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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 163 records · Page 9Linked to original sources
PubMed1999

[Clinical analysis of pneumonia in the elderly in a community hospital--comparison of community-acquired pneumonia and nosocomial pneumonia].

We experienced 530 elderly cases with pneumonia among 930 patients with pneumonia in Kawasaki Medical School Kawasaki Hospital between April 1986 and September 1998. Clinical analysis of all these patients and a comparison of one group consisting of 418 patients with community-acquired pneumonia and another group composed of 112 patients with nosocomial pneumonia were performed. In all of the elderly patients with pneumonia, respiratory symptoms and inflammatory findings were less frequent, but were frequent for those in poor general and nutritional condition. The causative microorganism was isolated in 42% of these patients. Streptococcus pneumoniae, MSSA and Klebsiella pneumoniae were frequently isolated from the sputum of the patients with community-acquired pneumonia, while Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Methicillin-sensitive Staphylococcus aureus (MSSA) were frequently isolated from that of nosocomial pneumonia patients. Mycoplasma pneumoniae, Chlamydia pneumoniae and some viruses were less frequent for patients in both groups. Although many intravenous antibiotics, such as cephem or carbapenem were administered to patients in both groups, the prognosis was relatively good for those with community acquired pneumonia but was extremely poor for those with nosocomial pneumonia despite mechanical ventilation or steroid pulse therapy for many patients.

Aged↗
PubMed1999

The effect of estrogen on aromatase and vascular endothelial growth factor messenger ribonucleic acid in the normal nonhuman primate mammary gland.

In the present study, the baboon was used as a model to investigate the effects of steroid hormones on vascular endothelial growth factor (VEG/PF) and aromatase expression and on proliferation of the normal mammary gland. Immunocytochemistry revealed that both aromatase and VEG/PF were expressed in the epithelial cells of the terminal ductal lobular units. Mammary tissue biopsies were obtained from female baboons during the follicular and luteal phases of the menstrual cycle, 4 weeks after ovariectomy (OVX), and after 2 weeks of treatment with estradiol benzoate (E2B; 500 microg/day, i.m.). Although there was little apparent difference in aromatase messenger ribonucleic acid (mRNA) in tissue from follicular and luteal phases or after ovariectomy, aromatase mRNA was decreased in tissue from ovariectomized (OVX) animals treated for 2 weeks with E2B. Furthermore, aromatase activity in tissue from these animals was markedly reduced compared to activity in tissue from the OVX animals before treatment (P < 0.001). In one animal in which mammary aromatase activity was measured sequentially during the follicular and luteal phases, aromatase activity was increased significantly after OVX and was reduced to the level in the intact animal by subsequent treatment with E2B. This effect on both aromatase activity and mRNA occurred rapidly 2 and 4 h after injection with E2B. In contrast to its effect on aromatase, E2B treatment of OVX animals stimulated VEG/PF mRNA 2 and 4 h after injection. In histoculture of mammary biopsies from these animals in the follicular and luteal phases of the menstrual cycle or after OVX, [3H]thymidine incorporation was increased significantly by incubation with testosterone (T) as well as estrogen (P < 0.01). The effect of T was blocked by aromatase inhibitor, 4-hydroxyandrostenedione, suggesting that the tissue is responsive to E produced by aromatization of T in the tissue. When mammary tissue from OVX animals was cultured with T, there was a significantly greater increase in [3H]thymidine incorporation than in histocultures of tissue from intact animals (P < 0.01). However, in histocultures of tissue from the OVX animals treated with E2B (500 microg) for 2 weeks, [3H]thymidine incorporation was similar to the level in tissue of intact animals incubated with T. No significant changes occurred in [3H]thymidine incorporation with the nonaromatizable androgen dihydrotestosterone or progesterone alone. These findings suggest that estrogens produced locally by aromatization of T have a functional role in mammary tissue. Aromatase expressed in the mammary gland could be important in maintaining local estrogen concentrations, particularly after menopause. Estrogen appears to regulate transcription of both aromatase and VEG/PF in the mammary gland, suggesting a regulatory loop by which local estrogens could stimulate VEG/PF production. Thus, paracrine/autocrine mechanisms that can enhance the proliferation of malignant cells and their metastatic spread already exist before transformation.

Animals↗
PubMed1999

In-vivo evaluation of indium-111-diethylenetriaminepentaacetic acid-labelling for determining the sites and rates of protein catabolism in mice.

