A giant epidermoid cyst demonstrated by magnetic resonance imaging.
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Aged↗
Biomedical subjects
T Fujii
Publications and source records attributed to T Fujii.
Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1.
Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.
Cell Cycle↗
Augmented expression of peroxiredoxin VI in rat lung and kidney after birth implies an antioxidative role.
A family of proteins with thioredoxin (TRx)-dependent peroxidase activity, referred to as peroxiredoxins (PRx), has been identified in many species. The sixth member of this family, PRxVI, contains only one conserved cysteine residue, while other members contain additional cysteines. We have isolated a cDNA for rat PRxVI and constructed a large scale baculovirus system to produce the recombinant protein. The protein was purified by a simple two-step procedure utilizing ion-exchange and gel-filtration chromatography. The purified PRxVI exhibited a low level of glutathione-dependent peroxidase but not TRx-dependent activity. PRxVI expression was the highest in lung, followed by brain, kidney, heart, testis, etc. as judged by Northern and Western blot analyses using a rabbit antibody to the purified PRxVI. Immunohistochemical analyses showed strong staining in the epithelium of the bronchus and bronchioles in lung and in the epithelial cells of kidney tubules. In addition, Sertoli cells in testis and islet of Langerhans cells in pancreas were strongly stained. The developmental changes of PRxVI expression in lung and kidney were low in the prenatal stage but induced postnatally. Moreover, intraperitoneal administration of chloroform induced PRxVI mRNA in kidney. When the distribution and the induced expression of PRxVI under conditions of oxidative stress are considered, a physiological role of it as an antioxidative enzyme is indicated.
Amino Acid Sequence↗
Localization of mitochondrial ribosomal RNA on the chromatoid bodies of marine planarian polyclad embryos.
Electron-dense cytoplasmic structures, referred to as chromatoid bodies, are observed in the somatic stem cells, called neoblasts, and germline cells in adult planarians. Although it has been revealed that the chromatoid bodies morphologically resemble germline granules in Drosophila and Xenopus embryos, what essential role it plays in the planarian has remained unclear. In the present study, to examine whether chromatoid bodies in planarian embryos are responsible for germline formation, the presence and behavior of chromatoid bodies during embryogenesis were examined. Mitochondrial large ribosomal RNA and mitochondrial small ribosomal RNA were used as candidate markers for components of the chromatoid body. Starting from the fertilized egg, extramitochondrial signals of both RNA (mtrRNA) were observed. At the ultrastructural level, mtrRNA were localized on the surface of the chromatoid bodies. At subsequent stages, the signals of mtrRNA were observed in certain restricted blastomeres that contribute to the formation of larval structures. The signals gradually decreased from the gastrula stage. These results suggest that the chromatoid bodies associated with mtrRNA in embryogenesis are not germline granules. The chromatoid bodies of blastomeres may be concerned with the toti- or pluripotency and cell differentiation as proposed in adult planarian neoblasts.
Animals↗
Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract.
BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.
Administration, Intravesical↗
The recognition and endoscopic treatment of early gastric and colonic cancer.
As the prognosis of both gastric and colonic cancer remains poor, the challenge is to detect lesions at an early and treatable stage. The benefit of early detection is not only improved survival, but also that patients may be treated with endoscopic mucosal resection, a low-cost, low-morbidity and low-mortality alternative to surgery. In spite of the increasing use of endoscopy in the West, we are not detecting as many early cancers as in Japan. This chapter will discuss the possible reasons for this discrepancy and give a practical guide to 'Japanese endoscopy techniques'. Finally, we have compiled a comprehensive review of the indications, techniques and complications of endoscopic mucosal resection. Throughout the chapter, controversies have been highlighted to give an insight into the limits of our knowledge and stimulate future research.
Colonic Neoplasms↗
Transcriptional activation of p21 by vitamin D(3) or vitamin K(2) leads to differentiation of p53-deficient MG-63 osteosarcoma cells.
p21 (WAF1/CIP1) is a downstream effector of p53 and mediates growth arrest by inhibiting the action of G(1) cyclin-dependent kinases. However, it has been reported that the p21 expression was triggered by multiple differentiation-inducing agents by a p53-independent pathway. These agents induced expression of p21 by binding to specific DNA elements and modulating transcriptional initiation. We demonstrated that the gene encoding p21 was not only a vitamin D(3) target gene but also a vitamin K(2) target gene in the cells and that their differentiation was well related to the transcriptional activation of the p21 gene. Transient overexpression of p21, using adenovirus-driven p21 expression plasmid, in MG-63 cells in the absence of vitamins D(3) and K(2) resulted in their differentiation. The transcriptional activation of p21 by vitamin D(3) or vitamin K(2) in p53-deficient osteosarcoma cells demonstrated the p53-independent role of p21 in human osseous differentiation. HUM PATHOL 32:410-416.
