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Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 379 records · Page 21Linked to original sources
PubMed1995

Changes in the binding capacity of alpha-1-acid glycoprotein in patients with renal insufficiency.

The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (Kd). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.

Adult↗
PubMed1995

Characterization of matrix-degrading proteinases and their inhibitors secreted by human gynecological carcinoma cells.

Matrix-degrading proteinases secreted by tumor cells play crucial roles in tumor cell invasion and metastasis. Serum-free conditioned media of 7 human gynecological carcinoma cell lines were examined for proteinases and their inhibitors by using gelatin zymography, reverse zymography and immunoblotting. All of three ovarian adenocarcinoma cell lines secreted urokinase-type plasminogen activator. Among them, a mucinous cystadenocarcinoma cell line also secreted tissue-type plasminogen activator, plasmin-like enzyme and trypsinogen. On the other hand, two ovarian undifferentiated carcinoma cell lines mainly secreted glatinase A or B. A choriocarcinoma cell line secreted multiple metalloproteinases in the highest amount, whereas an endometrial adenocarcinoma cell line (HEC-1) derived from an early clinical stage hardly secreted any gelatinolytic enzyme. The five high proteinases producers hardly secreted the corresponding inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)-1, -2 or plasminogen activator inhibitor-1. In contrast to these highly malignant cell lines, a poor proteinase producer, HEC-1, secreted a large amount of TIMPs. Therefore, an enhanced proteolytic tendency appears to be associated with gynecological cancer cells established from highly malignant tumors.

Adenocarcinoma, Clear Cell↗
PubMed1995

Anti-tumor activity of arginine deiminase from Mycoplasma argini and its growth-inhibitory mechanism.

Two kinds of arginine deiminase (AD, EC 3.5.3.6) were purified from cell extracts of Mycoplasma arginini (a-AD) and Mycoplasma hominis (h-AD), and their enzymic properties and anti-tumor activities were compared. The a-AD enzyme strongly inhibited the growth of mouse hepatoma cell line MH134 in vitro, and its concentration required for 50% growth inhibition (IC50) was estimated to be about 10 ng/ml. The IC50 value of h-AD against the same cell line was estimated to be about 100 ng/ml, due to its low enzyme activity under the physiological pH condition, i.e., pH 7.4. These results show that the reaction pH profile of the a-AD was superior to that of the h-AD as an anti-tumor enzyme. Moreover, the effects of L-arginine metabolism-related substances on the anti-tumor activity of the a-AD were examined to study the growth-inhibitory mechanism of this enzyme. The addition of 2 or 4 mM L-arginine restored, in a dose-dependent manner, the growth of mouse MH134 hepatoma and Meth A fibrosarcoma cell lines that had been inhibited by 20 ng/ml of the a-AD. The addition of 2 or 4 mM L-ornithine, which is biosynthesized from L-arginine in the urea cycle and is the starting material in the polyamine-biosynthesis pathway, also partially restored it in a dose-dependent manner. These results indicate that the tumor cell growth inhibition caused by a-AD originates from the depletion of the essential nutrient L-arginine, and that the resulting block of the polyamine-biosynthesis pathway is involved in part in the inhibitory mechanism.

Amino Acid Sequence↗
PubMed1995

Improving the oral bioavailability of sulpiride by sodium oleate in rabbits.

To improve the limited oral bioavailability of sulpiride, a dosage form containing sodium oleate as an absorption enhancer was developed and evaluated using gastric-emptying-controlled rabbits in a cross-over manner. In addition to the known properties of sodium oleate with respect to modifying the permeability of biomembranes, it was found to be capable of improving the physicochemical properties of sulpiride toward a higher lipophilicity (by ion-pair association) and a higher solubility (by micellar solubilization). Nonetheless, the incorporation of sodium oleate with sulpiride as a mixture filled in hard gelatin capsules failed to increase intestinal absorption, whereas the use of enteric capsules, instead of the hard gelatin capsules resulted in a significant increase (P < 0.05) in the oral bioavailability.

