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K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 361 records · Page 20Linked to original sources
PubMed1995

Comparison of the transport characteristics of ceftibuten in rat renal and intestinal brush-border membranes.

The transport characteristics of ceftibuten, a dianionic cephem antibiotic, in rat renal and intestinal brush-border membranes were compared. Ceftibuten transport was mediated by two transport systems in the renal brush-border membrane and by one transport system in the intestinal brush-border membrane. The apparent kinetic parameters for the uptake of ceftibuten by the renal brush-border membrane vesicles, respectively, were: Km1, Km2 values of 26 and 1946 microM and Vmax1, Vmax2 values of 105 and 1400 pmol/mg protein per 30 s. The apparent kinetic parameters for the uptake by the intestinal brush-border membrane vesicles were: Km of 425 microM and Vmax of 1701 pmol/mg protein per 30 s. In the renal brush-border membrane, L-Ala-L-Pro was partially competitive and competitive inhibitor for the uptake by the high and low affinity systems, respectively. However, L-Ala-L-Pro was a non-competitive inhibitor for the uptake by the intestinal brush-border membrane vesicles. L-Carnosine was a specific and competitive inhibitor for the high affinity system in the renal brush-border membrane, while it had no effect on the low affinity system of the kidney or on the transport system of the intestine. It was concluded that the transport characteristics of ceftibuten in the renal and intestinal brush-border membranes are similar in some aspects but they are not identical.

Animals↗
PubMed1995

Release of biological activities from quiescent fibronectin by a conformational change and limited proteolysis by matrix metalloproteinases.

We reported that specific biological activities are confined to three domains of the fibronectin (Fn) molecule [Fukai et al. (1991) J. Biol. Chem. 266, 8807; Fukai et al. (1993) Biochemistry 32, 5746]: the potent ability to stimulate the adipocyte differentiation of ST-13 cells is in the amino-terminal fibrin-binding (Fib 1) domain (referred to as Fib 1 domain activity); the RGD-dependent activities that stimulate NIH-L13 cell migration and inhibit adipocyte differentiation are in the central cell-binding (Cell) domain (Cell domain activity); and the activity that stimulates cell migration in a RGD-independent manner is in the carboxyl-terminal fibrin-binding (Fib 2) domain (Fib 2 domain activity). Human plasma Fn which was purified without exposure to a denaturant, such as urea, exhibited no Fib 1, Fib 2, or Cell domain activity. By exposure to urea or surface adsorption, Fn showed Cell domain activity but not those of the Fib 1 and Fib 2 domains. Whether the cryptic domain activities are disclosed or not depended on whether or not the responsible domains were irreversibly exposed from confined environments of Fn structure as confirmed by light-scattering measurement and enzyme immunoassay using domain-specific monoclonal antibodies. We then investigated the action of matrix metalloproteinases (MMPs) in liberating the Fib 1, Cell, and Fib 2 domain activities. Matrilysin released only the Cell domain activity. In contrast, stromelysin, collagenase, and especially gelatinase A additionally liberated the Fib 1 and Fib 2 domain activities. The Fib 1, Fib 2, and Cell domains acquired much higher activities when they were freed from linkage with adjacent domains.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Effect of membrane surface potential on the uptake and the inhibition of cationic compounds in rat intestinal brush-border membrane vesicles and liposomes.

The effect of membrane surface potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was investigated. In the presence of an inside-negative K(+)-diffusion potential, the manner of initial uptake of tryptamine appeared to be pH-dependent and the uptake in the acidic medium was lower than that in the neutral medium. Changes in surface potential of brush-border membrane vesicles were monitored using 8-anilino-1-naphthalenesulfonic acid (ANS) and the results suggested that the membrane surface potential (negative charge on the membrane surface) decreased in the acidic medium. A good correlation was observed between the K(+)-diffusion potential-dependent uptake of tryptamine and membrane surface potential monitored by ANS at various pH levels. The uptake of tryptamine by liposomes (large unilamellar vesicles), which contained various amounts of dipalmitoylphosphatidylserine (DPPS), was also examined. The uptake of tryptamine decreased with a decrease of DPPS content in the liposomes, and was correlated with the membrane surface potential monitored by ANS. Moreover, the effect of organic cations on the uptake of tryptamine by intestinal brush-border membrane vesicles was examined. The uptake of tryptamine was inhibited by tetracaine and imipramine. The inhibitory effect of these cations was well correlated with changes in the membrane surface potential in the presence of tetracaine or imipramine. These results suggest that the K(+)-diffusion potential-dependent uptake of tryptamine by intestinal brush-border membrane vesicles is affected by membrane surface potential, and the inhibition of tryptamine uptake originates in changes in the membrane surface potential caused by the organic cations.

