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Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 217 records · Page 12Linked to original sources

Fluorescence resonance energy transfer between points on tropomyosin and actin in skeletal muscle thin filaments: does tropomyosin move?

Fluorescence resonance energy transfer (FRET) spectroscopy has been used to determine spatial relationships between residues on tropomyosin and actin in reconstituted muscle thin filament, and to detect a positional change of tropomyosin relative to actin on the thin filament in the presence and absence of Ca2+ ions. In addition to Cys-190 which is a single cysteine residue in rabbit skeletal muscle alpha-tropomyosin, a new site, Cys-87 which is a unique cysteine residue in a mutant alpha-tropomyosin, was labeled with a resonance energy donor molecule, 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS). On the other hand, Gln-41, Lys-61, Cys-374, and the ATP-binding site of actin were selectively labeled with acceptor probes: fluorescein cadaverine, fluorescein 5-isothiocyanate, 4-dimethyl-aminophenylazophenyl 4'-maleimide, and TNP-ATP (or TNP-ADP), respectively. The distances between probes attached to position 87 of the mutant tropomyosin and Gln-41, Lys-61, Cys-374, or the nucleotide-binding site of actin on the reconstituted thin filament in the presence of Ca2+ ion were measured to be 43.2, 49.7, 45.4, and 35.2 A, respectively, and the distance between probes attached to position 190 of tropomyosin and Gln-41 or the nucleotide-binding site of actin were 51.6 and 43.1 A, respectively. The transfer efficiencies between these donor and acceptor molecules were large, so that the efficiency should be very sensitive to changes in distance between probes attached to tropomyosin and actin. However, the transfer efficiency did not change appreciably upon removal of Ca2+ ions, suggesting that tropomyosin does not change its position on the reconstituted thin filament in response to a change in Ca2+ ion concentration. The present results do not support the notion of tropomyosin movement on skeletal muscle thin filaments as proposed in the steric blocking theory.

Actins↗

Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial. METHODS: Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures. RESULTS: Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test). CONCLUSION: Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.

Aged↗

Macrofollicular variant of papillary thyroid carcinoma.

A rare case of a macrofollicular variant of papillary thyroid carcinoma occurring in an 18-year-old male is described. The extirpated tumor, 5.5 x 5.5 x 3.5 cm in size, was well demarcated and multinodular, and histopathologically showed a predominantly macrofollicular structure reminiscent of adenomatous goiter or macrofollicular adenoma. In the tumor tissue, however, there were several small foci of microfollicular or papillary structure with the nuclei characteristic of papillary carcinoma. Parts of the macrofollicular areas also showed similar nuclear characteristics with a transition to microfollicular or papillary areas. Incomplete capsular invasion and minimal vascular invasion were also present. Additional resected specimens contained small metastatic nodules in the residual left lobe and lymph nodes. Immunohistochemistry showed a small number of p53-positive tumor cells in the microfollicular or papillary areas. It is suggested that this tumor is a well-differentiated variant which should be distinguished from benign thyroid lesions, although there have been some cases of metastases which appear related to capsular and/or vascular invasion.

Adolescent↗

Sarcoidosis associated with multiple large pulmonary nodules.

Parenchymal manifestations of pulmonary sarcoidosis include a diffuse, symmetric, reticulonodular interstitial pattern, a fibrotic pattern, and an acinar pattern. Large pulmonary nodules in sarcoidosis are rare, and their frequency (> 1 cm in diameter) has been estimated at 2-4%. We report a rare case of sarcoidosis associated with large bilateral pulmonary nodules. These nodules reached up to 7 cm in diameter, which is larger than any others reported previously. Furthermore, these nodular lesions developed within only 6 months of normal chest X-ray results and were not found to accompany bilateral hilar lymph adenopathy, which is observed in the usual course of sarcoidosis. As described above, this case of pulmonary sarcoidosis was significant not only in terms of the large size of the nodules but also the unique chest X-ray course.

Adult↗

Ulcerative colitis with skip lesions at the mouth of the appendix: a clinical study.

OBJECTIVE: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. METHODS: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. RESULTS: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. CONCLUSION: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis.

Adult↗

Assessment of growth potential by MIB-1 immunohistochemistry in ameloblastic fibroma and related lesions of the jaws compared with ameloblastic fibrosarcoma.

Specimens from two ameloblastic fibromas (including one recurrent case), two ameloblastic fibro-odontomas, and one ameloblastic fibrosarcoma were subjected to investigation by MIB-1 immunohistochemistry in order to elucidate the growth potential of these tumors. MIB-1 labeling indices in the epithelial component of these tumors ranged from 2.9 to 7.5%, whereas those in the mesenchymal component ranged from 1.5 to 13.5%. Of these, labeling indices in the mesenchymal component of the recurrent ameloblastic fibroma and ameloblastic fibrosarcoma were quite high. These findings suggest that evaluation of growth potential in ameloblastic fibroma and related lesions could be of help in understanding tumor aggressiveness and in selecting appropriate surgical procedures.

