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E Murayama

Publications and source records attributed to E Murayama.

At least 19 recordsLinked to original sources
PubMed2001

Design and synthesis of N-terminal cyclic motilin partial peptides: a novel pure motilin antagonist.

Motilin antagonist was designed and synthesized on the basis of the structure-activity relationship analysis of porcine motilin that we reported recently. The drug design was performed on a specific concept to reduce a flexibility of peptide conformation of porcine motilin partial peptide by its cyclization. The cyclic peptide was synthesized using Boc (tert-butyloxycarbonyl) solid phase methodology, followed by cyclization using the azide procedure, and tested for the binding activity to motilin receptor and smooth muscle contractile activity. The cyclic peptides 3, 4, and 5 showed antagonistic property on contraction assay (pA2 [the negative logarithm of molar concentration of antagonist causing a 2-hold shift to the right of the concentration-response curve for motilin]: 4.5, 4.34, and 4.04, respectively, in rabbit duodenum) and no contractile activity even at high concentration.

Amino Acid Sequence↗
PubMed2000

Molecular cloning and expression of an otolith matrix protein cDNA from the rainbow trout, Oncorhynchus mykiss.

The fish otolith is a hard tissue consisting of calcium carbonate and organic matrices. The matrix proteins play important roles in otolith formation, but little is known about the nature of these proteins. In this study, matrix proteins were extracted from the otoliths of rainbow trout, Oncorhynchus mykiss, and chum salmon, Oncorhynchus keta. EDTA-soluble matrix proteins were separated by SDS-PAGE, revealing two major components in the otoliths of both species with apparent molecular masses of 55 and 43 kDa. N-terminal and some internal amino acid sequences of the 55-kDa otolith matrix protein were determined. A cDNA fragment encoding this protein of O. mykiss was amplified by reverse transcription PCR using two degenerate primers designed from the amino acid sequences. A cDNA encoding this protein was obtained by screening a saccular cDNA library using the amplified cDNA fragment as a probe. Nucleotide sequence analysis revealed that the cDNA clone has a sequence of 2.5 kb and the open reading frame encoding 344 amino acid residues. Northern blot analysis showed that mRNA of this protein is expressed specifically in the sacculus, and consistently during the day.

Amino Acid Sequence↗
PubMed1999

Structure-activity study of intact porcine motilin.

Biologically important sites on intact porcine motilin (pMTL) were explored using its partial peptides. The partial peptides were synthesized using Fmoc (9-fluorenylmethyloxycarbonyl) solid phase methodology, and tested for the binding activity to motilin receptor and the smooth muscle contractile activity. The results were as follows: important residues for the contractile activity were found to be Phe1, Ile4, and Tyr7, and an open space existed beyond the N-terminus between motilin and its receptor. On the model of interaction between motilin and motilin receptor evolved from these results, the three points of interaction, due to Phe1, Ile4, and Tyr7, and the presence of an open space were expected. The motilin agonist and antagonist, designed on this model, will help the inquiry into motilin associated diseases.

Amino Acid Sequence↗
PubMed1995

Divergent structural requirements exist for calcitonin receptor binding specificity and adenylate cyclase activation.

