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Biomedical subjects

Nobuyuki Tanaka

Publications and source records attributed to Nobuyuki Tanaka.

At least 37 records · Page 2Linked to original sources

Hrs, a mammalian master molecule in vesicular transport and protein sorting, suppresses the degradation of ESCRT proteins signal transducing adaptor molecule 1 and 2.

The degradation and sorting of cytoplasmic and cell-surface proteins are crucial steps in the control of cellular functions. We previously identified three mammalian Vps (vacuolar protein sorting) proteins, Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and signal transducing adaptor molecule (STAM) 1 and -2, which are tyrosine-phosphorylated upon cytokine/growth factor stimulation. Hrs and the STAMs each contain a ubiquitin-interacting motif and through formation of a complex are involved in the vesicle transport of early endosomes. To explore the mechanism and cellular function of this complex in mammalian cells, we established an Hrs-defective fibroblastoid cell line (hrs(-/-)); embryos with this genotype died in utero. In the hrs(-/-) cells only trace amounts of STAM1 and STAM2 were detected. Introduction of wild-type Hrs or an Hrs mutant with an intact STAM binding domain (Hrs-dFYVE) fully restored STAM1 and STAM2 expression, whereas mutants with no STAM binding ability (Hrs-dC2, Hrs-dM) failed to express the STAMs. This regulated control of STAM expression by Hrs was independent of transcription. Interestingly, STAM1 degradation was mediated by proteasomes and was partially dependent on the ubiquitin-interacting motif of STAM1. Revertant Hrs expression in hrs(-/-) cells not only led to the accumulation of ubiquitinated proteins, including intracytoplasmic vesicles, but also restored STAM1 levels in early endosomes and eliminated the enlarged endosome phenotype caused by the absence of Hrs. These results suggest that Hrs is a master molecule that controls in part the degradation of STAM1 and the accumulation of ubiquitinated proteins.

Adaptor Proteins, Signal Transducing↗

Possible etiology of calculi formation in salivary glands: biophysical analysis of calculus.

Sialolithiasis is one of the common diseases of the salivary glands. It was speculated that, in the process of calculi formation, degenerative substances are emitted by saliva and calcification then occurs around these substances, and finally calculi are formed. However, the exact mechanism of the formation of calculi is still unclear. In this study, we identify some possible etiologies of calculi formation in salivary glands through biophysical analysis. Calculi from 13 patients with submandibular sialolithiasis were investigated by transmission electron microscopy, scanning electron microscopy, X-ray microanalyzer, and electron diffraction. Transmission electron microscopic observation of calculi was performed in the submandibular gland (n = 13). In 3 of the 13 cases, a number of mitochondria-like structures and lysosomes were found near calcified materials. Scanning electron microscopic examination of these materials revealed that there were lamellar and concentric structures and that the degree of calcification was different among the calculi. X-ray microanalysis disclosed the component elements in the calculi to be Ca, P, S, Na, etc., and the main constituents were Ca and P. The calcium-to-phosphorus ratio was 1.60-1.89. Analysis of the area including mitochondria-like structures, lysosomes, and the fibrous structures by electron diffraction revealed the presence of hydroxyapatite and calcified materials. It is speculated that mitochondria and lysosomal bodies from the ductal system of the submandibular gland are an etiological source for calcification in the salivary gland.

Electron Probe Microanalysis↗

Quantitative computed tomography versus spirometry in predicting air leak duration after major lung resection for cancer.