Adolescent↗

Effect of thioridazine or chlorpromazine on increased hepatic NAD+ level in rats fed clofibrate, a hypolipidaemic drug.

The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short-term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body-weight gain, but increased liver weight and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as determined by the increased residual catalase activity. In hepatocytes prepared from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal but also mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+ was maintained at the high level until the phenothiazine concentration was increased to 0.2 mM. The result suggests that the increase of hepatic NAD+ in rats fed clofibrate is not related to peroxisomal fatty acid oxidation.

Animals↗

[Studies for dynamics of reverse transcriptase inhibiting antibody in sera from HIV-1 infected individuals].

Antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase activity (RTI-antibody), Binding inhibition antibody (BI-antibody) and polymerization inhibition antibody (PI-antibody) were investigated for their ability to inhibiting RT activity in 248 HIV-1 infected individuals and 99 healthy individuals. In BI-antibody, high titer samples were determined more in than in RTI- and PI-antibodies. No significance was indicated between AC, ARC and AIDS is any antibody, however, progression from AC to AIDS was poled to high titer and low titer in RTI- and BI-antibodies. Moreover, time course of each antibody levels in the same infected individuals were resulted in no change, going up or down through all the experimental term, though all samples were collected in AC. These results were suggested that the determination factor of each stage in HIV progression would be multiple, and that the various dynamics of RTI-, BI- and PI-antibodies in the same infected individuals might be caused in the term from HIV infection to AIDS progression, prognosis or appearing of the drug resistant strain but stages of the disease.

Acquired Immunodeficiency Syndrome↗

Symptomatic tonsillar ectopia.

OBJECTIVE: To determine if slight descent of the cerebellar tonsils (< 5 mm below the foramen magnum; tonsillar ectopia) may cause surgically treatable symptomatology. METHODS: A consecutive series of nine symptomatic patients with tonsillar ectopia seen between December 1990 and March 1993 are reported on. The same number of age and sex matched controls were selected at random from outpatients. Twelve asymptomatic subjects with tonsillar ectopia were found among 5000 people between January 1991 and March 1996. Diagnosis of tonsillar ectopia was based on midsagittal MRI. RESULTS: Patients presented mainly with chronic intractable occipital dull pain, vertigo, and dysequilibrium. In all patients MRI showed normal brain structure except for tonsillar ectopia (-2.9 (SD 0.8) mm), which has historically been thought to be of no clinical relevance. In the control group the tonsilar position was +2.1 (SD 2.8) mm (p<0.01). Neurotologically abnormal findings were detected with a monaural speech integration test (100%), eye tracking test (56%), optokinetic nystagmus test (89%), and visual suppression test (67%) which strongly suggested a CNS lesion. In accordance with the results of MRI and precise neurotological examination, posterior fossa decompression surgery was carried out, followed by improvement of preoperative symptoms and less severity of neurotological abnormalities in all patients. CONCLUSION: Tonsillar ectopia could cause neurological symptoms in small populations, which were surgically treatable. Neurotological assessment was necessary to verify the aetiological relation between tonsillar ectopia and various symptoms.

Adult↗

Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group.

BACKGROUND AND PURPOSE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. METHODS: Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. RESULTS: Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (P = .023, Wilcoxon rank sum test) but not at 3 months (P = .056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. CONCLUSIONS: Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.

Acute Disease↗

Isolation and characterization of a wound-inducible ribonuclease from Nicotiana glutinosa leaves.

A wound-inducible ribonuclease (RNase NW) was purified from leaves of Nicotiana glutinosa. The purified RNase NW has an optimum pH around 5 and 7, and its base specificity is suggested based on the relative rates of hydrolysis of homopolyribonucleotides to be a preference for guanine base. The complete amino acid sequence of RNase NW was deduced by a combination of protein and cDNA sequencings. The cDNA sequence includes the entire coding sequence for a polypeptide with 229 amino acids including a putative secretion signal peptide at the N-terminus composed of 25 amino acids. The amino acids identified by the protein chemical methods are unambiguously localized within the deduced amino acid sequence from the cDNA sequence. Comparison of the sequence of RNase NW with those of other known plant RNases showed that it was identical except for eight residues to that of N. alata RNase NE, which is present in the style and pollen under normal conditions and is induced in roots in response to phosphate starvation [Dodds et al., Plant. Mol. Biol., 31, 227-238 (1996)]. RNase NW shows considerable sequence similarity to other known RNases, sharing 57% to 84% identical residues. Northern blot analysis using an RNase NW cDNA fragment as a probe showed that the RNase NW transcript was not detected in leaves without wounding, but it was induced within 4 h after wounding and then gradually decreased during 20 h.

