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Biomedical subjects

J Yamamoto

Publications and source records attributed to J Yamamoto.

At least 109 records · Page 6Linked to original sources

Effects of clopidogrel on platelet activation and coagulation of non-anticoagulated rat blood under high shear stress.

Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.

Animals↗

Insulin resistance and angiotensin converting enzyme polymorphism in Japanese hypertensive subjects.

Renin-angiotensin system activity has been shown to affect insulin sensitivity. However, the relationship between I/D polymorphism and insulin resistance is controversial. Therefore, we examined the relationship between the ACE genotype and insulin sensitivity in 51 Japanese hypertensive patients using the glucose clamp technique. The ACE genotype distribution in the hypertensive subjects was: 7 subjects with DD, 20 subjects with ID, and 24 subjects with II. Insulin sensitivity in terms of the glucose disposal rate was not significantly different among the three ACE genotypes, although there was a tendency for insulin sensitivity to decrease in the order of II, ID and DD, DD being the lowest. These findings are contrary to previous reports that insulin sensitivity was increased in normotensive subjects with the DD genotype who were Caucasian or African-American. There might be a difference due to race and whether the subjects are hypertensive or obese. We concluded that insulin sensitivity was not different among the ACE genotypes in the Japanese hypertensive subjects, supporting a previous report on the Chinese population. To date, insulin sensitivity has not been found to differ with ACE genotypes in the oriental population.

Adult↗

Effects of papain on isolation of single smooth muscle cells from the guinea pig longitudinal ileum.

The methods for isolation of single cells from the guinea pig longitudinal ileum were investigated with focussing on the papain concentration for the digestion of the ileum. The ileal muscle was minced. The minced muscle was loaded with fluorescent probes of calcein or fura 2, and treated with papain for 30 min at various concentrations. Papain at concentrations more than 1 U/ml reduced both calcein fluorescence and fura-2-signal evoked by carbachol. Carbachol-induced fura-2-signal was more sensitive to papain than calcein fluorescence, suggesting that proteins related to the formation of receptors are more vulnerable than membrane lipids or proteins limiting the membrane permeability upon the exposure to papain. The resultant yield of single cells was highest at 0.56 U/ml of papain without affecting calcein and fura-2 fluorescence responses, thus this concentration appeared to be appropriate for the isolation of single cells from the ileum. Single cells alive contracted dose dependently by the exposure to carbachol (0.1-10 microM) under the microscopic measurement, and were appeared to grow confluent in culture for approximately 15 days. These results suggest that the low concentration, 0.56 U/ml, of papain in the isolation medium is better to obtain functional cells from the guinea pig ileum.

Animals↗

Effect of cisplatin on cell death and DNA crosslinking in rat mammary. Adenocarcinoma in vitro.

The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P < 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P < 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P < 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.

Adenocarcinoma↗

Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.

Albinism↗

Effects of intracranial pressure on the pial microcirculation in rats studied by a fiber-optic laser-Doppler anemometer microscope.

The fiber-optic laser-Doppler anemometer microscope (FLDAM) developed in our laboratory was applied to measure red cell velocity in individual pial microvessels in rats to determine the effect of intracranial pressure (ICP) on the pial microcirculation. The red cell velocity and the vessel diameter of pial microvessels were measured through a closed cranial window at controlled values of ICP between 0 and 50 mmHg. As ICP increased from 0 to 50 mmHg, the average relative diameter of venules with respect to the diameter at an ICP of 5 mmHg decreased from 1.18 +/- 0.12 (mean +/- SD) to 0.74 +/- 0.08 and the average relative velocity increased from 0.80 +/- 0.20 to 1.83 +/- 0.42 monotonically. The changes in diameter and velocity of arterioles with ICP were small, and they were not significantly different from those values at an ICP of 5 mmHg except for the diameter at an ICP of 20 mmHg. The mean volume flow rates calculated assuming a circular vessel cross-section did not show any statistically significant change with ICP between 0 and 50 mmHg in both arterioles and venules, which supports the concept of autoregulation.