Bone Neoplasms↗
Change in plasma viral load, and viral DNA and mRNA burdens, in peripheral blood mononuclear cells from patients infected with HIV-1.
OBJECTIVES: To clarify the virological state of human immunodeficiency virus (HIV)-1-infected patients, we compared the plasma HIV-1 RNA copy number (plasma viral load (VL)), viral DNA and mRNA burdens in peripheral blood mononuclear cells (PBMCs), and the other clinical predictors. METHODS: One hundred and thirty-one samples of PBMCs and plasma from 26 patients infected with HIV-1 were obtained during 20 consecutive months for the measurement of VL, viral DNA and mRNA burdens, and CD4 positive (CD4+) cells count. The quantitative polymerase chain reaction (PCR) method with detection by solid phase DNA was utilized for the assay of VL, viral DNA and mRNA burdens. RESULTS: Eighty-six VL, 101 viral mRNA and 129 viral DNA out of 131 samples were detected. There was a significant positive correlation between VL and the viral mRNA burden (r = 0.600, P < or = 0.001), and between VL and the viral DNA burden (r = 0.368, P < or = 0.001). Focused on individuals, the viral mRNA burdens varied in a manner relatively dependent on VL when both values were detectable. However, viral DNA burdens varied relatively independently of VL and the viral mRNA burdens. In six patients the viral mRNA burden was detectable and changed even if the VL was undetectable throughout the observation period. CONCLUSIONS: Both viral DNA and viral mRNA burdens still showed detectable changes even when the VLs became undetectable in most patients. The measurement of viral mRNA or DNA burdens may be clinically available to identify viral replication when VL is undetectable.
Adolescent↗
Chromoscopy during colonoscopy.
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Colonoscopy↗
Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?
BACKGROUND AND STUDY AIMS: Assessing the nature of lesions at the time of colonoscopy is important, and magnifying colonoscopy allows examination of mucosal crypt patterns. In this study, we assessed mucosal crypt patterns to see whether we could predict the histological findings. PATIENTS AND METHODS: This retrospective study of total colonoscopy using magnifying colonoscopy involved 4445 patients between December 1993 and July 1998 at the National Cancer Center Hospital East. The mucosal crypt patterns of 3438 lesions were observed under magnifying colonoscopy with 0.2% indigo carmine solution, and classified according to a modified Kudo classification (type I to V). After endoscopic or surgical resection (3291 cases and 147 cases, respectively), histopathological examination was performed. RESULTS: The diagnostic accuracy of magnifying endoscopy for non-neoplastic lesions was 75% (117/157), for adenomatous polyps it was 94% (3006/3186), and for invasive carcinomas it was 85 % (81/95). CONCLUSIONS: The combination of magnifying colonoscopy and dye spraying is helpful in determining the nature of colonic lesions as non-neoplastic, adenomas, or invasive carcinomas. Therefore it may be possible to determine, at the time of colonoscopy, which lesions require no treatment, which can be removed endoscopically, and which should be removed by surgery.
Adenocarcinoma↗
Endoscopic treatment for laterally spreading tumors in the colon.
BACKGROUND AND STUDY AIMS: Laterally spreading tumors (LST) of the colon are best removed by endoscopic mucosal resection (EMR) as they extend laterally rather than vertically. Since they sometimes invade deeply into the submucosal layer, it is important to assess the depth of invasion endoscopically before treatment. In the present study, we examined the endoscopic features of a large number of LSTs in order to assess which features correlated with depth of invasion. MATERIALS AND METHODS: 257 LSTs removed at the National Cancer Center Hospital, Tokyo, between January 1988 and September 1998 were retrospectively analyzed. RESULTS: With univariate analysis, unevenness of nodules, presence of large nodules, size, histological type, and presence of depression in the tumor were significantly associated with depth of invasion. Multivariate analysis revealed that histological type and depression in the tumor were independent factors predicting massive submucosal invasion. When an LST showed: 1) even nodules without depression, or 2) uneven nodules without depression and less than 3 mm in diameter, the risk of massive submucosal invasion was 0 % (0/121) and 3.7 % (3/82), respectively. CONCLUSION: When LSTs meet the above endoscopic criteria, EMR should be the first-line treatment because of the low risk of massive submucosal invasion.
