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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 235 records · Page 13Linked to original sources

Development of regulation of melatonin release in pineal cells in chick embryo.

Melatonin release in a pineal cell culture from 13- and 14-day-old chick embryos increased during the dark phase and decreased during the light phase of a 12 h light:12 h dark cycle. When the light-dark cycle was reversed, the pattern of melatonin release in the culture also reversed. 8-Bromo cyclic-AMP stimulated melatonin release in both the light and dark phases. However, no rhythm of melatonin release was detected under constant dark (DD) conditions in a cell culture from 14-day-old chick embryos. In 18-day-old chick embryos, the pineal cell culture expressed a circadian rhythm of melatonin release under DD conditions. These results indicate that mechanisms regulating melatonin synthesis in the avian pineal gland are established during embryonic life.

8-Bromo Cyclic Adenosine Monophosphate↗

Febrile responses induced in adrenalectomized rats by administration of interleukin-1 beta or prostaglandin E2.

1. The present study was carried out to investigate the effect of bilateral adrenalectomy on fevers induced in rats by systemic injection of interleukin-1 beta (IL-1 beta) or by central injection of prostaglandin E2 (PGE2). 2. Intraperitoneal (I.P.) injections of two doses of IL-1 beta (0.5 and 1.0 microgram kg-1) induced biphasic fevers in normal control rats in a dose-dependent manner. Adrenalectomized (ADX) rats showed higher fevers than sham-ADX rats after I.P. injection of small doses of IL-1 beta (0.5 micrograms kg-1). This fever enhancement was inhibited by acute or chronic glucocorticoid, dexamethasone (DEX), treatment. In contrast, there was no significant difference between fevers induced in ADX and sham-ADX rats by I.P. injection of large doses of IL-1 beta (1.0 g kg-1). 3. Dose-dependent fevers were observed in normal control rats after injections of several doses of PGE2 (5, 25 and 100 ng) into the preoptic hypothalamic area (POA). The injection of a large dose of PGE2 (100 ng) into the POA led to a lower fever in ADX rats, compared with that in sham-ADX rats. This fever in ADX rats was increased by acute or chronic treatment with DEX. On the other hand, adrenalectomy had no effect on fevers induced by the injections of small doses of PGE2 (5 and 25 ng) 4. The injections of PGE2 (100 ng) into the POA induced increases in oxygen consumptions in ADX rats that were significantly smaller than those in sham-ADX rats, suggesting that the lower PGE2 fever was, at least in part, due to attenuated thermogenesis in ADX rats. 5. There was no significant difference in plasma osmolality between the ADX and the sham-ADX rats. The ADX rats were given 0.9% salt water instead of tap water. 6. These results suggest that endogenous glucocorticoid is one of the important modulators of the IL-1-induced and the PGE2-induced fevers in rats.

Adrenalectomy↗

Suppression of interleukin-1 beta production in the circumventricular organs in endotoxin-tolerant rabbits.

Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits which show febrile tolerance to bacterial endotoxin, lipopolysaccharide (LPS). Febrile tolerance to LPS was induced by daily intravenous (i.v.) injections of LPS (4 micrograms/kg, i.v.) for 5 days. In the LPS-tolerant rabbits, the second phase of the biphasic fever induced by i.v. injection of LPS (4 micrograms/kg) disappeared, although the first phase remained intact. In situ hybridization and immunohistochemical studies revealed that IL-1 beta production was observed in the circumventricular organs, such as the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area posterema (AP), 1 h after the first exposure to i.v. injection of LPS (4 micrograms/kg) (acute rabbits). In contrast, IL-1 beta production in these circumventricular organs disappeared in the LPS-tolerant rabbits. IL-1 beta production was observed in the spleens of the acute and the LPS-tolerant rabbits after i.v. injections of LPS. The cells which produced IL-1 beta in the spleen following LPS injections were confirmed to be monocytes/macrophages and polymorphonuclear leukocytes by immunohistochemistry in both the acute and the LPS-tolerant rabbits. The LPS-injected acute rabbits showed a significant increase in the number of IL-1 beta-immunoreactive monocytes/macrophages, compared with that in the saline-injected acute rabbits. However, there was no significant difference in immunoreactive cell numbers between the saline-injected acute and LPS-injected tolerant rabbits, or between the LPS-injected acute and the LPS-injected tolerant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antihyperglycemic effects of M16209, a novel aldose reductase inhibitor, in normal and diabetic rats.

