Biomedical subjects

M Mukai

Publications and source records attributed to M Mukai.

At least 19 recordsLinked to original sources

PubMed2006

Epithelioid sarcoma arising on the forearm of a 6-year-old boy: case report and review of the literature.

Epithelioid sarcoma is a rare malignant tumor that occurs mainly in young adults and most frequently involves the distal portion of the upper extremities. The tumor is particularly rare in children and more frequently involves the head and neck; only one case involving the forearm has been reported in a child under 10 years of age, and he was treated with amputation. We report the case of a 6-year-old boy with an epithelioid sarcoma of the forearm whose initial management had been inappropriate. The patient was ultimately treated with limb sparing surgery. Two years later, no local recurrence was evident but pleural metastases were detected.

Forearm↗

PubMed2006

RhoC is essential for TGF-beta1-induced invasive capacity of rat ascites hepatoma cells.

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-beta1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-beta1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-beta1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-beta1 in MM1 cells plays a critical role in TGF-beta1-induced cell migration.

Animals↗

PubMed2005

Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia.

Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels of mammalian target of rapamycin (mTOR), a central regulator of cellular energy, are reported to be suppressed in hypoxia. We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia. Overexpression of the active form of S6K increased the sensitivity of LLC cells to hypoxia. On the other hand, inhibition of PI3K or mTOR dramatically reduced hypoxia-induced cell death under hypoxic conditions. Under hypoxic conditions, blockade of the PI3K or mTOR pathway increased levels of intracellular ATP and delayed decreases in pH and glucose level in culture medium, without affecting the cell cycle.

Adenosine Triphosphate↗

PubMed2005

Bilateral multiple malignant transformation of Ollier's disease.

We treated a 26-year-old man with a 19-year history of Ollier's disease. Secondary chondrosarcomas developed metachronously at four separate locations: both femora, left proximal tibia and fibular head. All four lesions were surgically excised, and each specimen was histologically identified as grade 1 or 2 chondrosarcoma. Clinical follow-up for 20 years beginning at the time of first tumor surgery has shown no evidence of local recurrence or metastasis. This is the first report of multiple bilateral metachronous malignant transformation of multiple chondromatoses in a patient with Ollier's disease.

Adult↗

PubMed2005

Insulin sensitivity independently influences brachial-ankle pulse-wave velocity in non-diabetic subjects.

AIMS: Measurement of pulse-wave velocity (PWV) is a non-invasive technique for assessing arterial stiffness. Although insulin resistance is associated with intimal-medial thickness of the carotid artery evaluated by B-mode ultrasonography, it is not known whether it is related to PWV. The aim of this study was to determine the relationship between homeostasis model assessment insulin sensitivity index (HOMA-%S) and PWV in non-diabetic subjects. We also examined the effects of oral glucose tolerance test (OGTT) 2-h glucose and plasma high-sensitivity C-reactive protein (CRP) on PWV, as these two parameters are associated with atherosclerosis. METHODS: A 75-g oral glucose tolerance test was performed in 1934 Japanese subjects who were undergoing health examinations. Of these subjects, we recruited 1541 non-diabetic subjects without chronic or acute inflammation, malignant diseases, autoimmune disorders, elevated serum creatinine levels, and abnormal hepatic function tests. Subjects who had an abnormal ankle/brachial blood pressure index of less than 0.9 were also excluded. Brachial-ankle PWV and plasma high-sensitivity CRP were measured on 1541 subjects who satisfied the admission criteria. RESULTS: PWV was 12.55+/-1.61 (mean+/-sd) m/s and plasma CRP concentration was 0.4 mg/l (median, range, 0.1-5.8 mg/l) in the study subjects. By multivariate regression analysis, HOMA-%S was found to be an independent negative risk factor for PWV, while systolic blood pressure, age and triglycerides were positively associated with PWV. OGTT 2-h glucose was weakly and independently related to PWV in male subjects. Plasma CRP was not independently associated with PWV. CONCLUSIONS: Insulin resistance is independently associated with PWV in non-diabetic subjects.

Adult↗

PubMed2005

Alterations of p53, cyclin D1 and pRB expression in the carcinogenesis of esophageal squamous cell carcinoma.

