Biomedical subjects

Y Yamazaki

Publications and source records attributed to Y Yamazaki.

At least 127 records · Page 7Linked to original sources

PubMed2000

Endogenous adenosine regulates the effects of low-frequency stimulation on the induction of long-term potentiation in CA1 neurons of guinea pig hippocampal slices.

A train of low-frequency afferent stimuli (LFS, 1 Hz, 1000 pulses), given 60 min prior to a tetanus (100 Hz, 100 pulses), suppresses the induction of long-term potentiation (LTP) in which a short-term potentiation decreases gradually back to the pre-tetanic level within 40-50 min (LTP suppression). We investigated the effects of adenosine A1 or A2 receptor antagonists (8-cyclopentyltheophylline (8-CPT) and CP-66713, respectively) on LTP suppression in CA1 neurons of guinea pig hippocampal slices. When the LFS was delivered in the presence of 8-CPT (1 microM), LTP suppression was not significantly affected. However, when LFS was delivered in the presence of CP-66713 (10 microM), LTP suppression was inhibited, leading to successful LTP induction. These results indicate that endogenous adenosine, acting via A2 receptors, is involved in the mechanism of LTP suppression.

Adenosine↗

PubMed2000

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLGA) capsules to regenerate bone by controlling the release rate of rhBMP-2. The rhBMP-2/PLGA capsules containing 12 microg of rhBMP-2 were implanted in seven 15-mm segmental defects of rabbits radii to examine the healing capacity of the rhBMP-2/PLGA capsules. For the control group, four segmental defects were left empty and two were implanted with ghost PLGA capsules. Healing of the defects was followed for 24 weeks and periodically evaluated by radiographs and histological examination. Mechanical testing was applied to three regenerated bone samples at 24 weeks postoperatively when the mature cortex was observed. Mechanical properties of regenerated bone were not significantly different from normal intact bone statistically. Histologically, the rhBMP-2/PLGA capsules disappeared completely during the process of bone regeneration. These results increased possibilities for clinical application of rhBMP-2/PLGA capsules.

Animals↗

PubMed2000

Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma.

PURPOSE: TNP-470 is a strong inhibitor of angiogenesis. The present study was designed to determine whether the angiogenesis inhibitor TNP-470 inhibits metastasis of mouse neuroblastoma cells to the liver and thus increases survival. METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. First, to demonstrate the inhibitory effects of TNP-470 on angiogenesis, we quantified the area of angiogenesis on images made with SP-500 image analyzer (Olympus) 7 days after implanting a millipore chamber and compared the areas for the TNP-470-treated mice and control mice. Next, to determine the inhibitory effect of TNP-470 on metastasis of neuroblastoma cells to the liver, we made a murine hepatic metastasis model by implanting C1300 cells (1 x 10(6)) in the spleen of the mice and compared histologic findings, sizes, and weights of the livers of treated mice and control mice 14 days after the beginning of a 7-day infusion of TNP-470 (60 mg/kg). We also compared survival rates using the Kaplan-Meier method. RESULTS: When the angiogenesis inhibitor TNP-470 was infused into mice that received tumor cells, the area of angiogenesis in the TNP-470-treated mice was smaller than that in the control mice (52.5 +/- 6.3 SD vs 94.1 +/- 27.6 mm(2), P < 0.001). After the same treatment in other mice, no histologic evidence of metastasis was found, whereas control mice had countless tumor cell masses. Similarly, the weight of the liver was less in TNP-470-treated mice (0.8 +/- 0.1 g vs 4.5 +/- 0.3 g, P < 0.001). Survival was longer in the TNP-470-treated mice than in controls (80% of treated mice were alive more than 60 days after treatment, whereas all control mice died by Day 20). CONCLUSION: TNP-470 inhibits metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.

Angiogenesis Inhibitors↗

PubMed2000

Radiographic analysis of lumbar spine for low-back pain in the general population.

We sought to demonstrate a correlation between low-back pain (LBP) and the plain radiographic findings of the lumbar spine in the general population based on an analysis of 838 persons, 387 of whom presented with complaints of low-back pain. The incidence of intervertebral narrowing and irregular ossification of the vertebral end-plate image increased consistently with age and was higher in the presence of LBP in any age or gender group. Multiregression analysis was performed with the imaging factors as multivariates. As a result, multiregression equations with irregular ossification of the vertebral end-plate image, intervertebral narrowing, spondylolisthesis and abnormal lumbar lordotic angle combined as variates showed the highest significance as predictors of a relationship with LBP. The discrimination analysis was performed using the linear discriminant function, resulting in a true discrimination rate of 65%. Plain radiography of the lumbar spine is thus significant as it provides information which can be evaluated as meaningful findings in the investigation of LBP. In addition, while the significance can be increased by considering multiple factors, it is important to understand the limits of the accuracy of this prediction.

