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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 19 recordsLinked to original sources

Expression of the MAGE gene family in human hepatocellular carcinoma.

BACKGROUND: The 12 members of the MAGE gene family encode tumor specific antigens that are recognized by autologous cytotoxic T lymphocytes (CTL). The MAGE genes are expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on their expression in hepatocellular carcinoma (HCC). The authors thus studied the expression of the MAGE gene family in human HCC and discuss the possibility of specific immunotherapy using MAGE peptides. METHODS: Tumor tissue samples of HCC and paired nontumor tissues of the liver were obtained from 22 HCC patients. Total RNA was extracted and cDNA was synthesized. Polymerase chain reaction amplification using each MAGE gene specific primer was then performed to detect the expression of each MAGE gene. Immunoblotting and immunohistochemical analysis were performed to confirm the expression of MAGE-3 gene product in HCC. RESULTS: The expression rate of each MAGE gene was as follows: MAGE-1 and -3 were expressed in approximately 68% of the tumors; MAGE-8 was expressed in 46%; and MAGE-2, -6, -10, -11, and -12 were expressed in approximately 30%. Nineteen (86%) of 22 tumors expressed at least 1 MAGE gene. On the other hand, no expression was detected in the noncarcinomatous liver tissue specimens. Actual expression of the gene product of MAGE-3 was detected in 50% of tumors. Clinicopathologic data on the MAGE positive and negative cases were compared. Significant differences were observed between MAGE expression status and a few clinicopathologic factors; however, further investigation is required to elucidate these correlations completely. CONCLUSIONS: These findings demonstrated that MAGE gene expression is frequent in HCC, thus suggesting that HCC patients may be good candidates for specific immunotherapy using MAGE peptides.

Aged

G-protein gamma 7 is down-regulated in cancers and associated with p 27kip1-induced growth arrest.

We previously identified and cloned human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in pancreatic cancer. We examined G-gamma 7 expression in other gastrointestinal tract cancers. In 24 of 30 patients with gastrointestinal tract cancer, Northern blot assay and immunohistochemical staining revealed significantly lower G-gamma 7 expression in tumors than in normal tissues from the same patients. Semiquantitative reverse transcription PCRs also showed lower G-gamma 7 expression in tumors than in corresponding normal tissues in 69 of 90 patients. To examine the biological role of G-gamma 7 in cancer, the G-gamma 7 cDNA was transfected into a human esophageal carcinoma cell line, KYSE150, that lacks G-gamma 7 expression. G-gamma 7 expression suppressed cell growth and tritiated-thymidine uptake when cells were confluent G-gamma 7 expression also suppressed tumorigenicity in BALB/c nude mice until 3 weeks after transplantation. G-gamma 7 expression increased the Go/G1 population and decreased the S phase population when cells were at high density. We confirmed that this change was associated with p27K1P1 expression. These findings suggest that human G-gamma 7 is associated with p27kip1-induced growth arrest and may be a therapeutic target in cancers.

Animals

Immunohistochemical expression of cytokeratins in intrahepatic cholangiocarcinoma and metastatic adenocarcinoma of the liver.

BACKGROUND AND OBJECTIVES: This study was designed to identify a difference in immunostaining that might help to distinguish between primary and metastatic liver neoplasms. METHODS: We examined immunohistochemical expression of cytokeratins (CKs) 7, 8, 19, and 20 in 12 intrahepatic cholangiocarcinomas (ICCs; 9 of the mass-forming and 3 of the infiltrating type), 25 metastatic colorectal carcinomas (MCCs), and 7 metastatic gastric carcinomas (MGCs) of the liver. RESULTS: CKs 7 and 19 were expressed in all ICCs of infiltrating type, while each was seen in 7/9 (77.8%) of mass-forming type. CK 7-positive/CK 20-negative was seen in 9/12 (75.0%) of ICCs and in none of the 25 MCCs, while CK 7-negative/CK 20-positive was seen in 1/12 (8.3%) of ICCs and 20/25 (80.0%) of MCCs. No differences were observed between MGCs and ICCs. CONCLUSIONS: These results suggest that immunohistochemical staining for both CKs 7 and 20 is useful for the differential diagnosis of ICCs and MCCs, whereas phenotypic expression of CKs appears to be different between mass-forming and infiltrating types of ICCs.

Adenocarcinoma

Clinicopathologic study of gastric cancer based on Dukes' classification.

