Biomedical subjects
Publications and source records attributed to J Mimura.
Two years have passed since the Ah receptor (AhR) and the AhR nuclear translocator (Arnt) were revealed to constitute a novel ligand-activated transcription factor by molecular biological studies on cloned cDNAs. Many interesting properties of the AhR/Arnt system have begun to be elucidated. We present here a brief summary of the molecular biology of AhR and Arnt.
Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.
Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection.
Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.
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Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.
Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.
Tumor hemodynamics including arterial vascularity (AV) and portal perfusion (PP) were evaluated in histologically confirmed 55 hepatic nodules associated with cirrhosis using ultrasonographic (US) angiography during intraarterial carbon dioxide microbubbles injection and CT during arterial portography. Tumor hemodynamic patterns were classified into 6 types as follows: Type I (n = 10): PP (+), AV (hypo); Type I' (n = 2): PP (+), AV (iso); Type II (n = 5): PP (-), AV (hypo); Type III (n = 8): PP (-), AV (iso); Type IV (n = 25): PP (-), AV (hyper), Type V (n = 5): PP (partially +), AV (vascular spot in hypovascular). Eight nodules of Type I were diagnosed as benign nodules histologically including adenomatous hyperplasia (AH) (n = 6) and regenerative nodule (n = 2). Hundred percent (5/5) of Type II and 88% (7/8) of Type III nodules were well-differentiated HCC, in contrast to 8% (2/25) of Type IV nodules, typical HCCs. Fatty metamorphosis was observed in 75% (6/8) of Type III nodules, in contrast to 16% (4/25) of typical (classical) HCC nodules (Type IV). We concluded that at the malignant transformation from AH to HCC, reduction of portal blood flow in the nodule precedes the initiation of the increase of the arterial tumor vessel. Moreover, early stage HCC could exhibit hypovascular (Type I, II), isovascular (Type III), or vascular spot in hypovascular pattern (Type V) compared with a typical HCC (Type IV). It was also suggested that the more mature as a neoplasms the HCC becomes, the more the arterial tumor vessel in the nodule increases and fatty metamorphosis of well-differentiated HCC is highly related with tumor hemodynamic condition, i.e., hypoperfusion state from both arterial and portal vessel.
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