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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 37 records · Page 2Linked to original sources

Ghrelin acts in the central nervous system to stimulate gastric acid secretion.

Ghrelin is a novel acylated peptide that functions in the regulation of growth hormone release and energy metabolism. It was isolated from rat stomach as an endogenous ligand for growth hormone secretagogue receptor. Ghrelin is also localized in the arcuate nucleus of rat hypothalamus. Intracerebroventricular (ICV) administration increases food intake and body weight. We examined the effect of ghrelin on gastric acid secretion in urethane-anesthetized rats and found that ICV administration of ghrelin increased gastric acid output in a dose-dependent manner. Vagotomy and administration of atropine abolished the gastric acid secretion induced by ghrelin. ICV administration of ghrelin also induced c-fos expression in the neurons of the nucleus of the solitary tract and the dorsomotor nucleus of the vagus, which are key sites in the central nervous system for regulation of gastric acid secretion. Our results suggest that ghrelin participates in the central regulation of gastric acid secretion by activating the vagus system.

Animals↗

Effect of melatonin on circadian rhythm, locomotor activity and body temperature in the intact house sparrow, Japanese quail and owl.

We compared the effect of melatonin on circadian rhythm, body temperature, and locomotion in the intact house sparrow, Japanese quail and owl. Daily treatment with melatonin at a fixed time did not entrain the free-running rhythm of locomotor activity in the house sparrow and the disrupted rhythm in Japanese quail under constant dim light. However, melatonin clearly inhibited movement for several hours after treatment. The duration of resting after injection of melatonin was dose-dependent. Body temperature was significantly decreased after melatonin treatment, the effect being more potent during the active phase than in the resting phase. Although this effect of melatonin on body temperature was also dose-dependent, the magnitude of the decrease in body temperature after injection of melatonin was greater in the house sparrow than in the Japanese quail. On the other hand, melatonin induced a further large decrease of body temperature in a nocturnal bird, the owl, whose pineal gland is degenerate. The decrease of body temperature was larger in the active phase than in the resting phase, and melatonin did not prevent movement in spite of the decrease in body temperature. These results suggest that the effects of melatonin on circadian rhythm, locomotor activity and body temperature differ among avian species, and that these mechanisms may not be linked to each other.

Animals↗

A role for ghrelin in the central regulation of feeding.

Ghrelin is an acylated peptide that stimulates the release of growth hormone from the pituitary. Ghrelin-producing neurons are located in the hypothalamus, whereas ghrelin receptors are expressed in various regions of the brain, which is indicative of central-and as yet undefined-physiological functions. Here we show that ghrelin is involved in the hypothalamic regulation of energy homeostasis. Intracerebroventricular injections of ghrelin strongly stimulated feeding in rats and increased body weight gain. Ghrelin also increased feeding in rats that are genetically deficient in growth hormone. Anti-ghrelin immunoglobulin G robustly suppressed feeding. After intracerebroventricular ghrelin administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the regulation of feeding, including neuropeptide Y6 (NPY) neurons and agouti-related protein (AGRP) neurons. Antibodies and antagonists of NPY and AGRP abolished ghrelin-induced feeding. Ghrelin augmented NPY gene expression and blocked leptin-induced feeding reduction, implying that there is a competitive interaction between ghrelin and leptin in feeding regulation. We conclude that ghrelin is a physiological mediator of feeding, and probably has a function in growth regulation by stimulating feeding and release of growth hormone.

Animals↗

Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration.

Ghrelin is a novel gut-brain peptide that binds to the growth hormone secretagogue receptor (GHS-R), thereby functioning in the regulation of growth hormone (GH) release and food intake. Ghrelin-producing cells are most abundant in the oxyntic glands of the stomach. The regulatory mechanism that governs the biosynthesis and secretion of ghrelin has not been clarified. We report that ghrelin mRNA expression in the gastric fundus was increased, but that ghrelin peptide content decreased after a 48-h fast. Both values returned to control levels after refeeding. The ghrelin plasma concentration in the gastric vein and systemic venous blood increased after 24- and 48-h fasts. Furthermore, des-octanoylated ghrelin and n-octanoylated ghrelin were found in rat stomach, with the ratio of des-octanoylated ghrelin to n-octanoylated ghrelin markedly increased after fasting. The ghrelin mRNA level in the stomach also increased after administration of insulin and leptin. Conversely, db/db mice, which are deficient in the leptin receptor, had lower ghrelin mRNA levels than control mice. These findings suggest that this novel gastrointestinal hormone plays a role in the regulation of energy balance.

