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Biomedical subjects

T Uno

Publications and source records attributed to T Uno.

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

Numerical densities of myonuclei and satellite cells in muscle fiber types in the aging human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy.

OBJECTIVE: This study determines the role of changes in numerical densities of myonuclei and satellite cells in age-related remodeling of the thyroarytenoid muscle (TA). DESIGN: Changes in numerical densities (N(V)) and ratios (N(N)) of myonuclei and satellite cells were estimated for the entire TA by use of stereological techniques. RESULTS: There was no age-related change or difference between fiber types for N(V myonucleus, fiber), but N(V myonucleus, fiber) increased with decreasing fiber diameter. There was a trend toward a decrease in N(V satellite cell, fiber) and a decrease in N(N satellite cell, myonucleus). N(V satellite cell, fiber) was higher for type 1 than for type 2 fibers, and type 1 satellite cells increased disproportionately with increasing total satellite cell numerical density. CONCLUSION: Decreased satellite cell proliferation may contribute to age-related fiber loss and atrophy in the TA. SIGNIFICANCE: Therapeutic techniques based on activation of satellite cells may block age-related fiber loss and atrophy in the TA.

Adult↗
PubMed2000

Induction of nitric oxide synthase activity in nucleus ambiguus motoneurons after injury to the rat recurrent laryngeal nerve.

Recent studies have implicated nitric oxide (NO) in neuronal degeneration and plasticity in the motor nervous system. In the present study, we investigated the induction of nitric oxide synthase (NOS) in the motoneurons in the nucleus ambiguus (NA) after injury to the rat recurrent laryngeal nerve (RLN) using nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPH-d) histochemistry. NADPH-d reactivity was clearly induced in motoneurons in the ipsilateral NA after transection or avulsion of the RLN, compared with control animals. This finding suggests that NO may play an important role in the pathogenesis of RLN paralysis. Another interesting finding in the present study was the induction of NADPH-d reactivity in nerve terminals of the NA after RLN injury. This finding suggests that RLN injury has some effect on nitrergic input to the NA and a direct effect on the motoneurons.

Animals↗
PubMed2000

Inhibition of topoisomerases by fatty acids.

The inhibitory effects of various fatty acids on topoisomerases were examined, and their structure activity relationships and mechanism of action were studied. Saturated fatty acids (C6:0 to C22:0) did not inhibit topoisomerase I, but cis-unsaturated fatty acids (C16:1 to C22:1) with one double bond showed strong inhibition of the enzyme. The inhibitory potency depended on the carbon chain length and the position of the double bond in the fatty acid molecule. The trans-isomer, methyl ester and hydroxyl derivative of oleic acid had no or little inhibitory effect on topoisomerases I and II. Among the compounds studied petroselinic acid and vaccenic acid (C18:1) with a cis-double bond were the potent inhibitors. Petroselinic acid was a topoisomerase inhibitor of the cleavable complex-nonforming type and acted directly on the enzyme molecule in a noncompetitive manner without DNA intercalation.

Animals↗
PubMed2000

Involvement of carbon monoxide in the innervation of the canine cervical esophagus and trachea.

We investigated the involvement of carbon monoxide (CO) in the innervation of the canine cervical esophagus and trachea by means of immunohistochemistry using an antiserum against heme oxygenase-2 (HO-2). We detected HO-2-immunoreactive nerve fibers around the blood vessels and submucosal glands of the esophagus and trachea. We found HO-2-immunoreactive neurons in ganglia in the trachea and in the myenteric plexus of the esophagus. These results suggest that CO is involved as a neurotransmitter in the innervation of the canine esophagus and trachea.