Adult↗

PubMed2000

Morphogenesis in cucumber seedlings is negatively controlled by gravity.

Seedlings of most cucurbitaceous plants develop a peg (protuberance caused by cell outgrowth) on the transition zone between the hypocotyl and root. The peg is necessary for removing the seed coat after germination. In our spaceflight experiments on the STS-95 space shuttle, Discovery, we found that cucumber (Cucumis sativus L.) seedlings grown under microgravity conditions developed two pegs symmetrically at the transition zone. Thus, cucumber seedlings potentially develop two pegs and do not require gravity for peg formation itself, but on the ground the development of one peg is suppressed in response to gravity. This may be considered as negative control of morphogenesis by gravity.

Cucumis sativus↗

PubMed2000

Ileal duplication presenting as perforation: report of a case.

We describe herein the case of a 10-year-old boy in whom generalized peritonitis was caused by perforation of a tubular communicating ileal duplication cyst. Alimentary tract duplication cysts are rare congenital malformations, found primarily in children under the age of 15 years. The perforation was caused by heterotopic gastric mucosa within the duplication, giving rise to peptic ulceration in the adjacent intestinal mucosa. The presence of heterotopic gastric tissue is a primary cause of perforation that has been reported in as many as one third of patients with small intestine duplications; however, the detection of such ectopic tissue is time-consuming, and there is no readily available method of diagnosing tubular duplications. Although very few patients present with peritonitis as the initial manifestation, the possibility should be borne in mind when diagnosing and planning therapy for such emergencies, particularly in children.

Child↗

PubMed2000

A new, safe, and easy technique of atrial septal defect creation.

We created an atrial septal defect (ASD) using a Ferris-Smith-Kerrison bone punch under transesophageal echocardiographic monitoring for infants with complex congenital heart diseases, eg, transposition of the great arteries. We describe a safe and easy technique of ASD creation instead of Blalock-Hanlon operation.

Echocardiography, Transesophageal↗

PubMed2000

Simplified dynamics model of planar two-joint arm movements.

A theoretical framework is presented that describes a way in which the inverse dynamics equations of motion of planar two-joint arm movements (EX-model) are reformulated in a simple form. A single point was assumed to define both the wrist and elbow joint centers, and thus the motion of two points in extrinsic space was represented by second-order differential equations to provide the variables in the reformulation (RE-) model. Through an analytical processes, it was shown that the RE-model for reproducing the shoulder joint torque consists of the linearly scaled moment per unit mass responsible for accelerating the wrist and elbow points about the shoulder joint, while that for reproducing the elbow joint torque consists of the linearly scaled moment per unit mass responsible for accelerating the wrist point about the elbow. The scaling factors for variables in the RE-model were based solely on the values for segment lengths, while in the EX-model the inertial parameter data for the segments are involved in its representation. The inertial parameter data of six-arm specimens from the cadaver experiment of Chandler et al. (1975, AMRL Technical Report, Wright-Patterson Air Force Base, OH) were used to develop and verify the numeric solutions of the RE-model. The adequacy of the model varied somewhat among subjects, but minor changes of the physical parameters of the arm segments enabled perfect reformulation, regardless of the specimens. The potential abilities of the RE-model to deal with the complexities in motor control with more simple control schemes are discussed.

Arm↗

PubMed2000

JTT-501, a new oral hypoglycemic agent, reverses hypertriglyceridemia in Zucker fatty and ventromedial hypothalamus-lesioned obese rats.

