Search PubMed⌕ Search

Biomedical subjects

S Iwasaki

Publications and source records attributed to S Iwasaki.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prevalence of mitochondrial gene mutations among hearing impaired patients.

The frequency of three mitochondrial point mutations, 1555A-->G, 3243A-->G, and 7445A-->G, known to be associated with hearing impairment, was examined using restriction fragment length polymorphism (RFLP) analysis in two Japanese groups: (1) 319 unrelated SNHL outpatients (including 21 with aminoglycoside antibiotic injection history), and (2) 140 cochlear implantation patients (including 22 with aminoglycoside induced hearing loss). Approximately 3% of the outpatients and 10% of the cochlear implantation patients had the 1555A-->G mutation. The frequency was higher in the patients with a history of aminoglycoside injection (outpatient group 33%, cochlear implantation group 59%). One outpatient (0.314%) had the 3243A-->G mutation, but no outpatients had the 7445A-->G mutation and neither were found in the cochlear implantation group. The significance of the 1555A-->G mutation, the most prevalent mitochondrial mutation found in this study of a hearing impaired population in Japan, among subjects with specific backgrounds, such as aminoglycoside induced hearing loss, is evident.

Aminoglycosides↗
PubMed2000

[Natural organic compounds that affect to microtubule functions: syntheses and structure-activity relationships of combretastatins, curacin A and their analogs as the colchicine-site ligands on tubulin].

Microtubules (MT) are cylindrical polymers of the protein tubulin (TN) alpha, beta-heterodimer, and are known to be the main component of spindles in mitotic apparatus of eucaryotic cells. MT are also involved in many other basic and essential cell functions. There are a number of natural and synthetic compounds that interfere with MT function to cause the mitotic arrest of eucaryotic cells. Such antimitotic agents show a broad biological activity, and can be used for medicinal and agrochemical purposes. On the other hand, they are important also as the biochemical tools for understanding the dynamics of MT network. Most of such antimitotic agents, with a few exceptions, bind to beta-TN. Among them, colchicine (CLC), vinblastine and taxol have played major roles in practical uses as well as in biochemical studies of MT functions. They all bind to beta-TN but their binding sites are different. We have worked on a variety of antimitotic agents that bind to either of colchicine-site, vinblastine-site and taxol-site, in discovery, structures, biological actions and/or interactions with TN. In this paper, the results of our studies on CLC-site ligands were summarized; (1) synthetic analogs of combretastatin A-4 (CBS A-4), isolated as a cytotoxic compound produced by a species of South African tree Combretum caffrum, (2) curacin A (CU-A), a cytotoxic metabolite of a marine cyanobacteria Lyngbya majuscula, and its related compounds. Interactions of these compounds with TN were studied and structure-activity relationships of these two classes of compounds were discussed.

Bibenzyls↗
PubMed2000

[Experimental study of esophageal covered stent for prevention of migration: use of clay to simulate stenosis of the esophagogastric junction or anastomosis site].

PURPOSE: An inner-covered Spiral Z-stent (IC-SZ) developed by our group was examined for its effectiveness in preventing migration by experimental comparison with commercially available esophageal covered stents. MATERIALS AND METHODS: The following six types of stents were used: inner-covered Spiral Z-stents with diameters of 16 mm (small IC-SZ) and 19 mm (large IC-SZ), outer-covered Spiral Z-stent (OC-SZ), covered Wallstent, covered Ultraflex stent, and Cook Z-stent. Experimental models were prepared using clay to simulate stenosis of the esophagogastric junction or anastomosis site due to tumor, and each stent was placed in the clay. After the stent had been fully expanded with a balloon catheter, one of its ends was pulled until the stent migrated out of the clay, and the traction force was measured. The inner cavity of the stent placed in the clay was observed using an endoscope. RESULTS: The mean maximal traction force required to pull the stents out of the clay were as follows, in decreasing order: 4.14 +/- 0.39 kg for the large IC-SZ, 4.12 +/- 0.83 kg for the small IC-SZ, 3.64 +/- 0.44 kg for the Cook Z-stent (p < 0.05), 3.34 +/- 0.62 kg for the covered Ultraflex stent (p < 0.05), 1.53 +/- 0.43 kg for the OC-SZ (p < 0.01), and 0.56 +/- 0.16 kg for the covered Wallstent (p < 0.01). The force required to pull out the large IC-SZ stent was the greatest, showing a significant difference from the values for the other four types of stents (excluding the small IC-SZ). Observation using an endoscope revealed that the wire of the IC-SZ stent was almost entirely embedded in the clay, whereas the wires of other stents were not. CONCLUSION: The IC-SZ stent may be less likely to migrate than other esophageal covered stents.

