Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 91 records · Page 5Linked to original sources

PubMed2001

Smoking, alcohol, sleep and risk of idiopathic sudden deafness: a case-control study using pooled controls.

Sudden deafness sometimes has an identifiable cause, but in most cases the cause is unknown (idiopathic sudden deafness). Vascular impairment has been proposed as an aetiological mechanism for this condition, but it is unclear whether traditional cardiovascular risk factors, such as smoking or alcohol intake, are associated with this condition. We accordingly investigated associations of idiopathic sudden deafness with smoking, alcohol intake and sleep duration in a case-control study. Cases were consecutive patients diagnosed with idiopathic sudden deafness between October 1996 and August 1998 at collaborating hospitals in Japan. Controls were obtained from a nationwide database of pooled controls, with matching for age, gender and residential district. Exposure variables were assessed from a self-administered questionnaire. Subgroup analyses were performed using audiometric subtypes of sudden deafness. Data were obtained for 164 cases and 20,313 controls. Increased risks of idiopathic sudden deafness were observed among participants who consumed two or more units of alcohol per day (OR=1.90, 95% CI=1.12-3.21), and among participants who slept less than seven hours per night (OR=1.61, 95% CI=1.09-2.37). The direct association with alcohol intake was particularly strong for the participants with profound hearing loss. There was little evidence of an association with smoking. This study suggests that alcohol intake and short sleep duration might be risk factors for idiopathic sudden deafness.

Alcohol Drinking↗

PubMed2001

The predictive value of p53, Ki-67 and angiogenetic factors in primary hypopharyngeal carcinoma.

To evaluate the predictive role of the oncogene p53, the proliferating marker Ki-67, angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and vascular endothelial growth factor (VEGF) in primary hypopharyngeal carcinoma, we immunohistochemically studied a series of 84 primary hypopharyngeal carcinoma patients who were treated at the Department of Otolaryngology of Kurume University Hospital between 1990 and 1997. The correlation of each score according to the intensity and percentage of the labeled cells with the TNM stage, histological grade, metastasis and survival status was analyzed. The positive rate of p53 was 52.4%. The percentages of Ki-67 labeled cells in patients with or without metastasis showed a significant difference (p = 0.011). VEGF also showed a significant difference between the live and death groups (p < 0.05) and also among the differentiation group (p < 0.05). A statistically significant correlation was also seen between the score of Ki-67 and VEGF (r = 0.438, p < 0.001) or the score of Ki-67 and PD-ECGF (r = 0.259, p < 0.001), respectively. In conclusion, the present study suggests that a correlation exists between proliferating and angiogenesis, and VEGF and Ki-67 are thus considered to be possible prognostic discriminators in hypopharyngeal carcinoma.

Adult↗

PubMed2001

[Analysis of 200 university hospital hearing aid clinic patients].

We statistically studied patients who visited our hearing aid clinic to determine what segment of the population may benefit from hearing aids. Subjects were 200 patients from 5 to 89 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, Nagoya University Hospital, between January 1998 and March 2000. This clinic lent out hearing aids. Subjects were divided into 2 groups those having their own hearing aids either new or earlier (HA group) and those giving up hearing aids after a trial (non-HA group). Mean better hearing levels in pure tone average were 50.6 dB in the HA group and 44.5 dB in the non-HA group. Mean better maximum speech recognition scores were 81.5% in the HA group and 85.3% in the non-HA group. The distribution of better hearing has shown that patients with mild hearing loss (better pure tone average < 40 dB) account for more than a quarter of all hearing aid clinic patients. Among patients with mild hearing loss, 60% had their own hearing aids. The need for rehabilitation in the mild hearing loss population thus appears large. Their intent to wear hearing aids influenced whether patients agreed or declined hearing aids after a trial. The period from use until patients made a decision was 2 weeks in 65% of those declining use and 35% of those agreeing to use. Over 15% of those agreeing called for a trial period longer than 8 weeks. Hearing aid trials provide useful information for both patients and surgeons before choosing surgery for a difficult ear condition. In this research, 18 patients needed counseling about both amplification and surgery. Bridging between ear surgery and hearing aid wearing is a vital role of hearing aid clinics at university hospitals.

Adolescent↗

PubMed2001

Synthesis and biological evaluation of cytogenin derivatives.

To enhance the stability in vivo, new derivatives of cytogenin were synthesized, and their biological activity and stability in mice were estimated. 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid (NM-3) was found to be the most stable among them. It modified collagen-induced arthritis in mice. It also showed potent anti-angiogenic activity in a mouse dorsal air sac assay.