JTT-501 is a new oral hypoglycemic agent that is reported to be effective in insulin-resistant diabetic animal models by improving insulin resistance. It also improves hypertriglyceridemia. We investigated the mechanism of the reversal of hypertriglyceridemia in two types of obese animals using JTT-501. In Zucker fatty obese rats, an animal model of genetic obesity, fasting plasma triglyceride and glucose significantly decreased after a single daily oral dose of JTT-501 (100 mg/kg) for 7 days. In ventromedial hypothalamus (VMH)-lesioned obese rats, an animal model of nongenetic obesity, fasting plasma triglycerides significantly decreased but fasting plasma glucose levels remained unchanged after treatment with this agent. In Sprague-Dawley (SD) rats, fasting plasma triglyceride and glucose levels remained unchanged. The JTT-501-treated Zucker fatty and VMH-lesioned obese rats showed a decrease in insulin, but it was not significant, while the treated SD rats showed a significant decrease in insulin. Postheparin plasma lipoprotein lipase (LPL) increased significantly in treated Zucker fatty obese and SD rats, but did not change in VMH-lesioned obese rats. The hepatic triglyceride secretion rate (TGSR) did not change in any species treated with JTT-501. There was a negative correlation between postheparin plasma LPL and plasma triglyceride levels in Zucker fatty obese rats, while no such correlation was observed in VMH-lesioned obese or SD rats. The fractional catabolic rate (FCR) for plasma triglyceride was increased significantly by JTT-501 in both Zucker fatty and VMH-lesioned obese rats. These results suggest that JTT-501 decreases plasma triglycerides mainly by increasing postheparin plasma LPL in Zucker fatty obese rats, while it ameliorates an impairment in the ability of adipose tissue to remove triglyceride from the circulation in VMH-lesioned obese rats.

Animals↗

PubMed2000

Toxicity of methylmercury conjugated with L-cysteine on rat thymocytes and human leukemia K562 cells in comparison with that of methylmercury chloride.

In order to reveal the implication of use of methylmercury chloride (MeHgCl) in in vitro study, the effects of 10 µM MeHgCl on rat thymocytes and human leukemia K562 cells were compared with those of methylmercury conjugated with L-cysteine (10 µM MeHg-Cys) using a flow cytometer and fluorescent probes to monitor cellular physiological and pathological parameters. MeHgCl hyperpolarized membranes of thymocytes, followed by depolarization within a few minutes after the application, while MeHg-Cys persistently hyperpolarized them. MeHgCl increased intracellular concentration of Ca(2+), decreased cellular content of glutathione and increased generation of superoxide anion in the cells. The effects of MeHg-Cys were much less than those of MeHgCl. MeHgCl greatly increased both numbers of the cells undergoing apoptosis and dead cells in cell suspension containing thymocytes, while this was not the case for MeHg-Cys. MeHgCl reduced the cell viability of human leukemia K562 cells and completely inhibited the cell growth. The effects of MeHg-Cys on K562 cells were less than those of MeHgCl. It can be concluded that the effects of MeHgCl on rat thymocytes and K562 cells are different from those of MeHg-Cys. The results obtained from the in vitro studies using MeHgCl may be less implicit to elucidate the mechanism of MeHg intoxication in humans and experimental animals because MeHg are present in forms of MeHg-Cys and/or MeHg-S conjugate under the in vivo conditions.

Journal Article↗

PubMed2000

Effects of A1 and A2 adenosine receptor antagonists on the induction and reversal of long-term potentiation in guinea pig hippocampal slices of CA1 neurons.

1. Using simultaneous recordings of the field EPSP and the population spike in the CA1 neurons of guinea pig hippocampal slices, we confirmed that delivery of a high-frequency stimulation (tetanus: 100 pulses at 100 Hz) produced robust long-term potentiation of synaptic efficacy (LTP) in two independent components, a synaptic component that increases field excitatory postsynaptic potentials (EPSPs) and a component that results in a larger population spike amplitude for a given EPSP size (E-S potentiation). 2. In the same cells, reversal of LTP (depotentiation; DP) in the field EPSP and in the E-S component is achieved by delivering low-frequency afferent stimulation (LFS: 1 Hz, 1000 pulses) 20 min after the tetanus. 3. When the tetanus or LFS was applied to CA1 inputs in the presence of an adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (1 microM), the field EPSP was enhances in LTP and attenuated in DP, while the E-S relationship was not significantly affected in either LTP or DP. 4. When similar experiments were performed using an A2 receptor antagonist, CP-66713 (10 microM), the field EPSP was blocked in LTP but facilitated in DP, while E-S potentiation was enhanced during both LTP and DP. 5. The results show that endogenous adenosine, acting via A1 or A2 receptors, modulates both the synaptic and the E-S components of the induction and reversal of LTP. Based on the results, we discuss the key issue of the contribution of these receptors to the dynamics of neuronal plasticity modification in hippocampal CA1 neurons.

Action Potentials↗

PubMed2000

Polymorphisms in the TNFA promoter region is not associated with palmoplantar pustulosis.

