Biomedical subjects
Publications and source records attributed to T Tamura.
The recommended phase II dose of paclitaxel 180 mg m(-2) given as a 3-h infusion followed by nedaplatin 100 mg m(-2) in a 1-h infusion every 3-4 weeks was determined in 52 chemo-naive patients with unresectable squamous cell carcinoma (SCC), with a promising response rate for lung SCC of 55%.
Several recent studies have quantified abnormalities in Parkinsonian gait. However, few studies have attempted to quantify the regularity of body motion during walking in patients with Parkinson's disease. The aim of the paper was to characterise body motion patterns in healthy, elderly subjects and patients with Parkinson's disease during walking. Body motion was recorded during walking for 16 patients with Parkinson's disease and ten healthy, elderly subjects using a tri-axial accelerometer device. To characterise the body motion patterns, time-frequency patterns of the body acceleration signal were estimated using a matching pursuit algorithm. Data from the study showed that the healthy, elderly subjects and patients with Parkinson's disease had different time-frequency patterns. The time-frequency patterns were classified into four distinct patterns based on their time durations: vertical (< 0.15 s), circular (0.15-0.5 s), short horizontal (0.5-2.0 s) and long horizontal (> 2.0 s). The data showed that the energy of the long horizontal patterns, representing long-term smooth and regular (rhythmic) activities, significantly decreased, but the energy of the circular patterns, representing irregular activities, increased in the patients with mild Parkinson's disease, compared with those of the healthy, elderly subjects (p < 0.01). Futhermore, these features were seen more clearly in the body motions of severe case patients than is that of mild case patients. It was concluded that these differences are probably due to a lack of ability to control normal and smooth movement is Parkinson's disease.
dsRNA is a powerful tool for gene-specific silencing in plants and animals. In this study, we examined the use of gene silencing in generating transgenic silkworms resistant to the Bombyx mori nucleopolyhedrovirus (BmNPV). Using a transposon piggyBac system, we first generated BmN cells (rBmN-lef1), which carried artificial genes designed for expressing dsRNAs with sequences of the essential viral gene lef-1. NPV DNA microarray analysis revealed that the accumulation of lef-1 mRNA was successfully inhibited in rBmN-lef1 infected with BmNPV. The virus titer in the culture medium of rBmN-lef1 at 48 hr post-infection (h.p.i.) was 50% of that of the control cells. Moderate BmNPV-resistance caused by transgenesis of the artificial dsRNA-expressing gene was confirmed in the transgenic silkworms. Virus production was reduced in transgenic silkworms relative to controls up to 96 hrs after viral inoculation. Although complete protection was not achieved and the transgenic larvae ultimately died, this is the first report to show the use of RNAi in confering enhanced viral resistance on transgenic animals.
BACKGROUND: Proliferation and apoptosis events are altered in Helicobacter pylori infection. However, whether H. pylori eradication has an effect on the disturbed kinetics in metaplastic mucosa has not been well elucidated. AIM: To investigate the effect of eradication on the gastric cell kinetics. SUBJECTS AND METHODS: Initially, biopsies were obtained from 74 H. pylori-infected subjects and repeated 12 and 24 months after eradication. Biopsies were immunohistochemically stained for apoptosis by single-stranded DNA, for proliferation by Ki-67 antibodies and for intestinal metaplasia MUC2, MUC5AC, MUC6 and CD10. RESULTS: While antral apoptosis in intestinal metaplasia was significantly lower than in non-intestinal metaplasia, proliferation was significantly higher (greater and lesser curvatures, P < 0.05, respectively). This resulted in a significantly lower apoptosis/proliferation ratio in intestinal metaplasia than in non-intestinal metaplasia (antrum greater and lesser curvatures and corpus greater curvature, P < 0.05). After successful eradication, apoptosis and proliferation decreased in both intestinal metaplasia and non-intestinal metaplasia. The pattern of reduction of apoptosis and proliferation differed in these two groups. However, in the corpus, the reduction resulted in a significant increase in the apoptosis/proliferation ratio in both. CONCLUSION: Proliferation and apoptosis are unevenly and disproportionately altered in H. pylori infection leading to an imbalance in cell kinetics. Eradication of the organism improves the balance and may possibly play a role in the prevention of malignancy transformation in the metaplastic mucosa.
