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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 55 records · Page 3Linked to original sources
PubMed2001

A novel ligation forceps can be used as a ligature carrier and knot pusher during laparoscopic surgery.

BACKGROUND: To extend the usefulness of laparoscopic operations, a secure and easy method for the ligation of large vessels is needed. Herein we describe a novel ligation forceps that can be used as a ligature carrier and knot pusher. METHODS: A 2-0 suture thread with a knot already tied near one end is hooked in the upper jaw of a novel ligation forceps. After the lower jaw is passed under the vessel or cystic duct, the forceps is closed. When one end of the thread is withdrawn, the knot is trapped in the indentation built into the lower jaw; the ligature is then passed under the pedicle. An extracorporeal ligation can then be performed continuously by the same forceps. RESULTS: The origins of large vessels were ligated safely and easily with this device during 65 laparoscopic procedures (four total colectomies, 12 colectomies, and 49 gastrectomies). Following temporary hemostasis of accidental bleeding with clamping forceps, ligation hemostasis can also be performed using this instrument. CONCLUSION: This novel ligation forceps permits the secure ligation of vessels or a cystic duct without the need for another device. The proposed method is both easy and inexpensive.

Gastrectomy↗
PubMed2001

Association analysis between two functional dopamine D2 receptor gene polymorphisms and schizophrenia.

The dopamine D2 receptor (DRD2) gene has been listed as one of the candidate genes for susceptibility to schizophrenia. To date, a significant association between schizophrenia and two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, in Japanese samples, has been reported by Arinami et al. [1994: Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582]. In the present study, we replicated the findings of Arinami et al. [1994: Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582] in the same ethnic groups (Japanese samples) with the same polymorphisms (Ser311Cys and -141C Ins/Del). We genotyped these two polymorphisms for 241 patients and for 201 controls. Neither polymorphism was associated with schizophrenia. Moreover, in a haplotype analysis of the present sample, combined pairs of two polymorphisms provided no evidence for the association of either haplotype with schizophrenia. Our findings indicate that an association between the two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, and schizophrenia is unlikely.

Aged↗
PubMed2001

Role of PKC and TGF-beta receptor in glucose-induced proliferation of smooth muscle cells.

The role of protein kinase C (PKC) and transforming growth factor (TGF)-beta in the proliferation of vascular smooth muscle cells (SMCs) under a high glucose condition was investigated. [3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531. The amount of active and total TGF-beta1 in the conditioned media did not differ between 5.5 and 20 mM glucose. However, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not. This increased expression of the TGF-beta receptor type II was prevented by LY333531. These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the accelerated proliferation of SMCs under a high glucose condition, leading to the development of diabetic macroangiopathy.

Activin Receptors, Type I↗
PubMed2001

Clara cell secretory protein (CC16) gene polymorphism and schizophrenia in humans.

An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with activation of the inflammatory response system, as indicated by lower serum concentrations of Clara cell secretory protein (CC16), an endogenous anti-inflammatory protein in patients with schizophrenia. In the present study, we investigated the genetic association between a functional polymorphism (A38G) in human CC16 gene and schizophrenia (248 Japanese schizophrenic patients and 206 healthy controls). No significant positive association between the CC16 gene polymorphism and schizophrenia was observed. In addition, even when schizophrenic patients were divided into those with a positive family history for schizophrenia and with a negative family history for schizophrenia, no significant association with A38G polymorphism of the CC16 gene was observed. Our results suggest that the CC16 gene polymorphism do not confer increased susceptibility for schizophrenia.

