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Biomedical subjects

M Sone

Publications and source records attributed to M Sone.

At least 19 recordsLinked to original sources
PubMed1999

Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1.

The Rho family GTPases are involved in a variety of cellular events by changing the organization of actin cytoskeletal networks in response to extracellular signals. However, it is not clearly known how their activities are spatially and temporally regulated. Here we report the identification of a novel guanine nucleotide exchange factor for Rac1, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosophila SIF proteins. STEF protein contains two pleckstrin homology domains, a PDZ domain and a Dbl homology domain. The in vitro assay showed that STEF protein specifically enhanced the dissociation of GDP from Rac1 but not that from either RhoA or Cdc42. Expression of a truncated STEF protein in culture cells induced membrane ruffling with altered actin localization, which implies that this protein also activates Rac1 in vivo. The stef transcript was observed in restricted parts of mice, including cartilaginous tissues and the cortical plate of the central nervous system during embryogenesis. These findings suggested that STEF protein participates in the control of cellular events in several developing tissues, possibly changing the actin cytoskeletal network by activating Rac1.

Amino Acid Sequence↗
PubMed1999

Extracellular signal-regulated kinase mediates renal regeneration in rats with myoglobinuric acute renal injury.

In vitro data support that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), members of mitogen-activated protein (MAP) kinases, mediate the signal transduction pathways responsible for the cell proliferation. However, in vivo role of these MAP kinases is poorly understood. Intramuscular injection of 50% glycerol solution induces acute renal failure in rats. This injury is known as a model of rhabdomyolysis in human. To investigate the molecular mechanism of the signaling pathway in this injury, we examined the role of ERK and JNK. After the glycerol injection JNK was rapidly and transiently activated at about 4 h, while the activation of ERK was gradually increased and the levels were sustained at least to 24 h. Next, we examined the expression of cell-cycle related proteins after the glycerol injection using Western blot analysis. The levels of proliferating cell nuclear antigen (PCNA) protein as a marker for cell proliferation were induced at 2 h and significantly increased to 24 h after the injection. In addition, cyclins D1, D2, and D3 as markers for G1 phase also increased with similar time courses. To examine whether activation of ERK and/or JNK are involved in the renal regeneration after the glycerol injection, we examined the effect of genistein, which is an inhibitor of tyrosine kinase, on the activation of ERK and JNK. Administration of genistein to rats with this injury decreased the activation of ERK, but not JNK. The induction of PCNA and cyclin D1 was also prevented by this treatment. In this condition, renal function was further worsened as compared to control rats. These results provide the first evidence that ERK may be involved in the repair process of renal tubules damaged by this injury.

Animals↗
PubMed1999

Neural expression of hikaru genki protein during embryonic and larval development of Drosophila melanogaster.

Hikaru genki (HIG) is a putative secreted protein of Drosophila that belongs to immunoglobulin and complement-binding protein superfamilies. Previous studies reported that, during pupal and adult stages, HIG protein is synthesized in subsets of neurons and appears to be secreted to the synaptic clefts of neuron-neuron synapses in the central nervous system (CNS). Here we report the analyses of distribution patterns of HIG protein at embryonic and larval stages. In embryos, HIG was mainly observed in subsets of neurons of the CNS that include pCC interneurons and RP5 motorneurons. At third instar larval stage, this protein was detected in a limited number of cells in the brain and ventral nerve cord. Among them are the motorneurons that extend their axons to make neuromuscular junctions on body wall muscle 8. Immunoelectron microscopy showed that these axonal processes as well as the neuromuscular terminals contain numerous vesicles with HIG staining, suggesting that HIG is in a pathway of secretion at this stage. Some neurosecretory cells were also found to express this protein. These data suggest that HIG functions in the nervous system through most developmental stages and may serve as a secreted signalling molecule to modulate the property of synapses or the physiology of the postsynaptic cells.

Animals↗
PubMed1999

Cholesteatoma otitis media with intact ossicular chain.