BACKGROUND: Emphysema is a well-known risk factor for developing air leak or persistent air leak after pulmonary resection. Although quantitative computed tomography (CT) and spirometry are used to diagnose emphysema, it remains controversial whether these tests are predictive of the duration of postoperative air leak. METHODS: Sixty-two consecutive patients who were scheduled to undergo major lung resection for cancer were enrolled in this prospective study to define the best predictor of postoperative air leak duration. Preoperative factors analyzed included spirometric variables and area of emphysema (proportion of the low-attenuation area) that was quantified in a three-dimensional CT lung model. Chest tubes were removed the day after disappearance of the air leak, regardless of pleural drainage. Univariate and multivariate proportional hazards analyses were used to determine the influence of preoperative factors on chest tube time (air leak duration). RESULTS: By univariate analysis, site of resection (upper, lower), forced expiratory volume in 1 second, predicted postoperative forced expiratory volume in 1 second, and area of emphysema (< 1%, 1% to 10%, > 10%) were significant predictors of air leak duration. By multivariate analysis, site of resection and area of emphysema were the best independent determinants of air leak duration. The results were similar for patients with a smoking history (n = 40), but neither forced expiratory volume in 1 second nor predicted postoperative forced expiratory volume in 1 second were predictive of air leak duration. CONCLUSIONS: Quantitative CT is superior to spirometry in predicting air leak duration after major lung resection for cancer. Quantitative CT may aid in the identification of patients, particularly among those with a smoking history, requiring additional preventive procedures against air leak.

Aged↗

Abnormal beta-catenin expression in oral cancer with no gene mutation: correlation with expression of cyclin D1 and epidermal growth factor receptor, Ki-67 labeling index, and clinicopathological features.

Beta-Catenin not only acts as a regulator of E-cadherin-mediated cell-cell adhesion but also plays an important role in Wnt signaling. To assess the prevalence of Wnt signaling, we examined beta-catenin mutation and its immunohistochemical protein expression in oral cancers. The results were linked with expression of cyclin D1, one of the target genes of Wnt signaling, expression of epidermal growth factor receptor (EGFR) relevant to beta-catenin tyrosine phosphorylation, Ki-67 labeling index, clinicopathological features, and survival. In the analysis based on membranous expression of beta-catenin, 75 (68.2%) of 110 cases showed a reduced membranous pattern, and the remaining 35 (31.8%) had a preserved membranous pattern similar to that in oral epithelium. In the analysis of another category of beta-catenin expression, a cytoplasmic/nuclear pattern was observed in 21 (19.1%) of the 110 tumors. Most (19/21, 90.5%) of these tumors had a concomitant reduction of membranous expression of beta-catenin. The reduced membranous or cytoplasmic/nuclear pattern of beta-catenin was significantly associated with an invasive growth pattern, EGFR expression, an increased Ki-67 labeling index, and shorter survival but not with cyclin D1 expression. Mutational analyses of beta-catenin were performed for 39 cases, including the 21 tumors with a cytoplasmic/nuclear pattern, but no mutations in the beta-catenin gene exon 3 were detected in these samples. Our data indicate that altered expression of beta-catenin may play an important role in tumor progression through increased proliferation and invasiveness under EGFR activation. However, mutations of beta-catenin do not appear to be responsible for tumor development and abnormal expression of beta-catenin in oral cancers.

Adult↗

Evaluation of skilled leg movements in patients with stroke using a computerized motor-skill analyzer for the lower limb.

The utility of a new computerized motor-skill analyzer for the lower limb was studied in healthy subjects and patients with stroke. The computerized motor-skill analyzer for the lower limb evaluated accuracy in a figure-tracking task with the foot. The intraclass correlation coefficients of measurements in subjects were .61 to .89 (p < .01). The trajectory errors of the unaffected lower limb in stroke patients were negatively correlated with physical ability. Trajectory errors of the patients were significantly larger than those of the healthy subjects. These results suggest that the computerized motor-skill analyzer is useful for quantitatively evaluating motor-skills of the lower limb.

Adult↗

Impaired visuo-motor skills in the unaffected lower limb of patients with stroke.

To study the motor skills of the unaffected lower limb of patients with stroke, the visuo-motor skills of the unaffected lower limb in patients with stroke was compared with those in healthy control subjects using a computerized motor skill analyzer that calculated the accuracy in the tracking task in terms of lap time and trajectory error. Trajectory errors in the task by the unaffected lower limb in the patients with stroke were significantly greater than those in the lower limb of healthy control subjects. These results suggest that patients with stroke have impaired visuo-motor skills of the unaffected lower limb.

Adult↗

Evaluation of skilled arm movements in patients with stroke using a computerized motor-skill analyser for the arm.