Female↗
PubMed2001

Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the human gastrointestinal tract. Previous studies of GISTs found gain-of-function mutations of the c-kit gene, which encodes a receptor tyrosine kinase (KIT). All the mutations were confined to exon 11, which encodes the juxtamembrane domain. By further examination of the whole coding region of c-kit complementary DNA in 35 GISTs, two were found to show the identical mutation at exon 9, which encodes the extracellular domain. The aims of the present study were to examine the frequency of the extracellular domain mutation and to determine whether the mutation is a gain-of-function type or not. Genomic DNA was extracted from paraffin-embedded tissues of 133 GISTs and exon 9 of the c-kit gene was amplified by polymerase chain reaction. Screening of the mutation was carried out by single-strand conformation polymorphism analysis and direct sequencing was done. Mutant c-kit cDNA was transfected into 293T human embryonic kidney cells and the magnitude of autophosphorylation of the mutant KIT was examined with or without the ligand of KIT, stem cell factor (SCF). In total, seven GIST cases (approximately 5%) were found with the identical mutation at exon 9. The mutant KIT exhibited constitutive autophosphorylation without SCF stimulation. The prognosis of the patients with the extracellular domain mutation was comparable to that of the patients with the juxtamembrane domain mutation.

Adult↗
PubMed2001

Ocular absorption behavior of palmitoyl tilisolol, an amphiphilic prodrug of tilisolol, for ocular drug delivery.

The objective of this study was to examine the ocular absorption behavior of an amphiphilic prodrug after instillation onto the cornea of rabbits. A micellar solution of O-palmitoyl tilisolol (PalTL), an amphiphilic prodrug, was prepared. After instillation of tilisolol (TL) and PalTL, the drug concentrations in the tear fluid, cornea, aqueous humor, iris-ciliary body, vitreous body, and blood were measured. In addition, in situ ocular absorption behavior was also evaluated. After instillation of TL, the concentration of TL in the tear fluid quickly decreased. After instillation of PalTL, prolonged retention and high concentrations of PalTL in tear fluid and the cornea were observed. In addition, more prolonged retention of the TL concentration after instillation of PalTL than after instillation of TL was observed in the cornea, aqueous humor, and iris-ciliary body. In situ experiments demonstrated that PalTL was mainly absorbed by the corneal route and the improvement effects of PalTL under in vivo conditions was due to an enhanced transit time of PalTL in ocular tissues. PalTL, an amphiphilic prodrug, exhibited increased retention in the precorneal area compared with the parent drug, TL, resulted in improved ocular absorption of the parent drug.

Absorption↗
PubMed2001

Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity.

AIMS/HYPOTHESIS: The protein kinase C (PKC), platelet-derived growth factor (PDGF) and polyol pathway play important parts in the hyperproliferation of smooth muscle cells, a characteristic feature of diabetic macroangiopathy. The precise mechanism, however, remains unclear. This study investigated the relation between polyol pathway, protein kinase C and platelet-derived growth factor in the development of diabetic macroangiopathy. METHODS: Smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without an aldose reductase inhibitor, epalrestat, or a PKC-beta specific inhibitor, LY333531. Protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, free cytosolic NAD+:NADH ratio, the contents of reduced glutathione, and proliferation activities were measured. RESULTS: Smooth muscle cells cultured with 20 mmol/l glucose showed statistically significant increases in protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, and proliferation activities, compared with smooth muscle cells cultured with 5.5 mmol/l glucose. Although epalrestat and LY333531 inhibited protein kinase C activation induced by glucose to the same degree, the effects of epalrestat on proliferation activities and expression of the PDGF-beta receptor were more prominent than those of LY333531. Epalrestat improved the glucose-induced decrease in free cytosolic NAD+:NADH ratio and reduced glutathione content, but LY333531 did not. The increased expression of membranous PKC-beta II isoform was normalized by epalrestat. CONCLUSION/INTERPRETATION: These observations suggest that polyol pathway hyperactivity contributes to the development of diabetic macroangiopathy through protein kinase C, PDGF-beta receptor, and oxidative stress, and that an aldose reductase inhibitor has a therapeutic value for this complication.

Aldehyde Reductase↗
PubMed2001

Physiological and morphometric analyses of neuropathy in sucrose-fed OLETF rats.