Animals↗
PubMed1995

Alpha-1-acid glycoprotein concentration and the protein binding of disopyramide in healthy subjects.

Age- and gender-related changes in serum alpha 1-acid glycoprotein (AAG) concentration and the serum protein binding of disopyramide were examined after intensive medical examination. Based on the clinical chemistry tests over 51 points, 245 subjects were diagnosed as healthy and 71 subjects (22.5%) revealed an abnormal value for at least one item. In the healthy subjects, serum AAG concentration in men was significantly higher than in women (men, 0.78 +/- 0.18 mg/mL, mean +/- SD; women, 0.67 +/- 0.16 mg/mL). In contrast, there were no significant differences in the AAG concentration between age groups for men and women and in the unbound fraction of disopyramide. Gender changes AAG concentration. Age, however, does not change AAG concentration and the protein binding of the basic drug.

Adolescent↗
PubMed1995

Activated (HLA-DR+) T-lymphocyte subsets in cervical carcinoma and effects of radiotherapy and immunotherapy with sizofiran on cell-mediated immunity and survival.

A prospective randomized trial on 312 patients with locally advanced cervical carcinoma (FIGO stages IB-IV) was carried out. The 5-year survival in 90 patients treated with radiotherapy and antitumor polysaccharide sizofiran, an extract from the culture broth of Schizophyllum commune Fries, in combination was significantly (P = 0.045) better than that in 82 patients treated with radiotherapy alone. Treatment with sizofiran and 5-fluorouracil in combination improved (P = 0.003) the 5-year survival in 60 patients treated with radiotherapy. In 244 cervical carcinoma patients, the percentage of activated CD8+ (CD8+HLA-DR+) T cells in the CD8+ T-cell subsets in peripheral lymphocytes increased significantly as the disease progressed. A similar tendency was observed in the percentage of activated CD4+ (CD4+HLA-DR+) T cells in the CD4+ T-cell subsets. These immunologic parameters were significantly increased by radiotherapy, but not by surgery. Sizofiran accelerated a recovery in the activated CD8+ T cells in the CD8+ T-cell subsets compared with that of sizofiran nontreated patients after radiotherapy. Our data show that possible immune impairment in cervical carcinoma may be caused by disturbances in cell-mediated immunity, and that sizofiran is an effective immunotherapeutic agent for cervical carcinoma because it stimulates a rapid recovery of the immunologic parameters impaired by radiotherapy.

CD4-CD8 Ratio↗
PubMed1995

Immunological disorder against the Epstein-Barr virus infection and prognosis in patients with cervical carcinoma.

Epstein-Barr virus antigen-specific killer T cell (EBV-KT) activity and Epstein-Barr virus (EBV) shedding at uterine cervix and oropharynx were examined in patients with cervical carcinoma. EBV-KT activity was determined by a modified EBV-induced B cell focus regression assay. EBV shedding was examined by infectivity assay. EBV-KT activity in the patients was decreased significantly compared with that of controls (P < 0.001) and became increasingly lower as the clinical stage of the disease advanced. EBV-KT activity was changed by treatment, and decreased EBV-KT activity after treatment was clearly related to patient survival. EBV shedding at oropharynx and uterine cervix were also higher in the patients than in the controls (P < 0.01 and < 0.05). These results suggest that EBV-KT activity is closely associated with the prognosis in patients with cervical carcinoma and that it may be a useful parameter in monitoring the cell-mediated immunity of patients with cervical carcinoma.

Adult↗
PubMed1995

Activated (HLA-DR+) T-lymphocyte subsets in early epithelial ovarian cancer and malignant ovarian germ cell tumors.

We examined peripheral blood T-lymphocyte subsets before initiation of therapy in 79 healthy controls, 3 patients with endometriosis, 95 patients with common epithelial tumors of the ovary, 15 patients with ovarian germ cell tumors, and 3 patients with ovarian sex cord-stromal tumors. In stage Ia/Ib patients with epithelial ovarian cancer, the percentages of activated CD4+ (CD4+HLA-DR+) T cells and activated CD4+ T cells in the CD4+ T-cell subsets were significantly higher than those of healthy controls and patients with benign or borderline epithelial tumors of the ovary. These immunologic parameters were subsequently decreased in patients in stage Ic and more advanced stages. In malignant ovarian germ cell tumors, a similar increase in the CD4+ T-cell subsets was observed. Moreover, the percentage of activated CD8+ T cells in the CD8+ T-cell subsets in stage Ia/Ib patients increased significantly compared with those in healthy controls and patients with benign tumors. Our findings indicate that activated T lymphocytes may play some roles in oncogenesis and progression of both epithelial ovarian cancer and malignant ovarian germ cell tumors.