The subchronic toxicity of enzymatically decomposed rutin, which consists mainly of isoquercitrin, was investigated in male and female Wistar rats with dietary administration at concentrations of 0, 0.2, 1 and 5% for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any groups. Body weight gain was reduced from week 10 to the end of the experiment in the 5% dosed males as compared to the 0% controls. Decreased erythrocytic parameters, i.e. red blood cell count, hemoglobin concentration and hematocrit, and significantly lowered serum triglyceride levels were also detected in the 5% males. Organ weight measurement, macro and microscopic observation revealed no test substance-related toxicological changes. Based on the above findings, no-observed-adverse-effect levels (NOAELs) for male and female rats were estimated to be 1 and 5%, respectively, translating into 539 and 3227 mg/kg b.w./day.
BACKGROUND: Olopatadine hydrochloride (olopatadine) is one of the second-generation antihistamines, which is prescribed for allergic disorders such as rhinitis, urticaria and eczema dermatitis. OBJECTIVES: To investigate the possible anti-inflammatory effect of olopatadine on the chronic contact hypersensitivity response to repeated topical application of oxazolone in mice. METHODS: The preventive and therapeutic effects of oral olopatadine were quantified by measurements of ear swelling, cytokine protein and mRNA expression in the ear lesion, and were compared with those of topical betamethasone 17-valerate (betamethasone). RESULTS: The ear receiving repeated applications of oxazolone exhibited erythema, oedema and abrasion. Both preventive and therapeutic administration of olopatadine (10 mg kg(-1) day(-1)) significantly inhibited the ear swelling and the increased production of interleukin (IL)-4, IL-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor. In the histopathological analysis, olopatadine ameliorated epidermal hyperplasia and infiltration of inflammatory cells. Consistent with these results, olopatadine significantly reduced the increased expression of interferon-gamma and IL-4 mRNA. Although betamethasone (0.012 mg ear(-1) day(-1)) showed similar activities to olopatadine against these responses, it caused atrophy of the ear skin. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.
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OBJECTIVE: This study was designed to assess the effect of stellate ganglion near-infrared irradiation (SGR) on glossodynia and the mechanism of action. STUDY DESIGN: Thirty-seven patients with glossodynia received SGR once weekly for 4 weeks. The response to treatment was evaluated on the basis of the change in pain intensity, assessed with a visual analogue scale (VAS) before and after 4 weeks of treatment. The temperature and blood flow of the tongue were also measured before and after first SGR. As control, eight healthy subjects were studied. RESULTS: Tongue pain as assessed by the VAS decreased in 28 of the 37 patients (75.7%). Mean pain intensity decreased significantly from 5.1 +/- 2.2 to 1.9 +/- 2.1 (P < 0.05). Tongue blood flow at rest in the patients with glossodynia [7.2 +/- 1.6 ml min(-1) (100 g)(-1)] was significantly lower than that in the healthy subjects [7.8 +/- 0.23 ml min(-1) (100 g)(-1)]. Five minutes after SGR, the temperature of the tongue rose 1.5 +/- 0.21 degrees C, and blood flow increased to 8.5 +/- 1.2 ml min(-1) (100 g)(-1). Tongue blood flow (at rest) after 4 weeks of SGR had increased to 7.7 +/- 1.1 ml min(-1) (100 g)(-1). CONCLUSION: SGR is an effective treatment for glossodynia. The mechanism by which SGR improves symptoms associated with glossodynia is thought to be as follows: SGR inhibits abnormally increased sympathetic activity associated with glossodynia. This is followed by normalization of decreased tongue blood flow, thereby alleviating pain.
