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Biomedical subjects

M Tachibana

Publications and source records attributed to M Tachibana.

At least 19 recordsLinked to original sources

Observation of all the components of elastic constants using tetragonal hen egg-white lysozyme crystals dehydrated at 42% relative humidity.

Success in measuring transverse sound velocity allowed us to determine, for the first time, all six elastic constants of a protein crystal. An ultrasonic pulse-echo method was used to perform sound velocity measurements on tetragonal hen egg-white (HEW) lysozyme crystals that were partially dehydrated at 42% relative humidity. The measurements were performed using the (110), (101), and (001) crystallographic faces. Thus, all six elastic constants of the dehydrated tetragonal HEW lysozyme crystals were determined: C11=C22=12.44 GPa, C12=7.03 GPa, C13=C23=8.36 GPa, C33=12.79 GPa, C44=C55=2.97 GPa, and C66=2.63 GPa. In addition, for the hydrated crystals, the longitudinal sound velocities along the [110] direction and the direction normal to the (101) face were measured. From these results, all the components of elastic constants in the hydrated crystals were extrapolated.

Animals↗

Multiplex polymerase chain reaction assay for simultaneous detection of black-pigmented Prevotella species in oral specimens.

Prevotella species are a major component of the oral microflora and some have been implicated in various forms of periodontal disease. Despite the importance of understanding the prevalence of these organisms in the oral microflora, no rapid, simultaneous detection system for these species has been reported. This study developed a multiplex polymerase chain reaction assay for the simultaneous detection of four oral black-pigmented Prevotella species in various oral specimens. This assay will be useful for determining the prevalence of these organisms in the oral ecosystem. Furthermore, this assay system should prove a useful tool for analyzing the role of black-pigmented Prevotella species in the mouth.

Bacteriological Techniques↗

Melting pattern of diquark condensates in quark matter.

Thermal color superconducting phase transitions in high density three-flavor quark matter are investigated in the Ginzburg-Landau approach. The effects of nonzero strange quark mass, electric and color charge neutrality, and direct instantons are considered. Weak coupling calculations show that an interplay between the mass and electric neutrality effects near the critical temperature gives rise to three successive second-order phase transitions as the temperature increases: a modified color-flavor locked (mCFL) phase (ud, ds, and us pairings) --> a d-quark superconducting (dSC) phase (ud and ds pairings) --> an isoscalar pairing phase (ud pairing) --> a normal phase (no pairing). The dSC phase is novel in the sense that while all eight gluons are Meissner screened as in the mCFL phase, three out of nine quark quasiparticles are always gapless.

Journal Article↗

Effect of intracrystalline water on longitudinal sound velocity in tetragonal hen-egg-white lysozyme crystals.

Longitudinal sound velocity of tetragonal hen-egg-white (HEW) lysozyme crystals was measured during air drying by ultrasonic pulseecho method. The sound velocity increases with exposure to open air and approaches a constant value. The maximum value is approximately 2900 m/s that is about 1.6 times as much as that of original one before drying. In addition, the sound velocity clearly recovers to original one after immersing the dried crystal in solution. Therefore, the sound velocity in tetragonal HEW lysozyme crystals can be reversibly changed due to dehydration and rehydration. These changes in sound velocity are discussed in the light of water-mediated intramolecular and intermolecular interactions in the crystals.

Animals↗

A MEK inhibitor (U0126) markedly inhibits direct liver invasion of orthotopically inoculated human gallbladder cancer cells in nude mice.

Primary cancer of the gallbladder is not unusual. Most cases of gallbladder cancer are found at an advanced stage, accompanied by the invasion to the liver, metastases to the lymph nodes and distant organs, and peritoneal dissemination. In this study, we first examined the effect of mitogen-activated protein kinase kinase (MEK) inhibitors on the production of matrix metalloproteinases (MMPs), urokinase-type plasminogen activator (uPA), and tissue inhibitors of metalloproteinases (TIMPs) in a human gallbladder cancer cell line, NOZ cells in vitro. MEK inhibitors (PD98059 and U0126) inhibited the production of MMP-2, MMP-9 and high MW uPA, and upregulated TIMPs (TIMP-1, TIMP-2 and TIMP-3). Subsequently, we examined the effect of U0126 on invasion and metastasis of orthotopically inoculated NOZ cells in nude mice. Direct liver invasion by cancer cells was detected in all of the mice in the control group, but in only one mouse in the U0126-treated group. Most of the primary tumors in the U0126-treated group expanded to the liver, but did not invade into the liver. Vessel invasion in the liver was evident in 4 out of 5 mice in the control group, but in only one mouse in the U0126-treated group. Lymph node metastases and peritoneal dissemination were recognized in all of the mice in both groups. All 5 mice in the U0126-treated group, and 4 out of 5 mice in the vehicle control group, had metastases in the lungs. The present results suggest that a MEK inhibitor, U0126, prolonged the survival of the mice with NOZ tumor by inhibiting direct liver invasion and vessel invasion of the cancer cells via down-regulation of the matrix degrading ability of the cancer cells.

