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Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 127 records · Page 7Linked to original sources

Regulation of cyclooxygenase-2 expression in human osteoblastic cells by N-acetylcysteine.

Cyclooxygenase (COX) plays a pivotal role in the inflammatory process of inflammatory arthropathies. Inflammatory cytokines induce COX-2 expression in osteoblasts of inflamed joints, followed by osteoclast activation. The inhibition of COX-2 expression could help prevent prostaglandin E2 secretion, followed by osteoclast activation for bone destruction and resorption. We examined whether the antioxidant N-acetylcysteine (NAC) inhibited COX-2 expression induced in the human osteoblastic cell line MG63 by interleukin-1beta (IL-1beta). According to Western blot and reverse transcription-polymerase chain reaction (RT-PCR) test results, NAC inhibited IL-1beta-induced COX-2 expression in protein and messenger RNA. We also demonstrated immunohistochemically that NAC inhibited NFkappaB nuclear translocation. These results suggested that NAC inhibited both COX-2 expression and NFkappaB nuclear translocation in MG63, which in turn indicated that NAC could inhibit the inflammatory process involved in bone resorption by regulating COX-2 expression at the level of transcription.

Acetylcysteine↗

Vestibular and cochlear toxicity of aminoglycosides--a review.

Recently, there have been many reports describing the efficacy of intratympanic aminoglycoside injection for the treatment of intractable vertigo in patients with Ménière's disease. However, the number of injections and the amount of drug injected varies, with concomitant variation in the side-effect of hearing deterioration. To identify drugs that are more selectively vestibulotoxic, we have reviewed the ototoxicity of aminoglycosides, focusing on differences between vestibulo- and cochleotoxicity. At present, the basis for the different effects of each drug is unknown. The mechanisms of vestibulo- and cochleotoxicity are deemed worthy of further study.

Aminoglycosides↗

Subglottic airway becomes stable with age in the human infant larynx.

Development of the mucosal defence system and its relationship to the pathogenesis of laryngeal diseases was studied by examining the changes in the laryngeal structures at the level of subglottic larynx of 59 human infants who died within 1 year of birth. By making a transverse section at the level of the cricoid cartilage, the area and diameter of each subglottic structure were examined using an image analysis system. The results were analysed, not only by their age at death, but also based on the total development score. The areas of the whole structure, cricoid ring, subglottic mucosa and inner cavity (available area) increased in close correlation with the total development score. In contrast to the increased diameter of the inner cavity, the thickness of the mucosa was almost the same size. These results indicate the stability of the subglottic airway with advancing age in the human infant larynx.

Age Factors↗

Fibroblasts in geriatric vocal fold mucosa.

Fifty fibroblasts in the macula flava (MF) and 50 fibroblasts in the Reinke's space (RS) of geriatric vocal folds were studied by transmission electron microscopy. Five larynges from autopsy cases in the age range 74-83 years were included in the study. The results were compared with those obtained previously from younger adults. The majority of fibroblasts in RS were spindle-shaped and those in MF were stellate. This was the case with younger adults. The nucleus/cytoplasm (N/C) ratio was 0.5-2.0 in most fibroblasts in RS and MF. Again, this was in common with the findings in younger adults. The development of rough endoplasmic reticulum (rER) and Golgi apparatus (GA) in MF was less marked in the geriatric group than in adults. Glycogen particles were observed in 28 fibroblasts in MF. Lipofuscin granules were found in 12 fibroblasts of RS and 9 cells of MF. The findings suggest a decrease in activities and the presence of ageing processes in fibroblasts of geriatric vocal fold mucosa, to which geriatric changes in the vocal ligament can be attributed.

Aged↗

Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid.

Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients.

Adult↗

Comparative histology of the maculae flavae of the vocal folds.

A light and electron microscopic comparative investigation of the maculae flavae of the vocal folds was carried out on excised human and canine adult larynges. The structure and functions of human adult maculae flavae (HMF) were found to differ from those of canine adult maculae flavae (CMF). The maculae flavae were composed of fibroblasts, elastic and collagenous fibers, and ground substance in humans and canines. The density of fibroblasts in HMF was found to exceed that in CMF. Fibroblasts in HMF were stellate with processes or spindle-shaped, and the nucleus-cytoplasm (N/C) ratio was small. Rough endoplasmic reticulum and Golgi apparatus were well developed in the cytoplasm. Fibroblasts in CMF were oval, and the N/C ratio was large. Endoplasmic organs were poorly developed in the cytoplasm. Synthesized elastic and collagenous fibers were more numerous in HMF than CMF, and the density of both in HMF was much greater than that in CMF. Ground substance was more abundant in CMF than HMF. Apparently, CMF did not produce elastic and collagenous fibers in amounts sufficient to develop vocal ligaments. The HMF contributes to the formation of the vocal ligaments and the layered structure of human vocal folds.

Adult↗

Ultrastructure of the vocal process of the arytenoid cartilage.

