Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 127 records · Page 7Linked to original sources

PubMed2000

[Clinical analysis of community-acquired pneumonia requiring hospitalization in a community hospital--comparison of elderly and non-elderly patients].

A comparative study of 890 patients with community-acquired pneumonia requiring hospitalization in a community hospital was performed. The patients were divided into an elderly patient group and a non-elderly patient group. The elderly patients with community-acquired pneumonia exhibited frequent atypical symptoms such as dyspnea, consciousness disturbance and complication of shock, and also were frequently in a poor nutritional condition. The causative microorganism was isolated in 40.8% of the elderly patients and in 44.0% of the non-elderly patients. Polymicrobial agents were detected frequently in the elderly patients. Streptococcus pneumoniae (19.4%), MSSA (16.8%), Klebsiella pneumoniae (15.1%) and Haemophilus influenzae (15.0%) were frequently isolated from the sputum of the elderly patients, while Mycoplasma pneumoniae (25.2%), H. influenzae (15.0%), S. pneumoniae (12.2%) and MSSA (10.2%) were frequently isolated from that of the non-elderly patients. Regarding treatment with antibiotics, therapy with a single antibiotic therapy, such as cephem or carbapenem was carried out for the elderly patients, while new quinolone or tetracycline was administered to the non-elderly patients. Although the treatment with antibiotics was adequate according to the guidelines of the American Thoracic Society, the prognosis was poor; i.e.) in the elderly patients an efficacy rate of 74.3% and a mortality rate of 9.5%. In the non-elderly patients, the prognosis was good; i.e.) an efficacy rate of 88.0% and a mortality rate of 1.7%. These results suggest that the most important factors affecting the prognosis were the general condition of elderly patients and delay in an adequate diagnosis and treatment because of atypical clinical findings.

Aged↗

PubMed2000

17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus.

The present study investigates the expression patterns of 17beta-hydroxysteroid dehydrogenase (17betaHSD) isozymes in human fetal tissues to understand how estrogenic activity is regulated in the human fetus. Using enzyme assay, high 17betaHSD activity was detected in the placenta and liver, and low levels of 17betaHSD activity were also present in the gastrointestinal tract and kidney. After Northern blot analysis, we detected the messenger ribonucleic acid for 17betaHSD type 1 (17betaHSD1) only in the placenta, whereas that for 17betaHSD type 2 (17betaHSD2) was detected in the placenta, liver, gastrointestinal tract, and urinary tract at 20 gestational weeks. In RT-PCR analysis of the messenger ribonucleic acid transcripts, 17betaHSD 1 was predominantly expressed in the placenta, brain, heart, lung, and adrenal, whereas 17betaHSD2 expression was predominantly detected in the liver, gastrointestinal tract, and kidney. In addition, we detected 17betaHSD2 immunoreactive protein in surface epithelial cells of the stomach, absorptive epithelial cells of the small intestine and colon, hepatocytes of the liver, and interstitial cells surrounding the urinary tubules of the renal medulla. 17betaHSD2 in these tissues may be functioning in the prevention of in utero exposure of the fetus to excessive estradiol from the maternal circulation and amniotic fluids.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

Pharmacokinetic prediction of the ocular absorption of an instilled drug with ophthalmic viscous vehicle.

We previously developed an in vivo pharmacokinetic model that accounts for the corneal diffusion in albino rabbits and predicts the concentration of beta-blockers in the anterior segments. The purpose of this study is to pharmacokinetically predict the ocular absorption and characterize the systemic absorption of instilled drug with ophthalmic viscous vehicle to assist in its design and evaluation. Tilisolol and carboxymethylcellulose sodium salt (CMC) were used as the model ophthalmic drug and viscous polymer, respectively. After instillation of tilisolol with CMC vehicle in rabbits, the disposition of the drug in tear fluid, aqueous humor, and plasma were determined by HPLC. The ocular and systemic absorption were analyzed by a mathematical model including a diffusion process and a two-compartment model with first-order absorption, respectively. CMC vehicle increased the area under the concentration-time curve (AUC) of tilisolol in the tear fluid and aqueous humor and slightly reduced the AUC in plasma. The concentrations of tilisolol in the aqueous humor after instillation with CMC vehicle were accurately predicted from the tear concentrations by using the in vivo ocular pharmacokinetic model. CMC vehicle improved the ocular delivery of tilisolol.

Absorption↗

PubMed2000

Modification of ocular permeability of peptide drugs by absorption promoters.