Animals↗
PubMed2000

A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is a major substrate of the insulin receptor and acts as a docking protein for Src homology 2 domain containing signaling molecules that mediate many of the pleiotropic actions of insulin. Insulin stimulation elicits serine/threonine phosphorylation of IRS-1, which produces a mobility shift on SDS-PAGE, followed by degradation of IRS-1 after prolonged stimulation. We investigated the molecular mechanisms and the functional consequences of these phenomena in 3T3-L1 adipocytes. PI 3-kinase inhibitors or rapamycin, but not the MEK inhibitor, blocked both the insulin-induced electrophoretic mobility shift and degradation of IRS-1. Adenovirus-mediated expression of a membrane-targeted form of the p110 subunit of phosphatidylinositol (PI) 3-kinase (p110CAAX) induced a mobility shift and degradation of IRS-1, both of which were inhibited by rapamycin. Lactacystin, a specific proteasome inhibitor, inhibited insulin-induced degradation of IRS-1 without any effect on its electrophoretic mobility. Inhibition of the mobility shift did not significantly affect tyrosine phosphorylation of IRS-1 or downstream insulin signaling. In contrast, blockade of IRS-1 degradation resulted in sustained activation of Akt, p70 S6 kinase, and mitogen-activated protein (MAP) kinase during prolonged insulin treatment. These results indicate that insulin-induced serine/threonine phosphorylation and degradation of IRS-1 are mediated by a rapamycin-sensitive pathway, which is downstream of PI 3-kinase and independent of ras/MAP kinase. The pathway leads to degradation of IRS-1 by the proteasome, which plays a major role in down-regulation of certain insulin actions during prolonged stimulation.

3T3 Cells↗
PubMed2000

[Chronic granulomatous disease accompanying a deep cervical abscess in a young child].

We report the diagnosis and otorhinological treatment of a rare case of cervical abscess in association with chronic granulomatous disease (CGD). A 19-month-old boy was admitted to our hospital's Department of Pediatrics with fever and a swollen neck. Antibiotic treatment (FMOX PIPC, and PAPM) was ineffective, so the patient was referred to our department for otorhinological treatment. A deep cervical abscess was drained using paracentesis in the Outpatient Department, but the condition did not improve. Surgery to drain the cavity was therefore performed. The wound was irrigated with oxydol, and the surgery was a success. Immunodeficiency was suspected, because of the antibiotic treatment's failure. Further examination clarified that the disease was CGD, but this diagnosis was difficult to establish. The result of the NBT test was 120%. However, some examination demonstrated that active oxygen production was impaired. The production of cytochrome b in this patient was confirmed using flow cytometric analysis. Both parents were confirmed to be carriers upon examination. The patient was therefore diagnosed as having CGD as a result of an autosomal recessive inheritance.

Abscess↗
PubMed2000

Stereospecific polymerization of alpha-(menthoxymethyl)acrylate

Novel alpha-(alkoxymethyl)acrylates bearing a chiral substituent, racemic and optically active benzyl alpha-(menthoxymethyl)acrylates ((+)- and (-)-BMnMA), were synthesized and polymerized by radical and anionic methods. The effects of the chiral substituent on the stereoregularity and chiroptical property of the obtained polymers were investigated. 13CNMR spectra of the polymers obtained by anionic polymerization of the racemic monomer showed sharper peaks than that of the radically obtained polymers, indicating that the former polymers possessed higher stereoregularity than the radically obtained polymers. The polymers prepared from optically pure (-)-monomer with anionic initiators had low solubility in common organic solvents. However, the THF-soluble parts were highly isotactic, and exhibited lower specific rotation ([alpha]25(365) = -92 degrees) than those of the monomer ([alpha]25(365) = -226 degrees) and the radically obtained polymer ([alpha]25(365) = -201 degrees). The circular dichroism (CD) spectra of the copolymers prepared from a (+)- and (-)-monomer mixture with various optical purity suggested that the highly isotactic (-)-polymer may possess a chiral helical conformation.

Journal Article↗
PubMed1999

Disinhibition of lower midbrain neurons enhances non-shivering thermogenesis in anesthetized rats.

