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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 109 records · Page 6Linked to original sources

An immunohistochemical study of hepatic atypical adenomatous hyperplasia, hepatocellular carcinoma, and cholangiocarcinoma with alpha-fetoprotein, carcinoembryonic antigen, CA19-9, epithelial membrane antigen, and cytokeratins 18 and 19.

Eight hepatic atypical adenomatous hyperplasias (AH), 30 hepatocellular carcinomas (HCC) consisting of 11 well-, 13 moderately and six poorly differentiated HCC, and 10 intrahepatic cholangiocarcinomas (CC) were investigated immunohistochemically with anti-alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9, epithelial membrane antigen (EMA), and cytokeratins (CK) 18 and 19 antibodies. Immunostaining was regarded as positive when more than 5% of cells were stained. Alpha-fetoprotein was positive, although focally, in five (17%) of 30 HCC but negative in all AH and CC. Carcinoembryonic antigen (polyclonal antibody) did not stain the cytoplasm of all AH and HCC, but stained two (25%) of eight AH and 10 (33%) of 30 HCC in a bile canalicular staining manner. Carcinoembryonic antigen showed intracytoplasmic or luminal border staining in six (60%) of 10 CC. CA19-9 was negative in all AH and HCC, while six (60%) of 10 CC were positive for CA19-9. Epithelial membrane antigen was positive in one (13%) of eight AH, seven (23%) of 30 HCC and in all 10 cases of CC. Cytokeratin 18 was positive in all AH, HCC and CC. Cytokeratin 19 was negative in both AH and HCC, whereas it stained the cytoplasm of tumor cells in all CC diffusely and intensely. These results suggest that immunostaining of AFP, CEA, CA19-9, EMA, CK18 and CK19 are not useful in the differential diagnosis between AH and well-differentiated HCC, and that CK19 is the most suitable reagent for the differential diagnosis between HCC and CC.

Adenoma↗

Recurrent bladder adenocarcinoma in an ileal conduit stoma: a case report.

BACKGROUND: The first case of a patient with recurrent adenocarcinoma in an ileal conduit stoma 7 months after radical cystectomy is reported. RESULTS/DISCUSSION: The most likely explanation of this case is hematogenous metastasis based on the clinical diagnosis and the pathological immunostaining examination of cytokeratin.

Aged↗

A case of renal metanephric adenoma: histologic, immunohistochemical and cytogenetic analyses.

BACKGROUND: A unique case of metanephric adenoma of the left kidney is reported in a 61-year-old woman presenting with an incidental renal mass on ultrasonography. METHODS/RESULTS: On radiographic examination, the presence of hypovascular renal cell carcinoma was suspected and left radical nephrectomy was performed. The resected tumor, measuring 4.9 x 4.7 x 4.5 cm, was well-circumscribed and solid and its cut surface was tan-pink with foci of focal hemorrhage and cystic change. Microscopically, the tumor was composed of uniformly small acini with hyperchromatic round nuclei. Some acini were dilated and occasionally contained glomeruloid-like bodies and psamoma bodies. Immunohistochemically, tumor cells showed positive immunoreaction for vimentin, cytokeratin and Leu 7. Cytogenetically, the tumor did not show numerical aberrations of chromosome 7 or 17 by fluorescence in situ hybridization. CONCLUSIONS: The patient is alive without recurrence or metastasis 4 years after surgery. Metanephric adenoma must be differentiated from other renal tumors, particularly Wilms' tumor or low-grade renal cell carcinoma. Immunohistochemical and cytogenetic analysis may be helpful in difficult cases.

Adenoma↗

Smooth muscle tumors of the esophagus: clinicopathological findings in six patients.