Animals↗

Macroscopic intrabiliary growth of liver metastases from colorectal cancer.

BACKGROUND: The clinicopathologic features of colorectal liver metastases that invade the bile duct were evaluated. METHODS: From 1992 to 1996, 149 patients who underwent a first hepatic resection were studied for a total of 377 colorectal liver metastases. Twenty-one second hepatic resections in these patients were also analyzed. RESULTS: Bile duct invasion was histologically observed in 62 (42%) of 149 patients with first colorectal liver metastasis. Eighteen patients (12%) had gross extension of the tumor in the bile duct ranging from 4 mm to 42 mm (median 17.0 mm). Histologically, two thirds (12 of 18) of the tumors with macroscopic bile duct invasion were well-differentiated adenocarcinomas with a tendency for less vascular involvement. The actuarial 3- and 5-year survivals were 62% and 57% for patients with no bile duct invasion, 56% and 48% for patients with microscopic bile duct invasion, and 94% and 80% for patients with macroscopic bile duct invasion. The 5-year survival rate was better for patients with macroscopic bile duct invasion than for those with only microscopic (P = .02) or no bile duct invasion (P = .03). In a multivariate analysis, macroscopic bile duct invasion was an independent prognostic variable for favorable outcome after hepatic resection. CONCLUSIONS: Macroscopic bile duct invasion of colorectal liver metastases may reflect an indolent biologic behavior, warrants an aggressive surgical approach, and confers a better prognosis.

Adenocarcinoma↗

A hyperalgesic effect of intracerebroventricular cytokine-induced neutrophil chemoattractant-1 in the rat paw pressure test.

Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a member of the chemokine superfamily. The effect of intracerebroventricular (i.c.v) injection of CINC-1 on the mechanical nociceptive threshold in the rat was examined using the paw-pressure test. An i.c.v. injection of CINC-1 at doses of 1 and 10 pg/rat tended to decrease the nociceptive threshold for mechanical stimuli at 15 min after the injection, and significantly lowered the threshold at 30 min. The threshold stayed at these lowered level over 180 min after the injection. Lower (100 fg/rat) and higher (30 and 100 pg/rat, and 1 and 10 ng/rat) doses of CINC-1 had no effect on the mechanical nociceptive threshold. The present results suggest that CINC-1 facilitates mechanical nociception in the central nervous system (CNS).

Animals↗

Effects of nicotine, pilocarpine, and tetrahydroaminoacridine on hippocampal theta waves in freely moving rabbits.

The effects of three cholinergic agents on hippocampal theta waves were investigated by analyzing electroencephalographic power spectra in freely moving rabbits. In the hippocampal spectra, nicotine (a nicotinic receptor agonist, 0.03 mg/kg) increased the theta wave frequency, but caused no change in its power. Pilocarpine (a muscarinic receptor agonist, 0.3 and 1.0 mg/kg) and tetrahydroaminoacridine (a cholinesterase inhibitor, 3.0 mg/kg) increased the power and deceased the frequency. These results suggest that the activating effect of nicotinic receptor agonists on the hippocampus may be different from that of muscarinic receptor agonists or cholinesterase inhibitors.

Animals↗

Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells.

The expression of the mRNAs for stromal cell-derived factor-1alpha and -1beta (SDF-1alpha and -1beta) and their receptor CXCR4 in cultured rat glial and neuronal cells was examined. SDF-1alpha mRNA was expressed intensely in astrocytes and weakly in neurons, but not in microglia. SDF-1beta mRNA was expressed weakly in these three types of cells. The expressions of SDF-1alpha and -1beta mRNAs in astrocytes were decreased by treatment with LPS (100 ng/ml) for 1-6 h but markedly increased by that for 24-72 h, whereas the expression of SDF-1beta mRNA in microglia was hardly changed by the treatment for 0.5-6 h, and was decreased by that for 24-48 h. The expression of CXCR4 mRNA was observed in astrocytes, microglia and neurons, and was not altered by LPS treatment.