Amino Acid Sequence↗

Comparison of bromodeoxyuridine labeling indices of smears and sections from mouse NR-S1 tumor.

Bromodeoxyuridine (BrdU) labeling indices (LIs) of smears and sections from mouse NR-S1 tumor were labeled in vivo or in vitro and compared to confirm the reliability of smears labeled in vitro. In vivo labeling was carried out by administering 40 mg/kg 5-bromo-2'-deoxyuridine while in vitro labeling was performed by incubating the tumor specimens in RPMI 1640 culture medium containing 200 microM 5-bromo-2'-deoxyuridine under 3 atmospheres. BrdU LIs of sections labeled in vitro (9.49 +/- 0.16) showed lower values than those labeled in vivo (14.95 +/- 0.36). BrdU LIs of smears labeled in vitro (9.87 +/- 0.23) also showed lower values than those labeled in vivo (14.83 +/- 0.49). However, the BrdU LIs of smears were similar to those of sections labeled in vivo and in vitro. In vitro BrdU immunochemistry in smears seems useful for evaluating the biological properties of tumor tissues.

Animals↗

[Basic calponin expressing human neuroblastoma cell line of KP-N-YS].

Recent studies have demonstrated that human neuroblastoma (NB) cell lines have at least two morphological appearance of neuroblastic (N-type) and substrate-adhesive (S-type) cells. Our previous study revealed that S-type cells expressed alpha-smooth muscle actin and/or desmin, suggesting the smooth muscle cell characteristics of S-type cells. In the present study, a new human NB cell line, KP-N-YS, was established from bone marrow metastasis of a four-year-old boy with advanced NB, originating from the left adrenal gland. Subsequently N-type cell clone (YS1n) and S-type cell clone (YS2s) was isolated from the parent cell line. Parent and clones cell lines were identified as NB by surface membrane antigen and cytoskeletal protein analysis, and these cell lines were demonstrated as common progenitors by chromosomal analysis. Furthermore the presence of basic calponin were determined by indirect immunofluorescence, Western blot, as well as by RT-PCR (reverse transcriptase-polymerase chain reaction). Our demonstration of basic calponin not in N-type cells, but in S-type cells supports the plausible smooth muscle cell characteristics of this NB cell line.

Antigens, Surface↗

[A case of male dysgenetic pseudohermaphroditism detected by the rapid growth of phallus].

A case of male dysgenetic pseudohermaphroditism detected by the rapid growth of phallus is reported. A 10-year-old girl with rapid growth of a phallus during the past 6 months was referred to our clinic. Physical examination revealed a normally located urethral meatus and introitus with a 1.5 cm x 4 cm phallus. Radiographic studies revealed a vagina, uterus and fallopian tube-like structures. Karyotype was a mosaicism with 46, XY (71.5%), 45, X (26%), and others (2.5%). Bilateral gonads were dysgenetic testicular tissue with gonadoblastoma. Focal dysgerminoma was developed on the left side. Bilateral gonadectomy and feminizing phalloplasty were performed.

Child↗

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes--effect of clofibrate-feeding.

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes was investigated. In the control hepatocytes, NAD+ synthesis from tryptophan was not affected by nicotinic acid from 0.026 to 0.26 mM. NAD+ synthesis from nicotinic acid was slightly inhibited with varying concentrations of tryptophan from 0.1 to 1.0 mM. In the clofibrate-treated hepatocytes, NAD+ synthesis from tryptophan was greatly increased (234% of the control), while that from nicotinic acid was decreased (71.2% of the control). Both, NAD+ synthesis from tryptophan and that from nicotinic acid were decreased by the coexisting nicotinic acid or tryptophan. Total amount of NAD+ synthesized from tryptophan and nicotinic acid at their physiological concentrations was significantly higher than that in the control hepatocytes as a result of a large increase of NAD+ synthesized from tryptophan. When the metabolic flux of 0.1 or 0.5mM tryptophan was investigated, the glutarate pathway was suppressed in the clofibrate-treated hepatocytes, the quinolinic acid-NAD+ flux being elevated. Similarly to clofibrate, DEHP and CPP revealed an increase in NAD+ synthesis from tryptophan. Mutual relationship of NAD+ biosyntheses from tryptophan and nicotinic acid in rat hepatocytes is discussed and the relevance with peroxisomal proliferation is suggested.

Animals↗