Preoperatively, it is difficult to discriminate leiomyoma and leiomyosarcoma of the esophagus, which are rare smooth muscle tumors. The objective of this study was to evaluate the clinicopathological findings of this unusual lesion. A search of the surgery archives of the Toyama Prefectural Central Hospital of Pathology revealed six cases of esophageal smooth muscle tumors. Clinicopathological findings were reviewed retrospectively. Only three patients (50%) presented with dysphagia, and the remaining three patients were asymptomatic. These patients underwent surgical excision. Histologically four of the six tumors were leiomyomas, and the other two tumors were leiomyosarcomas. Two tumors were in the upper to middle esophagus, and the remaining four were in the distal esophagus. On endoscopic examination, all tumors were noted to be polypoid. The two leiomyosarcomas measured over 5 cm and the four leiomyomas less than 4 cm. Neither ulceration nor necrosis proved to be of use in discriminating leiomyoma and leiomyosarcoma. The two patients with leiomyosarcoma died of liver metastasis 10 and 22 months after the treatment. Patients with leiomyosarcoma presented with distant metastasis and/or recurrence, with hematogeneous metastasis being the predominant type of recurrence.

Adult↗

Number of lymph node metastases influences survival in patients with thoracic esophageal carcinoma: therapeutic value of radiation treatment for recurrence.

We retrospectively investigated whether the number of involved lymph nodes and the radiation therapy for recurrence affect survival in patients with thoracic esophageal carcinoma. Eighty-nine patients underwent surgical resection and reconstruction for thoracic esophageal squamous cell carcinoma beyond the mucosal layer. Patients were classified into three groups: group 1 comprised 40 patients without lymph node involvement; group 2 comprised 34 patients with 1-3 positive nodes; and group 3 comprised 15 patients with > or = 4 involved lymph nodes. The 3-year and 5-year survival rates were 77.5% and 73.2% respectively in group 1, 64.8% and 55.8% respectively in group 2, and 28.1% and 0% respectively in group 3. The mean survival time (MST) mean +/- SD of the patients in group 3 (772.1 +/- 146.2 days) was significantly shorter than that of patients in group 1 (3728.5 +/- 320.7 days, p < 0.0001) and group 2 (2330.4 +/- 344.3 days, p = 0.0130). The MST of the patients in group 2 was also significantly shorter than that of patients in group 1 (p = 0.0366). Patients with recurrent lymph nodes that were localized were treated effectively with radiation therapy. We conclude that the number of lymph node metastases influences survival in thoracic esophageal cancer. Early detection as well as radiation therapy for recurrent lymph node metastases is effective in improving long-term survival.

Adult↗

MN/CA9 gene expression as a potential biomarker in renal cell carcinoma.

OBJECTIVE: To compare the levels of MN/CA9 expression with clinicopathological variables in renal cell carcinoma (RCC), and thus evaluate MN/CA9 expression as a possible biomarker for RCC. MATERIALS AND METHODS: The level of expression of MN/CA9 was evaluated in 76 surgically obtained tissue samples (49 from RCC, 22 from normal kidney and five from oncocytoma) using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. In RCC, MN/CA9 expression was compared with stage, grade and cell type. RESULTS: MN/CA9 was expressed in 42 of 49 (86%) RCC samples, but in only two of 22 (9%) normal kidney and none of five oncocytoma samples. Levels of MN/CA9 expression were significantly higher in tumours consisting only of clear cells than in those containing other cell types (P=0.0189), and MN/CA9 was expressed in 34 of 37 (92%) RCC samples consisting only of clear cells. Tumours of low clinical stage showed a striking increase in MN/CA9 expression, and high MN/CA9 expression was associated with a good patient outcome. CONCLUSION: These results suggest that MN/CA9 expression is a potential diagnostic biomarker of RCC, especially the clear-cell type, and can be targeted using molecular biological techniques.

Adult↗

Effect of ebselen on contractile responses in perfused rabbit basilar artery.