To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with or without sucrose and/or an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), for 24 weeks, and physiological, biochemical and morphological assessments were performed. Sucrose administration caused remarkable hyperglycemia in OLETF rats but not in LETO rats. Sucrose-fed OLETF rats demonstrated delayed nerve conduction velocity, decreased coefficient of variation of R-R interval, reduced sciatic nerve blood flow, increased platelet aggregation activity, a lower concentration of erythrocyte 2,3-diphosphoglycerate, and decreased Na+/K+-ATPase activity in sciatic nerves, compared with the non-sucrose-fed OLETF and LETO rats. TAT prevented all these deficits except hyperglycemia. Sorbitol and fructose accumulation and myo-inositol depletion in tail nerves of sucrose-fed OLETF rats were ameliorated by TAT. Myelinated fiber size and density in sural nerves of sucrose-fed OLETF rats were decreased and increased, respectively, compared with non-sucrose-fed OLETF and LETO rats. These morphological abnormalities were normalized by TAT. These observations suggest that the sucrose-fed OLETF rat developed diabetic neuropathy not only electrophysiologically but also histologically, and that an aldose reductase inhibitor, TAT, possesses therapeutic value for the treatment of diabetic neuropathy.

2,3-Diphosphoglycerate↗
PubMed2001

Protein kinase C-dependent and -independent inhibition of Ca(2+) influx by phorbol ester in rat pancreatic beta-cells.

Phorbol esters were used to investigate the action of protein kinase C (PKC) on insulin secretion from pancreatic beta-cells. Application of 80 nM phorbol 12-myristate 13-acetate (PMA), a PKC-activating phorbol ester, had little effect on glucose (15 mM)-induced insulin secretion from intact rat islets. In islets treated with bisindolylmaleimide (BIM), a PKC inhibitor, PMA significantly reduced the glucose-induced insulin secretion. PMA decreased the level of intracellular Ca(2+) concentration ([Ca(2+)](i)) elevated by the glucose stimulation when tested in isolated rat beta-cells. This inhibitory effect of PMA was not prevented by BIM. PMA inhibited glucose-induced action potentials, and this effect was not prevented by BIM. Further, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a non-PKC-activating phorbol ester, produced an effect similar to PMA. In the presence of nifedipine, the glucose stimulation produced only depolarization, and PMA applied on top of glucose repolarized the cell. When applied at the resting state, PMA hyperpolarized beta-cells with an increase in the membrane conductance. Recorded under the voltage-clamp condition, PMA reduced the magnitude of Ca(2+) currents through L-type Ca(2+) channels. BIM prevented the PMA inhibition of the Ca(2+) currents. These results suggest that activation of PKC maintains glucose-stimulated insulin secretion in pancreatic beta-cells, defeating its own inhibition of the Ca(2+) influx through L-type Ca(2+) channels. PKC-independent inhibition of electrical excitability by phorbol esters was also demonstrated.

Action Potentials↗
PubMed2001

Increased libido in a woman treated with fluvoxamine: a case report.

OBJECTIVE: The aim of this paper is to describe a case of increased libido during fluvoxamine therapy. METHOD: Single case report. RESULTS: The patient, a 27-year-old married Japanese woman with borderline personality disorder, developed an increased libido with the administration of fluvoxamine. The increased libido disappeared after fluvoxamine was discontinued. CONCLUSION: The present findings suggest that fluvoxamine can cause increased libido in some patients.

Adult↗
PubMed2001

Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies.