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Spontaneously hypertensive heart failure (SHHF) rats develop hypertension and heart failure. We hypothesized that induction of hyperthyroidism should accelerate development of heart failure in male SHHF rats. Male and female SHHF rats received diets containing desiccated thyroid glands (DTG) or a control diet for 8 wk. Male and female Wistar-Kyoto rats were used as normotensive controls. DTG treatment reduced body weight in male, but not female, SHHF rats but increased body temperature and heart weight-to-body weight ratio in both genders. In DTG-treated male SHHF rats, serum triiodothyronine levels doubled relative to SHHF controls, whereas O2 consumption increased in DTG-treated SHHF rats. Frequency of breathing in air increased in DTG-treated female rats, and ventilation increased in DTG-treated male rats. Ventilatory equivalents exhibited gender differences in SHHF rats, were decreased in both genders by DTG treatment, and reached levels similar to those of Wistar-Kyoto rats. DTG increased heart rate, right ventricular pressure, and contractility in both genders and increased left ventricular pressure in SHHF male rats. These results refute our hypothesis and suggest that cardiopulmonary function of SHHF male rats may be improved by DTG treatment.
The TBP-like protein (TLP/TRF2/TLF), which belongs to the TBP family of proteins, is present in all metazoan organisms. Although the human TLP has been reported to interfere with transcription from TATA-containing promoters, the transcription activation potential of TLP in higher animals is obscure. We previously demonstrated that artificially promoter-recruited TLP behaves like an unconventional transcriptional activator. In this study, we investigated the effects of TLP on TATA-less promoters of mouse and human terminal deoxynucleotidyl transferase (TdT) genes by transient reporter assays. As expected, TLP repressed both basal and activator-augmented transcription from the TATA-containing adenovirus major late promoter (MLP) and E1B promoter. On the other hand, however, TLP significantly stimulated both basal and activated transcription from TdT promoters. We investigated the strength of the promoters in chicken DT40 cells that lack the TLP gene. The MLP showed higher activity but the TdT promoter showed lower activity in TLP-null cells than in the wild-type cells. Moreover, ectopic expression of mouse TLP in the TLP-null cells considerably stimulated the TdT promoter. Insertion of a TATA element upstream from the TdT core promoter resulted in a loss of TLP-mediated activation. The mouse TLP was demonstrated to bind specifically to TFIIA with greater strength than TBP. We constructed mutated TLPs having amino acid substitutions that impair TFIIA binding. A representative TLP mutant lacking TFIIA-binding ability could not stimulate transcription from the TdT promoter, whereas that mutation suppressed TLP-mediated transcription repression of TATA promoters. The results of the present study suggest that the vertebrate TLP potentiates exogenous TATA-less promoters and that TFIIA plays an important role in the TLP function.
Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.
BACKGROUND: It is known that, although rare, mesenchymal chondrosarcoma can originate intracranially. However, no such malignant tumour has been described in the sellar region. CLINICAL PRESENTATION: We report a case of mesenchymal chondrosarcoma in a 21-year-old man who presented with double vision, right blepharoptosis and facial pain. Upon initial admission, no endocrinological abnormalities were found, and computed tomography and magnetic resonance imaging revealed a mass with calcification in the sella and right cavernous sinus. INTERVENTION: For this malignant tumour, three surgical resections, two sessions of gamma-knife radiosurgery, one session of fractional irradiation, and one cycle of chemotherapy were performed, resulting in only brief arrest of the tumour growth. Pathologically, the tumour consisted of undifferentiated small cells of high cellularity, and islands of hyaline cartilage. The undifferentiated small cells showed immunoreactivity for vimentin and ultrastructural features suggesting a mesenchymal origin. Lacunar cells in the islands were immunopositive for S-100 protein and vimentin. CONCLUSION: Although malignant tumours in the sellar region are rare, they should be considered in the differential diagnosis of various sellar tumours typified by non-functioning pituitary adenoma, and mesenchymal chondrosarcoma is one possible candidate.