OBJECTIVE: To evaluate the possible role of the antioxidant ebselen in the treatment of cerebral vasospasm, we examined the effects of ebselen on the vasoactive mechanisms induced by endothelin (ET)-1, oxyhemoglobin, and oxygen-derived radicals. METHODS: Isolated rabbit basilar arteries with intact endothelium were fixed in a perfusion system and perfused intraluminally. Contraction of the artery was detected as an increase in perfusion pressure. RESULTS: Ebselen, in a certain concentration range (3 x 10(-6) and 10(-5) mol/L), significantly reduced the contractile response to ET-1 (10(-10) to 10(-8) mol/L) but not the contraction induced by 40 mmol/L potassium. It reduced the contraction induced by 10(-4) mol/L 1,2-dioctanoyl-sn-glycerol, a protein kinase C activator. Addition of 10(-5) mol/L dithiothreitol, a sulfhydryl-reducing agent, partially reversed the inhibitory effects of ebselen on ET-1- and 1,2-dioctanoyl-sn-glycerol-induced contractions. Ebselen (10(-5) mol/L) as well as a combination of catalase (1000 units/mL) and superoxide dismutase (150 units/mL) inhibited the potentiating effects of oxyhemoglobin (10(-5) mol/L) on ET-1-induced contraction. Both ebselen and catalase inhibited the contractile response to hydroxyl radical generated by ferrous ion (10(-3) mol/L) plus hydrogen peroxide (10(-2) mol/L). Ebselen reduced the response to potassium when a high dose (3 x 10(-5) mol/L) was applied and failed to preserve contractility of the preparation after exposure to hydroxyl radical. CONCLUSION: Ebselen suppressed ET-1-induced contraction and synergetic interaction between oxyhemoglobin and ET-1, where free radical formation was involved. These effects may result from modification of the intracellular regulatory system including protein kinase C, as well as from protection against free radicals.

Animals↗

Benign familial neonatal convulsions followed by benign epilepsy with centrotemporal spikes in two siblings.

PURPOSE: To report on sibling cases with benign familial neonatal convulsions (BFNC) followed by benign epilepsy with centrotemporal spikes (BECT). METHODS: Case histories and EEGs were obtained for the two siblings with neonatal and subsequent epileptic seizures in one pedigree with BFNC. RESULTS: The family included six affected cases of BFNC in two generations: the proband, the proband's mother and two sisters, and the proband's maternal uncle and his daughter. The proband developed a generalized tonic convulsion 2 days after birth with no apparent cause and normal interictal EEG, and experienced a total of 18 episodes of tonic or clonic seizures or both by age 9 months. In the follow-up course, an EEG recording showed rolandic discharges at 2 years, and a sylvian seizure occurred at 4 years during sleep. On carbamazepine therapy, the last seizure was recorded at 9 years after a total of 11 episodes of sylvian seizures, with normal EEGs after 12 years. The proband's sister experienced nine episodes of brief tonic seizures between 7 and 9 days after birth, and also developed eight episodes of sylvian seizures from 4 to 7 years, with rolandic discharges on EEG until age 9 years. All of the family members had normal psychomotor development, with no neurologic sequelae. CONCLUSIONS: This report of BFNC followed by BECT in sibling cases is significant in view of the genetic analysis and the classification of epilepsies and epileptic syndromes.

Age of Onset↗

Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma.

OBJECTIVE: Recent epidemiological studies indicate that there is reduced risk of all digestive carcinomas in patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. Cyclooxygenase (COX) is a target enzyme for NSAIDs. We investigated the role of two isoforms, COX-1 and COX-2, in the development and metastasis of gastric carcinoma. METHODS: Fifteen gastric carcinoma tissue specimens and accompanying adjacent mucosa specimens were obtained from surgical resections. COX-1 and COX-2 protein expression were evaluated using Western blotting analysis, and their relative band densities were semi quantified using standard densitometry scanning techniques. RESULTS: Compared with paired noncancerous specimens, COX-2 was overexpressed in 10 of 15 carcinoma tissue specimens (66.7%). Overall, COX-2 levels in carcinoma tissue were significantly higher. Two early carcinomas (confined to the mucosa and submucosa) and three of 13 advanced carcinomas (extended below the submucosa into the muscular wall) had weak or similar COX-2 expression in paired tissue specimens. COX-2 overexpression in tumors significantly correlated with tumor invasion into the lymphatic vessels in the gastric wall and metastasis to the lymph nodes. Furthermore, the stage grouping in the TNM classification significantly correlated with COX-2 overexpression. In contrast, COX-2 overexpression did not correlate with histopathological grading, surface size, and venous vessel invasion of the tumors. COX-1 levels were similar between paired tissues. CONCLUSION: COX-2 overexpression might enhance lymphatic invasion and metastasis in patients with gastric carcinoma, implicating a poor prognosis. Therefore, the use of COX-2-specific inhibitor to suppress lymphatic metastasis in humans should be investigated.