Animals↗

PubMed2001

Hyperbaric oxygen therapy for the treatment of large vestibular aqueduct syndrome.

Eight patients with large vestibular aqueduct (LVA) syndrome and acute sensorineural hearing loss that had not responded to intravenous treatment were treated with hyperbaric oxygen(HBO2) therapy. This was performed daily, with 15 treatments per course. Pure tone and speech audiometry were performed on all patients. The mean hearing recovery following HBO2 therapy (20.8 +/- 12.1 dB) was significantly higher than after intravenous treatment (2.3 +/- 7.2 dB) (P < 0.01), although treatment duration was not different between the two therapies. Of the eight patients, five showed complete or partial recovery after one course of HBO2 therapy, and their hearing levels have not since changed. The other three patients showed heating recovery during therapy, but treatment had to be repeated for two or more courses because of progressive or fluctuating hearing loss.We consider HBO2 therapy should be used to treat acute hearing deterioration associated with LVA syndrome if patients do not recover their hearing ability following conventional treatment

Adult↗

PubMed2000

Particle control of emulsion by membrane emulsification and its applications.

Particle-size control of emulsion is very important for maintaining stability and giving emulsions new functional roles. Porous glass membrane, prepared by phase separation of a glass composition, is available as an emulsifying element, from which, one can obtain monodispersed emulsion with different particle sizes, and useful water/oil/water (W/O/W) emulsion in very high yield. The authors have called this new technology 'membrane emulsification'. Applications of membrane emulsification technology to drug delivery systems were carried out under cooperative research with Miyazaki Medical College. It was found that the clinical administration of a W/O/W drug emulsion that encapsulated an anticancer drug in its inner droplets was surprisingly effective for both terminal and multiple nodules of hepatocellular carcinoma when the drug was injected to damaged liver through a catheter inserted in the hepatic artery. Other applications have been tried and developed elsewhere.

Animals↗

PubMed2000

Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines.

A variety of humoral factors modulate the osteoclastogenesis. Receptor activator of NF-kappaB ligand (RANKL) expressed on osteoblast/stromal lineage cells plays a pivotal role to transduce an essential differentiation signal to osteoclast lineage cells through binding to its receptor, RANK, expressed on the latter cell population; however, the difficulty to detect RANKL protein expression hampers us in investigating the regulation of RANKL expression by humoral factors. To determine protein expression of RANKL, we have established a new method, named as a ligand-receptor precipitation (LRP) Western blot analysis, which can specifically concentrate the target protein by the use of specific binding characteristic between RANKL and RANK/osteoprotegrin (OPG). RANKL protein expression in the postnuclear supernatant was not detected by common Western blotting, but LRP Western blot analysis clearly showed that RANKL is produced as a membrane-bound protein on murine osteoblasts/stromal cells, and cleaved into a soluble form by metalloprotease. Cytokines stimulating the osteoclastogenesis, such as IL-1beta, IL-6, IL-11, IL-17, and TNF-alpha, increased the expression of RANKL with decrease of OPG expression in osteoblasts/stromal cells. In contrast, cytokines inhibiting the osteoclastogenesis, such as IL-13, INF-gamma, and TGF-beta1 suppressed the expression of RANKL and/or augmented OPG expression. Functional difference between membrane-bound and soluble RANKL was demonstrated, which showed that membrane-bound RANKL works more efficiently than soluble RANKL in the osteoclastogenesis developed from murine bone marrow cell culture. The present study indicates the usefulness of LRP Western blot analysis, which shows that the modulation of osteoclastogenesis by humoral factors is achieved, in part, by regulation of the expression of RANKL and OPG in osteoblast/stromal lineage cells.

Animals↗

PubMed2000

Evaluation of the effects of alpha-phenyl-N-tert-butyl nitrone pretreatment on the neurobehavioral effects of methamphetamine.

A relationship between formation of reactive oxygen species (ROS) and energy depletion has been proposed to play an important role in mediating methamphetamine (METH)-induced neurotoxicity. To evaluate this relationship, we examined the effect of the spin-trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) on hyperthermia and self-injurious behavior (SIB) and striatal dopamine (DA) depletion produced by METH (4 injections of 4 mg/kg, 2 hr intervals, s.c.) in BALB/c mice. Repeated administration of METH induced hyperthermia, incidence of SIB and striatal DA depletion (84% after 3 days). Pretreatment with PBN (4 injections of 60 or 120 mg/kg, i.p.) reduced METH-induced hyperthermia, but did not significantly attenuate METH-induced SIB or the striatal DA depletion. On the other hand, pretreatment with high doses of PBN (4 injections of 180 or 240 mg/kg, i.p.) protected against METH-induced hyperthermia and SIB, and PBN (180 mg/kg) also completely protected against the acute striatal DA depletion 60 min after the last injection of the drug. However, the long-lasting striatal DA depletion was only attenuated by 52 or 56%, respectively. These results indicate that METH-induced hyperthermia contributes to, but is not solely responsible for METH-induced neurotoxicity, and supports a role for formation of ROS and other mechanisms in the generation of METH-induced striatal dopaminergic neurotoxicity. In addition, the difference in the efficacy of PBN to protect against the acute or long-lasting striatal DA depletion induced by METH may indicate that both ROS formation and other mechanisms are required for METH-induced neurotoxicity to develop.