Pharmacokinetic analyses of protein pharmaceuticals are of prime importance for their clinical application. Because many proteins have pharmacological activity at low concentrations, radiolabelling of proteins is widely used to identify the sites and determine the rates of protein catabolism in-vivo due to the high sensitivity of detection of radioactivity. Recently, a metallic radionuclide, (111)In, has been used to trace the pharmacokinetics of proteins of interest after conjugation of the proteins with diethylenetriaminepentaacetic acid (DTPA). In this study, galactosyl-neoglycoalbumin (NGA) was reacted with the cyclic dianhydride of DTPA and labelled with (111)In to estimate the validity of this radiolabelling procedure for pharmacokinetic analyses. For comparison, we also evaluated direct radioiodination, because directly-radioiodinated proteins are widely used to assess the pharmacokinetics of proteins of interest. The hepatic radioactivity profile after intravenous injection of [131I]NGA or [(111)In]DTPA-NGA into mice was analysed pharmacokinetically, and the first-order rate constant representing the elimination of the respective radiometabolite from hepatic parenchymal cells was determined. The results indicated that direct radioiodination is inappropriate for pursuing the pharmacokinetics of the proteins, because of rapid elimination of the radioactivity from the sites of protein catabolism. These findings also implied that the [(111)In]DTPA label could be used to identify the catabolic sites and determine the rates of catabolism of proteins with relatively short biological half-lives, although characterization of radiolabelled species at the sites of accumulation would be required for accurate determination of the catabolic sites of proteins.

Albumins↗
PubMed1999

Characterization of ocular pharmacokinetics of tilisolol after instillation into anesthetized rabbits.

The purpose of this study was to characterize the ocular pharmacokinetics of a beta-blocker, tilisolol, after instillation into anesthetized rabbits using a mathematical model including a diffusion process. The samples were analyzed by HPLC. Anesthetized rabbit was used as a model of tear secretion deficiency. Anesthetized rabbits showed higher drug concentration in the tear fluid and aqueous humor after instillation than unanesthetized rabbits. A mathematical model including a diffusion process and in vivo penetration parameters well described the concentrations of tilisolol in the aqueous humor after instillation in anesthetized rabbits.

Administration, Topical↗
PubMed1999

Continuous microinstillation of phenol red on liver surface for liver site-selective delivery.

We report a very promising approach for liver site-selective drug delivery through drug instillation on liver surface. Phenol red, which was selected as a model drug, was accumulated in the instillation site after instillation on the rat liver surface. The site-selective localization was enhanced by gradually and continuously instilling a small amount of drug solution on the liver surface.

Animals↗
PubMed1999

Drug absorption behavior after periocular injections.

The purpose of this study was to investigate the absorption behavior of an ophthalmic drug injected in rabbit periocular tissues. After intracapsular, retrobulbar and palpebral conjunctival injections of 150 microl and 50 microl fluorescein isothiocyanate dextran (FITC-dextran, average molecular weight 11000), leakage of the dye into the tear fluid was dependent on the injection route and volume. After periocular injections (50 microl) of tilisolol, as a model beta-blocker, the concentrations in the tear fluid, blood, aqueous humor and vitreous body were determined by HPLC. Slight drug leakage was observed in the tear fluid after injections. The periocular injections showed a faster absorption and a higher area under the concentration-time curve (AUC) in the plasma and a lower AUC in the aqueous humor than those observed in instillation. They also showed a higher ratio of AUC of tilisolol in the vitreous body to AUC in the aqueous humor than that observed in the instillation. Among the periocular injections, retrobulbar injection showed the highest concentrations in the plasma and the lowest in the aqueous humor and vitreous body, while intracapsular injection showed the lowest in the plasma and the highest in the aqueous humor and vitreous body. Although the periocular injections showed a rapid systemic absorption of drug by a rich topical vasculature, it might be an effective approach to deliver the drug to the periocular tissues and vitreous body.

Absorption↗
PubMed1999

Topical delivery system of ophthalmic drugs by periocular injection with viscous solution.

The purpose of this study is to evaluate periocular injections with viscous solution as a topical delivery system of ophthalmic drugs. Tilisolol and carboxymethylcellulose (CMC) were used as a model beta-blocker and a viscous polymer, respectively. After intracapsular, retrobulbar and palpebral conjunctival injections (50 microl) of tilisolol with 3% CMC into rabbits, drug concentrations in the tear fluid, blood, aqueous humor and vitreous body were determined by HPLC. Periocular injection (50 microl) of tilisolol with 3% CMC showed slight leakage of the drug in the tear fluid from the injection site. The viscous vehicle decreased the absorption rate constant of the drug from the injection site to systemic circulation compared with the buffer solution. It suggests that the viscous solution improved the retention of drug at both the injection site and in periocular tissues. Although the periocular injections with viscous vehicle (3% CMC) showed lower AUC in the aqueous humor than that observed in instillation, they showed comparable AUC in the vitreous humor. Compared to the results after the periocular injections with buffer solution, CMC increased the AUCs in the vitreous body 3.1-fold with retrobulbar injection and 1.4-fold with palpebral conjunctival injection, respectively. As a result, periocular injections with 3% CMC showed higher delivery of tilisolol to the vitreous body against the aqueous humor than the instillation and periocular injections with buffer solution.

