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Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 73 records · Page 4Linked to original sources
PubMed2001

Smoking and drinking habits as risk factors for hearing loss in the elderly: epidemiological study of subjects undergoing routine health checks in Aichi, Japan.

In order to determine the risk factors for hearing loss in the elderly, a total of 496 subjects with bilateral hearing loss and 2807 age-matched persons without hearing disturbance were recruited from the participants in an automated multiphasic health screening examination, and their lifestyle and medical data were analysed. Current smokers showed a significantly increased risk of hearing loss compared with non-smokers (odds ratio after adjustment for sex, age, and potential confounders=2.10 (1.53-2.89)), while heavy drinkers did not show an increased risk compared to non-drinkers. Our findings might provide some clues for the primary prevention of age-related hearing loss.

Aged↗
PubMed2001

Fas/FasL mediated apoptosis of thyrocytes in Graves' disease.

We examined in the present study the possible involvement of Fas and its ligand (FasL) in the process of Graves' disease. Immunohistochemical analysis showed that few normal thyrocytes expressed Fas but many thyrocytes in Graves' disease expressed this molecule. The percentage of FasL-positive thyrocytes in Graves' thyroids was, however, less than in normal thyroids. Several apoptotic thyrocytes and infiltrating mononuclear cells (MNCs) were detected scattered throughout Graves' thyroid tissues and abundant proliferating cell nuclear antigen (PCNA)-positive thyrocytes were present. Apoptotic cells, as well as PCNA-positive cells, were scarcely detectable in normal thyroid glands, however. In vitro treatment of thyrocytes by IL-1beta a cytokine found to be expressed in Graves' thyroid glands, increased Fas but reduced FasL expression. IL-1beta-stimulated thyrocytes became sensitive to apoptosis by anti-Fas IgM monoclonal antibody (mAb). Activated T cells, which strongly expressed FasL, showed cytotoxic activity toward IL-1beta-stimulated thyrocytes but not toward unstimulated thyrocytes. This cytotoxic activity involved the Fas/FasL pathway. Importantly, unstimulated thyrocytes could kill activated, but not resting, T cells. IL-1beta-stimulated thyrocytes, with down-regulated FasL expression, could not efficiently kill activated T cells. The cytotoxic activity of unstimulated thyrocytes toward activated T cells was inhibited by anti-FasL mAb. Interestingly, unstimulated thyrocytes induced apoptosis in IL-1beta-stimulated thyrocytes but not in unstimulated thyrocytes. These interactions were also blocked by anti-FasL mAb. Our results suggest that the apoptotic cell death of both thyrocytes and infiltrating MNCs found in Graves' thyroid glands is regulated by IL-1beta through Fas/FasL interactions.

Apoptosis↗
PubMed2001

Novel immunosuppressive effect of FK506 by augmentation of T cell apoptosis.

We have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.

Animals↗
PubMed2001

Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis.

AIM AND METHODS: The effects of ursodeoxycholic acid (UDCA, 600 mg/day) on liver function test values, and serum and urinary bile acids levels in hepatitis C virus-related chronic hepatitis (CH, n = 39) and liver cirrhosis (LC, n = 25), and in primary biliary cirrhosis (PBC, n = 25) were compared. RESULTS: The percentages of improvement in alanine transaminase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) in CH were almost the same in LC. The rates of improvement in ALT in PBC were negatively correlated with histological stages in the liver. Total serum bile acid levels in LC rose to the same extent as in CH, but the increases in PBC were significantly smaller at stages 3-4 than stages 1-2. The urinary levels of hydroxylated metabolites of UDCA only slightly increased in LC, but they increased significantly at PBC stages 3-4. CONCLUSIONS: The efficacy of UDCA was preserved in LC, but diminished at PBC stages 3-4. The poor enrichment of UDCA in the bile acid pool and extensive biotransformation of UDCA may cause the limited efficacy of UDCA in the cirrhotic stage of PBC.

Adult↗
PubMed2001

Localized amyloidosis and extramedullary plasmacytoma involving the larynx of a child.

Extramedullary plasmacytoma of the larynx and localized laryngeal amyloidosis are 2 uncommon disease entities that are exceedingly rare in children. We report a case of a 12-year-old girl presenting with progressive hoarseness who was subsequently found to have extramedullary plasmacytoma coexisting with localized amyloidosis involving the larynx. Results from the immunohistochemical and molecular studies showed that the tumor cells of the plasmacytoma were monoclonal (kappa-restricted), strongly supporting their neoplastic nature. The biochemical nature of the amyloid deposits was also shown to be of kappa immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx of this patient. There was no other evidence of malignancy or amyloidosis elsewhere. On a follow-up period of 4 years, this patient was well and asymptomatic. We believe that this represents the first case in the literature showing the coexistence of extramedullary plasmacytoma and localized amyloidosis of the larynx in children. This case also supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.

Amyloidosis↗
PubMed2001

New disease-modifying antirheumatic drug 2 acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) selectively augments activation-induced T cell death.

We examined in this study whether the newly developed disease-modifying antirheumatic drug (DMARD) 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) augments activation-induced T cell death. Peripheral blood (PB) T cells, isolated from healthy donors, were activated by incubation with interleukin-2 (IL-2) followed by further culture with 12-0-tetradecanoyl phorbol 13-acetate (PMA) and ionomycin in the presence or absence of KE-298. The apoptosis of activated T cells was examined by flow cytometric determination of hypodiploid DNA. Fas expression and caspase-3 activity in activated T cells were also examined by flow cytometry, and expression of Fas ligand (FasL), Bcl-2-related proteins, and X chromosome-linked inhibitor of apoptosis protein (XIAP) was determined by Western blot analysis. Apoptosis was not obvious in resting T cells and was not augmented by KE-298. In contrast, apoptosis was clearly detected in activated T cells (activation-induced T cell death) with the increment of caspase-3 activity, and incubation of these cells with KE-298 further enhanced apoptosis. Treatment of activated T cells with KE-298 increased Bax expression but decreased XIAP expression without affecting the expression of Fas/FasL. Thus caspase-3 activity in activated T cells appeared to be increased by KE-298. Our results suggest that the newly developed DMARD, KE-298, selectively augmented activation-induced T cell death. This finding may contribute to the therapeutic efficacy of KE-298 in rheumatoid arthritis (RA) patients and provide new insight into the pharmacologic action of DMARDs.

Antirheumatic Agents↗
PubMed2001

Perilymphatic concentration of gentamicin administered intratympanically in guinea pigs.

Intratympanic gentamicin therapy has recently become popular for Meniere's disease, although the administration protocol remains controversial. To date, few studies have been conducted regarding the pharmacokinetics of drugs administered intratympanically. We measured gentamicin concentration in the perilymph close to the round window membrane using a microdialysis technique. A bolus of 0.5 mg gentamicin was put on the round window membrane or a clinically used solution of 5 mg gentamicin was placed in the tympanic bulla of guinea pigs. After 56 +/- 21 min of bolus administration, gentamicin concentration reached a maximum level of 2900 +/- 1200 microg/ml and then decreased, with a half-life of 117 +/- 47 min, characteristic of the kinetics expected with a one-compartment model. With solution administration, the maximum concentration did not differ, but the time to the maximum concentration and the half-life in the perilymph were longer, compared with the results of bolus administration. Our results suggest that even solution administration of gentamicin, which is simple and repeatable, provides a sufficient, stable and continuous supply to the perilymph.

Animals↗
PubMed2001

Japanese and Western diet and risk of idiopathic sudden deafness: a case-control study using pooled controls.

BACKGROUND: One of the proposed aetiological mechanisms for idiopathic sudden deafness is vascular disease. However, it is not known whether traditional cardiovascular risk factors, such as particular dietary factors, are associated with this condition. METHODS: A case-control study using pooled controls was conducted in Japan to investigate the relationship between idiopathic sudden deafness and diet. An m:n matched-pairs method was used to obtain age-, gender- and residential district-matched controls from a nationwide database of pooled controls. Food intake was assessed from a self-administered usual food frequency questionnaire that asked about intake of 35 foods (including four drinks). Participants were classified according to the frequency of intake of Western foods and the frequency of intake of traditional Japanese foods. Subgroup analyses were performed using audiometric subtypes of idiopathic sudden deafness. RESULTS: Data were obtained for 164 cases and 20,313 controls. An increased risk of sudden deafness was observed among participants who frequently consumed Western foods (OR = 1.82, 95% CI : 1.14--2.89), and a decreased risk of this condition was observed among participants who frequently consumed Japanese foods (OR = 0.52, 95% CI : 0.33--0.82). A direct association of sudden deafness with Western food intake was evident for flat-type hearing loss. CONCLUSIONS: This study suggests that a largely Western diet might be a risk factor for idiopathic sudden deafness, a traditional Japanese diet might be a preventive factor for this condition, or both. These findings are consistent with the hypothesis that vascular factors are an important cause of idiopathic sudden deafness, although the possibility of residual confounding by unmeasured confounders such as socioeconomic status cannot be ruled out.

Audiometry↗
PubMed2001

Reliable, minimally invasive oromandibular reconstruction using metal plate rolled with pectoralis major myocutaneous flap.

The purpose of this study was to minimize the surgical invasiveness to the donor site and the amount of the primary reconstruction time after oromandibular tumor resection. Oromandibular reconstruction was performed only using a pectoralis major myocutaneous flap and a metal plate. The pectoralis major myocutaneous flap was grafted to the oral cavity defect by rolling and wrapping around the metal plate with the muscle of the flap. No early postoperative complications have been noted in all seven patients. An average of 2 years and 1 month has past since surgery, and to date no infections, plate exposure, or plate breakage have been observed in any of the patients. The safety of the oromandibular reconstruction using a metal plate was improved by rolling the muscle of the pectoralis major myocutaneous flap around the metal plate. The present method was shown to be a rational technique that allowed primary reconstruction of the oral cavity and mandible in a minimally invasive manner in a short time.

Adult↗
PubMed2001

All-trans-retinoic acid enhances the effect of adenovirus-mediated wild-type p53 gene transfer in head and neck squamous cell carcinoma.

OBJECTIVES: Adenovirus-mediated p53 (AdCMVp53) gene therapy for cancer is currently undergoing phase III clinical trials. One problematic aspect of this therapy is that the current protocols result in low transduction of the therapeutic virus in vivo. To search new modalities that can enhance the effect of AdCMVp53 gene therapy, we focused on retinoids. METHODS: To study the effect of ATRA in combination with AdCMVp53 gene therapy, we pretreated head and neck squamous cell carcinoma (HNSCC) cells for 72 hours with a low-dose All-trans-retinoic acid (ATRA) (10-7 M-10-8 M) which will not affect the in vitro cell growth, and then infected the cells with low MOI (30MOI) AdCMVp53. In vitro cell proliferation assays, cell cycle assays were performed. Expression of p53 and p53-related gene products, BAX and p21, were examined. RESULTS: The combined treatment with ATRA and Ad-p53 suppressed cell growth and induced apoptosis significantly more than AdCMVp53 treatment alone (P <.05). p53 expression significantly increased more after the combined treatment than after either treatment alone, at both the transcription and protein levels. In addition, increased expression of p21 and BAX, which are downstream gene products of p53, was observed in the combination. ATRA also enhanced the expression of green fluorescent protein (GFP) transduced by an adenovirus-cytomegalovirus (CMV)-GFP vector suggesting ATRA enhances adenovirus-CMV-promoted vectors through transcription. CONCLUSIONS: Our results indicate that ATRA enhances AdCMVp53 expression through transcriptional mechanisms and can synergistically induce apoptosis in HNSCC cells. ATRA has a potential to enhance the effect of adenovirus-mediated p53 gene therapy for HNSCC.

Adenoviridae↗
PubMed2001

Importance of NF-kappaB in rheumatoid synovial tissues: in situ NF-kappaB expression and in vitro study using cultured synovial cells.

OBJECTIVES: To examine whether inhibition of NF-kappaB induces apoptosis of human synovial cells stimulated by tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and anti-Fas monoclonal antibody (mAb). METHODS: The expression of proliferating cell nuclear antigen (PCNA), NF-kappaB, and the presence of apoptotic synovial cells were determined in synovial tissues. Apoptosis of cultured synovial cells was induced by inhibition of NF-kappaB nuclear translocation by Z-Leu-Leu-Leu-aldehyde (LLL-CHO). The activation of caspase-3 and expression of XIAP and cIAP2 in synovial cells in LLL-CHO induced apoptosis was also examined. RESULTS: Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cells were also detected in the RA synovial tissues. Nuclear NF-kappaB was expressed in RA synovial cells. Electrophoretic mobility shift assay showed that treatment of cells with TNFalpha or IL1beta significantly stimulated nuclear NF-kappaB activity. A small number of apoptotic synovial cells expressing intracellular active caspase-3 were found after treatment of cells with LLL-CHO. Although treatment of RA synovial cells with TNFalpha or IL1beta alone did not induce apoptosis, apoptosis induced by LLL-CHO and caspase-3 activation were clearly enhanced in TNFalpha or IL1beta stimulated synovial cells compared with unstimulated synovial cells. Furthermore, induction of apoptosis of synovial cells with caspase-3 activation by anti-Fas mAb was clearly increased by LLL-CHO. The expression of cIAP2 and XIAP in synovial cells may not directly influence the sensitivity of synovial cells to apoptosis induced by LLL-CHO. CONCLUSION: The results suggest that NF-kappaB inhibition may be a potentially important therapeutic approach for RA by correcting the imbalance between apoptosis and proliferation of synovial cells in RA synovial tissue.

Antibodies, Monoclonal↗
PubMed2001

Thyroarytenoid muscle: functional subunits based on morphology and muscle fiber typing in cats.

Using parvalbumin immunohistochemistry to determine the distribution of muscle fiber types in the feline thyroarytenoid muscle (TA), we clearly distinguished the vocalis (with predominance of "slow" type 1 fibers) from the external TA (in which "fast" type 2 fibers predominated, especially in its rostral part). Reconstruction of serial frontal sections of the TA allowed the stereoscopic study of each division. The existence of a rudimentary laryngeal ventricle separating the true and false vocal folds in cats was demonstrated anatomically and histologically, and its relationships to each division of the TA were established. Our results suggest that the vocalis, fitted for enduring activities, is suited for voice control. The fast, rostral part of the external TA seems suited to laryngeal sphincteric demands, while its caudal counterpart may act in both functions. The anatomic individualization of the divisions of the TA may suggest that they play distinct physiological roles and may imply that they should not be considered a single functional unit.

Animals↗
PubMed2001

Stellate cells in the human vocal fold.

Cells have been discovered that are star-like in appearance and that actively synthesize extracellular matrices in the human adult vocal fold mucosa. These cells have no nomenclature and are thus designated as vocal fold stellate cells (VFSC) in this study. Light and electron microscopic investigation of VFSC in the human vocal fold mucosa was carried out on excised human adult larynges. A comparison between VFSC and conventional fibroblasts was made. The results are summarized as follows. 1) The VFSC are distributed in human adult maculae flavae. 2) The VFSC are irregular and stellate in shape, possessing slender cytoplasmic processes. 3) Lipid droplets are present in the cytoplasm. 4) The VFSC have a small nucleus-cytoplasm ratio and well-developed rough endoplasmic reticulum, suggesting active protein synthesis in these cells. 5) No basal lamina is present, and filaments can be seen in the cytoplasm. 6) The VFSC show strong cytoplasm staining with periodic acid-Schiff stain and type III collagen. 7) The VFSC actively synthesize collagenous fibers, including reticular fibers, as well as other extracellular matrices, such as elastic fibers and glycosaminoglycan (hyaluronic acid). 8) The VFSC, first demonstrated in this study, actively synthesize extracellular matrices in the human adult vocal fold mucosa under normal conditions. 9) The VFSC participate in the metabolism of the extracellular matrices essential for the viscoelastic properties of the lamina propria of the human adult vocal fold mucosa as a vibrating tissue.

Aged↗
PubMed2001

Fine structure of the human newborn and infant vocal fold mucosae.

This study was carried out to determine the fine structure of the membranous portion of the human newborn and infant vocal fold mucosae and to clarify how the human vocal fold mucosa begins to grow after birth. Light and electron microscopic observations were made on the vocal fold mucosae excised from human newborn and infant larynges. Our findings are summarized as follows. 1) Reinke's space of the newborn vocal fold is a loose structure composed of ground substance and sparse fibers. 2) Ground substance is abundant and glycoproteins (fibronectin) are present in the lamina propria. 3) In the maculae flavae of newborn vocal folds, fibroblasts begin to form collagenous, reticular, and elastic fibers. 4) In the infant maculae flavae, fibroblasts are activated to become stellate in shape and synthesize extracellular matrices such as collagenous and reticular fibers. 5) After birth, the collagenous and reticular fibers synthesized in the maculae flavae extend toward the middle of the membranous portion of the vocal fold mucosa. 6) Glycoprotein (fibronectin) determines the orientation of collagenous and reticular fiber deposition. 7) Glycoprotein (fibronectin) decreases with the increase of the fibrous components in Reinke's space. 8) Elastic fibers increase after collagenous and reticular fibers appear in Reinke's space. 9) Much hyaluronic acid (glycosaminoglycan) is actively produced in the infant maculae flavae. 10) The collagenous and reticular fibers serve as stabilizing scaffolds for the other extracellular matrices, such as elastic fibers and glycosaminoglycan. During infancy, the extracellular matrices synthesized in the maculae flavae appear in the membranous portion of the vocal fold, each at a different time, so as to initiate the 3-dimensional formation of the vocal fold mucosa.

Extracellular Matrix↗
PubMed2001

Associations of plasma endothelin concentration with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension.

We studied the association of endothelin (ET)-1 with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension. Neurologically normal patients with essential hypertension (n=293; 138 male, 155 female; mean age, 65 years) and age-matched control subjects (n=242) were studied with B-mode ultrasonography of the common and internal carotid arteries and magnetic resonance imaging of the brain. Plasma ET-1 was measured by enzyme immunoassay. Hypertensive patients were divided into groups with carotid plaques and low ET-1 concentrations (< 0.75 pg/ml; PL group); carotid plaques and mid-range ET-1 (0.75 to 1.55 pg/ml; PM group); carotid plaques and high ET-1 (> or = 1.55 pg/ml; PH group); no plaques and low ET-1 (NPL); no plaques and mid-range ET-1 (NPM); and no plaques and high ET-1 (NPH). Overall, ET-1 concentrations were significantly higher in patients than in control subjects. Carotid plaque prevalence was significantly related to ET-1 in hypertensive patients. ET-1 showed a significant positive relationship with the number of asymptomatic lacunar infarcts of the brain in hypertensive patients with carotid plaques (rho=0.48, p<0.001). No significant relationship was seen between ET-1 and periventricular hyperintensity scores in patients with plaques. ET-1 did not show a relationship to either brain lesion type in patients without carotid plaques. Thus, ET-1 may foster asymptomatic lacunar cerebral infarcts by promoting carotid atherosclerosis in patients with essential hypertension.

Adult↗
PubMed2001

Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene.

BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.

Adolescent↗
PubMed2001

Genetic alteration of penicillin non-susceptible Streptococcus pneumoniae observed throughout recurrence of acute otitis media detected by amplified fragment length polymorphism analysis.

The prevalence of penicillin non-susceptible Streptococcus pneumoniae (PNSSP) is increasing among isolates from acute otitis media (AOM). Repeated episodes of antibiotic exposure are a well-known risk factor for the isolation of PNSSP although otitis-prone or recurrent AOM cases frequently require repeated courses of antibiotic treatment. In order to evaluate the chronological alteration of S. pneumoniae during recurrences of AOM, strains of S. pneumoniae were isolated from 11 patients, each of whom had experienced 2-4 episodes of AOM, were examined. Every bacterial specimen obtained from a single episode of recurrent AOM was examined by PCR-based penicillin-binding protein (PBP) assay, serotyping, and amplified fragment length polymorphism (AFLP), then compared to other samples from the same case. Two cases (18.2%) showed strain diversity during repeated antibiotic treatments by serotyping or PBP-assay. By AFLP analysis, 6 cases (54.5%) demonstrated heterogeneous strains during recurrent AOM. Clonal survivors of previous episodes of AOM were not always the cause of subsequent episodes of AOM, even in otitis-prone cases.

Acute Disease↗