Biomedical subjects

Nobuhiko Harada

Publications and source records attributed to Nobuhiko Harada.

6 recordsLinked to original sources

PubMed2003

Gene expression of detoxifying enzymes in AhR and Nrf2 compound null mutant mouse.

The arylhydrocarbon receptor (AhR) regulates the expression of cytochrome P450 (CYP)-1 gene family members which catalyze xenobiotic Phase I metabolism, while Nrf2 exerts the concerted regulation of Phase II enzyme genes. We generated AhR and Nrf2 compound null mutant mice to examine the integrated function of AhR- and Nrf2-regulated enzymes in detoxification. Furthermore, we used this mouse model, by administering three different classes of chemical inducers, to examine how xenobiotic metabolism may be influenced in the absence of signals transduced by AhR or Nrf2. The compound mutant mice responded only weakly to AhR ligand or Phase II inducer, while they displayed a clear response to phenobarbital, an inducer of the CYP2B family through another, unrelated transcription factor. Here, we report an initial characterization of the AhR-Nrf2 double mutant mice, which may serve as a simplified bioassay system to evaluate xenobiotic toxicity and metabolic biotransformation of various drugs and environmental chemicals.

Animals↗

PubMed2003

Type C chronic hepatitis with the discovery of a small hepatocellular carcinoma 7 years after successful interferon therapy.

The patient, a 61-year-old man, had sustained injuries in a traffic accident at the age of 26, for which he received a blood transfusion. Since 1988 (age, 49 years), abnormal hepatic function had been detected, and, because of the presence of hepatitis C virus antibodies, he was diagnosed as having type C chronic hepatitis. Based on a liver biopsy that was conducted in July 1992 (age, 53), a histological diagnosis of chronic active hepatitis (F(1)/A(2)) was made. Over a period of 6 months, starting in 1992, the patient was treated with interferon (IFNalpha-2a; total dosage, 720 MU). At the end of this regimen, the alanine aminotransferase level was normalized and serum hepatitis C virus-ribonucleic acid was negative. This condition was maintained until August 1996 (age, 57), after which the patient stopped reporting to our hospital. In June 2000 (age, 61) when he was hospitalized for an adhesive ileus, a small hepatocellular carcinoma (a solitary lesion measuring 18 mm in diameter) at S(8) was found, and it was extirpated by a segmental excision in July. The case is introduced to call attention to the need for longterm follow-up observation, even after effective IFN therapy.

Antiviral Agents↗

PubMed2003

Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus.

Glucagonoma of the pancreas is a rare tumor with distinct clinical manifestations, such as necrolytic migratory erythema,weight loss, anemia, diabetes mellitus, and hypoamino-acidemia. We report the case of a 68-year-old Japanese man who underwent curative resection for malignant glucagonoma of the pancreas diagnosed through anemia and diabetes mellitus. The patient had had diabetes mellitus for 20 years. Anemia was diagnosed in 1998. On admission, the hemoglobin level was 8.3g/dl, but the levels of serum iron, vitamin B12, and erythropoietin and, the number of reticulocytes were within normal limits. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and DUPAN-2 were also within normal limits, and exocrine function of the pancreas (PFD, 75%) was normal. Ultrasonography (US) revealed a hypoechoic tumor in the distal pancreas. Computed tomography (CT) demonstrated a high-density area 4 cm in diameter with calcification. The serum glucagon level was very high (2360 pg/ml), but the levels of other hormones such as somatostatin or gastrin were within normal limits, while insulin was low. Glucagonoma of the pancreas was diagnosed, and distal pancreatectomy with splenectomy was performed. Histological examination revealed a malignant endocrine tumor,which was immunohistochemically positive for chromogranin A and glucagon. Two months after the operation, the serum glucagon level had decreased to within normal limits and the hemoglobin level had increased to 10.4 g/dl. The case of glucagonoma reported here was found through diagnostic examinations of anemia and treated by surgical resection, by which the patient's anemia was largely alleviated. Therefore, we recommend checking patients who have diabetes mellitus and anemia in order to diagnose and treat glucagonoma in its early stage.

Aged↗

PubMed2002

Stenting is unnecessary in duct-to-mucosa pancreaticojejunostomy even in the normal pancreas.