Thirty-one cases of cholesteatoma with intact ossicular chain were reviewed to examine the extension of cholesteatoma, operation procedures, pre- and postoperative hearing levels, and postoperative condition of the ear drum. They were operated on at Departments of Hyogo College of Medicine and Osaka University Medical School from 1989-1996, which were 20.4% of all of the primary cholesteatoma cases (n = 152). Twelve cases located at attic were operated by atticotomy or canal wall up and scutumplasty, 17 cases located at attic/antrum were operated by canal wall down and reconstruction, and two cases located around stapes were operated through the ear canal. Preoperative hearing level was mild (34.2 +/- 18.4 dB) and postoperative one was slightly improved (28.7 +/- 11.2 dB). In ossicular reconstruction, modified Wullstein type III method showed better hearing gain than Wullstein type I method. Postoperative attic retraction and/or pocket occurred in 15 cases (48.4%), but no recurrent cholesteatoma was found during the present follow-up period. These findings suggested that cholesteatoma with intact ossicular chain showed good postoperative hearing results, but postoperative retraction of the ear drum should be followed up for a long time.

Adolescent↗
PubMed1999

Study of systemic lupus erythematosus in temporal bones.

Despite some reports of sensorineural hearing loss with systemic lupus erythematosus (SLE), its pathologic correlate has remained unidentified due to the scarcity of human temporal bone studies. We here present findings in 14 temporal bones from 7 patients with SLE, examined histologically and immunohistochemically for pathologic conditions in the cochlea that might relate to their otologic histories. Blue-staining concretions were seen in the stria vascularis of 6 ears. Most of the cases showed a loss of spiral ganglion cells, with various degrees of hair cell loss and atrophy of the stria vascularis. One ear demonstrated formation of fibrous tissue and bone throughout the cochlea, with complete loss of the membranous labyrinth. Cochlear hydrops was found in only 1 ear. These findings in temporal bones from patients with SLE are discussed in relation to autoimmune disease of the inner ear.

Adolescent↗
PubMed1999

Expression of intercellular adhesion molecule-1 in rat inner ear due to bacterial otitis media.

Expressions of anti-Streptococcus pneumoniae antibody and anti-intercellular adhesion molecule-1 (ICAM-1) antibody in the inner ear were studied immunohistochemically in rats following inoculation of S pneumoniae type 6A into the middle ear cavity. Positive staining with anti-S pneumoniae antibody was detected in the marginal cells of the stria vascularis of rats sacrificed 3 days after S pneumoniae inoculation, but almost no staining was detected in those sacrificed at 14 days. Strong ICAM-1 expression was detected in the basal cell layer of the stria vascularis of rats sacrificed 3 days after inoculation, but the intensity of the staining had decreased by 14 days. These results suggest that the stria vascularis may be a site of the inner ear damage that follows bacterial inoculation into the middle ear cavity. The up-regulated expression of ICAM-1 in the basal cell layer may represent a reaction of the inner ear to the bacterial otitis media.

Animals↗
PubMed1999

Precocious estrus and reproductive ability induced by PG 600 in prepuberal gilts.

A total of 29 SPF Large White prepuberal gilts (mean age 152 days at treatment) were examined for estrous and ovulatory responses after PG 600 treatment. After treatment, 85.2% of the gilts showed standing estrus within 6 days. Whereas the treatment-to-estrus interval and duration were 3.7 and 1.9 days respectively. As ovulation occurred on Day 5 to 6, appropriate timing of artificial insemination would be about 4 days after treatment. Fertility of gilts revealed to be excellent, giving rise to a high percentage of normal embryos, 85.3%. Meanwhile, development and growth of fetuses were mostly normal. Other reproductive performances recorded were: mean litter size 6.8; mean birth weight 1.26 kg; weaning-to-return estrus interval 5 to 8 days. In conclusion, PG 600 was found to be useful in inducing fertile estrus in prepuberal gilts, a result which will be of interest for commercial pig farms.

Animals↗
PubMed1999

Elevated plasma immunoreactive neuropeptide Y concentrations and its increased urinary excretion in patients with advanced diabetic nephropathy.