Dukes' classification is a useful staging system in patients with colorectal cancer. The aim of this study was to present clinicopathologic characteristics and survival of patients with gastric cancer based on Dukes' classification. A total of 273 patients with gastric cancer curatively treated by radical gastrectomy and lymph node dissection (D2, D3) were studied. With the modified Dukes' classification, A includes tumors limited to the mucosa, submucosa, or muscularis propria; B includes tumors extending into the subserosa or serosa; Ca includes tumors with one to six positive lymph nodes; and Cb includes tumors with seven or more positive lymph nodes. Dukes' classification modified by the number of positive lymph nodes well correlated with the tumor size (p < 0.01), depth of wall invasion (p < 0.01), level of lymph node metastasis (p < 0.01), and degree of lymphatic permeation (p < 0.01) and venous permeation (p< 0.01). The 5-year survival rate was significantly different among Dukes' A (98%), Dukes' B (90%), Dukes' Ca (75%), and Dukes' Cb (44%) cases. The results indicate that Dukes' classification modified by the number of positive lymph nodes (Dukes' A, B, Ca, an Cb) significantly correlates with tumor progression and patient survival; and it may be a simple and useful staging system for gastric cancer.

Adenocarcinoma

Laparoscopic resection of a pancreatic mucinous cystadenoma using laparosonic coagulating shears.

A 71-year-old woman with a solitary mucinous cystic neoplasm of the pancreatic tail complained of back pain. A laproscopic distal pancreatectomy was performed. Laparosonic coagulating shears (LCS) were employed for dissection of the surrounding tissue and transection of the pancreas. The main pancreatic duct was clipped. There was no evidence of bleeding or pancreatic leakage from the transection surface. Pathologic examination showed the tumor to be a mucinous cystadenoma. The postoperative course was uneventful. The LCS was effective in this application.

Aged

Quality of life after laparoscopy-assisted Billroth I gastrectomy.

OBJECTIVE: To evaluate the quality of life of patients who had undergone laparoscopy-assisted Billroth I gastrectomy (LAG) for cure of cancer. SUMMARY BACKGROUND DATA: In 1994, the authors reported the first case of LAG for early gastric cancer, and this approach quickly has been adopted by Japanese surgeons. However, little is known about the subjective clinical results of this less invasive surgery. METHODS: Quality of life was estimated using the 24-item questionnaire with a scoring system of 1, 2, and 3 and was compared between 41 consecutive patients with LAG and 35 with conventional open gastrectomy. All patients underwent Billroth I gastrectomy for early gastric cancer from January 1993 to July 1997 and were alive without recurrence. RESULTS: Patients who had undergone LAG were taking a normal diet (100%) with >66% of volume at each meal (90%), showed no decreased performance status (90%), and were satisfied with their surgical results (88%). Patients with LAG, when compared with open gastrectomy, showed significantly better results with regard to weight loss, difficulty in swallowing, heartburn and belch, early dumping syndrome, and total score. LAG was better accepted by the patients. CONCLUSIONS: Quality of life after Billroth I gastrectomy was significantly better in patients in whom a laparoscopic technique was used than in those who underwent a conventional method. LAG is less invasive and better accepted by patients and is the procedure of choice for the treatment of early gastric cancer.

Aged

Clinical results and prognostic factors of radiologically node-positive gastric carcinoma.

Lymph node metastasis determined by histologic examination is an important prognostic indicator in gastric carcinoma. However, prognostic value of lymph node metastasis detected by computed tomography (CT) is unknown. The aim of this study was to evaluate clinical results and prognostic factors of patients with radiologically node-positive gastric carcinoma. The study included 78 patients with primary gastric carcinoma and lymph node metastasis confirmed by CT. The level of lymph node metastasis was simply graded as follows: level I included perigastric nodes; level II included intermediate nodes along the left gastric, common hepatic, and celiac arteries; and level III included distant nodes along the hepatoduodenal ligament, pancreas, spleen, and abdominal aorta. Sixty patients (79%) had stage IV tumors showing one or more of the following: level III lymph node metastasis in 37, pancreatic invasion in 27, peritoneal dissemination in 23, and liver metastasis in 19. Overall 1- and 5-year survival rates were 29% and 6%, respectively, and the 1-year survival rate was significantly influenced by the level of lymph node metastasis on CT (55% for level I, 27% for level II, 7% for level III, P < 0.01). In patients with gastrectomy, prognostic factors were tumor size (<10 cm versus >10 cm, P < 0.01), gross type (localized versus infiltrative, P < 0.01), histologic type (well differentiated versus poorly differentiated, P < 0.01), and curability of the disease (curative versus noncurative, P < 0.01). Our study indicates that prognosis of patients with radiologically node-positive gastric carcinoma is poor because of high frequency of extensive tumor spreads. Patients having only positive level I nodes on CT are candidates for curative gastrectomy, which may offer long-term survival.

Adenocarcinoma

A disposable sealing device (Dispo-sand) for conversion between pneumoperitoneum and minilaparotomy.