Many molecular alterations occur in esophageal carcinogenesis; however, little is known about the molecular genetic events responsible for the development of carcinoma. We investigated the expression of ki67, p53, cyclin D1 and pRB in 105 biopsy specimens using immunohistochemistry from iodine unstained lesions as indicators of carcinogenesis of the esophagus. Also, the genetic alternation of esophageal dysplasia from patients with accompanying esophageal squamous cell carcinoma (ESCC) was examined to study the evidence for field carcinogenesis in the esophagus. The expression of p53, cyclin D1 and pRB was detected in 31, 0 and 51.7% respectively of mild dysplasia; 40, 0 and 70% of moderate dysplasia; 40, 20 and 70% of severe dysplasia; and 48, 32 and 80% of carcinoma specimens. p53 expression was significantly increased in mild dysplasia, whereas cyclin D1 and pRB expression were significantly increased in carcinoma as compared to both normal epithelium and esophagitis. The ki67 LI and the rate of p53 expression were significantly higher in dysplasia with ESCC than in dysplasia without ESCC. Ki67, p53, cyclin D1 and pRB expression may be useful biomarkers for assessing the risk of developing esophageal cancer. Dysplasia observed at screening for secondary lesions has a highly malignant potential and careful follow-up studies are required.

Carcinoma, Squamous Cell↗

PubMed2005

Perineal-onset Fournier's gangrene in a patient undergoing hemodialysis--importance of perineal-onset manifestation.

We present a rare case of perineal-onset Fournier's gangrene in a patient undergoing hemodialysis. A 51-year-old Japanese man manifested an acute-onset perineal pain with perirectal abscess; subsequently, the pain extended to the abdomen, chest, and loin despite quick treatment. His consciousness deteriorated to delirium and he died of septic shock on the third day of admission. Computed tomography (CT) revealed soft-tissue air along the right rectal wall, moreover, the infection extended to the anterior wall of the bladder and the right peripsoas muscle. On the basis of the clinical course and CT findings, the patient was diagnosed as having the complications of Fournier's gangrene, however, no scrotal lesions were detected. Fournier's gangrene is considered to be easily diagnosed on the basis of skin lesions, such as scrotal erythema and swelling. However, in the early stage, the diagnosis of Fournier's gangrene is difficult in a patient with perineal pain before the detection of skin lesions. In conclusion, definitely the key to improving the prognosis of this fulminant infection is the prompt recognition of the pathological process. Therefore, Fournier's gangrene should always be considered when patients undergoing hemodialysis manifest perirectal disorders, even when no scrotal lesions are detected, because there is the possibility of intra-abdominal and intra-retroperitoneal infections resulting in septic shock.

Abscess↗

PubMed2004

Quantitative nested reverse transcriptase PCR vs. real-time PCR for measuring AML1/ETO (MTG8) transcripts.

A quantitative nested reverse transcriptase polymerase chain reaction (QN-RT-PCR) method was developed using a plasmid cDNA containing the AML1/ETO (MTG8) fusion transcript from Kasumi-1 cells, an acute-myelogenous leukemia cell line with the t(8;21) translocation. In this method, the plasmid was detectable at a concentration of 10(-17) m. The fusion transcript in a mixture of 10(7) Rice94 (Burkitt lymphoma cell line) cells containing two Kasumi-1 cells was detectable at 10(-17) m. In a previously published real-time PCR method, the plasmid containing the fusion transcript was detectable at 10(-16) m or higher, and 20 or more Kasumi-1 cells were detectable in 10(7) Rice94 cells. Thus, this QN-RT-PCR method is more sensitive than the real-time PCR. When the same samples were examined by real-time PCR and our QN-RT-PCR method, in one patient in clinical remission after chemotherapy and allogeneic-bone marrow transplantation (BMT), the transcript was detected by QN-RT-PCR 60 days prior to hematological relapse, in contrast to 10 days before hematological relapse by real-time PCR. The transcript level was below 10(-17) m (undetectable) with this QN-RT-PCR in patients in clinical remission after chemotherapy and BMT, while it was 10(-15)-10(-16) m in patients in clinical remission after chemotherapy alone. The quantitative difference of the transcript level in minimal residual disease (MRD) between these two different types of clinical remission was estimated to be at least 10(2)-fold. This QN-RT-PCR method is useful for predicting hematological relapse and for quantitatively estimating MRD in different types of clinical remission.

