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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 271 records · Page 15Linked to original sources
PubMed1995

Analysis of the relationship between cellular thymidine kinase activity and virulence of thymidine kinase-negative herpes simplex virus types 1 and 2.

The virulence of thymidine kinase-negative herpes simplex virus type 1 (HSV-1; VRTK- strain) and type 2 (HSV-2; UWTK- strain) was studied in comparison with that of their parental strains (VR-3 and UW-268, respectively) in an encephalitis model of adult (4-week-old) and newborn (3-day-old) mice. Viral thymidine kinase (TK) activity was essential for the maximum expression of virulence of HSV-1, because the 50% lethal dose (LD50) of VRTK- was 60 times higher than that of VR-3 in the brains of newborn mice expressing high levels of cellular TK activity. However, the UWTK- strain showed that replication of the UWTK- strain was completely supported by cellular TK activity. This difference in the role of viral and cellular TKs for virus growth between HSV-1 and HSV-2 was¿ confirmed with the one-step growth of virus strains in L-M and L-M(TK-) cells.

Amino Acid Sequence↗
PubMed1995

Percutaneous absorption of indomethacin from pluronic F127 gels in rats.

Thermally reversible gels of the poly(oxyethylene)-poly (oxypropylene)-(polyoxyethylene) triblock copolymer, Pluronic F127, were evaluated as vehicles for the percutaneous administration of drugs using indomethacin as a model drug. In-vivo percutaneous absorption studies using a rat model suggest that a 20% w/w aqueous gel of Pluronic F127 may be of practical use as a base for topical administration of the drug. The addition of isopropyl myristate or (+)-limonene to the gel formulation significantly improved percutaneous absorption, particularly when the gel was applied using an occlusive dressing technique.

Animals↗
PubMed1995

Identification of varicella-zoster virus strains by PCR analysis of three repeat elements and a PstI-site-less region.

We established a method of identifying varicella-zoster virus (VZV) strains, especially those of the Oka vaccine, in patients with clinical VZV infections. The DNAs of 30 clinically isolated strains and 4 laboratory strains including the Oka vaccine strain and its parent VZV strain, were analyzed by PCR with four sets of primers for the four variable regions, R2, R4, R5, and a region without a PstI site (PS). R4 was unstable in four laboratory VZV strains and was excluded from the study. The other regions were stable in several passages in cell culture. The number of copies in R2 and R5 were distributed from 2 to 13 and from 1 to 3, respectively, in the strains analyzed. The vaccine strain had seven copies in R2 and two copies in R5, and it was PS negative. Among 30 clinical isolates, 3, 23, and 11 strains had the same characteristics as the vaccine strain in R2, R5, and PS, respectively. Therefore, by this method, 97.2% of the isolates were distinguished from the Oka vaccine strain. This strategy will be useful in diagnosing VZV infections induced by the vaccine strain.

Adult↗
PubMed1995

Corticoid-induced differentiation of amiloride-blockable active Na+ transport across larval bullfrog skin in vitro.

The hormone-induced differentiation of an active Na+ transport across larval bullfrog skin during metamorphosis was investigated in vitro and in vivo. In in vitro experiments, EDTA-treated larval dorsal skin from which apical cells were removed was used. Even in the absence of thyroid hormone, corticoids induced the differentiation. Although aldosterone was the most potent hormone, hydrocortisone or corticosterone was also effective. Prolactin inhibited the corticoid-induced differentiation. The differentiation of the transport system coincided almost exactly with the appearance of adult features of the epidermis, namely, the epidermis at 7 days carried the human blood group antigen A, a specific molecular marker of adult-type bullfrog epidermis. The transport system appeared to develop in cells that had been newly generated from basal cells. On the contrary, in in vivo experiments, the effect of amiloride on the short-circuit current of the skin of tadpoles raised in the presence of aldosterone was very small, suggesting that a mechanism exists to inhibit the ability of aldosterone to induce the differentiation of the transport system in vivo.

Amiloride↗
PubMed1995

Prolactin inhibits corticoid-induced differentiation of active Na+ transport across cultured frog tadpole skin.