UNLABELLED: The hypothesis that the lower midbrain, specifically in and around the retrorubral field (RRF) and/or rubrospinal tract (rs), contains a tonic inhibitory mechanism on non-shivering thermogenesis (NST) was examined in urethane-anesthetized rats. It has been proposed that removal of the tonic inhibitory mechanism in the lower midbrain causes body temperature increase through disinhibition-induced activation of the central sympathetic nervous system. The present experiments were carried out to examine whether and where the proposed midbrain region contains cell bodies that tonically inhibit the NST, and if so, whether they receive any influence from the hypothalamus. Male Wistar rats were anesthetized with urethane (1. 0-1.2 g/kg, i.p.), and various agents were microinjected into the RRF and rs areas of one side before and after knife-cut in the other side of the lower midbrain or isolation of the hypothalamus from the midbrain. Changes in interscapular brown adipose tissue (IBAT), rectum, and tail skin temperatures were monitored. RESULTS: (1) unilateral midbrain procaine increased IBAT and rectal temperatures only after un-injected side of the midbrain had been pre-transected. (2) Effective midbrain sites for procaine to increase IBAT and rectal temperatures was laterally extended. (3) Tetrodotoxin microinjected into the midbrain site where procaine increased IBAT and rectal temperatures also raised both temperatures. (4) l-glutamate decreased IBAT and rectal temperatures when microinjected into one of the most inner midbrain area of procaine-sensitive sites without affecting tail skin temperature. (5) Isolation of the hypothalamus from the lower midbrain did not affect midbrain procaine-induced IBAT and rectal temperature increases. These results suggest that neurons that tonically inhibit the NST are located in the area close to the midline adjacent to the RRF and rs, and that the integrity of the neurons to tonically inhibit the NST is not affected by disconnecting the hypothalamus from the midbrain.

Anesthesia↗
PubMed1999

Late retinal complications of radiation therapy for nasal and paranasal malignancies: relationship between irradiated-dose area and severity.

PURPOSE: Radiation-induced cataract, once a notorious ocular complication of radiation therapy, is no longer considered a severe complication, because visual acuity can be restored by surgical treatment without significant complications. Late retinal complications of retinopathy and glaucoma, for which there is no effective method of treatment, have become serious complications of radiotherapy of the head and neck. We retrospectively investigated the risk of late retinal complications of radiotherapy for nasal and paranasal malignancies according to the radiation dose and area of the retina irradiated. METHODS AND MATERIALS: Between October 1982 and May 1996, 43 eyes of 25 patients were exposed to fractionated external-beam irradiation for treatment of advanced nasal and paranasal cancer. None of the patients had tumor invasion into the eyes. The patients were followed ophthalmologically for a minimum of 2 years (range 2.0-11, mean 4.5, median 3.3). The radiation dose and area of the retina irradiated were estimated from the dose distribution figures calculated using the portal films and CT scan. RESULTS: Major late adverse effects of radiotherapy were observed in the retina in 9 of 43 eyes (in 8/25 patients). Radiation retinopathy was observed in 7 eyes, and the cumulative incidence was 25%. The median interval before the onset of symptoms attributable to retinopathy was 32 months (range 16-60). Neovascular glaucoma developed in 3 of the 43 eyes, with a cumulative incidence of 7%. The median period to the onset of symptoms attributable to glaucoma was 22 months (range 16-26). Obstruction of the central retinal artery was observed in 1 eye. The irradiation doses to the retinas that developed late complications ranged between 54-75 Gy (mean 61, median 61). No patients who received less than 50 Gy developed retinal complications. The retina in 21 eyes was exposed to a dose of 50 Gy or more. In 13 of the 21 eyes, 60% or more of the retina was irradiated, and 8 of the eyes (62%) in this group (> or = 50 Gy, > or = 60%) developed severe retinal complications, whereas such complications only developed in 1 of the 8 eyes (13%) in the other group (> or = 50 Gy, > or = 60%). The results suggest that the radiation dose and area irradiated are the most important factors in the development of severe complications. CONCLUSION: Radiation-induced retinopathy and glaucoma are more serious late complications than cataracts, which are easily treated with surgery. We investigated the risk of late retinal complications of radiotherapy, and our findings suggested that the radiation dose and area irradiated are the most important factors in the development of severe complications. We recommend that the radiation dose and area of the retina irradiated be minimized in patients at risk of eye complications, and the patients should be closely followed by periodic ophthalmologic testing after treatment.

Adult↗
PubMed1999

Pharmacokinetic advantages of a newly developed tacrolimus oil-in-water-type emulsion via the enteral route.

We developed an oleic acid oil-in-water (o/w)-type emulsion of a new tacrolimus formulation that presented an improvement in the delivery of the drug for oral absorption. This investigation was undertaken to assess a sustained release drug delivery system and selective drug transfer into the lymphatic system. The whole blood concentration profiles after oral administration at a dose of 2 mg/kg and bone marrow, spleen, liver, lung, small intestine, kidney, brain, and whole blood distribution after oral administration at a dose of 1 mg/kg of o/w emulsion formulation of tacrolimus (O/W group) were compared with those of commercially available formulation (T group) in the rat. The mean diameter of the o/w emulsion droplets was 0.47 microm immediately after preparation. The tacrolimus entrapping efficiency of o/w emulsion was 71.3+/-5.0% in 12 h and did not change for 2 d. The area under the whole blood concentration-time curve (AUC) in the O/W group was significantly higher (P<0.01) than that in the T group. In contrast, the values of constant elimination rate and total clearance in the O/W group were significantly lower (P<0.01) than those in the T group, with a comparative bioavailability of 115.9%. The tissue concentration of tacrolimus in the O/W group was significantly higher levels in the bone marrow, spleen, liver, lung, and small intestine, and significantly lower in the brain and kidney, relative to the T group. The o/w emulsion of tacrolimus may be an improved dosage form via the enteral route.

Administration, Oral↗
PubMed1999

Age-related changes in muscle fiber types in the human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy.

A decline in motor performance contributes to laryngeal dysfunction in the elderly, but the pathogenetic mechanisms are unknown. Quantitative 3-dimensional, age-related changes in the muscle fiber content of the human thyroarytenoid muscle were estimated from geometric probability (stereology) by use of a technique that provided a statistically unbiased sample of all possible section orientations and locations in the entire muscle volume. There was a preferential 27% age-related loss in the length density (L(V type, muscle)) of type 1 (slow) fibers in contrast to the selective type 2 (fast) fiber loss typical of aging limb muscles. In type 2 fibers there was no significant loss in the L(V), but there was an age-related decrease (P < 0.05) in the surface density (S(V type, muscle)) and an increase (P < 0.05) in the atrophy factor, an index of the content of very small, atrophic fibers. There was also an age-related increase in the length fraction (L(L type, all fibers)) of muscle fibers that coexpress both fast and slow myosin heavy-chain isoforms (P < 0.05). These findings demonstrate a type-specific fiber loss and atrophy that differs from that in aging limb muscles and an age-related increase in motor unit remodeling.

Adult↗
PubMed1999

Protein interactions of Gts1p of Saccharomyces cerevisiae throughout a region similar to a cytoplasmic portion of some ATP-binding cassette transporters.

The GTS1 gene product, Gts1p, has pleiotropic effects on the timing of budding, cell size, heat tolerance, sporulation and the lifespan of the yeast Saccharomyces cerevisiae. In this study, we found (using the yeast two-hybrid system) that Gts1p forms homodimers throughout the 18-amino acid region 296-313 which has considerable similarity to a region downstream of the Walker nucleotide-binding motif A of some ATP-binding cassette (ABC) transporters. The region contains two aspartic acid residues at 301 and 310 preceded by hydrophobic amino acid residues, and Gts1p with an Asp310 to Ala substitution showed considerably reduced homodimerization, as shown by the two-hybrid assay. Overexpression of the point-mutated Gts1p did not efficiently induce the Gts1p-related phenotypes described above, suggesting that the homodimerization of Gts1p is required for it to function in vivo. The C-terminal cytoplasmic domain of the yeast ABC transporters Mdl1p (multidrug resistance-like transporter) and Ycf1p (yeast cadmium factor or glutathione S-conjugate pump) bound to Gts1p in the two-hybrid system, and the heterodimerization activity of the Gts1p with the Asp301 to Ala substitution was more affected than the Gts1p with the Asp310 to Ala substitution. Overexpression of GTS1 considerably reduced, and disruption of GTS1 slightly decreased, cellular resistance to cycloheximide, cadmium, cisplatin and 1-chloro-2,4-dinitrophenol, which (except for cycloheximide) are all substrates of Ycf1p. These results suggest that Gts1p interacts with some ABC transporters through the binding site overlapping that of homodimerization and modulates their activity.

