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Biomedical subjects

S Murata

Publications and source records attributed to S Murata.

At least 73 records · Page 4Linked to original sources
PubMed1999

Epidermolysis bullosa simplex associated with muscular dystrophy: phenotype-genotype correlations and review of the literature.

BACKGROUND: Epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is relatively rare, and gene defects have been elucidated only in a limited number of patients, the precise phenotype-genotype correlations have not yet been fully elucidated. OBJECTIVE: The purpose of this study was to define clinical features of EBS-MD and to clarify its phenotype-genotype correlations. METHODS: Clinical, ultrastructural, immunohistochemical, and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations reported in the literature were reviewed. RESULTS: In skin of the EBS-MD patients, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or markedly reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and experienced nail deformities. In addition, decayed teeth (5 cases), urethral strictures (3), mild palmoplantar hyperkeratosis (2), infantile respiratory complications (2), alopecia (1), and laryngeal webs (1) were present. All 8 patients who were older than 9 years demonstrated considerable muscle weakness, and the majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon (PTC) mutations in both alleles of the plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 in-frame deletion mutation that resulted in elimination of 3 amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. CONCLUSION: EBS-MD reveals clinical features not only characteristic of EBS and MD, but also other manifestations including urethral, dental, and respiratory complications. The majority of patients are products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with PTC mutations in both alleles typically showed severe clinical features of EBS-MD and ended up being wheelchair bound, a homozygous patient for an in-frame deletion mutation showed positive, yet attenuated, plectin expression and milder clinical phenotype. Thus plectin immunofluorescence, combined with identification of the underlying plectin mutations, is of value in predicting the severity of the muscle involvement that occurs later in life of patients with EBS-MD.

Child↗
PubMed1999

Determination of linezolid in plasma by reversed-phase high-performance liquid chromatography.

An HPLC-UV method was developed for assay of linezolid in dog, rat, mouse, and rabbit plasma. Linezolid and the internal standard were extracted on a solid phase cartridge (SPE) and separated on a reversed-phase column (C8, 4.6x150 mm, 5 microm) with 20% acetonitrile in water as mobile phase. The SPE quantitatively recovered linezolid and the internal standard from plasma samples. The chromatographic peak height ratio or peak area ratio based on UV absorbency at 251 nm was used for quantitative analysis. The assay procedures were simple and the assay was specific and had adequate precision and accuracy. Calibration standards with concentrations over the range of 0.01 20 microg/ml were validated for routine sample analysis to support the pharmacokinetic and toxicology studies with linezolid in dog, rat, mouse, and rabbit. Analysis of quality control samples showed the coefficients of variation were usually <10% and the measured and theoretical concentrations differed by <10% in most assays. Linezolid in the plasma samples was stable when stored at below -20 degrees C for at least 63 days, at room temperature (22-23 degrees C) for up to 24 h, and after three freeze-thaw cycles. This HPLC method has been successfully used in multiple laboratories to assay plasma samples from pharmacokinetic and toxicology studies with linezolid in the animal species.

Acetamides↗
PubMed1999

Pharmacological analysis of the novel, selective alpha1-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand.

Pharmacological profiles of tritiated KMD-3213, a new antagonist of alpha1-adrenoceptor (AR), were examined in recombinant and native alpha1-AR, and compared with those of prazosin (PZ) and tamsulosin (YM-617). In saturation experiments, [3H]-KMD (10-2000 pM) showed high affinity for alpha1a-AR (pK(D) = 10.5). However, no significant binding to alpha1b-AR and insufficient/unsaturated binding to alpha1d-AR were observed at concentrations up to 2000 pM. In contrast, [3H]-PZ and [3H]-YM bound to all subtypes with high affinity (pK(D)>9). In competition experiments, KMD-3213 also had higher affinity for alpha1a-AR than for other two subtypes; pKi = 10.4, 8.1 and 8.6 for alpha1a-, alpha1b- and alpha1d-AR, respectively. [3H]-KMD also bound to the native alpha1A-AR (rat submaxillary gland) with high affinity, but not to alpha1B-AR (rat liver). In rat kidney which expresses alpha1A- and alpha1B-AR, [3H]-KMD and [3H]-PZ bound to a single high-affinity site (pK(D) = 10.8 and 10.1, respectively) with distinct amount of binding sites (Bmax = 159 and 267 fmol mg(-1) protein, respectively). [3H]-PZ binding sites consisted of low- and high-affinity sites for KMD-3213 (pKi = 7.6 and 10.7, respectively), for WB4101 (pK = 8.1 and 10.0) and for YM-617 (pKi = 8.7 and 10.8). The proportion of the high affinity site was approximately 60% in these drugs which was compatible to the ratio between Bmax of [3H]-KMD and [3H]-PZ. [3H]-KMD binding sites consisted of a single site for these drugs with affinities which were similar to those of the high affinity sites in [3H]-PZ binding. In functional experiments, KMD-3213 antagonized the contractile responses to NS-49 or noradrenaline (NA) with higher affinity in functional alpha1A- (rat caudal artery, pA2= 10.0 against NS-49) and alpha1L-AR (dog mesenteric artery, pA2 = 9.9 against NA) than in alpha1B- (dog carotid artery, pA2 = 7.7 against NA) and alpha1D-AR (rat thoracic aorta, pA2 = 8.3 against NA). These results confirm the alpha1A-AR selectivity and high affinity of KMD-3213, and indicate that [3H]-KMD can label selectively alpha1A-AR.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.