Active Na+ transport differentiates in larval bullfrog skin cultured with corticoids. After 2 wk in culture, the epidermis became positive against human blood group antigen A, the marker for the adult-type cells of the epidermis, but was negative to the antibody against the acetylcholine receptor, the marker for the larval-type epidermis. Amiloride (10(-5) M) did not inhibit the differentiation of active Na+ transport. On the other hand, in skin cultured with prolactin (2 micrograms/ml), the epidermis remained negative against antigen A and positive against acetylcholine receptor, and the differentiation of active Na+ transport was inhibited. Thyroid hormone did not antagonize the inhibitory action of prolactin on this transport differentiation. Prolactin affected the basal cells of the larval epidermis and inhibited development of corticoid-induced adult features in the epidermis.

Adrenal Cortex Hormones↗
PubMed1995

Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer. Southern Osaka Lung Cancer Study Group.

PURPOSE: To evaluate the response rate, toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3N0-1M0 disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mg/m2 on days 1, 8, 29, and 36), cisplatin (100 mg/m2 on days 1 and 29), and mitomycin (8 mg/m2 on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), followed by 10-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. RESULTS: Of 61 eligible patients, 53 (86.9%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) are alive and disease-free after 2 years. The major toxicity was leukopenia (> or = grade 3, 95%). Other toxicities of > or = grade 3 included thrombocytopenia (45%), anemia (28%), nausea/vomiting (16%), fever (11%), and esophagitis (6%). Treatment-related death occurred in two patients. One patient died of pulmonary toxicity (interstitial pneumonitis) and the other of esophagobronchial fistula with pulmonary infection. CONCLUSION: Concurrent radiotherapy plus chemotherapy with mitomycin, vindesine, and cisplatin (MVP) can be safely administered to patients with stage III NSCLC, with excellent response rates and 2-year survival rates.

Adult↗
PubMed1995

The free form of insulin-like growth factor I increases in circulation during normal human pregnancy.

The main circulating insulin-like growth factor-binding protein (IGFBP) in human, IGFBP-3, markedly decreases during pregnancy, as determined by Western ligand blotting, and its decrease is due to an endogenous pregnancy-related serum IGFBP-3 proteolytic activity. Proteolysis of IGFBP-3 may result in the free form of IGF-I (fIGF-I) being liberated from or weakly bound to IGFBP-3 fragments. The purpose of this study was to determine the plasma concentration of fIGF-I and the mechanism of fIGF-I regulation during normal human pregnancy. We studied 19 normal pregnant women at 6-8 weeks gestation, 24 normal pregnant women at 28-30 weeks gestation, and 25 nonpregnant women. We measured plasma fIGF-I using a recently established immunoradiometric assay. We also measured plasma total IGF-I (free plus complexed forms of IGF-I) using immunoradiometric assay, and IGFBP-3 proteolytic activity using a IGFBP-3 protease assay. fIGF-I levels at 6-8 weeks gestation (4.11 +/- 0.23 ng/mL) and at 28-30 weeks gestation (3.67 +/- 0.21 ng/mL) were significantly higher than that in nonpregnant women (2.48 +/- 0.12 ng/mL; P < 0.001 in both). Total IGF-I levels at 6-8 weeks gestation (168.0 +/- 9.1 ng/mL) and at 28-30 weeks gestation (241.5 +/- 19.0 ng/mL) were significantly lower than that in nonpregnant women (283.9 +/- 12.3 ng/mL; P < 0.001 at 6-8 weeks gestation and P < 0.05 at 28-30 weeks gestation). All pregnant serum studied had IGFBP-3 proteolytic activity. These data indicate that during normal human pregnancy, circulatory fIGF-I increases, probably due to IGFBP-3 proteolytic activity.

Adult↗
PubMed1995

Thermally gelling poloxamine Synperonic T908 solution as a vehicle for rectal drug delivery.

Thermally reversible gels of the block copolymer, Synperonic T908, have been evaluated as vehicles for the rectal administration of indomethacin. Prolonged plasma levels of indomethacin following rectal administration in such gels was observed with the 40% w/w Synperonic T908 gels when compared with commercial suppositories. The release rate decreased with an increase in gel concentration over the range 30% to 40% w/w. Histological observation showed no damage to the rectal mucosal membrane in animals at 6 h after the administration of a 40% w/w gel.

Animals↗
PubMed1995

Na(+)- and energy-dependent transport of cadmium into LLC-PK1 cells.

Effects of sodium ions (Na+) and metabolic inhibitors on cadmium (Cd) uptake were investigated in LLC-PK1 cells derived from pig kidney under the nontoxic conditions of Cd. The inoculated cells became confluent on day 7 after the logarithmic growth phase. The initial uptake of Cd (1-60 microM) by the confluent cells (day 7) was assayed. The relationship between the Cd uptake at 37 degrees C and Cd concentration was nonlinear, but the relationship at 4 degrees C was linear. Subtraction of the Cd uptake at 4 degrees C from that at 37 degrees C showed a saturable uptake against the Cd concentration. By the Eadie-Hofstee analysis of saturable uptake, Km and Vmax were 24.6 microM and 164 pmol Cd/mg protein/min, respectively. The uptake of Cd by the cells was significantly decreased by ouabain and the metabolic inhibitors, and by the replacement of Na+ with potassium or choline ion in the incubation medium. These results suggest that Cd is incorporated into the confluent LLC-PK1 cells not only by simple diffusion but also by the carrier-mediated transport involved in Na(+)- and energy-dependent process(es).

2,4-Dinitrophenol↗
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

Biliary excretion of furosemide glucuronide in rabbits.

Furosemide (F) was administered to rabbits intravenously and intraduodenaly and the biliary excretion was studied. The major metabolite excreted in bile was furosemide glucuronide (FG). F and acyl migration isomers of FG (FG-iso) were also excreted in bile. The biliary excretion rates of total F (F+FG+FG-iso) following intraduodenal administration of F were much smaller than those following intravenous administration. The fraction of (F+FG-iso) in bile following intraduodenal administration of F were larger than those following intravenous administration. Stability of FG or FG-iso in bile and supernatant solution of the duodenum homogenate of rabbits was studied. FG was unstable in both media and its degradation followed apparent first-order kinetics in both media. In bile, FG degraded to produce several FG-iso and F, while in the supernatant solution of the duodenum homogenate, it hydrolyzed immediately to F. FG-iso were hardly detected in the supernatant solution. These results indicated that FG excreted in bile degraded easily to FG-iso and F. FG might easily hydrolyze to F enzymatically in the duodenum, and the resultant F might be reabsorbed from the intestinal tract. Unabsorbed FG-iso and F might be excreted in the feces.

Adult↗
PubMed1995

[The uptake of nalidixic acid and enoxacin by rat renal cortical slices in rat].

The mechanisms involved in the renal excretion of quinolone and new quinolone antibacterial drugs are still incompletely understood. The purpose of this study was to examine the renal handling of nalidixic acid (NA) and enoxacin (ENX), using the renal cortical slices uptake techniques in rats. It was demonstrated that both NA and ENX were taken against a concentration gradient by a saturable processes resulting from the ratio of slice to medium (ratio of S/M) being dependent on the time and the concentration. It was indicated that the inhibition of uptake by 2,4-dinitrophenol, ouabain and sodium cyanate was shown to be an energy dependence. Probenecid and cimetidine exhibited that they might inhibit NA uptake slightly. ENX uptake was inhibited by probenecid, cimetidine, guanidine and disopyramide, suggesting that ENX might possess an affinity for both anionic and cationic transport mechanisms.

Animals↗
PubMed1995

Chronic intramedullary infusion of prostaglandin E2 stimulates bone formation both in the bone marrow and in the periosteum.

Prostaglandin E2 (PGE2) has a potent bone resorbing activity in vitro, but some recent studies have shown that PGE2 stimulates bone formation in vivo. The effects of PGE2 on the bone are therefore still controversial. We attempted to reveal the effects of PGE2 on bone in vivo more directly; we injected PGE2 continuously into the bone marrow and onto the periosteum and examined the local effects of PGE2 histologically or by bone densitometry. Following PGE2 infusion into the bone marrow, new bone was formed in the bone marrow around the infused site and following PGE2 infusion onto the periosteum, extensive periosteal bone formation was observed. Bone mineral content was also increased significantly in the PGE2 infused bones. The administration of cyclic AMP did not mimic the effects of PGE2. In contrast to in vitro experiments, the in vivo effect of PGE2 is predominantly to produce bone.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Stachybocins, novel endothelin receptor antagonists, produced by Stachybotrys sp. M6222. I. Taxonomy, fermentation, isolation and characterization.

Stachybocins A, B and C, novel endothelin (ET) receptor antagonists, were isolated from the culture filtrate of Stachybotrys sp. M6222. They were extracted with ethyl acetate and then purified by alumina and silica gel column chromatographies. The molecular formulae of stachybocins were determined to be C52H70N2O10 (stachybocin A) and C52H70N2O11 (stachybocins B and C). It was supposed that they consisted of spirobenzofuran and terpene units from NMR spectra. They showed the inhibitory activity of 125I-ET-1 binding to rate ETA, human ETA and human ETB receptors.

Animals↗
PubMed1995

Significance of serum neuron-specific enolase as a predictor of relapse of small cell lung cancer.

We conducted a prospective study to evaluate the significance of serum neuron-specific enolase (NSE) as a predictor of relapse of small cell lung cancer (SCLC). Patients entered into the study were drawn from those who had shown a complete or partial response to first-line chemotherapy with a concurrent decline in the NSE level to less than 10 ng/ml. When the serum NSE level increased to more than 15 ng/ml, the patient was restaged on the basis of clinical, radiological, and bronchoscopic examinations. During the period from August 1988 to December 1990, 57 patients with SCLC were enrolled and followed up until May 1992. Of these patients, 45 had clinical relapses, and 14 (31%) of them showed a clear elevation of the serum NSE level prior to the clinical recognition of relapse. Although one false-positive case was noted, this involved only a transient elevation of the NSE level. In patients who showed increased NSE levels, the relapses occurred in more difficult to detect silent sites such as the adrenal gland, liver, and deep lymph nodes. In addition, the percentage of patients demonstrating high NSE levels who were able to benefit from salvage chemotherapy was higher than for those who did not (RHO < 0.05). Our results indicate that serial NSE measurements are useful for the early prediction of SCLC relapse and should help to facilitate early administration of salvage chemotherapy for affected patients.

Adult↗
PubMed1995

[Influence of genetic factors on family history of upper urinary stones].

The family history between patients with upper urinary tract stones and healthy subjects was compared to evaluate the possible involvement of genetic factors in obtaining information through a questionnaire. The patients showed a significantly more marked history than the healthy subjects (p < 0.001). In particular, recurrent stone formers showed a significantly more marked history than single stone formers (p < 0.05). Compared with the healthy subjects, a more marked family history was observed in the parents, brothers and sisters, and children, but not in the spouse (p < 0.05-0.005). However, the family history was not affected by consanguineous marriage. A more marked family history was observed in patients with upper urinary tract stones, suggesting the involvement of genetic factors in the development of upper urinary tract stones. In particular, genetic factors seem to be more closely involved in recurrent stone formers.

Adult↗
PubMed1995

[A model for sensitivity determination of anticancer agents against chemical-induced colon cancer in rats].

Chemically-induced colon cancer was used to test the sensitivity of tumors to chemotherapeutic agents. Thirty-four Sprague-Dawley rats received dimethylhydrazine (40 mg/kg) s.c. once weekly for 10 weeks to induce colon cancer. Twenty weeks after beginning the carcinogen treatment, a barium enema was performed to determine the size of colon tumors. The animals were divided into CDDP group and CPT-11 group, in which the maximum tolerable dose of each drug was given. After 5 weeks of treatment, the barium enema was repeated. "Response" was assessed on the basis of tumor doubling time. Response rates in the CDDP and CPT-11 groups were 6% and 35%, respectively. This reflects the clinical data of those drugs and confirms the results of our previous study. The present study may be a predictive model for screening anticancer drugs for human colorectal malignancy.

Animals↗