Biomedical subjects
Publications and source records attributed to T Nakashima.
A case of sarcoidosis involving the tongue is described in a 48-year-old Japanese man. A definite diagnosis of sarcoidosis was made for the clinical lesion and pathological examinations. Sarcoidosis is a multisystem granulomatous disease that may affect any organ. Sarcoidosis of the tongue is particularly rare.
OBJECTIVES: Shinrin-yoku (walking and/or staying in forests in order to promote health) is a major form of relaxation in Japan; however, its effects have yet to be completely clarified. The aims of this study were: (1) to evaluate the psychological effects of shinrin-yoku in a large number of participants; and (2) to identify the factors related to these effects. METHODS: Four hundred and ninety-eight healthy volunteers took part in the study. Surveys were conducted twice in a forest on the same day (forest day) and twice on a control day. Outcome measures were evaluated using the Multiple Mood Scale-Short Form (hostility, depression, boredom, friendliness, wellbeing and liveliness) and the State-Trait Anxiety Inventory A-State Scale. Statistical analyses were conducted using analysis of variance and multiple regression analyses. RESULTS: Hostility (P<0.001) and depression (P<0.001) scores decreased significantly, and liveliness (P=0.001) scores increased significantly on the forest day compared with the control day. The main effect of environment was also observed with all outcomes except for hostility, and the forest environment was advantageous. Stress levels were shown to be related to the magnitude of the shinrin-yoku effect; the higher the stress level, the greater the effect. CONCLUSIONS: This study revealed that forest environments are advantageous with respect to acute emotions, especially among those experiencing chronic stress. Accordingly, shinrin-yoku may be employed as a stress reduction method, and forest environments can be viewed as therapeutic landscapes. Therefore, customary shinrin-yoku may help to decrease the risk of psychosocial stress-related diseases, and evaluation of the long-term effects of shinrin-yoku is warranted.
The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.
OBJECTIVE: To evaluate the inner ear of a patient with an enlarged vestibular aqueduct and acute hearing deterioration, using three-dimensional fluid-attenuated inversion recovery (3D FLAIR) magnetic resonance imaging (MRI). BACKGROUND: Three-dimensional fluid-attenuated inversion recovery MRI has been recently developed to detect haemorrhage and high concentrations of protein. Application of this method to inner-ear diseases has not been fully described. METHOD: We used 3D FLAIR MRI to evaluate a patient with an enlarged vestibular aqueduct and acute hearing deterioration. RESULTS: On 3D FLAIR MRI, this patient had high signals in the endolymphatic duct and sac, the vestibule and the cochlea and was diagnosed as having a high protein concentration in the inner ear. These high signal areas were not detected by T1- and T2-weighted MRI. CONCLUSION: This is the first published case in which a high protein concentration in the cochlea of a patient with an enlarged vestibular aqueduct was detected by 3D FLAIR MRI. These findings strongly supported the theory of the pathophysiology of hearing deterioration in patients with an enlarged vestibular aqueduct, which states that hyperosmolar fluid in the enlarged endolymphatic sac refluxes into the cochlea, resulting in damage to the hair cells. Thus, these finding may help clarify the cause of hearing deterioration in the presence of a large endolymphatic duct and sac.
The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.
This study evaluates the in vitro ability of CAP, a bone graft substitute with osteointegration and osteoconductive properties, to restore the anatomy and strength of fractured distal radii. Ten pairs of cadaveric radii were imaged and tested to failure, simulating a fracture. The radii were reconstructed using CAP and were re-fractured and sequentially imaged. The deformities of the bones were determined through computerised evaluation of the radiographs. Radiographic analysis showed that CAP is capable of restoring the anatomy of the distal radius. The load and work required to fracture intact radii were compared to those required to fracture the reconstructed radii. The load to fracture was similar in the two situations. The work to fracture, however, was higher with reconstructed radii, suggesting that these are stronger than the original bones. Our study supports the hypothesis that CAP is capable of restoring the original anatomy and dimensions of the distal radius and re-establishing its mechanical strength.