The effect of a single oral administration of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on serum glucose was investigated. In normal rats, M16209 (100 mg/kg) had a weak hypoglycemic effect but markedly stimulated the disappearance of serum glucose in intravenous glucose tolerance tests. In diabetic rats, M16209 (100 mg/kg) significantly suppressed the hyperglycemia of streptozotocin-induced, mildly diabetic rats and stimulated serum glucose disappearance in neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM) rats in glucose tolerance tests. Additionally, M16209 augmented insulin secretion in glucose-loaded, normal and NIDDM rats and restored the reduced serum insulin in streptozotocin-induced, mildly diabetic rats. M16209, however, showed no hypoglycemic effect in severely diabetic rats. In contrast, gliclazide, a sulfonylurea, showed a much more potent hypoglycemic effect in normal rats than in mildly diabetic rats. These results suggest that M16209 suppresses hypoglycemia through augmentation of glucose-stimulated insulin secretion. The antihyperglycemic activity of M16209, combined with its potent aldose reductase inhibiting activity, is expected to be beneficial in the treatment of diabetic complications.

Aldehyde Reductase↗

Effects of M16209 on insulin secretion in isolated, perfused pancreases of normal and diabetic rats.

We investigated the stimulatory effect of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on insulin secretion using isolated, perfused pancreases of rats. In the pancreases from normal rats, M16209 (100 microM) greatly augmented glucose-stimulated insulin secretion, but showed no effect on unstimulated insulin secretion at 2.8 mM glucose. In contrast, gliclazide (10 microM), a sulfonylurea, strongly enhanced both glucose-stimulated and unstimulated insulin secretion. Sorbinil and epalrestat, potent aldose reductase inhibitors, had no stimulatory effect on insulin secretion. M16209 (100 microM) improved appreciably the decreased insulin response to 22.2 mM glucose and enhanced slightly unstimulated insulin secretion in the pancreases of rats with neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM). Gliclazide (10 microM), however, failed to affect the pancreases of NIDDM rats. Furthermore, M16209 showed no appreciable effect on ATP-sensitive K(+)-channels in pancreatic beta-cells. These results suggest that M16209, unlike sulfonylureas, selectively enhances glucose-stimulated insulin secretion in both normal and NIDDM rats through a direct action on the pancreas. The site of action remains unknown, but the inhibition of aldose reductase or the ATP-sensitive K+ channels is unlikely to be involved.

Aldehyde Reductase↗

Muscle fiber degeneration in distal myopathy with rimmed vacuole formation.

In 11 patients with distal myopathy with rimmed vacuole formation (DMRV), a well-known autosomal recessively inherited disorder, the rimmed vacuole formation appears to be the main pathological change accounting for the progressive muscle fiber degeneration. To gain a better understanding of the pathophysiology of the vacuole formation, we applied Congo red and immunohistochemical stains to muscle biopsies from these patients and the results were compared with those of patients with inclusion body myositis (IBM). The vacuoles in DMRV contained Congophilic amyloid material and deposits immunoreactive for beta-amyloid protein, both the NH2 and COOH termini of beta-amyloid protein precursor, ubiquitin, and tau protein. These results were similar to those seen in our present cases of IBM as well as in previously reported cases. Therefore, there may be no pathogenetic differences in the formation of rimmed vacuoles in DMRV and IBM. Nevertheless, the degenerative process involved in rimmed vacuole formation in various diseases may share a common pathogenetic mechanism with that in amyloid-plaque formation in Alzheimer's disease brain as has been proposed previously.

