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Biomedical subjects

R Yamamoto

Publications and source records attributed to R Yamamoto.

At least 19 recordsLinked to original sources

Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery.

BACKGROUND: Thrombus propagation on disrupted plaque is a major cause of acute coronary events and serious complication after coronary intervention. 5-Hydroxytryptamine (5-HT) is a potent vasoactive and platelet-aggregating substance that is predominantly mediated by 5-HT2A receptor. However, the roles of 5-HT2A receptor in occlusive thrombus formation on disrupted plaque remain obscure. OBJECTIVE: We investigated the role of 5-HT2A receptor in thrombus formation using a rabbit model of repeated balloon-injury. METHODS: Three weeks after a first balloon-injury of the femoral arteries, luminal diameter, neointimal growth, and vasoconstriction by 5-HT in vitro were examined. Thrombus propagation and the role of 5-HT2A receptor after a second balloon-injury were evaluated using sarpogrelate, a selective 5-HT2A receptor antagonist. RESULTS: Three weeks after the first balloon-injury, luminal stenosis was evident in the femoral arteries, where the neointima expressed tissue factor and 5-HT2A receptor. The hypercontractile response of the stenotic arteries to 5-HT was significantly reduced by sarpogrelate. Balloon-injury of the neointima with substantially reduced blood flow promoted the formation of occlusive thrombus that was immunoreactive against glycoprotein IIb-IIIa, 5-HT2A receptor and fibrin. Intravenous injection of sarpogrelate significantly inhibited ex vivo platelet aggregation induced by adenosine 5'-diphosphate, thrombin and collagen alone as well as with 5-HT, and significantly prevented occlusive thrombus formation in vivo. CONCLUSIONS: The 5-HT2A receptor appears to play a crucial role in occlusive thrombus formation in diseased arteries via platelet aggregation and vasoconstriction. Inhibition of 5-HT2A receptor might help reduce the onset of acute coronary events and of acute coronary occlusion after the intervention.

Animals↗

Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats.

The central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST) are key structures of the extended amygdala, which is suggested to be involved in drug addiction and reward. We have previously reported that the Ce plays a crucial role in the negative affective component of morphine withdrawal. In the present study, we examined the involvement of the neural pathway between the Ce and the BST in the negative affective component of morphine withdrawal in rats. Rats were rendered morphine dependent by s.c. implantation of a 75-mg morphine pellet for 3 days, and morphine withdrawal was precipitated by an i.p. injection of naloxone (0.3 mg/kg). In the place-conditioning paradigm, discrete bilateral excitotoxic lesions of the Ce or the BST significantly reduced naloxone-precipitated morphine withdrawal-induced conditioned place aversion. On the other hand, they had little effect on morphine withdrawal-induced somatic signs. In an immunohistochemical study for c-Fos protein, naloxone-precipitated morphine withdrawal dramatically induced c-Fos-immunoreactive neurons in the capsular part of the Ce, and the lateral and medial divisions of the BST. Bilateral excitotoxic lesion of the Ce reduced the number of morphine withdrawal-induced c-Fos-immunoreactive neurons in the lateral and medial BST, with significant decreases in the posterior, ventral and juxtacapsular parts of lateral division, and anterior part of the medial division, but not in the ventral part of the medial division of the BST. On the other hand, bilateral excitotoxic lesion of the BST had no effect on such c-Fos induction within the capsular part, nor the ventral and medial divisions of the Ce. These results suggest that activation of the BST mediated through the neural pathway from the Ce contributes to the negative affective component of morphine withdrawal.

Amygdala↗

Relaxant effect of adrenomedullin on bovine isolated iris sphincter muscle under resting conditions.

1. The mechanisms involved in the fine adjustment of iris sphincter muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated iris sphincter muscle. 2. The motor activity of the bovine isolated iris sphincter muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription-polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3. Adrenomedullin significantly decreased the resting tension of the muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22-52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8-37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22-52) and CGRP (8-37). 4. The relaxant effect of adrenomedullin was also significantly diminished by 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5. Reverse transcription-polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells. 6. These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the iris sphincter muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip.

