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Biomedical subjects

Takeshi Ito

Publications and source records attributed to Takeshi Ito.

30 records · Page 2Linked to original sources

High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases.

p21(WAF1/CIP1) (p21) protein is a universal inhibitor of cyclin-dependent kinases and is regulated transcriptionally by p53, which is activated by DNA stress. Hepatocytes in chronic hepatitis receive several DNA stresses by lymphocytes and Kupffer cells. Therefore, we analyzed p21 expression of hepatocytes in hepatitis C virus (HCV)-associated chronic liver diseases and investigated the possible involvement of p21 in hepatocarcinogenesis. We examined p21 expression in 35 cases of HCV-associated chronic hepatitis and 25 cases of HCV-associated liver cirrhosis by immunohistochemical analysis. The p21 labeling index (LI) was calculated as the ratio of positive cells to total cells. p21-positive hepatocytes were more numerous in areas of intense inflammation and spotty necrosis and areas close to fibrosis, and were increased according to the degrees of grading and staging. The p21 LI with liver cirrhosis was significantly higher than that with chronic hepatitis (14.4 +/- 5.9 versus 11.1 +/- 4.2, P = 0.014). The cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the p21 LI >or=14% group than in the p21 LI <14% group (P = 0.0079). Multivariate analysis demonstrated that p21 expression can be recognized as an independent significant factor for HCC development (relative risk 5.00, P = 0.039). p21 LI decreased significantly after interferon therapy. These results suggested that p21 is up-regulated by the stress of inflammation and fibrosis in HCV-associated chronic liver diseases and that high p21 expression might be related to hepatocarcinogenesis in cirrhotic patients.

Analysis of Variance↗

Restraint stress modulates brain, pituitary and adrenal expression of angiotensin II AT(1A), AT(1B) and AT(2) receptors.

Angiotensin II (Ang II) AT(1) receptors are involved in the regulation of the stress response. In adult male rats, acute restraint increased AT(1A) mRNA in paraventricular nucleus. Repeated restraint increased AT(1A) mRNA and AT(1) binding in paraventricular nucleus and AT(1) binding in subfornical organ and median eminence. AT(1B) and AT(2) receptors were not expressed in brain areas involved in the stress response. Acute restraint increased anterior pituitary AT(1A) mRNA and AT(1) binding and decreased AT(1B) mRNA. During repeated restraint, the increase in AT(1A) mRNA in the anterior pituitary was maintained, but AT(1B) mRNA and AT(1) binding returned to normal levels. In adrenal zona glomerulosa, AT(1B) mRNA, AT(1) binding, AT(2) mRNA and AT(2) binding decreased during acute restraint. Receptor mRNA and binding returned to normal after repeated stress, with the exception of rebound increase in adrenal zona glomerulosa AT(2) mRNA. In adrenal medulla, AT(1A) mRNA increased and AT(2) mRNA decreased during acute restraint. AT(1A) mRNA remained increased during repeated restraint, while alterations in AT(2) mRNA were no longer present. Expression of AT(1A), AT(1B) and AT(2) receptors in the hypothalamic-pituitary-adrenal axis is tissue specific and is different in acute and repeated stress. Increased brain, pituitary and adrenomedullary AT(1A) receptor expression correlates with hypothalamic-pituitary-adrenal axis stimulation, supporting the hypothesis of Ang II, through selective AT(1A) receptor stimulation, as an important determinant of the acute and repeated stress response. Decreased adrenal zona glomerulosa and anterior pituitary AT(1B) receptors during acute stress can be interpreted as compensatory to increased stimulation by Ang II. There may be additional roles for adrenal AT(2) receptors during acute stress, possibly related to interaction or cross-talk with AT(1) receptors.

Adrenal Glands↗

Protection against ischemia and improvement of cerebral blood flow in genetically hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist.