Adenocarcinoma↗

Gamma interferon production is critical for protective immunity to infection with blood-stage Plasmodium berghei XAT but neither NO production nor NK cell activation is critical.

We have examined the roles of gamma interferon (IFN-gamma), nitric oxide (NO), and natural killer (NK) cells in the host resistance to infection with the blood-stage malarial parasite Plasmodium berghei XAT, an irradiation-induced attenuated variant of the lethal strain P. berghei NK65. Although the infection with P. berghei XAT enhanced NK cell lytic activity of splenocytes, depletion of NK1.1(+) cells caused by the treatment of mice with anti-NK1.1 antibody affected neither parasitemia nor IFN-gamma production by their splenocytes. The P. berghei XAT infection induced a large amount of NO production by splenocytes during the first peak of parasitemia, while P. berghei NK65 infection induced a small amount. Unexpectedly, however, mice deficient in inducible nitric oxide synthase (iNOS-/-) cleared P. berghei XAT after two peaks of parasitemia were observed, as occurred for wild-type control mice. Although the infected iNOS-/- mouse splenocytes did not produce a detectable level of NO, they produced an amount of IFN-gamma comparable to that produced by wild-type control mouse splenocytes, and treatment of these mice with neutralizing anti-IFN-gamma antibody led to the progression of parasitemia and fatal outcome. CD4(-/-) mice infected with P. berghei XAT could not clear the parasite, and all these mice died with apparently reduced IFN-gamma production. Furthermore, treatment with carrageenan increased the susceptibility of mice to P. berghei XAT infection. These results suggest that neither NO production nor NK cell activation is critical for the resistance to P. berghei XAT infection and that IFN-gamma plays an important role in the elimination of malarial parasites, possibly by the enhancement of phagocytic activity of macrophages.

Animals↗

Plasma leptin levels and triglyceride secretion rates in VMH-lesioned obese rats: a role of adiposity.

To explore the role of adiposity on hypertriglyceridemia associated with obesity, we examined the relation between triglyceride secretion rate (TGSR) and plasma leptin, insulin, or insulin resistance in ventromedial hypothalamus (VMH)-lesioned rats in the dynamic and static phases (2 and 14 wk after lesions, respectively). VMH-lesioned rats gained body weight (BW) at fivefold higher rates in the dynamic phase compared with sham-operated control (sham) rats, and BW gain reached a plateau in the static phase. Parametrial fat pad mass was increased 2.5-fold in VMH-lesioned rats compared with sham rats in both phases. Leptin levels were sixfold higher in VMH-lesioned rats of the dynamic phase and even higher in the static phase. Insulin levels were twofold higher in VMH-lesioned rats than in sham rats in both phases. In the dynamic phase, VMH-lesioned rats had 2-fold higher plasma triglyceride (TG) levels and 2.6-fold higher TGSRs, whereas steady-state plasma glucose (SSPG) values, an indicator of insulin resistance, were lower. SSPG values became significantly higher in VMH-lesioned rats in the static phase, but TGSR was not further accelerated. TGSR was significantly associated with leptin, independent of insulin. Leptin was highly correlated with BW, fat mass, and nonesterified fatty acids (NEFA). These results suggest that adiposity itself plays a critical role in TGSR probably through increased NEFA flux from enlarged adipose tissues. Insulin resistance is not associated with the overproduction of TG in this animal model for obesity.