Absorption↗
PubMed1999

Bioactive saponins and glycosides. XV. Saponin constituents with gastroprotective effect from the seeds of tea plant, Camellia sinensis L. var. assamica Pierre, cultivated in Sri Lanka: structures of assamsaponins A, B, C, D, and E.

The saponin fraction from the seeds of the tea plant, Camellia sinensis L. var. assamica Pierre cultivated in Sri Lanka, was found to show a potent protective effect on gastric mucosal lesions induced by ethanol in rats. Nine new acylated polyhydroxyoleanene-type triterpene oligoglycosides called assamsaponins A-I were isolated from the active saponin fraction together with three known saponins, theasaponin E1 and E2 and camelliasaponin B1. The structures of assamsaponins A-E were elucidated on the basis of chemical and physicochemical evidence. Theasaponin E1 exhibited potent gastroprotective activity.

Animals↗
PubMed1999

Effects of aromatase inhibitors on the pathobiology of the human breast, endometrial and ovarian carcinoma.

It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed these changes using histoculture of 15 human endometrial cancers and 9 ovarian cancers. Five of the fifteen endometrial cancers and four of the nine ovarian cancers demonstrated decreased [3H]thymidine uptake or Ki67 labeling index after 14alpha-hydroxy-4-androstene-3,6,17-trione (NKS01) treatment. In ovarian cancer cases, the responsive cases tended to be associated with higher aromatase and estrogen receptor alpha (ER) expression compared with the other cases but this was not seen in the endometrial cancer cases. There were no changes in ER and aromatase expression before and after NKS01 treatment in either ovarian or endometrial cancer cases. We then studied the same primary human breast tumors before and after aminoglutethimide (AMG, n=3) and 4-hydroxyandrostenedione (4-OHA, n=3) treatment. Tumor aromatase activity increased in 3 cases and decreased or was unchanged in 3 cases but aromatase immunoreactivity in stroma and adipocytes was unaltered in 5 cases. There were no changes in the ER labeling index before or after treatment. Five of the six cases including the responsive cases tended to be associated with decreased cell proliferation or Ki67 expression and increased apoptosis when examined by the TUNEL method. These results indicate that aromatase inhibitors may exert their effects on human breast and other cancers through decreasing proliferation and increasing apoptosis, possibly without altering ER status.

Antineoplastic Agents↗
PubMed1999

A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats.

Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of diabetic retinopathy and nephropathy. However, the role of PKC in diabetic neuropathy remains unclear. The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ). Streptozotocin-induced diabetic rats were treated with or without LY and/or NZ for 4 weeks, and motor nerve conduction velocity (MNCV), coefficient of variation of R-R interval (CVR-R), sciatic nerve blood flow (SNBF), peak latencies of oscillatory potentials on electroretinogram, PKC activities in membranous and cytosolic fractions of sciatic nerves, and polyol contents in the tail nerves were measured. Untreated diabetic rats demonstrated delayed MNCV, decreased CVR-R, reduced SNBF, and prolonged peak latencies of oscillatory potentials. Treatment with LY as well as NZ prevented all these deficits in diabetic rats. There were no significant differences in PKC activities in membranous or cytosolic fractions of sciatic nerves between normal and diabetic rats. Treatment with neither LY nor NZ altered PKC activities. Nerve myo-inositol depletion in diabetic rats was ameliorated not only by NZ, but also by LY. These observations suggest that inhibition of PKC-beta by LY may have a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.

Aldehyde Reductase↗
PubMed1999

Enhancement of ocular drug penetration.