Animals↗

Quantitative air-plethysmographic venous function and ambulatory venous pressure in patients with primary varicose vein.

AIM: The purpose of this study was to investigate the relationship between air-plethysmographic volume parameters under standard exercise loading and foot venous pressure parameters under ideal exercise loading in patients with primary varicose veins. METHODS: Seventy-one lower limbs in 39 patients with primary varicose veins and 8 lower limbs in 4 healthy controls were examined. The patients included 12 males and 27 females, ranging in age from 36 to 79 years. Eighteen limbs were asymptomatic (class 0) limbs, 28 limbs had symptoms of swelling or heaviness (class 1), and 25 had skin lesions (class 2+3). The patients and controls were examined with duplex scanning, air-plethysmography, and ambulatory foot venous pressure measurement. RESULTS: The mean ambulatory venous pressure (AVP) was significantly higher in the class 2+3 limbs than in the other classes, but it was not significantly higher in class 1 than in class 0. There were no significant differences between the class 2+3 limbs and class 1 limbs in any of the air-plethysmographic parameters. However, the VFI in the class 0 limbs was significantly different from that in the other 2 groups. Among all parameters examined, the venous filling index (VFI) was the most closely correlated with the AVP. All air-plethysmographic parameters were negatively correlated with the VRT. CONCLUSIONS: Among non-invasive air-plethysmographic volume parameters, VFI is the most reliable indicator for quantitative evaluation of calf pump function.

Adult↗

Identification of dislocations in large tetragonal hen egg-white lysozyme crystals by synchrotron white-beam topography.

Large tetragonal hen egg-white (HEW) lysozyme crystals have been grown by a salt concentration-gradient method. The grown crystals, of thicknesses greater than 1.5 mm, were observed by means of X-ray topography using white-beam synchrotron radiation. Line contrasts clearly appeared on the Laue topographs. Extinction of the line images was observed in specific reflections. These results mean that the observed lines correspond to dislocation images. From the extinction criterion it is shown that the predominant dislocations are of screw character with <110> Burgers vectors. In addition, dislocation loops with [001] Burgers vectors have been found in a tetragonal HEW lysozyme crystal including some cracks. These results are discussed in the light of dislocation elastic energy and slip systems in the crystals.

Animals↗

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences. Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.

Aged↗

Impact of splenectomy on the early outcome after oesophagectomy for squamous cell carcinoma of the oesophagus.

AIM: Operative procedures for oesophageal malignancies are becoming more extensive and may result in fatal complications. Splenectomy compromises the immune system and can lead to increased susceptibility to infections. The aim of the present study was to report the early outcome of patients who underwent oesophagectomy and simultaneous splenectomy due to oesophageal squamous cell carcinoma (SCC). METHODS: Pre-operative risks and post-operative morbidity and mortality in 135 patients who had undergone extensive oesophagectomy without simultaneous splenectomy for SCC of the thoracic oesophagus were compared with those of 14 patients who had undergone oesophagectomy associated with splenectomy. RESULTS: Post-operative pneumonia, intra-abdominal abscess, post-operative sepsis and anastonotic leakage were significantly increased when splenectomy was added to the original operation. The incidence of in-hospital death was significantly higher among splenectomized than non-splenectomized patients (35.7% vs 8.1%, P<0.01). Pulmonary complications and leakage were the main causes of death. Multivariate analysis recognized splenectomy as an independent prognostic factor for in-hospital death following transthoracic oesophagectomy for SCC. CONCLUSION: The addition of splenectomy to transthoracic oesophagectomy for oesophageal carcinoma can be a fatal combination. Preservation of the spleen should be the primary intention. In circumstances that necessitate splenectomy precautions should be taken to prevent post-operative infectious complications.

Carcinoma, Squamous Cell↗

Significance of platelet-reactive antibody screening for patients facing frequent platelet transfusions.

It is not clear whether platelet-reactive antibody screening is clinically significant for patients facing frequent platelet transfusions. On the basis of data from 96 patients who had been examined for platelet-reactive antibodies by the mixed passive hemagglutination method for a variety of reasons, we investigated the following three issues retrospectively: (1) the relationship between platelet-reactive antibodies and the occurrence of problems in platelet transfusions, such as refractoriness or nonhemolytic reactions; (2) the influence of a history of transfusion on the production of those antibodies; and (3) the effect of screening for those antibodies on the prompt administration of appropriate platelet components. More than half of the platelet transfusion-related problems were associated with platelet-reactive antibodies. For patients with a history of transfusion, the mean period before a clinical problem occurred with platelet transfusions was 9 days,compared with 66 days for those without such a history. Accordingly, during the period, patients with a history of transfusions received fewer units of platelets and had fewer donor exposures than did patients without such a history. On the other hand, most patients who had been screened in advance for those antibodies received appropriate platelet components without delay, whereas an average of 10 days was needed before those who had not been screened received compatible platelets. The patients who had not been screened were transfused with 68 units of random platelets on average during the period. When frequent platelet transfusions are anticipated, especially for patients with a history of transfusion, screening for platelet-reactive antibodies beforehand would be helpful for prompt administration of appropriate platelets, although problems, such as the cost of those platelets and the burden on donors, remain to be resolved.