Adult↗

Reducing bodies in distal myopathy with rimmed vacuole formation.

A 42-year-old woman with distal myopathy with rimmed vacuoles had intracytoplasmic inclusion bodies similar to those described in reducing body myopathy. Since these inclusions were found in fibers with high acid phosphatase activity and occasional rimmed vacuoles, their formation appeared to correlate with active myofibrillar degeneration, but their origin remains unknown.

Adult↗

Tau protein immunoreactivity in muscle fibers with rimmed vacuoles differs from that in regenerating muscle fibers.

To determine whether tau protein found in muscle fibers with rimmed vacuoles and in regenerating fibers was phosphorylated, we examined eight muscle biopsy samples containing rimmed vacuoles (from five patients with distal myopathy with rimmed vacuole formation and three patients with inclusion body myositis) and three muscle biopsy samples from patients with Duchenne muscular dystrophy containing numerous regenerating fibers. Although both rimmed vacuolated and regenerating fibers had increased immunoreactivity against tubulin and tau protein, tau protein in the former was more highly phosphorylated than that in the latter. While very few microtubules in muscle fibers with rimmed vacuoles were recognizable by electron microscopy, regenerating fibers, especially immature ones, contained numerous microtubules. Since tau protein found in vacuolated fibers is hyperphosphorylated, it can be considered to have reduced ability to bind tubulin molecules. Thus, the tau protein cannot stabilize microtubules, resulting in their depolymerization even in the presence of tubulin molecules.

Adolescent↗

Fatal reducing body myopathy. Ultrastructural and immunohistochemical observations.

Two female infants who developed normally during infancy began to have progressive muscle hypotonia and weakness from 2 years 10 months and 2 years 3 months of ages, respectively. Both patients had rapidly progressive muscle weakness with death from respiratory failure at 4 years 11 months and 3 years 9 months, respectively. In addition to mild inflammation in their muscle biopsies, the most striking finding was the presence of numerous reducing bodies (RB) in almost all degenerating fibers. By electron microscopy, these bodies consisted of fine granular material, usually located around the degenerating nucleus. These bodies showed no immunohistochemical reaction to antibodies against structural, cytoskeletal and membrane proteins and a histone-specific antibody against nuclei and chromosomes. They were occasionally positively stained with a ubiquitin antibody. Although the origin of these bodies remains unknown, they appeared to be related to active myofibrillar degeneration, probably resulting from primary nuclear degeneration.

Cell Nucleus↗

Anti-tumour-promoting glyceroglycolipids from the green alga, Chlorella vulgaris.

Two new monogalactosyl diacylglycerols were isolated from the freshwater green alga, Chlorella vulgaris, as anti-tumour promoters, together with three monogalactosyl diacylglycerols and two digalactosyl diacylglycerols. The new monogalactosyl diacylglycerol containing (7Z,10Z)-hexadecadienoic acid showed a more potent inhibitory effect toward tumour promotion than the other glycerolipids isolated.

Anticarcinogenic Agents↗

Sarcolemmal indentation in cardiomyopathy with mental retardation and vacuolar myopathy.

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.

Adolescent↗

[Isolation of verotoxin-producing Escherichia coli from pediatric patients suffering from enteritis with bloody stool and intussusception].

We tried to isolate verotoxin-producing Escherichia coli (VTEC) on sorbitol-MacConkey (SMAC) agar and in part by the polymerase chain reaction (PCR) method from sporadic enteritis patients with bloody stools and intussusception patients who came to three pediatric clinics in the Fukuoka area from October 1990 to September 1994. VTEC O157:H7 strains were isolated from 6 (10.5%) of 57 patients with bloody stools, Campylobacter spp. 15 (26.3%), Salmonella spp. 14 (24.6%) and Yersinia enterocolitica 2. We were not able to detect VT genes by PCR from 11 of 20 patients from whose stools no causative bacteria were isolated. Massive fresh bloody stools following frequent watery diarrhea were typical of the VTEC enteritis patients. Only 1 patient had fever and 2 had leukocytosis, but the C-reactive protein in all of them was below 1+. The VTEC strains were isolated during the summer season, 1 in June, 2 in July, and 3 in September. Since in the area O157:H7 appeared to be the most prevalent VTEC serotype, SMAC is very useful for screening VTEC in bloody stools. VTEC seems to be a rare pathogen of intussusception because the organisms were detected from none of the 30 patients.