Polymorphisms of the 5'-flanking promoter/enhancer region of the TNAFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5'-flanking region of the TNFA gene from -1107 to 66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position 1031, -863, -857, -307 and -237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of the TNFB gene as well as HLA-DR9. The genotype at 1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA-B.

Genotype↗

PubMed2000

Involvement of cyclic AMP - PKA pathway in VIP-induced, charybdotoxin-sensitive relaxation of longitudinal muscle of the distal colon of Wistar-ST rats.

The intracellular mechanism of vasoactive intestinal peptide (VIP)-induced, charybdotoxin (ChTx)-sensitive relaxation of longitudinal muscle of the distal colon of Wistar-ST rats was studied. A single pulse or 100 pulses at 10 Hz of electrical field stimulation (EFS) induced rapid transient relaxation or that with a subsequent contraction of the longitudinal muscle in the presence of atropine and guanethidine, respectively. Rp-8 bromo cAMPS, an inhibitor of cyclic AMP dependent protein kinase (PKA), at 30 microM inhibited the relaxations induced by EFS with a single or 100 pulses maximally by about 80 or 60%, respectively. It also inhibited VIP (300 nM)-induced relaxation by 82%. VIP (100 nM - 1 microM) increased the cyclic AMP content of longitudinal muscle myenteric plexus preparations obtained from the distal colon. ChTx at 100 nM almost completely inhibited 8 bromo cyclic AMP-induced relaxation of the distal segments. EFS with two or three pulses at 10 Hz induced inhibitory junction potentials consisting of two phases, rapid and subsequent slow hyperpolarization in the membrane potential of longitudinal smooth muscle cells. Rp-cAMPS, another inhibitor of PKA, inhibited the delayed slow hyperpolarization. It also inhibited the exogenously added VIP-induced hyperpolarization of the cell membrane. Thus, the present study suggests that activation of PKA via activation of VIP receptors is associated with activation of ChTx-sensitive K(+) channels in relaxation of longitudinal muscle of the distal colon of Wistar-ST rats. British Journal of Pharmacology (2000) 129, 140 - 146

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Increase in participation of vasoactive intestinal peptide in relaxation of the distal colon of Wistar rats with age.

Changes in participation of vasoactive intestinal peptide (VIP) in nonadrenergic noncholinergic (NANC) relaxation of longitudinal muscle of the distal colon with age were studied in 2- to 50-week-old Wistar rats in vitro. The extent of the VIP-mediated component of the relaxation induced by electrical field stimulation (EFS) was determined by the effect of VIP(10 - 28), a VIP receptor antagonist. In 2-week-old rats, the extent of the VIP-mediated component of the relaxation was scarce, about 10%, whereas the component gradually increase with age and reached the maximum extent 66% at 50-week-old. Since our previous results suggest that VIP induces NANC relaxation via activation of charybdotoxin (ChTx, a blocker of large conductance Ca(2+)-activated K(+) channel)-sensitive K(+) channels with concomitant slow hyperpolarization in the muscle cells, we next studied whether ChTx-sensitive component and slow hyperpolarization changes with age. Extent of ChTx-sensitive component of the relaxation increased with age, showing a very similar pattern to VIP-mediated one. EFS induced monophasic inhibitory junction potentials (i.j.ps) in longitudinal muscle cells of the distal colon of 2- and 4-week-old. EFS also induced biphasic i.j.ps in many longitudinal muscle cells of 8- and 50-week-old: rapid and subsequent slow hyperpolarization. A VIP receptor antagonist selectively inhibited the slow hyperpolarization. Exogenously added VIP induced no appreciable change in the membrane potential of longitudinal muscle cells of 2-week-old, whereas it induced slight slow hyperpolarization of the cell membrane in 4-week-old and magnitude of the hyperpolarization increased with age. On the other hand, relaxant response of the longitudinal muscle to exogenously added VIP was high in younger rats. The present results suggest that the role of VIP in mediating NANC relaxation of longitudinal muscle of the Wistar rat distal colon is very little at neonatal stage, but it increases with age.

Age Factors↗

PubMed2000

Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine.

