Search PubMed⌕ Search

Biomedical subjects

N Chino

Publications and source records attributed to N Chino.

At least 73 records · Page 4Linked to original sources
PubMed1992

Unexpected racemization of proline or hydroxy-proline phenacyl ester during coupling reactions with Boc-amino acids.

When L-proline or O-benzyl-trans-4-hydroxy-L-proline phenacyl ester was coupled with Boc-amino acids in dimethylformamide using water-soluble carbodiimide (WSCI) in the presence of anhydrous 1-hydroxybenzotriazole (HOBt) as coupling reagents, extensive racemization was observed at the C alpha of the proline or hydroxy-proline residue. The extent of racemization was measured by HPLC after the coupling with Boc-L-Leu-OH in the presence or absence of HOBt. The extent of racemization increased when HOBt was added to the reaction mixture, but greatly decreased when it was not, indicating that HOBt was needed for inducing racemization. Almost no racemization was observed when the coupling reaction was carried out by the mixed anhydride procedure in tetrahydrofuran or by the carbodiimide method in dichloromethane without using HOBt. In the case of coupling reactions with ordinary L-amino acid phenacyl esters, no racemization was observed. Examination of some model systems yielded sufficient evidence to prove that HOBt is an efficient catalyst for racemizing proline or hydroxy-proline phenacyl ester not only in the stage of cyclic intermediate formation but also in the opening of the ring structure. Thus, the racemization reaction was found to be closely related to the formation of the cyclic carbinol-amine derivative.

Acetophenones↗
PubMed1991

The cystine-stabilized alpha-helix: a common structural motif of ion-channel blocking neurotoxic peptides.

Neurotoxic peptides from venoms of scorpions and honey bees exhibit a consensus pattern in the two disulfide bridgings related to the sequence portions Cys-X-Cys and Cys-X-X-X-Cys. A revised three-dimensional structure of charybdotoxin, as determined by two-dimensional nmr spectroscopy, confirms that the consensus cystine dislocation generates in all these toxins a common structural element, i.e., the cystine-stabilized alpha-helical (CSH) motif, which may be correlated with their common ion channel blocking activity.

Amino Acid Sequence↗
PubMed1991

Two types of abnormal somatosensory evoked potentials in chronic cerebellar ataxias.

To investigate subclinical sensory impairment in spinocerebellar degenerations, median nerve somatosensory evoked potentials (SEPs) were examined in 16 patients with chronic cerebellar ataxia who were originally diagnosed by clinical neurologists as having olivopontocerebellar atrophy (OPCA). Two types of abnormal SEP patterns were found in six patients. Two patients had the SEP pattern of peripheral neuropathy, which was also detected by peripheral sensory nerve conduction studies. Four patients had abnormal SEPs seen in patients with the lesions in the central nervous system (dorsal column, medial lemniscus). Magnetic resonance imaging (MRI) showed multiple sclerosis (MS). It is possible that clinically diagnosed OPCA sometimes includes a similar form of Friedreich's ataxia with subclinical sensory fiber neuropathy detected by SEPs and peripheral sensory conduction studies. In cases of lesions in the central nervous system demonstrated by both SEPs and MRI, there must be a follow-up in order to make a final diagnosis. In those cases, an alternative diagnosis of MS must be considered when the temporal profile of symptoms and signs characteristic of MS is observed.

Adult↗
PubMed1991

Somatosensory vertex potentials: comparison between bilaterally and unilaterally evoked potentials.

Somatosensory vertex potentials (SVPs), consisting of N1, P1, and N2, are obtained widely on the scalp between 100 and 500 msec of latency. To analyze interactions between SVPs evoked by right and left finger stimulation, the sum of N1-P1 or P1-N2 amplitude values in response to stimulation of independent right and left fingers were compared with those evoked by simultaneous stimulation of both fingers. SVPs were recorded at Cz, C3, and C4 in 12 healthy subjects. Three patterns of finger stimulation, namely, right, left, and both right and left, were randomly chosen until 80 responses had been obtained and averaged for each pattern of stimulation. Simultaneous bilateral responses were larger than either right or left finger SVPs. However, they were consistently smaller than summed SVPs from right and left fingers. These results suggest that the SVP generators be different between right and left. But they may be closely inter-related through occlusive connections.

Adult↗
PubMed1991

Fibrillation potentials do not originate in type 1 muscle fibers?

