other protein kinase antagonists also displayed no preferential inhibition. Furthermore, we demonstrated that herbimycin A has an antagonizing effect on the growth of transformed cells by a transfection of retroviral amphotrophic vector expressing P210bcr/abl into a murine interleukin (IL)-3-dependent myeloid FDC-P2 cell line. This inhibition was abrogated by the addition of sulfhydryl compounds, similar to the reaction previously described for Rous sarcoma virus transformation. The inhibitory effect of herbimycin A on the growth of Ph1-positive cells was associated with decreased bcr/abl tyrosine kinase activity, but no decrease of bcr-abl mRNA and protein, suggesting that the inactivation of bcr-abl tyrosine kinase activity by herbimycin A may be induced by its binding to the bcr-abl protein portion that is rich with sulfhydryl groups. The present study indicates that herbimycin A is a beneficial agent for the investigation of the role of the bcr-abl gene in Ph1-positive leukemias and further suggests that the development of agents inhibiting the bcr-abl gene product may offer a new therapeutic potential for Ph1-positive leukemias.

Benzoquinones↗
PubMed1992

Collection of acrosome-reacted human sperm using monoclonal antibody-coated paramagnetic beads.

A monoclonal antibody (MAb) against human acrosome-reacted sperm was attached to paramagnetic polystyrene beads. Human sperm prepared by the swim-up method were 1) incubated in m-BWW, 2) incubated and ionophore treated, or 3) incubated with 5% seminal fluid. After treatment, sperm were mixed with the beads and incubated for 1 hr. Variously treated sperm showed different binding abilities to the beads. Sperm bound to the beads were collected by a magnet and subjected to triple staining. Most of the collected sperm were acrosome reacted. The results suggested that the beads can be used to estimate the acrosomal status of sperm, and that the use of antibody-coated paramagnetic beads provides a convenient way of collecting acrosome-reacted sperm. The acrosomal status detected by the beads was also compared with the ability of sperm to fuse with zona-free hamster eggs. It was found that greater bead-binding ability correlated with more sperm fusing with zona-free hamster eggs.

Acrosome↗