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Biomedical subjects

Y Masui

Publications and source records attributed to Y Masui.

At least 55 records · Page 3Linked to original sources
PubMed1993

One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects.

A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride.

Administration, Intravesical↗
PubMed1993

[A study of testicular tumor on magnetic resonance imaging].

Magnetic resonance imaging (MRI) was performed on 13 testes of 12 patients with testicular abnormalities. In all cases, scrotal palpation and initial clinical course had suggested malignant testicular tumors. The normal testes showed homogeneous intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images such as the appearance of the corpus cavernosum penis. Ten patients proved to have testicular tumors. In eight of them, the tumors showed homogeneous intermediate signal intensity on T1-weighted images, while in the other two, these images showed heterogeneous signal intensity. In four patients, tumors were of homogeneous low signal intensity on T2-weighted images, while in the other six, these images showed heterogeneous signal intensity. The rate of correspondence about local staging of testicular tumor between MRI and pathological diagnosis was 70 percent. In three patients whose testes were undoubtedly malignant according to clinical findings and examination data, MRI enabled us to diagnose one case of testicular atrophy. However, MRI suggested benign disease in the other two patients; nevertheless, surgery was performed as indicated by the other findings.

Adolescent↗
PubMed1993

Structural analysis of recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor.

The recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor ([3-153]M-CSF) consists of 302 amino acid residues and has a molecular mass of about 32 kDa, as estimated by SDS-PAGE. Two covalently linked subunits constitute a bioactive homodimer. The structure of the purified protein, expressed in Escherichia coli and refolded from inclusion bodies, was studied. The amino acid sequence was determined by automated Edman degradation of fragments obtained from degradation with CNBr and iodosobenzoic acid as well as by digestion with Glu-C endopeptidase of reduced and alkylated M-CSF. The absence of free thiol groups in the molecule was confirmed with Ellman reagent, which indicated the presence of seven disulfide linkages per homodimer. Sequence analysis of cystine-containing peptides, identified by comparing the peptide maps from unmodified and performic acid-oxidized pepsin digests, gave the following results. (1) Six out of seven disulfide linkages were formed between Cys 7 and Cys 90, Cys 48 and Cys 139, and Cys 102 and Cys 146 at each pair of positions as either intra- or inter-chain disulfides. (2) The remaining disulfide linkage linked Cys 31 of one subunit to Cys 31 of the second subunit of M-CSF. Based on our findings, a two-dimensional model is proposed in which the possible covalent linkage is suggested between the two subunits of the bioactive [3-153]M-CSF molecule.

Amino Acid Sequence↗
PubMed1992

Activation of Xenopus laevis eggs in the absence of intracellular Ca activity by the protein phosphorylation inhibitor, 6-dimethylaminopurine (6-DMAP).

Xenopus laevis eggs pricked or microinjected with water or saline in medium containing a limited quantity of free Ca (1.0 to 2.0 microM) remain unactivated for at least 6 hr, even after transfer to oocyte medium containing Ca at higher concentrations (0.5-1.0 mM). These injected eggs, when later pricked in oocyte medium or exposed to A23187 or urethane are fully capable of activation. This confirms the observations of Wangh ('89). However, eggs injected in this Ca-limited medium (CaLM) with 6-DMAP as well as those simply exposed to this drug undergo changes characteristic of activation, including cortical contraction, cortical granule breakdown, a loss of MPF and CSF activities, and pronuclear formation. The time required for 6-DMAP to induce egg activation is inversely correlated to its concentration. Interestingly, eggs that have been injected with EGTA, and thus are unable to respond to activation stimuli such as pricking and A23187 or urethane treatment, can also be activated by exposure to 6-DMAP. In contrast, eggs exposed to or injected with a 6-DMAP analogue (6-aminopurine or puromycin) or a protein synthesis inhibitor (cycloheximide or emetine or puromycin) are not activated. As well, eggs injected in CaLM with 6-DMAP simultaneously with a phosphatase inhibitor (NaF or ammonium molybdate) fail to become activated. Although 6-DMAP-activated eggs remain at the pronucleus stage so long as 6-DMAP is present, they resume cell cycle activities after the drug is withdrawn. They form cleavage furrows, disassemble pronuclear envelopes, and recondense chromosomes. Also, MPF activity reappears and cycles at least twice, peaking each time shortly before cleavage furrow formation. These results suggest that activation of Xenopus eggs arrested at metaphase II by inhibition of protein phosphorylation does not require intracellular Ca release and that maintenance of the egg at metaphase II depends upon continuous protein phosphorylation.

Adenine↗
PubMed1992

Stable isotope aided nuclear magnetic resonance study to investigate the receptor-binding site of human interleukin 1 beta.

