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T Ueta

Publications and source records attributed to T Ueta.

At least 19 recordsLinked to original sources

Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma.

AIM: The lysosomal protease cathepsin D has been reported to be associated with tumour progression in malignant tumours. Expression of the gene encoding cathepsin D is known to be stimulated by oestrogen in mammary cancer cells. Recent experiments revealed that a p53 DNA binding site is located in the promoter region of the cathepsin D gene. This fact indicates that cathepsin D expression may correlate with p53 protein expression. The purpose of this study is to evaluate the expression patterns of the cathepsin D and p53 proteins in oesophageal squamous cell carcinoma (SCC). METHODS: In 154 patients with oesophageal SCC, expression of the cathepsin D and p53 proteins was measured in tumours by means of immunohistochemistry using monoclonal antibodies against cathepsin D (clone, 1C11) and p53 (clone, BP53-12). RESULTS: Cathepsin D was detected in tumour cells, although it was not found in normal oesophageal epithelium adjacent to carcinoma. High cathepsin D expression (positive tumour cells > 10%) was detected in 76 of 154 cases (49%) and high p53 nuclear expression (positive tumour cells > 50%) was detected in 70 cases (46%). High cathepsin D expression was significantly associated with invasive tumour growth (p = 0.002), poor prognosis (p = 0.049), and nuclear accumulation of p53 protein (p = 0.001). Overexpression of both p53 and cathepsin D was seen in 45 of the 154 cases (29.2%). In addition, there was a positive correlation between the cathepsin D index (percentage of cathepsin D positive tumour cells) and Ki-67 labelling index (percentage of Ki-67 positive tumour cells) in 154 oesophageal SCCs (rho = 0.257; p = 0.009). However, in multivariate survival analysis, cathepsin D expression by the tumours was not an independent prognostic factor in patients with oesophageal SCC (p = 0.236). CONCLUSIONS: The expression of cathepsin D by cancer cells may play an important role in the invasive growth of oesophageal SCC. Overexpression of both p53 and cathepsin D was seen frequently in tumours; p53 gene abnormalities may correlate with cathepsin D overexpression in oesophageal SCC.

Aged↗

Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma.

PURPOSE: Alterations in the cell cycle regulatory cyclin/retinoblastoma protein (pRB) pathway play a important role in tumor progression in esophageal squamous cell carcinoma (ESCC). In the present study, we evaluated the prognostic significance of the combined analysis of cyclin D1 and pRB in ESCC retrospectively. METHODS: Immunoreactivities of cyclin D1 and pRB were evaluated in 148 surgically resected ESCC by use of monoclonal antibodies. Disease-free survival of patients was compared among the four subgroups according to the phenotypes of cyclin D1 and pRB expressions. RESULTS: High immunoreactivities of pRB and cyclin D1 were detected in 64.2% and 40.5% of tumors, respectively. The loss of pRB expression and overexpression of cyclin D1 correlated with short survival. However, these factors were not detected as independently prognostic in multivariate analysis. In 107 surviving patients who underwent curative operation, co-expressed pRB and cyclin D1 (pRB+/cyclin D1 +: 29 patients) were correlated with unfavorable prognosis (disease-free 5-year survival rate: 42.7%) and high cancer recurrence rate (44.8%) compared with that of 40 patients with pRB +/cyclin D1- tumors (70.5% and 27.5%). The disease-free 5-year survival rate of patients with pRB+/cyclin D1- tumors was significantly better than that of other groups (P=0.001). However, the disease-free 5-year survival rate of 29 patients with pRB+/cyclin D1 + tumors was equivalent to that of 29 patients with pRB-/cyclin D1tumors (48.3%), and that of nine patients with pRB-/cyclin D1+ tumors (22.2%, P=0.237). CONCLUSIONS: Our results suggest that overexpression of cyclin D1 may suppress pRB function, and that combined analysis of pRB and cyclin D1 may be a useful parameter of patient prognosis in ESCC.

Aged↗

Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features.

Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT.

Adult↗

The expression of thymidine phosphorylase suppresses spontaneous apoptosis of cancer cells in esophageal squamous cell carcinoma.