Animals↗

PubMed2000

Genomic cloning, mapping, structure and promoter analysis of HEADPIN, a serpin which is down-regulated in head and neck cancer cells.

Headpin is a novel serine proteinase inhibitor (serpin) that is down-regulated in squamous cell carcinoma of the oral cavity and in squamous cell carcinoma cell lines of the head and neck. Using a panel of 18q21.3 YAC clones, we mapped and cloned the HEADPIN gene. The gene spans 10 kb and is composed of eight exons and seven introns. The genomic structure is identical with some other ovalbumin serpins (ov-serpins) in terms of the numbers, position and phasing of the intron/exon boundaries. HEADPIN was mapped within the serpin cluster in 18q21.3 between MASPIN and SCCA2 as follows: cen-MASPIN-HEADPIN-SCCA2-SCCA1-tel. The transcription start site was determined and the promoter activity of the 5'-flanking region was analyzed. Luciferase promoter assays in HaCaT cells showed that the -432 to -144 nucleotide region has functional promoter activity. The activity of the promoter/enhancer was not observed in head and neck cancer cell lines TU167 and UMSCC1 which lack headpin expression. These data suggest that the differential expression of headpin in normal and carcinoma-derived cells is regulated at the transcriptional level. Understanding the genomic organization and transcriptional regulation of the ov-serpins clustered within 18q21. 3 provides a critical framework for assessing their potential role in cancer.

Base Sequence↗

PubMed2000

Sensory innervation of the pharynx and larynx.

To shed light on supraesophageal complications of reflux disease, sensory innervation--particularly, distinct distribution, area, and density of sensory fibers--of the feline pharyngolaryngeal mucosa was reported. The investigations were performed by means of histochemistry (tracer techniques) and immunohistochemistry. The pharyngeal mucosa from the Eustachian cushion to the middle level of aryepiglottic fold, except the laryngeal surface of epiglottis, was supplied by the glossopharyngeal sensory fibers, whereas the laryngeal sensory fibers innervated between the apex of epiglottis and the level of the first tracheal ring in the larynx and between the middle level of aryepiglottic fold and the caudal end of piriform sinus in the pharynx. Most areas of the mucosa, except the subglottis, had unilateral innervation. The subglottis, including the caudal aspect of vocal fold and the posterior glottis, had bilateral supply with ipsilateral predominance. The density of sensory fibers in the vestibule of larynx involving the posterolateral aspect of arytenoid eminence was much heavier than the other parts. Sensory nerve fibers around the caudal pole of palatine tonsil, and in the root of tongue and the hypopharyngeal wall also were dense. Regional distribution and density of substance P and calcitonin gene-related peptide immunoreactive fibers showed almost the same pattern as did the sensory fibers.

Animals↗

PubMed2000

LPS-induced Fos expression in oxytocin and vasopressin neurons of the rat hypothalamus.

The aim of this study was to examine the involvement of the hypothalamic oxytocin (OXT) and vasopressin (AVP) neurons in acute phase reaction using quantitative dual-labeled immunostaining with Fos and either OXT and AVP in several hypothalamic regions. Administration of low dose (5 microg/kg) and high dose (125 microg/kg) of LPS induced intense nuclear Fos immunoreactivity in many OXT and AVP neurons in all the observed hypothalamic regions. The percentage of Fos-positive nuclei in OXT magnocellular neurons was higher than that of AVP magnocellular neurons in the supraoptic nucleus (SON), the magnocellular neurons in the paraventricular nucleus (magPVN), rostral SON (rSON), and nucleus circularis (NC), whose axons terminate at the posterior pituitary for peripheral release. The percentage of Fos-positive nuclei in AVP parvocellular neurons in the paraventricular nucleus (parPVN) was higher than that of OXT parvocellular neurons, whose axons terminate within the brain for central release. Moreover, the percentage of Fos-positive nuclei in AVP magnocellular neurons of the SON and rSON was significantly higher than that of the magPVN and NC when animals were given LPS via intraperitoneal (i.p.)-injection. This regional heterogeneity was not observed in OXT magnocellular neurons of i.p.-injected rats or in either OXT or AVP magnocellular neurons of intravenous (i.v. )-injected rats. The present data suggest that LPS-induced peripheral release of AVP and OXT is due to the activation of the magnocellular neurons in the SON, magPVN, NC, and rSON, and the central release of those hormones is in part derived from the activation of parvocellular neurons in the PVN. It is also suggested that the activation of AVP magnocellular neurons is heterogeneous among the four hypothalamic regions, but that of OXT magnocellular neurons is homogenous among these brain regions in response to LPS administration.