BACKGROUND AND PURPOSE: Pretreatment with angiotensin II AT(1) receptor antagonists protects against cerebral ischemia. We studied whether modulation of cerebral blood flow (CBF) and morphometric changes in brain arteries participated in this protective mechanism. METHODS: We pretreated adult spontaneously hypertensive rats with equally antihypertensive doses of candesartan (0.1 or 0.3 mg/kg per day), nicardipine (0.1 mg/kg per day), or captopril (3.0 mg/kg per day) for 3 or 28 days via subcutaneous osmotic minipumps followed by permanent left middle cerebral artery (MCA) occlusion distal to the origin of the lenticulostriate arteries. We measured CBF by autoradiography with 4-iodo-[N-methyl-(14)C]antipyrine 3 hours after operation and the areas of infarct and tissue swelling 24 hours after operation. Morphometric changes in the MCA were studied after antihypertensive treatment. RESULTS: Twenty-eight days of candesartan pretreatment decreased the infarct area by 31%; reduced the CBF decrease at the peripheral area of ischemia and the cortical volume of severe ischemic lesion, where CBF was <0.50 mL/g per minute; increased the MCA external diameter by 16%; and reduced the media thickness of the MCA by 23%. Captopril pretreatment for 28 days decreased the infarct area by 25%. Pretreatment with candesartan for 3 days or nicardipine for 28 days was ineffective. CONCLUSIONS: Angiotensin II system inhibition protects against neuronal injury more effectively than calcium channel blockade. Protection after AT(1) receptor blockade is not directly correlated with blood pressure reduction but with normalization of MCA media thickness, leading to increased arterial compliance and reduced CBF decrease during ischemia at the periphery of the lesion.

Angiotensin Receptor Antagonists↗

Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels detected by high-sensitive electrochemiluminescence system as an early predictive marker for hepatocellular carcinoma in patients with cirrhosis.

Serum concentration levels of des-gamma-carboxy prothrombin (DCP), alpha-fetoprotein (AFP) and Lens culinaris agglutinin-reactive fraction (AFP-L3) are useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Recently, a novel immunoassay using the electrochemiluminescence (ECLIA) was developed to enable measurement of low-concentration of DCP. This study investigated the usefulness of high-sensitive DCP for the early diagnosis of HCC. The subjects consisted of 90 patients with viral cirrhosis who could be followed for at least 24 months from 1992 to 1997. Fifty-six of these patients developed HCC and 34 patients had not by 1998. We measured the serum levels of high-sensitive DCP, AFP and %AFP-L3 every 3 months during 2 years before the detection of tumor in patients with HCC and during 2 years from 1995 to 97 in patients without HCC. Youden's index was calculated for evaluation of the ideal cut-off levels. The patterns of serial changes during 2 years were divided into two types: fluctuating type and non-fluctuating type. Cut-off levels of 40 mAU/ml for high-sensitive DCP (Youden's index = 0.435), 20 ng/ml for AFP (Youden's index = 0.442) and 10% for %AFP-L3 (Youden's index = 0.364) gave the highest index for each marker. When these markers were combined, the combination of high-sensitive DCP, AFP and %AFP-L3 gave the highest accuracy (sensitivity = 82.1%, specificity = 82.4%, accuracy = 82.2%). Fluctuating type of high-sensitive DCP, AFP and %AFP-L3 levels were found in 15 (17%), 29 (32%) and 11 (12%) patients, respectively. The rate of complication with HCC in the patients who showed the fluctuating type of high-sensitive DCP levels was significantly greater than that in the patients who showed non-fluctuating type (P<0.01). These results suggest that periodic measurement of serum DCP levels using ECLIA method is very useful for HCC screening and predicting the development of HCC.

Adult↗

Pneumothorax after diagnostic laparoscopy.

Here we want to call laparoscopist's attention to pneumothorax after diagnostic laparoscopy. Diagnostic laparoscopy has less complications, compared with laparoscopic surgery. In our experience, only one case (0.04%) developed pneumothorax during routine diagnostic laparoscopic procedure. This complication is presented in a 50-year-old female. She complained of dyspnea just after the decrease of intraabdominal pressure and deflation of intraperitoneal gas. The chest roentgenogram showed a right pneumothorax, and a right chest tube was inserted with immediate relief of tension. Pneumothorax during diagnostic laparoscopy is relatively rare but a major complication; Medline literature research showed six reported cases of pneumothorax after diagnostic laparoscopy from 1983 to 1998 including our case. The etiology was idiopathy in 5 and diaphragmatic injury in 1. Hypotension, elevation of inspiratory pressure, dyspnea, a decrease in systemic oxygen saturation, and loss of breath sounds suggest tension pneumothorax. The clinical condition of the patients improved rapidly because of the easy diffusion of the gas used in laparoscopy. Diagnostic laparoscopists should be aware of this complication and treat ventilatory problems.

