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Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 145 records · Page 8Linked to original sources

Alpha 1-adrenoceptor subtype distribution and the coupling to phosphoinositide hydrolysis in rat and rabbit ventricular myocardium.

The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.

Adrenergic alpha-Agonists↗

The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system.

The receptor for advanced glycation end products (RAGE), a newly-identified member of the immunoglobulin superfamily, mediates interactions of advanced glycation end product (AGE)-modified proteins with endothelium and other cell types. Survey of normal tissues demonstrated RAGE expression in situations in which accumulation of AGEs would be unexpected, leading to the hypothesis that under physiologic circumstances, RAGE might mediate interaction with ligands distinct from AGEs. Sequential chromatography of bovine lung extract identified polypeptides with M(r) values of approximately 12,000 (p12) and approximately 23,000 (p23) which bound RAGE. NH2-terminal and internal protein sequence data for p23 matched that reported previously for amphoterin. Amphoterin purified from rat brain or recombinant rat amphoterin bound to purified sRAGE in a saturable and dose-dependent manner, blocked by anti-RAGE IgG or a soluble form of RAGE (sRAGE). Cultured embryonic rat neurons, which express RAGE, displayed dose-dependent binding of 125I-amphoterin which was prevented by blockade of RAGE using antibody to the receptor or excess soluble receptor (sRAGE). A functional correlate of RAGE-amphoterin interaction was inhibition by anti-RAGE F(ab')2 and sRAGE of neurite formation by cortical neurons specifically on amphoterin-coated substrates. Consistent with a potential role for RAGE-amphoterin interaction in development, amphoterin and RAGE mRNA/antigen were co-localized in developing rat brain. These data indicate that RAGE has physiologically relevant ligands distinct from AGEs which are likely, via their interaction with the receptor, to participate in physiologic processes outside of the context of diabetes and accumulation of AGEs.

Animals↗

8-hydroxydeoxyguanosine levels in DNA of human breast cancer are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method.

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals, and a high level of 8-hydroxyguanine in breast cancers was previously demonstrated by the gas chromatography-mass-spectrometry method. To confirm the previous observation, the oh8dG levels of DNA of 22 breast cancers and corresponding adjacent non-cancerous breast tissues were analyzed by high performance liquid chromatography-electrochemical detector (HPLC-ECD) system, and the correlation of the oh8dG levels in breast cancer DNAs with clinical and immunohistochemical parameters was examined. However, the levels of oh8dG in DNA of breast cancers are not significantly different from those of corresponding non-cancerous breast tissues (P = 0.084) by the HPLC-ECD method. Furthermore, the oh8dG levels in breast cancers were not associated with p53 and erbB-2 immunoreactions, with expression of estrogen and progesterone receptors, and with clinical stage and histological grade. Thus, in contrast to the previous data, the present study using the HPLC-ECD method does not indicate an increase of oh8dG levels in breast cancers.

8-Hydroxy-2'-Deoxyguanosine↗

Involvement of beta-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte-stimulating hormone, in rats.

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.

Animals↗

Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats.

7-OH-DPAT ((+/-)-2-(dipropylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene) was recently identified as a dopamine receptor agonist having a > 100-, 1,000- and > 10,000-fold higher affinity for dopamine D3 than for D2, D4 and D1 receptors, respectively. Quinpirole (LY 171555) has also been reported to have a 113-fold greater affinity for dopamine D3 receptors than for D2 receptors. Therefore, we investigated the effects of these putative dopamine D3 receptor agonists on yawning, stereotypy and rectal temperature in rats (N = 424). 7-OH-DPAT and quinpirole administered subcutaneously (SC) at respective low doses of 10-250 micrograms/kg and 25-500 micrograms/kg elicited yawning behavior. The yawning induced by these agents was blocked by spiperone (0.5 mg/kg, SC) and scopolamine (0.5 mg/kg, SC) but was increased by intraperitoneal (IP) administration of pindolol (20 mg/kg). The yawning was also potentiated after treatment with reserpine. 7-OH-DPAT and quinpirole at respective high doses of 0.25 mg/kg (SC) and 0.5 mg/kg (SC) evoked slight stereotypy such as sniffing and licking, and this effect was enhanced by a selective dopamine D1 receptor agonist, SK&F 38393 (1-phenyl-2,3,4,5,-tetrahydro-(1H)-3-benzazepine-7,8-diol). 7-OH-DPAT (0.5 mg/kg, SC) and quinpirole (0.5 mg/kg, SC) decreased, but SK&F 38393 (10 mg/kg, SC) increased body temperature. However, the hyperthermia induced by SK&F 38393 was interestingly enhanced by 7-OH-DPAT and quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel.