The purpose of this study was to investigate the effect of absorption promoters on the ocular membrane permeability of thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) as model peptides. The permeabilities of TRH and LHRH were measured using a two-chamber glass diffusion cell mounted with isolated ocular membranes of albino rabbits. Saponin, EDTA, benzalkonium chloride and paraben were used as absorption promoters. These promoters enhanced the permeability of hydrophilic molecules through the cornea and conjunctiva. The promoting effects of the absorption promoters on the conjunctival drug penetrations were not as strong as those on the corneal penetrations. The different responses of the corneal and conjunctival drug penetrations to these promoters may be useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled drugs. The promotional effects of absorption promoters on the corneal drug penetration apparently increased with an increase in penetrant molecular weights, although those on the conjunctival drug penetrations did not depend on the molecular weights.

Absorption↗

PubMed2000

Bioactive saponins and glycosides. XVII. Inhibitory effect on gastric emptying and accelerating effect on gastrointestinal transit of tea saponins: structures of assamsaponins F, G, H, I, and J from the seeds and leaves of the tea plant.

Following the investigation of assamsaponins A, B, C, D, and E, four new saponins termed assamsaponins F, G, H, and I were isolated from the seeds of the tea plant (Camellia sinensis L. var. assamica PIERRE), while assamsaponin J was isolated from its leaves. The structures of assamsaponins F-J were elucidated on the basis of chemical and physicochemical evidence and found to be 16,22-O-diacetyl-21-O-angeloyltheasapogenol E 3-O-[beta-D-galactopyranosyl (1-->2)][beta-D-glucopyranosyl(1 -->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-angeloyl-22-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1-->3)]- beta-D-glucopyranosiduronic acid, 21-O-angeloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1-->2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-tigloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, and 16,21-O-diacetyl-22-O-cinnamoyltheasapogenol B 3-O-[beta-D-galactopyranosyl(l-->2)][beta-D-rhamnopyranosy(1-->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, respectively. The saponin mixture from the seeds of the tea plant was found to exhibit an inhibitory effect on gastric emptying and an accelerating effect on gastrointestinal transit in mice. Theasaponin E1 the principle saponin of the tea plant, showed potent activity, while theasaponin E2 showed none, so that the position of the acyl groups in the sapogenin moiety is important from a pharmacological point of view.

Animals↗

PubMed2000

[Target pharmacology of topiramate, a new antiepileptic drug].

Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (gamma-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.

Animals↗

PubMed2000

High level of CA19-9, CA50, and CEA-producible human cholangiocarcinoma cell line changes in the secretion ratios in vitro or in vivo.

The ascites of a 78-yr-old Japanese woman with cholangiocarcinoma was used for a primary culture. An established new cell line (designated TK from the Japanese description of cholangiocarcinoma; Tankan-gann) showed conspicuous tumor marker production. A high level of circulating serum tumor markers; carbohydrate antigen (CA) 19-9, 32,000 U/ml; CA50, 6900 U/ml; and carcinoembryonic antigen (CEA), 300 ng/ml (on an average from 10(6) cells/ml for 3 d culture) were detected in the tissue culture supernatant. With an inoculum of 2 x 10(7) TK cells, nude mice progressively developed tumors. The histological features of the tumors forming in nude mice showed well-differentiated adenocarcinoma. Within the tumor mass, large amounts of extra cellular fluid retained approximately 590,000 U/ml of CA19-9, 200,000 U/ml of CA50, and 2000 ng/ml of CEA. Alpha-feto-protein was undetectable in the TK culture supernatant. There are few cholangiocarcinoma cell lines producing stable human tumor markers. Newly established TK cells derived from cholangiocarcinoma showed a stable production of serum tumor markers in vivo and in vitro. The changes in the tumor marker secretion ratios were shown to be dependent upon type of tumor cells, i.e., whether they are in vitro or in vivo. These features make TK cells a valuable tool for studying tumor markers.

Aged↗

PubMed2000

Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.

Aldehyde Reductase↗

PubMed2000

[Insulin resistance induced by drugs or agents].

Glucocorticoids, oral contraceptives and nicotinic acid are associated with glucose intolerance, and the main cause of the glucose intolerance induced by these drugs is insulin resistance. Particularly glucocorticoids are difficult to substitute for another drugs, and frequency cause glucose intolerance. Now thiazolidinediones is available for reducing insulin resistance in clinical. And there are several evidences that thiazolidinediones can reduce insulin resistance induced by glucocorticoids in rats. But the clinical evidences are little. In future, it is necessary to investigate whether thiazolidinediones would be effective on reducing glucocorticoid-induced insulin resistance in clinical.

Animals↗

PubMed2000

[Problems concerning the prices of surgical operations in Japan. Union of Social Medical Insurance Committee Members of Surgical Societies in Japan].

