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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effect of viscous additives on drug absorption from the liver surface in rats using phenol red as a model.

The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use.

Absorption↗
PubMed2000

Tumor cells as the origin of elevated serum alpha1,3fucosyltransferase in association with malignancy.

We have previously reported that the elevated activities of serum alpha 1,3fucosyltransferase reverted to normal levels after curative removal of the tumors. To determine the origin of elevated serum alpha 1,3fucosyltransferase, blood samples were obtained from both the drainage vein and the artery in patients with different stages of colorectal cancer at surgery. The enzyme levels in all samples from the drainage vein were found to be higher than the levels in the artery that fed the tumor. Hence, the origin of elevated alpha1,3fucosyltransferase in serum was thought to be the tumor rather than the liver that is the normal source of serum alpha1,3fucosyltransferase. When serum samples not only from colorectal cancer patients but also from patients with gastric, liver, lung, pancreas, bladder and esophagus cancer were treated with anti-FUTVI antibody, the measured activities of alpha1,3fucosyltransferase were markedly reduced. Further, secretion of alpha1,3fucosyltransferase from human colorectal carcinoma cells was also detected in the culture medium by Western immuno-blot analysis with anti-FUTVI antibody.

Aged↗
PubMed2000

Visual perseveration: a new side effect of maprotiline.

OBJECTIVE: The aim of this paper is to describe a case of visual perseveration including palinopsia during maprotiline therapy. METHOD: A single case report. RESULTS: The patient, a 56-year-old depressive man, suffered from visual perseveration during maprotiline therapy. The visual perseveration was dose-related and disappeared with reduction and cessation of the therapy. CONCLUSION: The present findings suggest that maprotiline can induce visual perseveration including palinopsia in some patients.

Antidepressive Agents, Second-Generation↗
PubMed2000

Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of autoantibodies to desmocollin-1 and clinical review.

We describe a 40-year-old Japanese man with a 3-year history of vesiculopustular lesions resembling subcorneal pustular dermatosis. Histopathology showed subcorneal pustules containing a few acantholytic cells, and direct immunofluorescence disclosed IgA deposition in the intercellular space of the upper epidermis. Circulating IgA autoantibodies of very low titre were also demonstrated by indirect immunofluorescence. A novel cDNA transfection technique clearly detected IgA autoantibodies reactive with human desmocollin-1. Combined therapy with dapsone and etretinate improved the skin lesions. We review the clinical features of 49 patients in the literature who presented with vesiculopustular lesions and intraepidermal IgA deposition.

Adult↗
PubMed2000

Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations.

The aim of this paper is to describe two cases of clomipramine-induced delirium. One 61-year-old and one 67-year-old female depressive patients became delirious after beginning intravenous clomipramine injections in addition to their oral clomipramine administrations. Their plasma levels of both clomipramine and its metabolite, desmethylclomipramine, were acutely increased about twofold during delirium. The intravenous clomipramine administrations were discontinued. Their delirious state was gradually improved after stopping the intravenous clomipramine administrations. These findings suggest that acute increases of plasma levels of clomipramine and desmethylclomipramine after intravenous clomipramine injections might be related to the appearance of the delirious episodes.

Aged↗
PubMed2000

Hepatocyte transplantation in rats with decompensated cirrhosis.

Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL(4)) and animals were studied only when evidence of liver failure did not improve when CCL(4) was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P <.01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P <. 01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P <.01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

Animals↗
PubMed2000

The influence of HLA genotyping compatibility on clinical outcome after cord blood transplantation from unrelated donors.