Adenocarcinoma↗
A new endoscopic tattooing technique for identifying the location of colonic lesions during laparoscopic surgery: a comparison with the conventional technique.
BACKGROUND AND STUDY AIMS: Knowledge of the exact location of colorectal lesions is necessary but difficult to establish during surgery. Thus, endoscopic tattooing has been used as an important preoperative marker for identification. Using the conventional technique, we injected tattooing agents directly into the colonic wall. However, to make sure that the tattooing agents were adequately injected into the submucosal layer, and to prevent spillage into the peritoneal cavity, we modified the conventional method and developed a new tattooing technique: using India ink with prior and subsequent injection of saline into the submucosa. The aim of this study was to retrospectively assess the clinical utility and potential complications of the above two techniques of endoscopic tattooing using India ink. PATIENTS AND METHODS: A total of 153 patients underwent laparoscopically assisted colectomy at the National Cancer Center Hospital East, Kashiwa, Chiba, Japan, between June 1994 and December 1999, and 91 patients underwent preoperative endoscopic tattooing by either the conventional or the new technique. The conventional and new techniques were used from June 1994 to December 1997 (n = 36) and from January 1998 to December 1999 (n = 55), respectively. Informed consent was obtained from all the patients. RESULTS: Using the conventional technique, the exact location of the lesion was identified in 31 of 36 cases (86.1 %) during surgery. The complications of this procedure were silent local peritonitis in two patients and reactive lymph node swelling in one patient (3/36, 8.3 %). Using the new technique, in 54 of 55 cases lesions (98 %) were easily identified (p = 0.034),and in only one there was a small leakage of India ink into the peritoneal cavity (1/55; 1.8 %), no other serious complications were observed. CONCLUSIONS: The results demonstrate that our new technique for endoscopic tattooing is probably better than the conventional technique for clinical use, in terms of diagnostic accuracy and safety, but this would have to be proven in a randomized comparison.
Carbon↗
Endoscopic mucosal resection.
We are now finding more malignancies in their early stages than previously. Attempts to ablate these lesions are difficult and do not provide the histological information required to decide on further treatment. Surgery is difficult to justify, as only a minority of lesions are associated with lymph node metastases and lesions may not become clinically relevant within the lifetime of an elderly patient. Endoscopic mucosal resection allows cancers to be resected at minimal cost, morbidity and mortality. It is also the most reliable investigation when assessing lesions which are suspicious for containing early cancer. After endoscopic removal, histological assessment of depth of penetration and a search for invasion into lymphatics or venules allows the risk of microscopic lymph node metastases to be predicted. The risk of developing metastatic disease can then be balanced against the risks of surgery in view of the patient's age and health.
Biopsy↗
A 0.8-mm depressed adenoma of the colon with high-grade dysplasia.
Flat and depressed cancers of the colon have now been recognized in several centers throughout the world. We report here a case of a 0.8-mm depressed adenoma with high-grade dysplasia in a 70-year-old man. We believe this to be the smallest adenoma ever reported, and unusually (for a small lesion) it was positive for the K-ras mutation.
Adenoma↗
The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction.
Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive mitral flow pattern is well recognized as a finding of severely elevated LVEDP. On the other hand, an abnormal relaxation pattern can be interpreted many ways. For example, some patients who display an abnormal relaxation pattern have a mild impairment of left ventricular (LV) relaxation as a result of aging, and others have severely impaired LV diastolic function. To evaluate LVEDP in patients with abnormal relaxation mitral filling patterns, we studied 55 patients who had coronary artery disease with abnormal relaxation pattern who underwent elective cardiac catheterization. We recorded the transmitral and pulmonary venous flow velocity curves and measured the duration of the mitral A wave (MAd) and pulmonary venous reversal wave during atrial contraction (PAd). Positive correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd-MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV end-diastolic pressure in patients with an abnormal relaxation pattern in the transmitral flow velocity curve.