An investigation of the ultrastructure of the vocal process of the arytenoid cartilage was performed on excised human adult larynges. The results are summarized as follows. 1) The size of the chondrocytes is small and their density is high at the tip of the vocal process. 2) The size of the chondrocytes increases and their density decreases toward the posterior portion of the vocal process. 3) At the tip of the vocal process, the collagenous fibers are thin and run in various directions. 4) The thickness of the collagenous fibers increases and they form thick bundles toward the posterior portion of the vocal process. 5) The elastic fibers are dense at the tip of the vocal process, and their number decreases toward the posterior portion of the vocal process. 6) The elastic fibers, which are slender, branched, and anastomosed to form a loose network, run among the collagenous fibers at the tip of the vocal process. 7) Elaunin fibers are the predominant elastic fibers at the tip of the vocal process. 8) Even in the hyaline cartilage portion of the vocal process, elastic fibers are found. 9) The vocal processes are firm in forming the framework of the glottis and are more pliable toward the tip. 10) The 3-dimensional structure of the gradual changes in stiffness between the vocal fold and the vocal process makes a functional contribution to the roles of the vocal folds and the vocal processes.

Adult↗

A common downstream signaling activity of osteoclast survival factors that prevent nitric oxide-promoted osteoclast apoptosis.

Treatment with NO-releaser NOC18 significantly promoted apoptosis in murine osteoclast-like cells, with a transient increase in caspase-3-like protease activity. In contrast, the apoptosis was protected against by caspase inhibitors, most efficiently with the broadly acting caspase specific inhibitor z-Asp-CH2-DCB, indicating involvement of multiple caspases in progression of the apoptosis. Among osteoclast survival factors examined, calcitonin completely protected against morphologically defined-apoptosis and the increase of caspase-3-like protease activity. The effect of calcitonin was mimicked by treatment of cells with (Bu)2cAMP and forskolin, and abolished by protein kinase-A inhibitor H-89. Independently from the PKA activation, colony stimulating factor-1, interleukin-1beta and the receptor activator of NF-kappaB ligand also protected against the apoptosis but were less effective than calcitonin. All survival factors investigated inhibited conversion of procaspases-3 and -9 to their mature forms in the cells. Thus, downstream antiapoptotic signaling activity from each factor overlapped in inhibition of caspases. However, how this was attained seemed to be different from each other. Typically, only colony stimulating factor-1 up-regulated expression of endogenous caspase inhibitor protein, X-linked inhibitor of apoptosis (XIAP), in the osteoclast-like cells.

Animals↗

Alteration in membrane fluidity of rat liver microsomes and of liposomes by protoporphyrin and its anti-lipidperoxidative effect.

The effect of protoporphyrin (PP) on membrane fluidity was investigated by electron paramagnetic resonance spectroscopy using doxyl stearate spin probes in relation to the anti-lipidperoxidative effect of PP. PP decreased the membrane fluidity in rat liver microsomes at concentrations above 1 mM and also in phosphatidylcholine (PC)-cholesterol (Cho) (100:8, a molar basis) liposomes. The lipid peroxidation stimulated by Fe2+ and L-ascorbic acid in those membrane preparations was attenuated along with the decrease in membrane fluidity by PP. Similar results were also found in Cho-rich PC (100:30 to 100) liposomes having less fluidity. These results suggest that the decrease in the membrane fluidity caused by PP may be involved in the antioxidative action of PP.

Animals↗

Surgical approach to a giant fibrolipoma of the supraglottic larynx.

This paper describes the surgical procedures for a fibrolipoma that first appeared as a giant tumour in the hypopharynx and extended to the cardiac antrum of the oesophagus. At the initial surgery, a pedunculated tumour originating from the left arytenoid of the larynx was found to occupy the cervical as well as thoracic oesophagus and was thus removed through a lateral pharyngectomy. A histological examination revealed fibrolipoma. However there was a recurrence of the tumour in the arytenoid and the patient suffered from dysponea. In addition, a submucosal tumour was also found in the left false vocal fold. At the second surgery, the masses in the arytenoid and false vocal fold were subtotally removed without damaging the mucosa. The mucosa of the arytenoid was sutured to the thyropharyngeal muscle on the same side and the arytenoid swelling disappeared almost completely. The post-operative course has been uneventful for more than two years.

Humans↗

Efflux system for pyridoxine in Schizosaccharomyces pombe.

Pyridoxine-charged Schizosaccharomyces pombe released pyridoxine rapidly at 30 degrees C: very low amounts of three other B6 vitamers were also released. The rate of efflux was temperature-dependent. The initial rate of efflux was dependent on the concentration of pyridoxine in the cells: the rate was almost zero at lower than 0.02 mM and became saturated at higher than 0.2 mM. Na+, sodium azide, and dinitrophenol increased the rate in both the presence and absence of D-glucose. Mg++, thiamine, and menadione inhibited the efflux. The intracellular concentration of ATP did not significantly affect the efflux rate. The system may be dependent on a membrane potential of the yeast cells. It was found that the fission yeast cells have a gate or carrier system for efflux of pyridoxine, which was distinct from that in Saccharomyces cerevisiae.