We performed retrospective DNA typing of class I (A, B, Cw) and class II (DRB1, DQB1, DPB1) HLA alleles in 27 unrelated cord blood transplantation (CBT) cases donated from a single cord blood bank (Kanagawa Cord Blood Bank). The influence of HLA genotype matching on clinical outcome was evaluated. From Cox's model, we found that incompatibility of two or more HLA alleles between the donor and recipient of an unrelated CBT was suggested to be a risk factor for a worse event-free survival (EFS) (p = 0.04; RR, 4.06; 95% CI, 1.06-15.61). Furthermore, mismatches including HLA-DRB1 alleles had an adverse effect on EFS (p = 0.04; RR, 4.91; 95% CI, 1.01-24.02). For definite conclusions on the role of HLA allele typing in unrelated CBT, more accumulation of data and analysis will be required.

Actuarial Analysis↗
PubMed2000

Quantitation of DNA and hemoglobin adducts and apurinic/apyrimidinic sites in tissues of F344 rats exposed to propylene oxide by inhalation.

Propylene oxide (PO) is a relatively weak mutagen that induces nasal tumor formation in rats during long-term inhalation studies at high exposures (> or =300 p.p.m.), concentrations that also cause cytotoxicity and increases in cell proliferation. Direct alkylation of DNA by PO leads mainly to the formation of N:7-(2-hydroxypropyl)guanine (7-HPG). In this study, the accumulation of 7-HPG in tissues of male F344 rats exposed to 500 p. p.m. PO (6 h/day, 5 days/week for 4 weeks) by the inhalation route was measured by gas chromatography-high resolution mass spectrometry (GC-HRMS). In animals killed up to 7 h following the end of the last exposure the levels of 7-HPG (pmol/micromol guanine) in nasal respiratory tissue, nasal olfactory tissue, lung, spleen, liver and testis DNA were 606.2 +/- 53.0, 297.5 +/- 56.5, 69.8 +/- 3.8, 43.0 +/- 3.8, 27.5 +/- 2.4 and 14.2 +/- 0.7, respectively. The amounts of 7-HPG in the same tissues of animals killed 3 days after cessation of exposure were 393.3 +/- 57.0, 222.7 +/- 29.5, 51.5 +/- 1.2, 26.7 +/- 1.0, 18.0 +/- 2.6 and 10.4 +/- 0.1. A comparable rate of disappearance of 7-HPG was found among all tissues. DNA from lymphocytes pooled from four rats killed at the end of the last exposure was found to have 39.6 pmol adduct/micromol guanine. Quantitation of DNA apurinic/apyrimidinic sites, potentially formed after adduct loss by chemical depurination or DNA repair, showed no difference between tissues from control and exposed rats. The level of N:-(2-hydroxypropyl)valine in hemoglobin of exposed rats was also determined using a modified Edman degradation method followed by GC-HRMS analysis. The value obtained was 90.2 +/- 10.3 pmol/mg globin. These data demonstrate that nasal respiratory tissue, which is the target tissue for carcinogenesis, has a much greater level of alkylation of DNA than non-target tissues.

Animals↗
PubMed2000

A chemometric approach to the estimation of the absorption spectra of dye probe merocyanine 540 in aqueous and phospholipid environments.

Merocyanine 540 (MC540) is a widely used dye probe for membranous environments. However, fundamental knowledge of the spectral features of this dye in aqueous and hydrophobic environments is still lacking. Such knowledge is important because biomembranes involve a hydrophobic environment surrounded by a hydrophilic environment. Because many investigations so far have been performed based on indistinct spectral estimations, the interpretation of the data obtained using this dye as a fluorescent transmembrane probe remains controversial. In order to determine the exact spectra in both aqueous and hydrophobic environments, we adopted principal factor analysis (PFA), a method of multivariate analysis. The PFA method can also determine the number of molecular species present in the reaction mixture, which is three in pure water and two in phospholipid suspension. Two of the species in both water and phospholipid suspension were the monomer and dimer. The third species in water was the trimer, but its amount was so small at 10 microM MC540 solution that the spectral data in water can be approximated neglecting this molecular species. The monomer spectrum changed its form markedly with a bathochromic shift when transferred from the water to phospholipid environment, whereas the dimer remained similar in its shape except for a remarkable red shift. In water, the dissociation constants, K(1) and K(2), for the assumed stacking-model reactions, M+M <--> M(2) and M+M(2) <--> M(3), were 3.1 x 10(-4) M and 5.7 x 10(-4) M, respectively. In the phospholipid environment, the dissociation constant K* for the assumed stacking-model reaction, M(*)+M(*) <--> *M(2), was 1.9x10(-5)M. The fluorescent intensities of MC540 were also measured in both water and phospholipid environments. A comparison based on the absorption and fluorescence spectra suggested that the temporal increase in the amount of the monomer on the excitable membrane contributes to the fluorescent intensity change observed in the transmembrane potential change.

Fluorescent Dyes↗
PubMed2000

Effect of canal drying methods on the apical seal.

The purpose of this study was to observe the seal obtained in human root canals under different in vitro treatment conditions. Root canals of freshly extracted human maxillary incisors received traditional biomechanical preparation and irrigation with 10% NaClO, followed by a final rinse of distilled water. Teeth were divided into four groups. In group 1, each root canal was dried with one paper point. In group 2, each root canal was dried with four paper points. Group 3 was dried with four paper points, followed by a gentle burst of warm air. Group 4 was dried using four paper points, followed by an internal 200 degrees C heat probe. Twenty canals in each group were filled with a gutta-percha cone and a zinc oxide-eugenol sealer, whereas 20 were filled with a glass ionomer sealer. All teeth were immediately immersed in India ink for 1 or 4 wk. The teeth were cleared, and the dye penetration-leakage measured with an accuracy of +/- 0.01 mm. Optimum sealing conditions were observed when the canal was dried with paper points and a 200 degrees C probe. There were no significant differences between 1 and 4 wk immersion. Glass ionomer sealer appeared more susceptible to the wet condition of the root canal walls than zinc oxide-eugenol sealer. An additional 40 teeth were prepared in the same manner as the dye penetration tests to observe the drying conditions of the root canal walls, and the moisture inside the canals was measured to an accuracy of 0.0001 g. The highest degree of internal canal wall dryness was found in group 4.

Air↗
PubMed2000

The walking bleach procedure: an in vitro study to measure microleakage of five temporary sealing agents.

The purpose of this study was to compare the in vitro sealing capacity of five materials, each used as a temporary sealing agent for the walking bleach technique. All teeth received traditional biomechanical root canal instrumentation, after which the walking bleach agent was placed in the pulp chamber space. The occlusal access was sealed with one of five temporary materials: two hydraulic filling materials, a photoactivated resin composite, a zinc oxide-eugenol cement, and a zinc oxide phosphate cement with/without the placement of a piece of rubber sheet that was placed as a barrier to isolate filling material from the bleaching agent. All teeth were stored in a 1% solution of Alcian blue with thermal cycling stress. After 1 wk, they were sectioned longitudinally, and ranked by graded scores of 0 to 3, according to the degree of the dye penetration. Significantly less dye microleakage was observed in the two hydraulic materials than in the photoactivated resin. Both zinc oxide-eugenol and zinc phosphate cements showed a considerable amount of microleakage. There were no significant differences between the groups with and without a rubber sheet. Our data demonstrate that hydraulic filling materials provide the most favorable cavosurface seal when they are firmly packed into the cavity space to prevent microleakage.

Alcian Blue↗
PubMed2000

Prediction of lithium response using. m-chlorophenylpiperazine challenge test: A preliminary finding.