CD4-Positive T-Lymphocytes↗
PubMed1995

Marked induction of gelatinases, especially type B, in host fibroblasts by human ovarian cancer cells in athymic mice.

Two human ovarian adenocarcinoma cell lines, MCAS-3 and OVISE-3 were found to secrete little of any type of gelatinase in tissue culture. However, when these cell lines were implanted subcutaneously into nude mice the cyst fluids from the resultant tumors contained gelatinase A and/or B. The enzyme activities, especially of gelatinase B, were much higher in the malignant MCAS-3 tumors than in those of the less malignant OVISE-3 tumor cells. To elucidate the origin of gelatinase B in cyst fluids of the MCAS-3 tumors, murine skin fibroblasts (MSF) were isolated from a subcutaneous tumor in a nude mouse and tested for their proteinase secretion in culture. MSF cells, which secreted some gelatinase A and gelatinase B, were induced to secrete high levels of both enzymes, especially gelatinase B, by co-cultivation with MCAS-3 cells. In addition, gelatinase A activity was induced by incubation of MSF cells with the conditioned medium of either MCAS-3 or OVISE-3 cells, whereas gelatinase B was induced only with that of MCAS-3. Although cytokines or growth factors such as IL-1 beta, TGF-beta 1, TNF-alpha or EGF stimulated the secretion of gelatinases A and B from MSF cells, their effects on gelatinase B activity were far less than that of the MCAS-3 conditioned medium. These results indicate that the major part of gelatinase B activity in the cyst fluids of the ovarian tumors is secreted by host interstitial cells stimulated by tumor-derived humoral factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types.

Animals↗
PubMed1995

Selective localization of gelatinase A, an enzyme degrading beta-amyloid protein, in white matter microglia and in Schwann cells.

Gelatinase A is an enzyme capable of cleaving soluble beta-amyloid protein (beta AP), and may function as an alpha-secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (AD), amyotrophic lateral sclerosis, progressive supranuclear palsy and myasthenia gravis cases. The gelatinase A antibody stained only microglial cells in the white matter in all the brain tissues. In AD brain, the reactive microglia located in the center of classical senile plaques, as well as in other microglial cells in the gray matter, showed no immunoreactivity. Gelatinase A in white matter microglial cells may play a role in preventing local deposition of beta AP. In the posterior root, Schwann cells had positive immunoreactivity. As with other metalloproteases, gelatinase A in Schwann cells may play an antiproliferative role.

Aged↗
PubMed1995

Comparative clinical features of stage A1 and stage A2 prostate cancers. Is the concept of stage A changing from the current status?

We surveyed the comparative clinical features of patients with stage A1 and stage A2 prostate cancer. Preoperatively, prostate specific antigen (PSA) level was elevated in 50.0% of stage A2 patients as compared to 18.2% of stage A1 patients. Compared to low positivity of prostatic acid phosphatase in 12.5% of stage A2 and in 0% of stage A1, PSA was more sensitive to the presence of incidental carcinoma. During the observation period (mean 35.7 months) no stage A patient died of cancer. No evidence of the disease showed significantly higher rate, and death without cancer was significantly lower in stage A1.

Acid Phosphatase↗
PubMed1995

The occurrence of silicon-containing particles in calcified lesions of DBA/2NCrj mice.

The crystalline structure in calcified deposits of DBA/2 mice was analysed, because understanding this is essential in assessing the significance of this species as an animal model for spontaneous soft-tissue mineralization. In order to remove the thin soft tissue which covers the lesion, the samples were bombarded with an argon beam. The uncoated samples were analysed with an electron-probe microanalyser. The deposits were composed of a calcium phosphate material. At a higher magnification, smaller particles surrounding these large deposits were found. There were three types of particles: rod-shaped (calcium phosphate), polygonal (silicate) and round (about 1 microns dia).

Animals↗
PubMed1995

Stimulation of cyclic adenosine 3',5'-monophosphate-dependent protein kinase with brain gangliosides.