To study the utility of a new computerized motor-skill analyser (CMSA) for evaluating visuo-motor skilled movements of the arm, we examined (1) the reproducibility of measurement with the CMSA for the arm in 13 healthy participants and 14 patients with stroke and (2) the correlation between motor skills of the affected arm evaluated with the CMSA and clinical tests for upper extremity function in 20 patients with stroke. The CMSA for the arm was used to calculate the accuracy in tracking with the hand. The inter-class correlation coefficients for lap time, geometric trajectory error, trajectory error integrated over time and the marker trajectory error integrated over time were 0.45 (NS)-0.91 (P<0.01) in healthy participants and 0.62 (P<0.05)-0.90 (P<0.01) in patients with stroke. The trajectory error integrated over time and the geometric errors of the affected arm in stroke patients were negatively correlated with the Brunnstrom stage and the simple test for evaluating hand function. The marker trajectory error integrated over time in stroke patients was negatively correlated with the simple test for evaluating hand function. These results suggest that the CMSA for the arm is useful for quantitatively evaluating delicate visuo-motor skills of the arm.

Adult↗

Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.

Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia. We found that HTLV-2 Tax2 protein stimulated reporter gene expression regulated by the interleukin (IL)-2 promoter through the nuclear factor of activated T cells (NFAT) in a human T-cell line (Jurkat). However, the activity of HTLV-1 Tax1 was minimal in this system. T-cell lines immortalized by HTLV-2 but not HTLV-1 constitutively exhibited activated NFAT in the nucleus and constitutively expressed IL-2 mRNA. Cyclosporine A, an inhibitor of NFAT activation, abrogated the induction of IL-2 mRNA in HTLV-2-immortalized T-cell lines and concomitantly inhibited cell growth. This growth inhibition was rescued by the addition of IL-2 to the culture. Furthermore, anti-IL-2 receptor antibodies significantly reduced the proliferation of HTLV-2-infected T-cell lines but not that of HTLV-1-infected cells. Our results suggest that Tax2 activates an IL-2 autocrine loop mediated through NFAT that supports the growth of HTLV-2-infected cells under low-IL-2 conditions. This mechanism would be especially important in vivo, where this autocrine mechanism establishes a nonleukemogenic life-long HTLV-2 infection. The results also suggest that differences in long-term cytokine production between HTLV-1 and HTLV-2 infection are another factor for the differences in pathogenesis.

Base Sequence↗

New facilitation exercise using the vestibulo-ocular reflex for ophthalmoplegia: preliminary report.

OBJECTIVE: To study the effect of facilitation exercises using the vestibulo-ocular reflex on ophthalmoplegia due to brainstem injury. DESIGN: A single-baseline design (A-B: A without specific therapy, B with specific therapy) across individual subjects. SETTING: Inpatient rehabilitation facility. SUBJECTS: Eight patients with ophthalmoplegia (total of 15 affected muscles) due to brainstem injury. INTERVENTIONS: Basic rehabilitative treatment that included physical therapy, occupational therapy and/or speech therapy for impairments such as hemiplegia, ataxia or dysarthria was administered for two weeks (control treatment). Then, two facilitation exercise sessions (100 times/day, five days/week for two weeks) were administered in addition to the basic rehabilitative treatment for four weeks to the eight patients with ophthalmoplegia. Ophthalmoplegia was evaluated at study entry and at the end of each two-week session. The goal of the facilitation exercises is to facilitate voluntary eye movement using conjugated eye movements in the direction opposite to passive movements of the head. MAIN MEASURES: To assess ophthalmoplegia we measured the distance between the internal/external corneal margin and the canthus of the affected eye on images recorded on a video tape recorder. RESULTS: After the initial two-week basic rehabilitative treatment, the distance between the corneal margin and canthus decreased slightly. Subsequently, after each of the two facilitation exercise sessions, there were significant reductions in the distance between the corneal margin and canthus compared with that at the beginning of the respective facilitation exercise session. CONCLUSION: Facilitation exercises significantly improved the horizontal movement of eyes with ophthalmoplegia due to brainstem injury.

Adult↗

Role of quantitative CT in predicting hypoxemia and complications after lung lobectomy for cancer, with special reference to area of emphysema.