Aged↗
Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture.
Exquisitely regulated cytokine balance during early pregnancy is thought to be necessary for promoting survival of the fetal allograft. Our previous studies have demonstrated that membrane-bound human leukocyte antigen (mHLA-G) expressed on trophoblasts is one of the key factors in regulating cytokine balance by shifting the Th1/Th2 balance toward Th2 polarization, a favourable milieu for the maintenance of pregnancy. Given that trophoblasts secrete soluble HLA-G (sHLA-G), we examined its biological roles in comparison with mHLA-G. We cultured peripheral blood mononuclear cells (PBMC) with either the HLA-A and -B-deficient B lymphoblast cell line (721.221 cells) or the same cell line transfected with mHLA-G (721.221-G1 cells), in the presence or absence of recombinant sHLA-G. Cytokine concentrations in the culture media were determined by enzyme-linked immunosorbent assay. In contrast to mHLA-G protein, sHLA-G stimulated the release of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, whereas it reduced the release of interleukin (IL)-3, regardless of the presence of the presence of a stimulatory effect of the mHLA-G-expressing cells. Although mHLA-G reduced the release of IL-4, sHLA-G did not have any effect. Conversely, sHLA-G stimulated the release of IL-10 whereas mHLA-G was without effect. These results suggest that sHLA-G regulates the release of cytokines from PBMC chiefly by counterbalancing mHLA-G, and thereby may play a role in maintaining pregnancy.
Cell Line↗
Evidence for the expression of interleukin (IL)-18, IL-18 receptor and IL-18 binding protein in the human endometrium.
To see whether the interleukin (IL)-18 system is operative in the endometrium, we examined the expression of IL-18, IL-18 receptor (IL-18R) and IL-18 binding protein (IL-18BP), the substance known to neutralize IL-18 activity, in this tissue. Reverse transcription-polymerase chain reaction analyses showed that IL-18, IL-18R and IL-18BP mRNA were constitutively expressed without significant fluctuation throughout the menstrual cycle. When epithelial cells and stromal cells were cultured separately, the expression levels of IL-18 mRNA in epithelial cells were about 18-fold higher compared to those in stromal cells. Furthermore, the IL-18 precursor protein was detected by Western blot analysis in cultured epithelial cells but not in stromal cells. Recombinant human IL-18 stimulated the secretion of interferon (IFN)-gamma by resident bone marrow-derived cells in the endometrium. On the other hand, IFN-gamma up-regulated the IL-18BP expression both in cultured epithelial cells and stromal cells. Thus, we have presented evidence for the presence of the IL-18 system in the human endometrium. In light of its immunomodulatory roles in a variety of tissues, this system may afford protection against pathogenic micro-organisms and provide a regulatory mechanism for controlled trophoblast invasion by modulating a local cytokine network.
Bone Marrow Cells↗
Cyclic and linear peptides derived from alpha-amylase inhibitory protein tendamistat.
Tendamistat is a strong inhibitory protein of porcine pancreatic alpha-amylase (PPA) with a K(i) value of 0.2 nM. To develop potent alpha-amylase inhibitors, we synthesized six odd-length cyclic peptides (5-15 residues) and four even-length cyclic peptides (10 and 12 residues) having the inhibitory sequence of tendamistat. Their PPA inhibitory activities were evaluated, and, among them, the 11-residue cyclic peptide Ten(15-23) (K(i) = 0.27 microM) exhibited the strongest inhibitory activity (K(i) = 0.27-1.41 microM). To examine the effect of cyclic structure on PPA inhibition, ten linear peptides corresponding to the cyclic peptides were also synthesized, and their PPA inhibitory activities were evaluated (K(i) = 0.28-1.00 microM). Interestingly, the 11-residue linear peptide Ten(15-23) exhibited almost the same inhibitory activity (K(i) = 0.28 microM) as that of cyclic Ten(15-23). The results of a circular dichroism study indicated that stabilization of the beta-hairpin structure occurred only for cyclic Ten(15-23). Also, the results of proteolytic digestion experiments of the cyclic and linear Ten(15-23) peptides by trypsin and chymotrypsin suggested no differences in protease resistance between the cyclic and linear structures. Therefore, we demonstrated that both cyclic and linear peptides containing the inhibitory sequence of tendamistat exhibit potent PPA inhibitory activity.
Amino Acid Sequence↗