OBJECTIVE: Thymidine phosphorylase (TP) is an enzyme which converts thymidine to thymine. TP is expressed in a variety of human carcinomas and is known to be a potent angiogenic factor. A recent in vitro study indicated that TP is involved in the intracellular apoptotic signal transduction pathway. The aim of this study was to investigate the correlations between the expression of TP, microvessel density (MVD) and the occurrence of spontaneous apoptosis in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of TP, intratumoral MVDs and percentages of apoptotic cancer cells, expressed by the apoptotic index (AI), of 155 tumors from 155 patients with ESCC were analyzed by immunohistochemistry and compared. RESULTS: Positive TP expression in cancer and stromal cells was detected in 89 (57.4%) and 104 (67.1%) cases, respectively. The mean MVD and mean AI of the 155 tumors were 288/mm(2) (range: 36-668/mm(2)) and 2.1% (range: 0-20.4%). The mean MVD of 104 tumors with TP-positive stromal cells (336/mm(2)) was higher than that of 51 tumors with TP-negative stromal cells (188/mm(2), p < 0.001). However, the mean MVD of 89 tumors with TP-positive cancer cells (293/mm(2)) did not differ from that of 66 tumors with TP-negative cancer cells (280/mm(2), p = 0.509). On the other hand, the mean AI of 89 tumors with TP-positive cancer cells (1.2%) was lower than that of 66 tumors with TP-negative cancer cells (3.4%, p < 0.001). However, the mean AI of 104 tumors with TP-positive stromal cells (1.9%) did not differ from that of 51 tumors with TP-negative stromal cells (2.6%, p = 0.058). No significant correlation between the MVDs and the AIs was observed (rho = -0.067, p = 0.409). CONCLUSION: In ESCC, TP may play an important role in tumor progression by increasing microvessels and suppressing apoptosis of cancer cells.

Aged↗

Total laboratory automation in Japan. Past, present, and the future.

The history of systematized automation in clinical laboratories in Japan started in 1981. At that time, about 12 laboratory technicians worked in a typical private University hospital laboratory (average size 1000 beds), whereas in national university hospitals (typical size 600 beds), the number of technicians was as low as 18-25. In 1981, the Kochi Medical School was founded as a new national school, and laboratory staffing was limited by the Ministry of Education to only 19 technicians for the first 3 years. Therefore, we started to develop a fully automated laboratory system by ourselves rather than accepting an intolerable shortage of technicians. The system was based on conveyor and robotic technology, and we called this approach systematization. Ten years later, systematized automation was introduced into the Japanese market. As a result, 72% of the national university hospitals in Japan installed commercial systems for systematization. There is a trend now in hospitals with sufficient numbers of technicians, to introduce fully automated systems in their laboratories as well, and even small hospitals with less than 100 beds are planning to introduce such systems. However, current technology is too expensive and not sufficiently standardized to meet the needs of these market segments in Japan. We recommend that companies agree on common shapes and sizes of racks and include more flexible robotic technology in their sample handling systems, to allow for plug and play systems and to make systematization affordable for every laboratory in the world.

Automation↗

Different sensitivity to streptolysin-O of cells in macrophage lineage.

We have surveyed the sensitivity of cells in macrophage lineage to Streptolysin-O (SLO). SLO had cytotoxic activity on immature myeloid cell lines such as M1 and WEHI-3BD+. SLO was toxic to the cells after a 2-hr incubation. However, mature macrophage cell lines such as A640-BB-2, J774, and P388D1 were not sensitive to the same dose of SLO. After M1 cells were treated with leukemia inhibitory factor (LIF), a differentiation-inducer to macrophage, these cells became insensitive to SLO in one day. This cytotoxic action of SLO was inhibited by pretreatment with anti-Streptolysin-O antibody or cholesterol. These results indicate that SLO has different effects on macrophage lineage.

Antibodies, Blocking↗

[Adherent reaction among activated platelets, polymorphonuclear cells and vascular endothelial cells under thrombin stimulation or shear stress].