Although new drugs have recently been developed within the field of ophthalmology, the eye's various defense mechanisms make it difficult to achieve an effective concentration of these drugs within the eye. Drugs administered systemically have poor access to the inside of the eye because of the blood-aqueous and blood-retinal barriers. And although topical instillation of drugs is very popular in ophthalmology, topically applied drugs are rapidly eliminated from the precorneal area. In addition, the cornea, considered a major pathway for ocular penetration of topically applied drugs, is an effective barrier to drug penetration, since the corneal epithelium has annular tight junctions (zonula occludens), which completely surround and effectively seal the superficial epithelial cells. Various drug-delivery systems have been developed to increase the topical bioavailability of ophthalmic drugs by enhancement of the ocular drug penetration. The first approach is to modify the physicochemical property of drugs by chemical and pharmaceutical means. An optimum promoiety can be covalently bound to a drug molecule to obtain a prodrug that can chemically or enzymatically be converted to the active parent drug, either within the cornea or after the corneal penetration. Along these same lines, the transient formation of a lipophilic ion pair by ionic bonding is also useful for improving ocular drug penetration. The second approach is to modify the integrity of the corneal epithelium transiently by coadministration of an amphiphilic substance or by chelating agents that act as drug-penetration enhancers. The third approach modifies the integrity of the corneal epithelium transiently by physical techniques including iontophoresis and phonophoresis. This paper reviews the absorption behavior and ocular membranes penetration of topically applied drugs, and the various approaches for enhancement of ocular drug penetration in the eye.

Drug Carriers↗
PubMed1999

[A case report of diabetic scleredema in a patient with non-insulin-dependent diabetes mellitus].

A 70-year-old Japanese man with non-insulin-dependent diabetes mellitus showed scleredema diabeticorum. The patient complained of edematous feelings on his hands, both arms and face. The time of onset of these symptoms was not known. He had typical clinical and histopathological findings of diabetic scleredema. His diabetic control was poor and HbA1c level was 8.2% under insulin treatment. The patient had many complications such as diabetic retinopathy, diabetic nephropathy with benign nephrosclerosis, hyperlipidemia accompanied with a low level of high density lipoprotein cholesterol, hypertension and coronary heart disease. There were no abnormal laboratory findings except the diabetic controls and mild abnormal renal functions; however erythrocyte sedimentation rate was high.

Aged↗
PubMed1999

[Aldose reductase].

Explore the source record for details and available documents.

Aldehyde Reductase↗
PubMed1999

[Treatment policy for colon cancer liver metastases].

Hepatectomy provides the highest rates of cure among the methods for treating colon cancer liver metastases, but it cannot be performed in many cases. Hepatectomy is the treatment of choice for colon cancer liver metastases in our department, but we conduct transcatheter arterial embolization alone or in combination with MCT on patients in whom hepatectomy cannot be performed or those with residual tumor following hepatectomy. Transcatheter arterial embolization is conducted on patients shown to have tumor vessels, following a single intra-arterial shot of an anticancer drug. MCT is performed under general anesthetic percutaneously or by abdominal section in patients who have not responded well to transcatheter arterial embolization, in order to improve the effectiveness of treatment on the tumor overall. We consider the combination of transcatheter arterial embolization and MCT to be an effective treatment for patients with a colon cancer liver metastasis who present with tumor vessels.

Aged↗
PubMed1999

[Evaluation of the usefulness of a serodiagnosis kit, the determiner TBGL antibody for tuberculosis: setting reference value].

The determiner TBGL antibody developed by Kyowa-Medex co., ltd. is a new serodiagnostic kit for tuberculosis. To set cut-off point suitable for the kit, TBGL antibody titer of serum from healthy subjects were analyzed in relation to age, sex, previous and family history on tuberculosis. Based on results of healthy subjects, cut-off point was set by using several analytical methods. We propose 2U/ml as a cut-off point for screening of patients with tuberculosis considering the diagnostic efficiency by receiver operating characteristics (ROC) curve analysis and 4U/ml for diagnosis of tuberculosis, which was determined by parametric method considering its specificity.

Adolescent↗
PubMed1999

Clinical application of a fiberscope for periodontal lesions: case reports.

In dentistry, the endoscope has generally been used to visualize inaccessible areas, e.g., inside root canals or coronal surfaces of teeth; however, it has not been used in periodontally diseased lesions. In this study, a newly designed fine fiberscope (0.8- to 1.0-mm outer diameter) with an irrigation system was used to visualize root surfaces and periodontal tissues affected by periodontal disease. The fiberscope was inserted through fistulas, periodontal pockets, or root furcations in 5 patients to provide clear operational views without the obstruction of blood or soft tissues. The irrigation system of the endoscope effectively allowed differentiation of hard and soft tissues as well as restorative materials. The fiberscope system developed in this study was effective for diagnosis, for enhancing visualization for periodontal surgery, and for treating lesions such as fistulous tracts or furcation lesions.

Adult↗