BACKGROUND: Successful eradication of Helicobacter pylori infection after failure of standard triple therapy is difficult. The efficacy and safety of levofloxacin based triple therapy as a first-line therapy has-been studied. AIMS: The aim was to evaluate the efficacy and tolerability of levofloxacin based therapy after a failed standard triple therapy. PATIENTS: We conducted a prospective, uncontrolled study of a consecutive series of 33 patients who failed eradication with 1 week of lansoprazole-amoxicillin-clarithromycin triple therapy. METHODS: The subjects were retreated with 1 week of LA-LVFX triple therapy (lansoprazole, 30 mg twice daily; amoxicillin, 1000 mg twice daily: levofloxacin, 200 mg twice daily). Cure of infection was defined as negative results from culture, histology and a urea breath test 4 to 8 weeks after the second-line therapy. RESULTS: The eradication rate was 69.7% (23/33) by both intention-to-treat and per-protocol analyses (95% confidence interval=61-79%). Seven (21.2%) patients experienced mild side-effects, such as soft stools and taste disturbance. No patient stopped the medication on account of adverse effects. CONCLUSIONS: Levofloxacin based triple therapy is an effective second-line treatment after a failed standard triple therapy.
PROBLEM: In T lymphocytes, nuclear factor of activated T cells (NF-AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF-AT and pregnancy. METHOD OF STUDY: With informed consent, peripheral blood cells (PBCs) were obtained from non-pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The expression of NF-AT2 and NF-AT3 mRNAs in PBCs was measured by a quantitative reverse transcriptase-polymerase chain reaction method. RESULTS: In the early pregnancy period, in successful pregnancy, both NF-AT2 and NF-AT3 mRNAs increased significantly, whereas in cases of spontaneous abortion they did not change significantly. After peaking, they decreased gradually and were re-elevated in the ninth and tenth gestational month. In the puerperal period, NF-AT3 mRNAs decreased, but NF-AT2 mRNA showed a comparatively high expression level. CONCLUSION: These findings suggested that in humans NF-AT signal transduction might be involved in alloantigenic recognition and tolerance and play important roles, especially in the early and late period of pregnancy.
This study used functional magnetic resonance images (fMRI) to examine brain activity during clenching, gum chewing, and tapping tasks. It has been considered difficult to obtain sufficient fMRI data during jaw movement because the head motion associated with the jaw movements creates artifacts on the images. To avoid these artifacts, larger pixels were used, thus allowing some head motion of the subjects, and data from subjects where the heads were evaluated to have moved more than 0.5 mm were discarded. Further, all pixels obtained by fMRI were evaluated and pixels positively synchronized with the task, which were considered to show brain activity, were selected. Sufficient fMRI data was obtained from 30 experiments, 10 sets for each task. During the clenching and tapping tasks, the activated pixels were in the sensory, motor and pre-motor cortexes, and in the sensory and motor cortexes but not in the pre-motor cortex during the gum chewing task. There appears to be no significant differences between right- and left-hemispheres. It is conceivable that there are differences between voluntary jaw movements (clenching and tapping tasks) and mastication (gum chewing task) concerning the control of jaw movements.
BACKGROUND: The standard treatment for patients with locoregional recurrence of non-small cell lung cancer (NSCLC) after complete resection has not been established. The aim of this study was to evaluate clinicopathologic characteristics, type of locoregional recurrence, pattern of subsequent failure, and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995, we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found to have locoregional recurrence without distant metastasis or pleural or pericardial involvement. RESULTS: The median time to locoregional recurrence was 13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received further treatment for the recurrence: thoracic irradiation in 26, surgery in two, systemic chemotherapy in two, and a combination of the above in 3 patients. Subsequent distant failure was detected in 26 (68 %) of the 38 patients assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in 5, and others in 13. The median interval from the recurrence to distant failure was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A multivariate analysis showed that local therapy for the locoregional recurrence had no significant impact on postrecurrent survival or distant failure-free survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence developed distant metastases early after the first recurrence. Systemic chemotherapy in addition to local therapy may be of benefit in this population.
BACKGROUND: This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included. PATIENTS AND METHODS: Patients initially received a single oral dose of gefitinib followed by 10-14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial response (duration 35-361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40-127 days). CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe.