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Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 415 records · Page 23Linked to original sources
PubMed1995

A mild progression type of naphthalene-induced cataract in brown-Norway rats.

Naphthalene-induced rat cataract is a useful experimental cataract--however, because of its short survival period, studies using this model have been for limited purposes. Based on the consideration that the short survival might be caused by systemic toxicity of an overdose of naphthalene administration (1 g/kg body weight every other day), the authors successfully established a naphthalene-induced cataract with mild progression in Brown-Norway rats. The naphthalene administration proposed is to initially administer 0.5 g/kg and after a 1-week interval 1 g/kg of 10% naphthalene once or twice a week through a stomach tube. While the type of lens opacification induced in the two groups administered once and twice a week, respectively, was the same as that seen by the previous administration method, the progression of lens opacification seen in the groups showed a dose-dependent increase. The survival rate in the rats given naphthalene every other day according to the old method was 50% at the 6th week and 0% at the 9th week. Survival of the two new groups was 70 and 60% at the 30th week, respectively. This new type of naphthalene-induced rat cataract should be a suitable model for long-term observations.

Animals↗
PubMed1995

Antimetastatic activities of synthetic Arg-Gly-Asp-Ser (RGDS) and Arg-Leu-Asp-Ser (RLDS) peptide analogues and their inhibitory mechanisms.

We have investigated the inhibitory effect of the N-terminal modified Arg-Gly-Asp-Ser (RGDS) analogues, AcDRGDS and AcDRLDS, on tumor cell adhesion to the components of extracellular matrix and basement membrane, and also tested the antimetastatic effect of their conjugates with trimesic acid, Ar(DRGDS)3 and Ar(DRLDS)3. AcDRGDS significantly inhibited tumor cell adhesion to fibronectin, vitronectin and RGDS substrates, but not to CS1 substrate which is a ligand for the alpha 4 beta 1 tumor surface integrin receptor. In contrast, AcDRLDS variant peptide significantly inhibited tumor cell adhesion to laminin, in addition to RGDS-mediated adhesion to fibronectin and vitronectin. AcDRLDS also inhibited tumor cell adhesion to CS1 as well as the RGDS sequence within the fibronectin molecule in a concentration-dependent manner, although the inhibitory effect was less than that of the CS1 (EILDV) peptide. Ar(DRLDS)3 inhibited the laminin- and fibronectin-mediated invasion and migration of tumor cells, whereas Ar(DRGDS)3 selectively inhibited fibronectin-mediated invasion and migration. Ar(DRGDS)3 and Ar(DRLDS)3 were much more effective in inhibiting experimental lung or liver metastases of various types of murine and human tumors than the original RGDS-containing peptides or Ar(COONa)3. Multiple administrations of Ar(DRGDS)3 or Ar(DRLDS)3 potently inhibited spontaneous lung metastasis produced by intra-footpad injection of B16-BL6 cells without affecting the primary tumor size at the time of surgical excision, as compared with RGDS peptide or untreated control. Thus, Ar(DRGDS)3 and Ar(DRLDS)3 substantially increased the exhibiting any antimetastatic effect of the peptides without direct cytotoxicity.

Amino Acid Sequence↗
PubMed1995

Enzymatic formation of plant cerebroside: properties of UDP-glucose: ceramide glucosyltransferase in radish seedlings.

The activity of cerebroside synthase (UDP-glucose: ceramide glucosyltransferase) was found in the microsomal fraction of radish hypocotyls, and was studied. One % of the radioactivity due to UDP-[3H]glucose added to the membrane fraction was incorporated into cerebroside within 60 min. Optimum pH and temperature of the activity were pH 7.8 and 30 degrees C, respectively. No metal ions enhanced the cerebroside synthase activity, dissimilar to that in animal tissues. The apparent Km for UDP-glucose was approximately 200 microM. The same activity was also observed in radish roots and cotyledons, but proportions of UDP-[3H]glucose incorporation were slightly lower than that in hypocotyls. Exogenous ceramide species having trihydroxy sphingoid bases, which were major ceramide components of radish cerebrosides, usually stimulated cerebroside formation in microsomal fractions from radish seedlings, while any ceramide types having dihydroxy sphingoid bases were ineffective on the glucosylation reaction. It was assumed, therefore, that cerebroside synthase in radish seedlings would have substrate selectivity for ceramide species.

Brassica↗
PubMed1995

[Five-week intravenous toxicity study of montirelin hydrate (NS-3) in rats followed by 4-week recovery test].

A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male and female rats were given the drug intravenously for 5 weeks at doses of 0 (control), 0.05, 0.5, 5 and 50 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted in the 0, 0.5 and 50 mg/kg groups. No deaths related to the treatment were observed. Tremor was seen in the 50 mg/kg group. Polyuria was observed in the 5 and 50 mg/kg groups. There were decreases in body weight gain in the 0.5 mg/kg group and over of males, and in food consumption in all male dose groups and increase in water consumption in the 5 and 50 mg/kg groups. In blood chemical examination, decrease in triglyceride was observed in the 5 and 50 mg/kg groups of males. Urinalysis showed increase in urine volume in the 0.5 mg/kg group and over. Ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. Pathological examination disclosed serous cell hypertrophy of the submandibular gland in all dose groups and increase in its organ weight in the 0.5 mg/kg group and over. The changes mentioned above were satisfactorily reversible except for the serous cell hypertrophy of the submandibular gland in the 50 mg/kg group. The decrease in food consumption and serous cell hypertrophy of the submandibular gland in the 0.05 mg/kg group were considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.05 mg/kg for 5-week repeated dose toxicity in rats.

Animals↗
PubMed1995

Age-related changes in vascular smooth muscle and endothelium.

Aging is associated with structural and functional changes in the blood vessel wall. In vascular smooth muscle, the effects of aging on the response mediated by beta-adrenoceptors have been most intensively studied. beta-adrenoceptor-mediated relaxation decreases in most arteries, but not veins, with increasing age. In contrast, studies on contractile responses to alpha-adrenergic drugs are conflicting. The response to alpha-adrenoceptor agonists appears to be unchanged for decreased by aging. The endothelium takes part in the local regulation of vascular tone as a source of several vasoactive factors. Basal release of endothelium-derived nitric oxide decreases with age in vitro studies. Aging is also associated with reduced endothelium-dependent relaxations in response to vasoactive substances such as acetylcholine, histamine or adenosine. The impairment of the relaxation is, in most cases, achieved by a decreased release and/or decreased production of endothelium-derived relaxing factors (endothelium-derived nitric oxide, hyperpolarising factor and prostacyclin). An increased release of endothelium-derived, cyclo-oxygenase-dependent contracting factor is also responsible for reduced relaxation in some tissues. On the other hand, the release of endothelin-1 from the endothelium increases with age, while the response to the peptide decreases under the same conditions, especially in small resistance arteries. The alterations of vascular smooth muscle and endothelial cells occurring with age may have important clinical implications for the pathogenesis of cardiovascular disease.

Aging↗
PubMed1995

Effects of UFT (mixed compound of tegafur and uracil) on cell kinetics and inhibition of thymidylate synthase in L1210 ascites tumor.

Previous work in our laboratory showed that UFT (mixed compound of tegafur and uracil, molar ratio 1:4, respectively) caused the prolonged reduction of dTTP in L1210 leukemia cells in comparison with 5-fluorouracil (5-FU). The purpose of this study was to assess the effect of UFT on cell cycle distribution and thymidylate synthase activity of a leukemia cell line as compared with 5-FU. UFT and 5-FU were orally given to BDF1 mice bearing L1210 ascites tumor on day 3 after the tumor inoculation. Cell cycle distribution patterns at 24 hr after the drug administration showed a higher percentage of S phase in tumor cells treated with UFT than in those treated with 5-FU. Until 6 hr after the oral administration of the drugs, UFT inhibited the incorporation of [3H] deoxyuridine into DNA more long than 5-FU did. These results indicated that UFT has longer and stronger inhibitory effects on DNA replication than 5-FU in vivo under the employed experimental conditions (i.e., low and single doses of these fluorinated pyrimidines).

Animals↗
PubMed1995

[Effect of acupuncture on the overactive bladder].

BACKGROUND: We examined the effect of acupuncture for the overactive bladder. METHODS: Eleven patients (9 males and 2 females) with the overactive bladder were treated with acupuncture. The age of the patients ranged from 51 to 82 years (mean 71 years). Nine patients complained of urge incontinence and 2 patients of urgency. Uninhibited contraction was observed in all patients before the acupuncture. A disposable needle (0.3 mm in diameter, 60 mm in length) was inserted into bilateral BL-33 points at the depth of 50 to 60 mm and was rotated for 10 minutes manually. The treatment was performed 4 to 12 (average 7 times). RESULTS: Urge incontinence was controlled completely in 5 and partially in 2 of 9 patients. In 2 patients who complained urgency complete response was obtained after the treatment. Uninhibited contraction disappeared in 6 patients after the treatment. Acupuncture induced an increase of maximum bladder capacity and bladder compliance with statistical significance (p < 0.01 and p < 0.05), respectively. CONCLUSION: Acupuncture at the BL-33 point was effective for controlling the overactive bladder.

Acupuncture Therapy↗
PubMed1995

[Fournier's gangrene in a patient with perirectal abscess: a case report].

A case of an 81-year-old man with Fournier's gangrene was reported. The patient visited our hospital complaining of scrotal swelling and redness. Perirectal abscess was found and ultrasound study revealed thickness of scrotal skin and normal testes. The patient was immediately treated with antibiotics, incision and debridement of the scrotal skin. The lesion healed 8 weeks later.

Abscess↗
PubMed1995

[Cataract epidemiology survey in the three climatically different areas in Japan--prevalence of cataracts and types of lens opacification].

A cataract epidemiology study of 1,615 subjects from three climatically different places in Japan, village S in Hokkaido, town M in Noto and village Y in Okinawa, was conducted by one study group. Cataract diagnosis and grading of cataracts were objectively done with a photo-documentation system. The percentages of cataracts of over grade I classified by the Japanese Cooperative Cataract Epidemiology Study Group were 46.6%, 64.6% and 38.0% in village S, town M, and village Y, respectively. Those in their 50s, 60s, and 70s in the above places were 24.3%, 51.1% and 71.4% (village S), 38.4%, 65.3% and 84.6% (town M), and 25.2%, 42.9% and 65.4% (village Y), respectively. Cortical cataract was the most common, followed by nuclear and subcapsular types. Although the highest percentage of nuclear cataracts was seen in the subjects of village Y, subcapsular cataract was seen almost equally in the three areas. Lens transparency changes were evaluated by the light scattering intensities in the lens layers through photographed images. Intensity increased with ageing either linearly or exponentially.

Adult↗
PubMed1995

The substrate-specific impairment of oxidative phosphorylation in liver mitochondria from high-protein-fed chickens.

Chickens fed on semi-purified low (7%) or high (61%) protein-energy diets for 14 or 17 d were used for determinations of oxidative phosphorylation and specific amounts of mitochondrial protein in liver. The ADP:oxygen (ADP:O) values obtained when pyruvate+malate were used as substrates were significantly reduced in the high-protein-fed group after the 4th day compared with those for the group fed the low-protein diet, while the differences in ADP:O values between the two treatments when L-glutamate was used as substrate were found to be significant on the 14th day. At any feeding period no significant differences in ADP:O values were observed between the two groups when alpha-ketoglutarate, malate, or octanoate+malate were used as substrates, nor in specific amounts of mitochondrial protein in liver. The dependency of the pyruvate+malate-supported respiration rate on the temperature in the reaction medium was also determined. The results of an Arrhenius plot showed that transition temperatures, and the lower and upper energies of activation, were similar for the groups fed on low- and-high-protein diets. Furthermore, no morphological changes in mitochondria were observed among chickens fed on diets with various protein levels for 14 d. From these results we concluded that the reduction of ADP:O value with pyruvate+malate of L-glutamate substrates in chickens fed on a high-protein diet was substrate-specific, and was not due to functional damage to the respiratory chain for electron flow from NAD-linked substrates to the ubiquinone pool, nor to modulation of properties of the inner mitochondrial membrane.