Administration, Oral↗
PubMed1995

Adnexal masses: accuracy of characterization with transvaginal US and precontrast and postcontrast MR imaging.

PURPOSE: To determine the accuracy of transvaginal ultrasound (TVUS) and of precontrast and contrast material-enhanced magnetic resonance (MR) imaging in the differentiation of adnexal masses. MATERIALS AND METHODS: Five blinded readers analyzed images of 80 masses in 72 patients. MR and TVUS images were interpreted in separate sessions. Findings were confirmed at surgery or laparoscopy. RESULTS: Higher diagnostic accuracy was attained with MR imaging in mature cystic teratomas and endometriomas. However, better accuracy was achieved with contrast-enhanced MR imaging and TVUS in simple cysts, cystadenomas, and malignant tumors because internal details could be visualized. Receiver operating characteristic study indicated that observer confidence was significantly higher with contrast-enhanced MR imaging than with precontrast MR imaging (P = .011) or TVUS (P = .002) in the differentiation of benign and malignant masses. CONCLUSION: Contrast-enhanced MR imaging is superior to precontrast MR and TVUS imaging in the characterization and differentiation of adnexal masses.

Adnexal Diseases↗
PubMed1995

Transport mechanisms of enoxacin in rat brush-border membrane of renal cortex: interaction with organic cation transport system and ionic diffusion potential dependent uptake.

The mechanism of the renal transport of enoxacin (ENX) has been investigated using brush-border membrane vesicles (BBMVs) isolated from the rat renal cortex. The initial rate and time-course of ENX uptake were quite dependent upon the medium pH (pH 5.5 > pH 7.5). The pH dependence was in accordance with the degree of cationic form. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H(+)-gradient. The initial uptake was saturable, and transport kinetic parameters were given for a Km and Vmax of 0.59mM and 1.37nmol/(mg protein)/30s, respectively. On the other hand, an outward H(+)-gradient (pHin = 5.5, out = 7.5) dependent uptake of ENX was partially decreased by the voltage-clamped BBMVs. Furthermore, a valinomycin-induced K(+)-diffusion potential (interior negative) was found to increase the uptake of ENX at pH 5.5, which is cationic form-rich. These results suggest that ENX uptake participates in not only the H+/organic cation antiport system for organic cation secretion but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.

Animals↗
PubMed1995

Synthesis and antitumor activity of novel dolastatin 10 analogs.

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.

Animals↗
PubMed1995

Adenylyl cyclase activity in human decidua and myometrium during pregnancy and labour.

Adenylyl cyclase activity was studied in human decidua and myometrium in early pregnancy and at term before and after the onset of labour. Decidual basal, prostaglandin-, catecholamine- and forskolin-stimulated adenylyl cyclase activities at term before the onset of labour were significantly lower than those in early pregnancy. After the onset of labour at term, decidual basal, prostaglandin-, catecholamine-, NaF- and forskolin-stimulated adenylyl cyclase activities significantly increased compared with those at term before the onset of labour. Myometrial prostaglandin- and catecholamine-stimulated activities did not alter during pregnancy, except for basal and forskolin-stimulated activity. Myometrial basal, prostaglandin-, catecholamine-, NaF- and forskolin-stimulated activities at term showed no change after the onset of labour. At term, before the onset of labour, myometrial basal, prostaglandin, catecholamine-, NaF- and forskolin-stimulated activities were the same as those in the decidua. However, after the onset of labour at term, decidual basal and the stimulated activities were significantly higher than those in the myometrium. These results suggest that decidual prostaglandin- and catecholamine-stimulated adenylyl cyclase may play an important role in the initiation or maintenance of human labour or in both processes.

Adenylyl Cyclases↗
PubMed1995

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas.

