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H Isozaki

Publications and source records attributed to H Isozaki.

At least 19 recordsLinked to original sources
PubMed2001

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Aged↗
PubMed2001

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

Aged↗
PubMed2001

Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells.

E2F is a family of transcription factors implicated in the regulation of gene expression required for progression through the G(1)-S transition. We have previously detected tumor-specific mutations at a trinucleotide repeat coding sequence of E2F-4 gene in a subset of human sporadic colorectal cancers. The purpose of this study was to investigate the potential functional consequences of these E2F-4 mutations. We transfected NIH3T3 fibroblasts with expression constructs containing wild-type as well as mutant E2F-4 cDNA, and the effect of the E2F-4 mutations on proliferation was examined. Alteration in transactivation of the E2F consensus promoter sequence was also examined by transient cotransfection of a E2F-4 with a DP-2 construct into cultured human cells. Transfected cell clones overexpressing mutant E2F-4 grew more rapidly and showed higher proliferative activity by increased immunohistochemical staining for proliferating cell nuclear antigen (PCNA). All three mutant forms of E2F-4 showed elevated transactivation of the E2F consensus promoter sequence. Thus, expression of mutant E2F-4s confers a growth advantage in vivo, and this effect may be related to the acquisition of a neoplastic phenotype.

3T3 Cells↗
PubMed2001

Advanced gastric cancer with multiple lymph node metastasis successfully treated with etoposide, adriamycin and cisplatin.

Gastric cancer usually shows poor sensitivity to chemotherapy, and the presence of lymph node metastases is associated with extremely poor prognosis, especially when the number of such nodes is more than 10. We report here a case of advanced gastric cancer with histopathologically confirmed metastases in 15 regional lymph nodes, in which the recurrent tumor was sensitive to combination chemotherapy. Distal gastrectomy with lymphadenectomy was performed for the primary tumor. A hard (recurrent) tumor was detected in the upper abdomen 5 months postoperatively. Abdominal CT revealed two tumors measuring 3.5 x 1.8 and 3.3 x 2 cm in diameter at the front of the pancreatic head, which suggested recurrence. Etoposide, adriamycin and cisplatin (EAP) chemotherapy (20 mg/kg adriamycin, 100 mg/kg etoposide and 50 mg/kg cisplatin (CDDP)) was administered every 6 weeks. The tumors regressed and became undetectable on CT after four cycles. At that stage, CDDP was replaced with 400 mg/kg carboplatin, which was administered every 1 or 2 months. The patient had no recurrence 8 years after surgery. For treatment of advanced gastric cancer with multiple lymph node metastases, a wide resection of the tumor should be performed followed by treatment of the residual tumor cells with a suitable combination chemotherapy taking into consideration the characteristics of the tumor and the condition of the host. We present a patient with gastric cancer and histopathologically confirmed metastases in 15 regional lymph nodes, who was successfully treated by surgery followed by EAP adjuvant chemotherapy. The patient remains alive and well at 8 years after surgery.

Adult↗
PubMed2001

A family of multiple endocrine neoplasia type 2A with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of MEN-2 patients. We report here three generations of one MEN-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.

Adult↗
PubMed2001

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Carcinoma, Squamous Cell↗
PubMed2001

Successful resection of rectal carcinoma in an Evans' syndrome patient followed by predonisolone and high-dose immunoglobulin: report of a case.

A 69-year-old woman was admitted to our hospital because of anal bleeding and fatigue. The patient was previously diagnosed as having Evans' syndrome on the basis of hematological examination and had been treated with predonisolone for 8 years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy and Barium enema studies demonstrated an irregular tumor with hemorrhagic ulceration in the rectum, which was histopathologically confirmed as an adenocarcinoma. After red blood cells and platelets were transfused, and the patient was treated with high-dose gammaglobulin, predonisolone, and camostat mesylate, the platelet count gradually increased and hemolysis was well controlled. The patient then underwent Hartmann's operation and splenectomy without any postoperative complications. Predonisolone and high-dose immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome is considered useful in combination with surgical treatment. This is the first case report of rectal carcinoma resection in a patient with Evans' syndrome.

Adenocarcinoma↗
PubMed2000

Crohn's disease mimicking as bowel endometriosis. Are the symptoms reduced by nafarelin acetate?