The Union of Social Medical Insurance Committee Members of Surgical Societies in Japan was established in 1967. The union has tried to develop scientific methods to assess the price of surgical operations in Japan and proposed a tentative plan for the assessment of the price of operations. The price of an operation includes personnel expenses and other costs such as the prime costs to repay loans for land and buildings, and taxes. Personnel expenses are calculated by the grade of technical difficulties, the number of doctors and nurses and the duration of the operation. A more precise method to judge the difficulties of the operation seems to be necessary. To examine the recent increase in expenses for surgical materials, the cooperation of main hospitals authorized by surgical societies will be necessary. The prices of surgical operations presented by the Ministry of Health and Welfare of Japan correlated well with the prices proposed by the Union.

Fee-for-Service Plans↗

PubMed2000

[Photodynamic diagnosis and photodynamic therapy for experimental hepatoma with ME 2906].

We studied the effects of photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in confirming the existence of hepatoma, using the new photosensitizer mono-L-aspartyl chlorine 6. Japanese white rabbits were selected for abdominal incision under intravenous anesthesia, and VX 2 tumor cells were transplanted into the left liver lobe to create a hepatoma model. In the experiment, hepatoma of 1 cm in diameter (at one week after transplantation) was radiated with a semiconducter laser (664 nm, 200 J/cm2) for treatment.

Animals↗

PubMed2000

Clinicopathological features of gastric stromal tumors.

Stromal tumors in the gastrointestinal (GI) tract consist of myogenic tumors, neurogenic tumors and gastrointestinal stromal tumors (GISTs). Mutations in the c-kit gene have been found in GISTs, and GISTs with c-kit mutations showed aggressive clinical behavior and histological features. In the present study, we classified stromal tumors into four groups according to histological differentiation and c-kit mutation: myogenic tumors, neurogenic tumors, c-kit mutation (-) GISTs and c-kit mutation (+) GISTs, and examined their clinicopathological importance and validity using data obtained from 125 patients with gastric stromal tumors. There was no difference in preoperative symptoms and signs among the four groups. GISTs with c-kit mutations were large and showed invasion into neighboring structures compared with the other tumors, indicating the clinically aggressive features of mutation (+) GISTs. In histological examinations, c-kit mutation (+) GISTs were higher in cellularity (P < 0.0001) and mitotic cell count (P = 0.0086), and showed frequent histological necrosis (P = 0.0058) and hemorrhage (P = 0.0170), and consequently, were higher in histological grade (P = 0.0001). In prognostic analyses, overall, cause-specific and disease-free survival of patients in the mutation (+) GIST group was the poorest among the four groups. No significant differences were found among the other three groups of myogenic tumors, neurogenic tumors and c-kit mutation (-) GISTs, indicating a similar aggressiveness in clinical presentation and histological features. Thus, this classification is considered to be clinically and pathologically important in the diagnosis of gastric stromal tumors.

Adult↗

PubMed1999

Relationships between exposure, cell loss and proliferation, and manifestation of Hprt mutant T cells following treatment of preweanling, weanling, and adult male mice with N-ethyl-N-nitrosourea.

Experiments were performed to characterize the age-related patterns of appearance and frequency of hypoxanthine-guanine phosphoribosyl transferase (Hprt) mutant T lymphocytes in thymus and spleen following exposure of preweanling (12-day-old), weanling (22-day-old), and young adult (8-week-old) male B6C3F1 mice to ethylnitrosourea (ENU). Mice were given single i.p. injections of 0 or 40 mg ENU/kg and then groups of animals were necropsied from 2 h to 116 days after treatment to examine the relationships between exposure, cell loss and proliferation, and the frequency of Hprt mutant T cells in thymus and spleen. Hprt mutant frequency (Mf) data for thymus of ENU-exposed (0, 11.7, 35, 58, or 72 mg/kg, or five weekly doses of 1.7 mg/kg i.p.) male C57BL/6 mice (12- or 62-week-old), obtained during an earlier study of spleen cells [I.M. Jones, K. Burkhart-Schultz, C.L. Strout, T.L. Crippen, Factors that affect the frequency of thioguanine-resistant lymphocytes in mice following exposure to ethylnitrosourea, Environ. Mutagen, 9 (1987) 317-329.], were compared to results in B6C3F1 mice. Isolated T cells were cultured in the presence of mitogen, growth factor, and 6-thioguanine to detect Hprt mutants. The time required to achieve maximum Mfs in thymus was uniformly found at 2 weeks after ENU treatment, while the times needed to reach peak values in spleen were proportional to animal age at treatment. These data indicate that age-related differences in the appearance of Hprt mutant cells in spleen are largely defined by the physiologically based, age-dependent trafficking of mutant cells from or through the thymus. Three modes of handling the resulting Hprt Mf data were evaluated: (i) comparing the Mfs at a single time point, (ii) comparing the maximum Mfs observed, and (iii) comparing the change in Mfs over time (or the mutant T cell 'manifestation' curves in treated vs. control mice) in each age group post-exposure. Measuring the Mfs in spleen at multiple time points after cessation of exposure and integrating the frequency of mutants as a function of time appeared to be the superior method for comparing mutagenic responses in different age groups. Some of the underlying assumptions of this approach, as well as its strengths and weaknesses, are discussed.