STUDY OBJECTIVES: To determine the ability of quantitative CT, with special reference to area of emphysema, to predict early postoperative oxygenation capacity and outcome after lung lobectomy for cancer. METHODS: Sixty-two consecutive patients scheduled to undergo lung lobectomy for cancer were enrolled in this study. The area of emphysema (< - 910 Hounsfield units) was measured on a three-dimensional CT lung model. Arterial oxygen saturation (Sao(2)) was calculated from Pao(2) measured 1 day before and 1 day after surgery with patients at rest breathing room air. A patient was considered to have recovered at the completion of a standardized management regimen. RESULTS: Postoperative Sao(2) (postSao(2)) was predicted by the baseline value and the area of emphysema with the use of a regression equation. Ten of the 62 patients (16%) had postoperative cardiopulmonary complications (CPCs). The median time to postoperative recovery was 3 days (range, 1 to 17 days). Predicted postSao(2) and predicted postoperative FEV(1) were shown to be significant independent predictors of postoperative CPCs as well as postoperative recovery time. CONCLUSION: Determining the area of emphysema by quantitative CT is useful in predicting early postoperative oxygenation capacity. Predicted oxygenation capacity and predicted ventilatory capacity independently affect perioperative outcomes. Therefore, using quantitative CT in combination with spirometry may improve risk prediction in patients undergoing lung lobectomy for cancer. However, the role of quantitative CT in grading nonemphysematous lung diseases, such as interstitial lung diseases, must be investigated.

Aged↗

Nontuberculous mycobacterial infection: CT scan findings, genotype, and treatment responsiveness.

STUDY OBJECTIVE: The purpose of this study was to compare the imaging findings of nontuberculous mycobacterial (NTM) infection in patients with normal and abnormal cystic fibrosis (CF) genotypes, and normal and abnormal alpha1-antitrypsin (AAT) phenotypes. DESIGN: A retrospective review of medical records and chest CT scans from 85 patients with microbiologically proven NTM infection was performed. All patients had undergone genotype analysis for CF mutations, and phenotypic evaluation for AAT status. Patients with homozygous CF or AAT were not included. Two independent observers assessed the patterns and distribution of disease, according to a standardized score sheet. In 52 patients, follow-up CT scans were obtained 1 to 46 months (mean duration, 8 months) following the initial CT scan. The CT scan findings on the follow-up scan were visually compared with those on the initial CT scan for progression or regression of abnormalities. Statistical analysis was performed to evaluate the relationship between the dominant CT scan pattern and CF/AAT status, and between CT scan pattern and radiologic change on follow-up. RESULTS: Fifteen patients (18%) were found to carry a single CF mutation, and an abnormal AAT phenotype was seen in 13 patients (15%). Three patients (3%) were found to have both a heterozygous CF mutation and a heterozygous AAT phenotype. On the initial CT scans, bronchiectasis and nodules were the most frequent findings of NTM infection in all three groups (p > 0.05). The prevalence of nodules was slightly lower in the CF group, and the prevalence of linear scarring was greater in the AAT group than in the normal group (p < 0.05). Among the 52 patients who had a follow-up CT scan, 8 (15%) had a CF mutation and 6 (12%) had an abnormal AAT phenotype. The extent and pattern of abnormality seen on the initial CT scan did not predict change on follow-up evaluation. After treatment, 40 patients (56%) with a normal CF genotype had decrease in disease extent, compared with 4 patients (25%) with a CF mutation (p < 0.05). Bronchiectasis was improved in approximately 35% of those with normal genotype, but in none of those with a CF mutation. CONCLUSION: In patients with NTM infection, the CT scan findings show only minor differences according to phenotype and genotype. Initial CT scan findings do not predict change on follow-up CT scan evaluation. However, on follow-up CT scan, patients with CF mutations are less likely to improve, while those with AAT phenotype appear to have a radiographic outcome similar to those with normal phenotype.

Adult↗

Efficacy of edaravone, a free radical scavenger, for the treatment of acute lacunar infarction.