ATP-Binding Cassette Transporters↗
PubMed1999

Differential effects of palmitate on glucose uptake in rat-1 fibroblasts and 3T3-L1 adipocytes.

Non-esterified fatty acids are thought to be one of the causes for insulin resistance. However, the molecular mechanism of fatty acid-induced insulin resistance is not clearly known. In this study, we first examined the effect of palmitate on insulin signaling in 3T3-L1 adipocytes. We found that 1h treatment with 1 mmol/l palmitate had no effect on insulin binding, tyrosine phosphorylation of insulin receptors, 185 kDa proteins and Shc, and PI3 kinase activity in 3T3-L1 adipocytes. Then, the effects of palmitate on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocytes were compared with those in poorly differentiated 3T3-L1 cells and in HIRc-B cells. Palmitate treatment had no effect on MAP kinase activity in fully differentiated 3T3-L1 adipocytes, while it inhibited MAP kinase in poorly differentiated 3T3-L1 cells and HIRc-B cells. Glucose transport in 3T3-L1 adipocytes treated with palmitate for 1 h, 4 h and 16 h was higher than that in control cells, but palmitate treatment caused a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B cells. Palmitate treatment did not significantly affect basal and insulin-stimulated GLUT4 translocation. When the cells were treated with PD98059, a specific MEK inhibitor, insulin-stimulated glucose uptake was not affected in 3T3-L1 adipocytes, while it was almost completely inhibited in HIRc-B cells. These results suggest the primary effect of palmitate on adipocytes may not involve insulin resistance of adipocytes themselves.

3T3 Cells↗
PubMed1999

Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro.

BACKGROUND: Chemotherapeutic management of breast cancers is a difficult task as they show significant differences in chemosensitivity. The present study was undertaken to determine the usefulness of the apoptosis-related factors as indicators of tumor sensitivity to 5'-deoxyfluorouridine (5'-DFUR) in breast cancers. METHODS: (1) Forty-six breast cancer patients were randomly assigned to a group in which oral 5'-DFUR (1200 mg/day) was administered for more than 5 days before operation (24 patients) and a control group who received no preoperative chemotherapy (22 patients). Surgical specimens were examined for the frequency of apoptotic cells [apoptotic index (AI)] by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and for the expression of p53, BCL-2 and BAX by immunohistochemical staining. (2) Normal human diploid fetal lung fibroblast, IMR90 and SV40 transformed IMR90 were exposed to 5-FU. Apoptotic cells were detected by flow cytometry and BCL-2 and BAX mRNAs by real-time quantitative RT-PCR analysis. RESULTS: (1) No significant difference in the AIs or in BCL-2 and BAX scores was observed between the 5'-DFUR-treated and control groups. However, in the p53 negative subgroup (n = 36), AI and BAX scores were higher and BCL-2 scores lower in the 5'-DFUR group than in the control group (P = 0.006, 0.008 and 0.050, respectively). (2) The sensitivity of IMR90 was significantly decreased by SV40 transformation and the 5-FU-induced cytotoxicity was mainly due to induction of apoptosis. The BCL-2/BAX mRNA ratio was decreased in response to 5-FU in IMR90. These results correlated with our clinical data. CONCLUSIONS: Preoperative treatment with 5'-DFUR induced apoptosis and changes in BCL-2 and BAX expression in p53 negative breast cancers. p53 status, AI and the BCL-2/BAX ratio may be useful information for the choice of postoperative chemotherapy for breast cancer.

Antineoplastic Agents↗
PubMed1999

Neurotransmitters and neuromodulators involved in laryngeal innervation.