Animals↗
PubMed1995

[Experience with one stage repair of hypospadias and chordee without hyposradias using free graft of prepuce].

We treated 14 patients with moderately severe hypospadias and chordee without hypospadias using a free graft of prepuce by a modified Devine-Horton technique, between September 1993 and April 1995. There were 12 primary cases and 2 secondary cases in which prior operations had already been done. Four (33%) of the primary cases required a second procedure; 3 for urethrocutaneous fistula and 1 for urethral shrinkage. Both of the secondary cases needed further procedures; 1 for meatal stenosis and 1 for urethral stricture and diverticula. Although the need for reoperation is unfortunately high, six of the 7 recently treated patients experienced no complications. Thirteen of the 14 patients (93%) achieved excellent functional and cosmetic results with 1 or 2 procedures. We believe the use of free grafts allows a better functional and cosmetic outcome because the secondary torsion and bulkiness of the penile shaft caused by a vascular pedicle are eliminated.

Child↗
PubMed1995

Role of endogenous endothelin in the extension of myocardial infarct size studied with the endothelin receptor antagonist, TAK-044.

The effects of TAK-044 on the extension of ischemia/reperfusion-induced myocardial infarction were studied in rats. Acute myocardial infarction was induced by occlusion of the left coronary artery for 1 h followed by reperfusion for 24 h. Infarct size and the area at risk were determined histochemically. Infarct size as a percentage of the area at risk (IS) was significantly reduced in a dose-dependent manner by TAK-044 administered 30 min before reperfusion (0.3-3.0 mg/kg, i.v.). Size-limiting effects similar to those in rats were also obtained in rabbits and dogs. In addition, TAK-044 administered 3 h after reperfusion also reduced the IS significantly. Preconditioning (5 min of LAD occlusion preceding 1 h of coronary occlusion) inhibited the extension of the IS. These effects of preconditioning and TAK-044 were inhibited by glibenclamide (0.1 mg/kg, i.v.; an inhibitor of the ATP-sensitive K channel) but not by DPCPX (1 mg/kg, i.v.; an adenosine A1 receptor antagonist). These results indicate that endogenous endothelin plays an important role in the extension of myocardial infarction and that the cardioprotective effects of TAK-044 can be partially explained by a mechanism similar to that of preconditioning in rats.

Animals↗
PubMed1995

Combination of anti-cell adhesive synthetic Arg-Gly-Asp-Ser analogue and anticancer drug doxorubicin heightens their original antimetastatic activities.

A new compound containing the cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide was synthesized, i.e. tetrahydrofurantetracarboxylic acid (THFTCA)-RGDS conjugate [THFTCA- (RGDS)3, FC-243], and the inhibitory effect of FC-243 on lung metastasis of B16-BL6 melanoma in mice was examined in combination with or without the anticancer agent doxorubicin (DOX). FC-243 showed an inhibitory effect on lung metastasis of melanoma cells in a dose-dependent manner. A mixture of THFTCA and RGDS peptide or THFTCA alone did not show any inhibitory effect on experimental lung metastasis as compared with FC-243 on a molar basis. RGDS peptide, however, required a higher dose to obtain a sufficient antimetastatic effect. Intermittent IV administration of FC-243 after the inoculation of B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with multiple administration of RGDS or untreated control. The in vitro tumor invasion study showed that FC-243 as well as RGDS+THFTCA on a molar basis resulted in similar inhibition of the invasion of B16-BL6 cells into reconstituted basement membrane Matrigel. Combined treatment with FC-243 and DOX significantly inhibited lung metastasis of melanoma as compared with either treatment alone or the untreated control. Administrations of FC-243 and DOX in combination substantially prolonged the survival time of mice. These results demonstrate that combination therapy of the anti-cell adhesive FC-243 and the anticancer agent DOX, i.e. antiadhesion therapy and chemotherapy, is a new approach that offers enhanced inhibitory effects on tumor metastasis and invasion.

Animals↗