The effect of edaravone as an inhibitor of ischemic brain damage in addition to routine treatment was retrospectively examined in 70 patients with lacunar infarction who were admitted within 24 hours of symptom onset. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS). The modified Rankin Scale (MRS) was used to assess clinical outcomes at 3 months after onset, with a good outcome defined as MRS score < or =2. Risk factors were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, and a history of smoking longer than 2 months. The probability of a good outcome and independence at 3 months was assessed by backward stepwise logistic regression analysis based on the maximum likelihood ratio. Administration of edaravone yielded an odds ratio with multivariate adjustment of 6.49 (95% confidence interval, 1.35 to 50.32; p < 0.05) for a good outcome at 3 months. Higher baseline NIHSS score and higher age also adversely affected the outcome at 3 months (p < 0.005). Administration of edaravone improves the outcome of patients with lacunar infarction.

Acute Disease↗

Rheumatoid arthritis-related lung diseases: CT findings.

PURPOSE: To evaluate computed tomographic (CT) findings of rheumatoid arthritis-related lung disease and categorize findings according to pathologic features. MATERIALS AND METHODS: CT scans obtained in 63 patients (27 men, 36 women; mean age, 61.7 years +/- 11.2 [SD]; range, 28-81 years) with rheumatoid arthritis were assessed. Mean duration of disease was 7.6 years +/- 9.2. Lung parenchymal abnormalities that included airspace consolidation, ground-glass opacity (GGO), reticulation, honeycombing, nodules, bronchiectasis, and air trapping were assessed retrospectively by two chest radiologists. Final decision was reached with consensus of these radiologists and a third radiologist. Patients were classified according to the predominant CT pattern. One of the chest radiologists and a pulmonary pathologist compared CT findings with pathologic findings in 17 patients. Interobserver agreement between the first two radiologists was assessed. Correlation between CT finding extent score and pulmonary function test results was estimated with Spearman rank correlation coefficient. RESULTS: GGO (57 [90%] patients) and reticulation (62 [98%] patients) were the most common CT features. Four major CT patterns were identified: usual interstitial pneumonia (n = 26), nonspecific interstitial pneumonia (n = 19), bronchiolitis (n = 11), and organizing pneumonia (n = 5). Usual interstitial pneumonia and nonspecific interstitial pneumonia CT patterns overlapped; GGO was more extensive in patients with nonspecific interstitial pneumonia CT pattern (P =.028). In 17 patients who underwent biopsy, CT findings reflected pathologic findings. Exceptions were two patients classified with usual interstitial pneumonia at CT but with nonspecific interstitial pneumonia at pathologic analysis; one patient, with nonspecific interstitial pneumonia at CT but desquamative interstitial pneumonia at pathologic analysis; and one patient, with lymphoid interstitial pneumonia at CT but nonspecific interstitial pneumonia at pathologic analysis. CONCLUSION: Rheumatoid arthritis is associated with four CT patterns: usual interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis, and organizing pneumonia. The most common CT features of rheumatoid arthritis-related lung disease were GGO and reticulation.

Adult↗

Usefulness of interposition arthroplasty in the Sauvé-Kapandji procedure for rheumatoid wrist.

The aim of synovectomy combined with the Sauvé-Kapandji (S-K) procedure for the treatment of a rheumatoid wrist is to obtain a stable painless wrist that retains sufficient mobility for function. However, loss of motion occurs postoperatively in most cases. In our study of 59 rheumatoid patients, the results of the transposition of distal strips of retinaculum into the radiocarpal and ulnocarpal joints for interposition arthroplasty to maintain wrist motion (interposition group), and transposition below the extensors to provide a gliding surface (SK group) were evaluated. The distal end of the ulna was fixed to the radius with poly-L-lactic acid screws, and a proximal strip of retinaculum was placed above the extensors after synovectomy of the rheumatoid wrist. Clinical symptoms, radiographic changes, and postoperative complications were assessed 3-9 years (mean 5.9 years) postoperatively. Patients in the interposition group showed better postoperative results, including wrist motion, than those of patients in the SK group. Both procedures resulted in only minor complications such as superficial skin necrosis, hematoma, and superficial infection. We concluded that interposition arthroplasty combined with the S-K procedure using a distal strip of retinaculum might be a safe and appropriate method for wrist reconstruction following synovectomy of a rheumatoid wrist.

Journal Article↗

Clinical investigation of amelanotic malignant melanoma in the oral region.