Factors influencing the outcome for 39 children with haematological malignancy who were subjected to a cord blood transplantation (CBT) from genotypically HLA-mismatched unrelated donors were analysed. This retrospective study included 21 children with acute lymphoblastic leukaemia, 15 with acute myelogenous leukaemia and one each with chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML). Those subjected to CBT during the first or second complete remission (CR) and MDS without blasts were assigned to the standard-risk (SR) group (n = 16). Patients in third or subsequent remission, relapse or partial remission with refractory leukaemia at the time of CBT were considered to be in advanced phase, and placed in the high-risk (HR) group (n = 11). JMML and the second CR after a relapse (n = 8), or bone marrow failure after a rejection (n = 3), following haematopoietic stem cell transplantation (HSCT) in the first CR were included in the high-risk group. Kaplan-Meier estimates for neutrophil and platelet recovery were 83.7 +/- 12.2 at d 60 and 55.4 +/- 16.6% at d 100 respectively. The incidence of grades II-VI acute graft-versus-host disease was 58.5 +/- 16.8%. The Kaplan-Meier estimate for 3-year event-free survival (EFS) was 49.2 +/- 16.6. From multivariate analysis, the most important factor influencing EFS was disease status at CBT: SR patients had a 3-year EFS of 75.0 +/- 21.6%, compared with 29.6 +/- 20.6% for those with HR disease (P = 0.013, RR 4.746, 95% CI 1.382-16.298). These data confirm that HLA-mismatched, unrelated CBT is a feasible procedure to cure a significant proportion of children with leukaemia, especially if conducted in a favourable phase of the disease.

Adolescent↗
PubMed2001

Effects of endodontic instrument handle diameter on electromyographic activity of forearm and hand muscles.

AIM: To determine the influence of the handle diameter of endodontic instruments on forearm and hand muscle activity using electromyographic (EMG) recording. METHODOLOGY: Size 45 K-type files were fitted with four different handle diameters; 3.5, 4.0, 5.0, and 6.0 mm. Seven dentists then attempted to negotiate to the working length acrylic resin root canals with each of the four handle sizes using a reaming motion. EMG activities were recorded from the flexor pollicis brevis muscle (f.p.b.), the flexor carpi radialis muscle (f.c.r.), and the brachioradialis muscle (b) with bipolar surface electrodes. The time taken to negotiate the canals, the area of integrated EMG that corresponded to the amount of EMG activity required during penetration and the maximum amplitude of EMG were measured using the EMG data. Results were analysed statistically using a one-way factorial ANOVA test and multiple comparison tests. RESULTS: Reaming time and integrated EMG area of each muscle decreased with an increase in handle diameter. The most significant difference in time and area of integrated EMG was detected between handles of 6 mm and 3.5 mm diameter (time: P < 0.01, area of the f.p.b.: P < 0.01, area of the f.c.r. and b: P < 0.05), and between handles of 5 mm and 3.5 mm diameter (P < 0.05). Both 5 mm and 6 mm handles significantly decreased the maximum amplitude of EMG recorded from the f.p.b. compared with 3.5 mm handles (between 3.5 mm and 6 mm: P < 0.01, between 3.5 mm and 5 mm: P < 0.05). CONCLUSION: The results indicate that handle diameter has an effect on reaming time as well as on muscle activity. As a consequence, handle diameter influenced operator performance during instrumentation.

Acrylic Resins↗
PubMed2001

The influence of two concentrations of sodium hypochlorite on human blood: changes in haemolysis, pH and protein.

AIM: To evaluate the in vitro effect of 2.5% and 5.0% sodium hypochlorite (NaOCl) on human blood. METHODOLOGY: Each concentration of NaOCl was reacted with human blood for 5 min at volume ratios of 1 : 1, 1 : 6, 1 : 12, each creating changes in colour, pH and temperature. Reaction suspensions were separated by centrifugation, and absorption measurements made for separated bilirubin, Fe, and protein supernatants. Each supernatant was desalted, lyophilized, and treated by SDS polyacrylamide gel electrophoresis (SOS-PAGE). RESULTS: Increased ratios and concentrations of NaOCl caused an increase in both pH and temperature. Protein supernatants tended to decompose on SDS-PAGE. Supernatants showed increased decolourisation with 5.0% NaOCl. Concentrations of bilirubin, Ferrum and protein in supernatants decreased with increased NaOCl concentration. NaOCl had an effect on the protein component in blood. CONCLUSIONS: These data suggest that changes in molecular structure are due to the chemical effects of NaOCl. Protein bands tended to show low molecular weight, suggesting that haemoglobin components effect the oxidation-reduction reaction.