Biopsy↗

Endoscopic sclerotherapy (ethanolamine oleate injection) for acute rectal varices bleeding in a patient with liver cirrhosis.

Treatment for acute rectal bleeding from rectal varices in a patient with liver cirrhosis is often difficult. Herein, we report an elderly male with cirrhosis who successfully underwent endoscopic sclerotherapy for rectal bleeding from rectal varices. He had a history of esophageal varices, which were treated by endoscopic sclerotherapy. Three years after the treatment of esophageal varices, he developed massive bright red rectal bleeding. Taking into consideration the risk of treating rectal varices by surgery, we decided to try endoscopic sclerotherapy of the rectal varices. In this case, we injected 16.4 mL of 5% ethanolamine oleate with iopamidole to the rectal varices for the purpose of confirmation of the feeding vein for the varices. After six months, the rectal varices had disappeared. We believe endoscopic sclerotherapy might be an effective therapeutic modality for rectal varices with cirrhosis.

Aged↗

Focal spared area in fatty liver mimicking a tumor.

A focal fatty liver change may be associated with several conditions related to diffuse hepatic steatosis, such as a diffuse fatty liver change. Using ultrasonography, the focal fatty liver change appears more frequently as hyperechoic and less frequently as hypoechoic areas in the liver. We report a rare case of a focal fatty liver change in which an area was spared in fatty liver. The patient was a 42-year-old man. Abdominal ultrasonography showed focal hypoechogenicity with an irregular margin in S8 within a bright liver. Abdominal computed tomography and enhanced computed tomography showed a high-density mass in S8 of the right lobe. A microscopic examination of the specimens from the liver biopsy from the hypoechoic region revealed normal hepatic parenchymal cells, while tissue samples from the surrounding liver had a high fat deposition.

Adult↗

Detection of precore-mutant hepatitis B virus genome in patients with acute and fulminant hepatitis using mutation site-specific assay (MSSA).

BACKGROUND/AIMS: Precore mutation of hepatitis B virus was recently been suggested to be involved in the pathogenesis of fulminant hepatitis. In this study, we analyzed the occurrence of precore mutants in patients with acute and fulminant hepatitis B using new simple rapid and sensitive MSSA (mutation site-specific assay) and evaluated this method for predicting prognosis. METHODOLOGY: We analyzed HBV-DNA of 10 patients with fulminant hepatitis B, 15 patients with acute self-limited hepatitis, and 4 patients with acute severe hepatitis using MSSA. Precore point mutation (G to A; 83rd base of precore region) was examined using a mutation-trapped oligonucleotide primer, which would yield a polymerase chain reaction amplification product only with precore mutants. RESULTS: We distinguished precore mutants from wild type according to the presence or absence of the band at 203 bp, which was amplified in only precore mutants by polymerase chain reaction. Mutation of the precore region was observed in all 10 patients with fulminant hepatitis, in 3 of the 4 patients with severe hepatitis, and 11 of 15 patients with self-limited hepatitis. Negative pre-C mutants in patients with HBeAg indicates good prognosis of hepatitis. CONCLUSIONS: Precore mutant strains of HBV-DNA play an important role but are not specific for fulminant hepatitis, and the mere presence of precore mutants may not directly lead to fulminant hepatitis or severe hepatitis. However, this method is useful for predicting outcome of patients with acute HBV hepatitis, especially in HBeAg-positive state.

Adolescent↗

Hepatic angiosarcoma mimicking cavernous hemangioma on angiography.