Journal Article↗

Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells.

TRAIL has gained much attention for its specific induction of apoptosis in cancer cells but not in normal cells. This phenomenon has been explained thus: that cancer cells dominantly express death receptors while normal cells express decoy receptors. However, recent reports have shown that some cancer cell lines are resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and the presence of death receptors. This suggested the existance of an inhibitory factor. We herein showed that NF-kappaB is a key molecule underlying the TRAIL-resistant mechanism in renal cell carcinoma (RCC) cell lines. We observed that NF-kappaB is constitutively activated in resistant cell lines. Forced expression of antisense cDNA of IkappaBalpha, a specific inhibitor of NF-kappaB, in TRAIL-sensitive cell lines with a low NF-kappaB activity result in constitutive activation of NF-kappaB and resistance to TRAIL-induced apoptosis. Adenoviral expression of a stable form of IkappaBalpha in the TRAIL-resistant cell lines induced apoptosis. These data suggest that RCC can be classified into two subsets: TRAIL-sensitive RCC with a low NF-kappaB activity and TRAIL-resistant RCC with constitutively activated NF-kappaB. In the former group TRAIL can be a treatment option, while in the latter group a molecular approach targeting NF-kappaB appears to be a promising therapy.

Antineoplastic Agents↗

Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3.

The covalent modification of histone tails has regulatory roles in various nuclear processes, such as control of transcription and mitotic chromosome condensation. Among the different groups of enzymes known to catalyze the covalent modification, the most recent additions are the histone methyltransferases (HMTases), whose functions are now being characterized. Here we show that a SET domain-containing protein, G9a, is a novel mammalian lysine-preferring HMTase. Like Suv39 h1, the first identified lysine-preferring mammalian HMTase, G9a transfers methyl groups to the lysine residues of histone H3, but with a 10-20-fold higher activity. It was reported that lysines 4, 9, and 27 in H3 are methylated in mammalian cells. G9a was able to add methyl groups to lysine 27 as well as 9 in H3, compared with Suv39 h1, which was only able to methylate lysine 9. Our data clearly demonstrated that G9a has an enzymatic nature distinct from Suv39 h1 and its homologue h2. Finally, fluorescent protein-labeled G9a was shown to be localized in the nucleus but not in the repressive chromatin domains of centromeric loci, in which Suv39 h1 family proteins were localized. This finding indicates that G9a may contribute to the organization of the higher order chromatin structure of non-centromeric loci.

Amino Acid Sequence↗

Prognosis of T4 gastric carcinoma patients: an appraisal of aggressive surgical treatment.

BACKGROUND AND OBJECTIVES: Despite precipitous drop in the incidence of gastric carcinoma in Japan, it is still one of the leading causes of death associated with malignant disease. Once the contiguous organs are involved the prognosis becomes dismal. Prognostic factors governing the survival of patients with T4 gastric carcinoma remain unclear. METHODS: Between 1980 and 1998, 150 patients were treated for T4 gastric carcinoma. Results and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: With a 73% resectability, patients with tumor resection had a significantly (P < 0.0001) improved survival rate. Within an acceptable operative mortality (2.6%), apparently curative cases had survival benefit (P < 0.0001) over noncurative cases. In the multivariate analysis, the death risk increased by 2.18 (relative risk) when splenectomy was spared from the operative procedure (P < 0.0071). Presence of esophageal invasion was the other independent prognostic factor in T4 gastric carcinoma patients (relative risk 2.11). Conventional prognostic factors along with the type of organs invaded by the carcinoma had no impact on prognosis. CONCLUSIONS: Patients with T4 gastric carcinoma might be benefited from aggressive surgery with a curative intent. Whenever possible, splenectomy should be done along with invaded organ resection.

Adult↗

Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy.