BACKGROUND: There is a high risk of anastomotic leakage after pancreaticojejunostomy after pancreaticoduodenectomy (PD) in patients with a normal pancreas because of the high degree of exocrine function. These PD are therefore generally performed using a stenting tube (stented method). In recent years, we have performed pancreaticojejunostomy with duct-to-mucosa anastomosis without a stenting tube (nonstented method) and obtained good results. METHODS: The point of this technique is to preserve adequate patency of the pancreatic duct by carefully picking up the pancreatic duct wall with a fine atraumatic needle and monofilament thread. The results of end-to-side pancreaticojejunostomy of the normal pancreas were compared between the nonstented method (n = 109) and the stented method (n = 39). RESULTS: There were no differences in background characteristics between the groups, including age, gender and disease. The mean duration to complete pancreaticojejunostomy was 26.6 min in the nonstented group and 29.2 min in the stented group. The mean durations of surgical procedure and intraoperative blood loss were also similar in the groups. Morbidity rates due to early postoperative complications were 20.2 and 23.1%, with pancreatic leakage occurring in 7.3 and 7.7% of patients, respectively. These differences were not statistically significant. One patient in the stented group died of sepsis following leakage of pancreaticojejunostomy. There were also no significant differences in the mean time to initiation of solid food intake or postoperative hospital stay. CONCLUSION: We conclude that a stenting tube is unnecessary if the duct-to-mucosa anastomosis is completely performed. This operative technique can be considered a basic procedure for pancreaticojejunostomy because of the low risk.

Anastomosis, Surgical↗

PubMed2002

[Laparoscopic biliary surgery].

Laparoscopic cholecystectomy has become the standard treatment for patients with symptomatic gallbladder disease. However, there is a substantial proportion of patients in whom laparoscopic cholecystectomy cannot be successfully performed, and conversion to open surgery is required because of technical difficulties or complications. The incidence of bile duct injury has increased in laparoscopic cholecystectomy. Meticulous dissection and intraoperative cholangiography could significantly reduce the rate of that injury. Laparoscopic cholecystectomy for acute cholecystitis is still controversial because of surgical difficulty. In our experience, early laparoscopic cholecystectomy is a beneficial option for patients with acute cholecystitis, and it may even be safe in the acute stage. A better alternative for high-risk early operation and septic cases is percutaneous transhepatic gallbladder drainage. The coexistence of gallbladder cancer should be ruled out and preoperative diagnosis should be done carefully. Laparoscopic management of common bile duct (CBD) stones has many advantages. However it has been reported to be demanding and time-consuming to perform, which limits its widespread adoption. In our experience with 258 patients, laparoscopic CBD exploration was feasible for almost all CBD stones. The technical difficulties associated with laparoscopic CBD exploration could be overcome with the development of suitable equipment and increased expertise.

Cholecystectomy, Laparoscopic↗

PubMedDate not supplied

Thymidine phosphorylase expressed in macrophages enhances antitumor effect of 5'-deoxy-5-fluorouridine on human colorectal carcinoma cells.

BACKGROUND: Thymidine phosphorylase (dThdPase) is a key enzyme in the activation of the pro-drugs of 5-fluorouracil (5-FU), 5-deoxy-5-fluorouridine (5'-DFUR) and capecitabine. In colorectal carcinoma (CRC), the major cells expressing dThdPase have been shown to be stromal cells, particularly macrophages. MATERIALS AND METHODS: The present study was designed to clarify whether dThdPase expressed in macrophage-like cell lines, THP-1 and U937, and monocyte-rich mono-nuclear cells (MoMNCs) from human peripheral blood can modulate the antitumor effect of 5'-DFUR on CRC cells. RESULTS: dThdPase protein was found in THP-1 and U937 by ELISA, while little or no dThdPase could be detected in the CRC cell lines tested. Incubation of 5'-DFUR with the macrophage-like cells significantly enhanced the antitumor effect of 5'-DFUR in a 5-DFUR sensitivity assay compared with untreated 5'-DFUR. MoMNCs also showed a similar effect. When the media containing 5'-DFUR was treated with either THP-1 or U937 cells, detectable levels of 5-FU could be measured in the treated media. CONCLUSION: These data suggest that macrophages convert 5'-DFUR to 5-FU and release the converted 5-FU, resulting in an enhancement of the antitumor effect of 5'-DFUR.

Antimetabolites, Antineoplastic↗