Recent studies have identified five NMDA receptor subunits, which exhibit distinct cellular expressions in the normal rodent brain. The purpose of this investigation is to clarify the molecular-anatomical organization in the cerebellum of the reeler mutant mouse, in which various categories of the Purkinje cells are present as to the cell position and synaptic connectivity. In comparison with the distribution of the inositol 1,4,5-trisphosphate receptor mRNA, a molecular marker specific to the Purkinje cells, the epsilon 1 subunit mRNA of the NMDA receptor channel was found in the adjacent sections to be expressed in a subset of the Purkinje cells. In the rostrocaudal extent, the Purkinje cells expressing the epsilon 1 subunit mRNA were distributed preferentially in the rostral cerebellum, irrespective of the normal and heterotopic positions. In the mediolateral extent, they formed segregated cell clusters, interposed by epsilon 1 subunit mRNA-negative clusters. Hybridizing signals for the zeta 1 subunit mRNA were found in all the Purkinje cell population, whereas those for the epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were not detected in the cells. These findings suggest that the reeler cerebellum is topographically compartmentalized by two subpopulations of the Purkinje cells, one expressing the epsilon 1 and zeta 1 subunit mRNAs, and the other expressing the zeta 1 subunit mRNA alone.

Animals↗

Comparison of casual blood pressure and twenty-four-hour ambulatory blood pressure in high school students.

OBJECTIVE: To perform ambulatory blood pressure monitoring (ABPM) in high school students and to compare the 24-hour values with casual blood pressure (BP). METHODS: Ambulatory BP monitoring was carried out in 190 high school students, 15 or 16 years of age, with elevated casual BP during the first examination at school for hypertension; 66 had elevated casual BP at both the first and the second examinations (group H1), and 124 students were normotensive at the second examination (group H2). Sixty-two students who were consistently normotensive served as control subjects (group N). Average BPs for the 24-hour period, the awake period (10 AM to 10 PM), and the sleeping period (1 AM to 6 AM) were calculated. RESULTS: Average BP for each period was significantly higher in group H1 than in group N. Average BP in group H2 for these periods was intermediate between those of group H1 and of group N. The casual BP had a significant positive correlation with the average BP during the awake period (r = 0.55, p < 0.01 for systolic BP; r = 0.37, p < 0.01 for diastolic BP). In most subjects the casual BP readings were higher than BP during ABPM. CONCLUSIONS: Casual BP measurements correlated with 24-hour BP, but they tended to be higher than the measurements obtained during 24-hour ABPM.

Adolescent↗

Sensation in the anal region and rectum after surgery for anorectal malformations.

Sensation of the anal region and rectum after surgery for anorectal malformations was investigated in 32 patients (17 with high type, 6 with intermediate type and 9 with low type anomaly), aged 5 to 16 years. All patients were examined as to whether or not they could appreciate sensations of touch, pain, heat and cold in the circumanal skin and in the anal canal. Rectal sensation and compliance were also examined by anorectal manometry. All patients had normal sensation in the circumanal skin, but less than half of them had normal sensation in the anal canal. Patients with normal bowel control showed a significantly higher incidence of touch sensation in the anal canal than those with fecal incontinence or constipation. It was suggested that a sensation defect of the anal canal is related to a disturbance of discrimination between flatus and feces. The results of rectal sensation and compliance showed that reduced elasticity of the neorectum and low rectal compliance were important factors of fecal incontinence after surgery for anorectal malformations.

Adolescent↗

New biofeedback therapy in children with encopresis.