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide that is abundant in the brain and the peripheral sympathetic nervous system. In the present study we investigated possible changes in plasma immunoreactive (IR)-NPY concentrations and urinary IR-NPY excretion in patients with non-insulin dependent diabetes mellitus (NIDDM) and the relationship to diabetic complications, such as nephropathy and neuropathy. IR-NPY in plasma and urine was measured by radioimmunoassay in 69 patients with NIDDM. Plasma IR-NPY concentrations in patients with advanced nephropathy (creatinine clearance <30 ml/min) (100.5 +/- 10.3 pmol/l, n=9, mean +/- SEM) were higher than in the control subjects (55.0 +/- 6.8 pmol/l, n=15) (P<0.02). Urinary excretion of IR-NPY and fractional excretion of NPY were also increased in the patients with advanced nephropathy. Sephadex G-50 column chromatography of the urine extracts obtained from healthy subjects, diabetic patients with renal failure and non-diabetic patients with renal failure showed an immunoreactive peak eluting in the NPY position. On the other hand, neither plasma nor urinary IR-NPY was high in patients with retinopathy, or in patients with peripheral neuropathy. The present study has, for the first time, shown high plasma IR-NPY concentrations and urinary IR-NPY excretion in NIDDM patients with advanced nephropathy.

Adolescent↗
PubMed1998

Seroprevalence of Taenia solium cysticercosis in pigs in a rural community of Honduras.

Several retrospective studies have shown that human Taenia solium cysticercosis is endemic in Honduras, but very few reports of porcine cysticercosis in rural communities have been published. To determine the local prevalence of this disease in pigs, a serological survey has been undertaken in a rural community, Salamá, in the Department of Olancho in central Honduras. Eighty-five families raising pigs in the community were randomly selected and sera were obtained from pigs older than one month of age. The sera were examined by the enzyme-linked immunoelectrotransfer blot assay (EITB). Of 192 porcine sera, 27.1% (52) were positive by the EITB. Seropositivity did not correlate with age and sex by statistical analysis. With respect to the number and the frequency of recognition of the seven diagnostic glycoprotein bands in the EITB, 67.3% of the positive serum specimens recognized only one band and 80.8% of them recognized GP42-39. Since recognition of GP42-39 has been reported as a characteristic of late infection, these results suggest that most of the seropositive pigs were in the late stage of infection (more than 5-8 weeks postinfection). It seems that pigs in this community may be infected with this parasite soon after the birth and be in a hyperendemic steady state. In view of a high prevalence of antibodies to T. solium in pigs or characteristics of the antigen detected by the EITB, the infection pressure of T. solium appears to be very high in this community. This is probably the case in most of the communities in Honduras.

Animals↗
PubMed1998

The effects of acetazolamide on arterial pressure variability during REM sleep in the rat.

During rapid eye movement (REM) sleep, the arterial pressure (AP) undergoes large fluctuations in the rat, cat, and other mammals, including humans, and it has been suggested that this effect originates in the forebrain. In addition, acetazolamide (ACTZ), a carbonic anhydrase inhibitor, is known to be effective in the treatment of central sleep apnea or epilepsy. The aim of the present study was to analyze the effects of ACTZ on EEG theta rhythm and AP variability during REM sleep in rats. Treatment consisted of intraperitoneal injection of 5 mg of ACTZ in 0.5 mL of saline (n = 6) or 0.5 mL of vehicle alone (n = 6). We then recorded and analyzed the mean AP (MAP) variations during different sleep phases, using a telemetric system. Our results show: 1) Significant decreases in the coefficient of variation of MAP, in the very-low frequency (0.025 - 0.225 Hz) component of the power spectral density of the AP and in theta frequency in the electroencephalogram, were seen in the ACTZ-treated group during REM sleep compared with controls, whereas no significant difference was found between the two groups in non-REM sleep. There was no significant difference in sleep duration, average MAP, and heart rate between the groups. Our data suggest that ACTZ may act as a stabilizing factor preventing AP fluctuations during REM sleep.

Acetazolamide↗
PubMed1998

Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain.

Regional distribution of urocortin-like immunoreactivity (UCN-LI) in the human brain was studied by radioimmunoassay and was compared with that of corticotropin-releasing hormone (CRH). In addition, the expression of UCN mRNA was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method. UCN-LI was detected in every region of brain examined, including hypothalamus, pons, cerebral cortex, and cerebellum. The concentrations of UCN-LI in the human brain were approximately 3 pmol/g wet weight in any brain region, and no marked regional difference was noted. On the other hand, the highest concentrations of CRH-LI were found in the frontal cortex, temporal cortex, and hypothalamus and the lowest in the pons. Reverse phase high-performance liquid chromatography of the UCN-LI in the human brain extract showed two immunoreactive peaks; one peak eluting earlier and one in the position of synthetic human UCN. RT-PCR showed that UCN mRNA was expressed in every region of brain examined. These findings indicated that UCN and UCN mRNA were widely expressed in the human brain.