Platelet activation in addition to blood coagulation abnormality is regarded as a primary factor of thrombosis by atherosclerotic obstruction. Therefore, the platelet activation on atherosclerosis is considered to correlate with shear stress generated between blood cells and endothelial cells in blood flow. P-selectin on the surface of the platelet membrane is measured by flowcytometry as a marker of platelet activation. Herein, we examined the phenomena of platelet activation and adherent platelets with leukocytes (ad-P.L) on stored platelet concentration (PC) and chronic rheumatoid arthritis (RA), moreover, of the adherent platelets or polymorphonuclear cells (PMN) with endothelial cells (EC) in shear stress by using an apparatus we devised. The rate of platelet activation and ad-P.L increased in PC with storage, and the sensitivity of platelets to thrombin decreased. The rate of platelet activation and ad-P.L increased in RA in vivo. Many adherent platelets with EC were found at a low shear rate on normal EC but at a high shear rate on denatured EC without any specific adherent property. Adherent PMN with EC had several hundred times more denatured EC than normal EC and the relationship with shear rate disappeared on denatured EC. The platelet activation and relationship between platelets or leukocytes and EC as to the cause of thrombosis are important subjects for future studies.

Arteriosclerosis↗

Transpedicular fixation with Zielke instrumentation in the treatment of thoracolumbar and lumbar injuries.

STUDY DESIGN: Sixty-five patients who underwent transpedicular fixation for thoracolumbar and lumbar injuries were studied for type of injury, the severity of paralysis, the degree of postoperative correction, and instrumentation failures. OBJECTIVES: To evaluate the surgical approaches and the selection of instrumentation to determine indications for using the transpedicular fixation procedure. SUMMARY OF BACKGROUND DATA: Various transpedicular fixation devices have been used for different type of injuries, and satisfactory postoperative results were not obtained in some studies. METHODS: Forty patients had burst fractures, 19 had fracture dislocations, and six had chance-type fractures. An anterior decompression procedure was used for most cases of burst fracture and some cases of fracture dislocation where anterior compression factors were present. The Zielke or modified Zielke system was used as an internal fixator for posterior segmental fixation. RESULTS: No patient had neurologic deterioration after surgery. Twenty of 28 patients with incomplete lesions improved postoperatively according to Frankel grades. The instrumentation failed in only one patient, in whom a nonunion developed. CONCLUSION: With transpedicular fixation, it is possible to provide solid internal fixation that is circumscribed to the injured vertebral segments. The elasticity of the Zielke rod makes it an excellent transpedicular fixation device because it is easily attached and reduction is easily performed. Anterior decompression with fusion needs to be used with transpedicular fixation in the treatment of injuries (especially burst fractures).

Adult↗

Effects of compression on physiologic integrity of the spinal cord, on circulation, and clinical status in four different directions of compression: posterior, anterior, circumferential, and lateral.

The authors investigated the effects of focal compression on physiologic integrity; somatosensory evoked potentials, neurogenic motor evoked potentials and spine-to-spine potentials, on spinal cord circulation and clinical status in four different type of compression; posterior, anterior, circumferential, and lateral in 31 pigs. Spine-to-spine potentials degraded earlier in amplitude than somatosensory evoked and motor evoked potentials regardless of direction of compression. The first lost potential was the somatosensory evoked one during posterior, circumferential, and lateral compression and motor evoked potentials during anterior compression. Somatosensory evoked potential was the only wave to detect the side of lateral compression. Following release of compression somatosensory evoked potentials and motor evoked potentials returned almost to 100% in amplitude, whereas spine-to-spine potentials recovered to approximately 50%. At that time all animals showed grossly normal motion in hind-limb, therefore spine-to-spine potentials might be too sensitive to motor function. Spine-to-spine potentials should contain more tracts than either somatosensory evoked potentials or motor evoked potentials. Somatosensory evoked potentials probably show more posterior part, whereas motor evoked potentials do more of the anterior part of the spinal cord. The spinal cord revealed a complete ischemia regardless of direction of compression when at least one potential was gone, however it regained the shape and perfusion following release of compression although there were some hemorrhagic contusions remaining. These suggest that ischemic changes may play some part in degradation of potentials, however it does not influence much the recovery following release of compression because it regains quickly. The final recovery depends on the complication.

Animals↗

New metabolites of thiabendazole and the metabolism of thiabendazole by mouse embryo in vivo and in vitro.

Thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ], a teratogen in ICR mice, is known to be mainly metabolized to 5-hydroxy-TBZ (5-OH-TBZ) and its conjugates in domestic and laboratory animals. Besides the known metabolites of TBZ, 4-hydroxy-TBZ and 2-acetylbenzimidazole (ABI) were identified as new metabolites of TBZ in the urine of F344 rats and ICR mice. 5-OH-TBZ and ABI, as well as TBZ, were found in the embryos of ICR mice given TBZ orally on day 10 of gestation. In the whole-embryo culture system, 5-OH-TBZ and ABI in the medium, and TBZ, 5-OH-TBZ and ABI in the embryo were detected after 24 hr of culture in 25 or 50 micrograms TBZ ml. However, the amount of metabolites in the embryo in vitro was very small compared with that detected in vivo, whereas the amount of TBZ was comparable. Furthermore, the mouse embryo homogenate, at organogenesis, metabolized TBZ to 5-OH-TBZ or ABI. The specific activity required by this homogenate to form 5-OH-TBZ or ABI was less than 1/1000 of that of the liver microsomal fraction. The results suggested that mouse embryos at organogenesis could metabolize TBZ, although most of the metabolites in the embryo in vivo came from the dam.

Animals↗

Congenital myotonic dystrophy associated with a chromosome pericentric inversion.

We report two cases of congenital myotonic dystrophy (CMyD) associated with a chromosome abnormality of pericentric inversion. Case 1 was a two-month-old boy, presented with 46 XY, inv (9) (p 11q 13). His father had the same chromosome abnormality without any clinical manifestations. His mother had clinical manifestations of myotonic dystrophy (MyD) but had no chromosomal aberration. Case 2 is a one-month-old girl, presented with 46 XX, inv (4) (p15.31q25). Her mother had clinical manifestations of MyD and the same chromosome abnormality as Case 2, but her father was normal. Our case report may be of value in adding further information on the pathogenesis of CMyD.

Chromosome Inversion↗

Power spectral analysis of blood pressure variability in traumatic quadriplegic humans.

A study was performed on seven traumatic neurologically complete quadriplegic (QP) males and seven age-matched healthy males (control) while they were at rest in the supine position in a climatic chamber (temperature 30 degrees C, relative humidity 60%). Arterial blood pressure waveforms were measured by a continuous noninvasive blood pressure-monitoring system based on arterial tonometry. Furthermore, the spontaneous beat-to-beat systolic blood pressure (SBP) variabilities of subjects were investigated by means of autoregressive power spectral analysis. As shown by earlier studies with an invasive (intra-arterial) blood pressure-monitoring system, in the control group there were two major spectral components: a high-frequency (HF) component [center frequency 0.27 +/- 0.02 (SE) Hz eq, power 0.9 +/- 0.2 mmHg2] and a low-frequency (LF) component (0.10 +/- 0.01 Hz eq, 5.2 +/- 1.4 mmHg2). On the contrary, in the QP group only the HF component was observed (0.28 +/- 0.03 Hz eq, 3.2 +/- 1.4 mmHg2). The results suggest that 1) in the QP subject the disappearance of the LF component in the SBP variability (i.e., the Mayer waves in humans) is presumably caused by the interruption of the spinal pathways linking supraspinal cardiovascular centers with the peripheral sympathetic outflow and 2) the cervical spinal sympathetic pathways may be instrumental in the genesis of the Mayer waves in humans.

Adult↗

Arachidonate metabolism in bovine gallbladder muscle.

Incubation of (1-14C]arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of [1-14C]PGH2 was virtually identical to that of [1-14C]AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.

Animals↗

Thromboxane formation from arachidonic acid and prostaglandin H2 in rabbit spleen.

Incubation of [1-14C]arachidonic acid (AA) and [1-14C]prostaglandin (PG)H2 with rabbit spleen homogenate and microsomes resulted in the formation of a substance with the chromatographic properties of thromboxane (Tx)B2. The radiolabeled material was indistinguishable from authentic TxB2 on TLC in three solvent systems and on radiometric gas chromatography. The generation of TxB2-like material from AA and PGH2 was not observed after boiling of the homogenate and microsomes, and was completely inhibited by imidazole (5 mM). The transformation of AA into the TxB2-like material was not observed during incubation in the presence of indomethacin (28 microM). These results indicate that TxB2 is the principal product of arachidonic acid metabolism by the homogenate or microsomes of rabbit spleen.

Animals↗