PURPOSE: We tried to elucidate the effects of sulindac on human colorectal carcinoma. METHODS: Sulindac (300 mg/day) was administered for two weeks before operation to 33 patients with sporadic colorectal carcinoma (Sulindac Group). Resected specimens were used to detect apoptosis by terminal dUTP nick end labeling and transforming growth factor (TGF)-beta1 expression by immunohistochemistry. The results were compared with those from the historical Control Group. Twenty-nine available preoperative biopsies taken from carcinomas before sulindac prescription and 22 concurrent colorectal adenomas (9 and 13 in Sulindac and Control Groups, respectively) in the resected specimen were also examined regarding TGF-beta1 expression. RESULTS: In the resected carcinomas and adenomas, more frequent apoptosis and higher TGF-beta1 scores were observed in the Sulindac Group than in the Control Group. Overexpression of TGF-beta1 and apoptosis occurred in the same region in adenomas but not in carcinomas. A positive correlation between TGF-beta1 scores and apoptotic frequency was found in adenomas (P = 0.01, rho = 0.91) but not in carcinomas (P = 0.89, rho = 0.03). CONCLUSION: We conclude that sulindac induces apoptosis in human colorectal carcinomas as well as in adenomas. Also, one of the antineoplastic effects of sulindac might be mediated by upregulating TGF-beta1 expression, particularly in colorectal adenomas.

Adenoma↗

Dukes' classification as a useful staging system in resectable squamous cell carcinoma of the esophagus.

Dukes' classification for colorectal cancer is simple and has been widely used as a valuable prognostic indicator. It has been used as an assessment of gastric cancer, but it has not been evaluated for esophageal cancer. Of 251 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and April 1999, 155 patients underwent esophagectomy with a curative intent. Clinicopathologic characteristics of those 155 patients were retrospectively investigated according to the Dukes', tumor node metastasis (TNM) and Japanese staging systems. Dukes' classification showed a clear correlation between tumor stage and survival. The 3-year and 5-year survival rates of 64 Dukes' A cases were excellent (97.4% and 93.7%), good for 12 Dukes' B (75% and 75%), and poor for 79 Dukes' C (50.5% and 43.4%), respectively (P < 0.05; Dukes' A vs B, P < 0.0001; Dukes' A vs C, P < 0.10; Dukes' B vs C). TNM stage classification also showed a good correlation between tumor stage and survival, but there were no significant differences between stage 0, I and stage IIA cases (P = 0.2678) and between stage III and stage IV cases (P = 0.8298). In the Japanese staging system, there were no significant differences among stage 0, stage 1, and stage 2 cases (P = 0.4093). Dukes' classification was significantly correlated with tumor size, Borrmann type, histological type, and vessel invasion. Subdivision of Dukes' C according to the number of positive lymph nodes (1-4 vs > or = 5) showed a clearer correlation with survival rather than other subdivisions, such as the metastatic lymph node ratio (< 1.0 vs > 1.0) or the site of lymph node metastasis. Dukes' classification, which incorporates the number of positive lymph nodes, correlates well with tumor progression and provides a simple useful staging system after curative esophagectomy for esophageal cancer. Dukes' A tumor could be proposed as a criterion of early esophageal carcinoma.

Aged↗

Esophagectomy and hepatic arterial chemotherapy following hepatic resection for esophageal cancer with liver metastasis.

We report a patient who had simultaneous transthoracic esophagectomy and hepatic arterial cannulation for chemotherapy following hepatic resection for esophageal cancer with solitary liver metastasis. He had an uneventful postoperative course and received two cycles of postoperative arterial chemotherapy with cisplatinum and 5-fluorouracil. He developed multiple liver metastases 6 months after the surgery. He has been receiving arterial chemotherapy at the outpatient department and is alive 15 months after the surgery. Aggressive esophagectomy and hepatic arterial chemotherapy is the treatment of choice for esophageal cancer with liver metastasis when unresectable metastases are confined to the liver.

Antineoplastic Combined Chemotherapy Protocols↗

Esophageal resection in elderly esophageal carcinoma patients: improvement in postoperative complications.

BACKGROUND: Advanced age is considered to be a relative contraindication for radical esophagectomy with a three-field lymph node dissection. METHODS: Preoperative risks, postoperative morbidity and mortality, and long-term survival in 55 elderly patients (> or =70 years) who had undergone extensive esophagectomy for esophageal carcinoma were compared with those of 149 younger patients (<70 years). RESULTS: Elderly patients had worse preoperative cardiopulmonary function and had more frequent postoperative cardiopulmonary complications compared with younger patients (p < 0.05). The postoperative death rate was not statistically different between the elderly (10.9%) and younger groups (5.4%). When the study period was divided into an early and a late phase, the postoperative death rate dropped significantly (p < 0.05) in recent years (1.4%) when compared with the previous era (10.0%). The overall survival rates were not different between elderly and younger patients. CONCLUSIONS: Preoperative cardiopulmonary risk factors and postoperative complications after esophagectomy were more frequently noticed in elderly patients than in younger patients. A dramatic improvement in postoperative death was noticed in recent years. The long-term survival of elderly patients after extended esophagectomy was almost similar to that in younger patients.

Aged↗