Adult↗
PubMed1998

Expression of adrenomedullin mRNA in adrenocortical tumors and secretion of adrenomedullin by cultured adrenocortical carcinoma cells.

Immunoreactive-adrenomedullin concentrations and the expression of adrenomedullin mRNA were studied in the tumor tissues of adrenocortical tumors. Northern blot analysis showed the expression of adrenomedullin mRNA in tumor tissues of adrenocortical tumors, including aldosterone-producing adenomas, cortisol-producing adenomas, a non-functioning adenoma and adrenocortical carcinomas, as well as normal parts of adrenal glands and pheochromocytomas. On the other hand, immunoreactive-adrenomedullin was not detected in about 90% cases of adrenocortical tumors (<0.12 pmol/g wet weight (ww)). Immunoreactive-adrenomedullin concentrations ranged from 0.44 to 198.2 pmol/g ww in tumor tissues of pheochromocytomas and were 9.2 +/- 1.2 pmol/g ww (mean +/- SD, n = 4) in normal parts of adrenal glands. Adrenomedullin mRNA was expressed in an adrenocortical adenocarcinoma cell line, SW-13 and immunoreactive-adrenomedullin was detected in the culture medium of SW-13 (48.9 +/- 1.8 fmol/10(5) cells/24h, mean +/- SEM, n = 4). On the other hand, immunoreactive-adrenomedullin was not detectable in the extract of SW-13 cells (<0.09 fmol/10(5) cells), suggesting that adrenomedullin was actively secreted from SW-13 cells without long-term storage. These findings indicate that adrenomedullin is produced and secreted, not only by pheochromocytomas, but also by adrenocortical tumors. Undetectable or low levels of immunoreactive-adrenomedullin in the tumor tissues of adrenocortical tumors may be due to very rapid secretion of this peptide soon after the translation from these tumors.

Adrenal Cortex Neoplasms↗
PubMed1998

Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity.

Although pulmonary infections caused by Pseudomonas aeruginosa can hardly be eradicated in patients with cystic fibrosis (CF, the most common genetic disease among Caucasians), these patients are mainly treated with intravenous and nebulized tobramycin. Long-term treatment with tobramycin, however, may induce ototoxic effects. We assessed the clinical histories and postmortem temporal bones of six patients with CF for signs of this ototoxicity. Four bones showed typical manifestations of ototoxicity induced by aminoglycosides (AGs): loss of hair cells in the lower turns, and degeneration of ganglion cells. Six bones revealed no loss or scattered loss of hair cells, however, degeneration of the spiral ganglion cells was observed. This suggests that degeneration of the spiral ganglion may occur as a primary manifestation in some cases of ototoxicity due to aminoglycosides. Recent reports have shown that trophic factors (neurotrophins and acidic fibroblast growth factor) interacting with hair cells and the spiral ganglion protect the inner ear from damage. It may be that disturbances in supply of such trophic factors caused degeneration of ganglion cells without loss of hair cells in the cases we studied.

Adolescent↗
PubMed1998

Production and secretion of endothelin-1 by cultured choroid plexus carcinoma cells.

Choroid plexus carcinoma is a rare neoplasm derived from the epithelium of the choroid plexus. The production and secretion of endothelin-1 (ET-1) by cultured human choroid plexus carcinoma cells were studied by radioimmunoassay and Northern blot analysis. Immunoreactive (IR)-ET was detected in the culture medium (2.78 +/- 0.12 fmol/10(5) cells/24 h; n = 5; mean +/- SEM) but not in the unconditioned medium. Reverse-phase high-performance liquid chromatography of the extract of the culture medium showed a single peak eluting in the position of ET-1. Treatment with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) or a combination of interferon-gamma (IFN-gamma), TNF-alpha, and IL-1 beta caused significant increases in the IR-ET levels in the culture medium. Northern blot analysis of total RNA showed the expression of ET-1 mRNA in choroid plexus carcinoma cells. The expression levels of ET-1 mRNA were increased by treatment with a combination of IFN-gamma, TNF-alpha, and IL-1 beta. The present study has shown the production and secretion of ET-1 by cultured human choroid plexus carcinoma cells and suggests the possibility that ET-1 formation is related to the pathophysiology of this tumor.