Adrenomedullin↗

Herpes simplex esophagitis in the immunocompetent host.

We report here a case of herpes esophagitis with Mallory-Weiss syndrome in an immunocompetent host. A 26-year-old man was admitted to our hospital because of common cold symptoms and eruptions on the body. On day 2 after hospitalization, the patient showed high-grade fever, odynophagia and hematemesis. Upper gastrointestinal endoscopic examination showed multiple ulcerations throughout the mid- and distal esophagus. Bleeding from a Mallory-Weiss tear was also seen. Follow-up endoscopic examinations showed whitish exudates on day 5. Histological examination of biopsy specimens showed Cowdry type A intranuclear inclusion bodies in epithelial cells. Positive staining of a specific antibody against herpes simplex virus-1 (HSV-1) was seen in the nuclei of esophageal epithelial cells. Primary HSV-1 infection was suspected because ELISA titers of serum IgM antibody against HSV-1 were high and titers of serum IgG antibody against HSV-1 increased from an almost cut-off ratio. A diagnosis of herpes esophagitis in an immunocompetent host was made. Our case is the first report of herpes esophagitis with Mallory-Weiss syndrome in the immunocompetent host. It is important to remind herpes esophagitis in cases of severe odynophagia even in immunocompetent hosts.

Adult↗

Effects of agar (kanten) diet on obese patients with impaired glucose tolerance and type 2 diabetes.

AIM: The aim of this study was to evaluate the efficacy of agar diet in combination with a conventional diet (traditional Japanese food) for obese patients with impaired glucose tolerance and type 2 diabetes. METHODS: After a 4-week run-in period on their habitual diets, 76 patients were randomly assigned to have conventional diet or conventional diet with agar. Both groups were on these diets for 12 weeks. Body weight, body mass index (BMI), glycaemic control, blood pressure, insulin resistance, total body fat, fat distribution and lipids were assessed before and after the experimental period. RESULTS: In both groups, after 12 weeks, mean body weight, BMI, fasting glucose levels, homeostasis model assessment-insulin resistance, and systolic and diastolic blood pressures had decreased significantly from their baseline values. HbA(1)c, visceral fat area, subcutaneous fat area, total body fat, insulin area under the curve after oral glucose tolerance test and total cholesterol decreased significantly in the agar-diet group. After 12 weeks, mean changes of body weight (-2.8 +/- 2.7 kg vs. -1.3 +/- 2.3 kg, p = 0.008), BMI values (-1.1 +/- 1.1 kg/m(2) vs. -0.5 +/- 0.9 kg/m(2), p = 0.009) and total cholesterol (-7.6 +/- 27.5 mg/dl vs. + 2.4 +/- 23.4 mg/dl, p = 0.036) were significantly greater in the agar-diet group than in the conventional diet group. CONCLUSIONS: The agar diet resulted in marked weight loss due to the maintenance of reduced calorie intake and to an improvement in metabolic parameters.

Agar↗

Genetic mapping of quantitative trait loci affecting body weight, egg character and egg production in F2 intercross chickens.

Phenotypic measurements of chicken egg character and production traits are restricted to mature females only. Marker assisted selection of immature chickens using quantitative trait loci (QTL) has the potential to accelerate the genetic improvement of these traits in the chicken population. The QTL for 12 traits (i.e. body weight (BW), six for egg character, three for egg shell colour and two for egg production) of chickens were identified. An F2 population comprising 265 female chickens obtained by crossing White Leghorn and Rhode Island Red breeds and genotyped for 123 microsatellite markers was used for detecting QTL. Ninety-six markers were mapped on 25 autosomal linkage groups, and 13 markers were mapped on one Z chromosomal linkage group. Eight previous unmapped markers were assigned to their respective chromosomes in this study. Significant QTL were detected for BW on chromosomes 4 and 27, egg weight on chromosome 4, the short length of egg on chromosome 4, and redness of egg shell colour (using the L*a*b* colour system) on chromosome 11. A significant QTL on the Z chromosome was linked with age at first egg. Significant QTL could account for 6-19% of the phenotypic variance in the F2 population.