We report a new surgical procedure to treat intractable aspiration: closure of the larynx, using double hinged flaps of the vocal folds and false vocal folds. The anterosuperior portion of the thyroid cartilage is ablated. A small horizontal incision is made just above the anterior commissure and is continued posteriorly along the laryngeal ventricle; these incisions are continued across the posterior wall of the glottis. Incisions are made into the bilateral vocal folds and false vocal folds in order to create the hinged flaps. The glottis and the supraglottis are closed by approximating the bilateral vocal folds and false vocal folds hinged flaps. Superiorly or inferiorly based sternohyoid muscle pedicles are then inserted into the dead space between the approximated bilateral vocal folds and false vocal folds hinged flaps. The removed lamina of the thyroid cartilage is obliterated between both sternohyoid muscle flaps to enforce the closure of the larynx.
BACKGROUND: The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. AIM: To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. METHODS: 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. RESULTS: Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. CONCLUSIONS: Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.
Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.
OBJECTIVES: To evaluate the efficacy of simple tonsillectomy to treat obstructive sleep apnoea syndrome (OSAS) in adults. DESIGN: Prospective study. SETTING: Tertiary referral centre. PARTICIPANTS: Thirty patients (28 males) underwent simple tonsillectomy under general anaesthesia. The patients' mean age was 33.2 +/- 6.8 years and body mass index was 30.7 +/- 6.0 kg/m2. Seven patients (23%) were classified with grade 4, 16 patients (53%) with grade 3, and seven patients (23%) with grade 2 according to the tonsil size of Friedman's classification. MAIN OUTCOME MEASURES: The number of apnoea episodes per hour (apnoea index), the number of apnoea and hypopnoea episodes per hour (apnoea-hypopnoea index), lowest nocturnal oxygen saturation and oxygen desaturation time were measured during overnight polysomnography before and after surgery. A successful tonsillectomy was defined as an apnoea-hypopnoea index improvement ratio of > or =50% and an apnoea-hypopnoea index <20 after operation. RESULTS: Apnoea-hypopnoea index decreased from 69.0 +/- 28.4/h to 30.1 +/- 24.0/h (P < 0.0001). Simple tonsillectomy was successful in all six patients with body mass index <25 kg/m2. Concerning success rate of simple tonsillectomy with tonsil, size 2 was lowest (42.9%). Eight of the 13 patients who used continuous positive airway pressure before simple tonsillectomy did not use continuous positive airway pressure after simple tonsillectomy because of a significant reduction of excessive daytime sleepiness. Continuous positive airway pressure decreased significantly after simple tonsillectomy from 13.6 +/- 2.5 cmH2O preoperatively to 10.6 +/- 1.3 cmH2O postoperatively (P < 0.05). CONCLUSIONS: These data suggest that simple tonsillectomy is a beneficial modality to treat OSAS in selected patients (larger tonsil, low body mass index), even in adults.
OBJECTIVE: To investigate Schwartze sign with measurements of blood flow to the promontory in patients with cochlear otosclerosis. DESIGN: Prospective clinical study. SETTING: Tertiary referral centre. PARTICIPANTS: Five patients with cochlear otosclerosis and five control subjects. Significant decalcification around the cochlea was observed by computed tomography (CT) in patients with cochlear otosclerosis. However, no recognizable lesion was observed at the oval window in two patients. One patient had mixed hearing loss and four patients had sensorineural hearing loss without an air-bone gap. MAIN OUTCOME MEASURES: The relationship between CT findings and the presence or absence of Schwartze sign was investigated. Blood flow to the promontory was measured through the tympanic membrane using laser speckle flowgraphy and laser Doppler flowmetry. RESULTS: The Schwartze sign correlated significantly with otosclerotic lesions invading the promontory. Patients with otosclerosis exhibited elevated and pulsating blood flow to the promontory with the Schwartze sign. CONCLUSIONS: Computed tomography demonstrated that cochlear otosclerosis can exist without the oval window lesion. Schwartze sign can be used as a sign of the otosclerotic invasion to the promontory. The reddening of the Schwartze sign is likely due to increased blood flow.