1. The human recombinant alpha1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg(-1) protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates. 2. Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities. 3. Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the alpha1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments. 4. These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of alpha1a-AR.

Adrenergic alpha-Antagonists↗
PubMed1999

Displacement and stress distribution in the temporomandibular joint during clenching.

The aim of this study was to analyze biomechanical reactions in the mandible and TMJ during clenching under various restraint conditions. A three-dimensional finite element model of the mandible, including the TMJ, was created for test purposes. The results were as follows: (1) Under any restraint conditions, displacement was greatest on the surface of the condyle and less on the articular disc and the surface of the glenoid fossa, in that order. Resultant stresses followed the same trend. (2) Displacement and stress were greatest when the lower central incisor was restrained and attenuated as the posterior teeth were restrained. Because the biomechanical reaction of the TMJ during clenching was greatest when the lower central incisor was restrained, premature contact of these teeth may be one of the factors involved in the initiation of temporomandibular arthrosis.

Biomechanical Phenomena↗
PubMed1999

Prevention of cerebral vasospasm by a novel endothelin receptor antagonist, TA-0201.

This study was designed to examine the preventive effect of a novel endothelin (ET)-receptor antagonist TA-0201 on the cerebral vasospasm in a canine double-hemorrhage model. TA-0201 (10(-9)-10(-7) M) inhibited ET-1-induced vasoconstriction in the isolated canine basilar artery without endothelium in a concentration-dependent manner. Its pA2 value was 9.2 (ET(A) antagonism). In a canine double-hemorrhage model, intravenous treatment with TA-0201 (3 mg/kg, twice a day for 7 days) ameliorated the basilar artery narrowing significantly on day 7 compared with that in nontreated dogs. The reductions of the basilar artery diameter were 26.1+/-3.9% and 40.5+/-4.1% with and without TA-0201 treatment, respectively (p<0.05). Histologic study on day 7 indicated that treatment with TA-0201 inhibited vessel-wall damage such as disintegration of endothelium architecture and degeneration of medial smooth-muscle cells. We conclude that intravenous treatment with TA-0201 prevents the development of cerebral vasospasm and accompanying pathologic changes of the vessel wall, probably through blockade of ET(A) receptors.

Animals↗
PubMed1999

Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome.

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Cytotoxicity and mutagenicity of UVB assessed using cultured rat fibroblast.

A retroviral vector carrying both positive (neo) and negative (herpes simplex virus thymidine kinase or HSV-tk) selection markers was constructed as a substrate for mutational assay in mammalian cells. Using a population of rat fibroblast cells carrying a single copy per cell of retroviral DNA randomly integrated in their chromosomes, we examined the cytotoxic and mutagenic activities of ultraviolet light (UV) at four wavelengths (254, 290, 300, and 320 nm). The action spectra for these activities are similar to some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing, and mouse skin carcinogenesis, except at 290 and 320 nm. At 290 nm, no significant mutagenicity was observed. At 320 nm, both cytotoxic and mutagenic activities were 10 times higher than the values expected from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of some of the HSV-tk mutants obtained after irradiation with 300 and 320 nm UV revealed partially different patterns of mutation specificity, suggesting the involvement of multiple molecular mechanisms in the genotoxicity associated with this range of UV.

Animals↗
PubMed1999

Autolysis of the proteinase from Pseudomonas fluorescens.