Biomechanical Phenomena↗
PubMed2000

[A case of autosomal recessive juvenile parkinsonism (AR-JP) with onset at the age of 6 years].

We report a 26-year-old woman with autosomal recessive juvenile parkinsonism (AR-JP). Her parents made consanguineous marriage. The disease started with dystonic posture of legs 20 years prior to the admission (6 years old). The equinovarus foot appeared at 9 years old and parkinsonism gradually developed. These symptoms were remarkably improved after sleep. Levodopa was effective on her parkinsonian symptoms. However, the response to levodopa gradually reduced. On admission, she presented with a masked face, marked rigidity, moderate retropulsion, postural tremor in the upper limbs and mild hyperreflexia in the lower limbs. Mutational analysis revealed homozygous deletion of exon 4 in perkin gene. This patient has youngest age of onset for ARJP to our knowledge.

Adult↗
PubMed1999

Specific activation of the p38 mitogen-activated protein kinase signaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2.

Bone morphogenetic protein (BMP)-2 has the capacity to induce the neuronal differentiation of PC12 cells. Unlike nerve growth factor, however, BMP-2 failed to induce the activation of the 41-/43-kDa mitogen-activated protein (MAP) kinase pathway in these cells. In contrast, BMP-2 characteristically induced the sustained activation of the p38 MAP kinase pathway. Pretreatment of PC12 cells with SB203580 inhibited the BMP-2-induced neurite outgrowth formation in a dose-dependent manner; this inhibition coincided well with the ability of SB203580 to inihibit the BMP-2-induced activation of the p38 MAP kinase pathway. Overexpression in PC12 cells of wild-type MAP kinase kinase (MKK)-6 enhanced the BMP-2-induced activation of p38 MAP kinase, whose activation correlated well with the ability of these cells to induce neurite outgrowth in response to BMP-2. Transient expression of kinase-negative forms of MKK3/6 inhibited the formation of neurite outgrowth in response to BMP-2. Furthermore, expression of constitutively active forms of MKK3/6 induced neurite outgrowth without BMP-2 stimulation, and SB203580 inhibited this induction. These results clearly indicate that activation of the p38 MAP kinase pathway is necessary for BMP-2-induced neuronal differentiation of PC12 cells. Our results also suggest that activation of the p38 MAP kinase pathway alone can induce the neuronal differentiation of PC12 cells.

Amino Acid Sequence↗
PubMed1999

Adhesive Force between Hydrophilic Surfaces in Alcohol-Water Solutions.

The interaction and adhesive forces between a mica plate and SiO(2) surfaces in water-alcohol (ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol) mixtures were investigated on the molecular scale, using an atomic force microscope. The following results were obtained: (i) alcohols higher than 1-propanol adsorb standing on the hydrophilic surface vertically to form a structured monolayer, when the alcohol concentration is high enough; (ii) the adhesive force between surfaces depends on how closely two surfaces can be brought by breaking the adsorbed layers; (iii) the adhesive force between surfaces is maximized at w(w)/w(ws) approximately 0.25, independent of the kind of alcohol, where w(w) and w(ws) are the weight fractions of water and saturated water, respectively; and (iv) the adhesive force for a particle of rough surface is much smaller than the adhesive force predicted for a particle of smooth surface. It is hypothesized that this adhesive force much greater than the van der Waals attractive force originates from the water bridging between surfaces, and this hypothesis is confirmed by the predictions given by the Laplace equation and the Kelvin relation. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Effects of corticosteroid, contrast medium and ATP on focal microcirculatory disorders of the cochlea.

We evaluated the ability of various drugs to prevent the decrease in focal cochlear blood flow induced by photochemical reaction and investigated the mechanisms underlying this decrease. By means of a photochemical reaction, which produces reactive oxygen species, focal lesions measuring about 1 mm in diameter were induced in the lateral wall of the guinea pig cochlea. The protective effects of hydrocortisone, amidotrizoate and ATP on cochlear blood flow and cochlear vascular conductance changes were evaluated by using a non-contact laser flowmeter. Cochlear blood flow and cochlear vascular conductance were decreased to 65.1+/-4.9% (mean +/- S.E.M.) and 57.0+/-3.7% (mean +/- S.E.M.) of the initial level 30 min after the start of the photochemical reaction, respectively. Hydrocortisone significantly prevented the decline in the cochlear blood flow and cochlear vascular conductance and reduced the area of stria vascularis degeneration in a dose-dependent manner. Neither amidotrizoate nor ATP significantly prevented the decrease in cochlear blood flow or cochlear vascular conductance. Hydrocortisone was more effective than vasodilators or other agents which increase cochlear blood flow in preventing the photochemically induced decrease in cochlear blood flow. This might be due to the antioxidative effects of hydrocortisone.

Adenosine Triphosphate↗
PubMed1999

The ability of anti-carbonic anhydrase II antibody to distinguish autoimmune cholangitis from primary biliary cirrhosis in Japanese patients.

Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P < 0.05), but not in patients with autoimmune hepatitis and patients with obstructive jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.

Autoantibodies↗
PubMed1999

A new pregnane glycoside from Dioscorea collettii var. hypoglauca.

During further bioactivity-guided fractionation, a new pregnane glycoside, hypoglaucin G (1), and a known compound, pregna-5, 16-dien-3beta-ol-20-one 3-O-alpha-L-rhamnopyranosyl-(1-->2)- [alpha-L-rhamnopyranosyl-(1-->4)] -beta-D-glucopyranoside (2), were isolated from the EtOH extract of Dioscorea collettii var. hypoglauca rhizomes, which induced morphological deformation of Pyricularia oryzae mycelia with minimum morphological deformation concentration values of 135 microM and 236 microM, respectively. The structure of 1 was established as 16beta-(4'-methyl-5'-O-beta-D-glucopyranosyl- pentanoxyl)-pre gn-5-en-3 beta-ol-20-one 3-O-alpha-L- rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D- glucopyranoside on the basis of chemical evidence and spectral analysis, especially by 2D NMR techniques.

Antifungal Agents↗
PubMed1999

Ultrastructural study of the relationship between the morphogenesis of filiform papillae and the keratinisation of the lingual epithelium in the rat.

Tongues were removed from rat fetuses on d 16 of gestation (E16) and from newborn (P0) and juvenile rats on d 7 (P7) and d 21 (P21) postnatally for examination by light and transmission electron microscopy. In the fetuses at E16, no rudiments of filiform papillae were visible on the dorsal surface of the tongue. No evidence of keratinisation could be recognised over the entire dorsal lingual epithelium. At P0, rudiments of filiform papillae showed a similar distribution to that seen in the adult, but had a more rounded appearance. The columnar structure of cells in the epithelium, with the different degrees of keratinisation as observed in the mature adult, was indistinct, but a keratinised layer was clearly located at the tip of each filiform papilla. In juveniles at P7, the filiform papillae on the anterior part of the tongue were long and slender, and the anterior and posterior cell columns of the filiform papillae and the interpapillary cell columns were clearly distinguishable. In juveniles at P21, the structure of filiform papillae was identical to that in the adult. These results indicate that, in rats, the morphogenesis of filiform papillae advances in parallel with keratinisation of the lingual epithelium from just before birth to a few weeks after birth.