Cell Line, Tumor↗

PubMed2003

Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women.

A fluid-based Papanicolaou test has been established to improve sample collection and preparation. This study was the first large-scale investigation in Japan to examine the feasibility of using fluid-based Papanicolaou specimens to detect human papillomavirus (HPV) using Hybrid Capture II and polymerase chain reaction (PCR). Three thousand patients who visited Keio University Hospital between October 2000 and February 2001 were enrolled in the study. The results of the fluid-based Papanicolaou tests corresponded well with those of conventional Papanicolaou smears (96.8% concordance). The sensitivities of cervical neoplasia detection using the fluid-based Papanicolaou test (73.9%) and Hybrid Capture II (76.3%, P=0.55) were not significantly different. Among the cervical intraepithelial neoplasia 3 and squamous cell carcinoma specimens, HPV 16 and HPV 52 were predominantly detected using the PCR method. Although some DNA samples extracted from the fluid-based specimens were degradaded, PCR and direct sequencing could be performed without difficulty even after 1 year of specimen storage. We conclude that fluid-based Papanicolaou specimens can be applied to investigate HPV infection.

DNA, Viral↗

PubMed2003

Endoscopic mucosal resection of superficially spreading colonic neoplasms larger than 5 cm in the right colon after injection of dilute sodium hyaluronate: report of two cases.

Submucosal injection is the most important procedure for the safe performance of endoscopic mucosal resection in the large intestine while avoiding the risk of perforation. We used dilute sodium hyaluronate containing Bosmin and achieved safe piecemeal resection of large superficial tumors in the right colon in two patients. Piecemeal snare resection is considered to be acceptable if all the tissue pieces can be collected for histopathological diagnosis.

Colonic Neoplasms↗

PubMed2003

Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study.

BACKGROUND: Recent mucosal biopsy criteria combined with endoscopy effectively differentiate patients with ulcerative colitis ultimately requiring surgery (UC-S) from those receiving medication alone (UC-M). However, the criteria were inconvenient in practical use because of the need for complicated calculations, and the validity has not been verified in other institutes where the indications for surgery may differ. The aims of this multicenter study were to propose simple criteria in which calculation can be performed by mental arithmetic and to measure their validity. METHODS: Based on the above original criteria, we constructed simple criteria in which coefficients and constant were simplified to integral numbers. The criteria consisted of the diagnostic categories, highest-risk, high-risk, unpredictable, low-risk, and lowest-risk of surgery. The validity of these proposed criteria was evaluated in 121 patients with UC-S and 186 with UC-M from 11 institutes. RESULTS: The categories of high-risk and low-risk had sensitivities exceeding 86.0% and specificities exceeding 95.2%, and the validities were maintained at high levels in most individual institutes. There was little difference in validity between the proposed and original criteria when testing using the same patients. CONCLUSIONS: Despite simplified coefficients and constant, the proposed criteria reliably predicted the eventual clinical outcome of patients with ulcerative colitis and would be helpful in determining the necessity of surgery.

Adolescent↗

PubMed2002

Successful allogeneic blood stem cell transplantation for aplastic anemia in a patient with renal insufficiency requiring dialysis.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Adult↗

PubMed2002

Radio-guided sentinel node detection for gastric cancer.

BACKGROUND: Radio-guided detection of sentinel nodes (SNs) has been used to predict regional metastases in patients with malignant melanoma and breast cancer. However, the validity of the SN hypothesis is still controversial for gastrointestinal cancers including gastric cancer. The aim of this study was to test the feasibility and accuracy of radio-guided mapping of SNs for gastric cancer. METHODS: Some 145 consecutive patients with gastric cancer diagnosed as T1 or T2 and evaluated clinically as N0 were enrolled. Endoscopic injection of technetium-99m-radiolabelled tin colloid was performed before operation and radioactive SNs were identified with a gamma probe. Standard radical gastrectomy with lymphadenectomy was performed in all patients and all resected nodes were evaluated by routine histopathological examination. RESULTS: Using radio-guided methods, SNs were detected in 138 (95.2 per cent) of 145 patients. The SN was positive in 22 of 24 patients with lymph node metastasis. The incidence of metastasis in the SNs (7.8 per cent) was significantly higher than that in the non-SNs (0.3 per cent) (P < 0.01). The diagnostic accuracy according to SN status was 98.6 per cent (136 of 138). CONCLUSION: Radio-guided SN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with early-stage gastric cancer.