The gene expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was studied in human gliomas in vivo and in vitro to evaluate their roles in glioma invasion. Simultaneous expression of one to four MMP genes and two TIMP genes was found in 17 surgical glioma specimens, and one MMP (gelatinase A) gene and two TIMP genes were simultaneously expressed in tissue of three brains. The concomitant overexpression of gelatinase A, gelatinase B, and occasional matrilysin genes was associated with the malignancy of gliomas and accompanied by overexpression of the TIMP-1 gene. In five human glioma cell lines, gelatinase A, TIMP-1, and TIMP-2 genes were constitutively expressed in alll cell lines: the matrilysin gene in three cell lines; the stromelysin gene in two cell lines; and the interstitial collagenase gene in one cell line. There was a clear difference in the expression of gelatinase B and stromelysin genes between surgical glioma specimens and glioma cell lines: the gelatinase B gene was not expressed constitutively in vitro but was overexpressed in vivo, whereas the stromelysin gene was not expressed in vivo but was expressed in some cell lines. To find the cause of that difference in vivo and in vitro, the transcriptional regulations of MMP and TIMP genes by tumor promoter, growth factors, or cytokines were studied in vitro. Interstitial collagenase, gelatinase B, stromelysin, and TIMP-1 genes were upregulated in many cell lines by phorbol-12-myristate-13-acetate (PMA) and in some cell lines by epidermal growth factor, tumor necrosis factor-alpha, or interleukin-1 beta. Transforming growth factor-beta 1 (TGF beta 1) upregulated gelatinase A and matrilysin genes in some cell lines, and there were no clear responses from any MMP and TIMP genes to interleukin-6. Thus, the transcriptional modulation of MMP genes by these growth factors and cytokines seemed insufficient to explain the difference in gelatinase B and stromelysin gene expressions in vivo and in vitro and was suggestive of the genetic alteration of glioma cells in vitro, the heterogeneous cell population in glioma tissues, or both. Furthermore, the in vitro invasion of glioma cells through Matrigel in response to PMA, TGF beta 1, or TIMP-1 was assessed by chemoinvasion assay. In most cell lines, invasion was significantly stimulated by PMA or TGF beta 1 but suppressed by TIMP-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Perception of relative pitch with different references: some absolute-pitch listeners can't tell musical interval names.

Two experiments were conducted to examine the effect of absolute-pitch possession on relative-pitch processing. Listeners attempted to identify melodic intervals ranging from a semitone to an octave with different reference tones. Listeners with absolute pitch showed declined performance when the reference was out-of-tune C, out-of-tune E, or F#, relative to when the reference was C. In contrast, listeners who had no absolute pitch maintained relatively high performance in all reference conditions. These results suggest that absolute-pitch listeners are weak in relative-pitch processing and show a tendency to rely on absolute pitch in relative-pitch tasks.

Female↗
PubMed1995

Contrast-enhanced dynamic MR imaging of postmolar gestational trophoblastic disease.

Conventional spin-echo (SE) and contrast-enhanced dynamic MR imaging were performed on a 1.5 T superconductive unit for evaluation of myometrial lesions in postmolar gestational trophoblastic disease (GTD) in 10 women. MR imaging was done at the time of the initial examination (n = 10), during (n = 6), and after repeated courses of chemotherapy (n = 10). The T2-weighted SE image revealed an enlarged uterus (n = 7), disappearance of zonal anatomy (n = 6), and heterogeneous signal intensities (n = 8) with prominent flow voids (n = 7). However, these abnormalities remained after repeated courses of chemotherapy, when the S-beta-HCG level returned to the normal range. Myometrial lesions characteristically had marked enhancement with areas of unenhancement on dynamic MR images in patients with highly elevated S-beta-HCG. Areas of contrast enhancement correlated with changes in S-beta-HCG level. The enhancement was reduced with decrease in S-beta-HCG level after repeated courses of chemotherapy. Six of 8 masses seen on T2-weighted images proved to be active trophoblastic lesions and 2 masses proved to be hematoma or necrosis. In 2 patients, abnormal myometrial lesions were detected only on contrast-enhanced dynamic MR imaging. These preliminary data indicate that contrast-enhanced dynamic MR imaging more clearly demonstrates myometrial involvement of postmolar GTD than conventional SE imaging.

Adult↗
PubMed1995

Sulphate reduction and methanogenesis in the ovine rumen and porcine caecum: a comparison of two microbial ecosystems.