Animals↗
PubMed1999

Bone morphogenetic protein-2 promotes survival and differentiation of striatal GABAergic neurons in the absence of glial cell proliferation.

We examined the potential neurotrophic effects of bone morphogenetic protein (BMP)-2 on the survival and differentiation of neurons cultured from the rat developing striatum at embryonic day 16, a period during which the mRNAs for BMP-2 and its receptor subunits (types IA, IB, and II) were detected. BMP-2 exerted potent activity to promote the survival of striatal neurons and increased the number of surviving microtubule-associated protein-2-positive cells by 2.4-fold as compared with the control cultures after 4 days in vitro. Although basic fibroblast growth factor (bFGF) also showed relatively high activity to promote the survival of striatal neurons, transforming growth factor-beta1, -beta2, and -beta3, glial cell line-derived neurotrophic factor, or brain-derived neurotrophic factor promoted their survival weakly. Striatal neurons cultured in the presence of BMP-2 or bFGF possessed extensive neurite outgrowths, the majority of which were GABA-immunoreactive. Inhibition of glial cell proliferation by 5-fluorodeoxyuridine did not affect the capacity of BMP-2 to promote the survival of striatal GABAergic neurons. In contrast, the ability of bFGF to promote the survival of striatal neurons was inhibited significantly by the treatment of cells with 5-fluorodeoxyuridine. All these results suggest that BMP-2 exerts potent neurotrophic effects on the striatal GABAergic neurons in a glial cell-independent manner.

Animals↗
PubMed1999

Antineoplastic agents. III: Steroidal glycosides from Solanum nigrum.

By bioactivity-guided fractionation, three known steroidal glycosides, beta 2-solamargine (1), solamargine (2), and degalactotigonin (3), were isolated from Solanum nigrum. Compounds 1-3 induced morphological abnormality in Pyricularia oryzae mycelia with MMDC (minimum morphological deformation concentration) values of 63.0, 38.5, and 97.2 microM, respectively. This is the first report on the isolation of 1 from this species and on the cytotoxicity of 1-3 on six cultured human solid tumor cell lines HT-29 (colon), HCT-15 (colon), LNCaP (prostate), PC-3 (prostate), T47D (breast), and MDA-MB-231 (breast) in vitro. The cytotoxic assay indicated that 2 is the main antineoplastic agent in S. nigrum. The structures of 1-3 were elucidated on the basis of chemical evidence and spectral analysis, especially by 2D-NMR analysis.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Retrovirus integration site Mintb encoding the mouse homolog of hnRNP U.

Retroviral genes are not usually expressed in mouse embryonal carcinoma (EC) cells, but they are readily expressed upon differentiation of these cells. We previously reported the isolation of EC cell lines that express a neomycin resistance (neo) gene introduced by a recombinant transducing Moloney murine leukemia virus from specific integration sites, Minta, Mintb, Mintc, or Mintd. In some of these clones, the entire 5' long terminal repeat (LTR) was deleted, and the neo gene was expressed by read-through transcription from upstream cellular promoters in a "promoter-trap" fashion. One such promoter ("promoter B" at the Mintb locus) was found in a CpG island, associated with an upstream enhancer ("enhancer B"). Although enhancer B caused expression of the neo gene in the transductant EC cell line, no endogenous transcription from promoter B was detected in the parental EC or NIH3T3 cells. In contrast, we found a strong counter-flow endogenous transcription unit ("R" for reverse), which apparently interfered with transcription from promoter B. Promoter R turned out to have a bidirectional activity in transfection assays. In normal tissues, promoter R activates gene R, which encodes an 800-residue protein that is highly homologous to the rat and human heterogeneous nuclear ribonucleoprotein U (hnRNP U). Northern and in situ hybridization analyses revealed that gene R was abundantly expressed in the testis, especially in the pachytene spermatocytes and round spermatids.