Analysis of Variance↗

(-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.

Group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) modulate neurotoxicity of excitatory amino acids and beta-amyloid-peptide (betaAP), as well as epileptic convulsions, most likely via presynaptic inhibition of glutamatergic neurotransmission. Due to the lack of subtype-selective ligands for group-III receptors, we previously utilized knock-out mice to identify mGluR4 as the primary receptor mediating neuroprotection of unselective group-III agonists such as L-AP(4) or (+)-PPG, whereas mGluR7 is critical for anticonvulsive effects. In a recent effort to find group-III subtype-selective drugs we identified (+/-)-PHCCC as a positive allosteric modulator for mGluR4. This compound increases agonist potency and markedly enhances maximum efficacy and, at higher concentrations, directly activates mGluR4 with low efficacy. All the activity of (+/-)-PHCCC resides in the (-)-enantiomer, which is inactive at mGluR2, -3, -5a, -6, -7b and -8a, but shows partial antagonist activity at mGluR1b (30% maximum antagonist efficacy). Chimeric receptor studies showed that the binding site of (-)-PHCCC is localized in the transmembrane region.Finally, (-)-PHCCC showed neuroprotection against betaAP- and NMDA-toxicity in mixed cultures of mouse cortical neurons. This neuroprotection was additive to that induced by the highly efficacious mGluR1 antagonist CPCCOEt and was blocked by MSOP, a group-III mGluR antagonist. Our data provide evidence for a novel pharmacological site on mGluR4, which may be used as a target-site for therapeutics.

Amyloid beta-Peptides↗

Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST).

We reviewed medical records of 256 patients to investigate the frequency and characteristics of hemorrhagic cystitis (HC) associated with reduced-intensity stem cell transplantation (RIST) as opposed to conventional stem cell transplantation (CST); 137 patients underwent CST and 119 RIST. Diagnosis of HC was made based on two or more episodes of sterile, macroscopic hematuria with normal coagulation profiles, without any evidence of renal stones or genitourinary malignancy. Actuarial frequency of HC development in RIST group was 7.6% (9/119), which gave a cumulative annual incidence of 11.7%. In CST group, 13 of 137 patients (9.5%) developed HC, giving an estimated annual incidence of 9.7%. The probability of developing HC was similar between the two groups (P=0.77). The viral etiologies of HC, adenovirus (n=12) and BK virus (n=2), were documented in eight patients after RIST and in six after CST. HC was milder and of a shorter duration, with less blood transfusion requirements, in RIST group than in CST group. A multivariate analysis revealed that HC was associated with antiadenovirus antibody positivity in the recipients, total dose of busulfan, and chronic GVHD. Although HC following RIST is less severe than that following CST, it is still a significant problem.

Adenoviridae↗

Magnetic structure, phase diagram, and a new type of spin-flop transition dominated by higher order interaction in a localized 5f system U3Pd20Si6.

The magnetic structure of the localized-5f uranium intermetallic compound U3Pd20Si6 has been determined by means of a neutron diffraction experiment. Our data demonstrate that this compound has a collinear coupling of the sublattice ordering of the uranium spins on the 4a and 8c sites. We conclude that higher-order exchange and/or quadrupole interactions are necessary to stabilize this unique collinear structure. We discovered a new type of spin-flop transition against the uniaxial anisotropy induced by this collinear coupling.

Journal Article↗

The diagnostic value of kappa/lambda ratios determined by flow cytometric analysis of biopsy specimens in B-cell lymphoma.

Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver-operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.

Adolescent↗

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Simple prognostic model for patients with multiple myeloma: a single-center study in Japan.