A series of experiments was conducted to study the relationship between methanogenesis and sulphate reduction in ovine rumen and porcine caecum. Effect of 2-bromoethane sulphonate on hydrogen production by digesta suggested that the most important H2-disposal system in the rumen is methanogenesis and that methanogenesis is not predominant H2-disposal system in the porcine caecum. This inference was supported by the difference in predominant H2-utilizers in these two microbial ecosystems; Methanogenic bacteria (MB) were predominant in the rumen and sulphate reducing bacteria (SRB) were predominant in porcine caecum. Free sulphate levels in digesta appear to affect the relationship between MB and SRB. Sulphate levels in the rumen were likely to be insufficient for SRB to outcompete MB.

Animals↗
PubMed1995

[TIMPs (tissue inhibitors of metalloproteinases): their species, functions and effects on tumor metastasis].

TIMPs (tissue inhibitors of metalloproteinases) belong to a family composed of three members: TIMP-1, -2 and -3. They possess a high degree similarity in their structure including 12 conserved cystenyl residues at the same relative positions. Recently, they have been shown to inhibit not only proteolytic activities of metalloproteinases but also tumor cells metastasis in vitro and in vivo. In this review, we summarize their structure information, inhibitory mechanism of metalloproteinases, TIMPs-like secretory inhibitors, other biological functions of TIMPs such as growth-regulating activity, their chromosomal localizations and related diseases. We also mention their inhibitory effects on tumor cells metastasis in vitro and in vivo, and their clinical applications.

Glycoproteins↗
PubMed1995

[Increased expression of gelatinases A and B, matrilysin and TIMP-1 genes in human malignant gliomas ].

Malignant glioma is a local invasive tumor in the central nervous system. The mRNA expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was examined in surgical specimens of three brain tissues, two astrocytomas, four anaplastic astrocytomas and eleven glioblastomas, including recurrent one anaplastic astrocytoma and two glioblastomas. In the control brain tissues, mRNA expression was high for TIMP-2, low for gelatinase A and TIMP-1, and undetectable for gelatinase B, interstitial collagenase, stromelysin and matrilysin. Gelatinase B and TIMP-1 were concomitantly overexpressed in primary glioblastomas. In addition, the average expression level of gelatinase A increased 3.0 fold in astrocytomas and anaplastic astrocytomas and 6.0 fold in glioblastomas, compared to the brain tissues. Matrilysin was induced variably in more than half of the primary glioblastomas, and interstitial collagenase was slightly induced in some primary and recurrent glioblastomas. Stromelysin was characteristically not expressed in any gliomas, and the expression level of TIMP-2 did not significantly change in the gliomas. These results suggest that the concomitant increased expression of gelatinase A, gelatinase B and occasional matrilysin genes is associated with the malignancy of gliomas and accompanied by the increased expression of TIMP-1 gene.

Astrocytoma↗
PubMed1995

Hepatopancreatoduodenectomy for squamous and adenosquamous carcinoma of the gallbladder.

The characteristics of squamous or adenosquamous cell carcinoma of the gallbladder differ quite markedly from those of adenocarcinoma, although the incidence is extremely low. Recently, we encountered both of the former types of gallbladder carcinoma: a 77-year-old man with squamous cell carcinoma and a 70-year-old man with adenosquamous cell carcinoma of the gallbladder. Both had a large mass in the gallbladder fossa region with infiltration to the liver and invasion of the duodenum. Hepatopancreatoduodenectomy was performed on both of these patients. The TNM stage of the former was IV (T4N0M0) and of the latter IV (T4N0M0) and of the latter IV (T4N1bM0). The former has remained well without recurrence for about 1 year and 4 months after the operation, while the latter died of recurrent disease 6 months after operation. The true reason for the difference in the prognosis of these two patients was not known. However, hepatopancreatoduodenectomy is considered to be a most adaptable operative procedure for squamous or adenosquamous cell carcinoma of the gallbladder in view of their mode of spread, and the presence of lymph node metastasis might be a factor of poor prognosis.

Aged↗