Animals↗

Usefulness of MR imaging in the postsurgical monitoring of gallbladder cancer in a patient with bile duct cancer that developed 7 years after resection of mucinous adenocarcinoma of the gallbladder.

We encountered a case of left hepatic duct cancer that developed 7 years after surgical resection of early-stage adenocarcinoma of the gallbladder. A 65-year-old woman was hospitalized with high fever and general fatigue. She also had elevated serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, and carbohydrate antigen 19-9. Seven years earlier, she had undergone extended cholecystectomy and resection of the extrahepatic bile duct for early-stage mucinous adenocarcinoma of the gallbladder. Conventional examinations did not reveal any responsible lesions. Magnetic resonance (MR) cholangiography, however, showed a tumor obstructing the left hepatic duct, and dynamic MR images revealed multiple foci of bacterial abscess in the liver. Surgically resected tissue again revealed mucinous adenocarcinoma. The present case is rare in that metachronous mucinous adenocarcinoma of the biliary system occurred after a long interval. This case suggests the usefulness of MR imaging in the postsurgical monitoring of patients with gallbladder carcinoma.

Adenocarcinoma, Mucinous↗

A population-based neuroepidemiological survey of West syndrome in Okayama Prefecture, Japan.

It is important for the fields of child neurology and child public health to clarify the prevalence and incidence rates of West syndrome because this syndrome is a major cause of developmental disorders.However, there have been few reports in Japan on the prevalence rate of West syndrome in the general population. We carried out a population-based survey in Okayama Prefecture, in western Japan in 1994. The population under 2 years of age in Okayama Prefecture in 1994 was 37,085. Six cases of West syndrome were identified. The prevalence rate was 0.16 per 1000.

Data Collection↗

Ghrelin in domestic animals: distribution in stomach and its possible role.

Ghrelin, a novel growth-hormone-releasing acylated peptide, was recently isolated from rat and human stomachs. In rat, peripheral or central administration of ghrelin stimulates the secretion of growth hormone (GH) from the pituitary gland. Recent work suggests that ghrelin plays an important role in energy homeostasis, body weight, and food intake. We examined the distribution of cells immunoreactive to ghrelin in the stomachs of domestic animals and rats, using a polyclonal antibody for the N-terminal fragment of rat ghrelin [1-11]. We measured the plasma levels of ghrelin before and after feeding in cows, and GH levels after central administration of ghrelin in Shiba goats, to elucidate the possible role of ghrelin. Immunostained cells were widely distributed from the neck to the base of the oxyntic gland in all animals. The plasma ghrelin concentration in cows decreased significantly 1 h after feeding, and then recovered to pre-feeding levels. Administration of ghrelin into the third ventricle in Shiba goats dramatically increased the plasma GH concentration dose-dependently. These results suggest that ghrelin plays an important role in GH secretion and feeding regulation in domestic animals.

Animals↗

Predictors and underlying causes of medically intractable localization-related epilepsy in childhood.

The goal of this study is to clarify the prognostic factors in childhood localization-related epilepsy in a tertiary medical center. Children (n = 113) with symptomatic and cryptogenic localization-related epilepsy were divided into groups of intractable patients (average seizure frequency: one or more per month during the 6 months before the last follow-up; n = 40) and well-controlled patients (no seizures for at least 1 year before the last follow-up; n = 73). Clinical and electroencephalogram (EEG) factors were examined to elucidate prognostic factors. The subtypes of epilepsies and causes were also investigated. Univariate analyses indicated that the following factors were correlated with seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3) underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring as the first seizure and before the first visit; and (6) diffuse epileptic discharges on first visit interictal EEGs. Multivariate analyses revealed that seizure type at the first visit, seizure frequency, status epilepticus before the first visit, and underlying causes were significant independent predictive factors. The rate of intractable patients was highest in multilobar epilepsy, followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group contained nine patients with encephalitis of unknown origin and three each with localized cortical malformation and mesial temporal sclerosis.

Brain↗

Participation of the beta-hydroxyketone part for potent cytotoxicity of callystatin A, a spongean polyketide.

The participation of the beta-hydroxyketone part of callystatin A in the potent cytotoxicity was analyzed through the analogue-syntheses and the assessment of their biological potencies. The ketonic carbonyl, the 19-hydroxyl, and the three asymmetric methyl groups located in the beta-hydroxyketone part of callystatin A were revealed to contribute to the cytotoxic potency, respectively. Moreover, the alpha,beta-unsaturated delta-lactone portion was shown to serve as a conclusive functional group for the cytotoxic activity.

Animals↗

Intracellular Ca2+ signaling pathway is involved in light-induced phase advance, but may not be in phase delay, of the circadian melatonin rhythm in chick pineal cell.