The basis of the high potency of salmon calcitonin (sCT) in radioligand binding competition and cAMP accumulation studies with cloned calcitonin (CT) receptors from rats, pigs, and humans was examined using two sets of CT analogues, i.e., chimeric sCT/human CT (hCT) analogues and analogues of sCT with differing capacities to form an amphipathic alpha-helix. In competition for 125I-sCT binding the following relative specificities were observed for the chimeric peptides: rat C1a CT receptor, sCT > or = (1-16)hCT/(17-32)sCT (ACT-15) > (1-16)sCT/(17-32)hCT (ACT-27); rat C1b CT receptor, sCT >> ACT-15 > ACT-27; hCT receptor, sCT = ACT-15 > ACT-27; porcine CT receptor, sCT > ACT-27 > ACT-15. In contrast, in ligand-induced cAMP accumulation studies the relative efficacies were as follows: rat C1a CT receptor, sCT = ACT-15 > ACT-27; rat C1b CT receptor, sCT = ACT-15 > ACT-27; hCT receptor, sCT = ACT-15 > or = to ACT-27; porcine CT receptor, sCT = ACT-15 = ACT-27. The data demonstrate that residues present in the carboxyl-terminal half of sCT are more important for binding competition with the rat C1a, rat C1b, and human CT receptors, whereas residues in the amino-terminal half of sCT are more important for binding competition with the porcine CT receptor. Carboxyl-terminal sCT residues are also important for full potency in adenylate cyclase activation with the rat C1a and rat C1b CT receptors but are less important for activation via the hCT receptor. The disparity in the relative potencies of the peptides in studies of binding competition and cAMP accumulation is suggestive of significant differences in the relative affinities of the peptides for active and inactive conformations of the CT receptor. The use of sCT analogues with varying capacities to form alpha-helices also revealed divergence in the responses of different receptors. This was most apparent for the stimulation of cAMP production by the rat receptor isoforms C1a and C1b. In cells expressing the C1a receptor, the helical analogues sCT and des-Ser2-sCT were equipotent with [Gly8]-des-Leu19-sCT and des-1-amino-[Ala1,7,Gly8]-des-Leu19 sCT, analogues that have reduced or absent helical structure, respectively. In contrast, the nonhelical analogues were 100-1000-fold less potent than sCT and des-Ser2-sCT at the C1b receptor. In general, reduction in the ability of sCT analogues to form helix structures had a greater impact on the potency of the analogues in competition for 125I-sCT binding than in cAMP accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1993

Synthetic studies of vitamin D analogues. XIV. Synthesis and calcium regulating activity of vitamin D3 analogues bearing a hydroxyalkoxy group at the 2 beta-position.

Four vitamin D3 analogues (7a, 7b, 7c and 7d) bearing a hydroxyalkoxy group at the 2 beta-position were synthesized from the alpha-epoxide (5). The C-3 analogue (7b) showed the highest potency for elevating plasma calcium levels in rats. Furthermore, the 25-hydroxylated C-3 analogue (ED-71) (3), prepared from the 25-hydroxylated alpha-epoxide (9), significantly increased plasma calcium to levels much higher than those in rats administered 1 alpha,25-(OH)2-D3 (1).

Administration, Oral↗
PubMed1989

The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion.

1,25-Dihydroxyvitamin D (1,25-(OH)2D3) directly suppresses the secretion and synthesis of PTH in vivo and in cell culture. This compound has been used to treat secondary hyperparathyroidism associated with renal failure, but in some patients prolonged treatment with 1,25-(OH)2D3 results in hypercalcemia. An analogue of 1,25-(OH)2D3 with little or no calcemic activity, 22-oxacalcitriol (OCT), was recently developed. We confirmed this lack of calcemic activity by acute and chronic administration to normal rats. A single intraperitoneal injection of vehicle (propylene glycol), OCT, or 1,25-(OH)2D3 (1.0 micrograms/rat) increased calcium by 0.32, 0.30, and 1.40 mg/dl, respectively. When rats were given daily injections of vehicle or 0.5 micrograms of either 1,25-(OH)2D3 or OCT for 4 d, calcium did not change in the rats receiving vehicle or OCT, but increased from 8.4 to 11.4 mg/dl in the rats treated with 1,25-(OH)2D3. In primary cultures of bovine parathyroid cells, 10 nM OCT was as active as 10 nM 1,25-(OH)2D3, suppressing PTH release by 33%. This suppression is due, at least in part, to blocking of transcription of the PTH gene. Using a probe prepared by random prime labeling of an Msp I fragment of plasmid PTHm122, we found that a single 40-ng dose of OCT or 1,25-(OH)2D3 depressed PTH mRNA levels by 70-80% by 48 h when compared with vehicle. Thus, OCT is a very effective suppressor of PTH secretion with virtually no calcemic activity. This analogue may be a valuable tool for the treatment of secondary hyperparathyroidism.