Biofeedback therapy was performed in 13 patients with encopresis using newly devised computerized equipment. The patients were children, aged 6 to 11 years, who had not responded to trials of conventional therapy with a mean follow-up period of three years and two months. The biofeedback therapy was effective in 12 of the 13 patients after one course of therapy. This positive results was attributed to the computerized equipment. The patients could more easily recognize how to squeeze their anal sphincters after seeing a colored ellipse representing sphincter pressure on a monitor. The results of anorectal manometry and electromyography (EMG) showed that biofeedback therapy improved the voluntary sphincter function and rectal sensation. Therefore, biofeedback therapy might be effective in patients with encopresis whose sphincter functions are intact.

Anal Canal↗

Formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine, in mouse lung DNA after intratracheal instillation of diesel exhaust particles and effects of high dietary fat and beta-carotene on this process.

Diesel exhaust particles (DEP) cause tumors in the respiratory tracts of experimental animals. It was previously shown that DEP produced superoxide and hydroxyl radical. To examine whether oxygen radicals are involved in mouse lung tumorigenesis induced by DEP, formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine (oh8dG), by DEP was investigated. Furthermore, the role of high dietary fat and beta-carotene on this process was studied. After intratracheal instillation of DEP, a significant increase of oh8dG in mouse lung DNA was observed. High dietary fat enhanced the formation of oh8dG in lung DNA. Intake of beta-carotene suppressed the formation of oh8dG in lung DNA, but the protective effect of beta-carotene against this process was not statistically significant. These results suggest that formation of oh8dG in lung DNA was induced by oxygen free radicals produced by DEP. Thus, it is possible that oh8dG is a promutagenic lesion in DEP-induced lung tumorigenesis in mice and high dietary fat enhances this process through the generation of oh8dG in mouse lung DNA.

8-Hydroxy-2'-Deoxyguanosine↗

A rare presentation of acantholytic dyskeratosis.

We describe an elderly woman who presented with numerous papular, keratotic lesions on the scalp. Histology of a biopsy specimen revealed epidermal invaginations, with large keratotic plugs, at the sites of hair follicles. In addition, there was acantholytic epidermal cell separation at a suprabasal level, and a large number of corps ronds were present above the split. It is likely that this case represents a rare presentation of acantholytic dyskeratosis. The relationship to other conditions which show acantholysis and dyskeratosis histologically is discussed.

Acantholysis↗

Erythema nodosum, lichen planus and lichen nitidus in Crohn's disease: report of a case and analysis of T cell receptor V gene expression in the cutaneous and intestinal lesions.

A wide variety of cutaneous manifestations have been described in association with Crohn's disease (CD). We describe a patient with a 2-year history of CD who developed both lichen planus (LP) and lichen nitidus (LN) in addition to erythema nodosum (EN) lesions. The clinical course of EN reflected the activity of the bowel disease, whereas LP and LN appeared to persist independently of the ongoing disease activity. Immunohistochemical studies of the infiltrates in these cutaneous and intestinal lesions showed that the majority of the infiltrates were T cells expressing T cell receptor (TCR)-alpha beta. Analyses of TCR V gene expression in these infiltrating T cells demonstrated a different pattern of V beta expression that provides an explanation for the difference in the clinical courses of these lesions. LP and LN lesions are likely to be mediated by T cells with antigen specificity distinct from those that cause EN and intestinal lesions.

Adult↗

Long-term follow-up of idiopathic ventricular arrhythmias in otherwise normal children.

Clinical characteristics and long-term prognosis of 163 children with ventricular arrhythmias without underlying heart diseases (78 with ventricular premature contractions (VPC group), 39 with ventricular couplets (CPLT group), and 46 with ventricular tachycardia (VT group)) were studied by Holter electrocardiographic monitoring (Holter ECG) and treadmill exercise testing. The age of the subjects at the initial examination was 8.9 +/- 3.4 years in the VPC group, 9.9 +/- 3.5 years in CPLT group, and 9.4 +/- 3.1 years in the VT group. The duration of the follow-up was 71.7 +/- 32.1 months in the VPC group, 65.9 +/- 32.8 months in the CPLT group, and 84.0 +/- 31.9 months in the VT group. VPC's disappeared during the follow-up period in 22 (28%) of the 78 children in the VPC group. CPLT's disappeared in 15 (38%) and VPC's disappeared in 9 (23%) of the 39 children in the CPLT group. In the 46 children in the VT group, VT disappeared in 30 (65%), and VPC's disappeared in 17 (37%). One child (2%) in the VT group died of heart failure due to drug-resistant sustained VT. The mean time until the disappearance of VPC's in the 163 patients was estimated to be 115.2 +/- 4.3 months. The mean time until the disappearance of VT in the 46 children in the VT group was estimated to be 89.0 +/- 4.9 months. Multivariate analysis of prognostic factors related to the disappearance of VPC's indicated that nighttime VPC's were significantly more likely to disappear (p = 0.018), and that symptomatic VT was significantly more likely to disappear than asymptomatic VT (p = 0.032), probably because more symptomatic cases received antiarrhythmic therapy. Ventricular arrhythmias in children without underlying diseases often disappeared, and the prognosis was generally favorable. However, appropriate treatment and follow-up were required in children with sustained VT, symptomatic VT, or VT with a high rate of VT.