The range of survival duration in myeloma patients is wide and several percent of patients live longer than 10 years. Therefore, a precise prediction of survival for the individual patient is required to decide treatment. We evaluated possible prognostic factors at diagnosis for 116 Japanese patients with multiple myeloma. Twelve parameters reported to affect survival were analyzed using a log rank test and stepwise Cox proportional hazards regression. Factors identified as adversely affecting survival were age over 60 years, male sex, blood hemoglobin less than 8.5 g/dl, platelets less than 100 x 10(9)/l, serum creatinine level more than 2.0 mg/dl, serum C-reactive protein (CRP) level more than 6.0 mg/l, and serum beta2-microglobulin level more than 6.0 mg/l. Among them, only high age and high serum CRP level were independently prognostic for poor survival. In conclusion, we have established a simple prognostic model for Japanese myeloma patients only, using factors that can be determined in routine examinations without the need of subjective information.

Adult↗

Simulating particle dispersions in nematic liquid-crystal solvents.

A new method is presented for mesoscopic simulations of particle dispersions in nematic liquid-crystal solvents. It allows efficient first-principles simulations of the dispersions involving many particles with many-body interactions mediated by the solvents. A simple demonstration is shown for the aggregation process of a two dimensional dispersion.

Colloids↗

Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator.

We investigated the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), which is reported to accelerate glutamate uptake, on the development of morphine tolerance and physical dependence in mice. For the induction of morphine tolerance and dependence, mice were twice daily treated with morphine (10-45 mg/kg, s.c.) for 5 days. First, co-administration of MS-153 (12.5 mg/kg, s.c.) did not affect the morphine's potency for its acute antinociceptive effect (1 and 3 mg/kg, s.c.). Next, co-administrations of MS-153 (1, 3 and 12.5 mg/kg, s.c.) during repeated morphine treatments significantly attenuated the development of tolerance to the antinociceptive effect of morphine (3 mg/kg, s.c.) and suppressed the naloxone (10 mg/kg, i.p.)-precipitated withdrawal signs (jumps and body weight loss). The inhibitory effect of MS-153 on the withdrawal signs was due to the attenuation of the development of dependence rather than that of expression of withdrawal signs. These results suggest that MS-153, a glutamate transporter activator, has an inhibitory effect on the development of morphine tolerance and physical dependence.

ATP-Binding Cassette Transporters↗

Down-regulation of cell surface insulin receptors by sarco(endo)plasmic reticulum Ca2+-ATPase inhibitor in adrenal chromaffin cells.

Long-term (> or =12 h) treatment of cultured bovine adrenal chromaffin cells with thapsigargin (TG), an inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), caused a time (t(1/2)=16.3 h)- and concentration (IC50=37.8 nM)-dependent decrease of cell surface 125I-insulin binding by 35%, but did not change the Kd value. TG caused a sustained increase of cytoplasmic concentration of Ca2+ ([Ca2+]c) in a biphasic manner, and the effect of TG on 125I-insulin binding was abolished by BAPTA-AM. Western blot analysis showed that TG lowered insulin receptor (IR) beta-subunit level in membrane, but did not alter total cellular levels of IR precursor and IR beta-subunit. Internalization of cell surface IR, as measured by using brefeldin A, an inhibitor of vesicular exit from the trans-Golgi network (TGN), was not changed by TG. These results suggest that inhibition of SERCA by TG and the subsequent increase of [Ca2+]c down-regulates cell surface IR by retarding externalization of IR from the TGN.

Adrenal Glands↗

Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells.

We studied whether a novel proadrenomedullin derived peptide was present and what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of proadrenomedullin N-terminal 12 peptide (PAMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12 was added in the incubation medium, this peptide inhibited nicotinic receptor-mediated catecholamine release and influx of Na(+) and Ca(2+) into the cells. PAMP-12 did not affect catecholamine release evoked by histamine or by depolarization by high concentration of potassium. PAMP-12 also inhibited synthesis of catecholamines as well as the activation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamines by acting on nicotinic cholinergic receptors in an autocrine manner in adrenal chromaffin cells.

Adrenal Medulla↗

Clinical and pathologic findings in 52 consecutively autopsied cases with multiple myeloma.

We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998. Distant extraosseous involvement was found in 33 patients (63.5%). Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection. Amyloidosis was shown in 8 patients. Second malignancies were observed in 4 cases. The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients. Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection.

Aged↗