The holoenzyme of cAMP-dependent protein kinase (cAMP-kinase) partially purified from the particulate fraction of rat brain was stimulated by gangliosides. Among various gangliosides tested, GM1 was most potent, giving Ka value of 19.5 microM. The maximal activation of the kinase was obtained with 100 microM GM1 using kemptide as substrate. Gangliosides inhibited the kinase activity of the catalytic subunit of cAMP-kinase. Of various substrates tested, the ganglioside-stimulated cAMP-kinase could phosphorylate microtubule-associated protein 2, synapsin I and myelin basic protein, but not histone H1 and casein. The molecular mechanisms of the stimulatory effect of gangliosides were investigated. The kinase activated with GM1 was inhibited by the addition of PKItide, a specific inhibitor for cAMP-kinase. However, GM1 did not dissociate the holoenzyme into the catalytic and regulatory subunits and did not interfere with the binding ability of cAMP to the holoenzyme. These results suggest that the gangliosides can directly activate cAMP-kinase in a different manner from cAMP.

Animals↗
PubMed1995

A rare case of absence of the celiac trunk: the left gastric, the splenic, the common hepatic and the superior mesenteric arteries arising independently from the abdominal aorta.

This report describes a rare case of absence of the celiac trunk, which was encountered in a Japanese female cadaver in the dissecting room at Kurume University School of Medicine in 1993. In this case, the left gastric, the splenic, the common hepatic and the superior mesenteric arteries arose independently in that order from the abdominal aorta. In addition, the left aberrant hepatic artery arose from the left gastric artery. This anomalous case belongs to type 5 (Typus primitivus) of Morita's classification (1935), and is the fifth case of this kind of vascular variation to be reported in Japan.

Aged↗
PubMed1995

The intestinal transport mechanism of fluoroquinolones: inhibitory effect of ciprofloxacin, an enoxacin derivative, on the membrane potential-dependent uptake of enoxacin.

PURPOSE: To clarify the absorption-structure relationship for the fluoroquinolones from the point of view of inhibitory behavior. METHODS: The inhibitory effects of ciprofloxacin on the transport process of enoxacin across the rat intestinal brush-border membrane was examined. RESULTS: Ciprofloxacin, which has a similar structure to enoxacin, exhibited a pH-dependent interference with enoxacin absorption from rat jejunal loops. The uptake experiments using BBM vesicles showed that ciprofloxacin significantly reduced not only the initial binding of enoxacin to the membrane surface, but also the K(+)- or H(+)-diffusion potential-dependent transport across the membrane. Furthermore, an H(+)-diffusion potential (interior negative) also exhibited a stimulative uptake of ciprofloxacin. CONCLUSIONS: These results suggest that the inhibition behavior of ciprofloxacin from the jejunal loop was closely related to the ionic diffusion potential-dependent uptake of enoxacin across the brush-border membrane.

Animals↗
PubMed1995

Transport mechanism of ceftibuten, a dianionic cephem, in rat renal brush-border membrane.

The uptake mechanism of ceftibuten by rat renal brush-border membrane vesicles was investigated. Uptake was found to be independent of a Na+ gradient and partially dependent on an inwardly directed H(+)-gradient. Competition experiments between ceftibuten and several compounds demonstrated that the peptide-like structural features of inhibitors are more essential than their charge properties for inhibiting uptake. Anionic compound, such as p-aminohippuric acid, also inhibited ceftibuten uptake by renal brush-border membrane vesicles in the presence of an H(+)-gradient. We conclude that ceftibuten, in spite of its anionic structure, is transported via the dipeptide transport systems, rather than the organic anion transport system.

Animals↗
PubMed1995

Changing autoantibody profiles with variable clinical manifestations in a patient with relapsing systemic lupus erythematosus and polymyositis.

The production of autoantibodies characteristic of different autoimmune disease subsets is thought to be controlled primarily by genetic factors, whereas non-genetic factors are generally believed to be of secondary importance. A patient with systemic lupus erythematosus (SLE) and polymyositis (PM) who experienced frequent relapses associated with changing clinical manifestations and autoantibody specificities is reported. Her initial presentation as SLE with anti-Sm antibodies shifted to the onset of PM with temporal production of a different set of autoantibodies. The latter antibodies disappeared when myositis resolved, followed by the reappearance of autoantibodies and clinical manifestations characteristic of SLE. The shifts of autoantibody profiles in association with variable clinical manifestations in this patient argue that environmental factors may play a more important role in autoimmunity than previously supposed, and that interplay between environmental triggers and genetic predisposing factors may lead to the constellation of autoimmune disease manifestations exhibited at a particular time.

Adult↗