Electrophysiological and muscle histochemical studies of denervated muscle were performed simultaneously in order to determine the relationship between fibrillation potentials and muscle fiber type. Fibrillation potentials recorded in the soleus muscle 2 weeks after resection of the sciatic nerve revealed a lower firing rate than in the extensor digitorum longus (EDL) muscle of the same rats. The majority of muscle fibers stained for adenosine triphosphatase (ATPase) activity after preincubation at pH 9.4, 4.6, and 4.3 in the soleus muscle were type 1 fibers, while most of those in the EDL were of type 2. Moreover, one of the rats, which demonstrated no fibrillation potentials in the soleus muscle, was found to have no type 2A or 2B fibers histochemically, in the same soleus muscle. These findings suggest that fibrillation potentials may not originate in type 1 fibers.

Action Potentials↗
PubMed1990

Solution synthesis of charybdotoxin (ChTX), a K+ channel blocker.

Charybdotoxin, a 37 amino acid peptide which is a minor component of Leiurus quinquestriatus venom, was synthesized by the solution procedure applying our maximum protection strategy. After formation of the three disulfide bonds, for which a redox buffer was necessary, the final product was purified to homogeneity and found to have similar biological potency to that reported by others for the natural product. The disulfide bond configuration was found to be: Cys7-Cys28; Cys13-Cys33; Cys17-Cys35. Conformational analysis by 1H-NMR showed that the molecule exists as a very tightly folded structure, in which residues 1-7 and 24-37 form a triple-stranded beta-sheet, with a turn at positions 30-31. The region from 11-20 appears to adopt an alpha-helical conformation.

Amino Acid Sequence↗
PubMed1989

Structure-activity relationship of endothelin: importance of charged groups.

Endothelin (ET)-related peptides including ET-1 (1-39) were synthesized, and their constricting activity in rat pulmonary artery rings and pressor activity in unanesthetized rat were measured to elucidate their structure-activity relationship. The vasoconstrictor activities of ET-2, ET-3 and sarafotoxin S6b were one-half, one-60th and one-third that of ET-1, respectively. Such differences in biological activities should mainly arise from sequence heterogeneity at the N-terminal portion, especially at positions 4 to 7. All of the blocked ETs at the amino or carboxyl termini showed greatly decreased activities. A monocyclic analog, in which Cys3 and Cys11 were replaced by Ala, showed one-third the activity of ET-1; however, its deamino dicarba analog was almost completely inactive. Significant activities were retained even with replacement of amino acids at positions Ser4, Ser5, Leu6, Met7, Lys9, Tyr13, and Trp21 by Ala, Ala, Gly, Met(0), Leu, Phe, and Tyr or Phe, respectively. On the other hand, replacement of Asp8, Glu10 and Phe14 by Asn, Gln and Ala, respectively, resulted in complete loss of the biological activity. These results indicated that two disulfide bonds in ET molecule were not essential for the expression of vasoconstricting activity. Both terminal amino and carboxyl groups, carboxyl groups of Asp8 and Glu10, and the aromatic group of Phe14 seemed to be contributing, more or less, to the expression of the biological activities.

Animals↗
PubMed1989

[A case of ankylosing spondylitis complicating Crohn's disease].

A 20-year-old man, who had suffered from ankylosing spondylitis for about 1 year, was admitted to our hospital due to melena and syncope. Physical examination revealed tenderness of abdomen and sacroiliac joint, and decreased spinal mobility. X-ray examination showed sacroiliitis and squaring of vertebral bodies. RA test and RAHA, negative; CRP, strongly positive; HLA-B 27 positive. Intestinal barium enema revealed skipping longitudinal fissure at terminal ileum, and a biopsy specimen of the colon revealed non-caseating granuloma. The association of ankylosing spondylitis and Crohn's disease has widely been known in Europe and United States; but this is the first case reported in detail in Japan, where incidences of both diseases were much lower than those found in Caucasians.

Adult↗
PubMed1988

Synthesis of porcine C5a anaphylatoxin by the solution procedure and confirmation of the reported structure.