Blotting, Northern↗
PubMed1998

Production and secretion of two vasoactive peptides, endothelin-1 and adrenomedullin, by a colorectal adenocarcinoma cell line, DLD-1.

Production and secretion of endothelin-1 (ET-1) and adrenomedullin (ADM) by a cultured human colorectal adenocarcinoma cell line, DLD-1, were studied by radioimmunoassay and Northern blot analysis. Both immunoreactive (IR)-ET and IR-ADM were detected by radioimmunoassay in the culture medium of DLD-1 (IR-ET 0.86 +/- 0.05 fmol/10(5) cells/ 24 h; IR-ADM 1.20 +/- 0.09 fmol/10(5) cells/24 h; n = 5, mean +/- SEM). An analysis by reverse-phase high-performance liquid chromatography (HPLC) of the IR-ET in the culture medium showed a major immunoreactive peak in the position of ET-1. Reverse-phase HPLC of the IR-ADM in the medium showed three immunoreactive peaks, one of which eluted in the position of human ADM. Northern blot analysis showed the expression of ET-1 mRNA and ADM mRNA in the DLD-1 cells. Treatment with interferon-gamma (1-100 U/ml) for 24 h decreased the IR-ET levels in the culture medium but significantly increased IR-ADM levels. This study has shown the production and secretion of two vasoactive peptides, ET-1 and ADM, by DLD-1 colorectal adenocarcinoma cells. The secretion of IR-ET was decreased by treatment with interferon-gamma. These findings suggest possible pathophysiologic roles for ET-1 and ADM in colon mucosal epithelial cells and tumors derived from them.

Adenocarcinoma↗
PubMed1998

Expression of glycoconjugates in human eustachian tubes with otitis media.

OBJECTIVES: To characterize glycoconjugate expression in normal human eustachian tubes and study the alterations in glycoconjugate expression found in eustachian tubes with otitis media. STUDY DESIGN: Using lectin histochemistry, alterations in glycoconjugates were studied in three normal temporal bones, in four temporal bones with mucoid otitis media (MOM), and in five with serous otitis media (SOM). METHODS: Sections of previously processed temporal bones were decelloidinized, and then incubated with seven biotinylated lectins--WGA, SNA, MAA, BPA, PNA, UEA-1, and LcH--that reflect seven carbohydrate residues of glycoconjugates, respectively: GlcNAc/NeuNAc, NeuNAc alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc, Gal beta(1-3) GalNAc, L-fucose, and alpha-mannose residues. Control sections were incubated with inhibitory carbohydrates or without biotinylated lectins. RESULTS: In the normal temporal bones, five carbohydrate residues in goblet cells and cilia of the eustachian tube demonstrated moderate to strong activity--NeuNAc alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc, GalNAc, Gal beta(1-3)GalNAc, and L-fucose. Two residues demonstrated weak activity--GlcNAc/NeuNAc and alpha-mannose. Temporal bones with MOM revealed increases in sialic acid and alpha-mannose, and a decrease in L-fucose. Residues of carbohydrates in the cilia of bones with SOM were notably decreased, especially for GalNAc, Gal beta(1-3)GalNAc, and NeuNAc alpha(2-6)GalNAc. CONCLUSIONS: Glycoconjugates in the normal human eustachian tube are rich in GalNAc, Gal beta(1-3)GalNAc, L-fucose, and NeuNAc alpha(2-3/2-6) GalNAc, but low in alpha-mannose and sialic acid. Eustachian tubes from cases with SOM or MOM demonstrated alterations in glycoconjugate expression in cilia and goblet cells, which may reflect disorder of the carbohydrate metabolism during otitis media, especially in SOM.

Eustachian Tube↗
PubMed1998

Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting tumors.

OBJECTIVE: To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors. METHODS: Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors. RESULTS: Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 +/- 3.6 pmol/l, mean +/- S.D., n = 12). CONCLUSIONS: These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors.

Adrenocorticotropic Hormone↗