Adipose Tissue↗

Highly aggressive behavior and poor prognosis of small-cell carcinoma in the alimentary tract: flow-cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen.

The purpose of this study was to determine the clinical course, and effects of the histopathologic characteristics of specific tumors, including DNA contents and immunohistochemical aspects, in patients with small-cell carcinoma of the alimentary tract. Medical records of 14 patients who presented with small-cell carcinoma of the alimentary tract were retrospectively reviewed. Primary tumors were studied by immunohistochemical and flow cytometric analyses. Of these 14 small-cell carcinomas, 4 were esophageal, 8 gastric, and 2 colonic tumors. DNA aneuploidy was observed in 8 tumors. Staining for the p53 product was positive in 57.1% of all the tumors. The average proliferating cell nuclear antigen (PCNA) labeling rate (LR) was 72.4 +/- 11.6%. The average PCNA LR was significantly higher for the p53-positive group (p < 0.05). The estimated median survival was 253 days for all patients. Noncurative resection was associated with a significantly less favorable prognosis (p < 0.01). Distant metastases were observed in 13 of 14 patients. A higher PCNA LR of small-cell carcinoma may be an unfavorable characteristic of biological behavior. The patients with disseminated disease should undergo a symptomatically palliative operation combined with chemotherapy.

Adult↗

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Aged↗

Retinoid X receptor-antagonistic diazepinylbenzoic acids.

Several dibenzodiazepine derivatives were identified as novel retinoid X receptor (RXR) antagonists on the basis of inhibitory activity on retinoid-induced cell differentiation of human promyelocytic leukemia cells HL-60 and transactivation assay using retinoic acid receptors (RARs) and RXRs in COS-1 cells. 4-(5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-n- propyldibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX603, 6c) is an N-n-propyl derivative of an RXR pan-agonist HX600 (6a), and exhibited RXR-selective antagonistic activity. Similar RXR-antagonistic activities were observed with 4-(5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyl- 8-nitrodibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX531, 7a) and 4-(5H-10,11-dihydro-5,10-dimethyl-2,3-(2,5-dimethyl- 2,5-hexano)-dibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX711, 8b), which also inhibited transactivation of RARs induced by an RAR agonist, Am80. These compounds inhibited HL-60 cell differentiation induced by the combination of a low concentration of the retinoid agonist Am80 with an RXR agonist (a retinoid synergist, HX600). These results indicated that HX603 (6c), and the related RXR antagonists inhibit the activation of RAR-RXR heterodimers as well as RXR homodimers, which is a distinct characteristic different from that of the known RXR antagonist, LG100754 (9).

Animals↗

Dicarba-closo-dodecaboranes as a pharmacophore. Retinoidal antagonists and potential agonists.

Synthesis and biological evaluation of the first dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for retinoic acid receptor (RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. The 4-carboranyl-substituted compounds (7, 11) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630. On the other hand, the 3-carboranyl-substituted compounds (8, 12) showed potential agonistic activity, but no antagonistic activity. The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules.

Boron Compounds↗

Inhibitory effects of Sasa senanensis Rehder extract (SE) on calcium-ionophore A23187-induced histamine release from rat peritoneal exudate cells.

The effects of Sasa senanensis Rehder extract (SE) by alkaline hydrolysis on histamine release from rat peritoneal exudate cells (PECs) were examined. Preincubation with SE for 5 min suppressed calcium-ionophore A23187-induced histamine release in a concentration-dependent manner. A23187 evoked a quick increase in cytoplasmic free calcium ([Ca2+]i) levels in the presence of extracellular calcium. Preincubation with SE also had an inhibitory effect on calcium influx increases induced by A23187. These results indicate that SE prevents degranulation from rat PECs by inhibiting [Ca2+]i level elevation.

Animals↗