Resonance assignments for interleukin 1 beta at neutral pH were made by using three-dimensional NMR in combination with specific labeling and double-labeling methods with stable isotopes. On the basis of the present assignments, 15N single-quantum coherence spectra of N-terminal truncated and fusion mutants were compared with that of the wild-type. Although these mutants have reduced biological activity, they showed 15N-SQC spectra similar to that of the wild-type. However, small but significant chemical shift changes were observed for amino acid residues within a loop 86-99, in spite of the modification at the N-terminus, supporting the idea that this loop forms a biologically active part of interleukin 1 beta. Receptor-binding activity was studied for mutants (Asp-93)-, (Leu-93)- and des-(Arg-98)interleukin 1 beta's. The results show significant loss of the receptor-binding activity. The N-terminus, the C-terminus, and the loop 86-99 form a part of the open end of a beta-barrel [Finzel, B. C., Clancy, L. L., Holland, D. R., Muchmore, S. W., Watenpaugh, K. D., & Einspahr, H. M. (1989) J. Mol. Biol. 209, 779-791; Clore, G. M., Wingfield, P. T., & Gronenborn, A. M. (1991) Biochemistry 30, 2315-2323], which forms the receptor-binding site of IL-1 beta.

Amides↗
PubMed1992

Functional implications of interleukin-1 beta based on the three-dimensional structure.

The molecular structure of interleukin-1 beta, a hormone-like cytokine with roles in several disease processes, has been determined at 2.0 A resolution and refined to a crystallographic R-factor of 0.19. The framework of this molecule consists of 12 antiparallel beta-strands exhibiting pseudo-3-fold symmetry. Six of the strands make up a beta-barrel with polar residues concentrated at either end. Analysis of the three-dimensional structure, together with results from site-directed mutagenesis and biochemical and immunological studies, suggest that the core of the beta-barrel plays an important functional role. A large patch of charged residues on one end of the barrel is proposed as the binding surface with which IL-1 interacts with its receptor.

Humans↗
PubMed1992

Studies on the retention of the mucous-membrane-adhesive anticancer agent hydroxypropylcellulose doxorubicin.

Incorporation of hydroxypropylcellulose (HPC-)doxorubicin, which we developed as a mucous-membrane-adhesive drug preparation, was instilled into the urinary bladder in 10 clinical cases. Tumor of the urinary bladder was a single tumor in all 10 cases, and preclinical histology showed transitional cell carcinoma, grade 1 or 2, and a lower stage than T1. HPC-doxorubicin, 20 mg/20 ml, was administered in 5 cases, and the other 5 cases received the conventional aqueous doxorubicin, 20 mg/20 ml by way of a catheter and the urethra. Cold punch biopsy was performed after 3 days of instillation, and the incorporation of doxorubicin into both tumorous and normal tissue was measured by high-pressure liquid chromatography. After 3 days, it was found that in the HPC-doxorubicin-administered group, doxorubicin was detected in both tumorous and normal tissue, but it was not detected in either tissue after aqueous doxorubicin administration. In 5 cases of the HPC-doxorubicin group, doxorubicin levels in the tumorous and normal tissue were examined, and it was found that significantly more doxorubicin was detected in the tumorous tissues. Thus, it may be said that our HPC-doxorubicin remained longer within the urinary bladder than the conventional aqueous doxorubicin preparation. Instilled HPC-doxorubicin is more highly concentrated in the tumorous tissue than in the normal bladder tissue, and thus, HPC-compounded anticancer drugs may be therapeutically more useful.

Administration, Intravesical↗
PubMed1992

Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.

Animals↗
PubMed1992

WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS009 A and B novel endothelin receptor antagonists, have been isolated from the fermentation broth of Streptomyces sp. No. 89009. These antagonists were purified from the culture filtrate followed by Diaion SP-207, DEAE Toyopearl column chromatography and HPLC. WS009 A and B showed selective activity in an endothelin receptor binding assay with IC50 of 5.8 x 10(-6) M and 6.7 x 10(-7) M, respectively. On the basis of spectroscopic and chemical evidence, the structures of WS009 A and B have been established as 1 and 3, and are highly hydroxylated benz[a]anthraquinone chromophores.

Anthraquinones↗
PubMed1992

WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS-7338 A, B, C and D, novel endothelin receptor antagonists, have been isolated from fermentation broth of Streptomyces sp. No. 7338. These antagonists were purified from the culture mycelium by extraction with acetone, followed by carbon column chromatography and HPLC. Among them, WS-7338 B showed good activity in an endothelin receptor binding assay with an IC50 of 2.7 x 10(-7) M.

Amino Acid Sequence↗
PubMed1992

Effects of repetitive administration of recombinant human interleukin-1 beta, an analog or corticotropin-releasing hormone combined with lysine vasopressin on rats with glucocorticoid-induced secondary adrenocortical insufficiency.