During laparoscopic procedures, minilaparotomy is a safe technique for removal of large specimens and for the performance of complicated procedures. However, it is time consuming and troublesome to close the minilaparotomy to recreate the pneumoperitoneum. We describe a new device (Dispo-sand) that enables instant conversion between pneumoperitoneum and minilaparotomy.

Disposable Equipment

1alpha,25-dehydroxyvitamin D3 synergism toward transforming growth factor-beta1-induced AP-1 transcriptional activity in mouse osteoblastic cells via its nuclear receptor.

The present study demonstrates 1alpha,25-dehydroxyvitamin D3 (1alpha-25-(OH)2D3) synergism toward transforming growth factor (TGF)-beta1-induced activation protein-1 (AP-1) activity in mouse osteoblastic MC3T3-E1 cells via the nuclear receptor of the vitamin. 1alpha-25-(OH)2D3 synergistically stimulated TGF-beta1-induced expression of the c-jun gene in the cells but not that of the c-fos gene. We actually showed by a gel mobility shift assay 1alpha-25-(OH)2D3 synergism of TGF-beta1-induced AP-1 binding to the 12-(O-tetradecanoylphorbol-13-acetate response element (TRE). 1alpha-25-(OH)2D3 markedly stimulated the transient activity of TGF-beta1-induced AP-1 in the cells transfected with a TRE-chloramphenicol acetyltransferase (CAT) reporter gene. Also, a synergistic increase in TGF-beta1-induced CAT activity was observed in the cells cotransfected with an expression vector encoding vitamin D3 receptor (VDR) and the reporter gene. However, the synergistic CAT activity was inhibited by pretreatment with VDR antisense oligonucleotides. In addition, in a Northern blot assay, we observed 1alpha-25-(OH)2D3 synergism of TGF-beta1-induced expression of the c-jun gene in the cells transfected with the VDR expression vector and also found that the synergistic action was clearly blocked by VDR antisense oligonucleotide pretreatment. The present study strongly suggests a novel positive regulation by 1alpha-25-(OH)2D3 of TGF-beta1-induced AP-1 activity in osteoblasts via "genomic action."

Animals

Identification and cloning of human G-protein gamma 7, down-regulated in pancreatic cancer.

Differentially expressed genes between normal and cancer tissues of the pancreas were investigated using differential display. Consequently, we identified a fragment cDNA that was expressed in the normal tissue but was rarely expressed in the cancer tissue. This cDNA was screened in cDNA library prepared from the normal pancreatic tissue by rapid amplification of cDNA ends (5'RACE). 859 bp of cDNA was cloned and sequenced, and the inferred amino acid sequence was found to encode a G protein gamma subunit with 98% homology to cow G protein gamma 7 and complete homology to human G protein gamma 7. The decreased expression of the G protein gamma 7 was confirmed by Northern blot assay in twelve pancreatic malignancies which included nine duct cell carcinomas, two cystoadenocarcinomas and one blastoma. Reverse transcriptase (RT)-polymerase chain reaction (PCR) assay showed no expression of G protein gamma 7 in five of six pancreatic carcinoma cell lines and two pancreatic cancer tissues. Immunohistochemical analysis also displayed positive staining in the normal tissue but no staining in the cancer tissue. The findings demonstrated that the reduced or suppressed expression of human G-protein gamma 7 may play an important role in pancreatic carcinogenesis.

Amino Acid Sequence

Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts.

Recent studies have demonstrated that ceramide plays an important role as a second messenger in many kinds of cells. However, it is not known whether apoptosis of and bone resorption by mature osteoclasts are mediated via sphingomyelinase (SMase) and ceramide. Thus, we examined the possible involvement of SMase and ceramide in the induction of apoptosis in and bone resorption by rabbit mature osteoclasts. SMase and C2-ceramide inhibited strongly F-actin ring formation of and bone resorption by the osteoclasts. However, the osteoclast apoptosis was not induced by C2-ceramide. The ceramide inhibition of the bone resorption was suppressed by DL-threodihydrosphingosine, an inhibitor of sphingosine kinase. In addition, we observed that sphingosine-1-phosphate is able to inhibit bone resorption by the osteoclasts. These results suggest an important role of the sphingomyelin pathway in bone resorption by rabbit mature osteoclasts.

Actins

Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes.

EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway.

Aging

Vasopressin antagonist improves renal function in a rat model of pneumoperitoneum.

Pneumoperitoneum (PP) is associated with oliguria and increased plasma arginine vasopressin (AVP) levels. This study investigated the role of AVP in the pathogenesis of oliguria due to PP. Anesthetized and ventilated rats (n = 12) were subjected for 1 h to carbon dioxide PP with an intra-abdominal pressure of 8 mmHg or, as control, at 0 mmHg, before the determination of plasma AVP level. Another group of rats (n = 48) subjected to PP or control conditions was pretreated with the AVP V2 receptor antagonist, OPC-31260 (5 mg/kg), or vehicle, and their renal parameters were measured. Glomerular filtration rate (GFR) was determined by inulin clearance in an additional group of rats (n = 12) subjected to PP with or without pretreatment with OPC-31260. Rats subjected to PP had higher plasma AVP levels than did controls (17.3 +/- 8.1 pg/ml vs 1.5 +/- 0. 6 pg/ml, P < 0.05). In rats pretreated with vehicle, PP decreased urine output, excretion of water, and urea nitrogen, leading to reduced serum osmolality and serum sodium levels as well as elevated blood urea nitrogen levels. OPC-31260 pretreatment improved urine output, excretion of water, and urea nitrogen, thereby preventing changes in serum osmolality, serum sodium levels, and blood urea nitrogen levels. OPC-31260 pretreatment did not affect GFR. Results suggest that plasma AVP contributes to the oliguria due to PP. OPC-31260 may be useful in treating the water retention associated with PP.

Animals

Clinical significance of ventricular size in shunted-hydrocephalic children.

For maintaining the intracranial buffering capacity against shunt obstruction, we tried to seek the most suitable size of the lateral ventricles in hydrocephalic children. Thirty-seven shunted-hydrocephalic children who required emergent revision of the shunt were analyzed. At the time of shunt obstruction, the lateral ventricle remained small (0.35 or less than 0.35 on the Evans' index) in 13 patients (Slit-like group), but it enlarged (more than 0.35 on the Evans' index) in 24 patients (Dilated group). The mean age in the Slit-like group was significantly older than in the Dilated group and there was no patient younger than 3 years in the Slit-like group. Compared with the Dilated group, the Slit-like group showed significantly rapid deterioration into lethargy after shunt obstruction. Also, at the time of obstruction CT scans showed a significantly higher rate of narrowing of the ambient cistern. While the shunt was working well before shunt obstruction, the Evans' index was less than 0.33 in all patients of the Slit-like group. In conclusion, because small ventricles after shunt strongly suggest the presence of ventricular tautness, the lateral ventricular size should be maintained at more than 0.33 on the Evans' index in shunted children at an age of 3 or more than 3 years.

Adolescent

Bone mineral density in patients taking H2-receptor antagonist.

Osteoporosis after gastrectomy is a common clinical disorder. In gastrectomized patients, decreased gastric acidity may be associated with impaired calcium absorption. This study was undertaken to determine whether patients with chronic use of H2-receptor antagonists (HRA) had demonstrable decreases in bone mineral density (BMD). Thirty-three patients taking cimetidine, ranitidine, or famotidine for more than 2 years were analyzed. We measured BMD of L2-L4 using dual energy X-ray absorptiometry (DXA). Osteoporosis (BMD less than 0.70 g/cm2) was found only in three patients (9%). As compared with healthy controls, age- and sex-matched BMD ranged from 74.4% to 132.9%, with a mean of 97.0%, and was not influenced by the period of HRA use (<5 years versus >5 years or more). Although the age- and sex-matched BMD was different among the kinds of HRA (98.6% for cimetidine, 101.3% for ranitidine, and 85.5% for famotidine), the relationship between the BMD and type of drug was not significant by multivariate analysis. These results indicate that chronic use of HRA has little influence on the degree of BMD, and suggest that decreased gastric acidity is not always associated with osteoporosis after gastrectomy.

Adult

Comparison of pneumoperitoneum and abdominal wall lifting as to hemodynamics and surgical stress response during laparoscopic cholecystectomy.

BACKGROUND: Impairments in hemodynamics during pneumoperitoneum (PP) have been noted. This study compared changes in hemodynamics and surgical stress response with PP and abdominal wall lifting (AWL) during laparoscopic cholecystectomy. METHODS: Twenty patients with symptomatic cholecystolithiasis were assigned to PP (n = 10) or AWL (n = 10). Cardiac output (CO), stroke volume (SV), and ejection fraction (%EF) were measured by transesophageal echocardiography. Clearances of para-aminohippurate (CPAH) and sodium thiosulfate (CSTS) were determined as measures of renal function. Levels of interleukin-6, C-reactive protein, white cell count, and neutrophil elastase were evaluated as indicators of surgical stress. RESULTS: In the PP group, CO, SV, and %EF were depressed significantly during pneumoperitoneum. Immediately after and 15 min after insufflation, the CPAH and CSTS were decreased by 78.0% and 73.8%, respectively. None of the hemodynamic parameters changed significantly in the AWL group. Surgical stress response was not different significantly between the two groups. CONCLUSIONS: In contrast to pneumoperitoneum, AWL did not alter cardiac function or renal hemodynamics. AWL may be useful in patients with cardiovascular or renal disorders.

Abdominal Muscles