Animals↗
PubMed1981

Autosomal recessive prolidase deficiency. Three patients with recalcitrant ulcers.

Three patients had prolidase deficiencies. The family pedigree of these three patients suggests that this rare disorder is inherited through an autosomal recessive gene. this genodermatosis is characterized by a number of signs and symptoms referable to the skin, CNS, teeth, ears, nose, throat, eyes, bones, and joints. Among the skin changes, recalcitrant leg ulcers are the most characteristic. At this time, there is no established method of treatment of this rare disorder, but the use of dapsone was helpful in the treatment of one of our patients.

Adult↗
PubMed1978

Pathological changes of peripheral nerve and muscle of patients with hemiatrophy.

Peripheral nerve and muscle of patients with hemiatrophy were biopsied and examined by means of light and electron microscope. The unmyelinated nerve fibers decreased in number and remaining fibers were atrophic with irregular shape and high electron density, while myelinated nerve fibers slightly decreased in number. The Schwann cells enveloping nerve fibers were also atrophic with high electron density. The muscles contained numerous glycogen granules in the myofilaments and between the myofilaments. The mitochondria in the muscles showed atrophy with high electron density. Some parts of severe atrophy showed honeycomb-like structure forming large vacuoles in the muscle fibers. From the findings mentioned above, it is speculated that primary change was nerve fibers, especially unmyelinated nerve fibers.

Adult↗
PubMed1976

Late changes in human sural nerves in Minamata disease and in nerves of rats with experimental organic mercury poisoning.

The sural nerves of 2 human cases with Minamata disease and poisoned rats were examined histopathologically. Both showed similar findings: the myelinated nerve fibres were decreased in number, but small myelinated nerve fibres were increased: The latter were irregular in shape and their Schwann cells showed regressive changes, with high electron density of the cytoplasms and many glycogen granules. Onion bulb formation was not found. According to fibre diameter histograms, the ratio of small myelinated nerve fibres of 2-5 mum showed a high percentage. A large number of the small myelinated nerve fibres were presumed to be regenerated nerve fibres. These findings are different from other peripheral neuropathies and may be characteristics of the late changes of the sural nerve induced by organic mercury compound.

Adolescent↗
PubMed1976

Neuro-Behcet's disease showing severe atrophy of the cerebrum.

A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.

Adult↗
PubMed1976

[Histopathological findings of the nerve and muscles in familial primary amyloidosis, with special reference to the mechanism of amyloid fibril production].

T. I., a male aged 38, had a hereditary primary amyloidosis over four generation in his family history. He had peripheral neuropathy with dissociated sensory disturbances in the lower limbs, impotence, gastrointerstial dysfunction and orthostatic hypotention. N. suralis and M. quadriceps femoralis taken from him were examined by light and electron microscopy. N. suralis contained a lot of amyloids reacting with congo-red in the nerve fibres. Amyloid fibrils were remarkably observed around the blood vessels. They were continuous with the basement membrane of the endotherial cells. A few deposites were observed around the Schwann cell and fibroblasts. In M. quadriceps femoralis, amyloid like fibrils were noted in the perivascular spaces. Especially, a great deal of amyloid fibrils were continuous with the basement membranes. From this finding, it might be speculated that the basement membrane may play an important role in the production of amyloid fibrils.

Adult↗
PubMed1976

An autopsy case of the "demyelinating type" of Wilson's disease.

A 17 year-old male, who was mentally and bodily retarded from the age of 7 years. At the age of 16 years, several neurological signs appeared. Pathologically, there was widespread myelin loss and tissue sponginess in the white matter of the cerebrum and cerebellum, bilaterally and symmetrically. A great many Alzheimer type II glia and Opalski glia were widely distributed in the cerebral cortex and the basal ganglia. Despite severe destruction of the white matter, mesenchymal and gliofibre proliferation were not noticed. In the liver, Laennec's cirrhosis and a great many copper granules in the cytoplasm of the parenchymal cells were identified. From the above mentioned findings the present case, being a new type, could be called "Demyelinating type of Wilson's disease".

Adolescent↗