PURPOSE: Amelanotic oral malignant melanoma (AOMM) is a rare tumor that is difficult to diagnose. We studied the clinical and pathologic features of nine cases of this tumor to define diagnostic criteria and estimate prognoses for 2 different types of AOMM. PATIENTS AND METHODS: Nine patients with 2 different types of primary AOMM were examined between 1970 and 2002. The histopathology of surgical specimens was studied, uncertain diagnoses were supported by immunohistochemical reactions, and electron microscopy and prognoses were reviewed retrospectively. RESULTS: AOMM without radial growth phase may be particularly difficult to diagnose correctly without immunohistochemical assistance. Tumors consisted of a mixture of polygonal and spindle cells in different ratios in tumors with and without radial growth phase. The life span ranged from 3 months to 6 years 3 months, and all 9 patients died of the tumor. In 7 of the 9 cases, distant metastases were found. CONCLUSIONS: AOMM without radial growth phase may be misdiagnosed as epulis or squamous cell carcinoma. Questionable lesions, particularly maxillary and palatal lesions, must be biopsied for histopathologic and possibly immunohistochemical examinations followed by rapid treatment. The prognosis of AOMM was poor.

Aged↗

Induction of myogenin messenger ribonucleic acid in rat skeletal muscle after 1 hour of passive repetitive stretching.

OBJECTIVE: To investigate the effect of repetitive passive stretch of living rat muscle on myogenin messenger ribonucleic acid (mRNA) expression. DESIGN: Case-controlled study. SETTING: University laboratory. ANIMALS: Seventeen female 8-week-old Wistar rats. INTERVENTIONS: Repetitive stretch (15 times/min) was performed manually on gastrocnemius muscle of anesthetized rats for 15, 30, and 60 minutes. MAIN OUTCOME MEASURES: Total RNA was extracted, after the animals were killed, from the gastrocnemius muscle, and Northern blotting was performed using oligonucleotide complementary to myogenin. RESULTS: Repetitive stretch to gastrocnemius muscles of anesthetized rats for 1 hour induced a 21.5% increase in the expression of myogenin mRNA. CONCLUSIONS: Repetitive passive stretch of the rat skeletal muscle for 60 minutes induced the expression of myogenic transcription factor myogenin mRNA. These findings suggest the clinical utility of passive repetitive stretch to maintain muscle strength in patients who are unconscious or paralyzed.

Animals↗

Addition of intensive repetition of facilitation exercise to multidisciplinary rehabilitation promotes motor functional recovery of the hemiplegic lower limb.

OBJECTIVE: To evaluate the effects of the intensive repetition of movements elicited by the facilitation technique to improve voluntary movement of a hemiplegic lower limb in patients with brain damage. DESIGN: A multiple-baseline design (A-B-A-B: A without specific therapy, B with specific therapy) across individuals. PATIENTS: The sample comprised 22 subjects with stroke and 2 brain tumour-operated subjects (age: 50.7 +/- 9.6 years, time after onset: 7.1 +/- 2.6 weeks). They were selected from among 165 patients with stroke who were admitted to our rehabilitation centre from September 1, 1995 to March 31, 1997. METHODS: Two 2-week facilitation technique sessions (more than 100 repetitions a day for each of 5 kinds of movement) were applied at 2-week intervals in patients with hemiplegia, who were being treated with continuous conventional rehabilitation exercise without the facilitation technique for hemiplegia. Motor function of the affected lower limb (Brunnstrom Recovery Stage of hemiplegia, the foot-tap test and the strength of knee extension/flexion) and walking velocity were evaluated at 2-week intervals. RESULTS: Significant improvements in Brunnstrom Stage, foot-tapping and the strength of knee extension/flexion of the affected lower limb were seen after the first conventional rehabilitation exercise session and after the first and second facilitation technique and conventional rehabilitation exercise sessions. The improvements after facilitation technique and conventional rehabilitation exercise sessions were significantly greater than those after the preceding conventional rehabilitation exercise sessions. CONCLUSION: Intensive repetition of movement elicited by the facilitation technique (chiefly proprioceptive neuromuscural facilitation pattern, stretch reflex and skin-muscle reflex) improved voluntary movement of a hemiplegic lower limb in patients with brain damage.

Activities of Daily Living↗