We report a 27-year-old female with Crohn's disease clinically misdiagnosed with intestinal endometriosis. Her complaints were abdominal pain and fullness, which occurred monthly during her menstrual period. Although we had no histopathological evidence, we diagnosed her as bowel endometriosis on the basis of her clinical course. Since nafarelin acetate therapy started, the symptoms due to mechanical subileus have improved. The transverse colon, a 70 cm segment of the ileum, including the terminal ileum, were resected because of repeated symptoms of bowel obstruction despite prolonged nafarelin therapy. Histopathological findings of the resected specimen revealed Crohn's disease without endometrial tissue. In our patient, an increased cortisol and ACTH secretion, a side effect of nafarelin, was noted during the therapy. This case showed that nafarelin therapy could increase serum concentration of ACTH and cortisol, which was considered to suppress the pathology of Crohn's disease by its anti-inflammatory action. We emphasize that intestinal examination must be performed with Crohn's disease in mind, even if nafarelin acetate is effective.

Adrenocorticotropic Hormone↗
PubMed2000

Acute appendicitis caused by amebiasis.

We report a case of appendicitis caused by amebiasis in a 45-year-old Japanese man. He presented to our hospital with bloody stools in June 1998. Sigmoidoscopy disclosed erosion, and a biopsy of the erosion showed colitis caused by Entamoeba histolytica infection. Four months later, he was admitted to our hospital with a small elastic mass and severe pain in the lower quadrant of the abdomen, which was diagnosed as acute appendicitis. He underwent appendectomy. Histopathological examination revealed numerous E. histolytica trophozoites, and we diagnosed acute appendicitis caused by E. histolytica. The patient has been free of symptoms, colonoscopy has revealed no erosion, and biopsy has revealed no E. histolytica for 12 months after the operation.

Appendicitis↗
PubMed2000

Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis.

We report a rare case of hepatic adenomas (HA), in a 20-year-old Japanese girl treated for 6 years with anabolic androgens for aplastic anemia. In a review of the world literature using computer MEDLINE search, we found only 17 cases of androgen-induced HA published between 1975 and 1998 in the English-language literature. The patient was referred to us because of liver lesions detected during a follow-up examination for familial adenomatous polyposis. After being diagnosed with aplastic anemia at 14 years of age, she had been treated with oxymetholone (30 mg/day) for 6 years. Laboratory evaluation revealed normal liver function. Ultrasonography (US) and computed tomography (CT) demonstrated multiple liver lesions. Histopathological examinations of biopsied specimens from the liver tumor showed HA. After the patient was diagnosed with HA, oxymetholone was tapered off. Patients taking androgenic-anabolic steroids should be carefully monitored with US and CT and tumor markers should be measured. This report may be helpful in identifying the population who is at risk of developing hepatic sex hormone-related tumors.

Adenoma↗
PubMed2000

Immunohistochemical studies of colorectal cancers that developed following pelvic irradiation.

Radiation therapy is believed to be a predisposing factor in the development of carcinoma. During the period from 1974 to 1997, we treated five colorectal cancers in four patients who had undergone pelvic irradiation for cervical cancer. Radiation-induced changes in the remaining bowel were recognized in all of these patients. Of the five tumors, two were histologically diagnosed as mucinous adenocarcinoma, demonstrating a higher distribution than usual: To clarify the characteristics of the tumors, we examined the frequency of mutation in K-ras and p53 genes, and the proliferating cell nuclear antigen (PCNA) proliferation activity. The K-ras and PCNA stains did not show any clear characteristics of radiation-induced colorectal cancers in comparison with ordinary colorectal cancers; however, it was of interest that strongly positive staining was observed in our mucinous adenocarcinomas, even though a low frequency of p53 gene mutation has been reported in ordinary mucinous adenocarcinomas.

Adenocarcinoma, Mucinous↗
PubMed2000

Gastric perforation caused by a bulimic attack in an anorexia nervosa patient: report of a case.