Chick pineal cells have photoreceptive, circadian clock and melatonin synthetic capacities, and express circadian oscillation of melatonin release in vitro. Light pulses cause phase-dependent phase shift of the melatonin rhythm. The purpose of this study was to address the questions whether intracellular calcium is involved in both light-induced phase advance and delay. Thapsigargin and cyclopiazonic acid, which deplete the intracellular calcium stores, blocked the light-induced phase advance in a dose-dependent manner. The pulses of ryanodine receptor antagonist (dantrolene sodium or ruthenium red) also blocked the light-induced phase advance. Most agents did not cause a significant phase shift by themselves. On the other hand, all the agents used, failed to block the light-induced phase delay, even if the magnitude of phase delay was decreased using low intensity light. An antagonist of nitric oxide synthase blocked neither light-induced phase advance nor phase delay. These results indicate the following possibilities: (1) the mechanism of light-induced phase advance and delay may be different in chick pineal cells, or (2) if intracellular calcium is involved in both light-induced phase advance and delay, the sensitivity to light and/or agents used in this study may differ according to Zeitgeber time.

Animals↗

A biodegradable polymer as a cytokine delivery system for inducing bone formation.

Bone morphogenetic proteins (BMPs) that have the potential to elicit new bone in vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when tested in vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair.

Animals↗

The 'superficial' peroneal artery: a variation in cutaneous branching from the peroneal artery, nourishing the distal third of the leg.

Two different vascular patterns were encountered in cutaneous branches from the peroneal artery to the posterolateral aspect of the distal third of the leg in 22 flaps from 22 patients who underwent cutaneous or osteocutaneous peroneal flap surgery. In the type 1 vascular pattern, a branch from the peroneal artery, named the 'superficial peroneal artery', nourished the posterolateral aspect of the leg by splitting into several septocutaneous branches. In the type 2 pattern a few septocutaneous branches originated directly from the main peroneal artery and nourished the same area as that fed by the type 1 branch. The type 1 vascular pattern has not been reported to date but was seen in nine out of the 22 consecutive peroneal flaps. The superficial peroneal artery, with its considerable vascular diameter, may serve as a recipient vessel for free flaps or may serve as a donor nutrient vessel for a cutaneous flap, which can be transferred without sacrificing the main peroneal artery. Awareness of these two vascular patterns in the distal third of the leg should also help to reduce the small percentage of skin-flap failures that occur when the cutaneous or osteocutaneous peroneal flap is used.

Adult↗

Hyperbaric oxygen therapy given 30 minutes after spinal cord ischemia attenuates selective motor neuron death in rabbits.

OBJECTIVE: Spinal cord ischemia sometimes causes paraplegia because the spinal motor neuron cells are vulnerable to ischemia. Although various protective remedies for spinal cord injury have been reported, there have been few established clinical methods. Although hyperbaric oxygen (HBO) has been used clinically as a treatment for ischemia, the reason for its effectiveness is still uncertain because sufficient experimental data are lacking. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Twenty-three Japanese white rabbits, weighing 2-3 kg. INTERVENTIONS: A modified rabbit spinal cord ischemia model of infrarenal aortic occlusion for 15 mins was employed. Rabbits were randomly assigned to four groups; the rabbits in group A did not undergo ischemic insults (n = 5). The rabbits in groups B and C underwent ischemic insult for 15 mins, followed by 1 hr of HBO treatment at 3 atm absolute with 100% oxygen at 30 mins (n = 6) or 6 hrs (n = 7) after reperfusion, respectively. The rabbits in group D underwent ischemic insult for 15 mins without HBO treatment (n = 5). MEASUREMENTS AND MAIN RESULTS: We observed neurologic functions for 14 days. The sections of the spinal cords were stained with hematoxylin and eosin, and the number of spinal motor neurons in ventral region was counted by light microscopy. All rabbits in groups A and B could stand, whereas all rabbits in groups C and D showed irreversible paraplegia on days 2 and 14 after reperfusion. Spinal motor neurons in ventral gray matter in groups C and D decreased significantly compared with those in groups A and B. CONCLUSIONS: HBO therapy shortly after ischemic insult had protective effects against ischemic spinal cord damage. However, delayed treatment with HBO did not change the prognosis.

Animals↗

Glassy cell carcinoma of the uterine cervix: combination chemotherapy with paclitaxel and carboplatin in recurrent tumor.

Combination chemotherapy with paclitaxel and carboplatin every 4 weeks for 3 cycles was administered for recurrent glassy cell carcinoma of the uterine cervix in a 67-year-old Japanese female. The response rate was 56% under computed tomography (partial response). However, the effect was transient even with follow-up radiotherapy, and further cases need to be accumulated to determine a successful treatment modality.