It is important to be able to predict a response to lithium before lithium administration because it usually takes 2 or 3 weeks for lithium to manifest its effect sufficiently. We hypothesized that lithium responders have a high post-synaptic serotonergic receptor function, whereas non-responders have low one. This is because it has been suggested that lithium's primary actions on the serotonergic neuron may be presynaptic and several reports have shown that lithium enhances serotonin synthesis and secretion at the presynaptic serotonergic neuron. As a preliminary study, we investigated the relationship between several responses to meta-chlorophenylpiperazine (a serotonergic agonist) reflecting the serotonergic receptor function and the clinical lithium response of 10 patients. No significant relationship between hormone responses and improvement ratios was found. However, there were significant relationships found between 'anger' during the challenge test and the improvement ratio and between 'tension' during the test and the improvement ratio. Thus, it seems that the hormone response to a serotonergic agonist is not useful for predicting lithium response. However, subjective responses such as anger and tension to a serotonergic agonist are possible candidates for predicting lithium response. In any case, further studies with larger numbers of participants are required to investigate whether subjective responses to a serotonergic agonist are useful for predicting lithium response.

Adult↗
PubMed2000

Treatment of Charles Bonnet syndrome with valproate.

Charles Bonnet syndrome (CBS), as described in the psychiatric literature, refers to pseudohallucinations in elderly people who frequently suffer from reduced visual acuity. There is no established treatment for CBS. We report two cases involving elderly women with CBS who were successfully treated with valproate. The present results suggest that valproate can be useful for CBS in some patients.

Age Factors↗
PubMed2000

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement.

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.

Adolescent↗
PubMed2000

Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine.

The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and found that the low dosage of levomepromazine was effective in counteracting the fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels. These results suggest that the inhibition of CYP2D6 by levomepromazine has little effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine, used as a hypnotic agent, appears to be effective and safe when coadministered with fluvoxamine. Since this was a pilot study without a placebo control, a double-blind placebo-controlled study is needed to confirm our preliminary findings.

Adult↗
PubMed2000

Dietary fat-induced increase in blood pressure and insulin resistance in rats.

OBJECTIVES: To determine whether the dietary-fat-induced increase in blood pressure is caused by excess energy intake or the fat composition of the diet, what type of fat increases the blood pressure, and whether insulin resistance is involved in the dietary-fat-induced increase in blood pressure. METHODS: In a series of experiments, rats received: chow alone or chow supplemented with lard or sucrose to provide 33% of a total energy content increased by 50%; chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil or medium-chain triglyceride oil; or chow alone or chow in which 50% of the energy content was from substituted lard, with or without troglitazone. Systolic blood pressure (SBP) was measured every week during each 8-week feeding period. A steady-state serum glucose method was used to determine the insulin sensitivity after the lard substitution with or without troglitazone. RESULTS: Both the lard and sucrose enrichment increased SBP and body weight compared with controls. Lard substitution significantly increased SBP and immunoreactive insulin, although body weight did not differ from control. Neither a diet substituted with safflower oil nor one substituted with medium-chain triglyceride oil influenced SBP. Troglitazone completely inhibited the increase in SBP and immunoreactive insulin induced by the lard. The steady-state serum glucose concentration was significantly greater after the lard substitution than after isoenergetic chow; this effect also was reversed by troglitazone. CONCLUSION: Chronic feeding with lard increased SBP in rats, independently of excess energy intake. Of the fats tested, lard exerted an intrinsic pressor effect. Troglitazone reversed the lard-induced increase in SBP.

Adipose Tissue↗
PubMed2000

Polymorphisms of tryptophan hydroxylase gene and the symptomatology of schizophrenia: an association study.

Serotonergic neurotransmission may be involved in the etiology of schizophrenia. We systematically searched for human tryptophan hydroxylase (TPH) coding polymorphisms, and detected a novel pentanucleotide repeat deletion polymorphism (GTTTT)4/5 in TPH intron 1b. We also confirmed A779C intron 7. Neither polymorphism showed a significant association with schizophrenia (182 patients with schizophrenia, 148 controls). A significant association, however, between A779C genotypes and the total Manchester Scale (MS) scores was found in male patients (P = 0.045). Subsequently, a significant association was also found between A779C genotypes and the MS negative symptoms scores in male patients (P = 0.030). These results suggest that the TPH gene may play a role in the negative symptoms in male patients with schizophrenia.

Alleles↗