Animals↗

PubMed2000

Tetrocarcin A inhibits mitochondrial functions of Bcl-2 and suppresses its anti-apoptotic activity.

Bcl-2 is an integral, intracellular membrane protein that prevents cells from undergoing apoptosis in response to a variety of cell death signals. It negatively regulates the activation of Caspase-3, which functions as effector of mammalian cell death pathways. Overexpression of Bcl-2 inhibits the caspase activities and apoptosis. A microbial secondary metabolite, Tetrocarcin A (TC-A), was identified as an inhibitor of the anti-apoptotic function of Bcl-2. Apoptosis could be induced in cell lines that overexpressed Bcl-2 or Bcl-XL when the cells were treated with anti-Fas antibody, tumor necrosis factor alpha, staurosporine, or Bax, in addition to TC-A. TC-A showed selectivity against the pro-apoptotic Bcl-2 family members, in that cells overexpressing CrmA or dominant-negative FADD could not undergo apoptosis with TC-A treatment. In Bcl-2-overexpressing cell lines, TC-A inhibited mitochondrial functions regulated by Bcl-2, resulting in Fas-triggered mitochondrial transmembrane potential loss and cytochrome c release. Inhibition of the mitochondrial functions of Bcl-2 and, thereby, its anti-apoptotic effect could serve as useful pharmacological targets. Thus, TC-A should serve as an archetype for specific inhibitors of Bcl-2 functions.

Aminoglycosides↗

PubMed2000

The effect of endothelin-1 on lipopolysaccharide-induced cyclooxygenase 2 expression in association with prostaglandin E(2).

We demonstrated previously that endothelin-1 (10(-14) to 10(-8) M) promotes lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E(2) production through endothelin ET(B) receptors effects which are up-regulated by lipopolysaccharide. In the present study, we confirmed these findings and showed that prostaglandin E(2) (10(-6) to 10(-5) M) inhibited the lipopolysaccharide plus endothelin-1-induced cyclooxygenase 2 expression more profoundly as compared to its inhibition of the lipopolysaccharide-induced cyclooxygenase 2 expression. The endothelin ET(B) receptor selective antagonist, N-cis-2, 6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-methoxy carbon yl-tryptophanyl-D-norleucine (BQ788), partly inhibited this suppression. Interestingly, the expression of endothelin ET(B) receptors in macrophages was increased by lipopolysaccharide plus prostaglandin E(2) (10(-8) to 10(-5) M) about 1.6-fold compared with that evoked by lipopolysaccharide stimulation alone. We also showed that treatment with endothelin-1 at 10(-14) M (15 min) elevated an intracellular cyclic AMP concentration in macrophages stimulated by lipopolysaccharide or lipopolysaccharide plus prostaglandin E(2) (10(-6) M) for 6 h, and the elevation in the latter cells was more pronounced. These results suggested that endothelin-1 shows an opposite modulation of lipopolysaccharide-induced cyclooxygenase 2 expression in macrophages through endothelin ET(B) receptors, depending on the level of extracellular prostaglandin E(2), and the changes of intracellular cyclic AMP by endothelin-1 may be involved in this mechanism.

Animals↗

PubMed2000

Methamphetamine-induced striatal dopamine neurotoxicity and cyclooxygenase-2 protein expression in BALB/c mice.

The expression of cyclooxygenase-2 (COX-2) and striatal dopamine (DA) depletion in BALB/cAnNcrj (BALB/c) mice following a neurotoxic dose of methamphetamine (METH) was investigated. METH-treatment (4 mg/kg x 4, 2 h intervals, s.c.) induced a significant hyperthermia and a persistent depletion of striatal DA levels 72 h after the treatment. COX-2, a marker of the cytotoxic effect of inflammation and oxidative stress and thiobarbituric acid (TBA) were significantly induced in the striatum 72 h after the METH-treatment, but not in the hippocampus. These results suggest that COX-2 may participate in METH-induced neurotoxicity in striatum.