Aged↗

Safe and effective treatment of refractory facial lesions in atopic dermatitis using topical tacrolimus following corticosteroid discontinuation.

BACKGROUND: Topical corticosteroids are commonly applied in atopic dermatitis (AD) treatment. However, their chronic use may be associated with significant side effects at the application site. Skin atrophy and other undesirable effects are frequently seen after long-term corticosteroid treatment. In addition, when application of corticosteroids is discontinued, a rebound phenomenon in the facial lesions can occur within several days. Topical tacrolimus, an immunosuppressant currently used to prevent rejection after solid-organ transplantation, presents a potential alternative therapeutic agent for AD. OBJECTIVE: The present study is the first trial designed to evaluate the efficacy and safety of topically applied tacrolimus ointment after corticosteroid discontinuation without a washout phase in severe, long-term facial AD. PATIENTS/METHODS: Forty-seven patients with facial refractory AD were recruited, of whom 38 had undergone topical corticosteroid treatment for at least 4 weeks before enrollment (group 1) and the other 9 had not received steroid treatment (group 2). All 47 patients received 0.1% tacrolimus ointment, and the severity index and pruritus score were assessed as an AD clinical activity index every week and compared with baseline data. RESULTS: Both the severity index and pruritus score improved significantly in group 1 after 1 and 2 weeks of application (p < 0.01, respectively). Group 2 showed the greatest improvement at 4 weeks (p < 0.05). In this trial, none of the patients experienced a rebound phenomenon associated with tacrolimus treatment. A transient sensation of burning at the application site was the only adverse event in 31 of the 47 (66%) enrolled patients, but this condition improved after several days. Spectrophotometric assessment of the facial lesion following treatment revealed significant improvement in group 1 (p < 0.05). CONCLUSION: The present results indicate that topical tacrolimus treatment following corticosteroid discontinuation is safe and effective in refractory facial AD.

Administration, Topical↗

Production of monoclonal antibody against Scrippsiella trochoidea cysts and its application to analysis during cyst formation and enzyme-linked immunosorbent assay.

A monoclonal antibody was produced by the fusion of mouse myeloma cells with spleen cells from a mouse immunized with the cysts of Scrippsiella trochoidea, marine phytoplankton. Immunofluorescence microscopic observation showed that the antibody reacted with the spines on the cyst but not with the vegetative cells and cyst walls. An enzyme-linked immunosorbent assay could be used to measure the cysts in muddy bottom sediments using the purified antibody conjugated with horseradish peroxidase.

Animals↗

Immunization against intestinal bacterial endotoxin prevents alcoholic fatty liver in rats.

Accumulating evidences indicate that an endotoxin originating from intestinal gram-negative bacteria may be involved in alcohol-induced liver injury including fatty liver. Therefore, whether immunization against intestinal bacterial endotoxin blocked fatty liver induced by chronic alcohol and diet including much-unsaturated fatty acid was investigated in rats. The titer of antibody against the endotoxin increased significantly after 13 weeks of continuous immunization. Daily alcohol treatment was initiated at 12 weeks and continued for 4 weeks. Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and triglyceride (TG) levels increased significantly in non-immunized rats receiving alcohol, but not in immunized rats. Continuous alcohol treatment gradually decreased the survival rate to 60% from 13 days after beginning administration in non-immunized, but not immunized, rats. A histochemical study revealed that continuous treatment with alcohol and unsaturated fatty acids caused fatty liver in non-immunized, but not immunized, rats. This study strongly supports the hypothesis that alcohol-induced fatty liver is due to a circulating endotoxin, and suggests that immunization for endotoxin prevent the alcoholic fatty liver.

Alanine Transaminase↗

Evaluation of the epidermal growth factor receptor (EGFR) and c-erbB-2 in superspreading-type and penetrating-type gastric carcinoma.

The expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGF alpha), and of c-erbB-2 was immunohistochemically investigated in resected gastric carcinoma (in 39 cases of superspreading type and in 11 cases of penetrating type), to understand the differential biological features of these two types of gastric carcinoma. EGF, EGFR and c-erbB-2 positive cases were preferentially found in penetrating type rather than in superspreading type (p < 0.05, p < 0.01, and p < 0.05, respectively). The positive rates of EGFR and c-erbB-2 were significantly higher in submucosal gastric carcinoma than in intramucosal gastric carcinoma (p < 0.01, p < 0.05, respectively). These results suggested that the autocrine mechanism of the growth factors and the expression of c-erbB-2 were correlated to the degree of gastric wall invasion.

Adult↗