We report a rare case of gastric perforation due to a bulimic attack in a 17-year-old girl suffering from anorexia nervosa. She was admitted to our hospital with the chief complaint of abdominal pain following bulimia. Initially, her symptoms were reduced after drainage using a nasogastric tube. Eight hours later, however, she fell into a state of preshock. Abdominal radiography revealed subphrenic free air. We diagnosed the patient as having diffuse peritonitis. At laparotomy, the stomach was dilated and necrotic with perforation. Almost the entire stomach was resected. Postoperatively, the patient recovered uneventfully. We should therefore be aware of this condition when treating patients with anorexia nervosa who complain of abdominal pain.

Adolescent↗
PubMed2000

Generalized peritonitis due to spontaneously perforated pyometra presenting as pneumoperitoneum: report of a case.

We report a rare case of generalized peritonitis due to a ruptured pyometra in an 86-year-old woman, and also conduct a review of the previous Japanese literature. The patient presented with muscle guarding and rebound tenderness. Computed tomography (CT) disclosed a cystic mass in the peritoneal cavity, in which an air-fluid level was noted. Pneumoperitoneum around the uterus due to gas production of anaerobic bacteria was noted on a CT. At laparotomy, the uterus was markedly enlarged with a necrotic area on the uterine fundus, which was found to be perforated. A supravaginal hysterectomy and drainage were performed. We found only eight cases of a ruptured pyometra presenting as pneumoperitoneum in the Japanese literature between 1977 and 1999. The most common cause of pneumoperitoneum is a perforation of the gastrointestinal tract. However, other possible causes, as seen in our patient, should also be taken into consideration. Although it is rare, a perforated pyometra should therefore also be considered when elderly women present with acute abdominal pain.

Aged↗
PubMed2000

Calcium concentration in hepatocytes during liver ischaemia-reperfusion injury and the effects of diltiazem and citrate on perfused rat liver.

OBJECTIVE: To clarify the role of the calcium concentration in hepatocytes in liver ischaemia-reperfusion injury in relation to the protective effect of calcium-related agents. DESIGN: Serial calcium concentrations of extramitochondrial cytosolic sites (EMCa) and in mitochondria (MCa) in hepatocytes of isolated perfused rat liver were measured by an electron probe X-ray microanalyser, and the effects of calcium-related agents were evaluated. METHODS: Ischaemia was induced for 2 h, followed by 2 h of reperfusion in group I (without drug), group II (with diltiazem, 9.3 microM) and group III (with citrate, 5 mM). RESULTS: In group I, EMCa increased rapidly after reperfusion (before ischaemia, 2.0 mmol/kg wet weight; 1 min after reperfusion, 4.4 mmol/kg), and MCa increased (before ischaemia, 2.6 mmol/kg; 1 min after reperfusion, 5.07 mmol/kg). Thereafter the levels decreased, but remained high at 120 min after reperfusion in group I (EMCa, 3.2 mmol/kg, MCa 4.1 mmol/kg). At 1 min after reperfusion, EMCa in group III (2.9 mmol/kg) and MCa in groups II (3.4 mmol/kg) and III (4.0 mmol/kg) were significantly lower than in group I. At 120 min after reperfusion, the EMCa and MCa in groups II (2.5 and 3.1 mmol/kg, respectively) and III (2.4 and 3.0 mmol/kg, respectively) remained at significantly lower levels. Mitochondrial function in groups II and III was better preserved than in group I. The levels of hepatic enzymes in the perfused fluid of group III were lower than in group I. CONCLUSIONS: Calcium concentration in hepatocytes may play an important role in ischaemia-reperfusion injury. Diltiazem and citrate demonstrated a protective effect by maintaining a low calcium level in hepatocytes.

Adenosine Triphosphate↗
PubMed2000

Multiple tumors and a novel E2F-4 mutation. A case report.

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.

Adult↗
PubMed2000

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

Aged↗
PubMed2000

[Genetic analysis for colorectal cancer: what can we learn from microsatellite research?].

Recent advances in molecular biology have unveiled the mechanisms of carcinogenesis, especially colorectal carcinogenesis. A large body of evidence supports the idea that accumulated genetic changes due to inherited as well as environmental factors underlie colorectal cancer development. Recently, several reports have suggested that aberrant methylation of the CpG island may also play an important role in colorectal carcinogenesis. This genetic information is not yet sufficient but some useful genetic information can be applied clinically. This paper presents the results of intensive study of microsatellite instability in colorectal cancers and some clinically applicable discoveries. Future problems are also discussed.

Colorectal Neoplasms↗