Animals↗

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Amino Acid Sequence↗

The antithrombotic effect of potent bifunctional thrombin inhibitors based on hirudin sequence, P551 and P532, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.

The antithrombotic effect of potent synthetic bifunctional non-substrate type thrombin inhibitors based on hirudin sequences, P551 and P532, on Helium-Neon laser-induced thrombosis was investigated in rat mesenteric microvessels and compared with other types of thrombin inhibitors. P551 and P532, when given intravenously, inhibited platelet-rich thrombus formation in both arterioles and venules in a dose-dependent manner. The inhibitory effect was maximal immediately after intravenous administration and persisted for 20-30 minutes in both arterioles and venules. The minimal effective doses of P551 and P532 were 1.0 mg/ kg (intravenously) in both. However, the time course of the antithrombotic effect was not in keeping with the inhibitory effect measured by an activated partial thromboplastin time and was similar to other types of inhibitors in spite of different half-lives. The current findings show that P551 and P532 had significant inhibitory effects on platelet-rich thrombus formation and suggest that these bifunctional thrombin inhibitors could be potent antithrombotic agents.

Animals↗

Putative pheromone receptors related to the Ca2+-sensing receptor in Fugu.

By a combination of PCR with degenerate primers and low stringency probing, we have isolated a large family of genes related to the Ca2+-sensing receptor from the genome of Fugu rubripes. One of the genes (type I) is the Fugu homologue of the Ca2+-sensing receptor. The remaining genes can be divided into five classes (type II-VI) on the bases of gene structure. In several types, the genes occur in clusters as tandem arrays. These genes appear to be the homologues of the vomeronasal pheromone receptors recently described in rodents. The Fugu genes are expressed in the tissues of the nose, suggesting that they may have a similar physiological role.

Animals↗

Effects of cyclosporine and FK506 on in vitro high shear-induced platelet reactivity in rat and human non-anticoagulated blood.

BACKGROUND: The immunosuppressants cyclosporine and FK506 have been used successfully in clinical transplantation, but both agents have various side effects. We have previously found that cyclosporine is prothrombotic and that FK506 is antithrombotic in an in vivo system. The aim of the present study was to assess the effects of these agents on platelet reactivity and coagulation using an in vitro shear-induced hemostatic platelet plug-forming instrument, the hemostatometer. METHODS: A purpose-built hemostatometer was constructed in our laboratory. The effects of cyclosporine and FK506 on platelet reactivity and coagulation were assessed under high shear stress using non-anticoagulated rat and human blood. RESULTS: FK506 significantly inhibited both platelet reactivity and coagulation. Cyclosporine also significantly inhibited coagulation, but a proaggregatory effect was observed at a final blood concentration of 0.05 mg/ml. CONCLUSIONS: The present in vitro results support our previous in vivo findings regarding the prothrombotic and antithrombotic effects of cyclosporine and FK506, respectively.

Adult↗

Thoracic spinal angiomyolipoma with extracanal extension to the thoracic cavity. A case report.

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To describe a 72-year-old man with thoracic spinal angiomyolipoma in the ventral aspect of the epidural space and extracanal extension to the posterior mediastinum, to discuss the clinical and radiologic features and unique biologic behavior of this entity, and to review of the literature on angiolipoma and angiomyolipoma. SUMMARY OF BACKGROUND DATA: Spinal angiolipoma and angiomyolipoma are rare tumors, which are localized almost exclusively in the dorsal epidural space of the thoracic spine. Most reported cases have no tendency to involve the surrounding tissue. METHODS: The authors describe the radiologic, surgical, and pathologic findings of this patient and review the findings from other reported cases. RESULTS: Anterior decompression was performed using a right transthoracic incision, and the neurologic symptoms improved immediately. There were no signs of recurrence of the tumor or neurologic deficit within a 2-year follow-up period. CONCLUSION: Results of a literature survey of these tumors support management by prompt and radical surgical intervention for long-term cure, even in cases in which the infiltrating nature is recognized.

Aged↗