A 60-year-old woman was admitted to our department for evaluation of a hepatic mass. The mass was diagnosed as a hemangioma of the liver by abdominal angiography because of typical cotton wool appearance and stretched arterial vessels and no peripheral staining. However, one month later, the mass was surgically removed because of extravasation. Histological findings of a specimen of the mass revealed that it entirely contained abundant necrotic tissue, and a small residual part after transcatheter arterial embolization was consistent with hemangioma. However, she complained of hemoptysis and thigh pain after several weeks. Computed tomography revealed multiple lung masses and a mass of right musculus gluteus medius. Reexamined histological findings of the liver tumor showed hemangiosarcoma. We should pay attention to the fact that it is sometimes difficult to differentiate cavernous hemangioma from angiosarcoma by angiography.

Angiography↗

The effect of endoscopic injection sclerotherapy on portal blood flow and liver function.

BACKGROUND/AIMS: It is still controversial whether endoscopic injection sclerotherapy can affect portal blood flow and liver function. To clarify this issue, we investigated the change in portal blood flow velocity and the relationship between liver function and portal blood flow after sclerotherapy. METHODOLOGY: Ten liver cirrhosis patients with F2 esophageal varices were enrolled in this study. All patients underwent sclerotherapy until all varices were eradicated. Portal blood flow velocity was measured using Doppler ultrasonography. The changes in laboratory parameters and the portal flow velocity were analyzed in each patient. RESULTS: Total mean portal blood flow velocity was changed from 7.5 +/- 5.3 cm/s to 10.3 +/- 3.5 cm/s by sclerotherapy. Six of ten cases had increase in portal blood flow velocity. Among them, 5 cases demonstrated improvement in serum albumin and total cholesterol level 3 months after sclerotherapy. CONCLUSIONS: Prophylactic endoscopic injection sclerotherapy among patients with early liver cirrhosis can improve liver function by increasing the portal blood flow.

Aged↗

Long-term follow-up of chronic hepatitis C in Japan.

BACKGROUND/AIMS: Chronic hepatitis C which exhibits a varied natural course, is becoming a major problem worldwide. METHODOLOGY: In this study, we investigated 161 patients with chronic hepatitis C by repeated liver biopsies. From initial biopsies, we diagnosed 56 patients with chronic persistent hepatitis, 74 with chronic active hepatitis 2A, and 31 with chronic active hepatitis 2B. RESULTS: During the follow-up period, a progression from chronic hepatitis to liver cirrhosis was recognized among all stages, however the rate of progression to liver cirrhosis was less in chronic persistent hepatitis than in chronic active hepatitis 2A and chronic active hepatitis 2B. Hepatocellular carcinoma was detected in chronic active hepatitis 2A and chronic active hepatitis 2B at the initial stage, however, no tumors developed in chronic persistent hepatitis at the initial stage. Most hepatocellular carcinomas were concomitant with liver cirrhosis. CONCLUSIONS: We suggest a close follow-up of patients with chronic hepatitis C, especially those patients with chronic active hepatitis 2A or 2B and exhibiting successive active inflammation of liver.

Biopsy↗

Transcatheter arterial embolization and extrabeam radiation therapy for subcutaneous seeding of hepatocellular carcinoma by percutaneous ethanol injection.

A 74-year-old man with a hepatocellular carcinoma received percutaneous ethanol injection twice following the needle biopsy of the tumor. Two years and 6 months after percutaneous ethanol injection, a subcutaneous tumor, which appeared to be a needle tract seeding by percutaneous ethanol injection, was recognized in the right lower anterior chest wall. A curative surgical resection was impossible because of the patient's decreased coagulopathy and severe liver dysfunction. The disseminated tumor was treated with extrabeam radiotherapy (20 fractions; total dose of 50 grays) followed by transcatheter arterial embolization by means of superselective catherization. The size of the subcutaneous tumor was decreased to about 15 mm in diameter. Contrast medium enhanced computed tomography demonstrated no enhancement in the tumor. The patient is currently doing well without further recurrence of hepatocellular carcinoma and without enlargement of the subcutaneous tumor after extrabeam radiation therapy and transcatheter arterial embolization.

Aged↗