An 80-year-old man was admitted to our hospital because a routine chest X-ray had revealed a nodular shadow in the right lower lung field. Transbronchial lung biopsy (TBLB) failed to give at definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Rapid intraoperative pathological examination diagnosed the tumor as large cell carcinoma. However, bloody pleural effusion was classified as class V. It was judged difficult to perform a curative operation, so the operation was interrupted. Pathological diagnosis was combined large cell neuroendocrine carcinoma and squamous cell carcinoma. Pleurodesis was done, and the patient is under observation at 7 months after the operation.
We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II-III NSCLCs. In patients with stage II-III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.
Immunohistochemical analyses of the effects of hepatocyte growth factor (HGF) and c-Met expression on tumour growth and angiogenesis were performed on 88 patients with non-small-cell lung cancers (NSCLCs). In all, 22 carcinomas (25.0%) were intratumoral HGF-positive, 14 carcinomas (15.9%) were stromal HGF-positive, and 36 carcinomas (40.9%) were intratumoral c-Met-positive. None of the carcinomas were stromal c-Met-positive. Examination of tumour growth revealed that the frequency of tumours with a high Ki-67 index was significantly greater for stromal HGF-positive tumours than for stromal HGF-negative tumours (P=0.0197). The frequency of tumours with a high Ki-67 index was also significantly greater for intratumoral c-Met-positive tumours than for intratumoral c-Met-negative tumours (P=0.0301). However, there was no significant difference in tumour vascularity with relation to intratumoral HGF status, stromal HGF status, and intratumoral c-Met status. The survival rate of patients with intratumoral c-Met-positive tumours was significantly lower than for patients with c-Met-negative tumours (P=0.0095). Furthermore, the survival rate of patients with both intratumoral c-Met-positive and stromal HGF-positive tumours was significantly lower than for patients with either positive tumours, and that of patients with both negative tumours (P=0.0183 and P=0.0011, respectively). A univariate analysis revealed that intratumoral c-Met expression was a significant prognostic factor of NSCLC patients (relative risk=2.642, P=0.0029). The present study demonstrates that tumour-stromal interaction between tumour cell-derived c-Met and stromal cell-derived HGF affects tumour growth and the prognosis of NSCLC patients.
OBJECTIVES: Our recent work showed that fibroblast-like synovial cells (FLS) could differentiate into adipocyte-like cells in vitro in response to stimulation with peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand. The aim of the present study was to determine the role of cytokines in the regulation of FLS differentiation to adipocyte-like cells. METHODS: FLS isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from normal synovial tissues were incubated with the synthetic PPAR gamma ligand troglitazone to induce adipocyte-like differentiation of the cells. RESULTS: Production of interleukin (IL)-6, IL-8 and matrix metalloproteinase-3 was reduced in adipocyte-like cells compared with FLS. DNA binding activity of nuclear factor kappa B (NF-kappa B) was clearly inhibited in adipocyte-like cells. Cultivation of FLS with interferon gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) or IL-1 beta inhibited the expression of PPAR gamma as well as CCAAT/enhancer binding protein (C/EBP) nuclear activity, and thus suppressed adipocyte-like cell differentiation in vitro. CONCLUSION: Our results indicate the importance of PPAR gamma and C/EBP in adipocyte-like cell differentiation of FLS and that the process is influenced by inflammatory cytokines, and suggest that the proinflammatory character of FLS in patients with RA is diminished during adipocyte-like cell differentiation.
Implant surface roughness is an important parameter governing the overall mechanical properties at the implant-cement interface. This study investigated the influence of surface roughness using polymethylmethcrylate (PMMA) and a Bisphenol-a-glycidylmethacyrlate resin-hydroxyapatite cement (CAP). Mechanical fixation at the implant-cement interface was evaluated in vitro using static shear and fatigue loading with cobalt chrome alloy (CoCr) dowels with different surface roughness preparations. Increasing surface roughness improved the mechanical properties at the implant-cement interface for both types of cement. CAP cement fixation was superior to PMMA under static and dynamic loading.