The gene encoding the proteinase from Pseudomonas fluorescens was cloned and sequenced in an effort to identify the cleavage sites involved in its autolysis at 50 degrees C. A single open reading frame consisting of 1449 nucleotides, encoding a protein of 482 amino acids, was found. Analysis of the N-terminal amino acid sequence of the purified proteinase indicated the presence of a prosequence consisting of 13 amino acid residues. The molecular weight of the mature protein was calculated as 48,900 based on the deduced amino acid sequence, which was consistent with that of the purified proteinase as determined by sodium dodecylsulfate-PAGE. Greater than 90% loss of proteolytic activity was observed upon heating at 50 degrees C for 2 min compared with the unheated enzyme. Incubation of the proteinase at 50 degrees C led to disappearance of the intact enzyme, as shown by sodium dodecyl sulfate-PAGE, whereas it was stable in the presence of the protease inhibitor o-phenanthroline. Autolytic fragments were fractionated by reverse-phase HPLC and subjected to N-terminal amino acid sequence analysis in an effort to determine the cleavage sites. The cleavage profile was not definitive; however, amino acid residues with small side chain groups, such as glycine or alanine, were frequently found adjacent to the cleavage sites.

Amino Acid Sequence↗
PubMed1999

The mechanism of the increasing action of TA-993, a new 1,5- benzothiazepine derivative, on limb blood flow in anesthetized dogs: selective suppression of sympathetic nerve activity.

TA-993, (-)-cis-3-acetoxy-5-(2-(dimethylamino)ethyl)-2, 3-di-hydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin-4(5H)one maleate, a new 1,5-benzothiazepine derivative with l-cis configuration, has a unique and selective increasing action on limb blood flow with little influence on arterial pressure besides an antiplatelet action. We studied the mechanism of increasing action of TA-993 on limb blood flow in anesthetized dogs. In a canine blood-perfused hindlimb preparation with a donor dog, TA-993 (100 microg/kg i.v.) did not increase femoral blood flow when administered to the donor dog, but did when administered to a recipient dog. TA-993 did not show the increasing action on femoral blood flow in the presence of hexamethonium or phentolamine, whereas it did in the presence of propranolol or atropine. TA-993 also showed a weak increasing effect on heart rate, which was inhibited by any one of these blockers. TA-993 (300 microg/kg i.v.) did not alter the phenylephrine (1-100 ng/kg i.a.)- or the talipexole (3-100 ng/kg i.a.)-induced increase in perfusion pressure in an autoperfused hindlimb. These results suggest that the increasing action of TA-993 on limb blood flow is mediated by the sympathetic nervous system but that the adrenergic receptors are not likely to be the central point of action of this new agent. There is a possibility that the mechanism of the increasing action on heart rate is different from that of its increasing action on limb blood flow.

Animals↗
PubMed1999

New alpha1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries.

PURPOSE: We compared the affinities of a new alpha1-adrenoceptor (AR) antagonist, JTH-601 with those of several alpha1-AR antagonists in human prostates and arteries. RESULTS: In the functional study, noradrenaline produced concentration-dependent contractions in human prostates and mesenteric arteries. The pA2/pKB values for the antagonists in the human prostate were 9.78 for tamsulosin, 8.84 for JTH-601, 8.39 for WB4101, 8.23 for prazosin, 8.12 for JTH-601-G1 (a main metabolite of JTH-601 in human) and 6.57 for BMY7378. Compared these affinities with those in the mesenteric artery, only JTH-601 and JTH-601-G1 exhibited unique uroselectivity, showing 10- to 20-fold higher affinity for the human prostate than for mesenteric artery. The affinity profile of these antagonists suggested that the noradrenaline-induced contractions in the human prostate and the mesenteric artery were mediated by the alpha1L-AR and alpha1B-AR, respectively. In the competition binding study, the pharmacological profiles of the antagonists against [3H]-prazosin were examined in the human prostate and aorta. The resulting pKi values for JTH-601 and JTH-601-G1 were also approximately 10- to 20-fold higher for the human prostate than for the human aorta. CONCLUSION: These results have suggested that JTH-601 and JTH-601-G1 are unique uroselective alpha1-AR antagonists that show higher affinity for the human prostate than for the human arteries.

Adrenergic alpha-Antagonists↗
PubMed1998

Resection of both hepatic and pulmonary metastases in patients with colorectal carcinoma.