We investigated effects of corticotropin-releasing hormone (CRH), lysine vasopressin and interleukin (IL)-1 beta[1-148], a less pyrogenic analog of human IL-1 beta, on the hypothalamo-pituitary-adrenal axis in a rat model of secondary adrenocortical insufficiency. After 2 weeks of corticosterone 21-sodium succinate treatment, hypothalamic CRH, anterior pituitary adrenocorticotropic hormone (ACTH) and the adrenal weight of the rats decreased significantly and their plasma ACTH showed a significantly smaller response to ether stress, as did plasma corticosterone level. A mixed solution of CRH (10 micrograms) and lysine vasopressin (2 micrograms) or recombinant human IL-1 beta[1-148] (1 micrograms), administered to these rats for 7 days, apparently accelerated the recovery of the pituitary and adrenocortical responsiveness to ether stress and significantly increased the recovery rate of anterior pituitary ACTH contents and adrenal weight. The IL-1 beta analog also increased hypothalamic CRH. These data indicated that, in a rat model with glucocorticoid-induced adrenocortical insufficiency, synthesis and release of hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid were all considerably affected. CRH combined with lysine vasopressin or a less pyrogenic IL-1 beta analog, when administered to these rats, accelerated the recovery of the pituitary and the adrenocortical functions significantly, suggesting the potential clinical usefulness of these peptides.

Adrenal Insufficiency↗
PubMed1992

[Influence of aging and circadian fluctuation of fibrinolytic factors to the responses of these factors during venous occlusion test in healthy subjects].

This study was aimed to clarify the influence of aging and circadian fluctuation of fibrinolytic factors to changes of tissue plasminogen (t-PA) and its inhibitor (PAI-I) during venous occlusion test. Venous occlusion was achieved by application of a sphygmomanometer cuff to the upper arm of elderly healthy subjects (n = 12) and young healthy subjects (n = 12) at 10:00 am and 4:00 pm. Plasma concentration of t-PA, free PAI-1 and total PAI-1 were measured by ELISA. The activity of t-PA was measured by bioimmunoassay using monoclonal antibody for t-PA. Circadian variation was observed in the change of t-PA activity and total PAI-1. These were highly increased in the evening. However, this phenomenon was different between age groups and increase of t-PA activity occurred in elderly subjects, whereas PAI-1 was observed in young subjects. In conclusion, circadian variation and the influence of age should be considered to evaluate results of venous occlusion test.

Adult↗
PubMed1991

Promyelocytic leukemia cell line, HL-60, produces human hepatocyte growth factor.

The human promyelocytic leukemia cell line, HL-60, stimulated with PMA, produced human HGF-like immunoreactivity (HL-60 HGF), which was detected with human HGF-specific ELISA. The purified HL-60 HGF was indistinguishable from human HGF in the plasma of patients with fulminant hepatic failure by studies of subunit constitution and amino acid composition. The HL-60 HGF mRNA corresponded to 6 kb, which was consistent with previous reported data in rat and human HGF mRNA, was detected in stimulated HL-60, by northern hybridization analysis using human HGF cDNA probe. These findings indicated that HL-60 HGF was identical to, or closely resembled, human plasma HGF. The HL-60 cell is an attractive model for studies of HGF-producing mechanisms, the manner of secretion and the nature of induction signals.

Amino Acids↗
PubMed1990

Interleukin-1 beta analogues with markedly reduced pyrogenic activity can stimulate secretion of adrenocorticotropic hormone in rats.

We examined the adrenocorticotropic hormone-releasing activities of several human interleukin-1 beta analogues that have markedly reduced pyrogenic activities in rats. Among the analogues tested, [Gly4]-, [Leu93]- and [1-148]-interleukin-1 beta increased the plasma adrenocorticotropic hormone level to almost that induced by authentic human interleukin-1 beta. Modifications of the N-terminus of the authentic molecule, i.e., [7-153]- and [Des-Ala1, Asp4]-interleukin-1 beta, significantly reduced the hormone-releasing activity. These data suggest that the adrenocorticotropic hormone-releasing activity of human interleukin-1 beta resides in the N-terminal structure of the authentic peptide and can be separated from its pyrogenic activity.

Adrenocorticotropic Hormone↗
PubMed1990

The effect of cytochalasin D on protein synthesis in Xenopus laevis oocytes.

Defolliculated fully grown oocytes of Xenopus laevis were treated with cytochalasin D (10 micrograms/ml) and their protein synthesis was studied by labelling with S-35 methionine. This treatment brought about an alteration in pigment pattern as well as a reduction in amino acid uptake by the oocytes. However, the radioactive amino acid taken by cytochalasin-treated oocytes was incorporated into protein in the same proportion as in untreated oocytes. These results suggested that subcortical pigment distribution and amino acid uptake in fully grown oocytes were microfilament-dependent processes, whereas protein synthesis in the oocyte was not.

Actin Cytoskeleton↗