Chi-Square Distribution↗

PubMed2002

Novel three-channel and three-slit stiffening tube for total colonoscopy.

BACKGROUND AND STUDY AIMS: Because of the recent marked reduction in the diameter of colonoscopes, existing stiffening tubes require modification of their tips and hardness. The aim of this study was to develop a new stiffening device with a flexible soft tip which closely fitted the colonoscope. It was also designed with three slits, to improve the fit of the stiffening tube itself to the colonoscope and to extend the effective colonoscope length, and equipped with three channels for endoscopic treatment. MATERIALS AND METHODS: The standard stiffening tube which has been used routinely and a novel three-channel, three-slit (TCTS) stiffening tube were employed alternately (in 160 and 161 patients, respectively). The two tubes were compared for severity of pain experienced by patients, ease of intubation, and complications. RESULTS: Among the 160 patients examined with the standard stiffening tube, one (0.63 %) complained of mild anal pain on intubation and intubation was incomplete in two (1.25 %), because of resistance in the rectum and sigmoid colon. Among the 161 patients examined with the TCTS stiffening tube, three patients who presented early in the series (1.86 %) developed mild proctal redness and erosions, but incomplete intubation or serious complications were not recorded. CONCLUSION: The TCTS stiffening tube was as easy to use as the standard stiffening tube, and is considered to be both safe and useful.

Colonic Diseases↗

PubMed2002

[Expression of telomerase activity in thymoma and thymiccarcinoma tissues; a clinicopathological study].

BACKGROUND: Telomerase is a nucleoprotein complex that caps the physical termini of all eukaryotic chromosomes. It is suggested that telomerase play important roles in unlimited cell division acquisition of the malignant phenotype. We studied the relation of telomerase activity in thymoma and thymic carcinoma to the clinicopathological features of these lesions. METHODS: Tissue specimens were surgically resected from patients with thymoma and thymic carcinoma. Telomerase activity was evaluated according to a modified telomeric repeat amplification protocol (TRAP) assay. RESULTS: Telomerase activity was detected in all thymic epithelial tumors. The activity (mean +/- SD: unit/microgram.protein) in thymoma (n = 17) was significantly higher than that in thymic carcinoma (n = 7) [431.8 +/- 400.1 vs. 68.8 +/- 39.8: p < 0.01]. Telomerase activities in thymoma and thymic carcinoma were significantly higher than that in primary lung adenocarcinoma (33.5 +/- 39.2: n = 47), studied as control (p < 0.01). In patients with thymoma, telomerase activity did not correlate with tumor stage according to Masaoka classification (p = 0.776). In patients with thymic carcinoma, however, telomerase activity positively correlated with tumor stage (p = 0.02). In thymoma, telomerase activity positively correlated with the ratio of induced lymphocytes according to Rosai's classification (p = 0.045). CONCLUSION: In thymoma, telomerase activity reflects the presence of immature T-cell lymphocytes in tumor tissue rather than tumor stage or malignant phenotype. In thymic carcinoma, telomerase activity derived directly from cancer cells may relate to tumor stage.

Adenoma↗

PubMed2001

Tumor imprint cytology of ovarian ependymoma. A case report.