3T3 Cells↗
PubMed1999

Development of androgen-independent carcinomas from androgen-dependent preneoplastic lesions in the male accessory sex organs of rats treated with 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate.

Two kinds of cancer can be induced in rat male accessory sex organs, one a non-invasive carcinoma arising in the ventral lobe and the other an invasive lesion which develops in the dorsolateral and anterior lobe as well as the seminal vesicles. In the present study, one group of male rats were given biweekly s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 weeks for induction of non-invasive carcinomas and the other group received DMAB with 40-week testosterone propionate for induction of invasive carcinomas. Half of the animals in each group were then subjected to bilateral orchiectomy at week 41 to remove testicular androgen, in order to examine the androgen dependence of both types of carcinomas as well as precancerous lesions. Animals were killed at weeks 41, 46 and 60. All parts of the prostate complex showed involution and significant weight reduction after castration, with a complete disappearance of atypical hyperplasias and carcinomas of the ventral prostate. However, in spite of suppression of development of atypical hyperplasias in the anterior prostate and seminal vesicles, the incidence of invasive carcinomas was not changed. Normal epithelial cells and atypical hyperplasias of all parts of the prostate and seminal vesicles and carcinomas of the ventral prostate were immunohistochemically positive for nuclear androgen receptor, while invasive carcinomas that developed in either castrated or non-castrated animals were negative. These findings suggest that in the ventral prostate, both precancerous and cancerous lesions are androgen-dependent, but in the anterior and seminal vesicles, cancerous lesions (invasive carcinomas) are androgen-independent while precancerous lesions are hormone-dependent.

Aminobiphenyl Compounds↗
PubMed1999

ADP-ribosylation as an intermediate step in inactivation of rifampin by a mycobacterial gene.

Mycobacterium smegmatis DSM43756 inactivates rifampin, and the inactivated antibiotic product recovered from culture medium was ribosylated on the 23-OH group. To study this process, the gene responsible for the inactivation was expressed at high levels by the lac promoter in Escherichia coli conferring resistance to >500 microg of antibiotic per ml. Cell homogenates generated a novel derivative designated RIP-TAs; in this study, we determined that RIP-TAs is 23-(O-ADP-ribosyl)rifampin. Our results indicated that RIP-TAs is an intermediate in the pathway leading to ribosylated rifampin and that the previously characterized gene encodes a mono(ADP-ribosyl)transferase which, however, shows no sequence similarity to other enzymes of this class.

ADP Ribose Transferases↗
PubMed1999

Ultrastructural study of the relationship between the morphogenesis of filiform papillae and the keratinization of the lingual epithelium in the mouse.

Tongues were removed from fetuses of mice on the 15th day of gestation (E15), from newborns (P0), and from juveniles on the 7th day (p7) and on the 21st day (P21) after birth for examination by light microscopy and transmission electron microscopy. In the fetuses at E15, no rudiments of filiform papillae were visible on the dorsal surface of the tongue. No evidence of keratinization was recognized throughout the entire dorsal lingual epithelium. At P0, rudiments of filiform papillae were compactly distributed over the dorsal surface, as are the filiform papillae in the adult, but their tips were rounder than those of the filiform papillae in the adult. Cell columns in the epithelium, with different degrees of keratinization of the type observed in the matured adult were indistinct. However, a keratinized layer was clearly visible on the tip of each filiform papilla. In juveniles at P7, the filiform papillae on the anterior part of the tongue were long and slender, and the anterior and posterior cell columns of the filiform papillae were identical to those in the adult. These results indicate that, in mice, the morphogenesis of filiform papillae advances in parallel with keratinization of the lingual epithelium from the stage just before birth to a stage a few weeks after birth.

Animals↗