Adult↗
PubMed2001

Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment.

We demonstrated the effect of clonazepam (2 mg/day) on Meige syndrome in two schizophrenic patients under continuous treatment with antipsychotic drugs, and changes in the plasma levels of gamma-aminobutyric acid (GABA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in these cases. The plasma levels of HVA and MHPG during treatment with clonazepam were decreased in the responder, while not changed in the non-responder to clonazepam. A difference between the responder and the non-responder was not found in the plasma GABA levels. These results suggest that hyperactivities of the central dopaminergic and noradrenergic neurones are involved in the pathophysiology of Meige syndrome.

Adult↗
PubMed2001

Dual phases of functional change in norepinephrine transporter in cultured bovine adrenal medullary cells by long-term treatment with clozapine.

The effects of long-term treatment with clozapine, a prototype of atypical antipsychotic drugs, on the functional activity, synthesis and mRNA of norepinephrine (NE) transporter were examined in bovine adrenal medullary cells in culture. Treatment of cells with clozapine at 0.1-3.0 microM concentrations produced dual phases of changes in [(3)H]NE uptake, i.e. the first phase showed a decrease in [(3)H]NE uptake at 2-48 h, and the following phase showed an increase in uptake at 72-168 h. Treatment with clozapine for 6 h decreased V(max) to 40% of the control without changing the K(m) value for [(3)H]NE uptake. However, treatment with clozapine for 96 h increased V(max) by 56% over the control without a change in K(m). Scatchard plot analysis of [(3)H]desipramine (DMI) binding to membranes isolated from cells treated with clozapine for 6 h revealed a decrease in B(max) without any change in K(d); in contrast, treatment with clozapine for 96 h caused an increase in B(max) without any change in K(d). Both actinomycin D and cycloheximide, which are inhibitors of protein synthesis, suppressed the clozapine (96 h)-induced increase in [(3)H]NE uptake. Treatment of cells with clozapine for 12-96 h increased the level of NE transporter mRNA in a concentration-dependent manner (0.3-3.0 microM). These findings suggest that treatment of cells with clozapine results in the down-regulation and subsequent up-regulation of NE transporter. The latter change may be caused by the synthesis of new proteins of NE transporter via an increase in its mRNA.

Adrenal Medulla↗
PubMed2001

An easy method for the intraluminal administration of peppermint oil before colonoscopy and its effectiveness in reducing colonic spasm.

BACKGROUND: Systemic administration of a cholinergic blocking agent or glucagon is used to reduce spasms, but it is inconvenient and sometimes causes side effects. This study is an evaluation of the intracolonic administration of peppermint oil during colonoscopy for the control of colonic spasm. METHODS: Each patient in the treated group (n = 409) was given approximately 200 mL of the solution (a mixture of 8 mL of peppermint oil and 0.2 mL of Tween 80 per 1 L of water with 0.04% indigo carmine) by using a hand pump attached to the accessory channel of the colonoscope. Changes in patient posture were made to distribute the solution. The patients in the control group (n = 36) were given the solution without peppermint oil. RESULTS: A satisfactory spasmolytic effect was seen in 88.5% of the treated patients and in 33.3% of those in the control group (p<0.0001). No adverse effect was observed. The mean time to onset was 21.6 +/- 15.0 seconds, and the effect continued for at least 20 minutes. In patients with irritable bowel syndrome, efficacy was significantly lower (p < 0.0001). CONCLUSIONS: The intraluminal administration of peppermint oil by using a hand pump is a simple, safe, and convenient alternative to the systemic injection of a cholinergic blocking agent or glucagon during colonoscopy.

Adult↗