BACKGROUND: Ependymoma is a tumor that usually develops in the central nervous system and is extremely rare in the ovary. The first case of ovarian ependymoma was reported by Kleinman et al. (Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol 1984;15:632-8.) in 1984, and only eight cases have been reported since then. Criteria for the histopathologic diagnosis of ependymoma are already established, but there has been no investigation of the cytologic diagnosis of ovarian ependymoma. METHODS: An imprint cytologic specimen was obtained from a recurrent ovarian ependymoma. The imprint cytologic features were compared with the findings of histologic examination, immunostaining, and electron microscopy. RESULTS: Imprint cytology revealed clusters of small cells with tapering cytoplasmic processes and a round nucleus. On the basis of these features, a neurogenic tumor could be included in the differential diagnosis. Furthermore, many rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes, characteristic of ependymoma, were found. The presence of ependymal rosettes and perivascular pseudorosettes also were confirmed by the histopathologic examination. Together with positive immunostaining for glial fibrillary acidic protein, this led to the diagnosis of ependymoma, which also was supported by the electron microscopic findings. CONCLUSIONS: Careful observation of the imprint cytologic specimen of an ovarian ependymoma should reveal numerous rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes. In addition, if we remember that ependymoma can develop in the ovary and find cells with tapering processes that suggest a neurogenic tumor, it may be possible to detect histologic features characteristic of ependymoma by the imprint cytology. To our knowledge, this is the first report on the imprint cytologic diagnosis of ependymoma originating in the ovary.

Adult↗

PubMed2001

Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

The purpose of this study was to analyze changes in the T-helper cell 1/T-helper cell 2 (Th1/Th2) balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation (auto-PBSCT) for non-Hodgkin's lymphoma (NHL) and to evaluate the effects of chemotherapy and granulocyte colony-stimulating factor (G-CSF) on the Th1/Th2 balance. A series of peripheral blood samples from four patients with NHL were collected before peripheral blood stem cell harvest and after auto-PBSCT. Using flow cytometry, Th1 and Th2 cells were identified by their intracellular cytokines: interleukin (IL)-4-/interferon (IFN)-gamma+ and IL-4+/IFN-gamma-, respectively. The Th1/Th2 balance was estimated as the ratio of IL4-/IFN-gamma+ cells to IL-4+/IFN-gamma- cells. Although the Th1/Th2 balance decreased initially, it increased markedly 28 days after the cessation of G-CSF, following auto-PBSCT, in parallel with an increase in lymphocytes. This increase was mainly due to an increase in the proportion of Th1 cells. The Th1/Th2 balance did not change appreciably before PBSC harvest. Serum IFN-gamma increased after auto-PBSCT in three patients. These preliminary data demonstrate that, after auto-PBSCT for NHL, the Th1/Th2 balance decreases initially and then increases after 1 month to levels above pretreatment levels and that the effects of chemotherapy and G-CSF on the Th1/Th2 balance are negligible before PBSC harvest. Further evaluation of the Th1/Th2 balance after allogeneic PBSCT at the single-cell level should be undertaken using this method.

Aged↗

PubMed2001

Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors prevent the conversion of HMG-CoA to mevalonate and thereby inhibit the synthesis of other products derived from this metabolite. This includes a number of small prenylated GTPases involved in cell growth, motility, and invasion. We studied the effect of HMG-CoA reductase inhibitors (fluvastatin and lovastatin) on in vitro invasion of human pancreatic cancer PANC-1 cells. Epidermal growth factor (EGF) induced a dose-dependent increase of PANC-1 cell invasion in a modified Boyden chamber assay. Stimulation of cancer cells with EGF induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly. Furthermore, Clostridium botulinum C3 transferase, a specific inhibitor of Rho, inhibited the ability of EGF to promote invasion, indicating that EGF-induced cancer cell invasion is regulated by Rho signaling. Treatment of PANC-1 cells with fluvastatin markedly attenuated EGF-induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly, whereas it did not inhibit the tyrosine phosphorylation of EGF receptor and c-erbB-2. The induction of cancer cell invasion by EGF was inhibited by the addition of fluvastatin or lovastatin in a dose-dependent manner. The effects of fluvastatin or lovastatin on cell morphology and invasion were reversed by the addition of all-trans-geranylgeraniol but not by the addition of all-trans-farnesol. These results suggest that HMG-CoA reductase inhibitors affect RhoA activation by preventing geranylgeranylation, which results in inhibition of EGF-induced invasiveness of human pancreatic cancer cells.

ADP Ribose Transferases↗