The distribution and role of neurotransmitters and neuromodulators in laryngeal innervation are reviewed, and our recent findings regarding the nitrergic innervation of the larynx are demonstrated for the better understanding of the complexity of the laryngeal innervation system. Noradrenergic innervation of the larynx was studied with fluorescence histochemistry and electron microscopy after application of 5-hydroxydopamine. These studies confirmed the existence of noradrenergic innervation for the submucosal glands and blood vessels, and the origin and course of noradrenergic nerve fibers contained in the laryngeal nerves and their destinations in the larynx. Cholinergic innervation of the larynx has not been clarified in detail. Many kinds of neuropeptides have been demonstrated to be involved in laryngeal innervation. Vasoactive intestinal polypeptide originating from intralaryngeal ganglionic neurons participates in laryngeal vasodilation and reduction of laryngeal seromucous secretion. Neuropeptide Y nerve fibers are few in the larynx, and most originate from the superior cervical ganglion. They are distributed around the large or medium-sized blood vessels, especially arteries. They are also associated with excretory structures. Substance P was the first neuropeptide found to be a sensory neurotransmitter in the laryngeal afferent system. It is also involved in regulation of laryngeal blood flow and secretion. Calcitonin gene-related peptide is associated with the sensory, autonomic, and motor innervation of the larynx. The majority of enkephalin nerve fibers are located close to excretory structures, although no information on the physiological significance of enkephalin is available. In addition to the above neuropeptides, the peptides histidine isoleucine, histidine methionine, and helospectin have been shown to exist in the larynx. The nitrergic innervation of the larynx has been recently studied with NADPH-diaphorase histochemistry and immunohistochemistry using antiserum against nitric oxide synthase. Nitric oxide originates from the neurons in the intralaryngeal ganglia and is believed to modulate blood flow and secretion of the larynx. It controls the laryngeal exocrine secretion in cooperation with intrinsic vasoactive intestinal polypeptide and/or extrinsic calcitonin gene-related peptide. Nitric oxide from the nodose ganglion may modulate nociception of the larynx. The existence of nitrergic neurons located in the intrinsic laryngeal muscles has been demonstrated. Many of them are bipolar or pseudounipolar, so they might be sensory in nature. The effect of injury of the recurrent laryngeal nerve on the induction of nitric oxide synthase in the laryngeal motoneurons is also discussed.

Acetylcholine↗
PubMed1999

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

This study was performed to determine the effect of radiotherapy (RT) combined with transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) on large HCC. Between 1988 and 1996, 102 patients with unresectable, biopsy proven HCC underwent uniform pretreatment assessment followed by TAE and PEI. Of the 102 patients, 68 (67%) had more than 2 lesions in the liver, and the largest tumor sizes in each patient ranged from 3 to 8 cm in diameter. Immediately after TAE and PEI, external beam RT (36 to 70 Gy) was administered to the largest tumors only in 44 patients. The cause-specific 5-year survival rate for all patients was 39.9%. The 3-year survival rate of the RT group was better than that of the no RT group (81.1% vs. 54.6%). The cumulative local control rates of the largest treated tumors were 53.2% in the RT group and 32.7% in the no RT, respectively (p=0.006). When the survival rate was compared between patients with and without local control in the RT group, that of patients with local control was significantly better than that with local recurrences (p=0.048). No deaths or major treatment related complications occurred. RT combined with TAE and PEI did not clearly show improvement of the survival, however, it effectively controlled large HCC, and demonstrated minimal toxicity. This treatment may represent therapeutic option for some patients with unresectable large HCC.

Aged↗
PubMed1999

Laparoscopic surgery for gonadal dysgenesis in children.

Three pediatric phenotypic females presented with gonadal dysgenesis. Their gonads were removed laparoscopically. These phenotypically normal females, who do not have any intersex problems or ambiguous genitalia, represent a unique group of patients having a Y chromosome or a fragment of it in their genetic constitutions. We performed laparoscopic adnexectomy with Endoloop ligatures or an ultrasonically activated scalpel. No significant complication occurred in any of the cases. Pathologic examination revealed gonadoblastoma in one of the gonads of one patient. We propose that laparoscopic surgery is a safe and minimally invasive procedure for prophylactic gonadectomy to prevent neoplasia, even when performed on pediatric patients.

Child↗