Adolescent↗

Effects of an HMG-CoA reductase inhibitor on cytokine production by human monocytes/macrophages.

It has been reported that the HMG-CoA reductase inhibitor simvastatin does not always effectively lower plasma LDL. This drug acts to monocytes/macrophages directly and inhibits cholesterol ester accumulation in these cells. However cytokine production in macrophages when simvastatin was administrated has not been described. In this study, we examined whether simvastatin affects cytokine production in human monocyte-derived macrophages. Simvastatin at doses ranging from 10(-9) to 10(-5) M did not affect the synthesis of proinflammatory cytokines (IL-1 beta, IL-6, IL-8) from human peripheral mononuclear cells. In addition, any changes in cytokine-induced cytokine production (IL-1-induced IL-8 synthesis) were not detected after the addition of simvastatin. The present results suggest that simvastatin suppresses foam cell formation in monocyte/macrophage, without affecting the immunological or inflammatory functions of these cells.

Cells, Cultured↗

Sex differences in the shapes of several parts of the young Japanese face.

For the purpose of studying the sex differences of the human face we collected five separate images, which consist of several parts of the face, from frontal view photographs of 48 male and 52 female college students. We traced outlines of their faces with simple lines (traced items), and made reproductions of the photographs of their eyes, mouth and nose by using a copying machine (reproduced items). The test subjects were 16 males and 8 females. They looked at parts of the face shown in each image, and categorized them individually by judging on their sex. Then, we calculated the percentages of correct judgments (percentage correct) for each image. By comparing the percentage correct between male and female we concluded that the sex of the subjects did not affect the results of their judgments. In the traced items the percentage correct for the face as a whole, which contained the outlines of the eyes, mouth, nose and the lower jaw, was 69%, but it decreased to 61% when the outline of the lower jaw was removed. Hence, the outline of the lower jaw apparently has a characteristic shape easily noticed by males. In the reproduced items the percentage correct was 65% for the eyes, 68% for the mouth and 58% for the nose. The mouth, therefore, has more distinguishing characteristics than the eyes or nose, especially with females. On the other hand, there is no correlation between the percentage correct for the eye, mouth and nose items. Hence, we concluded that the sexual specificity for the shape of the young Japanese face appears on their parts independently.

Adult↗

[A successful surgical case of bilateral partial anomalous pulmonary venous connection without atrial septal defect].

We performed the new operative method for bilateral partial anomalous pulmonary connections (PAPVC) without atrial septal defect (ASD). A 11-years-old boy was admitted for operation. The right upper pulmonary vein returned to the superior vena cave (SVC), and left upper pulmonary vein returned to the innominate vein. Atrial septum was intact. The Qp/Qs was 1.94. The right atrium (RA) was opened and ASD was created. Continuity between the distal end of the SVC and RA was re-established by end-to-end anastomosis to the right atrial appendage. The proximal end of the SVC was closed. The right anomalous pulmonary vein remained in situ on the lower segment of SVC, blood being directed to the left atrium (LA) through the created ASD by suturing the posterior flap of RA incision to the atrial septum well away from the sinoatrial node and artery, anomalous pulmonary vein and cavoatrial junction. The anomalous left vertical vein was dissected up to the innominate vein. The left pulmonary vein was mobilized as much as possible, and was anastomosed to the posterior wall of LA by end-to-side fashion. He has normal sinus rhythm and no evidence of pulmonary venous obstructions on both sides. We support the efficacy of this method as an alternative in the management of this disorder.

Brachiocephalic Veins↗