Porcine C5a anaphylatoxin, the primary structure of which was first determined by Gerard and Hugli in 1980 as a 74-amino acid peptide having three intramolecular disulfide bonds, was synthesized by the solution procedure applying our maximum protection strategy. The fully deprotected peptide was subjected to air oxidation in an acetate buffer at pH 7.5, and the product was isolated as a single entity by HPLC. Amino acid analysis and biological activities of the synthetic peptide agreed well with the reported values. However, the retention time of the synthetic C5a was different from that of the natural product, supplied by Dr. Hugli, on both reversed phase (RP) and ion-exchange (IEX) HPLC systems. The tryptic peptide mapping on HPLC revealed that Gln which was incorporated into the peptide at position 65 was replaced by Glu in the natural product. The elution pattern of tryptic peptides containing three disulfide bonds was identical with natural and synthetic C5a. It was also identical with that of a peptide which was synthesized following the estimated secondary structure proposed by Zimmermann and Vogt in 1984.

Amino Acid Sequence↗
PubMed1988

Structure-activity relationships of alpha-human atrial natriuretic peptide.

The spasmolytic activity of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) and its related peptides was determined in vitro using the chick rectum and the rat aorta. Natriuretic activity was also measured in the anesthetized rat, alpha-hANP-(7-28), with the NH2-terminal hexapeptide truncated, had greater spasmolytic and natriuretic effect than did alpha-hANP-(1-28). These responses were reduced by truncation of the COOH-terminal residues. alpha-hANP-(7-23), the cyclic structure of alpha-hANP-(1-28), exhibited weak aortic relaxation and natriuretic activities. However, alpha-hANP-(7-23) produced a greater relaxation than did alpha-hANP-(1-28) in the chick rectum. Elimination of Gly at position 9 reduced the spasmolytic and natriuretic activity. Substitution of amino acid residues at position 8, 12 and 13 changed these activities. Analogues containing the ethylene linkage instead of the disulphide bond had weak biological activity. These results indicate that the size of the 17-amino acid ring and the COOH-terminal residues of alpha-hANP are important for the expression of spasmolytic and natriuretic activity.

Amino Acids↗
PubMed1988

Molecular mechanism of action by atrial natriuretic peptide in rat vascular smooth muscle cells.

The mechanism by which atrial natriuretic peptide (ANP) acts on cells remains obscure. Using cultured vascular smooth muscle cells (VSMC) from rat aorta, we studied the structure-activity relationship of alpha-human(h) ANP and attempted to clarify its cellular mechanism of action. Binding studies using a variety of synthetic alpha-hANP analogs with deletion and substitution of amino-acid residue(s) within the ring structure and deamino-dicarba analogs with replacement of the disulfide bond with an ethylene linkage, suggested that the original cyclic structure is a minimum requirement for biological activity and the disulfide bond is not essential for receptor binding. The present study using VSMC loaded with a fluorescent Ca2+ indicator quin-2 revealed that alpha-rat(r) ANP has no effect on increases in cytosolic free Ca2+ concentration stimulated by angiotensin (A) II or arginine-vasopressin (AVP). While both vasoconstrictive hormones rapidly stimulated phosphatidylinositol (PI) response in VSMC, pretreatment with rANP did not affect AII- or AVP-induced PI response. However, AII-stimulated phosphorylation level of 20 K-dalton (Da) myosin light chain (MLC), a regulatory contractile protein of VSMC, was attenuated by pretreatment with rANP. These data suggest that ANP may not act at site of either agonist-induced membrane PI hydrolysis or intracellular Ca2+-signal system, but may partly be involved in phosphorylation/dephosphorylation of 20 K-Da MLC in cultured rat VSMC.

Angiotensin II↗
PubMed1988

Stroke rehabilitation outcome studies: comparison of a Japanese facility with 17 U.S. facilities.

A Japanese university hospital collaborated with a mixed group of 17 American hospitals in using common measures of functional status and outcomes for patients undergoing rehabilitation after stroke. Management protocols were similar for all facilities. Philosophies and operational factors concerning length of stay and discharge destinations varied among facilities. In Japan there was little pressure for discharge of rehabilitation patients. Japanese patients were kept in the hospital as long as they improved in their functional scores. The Japanese sample had fewer patients with bilateral involvement, patients were younger, were admitted after a longer period of time following the onset of the stroke, had less severe disability on admission, and had longer lengths of stay, and this may have accounted for higher Barthel score gains for the Japanese sample. These factors may have worked together with the family support system in Japan to account for higher discharge rate to the community for the Japanese sample.

Activities of Daily Living↗