2,4-Dinitrophenol↗

Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression.

The mechanism controlling the disappearance of osteoclasts from bone surfaces after bone resorption in vivo is largely unknown. This is because there is no suitable experimental system to trace the final fate of osteoclasts. Here, we used an experimental model of tooth movement in rats to show that preexisting osteoclasts disappeared from the bone surface through apoptosis during a force-induced rapid shift from bone resorption to formation. On the distal alveolar bone surface of the maxillary molar in growing rats, many mature osteoclasts were present. When light tensional force was applied to the bone surface through an orthodontic appliance, these preexisting osteoclasts gradually disappeared. One day after the application of force, about 24% of the osteoclasts exhibited apoptotic morphology and the proportion of apoptotic cells was increased to 41% by day 2, then decreased afterward. These changes were undetectable on the control distal alveolar bone surface, which is free from tensional force. As shown by in situ hybridization, a marked increase in transforming growth factor beta1 (TGF-beta1) and osteoprotegerin (OPG) messenger RNA (mRNA) was observed in the stretched cells on the tensioned distal bone surface, simultaneously with the loss of osteoclasts. Both of these factors are known to have a negative effect on osteoclast recruitment and survival. As early as 2 days after force application, some of these stretched cells were identified as cuboidal osteoblasts showing intense signals for both factors. Our data suggest there may be a sequential link in tensional force applied on the bone lining cells, up-regulation of TGF-beta1/OPG, and disappearance of osteoclasts.

Acid Phosphatase↗

Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts.

Production of matrix metalloproteinases (MMPs) influences bone resorption. We investigated the role of bisphosphonates, potent inhibitors of bone resorption, on the production of MMP-2 from human osteoblasts. Bisphosphonates alone did not influence the amount of MMP-2 produced by human osteoblasts. However, in the presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP-2 in osteoblasts-conditioned media. Furthermore, bisphosphonates treatment induced degradation of MMP-2 in the presence of plasmin. Our results indicated that bisphosphonate, a divalent cation chelator, negatively regulated the longevity of MMP-2 in soluble phase plasmin-containing environment. These findings suggest that bisphosphonates inhibit bone resorption by abrogating MMP-2 protection induced by plasmin-mediated degradation.

Antibodies, Monoclonal↗

Cell size and oxidative enzyme activity of different types of fibers in different regions of the rat plantaris and tibialis anterior muscles.

The cross-sectional areas and succinate dehydrogenase activities of different types of fibers in different regions of the plantaris and tibialis anterior muscles in 10-week-old male rats were determined using quantitative histochemistry. The muscle fibers were classified as type I, type IIA, or type IIB according to their adenosine triphosphatase activities. There were no regional differences in either the mean cross-sectional area or the mean succinate dehydrogenase activity of type IIA fibers in both muscles. In contrast, type IIB fibers in the deep region of both muscles had smaller cross-sectional areas and higher succinate dehydrogenase activities than those in the superficial and middle regions. These data suggest the presence of regional differences in the cross-sectional area and succinate dehydrogenase activity of type IIB fibers in the muscle.

Adenosine Triphosphatases↗

The effects of age on hearing and middle ear function.

Audiometric test results from 933 community dwelling males and females were presented to obtain the norm for each generation after middle age. Three aspects were adopted in this analysis; the cross-sectional aging transition of pure tone thresholds, the comparison in the self-perceived hearing difficulty among generations and the evaluation of middle ear function using multifrequency tympanometry. Subjects were divided into four age groups; 40s, 50s, 60s and 70s. There were statistically significant differences in pure tone thresholds between almost any two age groups at each frequency in both genders, especially at higher frequencies. The pure tone thresholds were also discussed in regard to gender difference and laterality. A contradiction between self-perceived hearing difficulty and auditory accuracy was observed in the elderly generation. Analysis of tympanometric measurements was performed on static admittance at 226 Hz, tympanometric peak pressure at 226 Hz and resonance frequency of the middle ear. These variables did not show any systematic aging change. However, it was considered they represented the reference values of each generation.

Acoustic Impedance Tests↗

[Laser arytenoidectomy for bilateral vocal fold paralysis].

Laser arytenoidectomy can be performed via an intralaryngeal approach which preserves airway and voice quality without aspiration. Laser arytenoidectomy is minimally invasive surgery, and a useful surgical procedure for bilateral vocal fold paralysis. CO2 laser arytenoidectomy was performed for 12 cases of bilateral vocal fold paralysis. Recommended methods for this surgical procedure are: 1) Submucous laser arytenoidectomy should be done. 2) To widen the posterior glottis, not only the arytenoid cartilage but also the posterior part of the thyroarytenoid muscle should be removed. 3) Membranous portions of the vocal folds should not be vaporized. 4) The wound should be covered with mucosa with fibrin glue.

Aged↗