Animals↗

PubMed2000

Antisense inhibition of cyclin D1 in human head and neck squamous cell carcinoma.

OBJECTIVE: To study the role of cyclin D1 in regulating the biological behavior of head and neck cancer. DESIGN: Squamous cell carcinoma of the head and neck (SCCHN) cells were stably transfected with an antisense cyclin D1 using lipofectin-mediated transfection. In vitro growth assays, cell cycle analyses, cytotoxicity assays, and in vivo tumorigenicity assays were performed. MATERIALS: Human SCCHN cell lines TU138, TU167, TU177, TU182, MDA183, and MDA1386 and athymic nude mice were used for this study. RESULTS: The antisense cyclin D1 transfected cells revealed decreased growth rates in vitro and decreased tumorigenicity in athymic nude mice. Furthermore, antisense cyclin D1 transfection enhanced the chemosensitivity against cisplatin. CONCLUSIONS: These studies provided evidence that overexpression of cyclin D1 may play an important role in growth rates and biological behavior of human head and neck cancer. Additionally, expression of cyclin D1 may make human head and neck cancer cells resistant to platinum-based chemotherapeutic approaches. The ability to suppress the malignant phenotype by down-regulating cyclin D1 expression may provide a new gene therapy approach for patients with head and neck cancer.

Animals↗

PubMed2000

Developmental changes in capacitative Ca(2+) entry in mouse mammary epithelial cells.

Developmental changes in capacitative Ca(2+) entry and Ca(2+) release from intracellular stores were measured using fura-2 fluorescence method during the pregnancy period (day 3-;18) in mouse mammary epithelial cells. Ca(2+) release was identified with the transient intracellular Ca(2+) ([Ca(2+)](i)) increase induced by thapsigargin addition in a Ca(2+)-free solution. Capacitative Ca(2+) entry was measured by the transient [Ca(2+)](i) increase induced by re-addition of extracellular Ca(2+) after depletion of Ca(2+) stores by thapsigargin. The capacitative Ca(2+) entry was greatest at the early stage of pregnancy (i.e. day 3 of pregnancy) and decreased as pregnancy progressed, while Ca(2+) release remained unchanged throughout the developmental stages. These findings indicate that in contrast to Ca(2+) release, a close correlation exists between capacitative Ca(2+) entry and pregnancy-induced development in mammary epithelial cells.

Animals↗

PubMed2000

Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent paracrine angiogenic factor involved in angiogenesis. We determined whether antisense VEGF transfection can suppress angiogenic activity of a human squamous cell carcinoma of the head and neck (SCCHN) cell line. METHODS: Human SCCHN cell lines were screened for VEGF secretion by ELISA. The highest VEGF secreting cell line was transfected with an antisense VEGF vector. Endothelial cell migration assays were performed using the conditioned medium from the transfected clones. Tumorigenicity assays of the transfectants in nude mice were also performed. RESULTS: Antisense VEGF expression exhibited a 20-fold inhibition of VEGF secretion. The addition of conditioned medium from the antisense clones resulted in 50% reduction of endothelial migration. There was no effect on in vivo tumorigenicity. CONCLUSIONS: Antisense VEGF transfection effectively down-regulated VEGF secretion from SCCHN cells that had high VEGF secretion. Targeting VEGF expression may be useful for suppressing angiogenesis in head and neck cancer.

Angiogenesis Inducing Agents↗

PubMed2000

Decreased CD44H expression in early-stage tongue carcinoma associates with late nodal metastases following interstitial brachytherapy.

BACKGROUND: Late nodal metastases is a critical factor that worsens the prognosis of T1/T2N0 tongue cancer treated by interstitial brachytherapy. If we could better predict the patients at high risk for late nodal metastases developing before treatment, more appropriate choices of treatment could be selected. In recent studies of colon cancer, prostate cancer, and laryngeal cancer, CD44H has been postulated to be a metastasis suppressor. METHODS: On the basis of this phenomenon, we immunohistochemically evaluated the expression of CD44H in 38 cases of primary T1/T2N0 tongue cancer treated by interstitial brachytherapy. Formalin-fixed, paraffin-embedded biopsy specimens obtained before treatment were examined. RESULTS: The group that had late nodal metastases revealed a significantly lower (p =.0035) CD44H expression. CONCLUSIONS: A decreased CD44H expression may therefore be useful as a new predictor of late nodal metastases in patients with T1/T2N0 tongue carcinoma. For patients with a decreased CD44H expression, a partial glossectomy and an elective neck dissection may therefore be an appropriate treatment modality.

Adult↗