BACKGROUND: Plasma levels of adrenomedullin, a potent vasodilator peptide, are increased in cirrhotic patients, whereas its role in vascular hyporeactivity in cirrhosis has not been clarified. METHODS: Adrenomedullin expression was evaluated by radioimmunoassay and reverse-transcription polymerase chain reaction. Vascular reactivity to phenylephrine, alpha-adrenoceptor agonist, was investigated in the aortic rings from control rats and CCl-induced cirrhotic rats with ascites in the presence of the neutralizing antibody against adrenomedullin, human adrenomedullin and/or N-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor. RESULTS: Plasma adrenomedullin levels were significantly higher in cirrhotic rats than in controls (16.3 +/- 2.9 versus 7.4 +/- 1.7 fmol/mL, P < 0.05) and correlated negatively with systemic arterial pressure (r = -0.62, P < 0.05). Gene expression of adrenomedullin in various organs (liver, kidney, lung) and vessels (portal vein, aorta) was enhanced in cirrhotic rats compared with controls. Neutralizing antibody against adrenomedullin ameliorated the blunted contractile response to phenylephrine in cirrhotic aorta (Rmax: 1.5 +/- 0.1 versus 1.0 +/- 0.1 g/mg tissue, P < 0.05), whereas contraction remained unchanged in control aorta (Rmax: 1.9 +/- 0.2 versus 1.9 +/- 0.2 g/mg tissue). Intravenous infusion of human adrenomedullin induced a reduction of mean arterial pressure together with an increase of serum nitrate levels, which was abolished by neutralizing antibody against adrenomedullin. Human adrenomedullin caused a blunted contractile response to phenylephrine in both control and cirrhotic aortas, which was not observed in the presence of N-nitro-L-arginine methyl ester. CONCLUSIONS: These findings indicate that the overproduction of adrenomedullin may contribute to vascular hyporeactivity in cirrhosis via a release of nitric oxide.
We examined the role of osteoprotegerin (OPG) on tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in rheumatoid fibroblast-like synovial cells (FLS). OPG protein concentrations in synovial fluid from patients with rheumatoid arthritis (RA) correlated with those of interleukin (IL)-1beta or IL-6. A similar correlation was present between IL-1beta and IL-6 concentrations. Rheumatoid FLS in vitro expressed both death domain-containing receptors [death receptor 4 (DR4) and DR5] and decoy receptors [decoy receptor 1 (DcR1) and DcR2]. DR4 expression on FLS was weak compared with the expression of DR5, DcR1 and DcR2. Recombinant TRAIL (rTRAIL) rapidly induced apoptosis of FLS. DR5 as well as DR4 were functional with regard to TRAIL-mediated apoptosis induction in FLS; however, DR5 appeared be more efficient than DR4. In addition to soluble DR5 (sDR5) and sDR4, OPG administration significantly inhibited TRAIL-induced apoptogenic activity. OPG was identified in the culture supernatants of FLS, and its concentration increased significantly by the addition of IL-1beta in a time-dependent manner. Neither IL-6 nor tumour necrosis factor (TNF)-alpha increased the production of OPG from FLS. TRAIL-induced apoptogenic activity towards FLS was reduced when rTRAIL was added without exchanging the culture media, and this was particularly noticeable in the IL-1beta-stimulated FLS culture; however, the sensitivity of FLS to TRAIL-induced apoptosis itself was not changed by IL-1beta. Interestingly, neutralization of endogenous OPG by adding anti-OPG monoclonal antibody (MoAb) to FLS culture restored TRAIL-mediated apoptosis. Our data demonstrate that OPG is an endogenous decoy receptor for TRAIL-induced apoptosis of FLS. In addition, IL-1beta seems to promote the growth of rheumatoid synovial tissues through stimulation of OPG production, which interferes with TRAIL death signals in a competitive manner.