A novel gene transfer system was developed by using liposomes modified with cetylated polyethylenimine (PEI, MW 600). This polycation liposome, PCL, showed remarkable transfection efficiency as monitored by the expression of the GFP reporter gene. Most conventional cationic liposomes require phosphatidylethanolamine or cholesterol as a component, although PCLs did not. Egg yolk phosphatidylcholine- and dipalmitoylphosphatidylcholine-based PCL were as effective as dioleoylphosphatidylethanolamine-based PCLs for gene transfer. Concerning the cytotoxicity against COS-1 cells and hemolytic activity, the PCL was superior to conventional cationic liposome preparations. Furthermore, the transfection efficacy of PCLs was enhanced, instead of being diminished, in the presence of serum. Effective gene transfer was observed in all eight malignant and two normal cells line tested, as well as in COS-1 cells. We also examined the effect of the molecular weight of PEI on PCL-mediated gene transfer, and observed that PEI with a MW of 1800 Da was as effective as that with one of 600, but that PEI of 25,000 was far less effective. Finally, an in vivo study was done in which GFP was effectively expressed in mouse liver after injection of PCL via the portal vein. Thus, PCL represents a new system useful for transfection and gene therapy.

Animals↗

PubMed2000

Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis.

BACKGROUND: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established. AIM: To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients. METHODS: Serum levels of clarithromycin and its metabolite. 14-(R)-hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2-week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori-positive out-patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy. RESULTS: Values for the area under the 0-6 h concentration-time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0-6 h) values of 14-(R)-hydroxyclarithromycin were significantly lower in the Child-Pugh C group than in either the normal controls or the Child-Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%-88%) and 81% on an intention-to-treat analysis (95% CI: 77%-85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%-99%) and 83% in an intention-to-treat analysis (95% CI: 70%-97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study. CONCLUSION: The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication in patients with liver cirrhosis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2000

Endoscopic [13C]-urea breath test for quantification of Helicobacter pylori infection.

BACKGROUND: We previously developed a new diagnostic method for Helicobacter pylori infection and called it the endoscopic [13C]-urea breath test (EUBT). Here we evaluate the relationship between the EUBT results and the histological findings. METHODS: The EUBT was performed on 137 patients with gastroduodenal diseases. After the collection of a baseline breath sample, gastroduodenal endoscopy was performed. Twenty milliliters of 0.05% phenol red solution containing 100 mg of [13C]-urea was sprayed over the entire gastric mucosa under endoscopic observation. A breath sample was collected 15 min after spraying. The content of 13CO2 in the breath samples was measured by ratio mass spectrometry. Two biopsy specimens each from the antrum and the middle corpus were obtained for culture and histology. Helicobacter pylori colonization, activity, inflammation, atrophy and intestinal metaplasia were classified on a four-point scale according to the Updated Sydney System. RESULTS: We found positive correlations between the EUBT values and the H. pylori colonization and activity score in the antrum and corpus, and negative correlations between the EUBT values and the atrophy and intestinal metaplasia scores in the corpus. CONCLUSIONS: The EUBT can be an indicator of the intragastric bacterial load and the histological findings for H. pylori.

Breath Tests↗

PubMed2000

Helicobacter pylori infection occurs via close contact with infected individuals in early childhood.

BACKGROUND: The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet, to date, the exact mode of transmission remains uncertain. METHODS: The seroprevalence of H. pylori in a relatively isolated rural town in Japan (A-town) was examined to analyse the H. pylori infection route. The immunoglobulin G antibodies against H. pylori in 1684 subjects who had received public health examinations in A-town were determined with an enzyme-linked immunosorbent assay. The seroprevalence was compared in five areas according to the water source. The possibility and frequency of intrafamilial infection was analysed by comparing the seroprevalence among family members residing in the same home. RESULTS: The seroprevalence of H. pylori did not differ significantly between the five areas examined. Seropositivity was significantly more common in the children whose mothers were seropositive (45.0%, 27/60) than in the children whose mothers were seronegative (10.0%, 2/20; odds ratio (OR) = 7.36, P = 0.0036, 95% confidence interval (CI) = 1.57-34.59). Seropositivity was significantly more common in the children whose older siblings were seropositive (55.0%, 22/40) than in the children whose older siblings were seronegative (23.5%, 20/85; OR = 3.97, P = 0.00051, 95% CI = 1.79-8.84). There was no significant relationship in seroprevalence between children and fathers, grandchildren and grandfathers, grandchildren and grandmothers, or within couples. Seropositivity was significantly more common in the adolescents who had attended a nursery school (44.4%, 20/45) than in the adolescents who had not attended a nursery school (25.6%, 109/426) (OR = 2.33, P = 0.0070, 95% CI = 1.24-4.36). CONCLUSIONS: The acquisition of H. pylori infection occurs by close contact with infected individuals in early childhood, especially via contact with infected mothers and other infected children.

Adolescent↗