Adolescent↗

Graves ophthalmopathy: MR evaluation of 10-Gy versus 24-Gy irradiation combined with systemic corticosteroids.

PURPOSE: To establish the most effective radiation dose for treatment of Graves ophthalmopathy (GO). MATERIALS AND METHODS: A combination of 10 Gy (n = 15) or 24 Gy (n = 16) of radiation and corticosteroids was used to treat 31 patients with GO. Magnetic resonance (MR) images obtained before treatment showed swollen extraocular muscles with prolonged T2 relaxation times in all patients. RESULTS: Before therapy, T2 relaxation time of extraocular muscle was 79.6 msec (95% confidence interval, 76.3, 82.9) in the 24-Gy group and 77.4 msec (95% confidence interval, 74.6, 80.1) in the 10-Gy group (P = .32). After therapy, T2 relaxation time was 62.8 msec (95% confidence interval, 61.2, 64.4) in the 24-Gy group and 68.9 msec (95% confidence interval, 66.8, 71.1) in the 10-Gy group. In the 24-Gy group, there was a significant decrease in T2 relaxation times (P = .001) and clinical response to initial treatment was better. At 1- and 3-month follow-up, the resistance rate was lower in the 24-Gy group. CONCLUSION: In treatment of GO, 24 Gy of radiation is a more effective dose than 10 Gy when combined with systemic corticosteroids.

Conjunctival Diseases↗

Rhodiocyanosides A and B, new antiallergic cyanoglycosides from Chinese natural medicine "si lie hong jing tian", the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey.

Two new antiallergic cyanoglycosides named rhodiocyanosides A and B were isolated from the Chinese natural medicine "Si Lie Hong Jing Tian" (Shiretsukoukeiten in Japanese), the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey., together with two new glycosides, octyl alpha-L-arabinopyranosyl(1-6)-beta-D-glucopyranoside and gossypetin 7-O-beta-D-glucopyranosyl(1-3)-alpha-L-rhamnopyranoside. Their chemical structures were determined on the basis of chemical and physicochemical evidence. Rhodiocyanosides A and B exhibited inhibitory activity on the histamine release from rat peritoneal exudate cells sensitized with anti-DNP IgE. In addition, rhodiocyanoside A was found to inhibit the PCA reaction in rats.

Animals↗

Chemical constituents of Chinese natural medicine, morindae radix, the dried roots of morinda officinalis how.: structures of morindolide and morofficinaloside.

A new iridoid lactone, morindolide, and a new iridoid glucoside, morofficinaloside, have been isolated from a Chinese natural medicine, Morindae Radix, the dried root of Morinda officinalis How. together with a number of known compounds: five anthraquinones, four iridoid glucosides, a monoterpene glycoside, two sterols, an ursane-type triterpene, and a lactone compound. The chemical structures of the new compounds were determined on the basis of chemical and physicochemical evidence.

Acetylation↗

Syntheses, immunosuppressive activity, and structure-activity relationships of myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxyomyriocin, and nor-deoxomyriocins.

Nine myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins, were synthesized from 2-deoxy-D-glucose via common intermediates used in previous myriocin and Z-myriocin syntheses. Immunosuppressive activities of those myriocin analogs on mouse allogeneic mixed lymphocyte reaction were examined, and Z-14-deoxomyriocin was found to show the most potent activity among them. The structure-activity relationships are discussed.

Animals↗