Age Factors↗

PubMed1999

[The influence of clomipramine-induced mania on rapid cycling affective disorder].

Rapid cycling affective disorder (RC) is defined as the presence of at least four affective episodes per year. We report two RC patients whose first manic episodes were considered to be induced by clomipramine. The first case, a 61-year-old female, suffered from RC after a manic episode with respect to oral administration of clomipramine. The second case, a 45-year-old female, showed cycle acceleration after a manic episode regarding intravenous drip infusion treatment with clomipramine. They had no manic or hypomanic episodes before the administration of clomipramine. We discuss the possible induction and worsening of RC through clomipramine-induced mania.

Adult↗

PubMed1999

An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells.

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [(3)H]-thymidine incorporation, [(125)I]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein.

Aldehyde Reductase↗

PubMed1999

Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues.

Apurinic/apyrimidinic (AP) sites are one of the most frequent lesions in DNA. Using a highly sensitive slot blot assay, we determined the number and condition of endogenous AP sites in normal tissues of rats and human liver. The number of AP sites (50,000-200,000 per mammalian cell) was greatest in brain, followed by colon and heart, and then liver, lung, and kidney. The majority of endogenous AP sites were cleaved 5' to the AP site. These data suggest that removal of the deoxyribosyl phosphate moiety is the rate-limiting step in base excision and AP site repair in vivo.

Animals↗

PubMed1999

Kupffer cell-mediated down regulation of rat hepatic CMOAT/MRP2 gene expression.

Lipopolysaccharides (LPS) induces intrahepatic cholestasis and canalicular multispecific organic anion transporter (CMOAT/MRP2) plays a central role in hepatic bilirubin transport. This study examined the role of Kupffer cell in LPS-induced cholestasis. Rats were injected intravenously with LPS. Kupffer cells were inactivated with gadolinium chloride (Gd). CMOAT/MRP2 mRNA expression was time- and dose-dependently decreased by LPS injection with a decrease in bile flow and an increase in serum bilirubin level. Gd pretreatment inhibited decrease in CMOAT/MRP2 mRNA and bile flow, and increase in serum bilirubin. Kupffer cell-conditioned medium decreased CMOAT/MRP2 expression. Addition of anti-IL-1 or anti-TNFalpha antibody restored CMOAT/MRP2 expression, whereas IL-1 and TNFalpha decreased the expression. MAP kinases were activated by addition of the conditioned medium, and addition of PD98059 or SB203580 restored CMOAT/MRP2 expression. These results suggest that LPS activates Kupffer cells to secrete IL-1 and TNFalpha, which in turn activate MAP kinases and decrease CMOAT/MRP2 expression.

Animals↗

PubMed1999

Functional MRI of brain activation by eye blinking.

Functional magnetic resonance imaging (fMRI) was used to map cortical areas that control eye blinking. T2*-weighted asymmetric spin-echo MRI (or BOLD-blood oxygen level dependent-MRI) was used to detect changes caused by focal variations in blood oxygenation. Six normal volunteers and two cases of dry eye (less than 5-mm Schirmer's test) entered the study. The experimental scheme consisted of three cycles of a two-step sequence: (eyes closed)-(blink or blink inhibition). And to minimize contamination from photic activation, the experiments were carried out in a dark environment and the volunteers reported no light perception during the MR scans. In all eight cases, normal blinking (about one blink every 4 sec) activated areas in the orbitofrontal cortex and in some cases, the visual cortex including the anterior portion of the visual cortex and the primary visual cortex. In severe dry eye, blink-inhibition strongly activated the visual cortex even after irritation due to corneal desiccation was removed by topical anesthesia. The blinking process, especially the rate, appears to be controlled in the orbitofrontal cortex. The significance of visual cortex activation in the dark and in the case of severe dry eye still remains unclear; although it may be associated with attention and arousal.

Adult↗