BACKGROUND: More than 40% of patients who undergo curative resection of advanced colorectal carcinoma can be expected to have recurrence of the disease. The most frequent sites of recurrence are the liver (33% of patients) and lung (22%). Interest has therefore focused on treating hepatic or pulmonary metastases, or both, to improve the outcomes of these patients. Although surgical resection has become an increasingly accepted treatment for resectable localized hepatic or localized pulmonary metastases from colorectal carcinoma, the value of aggressive surgery for the removal of both hepatic and pulmonary metastases from patients with primary colorectal carcinoma remains to be clarified. METHODS: Data on 30 patients who had undergone resection of both hepatic and pulmonary metastases from colorectal carcinoma were included in the study. RESULTS: Independent, significant prognostic features were found to be the time that hepatic or pulmonary metastases occurred and the distribution of pulmonary metastases. Median survival times were 30 months (range, 7-108 months) after resection of both hepatic and pulmonary metastases and 48.5 months (range, 11-149 months) after excision of the primary colorectal tumor. Actuarial 1-, 3-, and 5-year survival after resection of both hepatic and pulmonary metastases was 86.7%, 49.3%, and 43.8%, respectively. No perioperative mortality occurred. There were three cases of minor morbidity, which the authors considered acceptable. CONCLUSIONS: Resection of both hepatic and pulmonary metastases from colorectal carcinoma may help to prolong the survival of a small group of patients with these metastases.

Adult↗
PubMed1998

[Two surgical cases of right parasternal minimal incision for aortic valve replacement].

Although median sternotomy has been used as a good approach to all cardiac valves and coronary arteries, advantages of the minimal invasive cardiac operation have been reported recently. We employed the right parasternal minial incision, reported by Cosgrove et al. for two cases of aortic valve replacement. In the first case, we were able to get a good operation field and easily implanted a mechanical prosthesis. In contrast, we had some difficulties with the second case where in addition to the third and fourth cartilages, a second cartilage resection was necessary because the aortic root lay at a cephalic level. Moreover, the operation field was restricted because we left several rib cartilages to preserve the right internal thoracic artery. The cannula had to be inserted via the right atrium as we failed to insert it in the right femoral vein, and the aortic root deviated more medially than usual. From these experiences, it is important to check the position of aortic root, and if the cannula cannot be inserted in the femoral vein, cannulation via the right atrium can ve utilized in the minimal invasive cardiac operation.

Aortic Valve↗
PubMed1998

Conflict among individual mitochondrial proteins in resolving the phylogeny of eutherian orders.

The phylogenetic relationship among primates, ferungulates (artiodactyls + cetaceans + perissodactyls + carnivores), and rodents was examined using proteins encoded by the H strand of mtDNA, with marsupials and monotremes as the outgroup. Trees estimated from individual proteins were compared in detail with the tree estimated from all 12 proteins (either concatenated or summing up log-likelihood scores for each gene). Although the overall evidence strongly suggests ((primates, ferungulates), rodents), the ND1 data clearly support another tree, ((primates, rodents), ferungulates). To clarify whether this contradiction is due to (1) a stochastic (sampling) error; (2) minor model-based errors (e.g., ignoring site rate variability), or (3) convergent and parallel evolution (specifically between either primates and rodents or ferungulates and the outgroup), the ND1 genes from many additional species of primates, rodents, other eutherian orders, and the outgroup (marsupials + monotremes) were sequenced. The phylogenetic analyses were extensive and aimed to eliminate the following artifacts as possible causes of the aberrant result: base composition biases, unequal site substitution rates, or the cumulative effects of both. Neither more sophisticated evolutionary analyses nor the addition of species changed the previous conclusion. That is, the statistical support for grouping rodents and primates to the exclusion of all other taxa fluctuates upward or downward in quite a tight range centered near 95% confidence. These results and a site-by-site examination of the sequences clearly suggest that convergent or parallel evolution has occurred in ND1 between primates and rodents and/or between ferungulates and the outgroup. While the primate/rodent grouping is strange, ND1 also throws some interesting light on the relationships of some eutherian orders, marsupials, and montremes. In these parts of the tree, ND1 shows no apparent tendency for unexplained convergences.

Animals↗
PubMed1998

Cystic dilatation of ventriculus terminalis in adults: MRI.

We report the MRI findings in two patients with cystic dilatation of the ventriculus terminalis. The latter is usually a tiny ependyma-lined cavity of the conus medullaris. In both cases the markedly dilated ventriculus terminalis was seen as a rounded cavity with regular margins, the content of which gave the same signal as cerebrospinal fluid with all MR pulse sequences. No contrast enhancement was seen.

Adult↗
PubMed1998

A combination of preductal aortic coarctation and type B dissection: report of a case.

We present herein the case of a 39-year-old man found to have significant coarctation of the preductal aorta combined with a type B dissection, associated with Marfan's syndrome. This extremely rare pathological combination could be defined preoperatively only by a three-dimensional computed tomography scan. By means of selective cerebral perfusion, the coarctation was resected, and the total aortic arch was replaced with a Dacron graft.

Adult↗