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S Hirano

Publications and source records attributed to S Hirano.

At least 19 recordsLinked to original sources
PubMed1992

Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization.

The function of cadherin cell adhesion molecules is thought to be regulated by a group of cytoplasmic proteins, including alpha-catenin. We identified a subtype of alpha-catenin, termed alpha N-catenin, which is associated with N-cadherin and expressed mainly in the nervous system. cDNA transfection experiments showed that alpha N-catenin can also bind with E-cadherin. To investigate the role of alpha N-catenin, we transfected lung carcinoma PC9 cells, which express E-cadherin and beta-catenin but neither alpha- nor alpha N-catenin, with alpha N-catenin cDNA. While parental PC9 grew as isolated cells, the transfectant lines formed aggregates in which cells were tightly adhered to each other, showing epithelial arrangements, and they occasionally gave rise to cystic spheres. These results suggest that alpha N-catenin is crucial not only for cadherin function but also for organization of multicellular structures.

Amino Acid Sequence↗
PubMed1992

Influence of altered afferent input on the number of trochlear motor neurons during development.

A loss of about half of the trochlear motor neurons occurs during the course of normal development. The present investigation was undertaken to examine the role of afferent input in regulating the number of surviving or dying trochlear motor neurons. A majority of the afferent input to the trochlear nucleus comes from the vestibular nuclei of the hindbrain via the medial longitudinal fasciculus. Portions of the hindbrain were lesioned in duck embryos on embryonic day 3, considerably prior to the time motor neurons send their axons out and cell death begins. The effectiveness of hindbrain lesion was verified by electron microscopical examination of synapses. There was a significant decrease in the number of synapses on trochlear motor neurons following hindbrain lesion. Cell counts made after the period of cell death indicated a significant decrease in the final number of surviving trochlear motor neurons. Cell counts made prior to the onset of cell death indicated that there was a drastic reduction in the initial number of trochlear motor neurons produced in hindbrain lesion embryos. In spite of a significant reduction in the initial number of neurons, the percentage loss of neurons was about the same as during normal development. Since trochlear motor neurons are generated prior to the formation of afferent synapses on them, it is unlikely that the reduction in the number of motor neurons initially produced is due to reduced afferent synaptic input. Since the percentage of cell loss in hindbrain lesion and normal embryos is about the same, it seems that the magnitude of cell death is genetically programmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Disposition and excretion of 2-chlorodibenzofuran in the rat.

When 2-chloro[14C]dibenzofuran was intravenously administered to the rats, about 86% of radioactivity was found in the urine, the large intestinal contents and the feces within 24 h. Approximately 3% of 2-chlorodibenzofuran (2CDF) radioactivity was present in the adipose tissue 48 h after an intravenous administration. A similar excretion pattern of the compound was observed in orally administered rats. From experiments in vitro, approximately 80% of 2CDF was present in the red blood cell fraction and the remainder in the plasma fraction. Bile cannulation studies revealed involvement of enterohepatic circulation in the metabolism of the compound. Bile specimens that were subjected to enzymatic hydrolysis by arylsulfatase and/or beta-glucuronidase showed the presence of various yet unidentified conjugated substances. A comparative study using 3-chlorodibenzofuran (3CDF) showed a similar distribution pattern in the 2CDF-treated rats, but 2CDF appeared to accumulate more in the adipose tissue and red blood cells. The present study demonstrates that most of 2CDF is quickly metabolized to give rise to a number of metabolites and excreted from the body, but suggests that the compound once distributed in the adipose tissue may remain there for a relatively long period of time.

Animals↗
PubMed1992

Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer.

E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.

Adenocarcinoma↗
PubMed1992

Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal tumour cells.

The cadherin family of adhesion molecules are prime mediators of cell-cell interactions while the integrins predominantly mediate cell-matrix and to a lesser extent cell-cell binding specificity. We have recently shown that a human colon carcinoma cell line (SW1222) organizes into glandular structures, with well defined polarity when cultured in three-dimensional type I collagen gel. The current study indicates that SW1222 cells display high levels of E-cadherin (E-cd, epithelial cadherin) by western blotting and immunohistochemical staining. A monoclonal antibody (HECD-1) specific for human E-cd blocks cell-cell adhesion (100%) and inhibits (up to 75%) the glandular differentiation of SW1222 cells growing in collagen gel. Furthermore the anti-beta 1 integrin monoclonal antibody (mAb13) inhibits the glandular differentiation of SW1222 cells (61%) and their cellular binding to type I collagen (60%). However, no significant inhibition of cell-cell adhesion was demonstrated using mAb13 nor the anti-carcinoembryonic antigen monoclonal antibody (PR3B10). These results are consistent with E-cd being a cell-cell adhesion molecule expressed by SW1222 cells. These data indicate that E-cd and beta 1 integrins mediate cell-cell and cell-collagen interactions required for the induction and maintenance of the glandular differentiation of colorectal tumour cells. Thus the down-regulation or loss of E-cd and beta 1 integrins seen in poorly differentiated colorectal tumours may represent one of the abnormalities underlying their progression towards an undifferentiated phenotype in vivo.

Blotting, Western↗
PubMed1992

Altered expression of E-cadherin in gastric cancer tissues and carcinomatous fluid.

Expression of E-cadherin in 21 patients with various histological types of gastric carcinomas was studied by immunoperoxidase staining. Intercellular boundaries of almost all cancer cells in well and moderately differentiated adenocarcinomas stained as deeply for E-cadherin as normal gastric mucosa. However, singly infiltrating cells of those histological types were poorly stained. In poorly differentiated adenocarcinomas, cancer cells forming clusters stained lightly and those infiltrating singly stained even less. In signet ring cell carcinomas, hardly any staining was observed. In each histological type, the staining patterns and intensity at different layers of the gastric wall, were essentially the same. Cancer cells from carcinomatous ascites of gastric adenocarcinomas and pancreatic adenocarcinomas, and those from pleural effusion of lung adenocarcinomas were also studied by immunofluorescence staining. Of 11 specimens, ten were negative and only one from a lung adenocarcinomas was positively stained. By phase-contrast microscopic observations, none of these cancer cells including those from the lung adenocarcinomas, formed obvious cell-cell contacts. Cell aggregation assays confirmed the above results. The molecular weight of E-cadherin of cancer cells of lung adenocarcinomas was less than intact E-cadherin as revealed by Western blot analysis. These results suggest that depressed expression and/or impaired function of E-cadherin in cancer cells, facilitates their liberation from primary sites to infiltrate freely into tissue or fluid.

Adenocarcinoma↗
PubMed1992

Neuronal ganglioside increases dependent on the neuron--glia interaction in primary culture.

Dissociated neuronal cells from rat embryonic hemispheres were cultivated on astroglial layers. The increase in ganglioside content of the cocultures was more rapid than that of neuronal cultures seeded on polylysine surfaces for the first 24 h, and the extent of the increase was greater 7 days after inoculation, probably because of interaction between the preformed astroglial layers and the neuronal cells in vitro. The promoted expression of the a-pathway gangliosides, GM1 and GD1a, was recognized by TLC and the increase in GM1 was immunologically ascertained. The incorporation of 3H-labeled N-acetyl-D-mannosamine into GD3 and b-series gangliosides was elevated for the first 24 h. However, cocultures in which there was no contact between neuronal cells and the astroglial sheet showed no appreciable increase in incorporation. Thus, cell surface changes were induced at the membrane glycolipid level in the neuronal cells by contact with astroglial layers. The synthesis and expression of neuronal gangliosides are discussed in relation to the onset of neuron--glia interaction.

Animals↗
PubMed1992

A possible mechanism of endothelium-dependent relaxation induced by pirarubicin and carbachol in rat isolated aorta.

The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)-4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 mM Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3) M), or with K(+)-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na(+)-Ca2+ exchange process is involved.

Amiloride↗
PubMed1992

Inhibitory effects of tiamulin on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs.

The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.

Action Potentials↗
PubMed1992

Effect of colchicine on ganglioside composition of rat primary culture neurons.

Developmental changes in gangliosides in the course of neurite outgrowth were examined in dissociated fetal rat cerebral neurons in culture. About a 2-fold increase in ganglioside levels was seen with the progression of neurite formation for up to 24 h in predominantly neuronal cultures. Ganglioside patterns appeared to be unchanged during the first 24 h, subsequently consisted of higher amounts of GD3 and b-series gangliosides (such as GD1b, GT1b, and GQ1b), and lower amounts of a-series gangliosides (GM1 and GD1a). Although the addition of colchicine to the cell growth medium inhibited neurite outgrowth in developing neurons, little if any differences in ganglioside patterns were found between control and colchicine-treated cells. Ganglioside levels decreased slightly in colchicine-treated cells in agreement with the decrease in cell attachment to culture dishes. Although colchicine treatment 8 h after plating caused complete retraction of formed neurites, the ganglioside level of the cells continued to increase during the following 16-hour incubation. Thus, the data suggest that ganglioside synthesis in differentiating neurons does not primarily accompany the expansion in cell surfaces due to neurite formation, and raises the possibility that a large proportion of gangliosides is retained in intracellular compartments.

Animals↗
PubMed1992

Lack of cell density-dependent changes in gangliosides of rat primary culture neurons.

Cell density-dependent changes in neuronal gangliosides, primarily relating to neurite outgrowth under dense to sparse conditions, were examined at cell seeding densities over an 8-fold range. During the first 24 h of incubation, the dissociated fetal rat neurons showed characteristic protrusion of neurites as a function of cell density. Ganglioside and protein contents per the same cell numbers were higher in dense cultures than sparse ones. However, the ganglioside pattern was essentially unchanged from dense to sparse culture, showing a predominance of GD3 and GT1b. The biosynthetic activity of gangliosides, as estimated by the incorporation of 3H-labeled N-acetyl-D-mannosamine, a precursor of sialic acid, was similar at various cell densities, with the labeling of b-series gangliosides predominating. The expression of neuronal gangliosides was monitored by indirect immunofluorescence using anti-GM1 antibody, but was found to be poor. A2B5 antigen, which was mainly identified as GT1b, appeared to be readily expressed on cell surfaces in sparse cultures. In contrast, the highly polysialylated form of the neural cell adhesion molecule (NCAM-H) was fully expressed on both the neurites and cell soma at various cell densities. The results suggest that the polysialic acids in NCAM have more important roles in neurite outgrowth than gangliosides, since the composition and synthesis of gangliosides are not affected by cell seeding density.

Animals↗
PubMed1992

Compressive creep and recovery of composite resins with various filler contents in water.

The compressive creep and the recovery of composites in water were examined. The creep strain of the composites after a 500h test linearly decreased with the increase of their filler content. Their water sorption during testing decreased with the increase of applied stress on the composites containing low filler contents. In the composites containing high filler content, the water sorption was almost constant for some stress levels. The recovery of the composites after testing was significant immediately after testing. From the measurement of the water sorption of the composites, the microcrack or the craze should occur at the filler/matrix interface or in the matrix itself during the creep test, and water could diffuse to the microcrack or the craze after testing in unstressed conditions. This would explain the increase in the water absorbed in the composites in the recovery period.

Absorption↗
PubMed1992

[Study on analysis of viscoelastic property of palatal mucoperiosteum--about the creep recovery].

The purpose of this study was to analyze the creep phenomena of the palatal mucosa under pressure and after pressure release. The measuring device consisted of the control box, which regulated the loading force by air pressure, and the pick-up, which was fixed to the teeth and applied the load onto the mucosa, detected the displacement of the mucosa. The creep was analyzed by the Voigt 4 element model. The ratio of the recovery (S1'/S1, S2'/S2) and the recovery percentage were analyzed on the creep after the pressure release and evaluated from the point of expressing exactly the viscoelastic recovery. The results were as follows: 1. Both the amount of the displacement under pressure and the recovery of the palatal mucosa showed the least value at the center site and at the other sites less at the distal site than the mesial site. 2. The ratio of S1'/S1 was about 0.5 at all sites. On the other hand, the ratio of S2'/S2 showed values higher than 1 except at the center site and was significantly different among the other sites. 3. It was pointed out that the recovery percentage was more suitable than the ratio of the recovery to explain the viscoelastic recovery of the palatal mucosa.

Adult↗
PubMed1992

[Experimental studies of urinary incontinence. Effect of tiropramide on the urinary stage and evacuation].

Tiropramide, a tyrosine derivative, has an antispasmodic effect on the gastrointestinal smooth muscles and it is suggested that the effect is mediated by cAMP. Therefore, we studied the effects of tiropramide on the lower urinary tract smooth muscle functions. In animal experiments, the effects of tiropramide on vesicourethral smooth muscle contraction were investigated and cAMP and cGMP levels following tiropramide administration were measured in the vesicourethral and gastrointestinal smooth muscles. In clinical trials, five healthy volunteers and five patients with neurogenic bladder dysfunction were treated orally with tiropramide 300 mg a day for two weeks and examined for urodynamic parameters before and after tiropramide treatment. Tiropramide significantly inhibited contraction of the vesicourethral smooth muscle and the inhibitory effect upon the bladder was remarkable particularly at the lower concentrations. Tiropramide remarkably increased cAMP level but it had no effect on cGMP level in the bladder at the lower concentrations. Tiropramide at the lower concentrations did not affect cAMP and cGMP levels in the smooth muscles of the urethra, stomach and intestines. In the patients with neurogenic bladder dysfunction treated with tiropramide orally, the urine volume at first desire to void and maximum bladder capacity increased significantly, but the volume of residual urine did not significantly increase. In the healthy volunteers, there were no significant changes in urodynamic parameters. These findings indicate that tiropramide relaxes the urinary bladder smooth muscle via cAMP to increase the urinary bladder capacity.

Adult↗
PubMed1992

[Ataxic cerebral palsy and brain imaging].

Five cases diagnosed as having ataxic cerebral palsy were presented with their brain imaging. Case 1, a 3-year-old-girl had been floppy since 7 months of age and began ataxic walk with spastic legs from 18 months of age. MRI revealed generalized atrophy of cerebellum (especially in anterior superior part) and slight atrophy of pons. Her mother also had ataxia with spastic legs of early onset. She and her mother were thought to have an early-onset inherited non-progressive cerebellar ataxia syndrome. Case 2, a 8-year-old-girl had ataxic walk since 17 months of age. MRI revealed cerebellar atrophy especially in anterior superior part. Case 3, a 10-year-old boy was floppy since 4 months of age and suspected as ataxic at 4 years of age. He could walk only with cruches. He had dwarfism and cataracts since 4 years of age. CT and MRI revealed generalized spino-ponto-cerebellar atrophy. Final diagnosis was Marinesco-Sjörgren syndrome. Case 4, a 10-year-old girl had opisthotonus and floppiness since 4 months of age. She could walk only with cruches. CT and MRI revealed generalized spino-ponto-cerebellar atrophy. Case 5, a 8-year-old boy showed head nodding and nystagmus since 4 months of age. He started ataxic gait at 8 years of age. He could vocalize only single sound for speech. MRI revealed cranium bifida and agenesis of anterior medullar velum. Ataxic cerebral palsy is the term often used to describe very different conditions, the clinical picture starts as hypotonia and changes into the ataxic symptoms in a few years.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia↗
PubMed1992

[Clinical evaluation of flucytosine in patients with urinary fungal infections].

The clinical effectiveness of flucytosine (5-FC) was evaluated in 52 patients with urinary fungal infections which were diagnosed because of the presence of both funguria (greater than or equal to 10(4) cfu/ml) and pyuria (greater than or equal to 5 WBC/hpf). The patients received oral daily doses of 5-FC ranging 20 to 150 mg/kg, with a mean treatment duration of 11 days. The 57 fungus strains isolated from urine specimens consisted of 51 Candida spp. including 28 Candida albicans, 10 Candida glabrata, 4 Candida tropicalis and 6 Trichosporon beigelii. Forty-seven (92.2%) and 4 (66.7%) of the 51 Candida spp. and 6 T. beigelii strains isolated were eradicated by the treatment, respectively, giving an overall eradication rate of 89.5%. Clinical responses in 32 patients, from whom only fungi were submitted, were excellent in 5, moderate in 22, and poor in 5, thus the overall efficacy rate was 84.4%, based on the criteria of Japanese UTI Committee. Of the 18 strains of Candida spp. tested, 5-FC showed 0.20 micrograms/ml or less of the minimum inhibitory concentrations (MICs) against 16 strains and higher than 100 micrograms/ml against the remaining 2 strains. The MICs of the 5 T. beigelii strains tested were between 3.12 and 6.25 micrograms/ml. As adverse reactions, only 2 patients (3.8%) experienced diarrhea but did not require treatment cessation. These results suggest that flucytosine is an effective drug for urinary fungal infections.

Adult↗
PubMed1992

[Occurrence of anomalies of the central nervous system in handicapped children].

We surveyed anomalies of the central nervous system using cranial CT scan in handicapped children who were institutionalized or staying at their homes. At the institutions for severely retarded children, fourteen cases were found and the rate was 6.1%. All of them were very severely retarded. At the institution for physically handicapped children, 12 cases including 10 cases of hydrocephalus were found and the rate was 9.3%. Most of them could take care of themselves. Nineteen cases were found among children staying at their homes and the rate was 9.4%. Most of them were very severely retarded. We conclude that the anomalies of the central nervous system play an important role in the pathogenesis of handicapped children, especially severely retarded children, and that the burden derives from them is a big problem in our daily clinic and special education.

Anencephaly↗