Effect of intrahepatic omental implantation on angiogenesis in rat liver with hepatic artery ligation.

Despite early surgical intervention, the results of treating hepatic artery thrombosis remain poor. The use of omental flaps is well documented for its angiogenic potential in promoting neovascularization in ischemic tissues. This experimental study evaluated the formation of new blood-vessels after omental implantation (OI) in rats after ligation of the hepatic artery. Wistar rats were used and divided into the following groups: I OI with HAL, II OI without HAL, III hepatic artery ligation (HAL). For angiography, measurements were made of liver tissue blood flow by the laser Doppler method and of hepatic artery flow by the colored microsphere method (CMS), and immunohistochemical study was done for vascular endothelial growth factor (VEGF). The rats were killed at 1, 3, 7 or 30 days after laparotomy. Relative arterial hepatic blood flow in the implanted lobe of group I, as determined by CMS, reached 50% of control values 7 days after surgery. Angiography and microscopic studies of the excised liver revealed distinct angiogenesis surrounding the omental implant in the liver for 7 days postoperatively. The formation of new blood-vessels after OI was not observed in livers without HAL. Omental implantation appears to be useful in preventing organ anoxia after hepatic artery thrombosis.

Experimental and clinical studies on liver regeneration following transcatheter portal embolization.

BACKGROUND/AIMS: We studied compensatory hypertrophy following transcatheter portal embolization experimentally in dogs and clinically under the condition of cholestasis. METHODOLOGY: Experimental study: Sixteen dogs were used for this study. Transcatheter portal embolization was performed in the left lobes (70% of the total liver) using Gelfoam powder in dogs with 2-week obstructive jaundice. Liver weight, liver blood flow and the intracellular adenosine triphosphate content of isolated hepatocytes were measured after transcatheter portal embolization. Clinical Study: transcatheter portal embolization of the right portal branch was performed in 13 patients with cancer of the biliary tract and 3 patients with hepatocellular carcinoma before (extended) right lobectomy, using Gelfoam powder and thrombin. Six patients who had a total bilirubin level > 5 mg/dLunderwent a percutaneous transhepatic biliary drainage before transcatheter portal embolization. Liver function tests, a volumetric study with computed tomography and immunohistochemical staining for profilerating cell nuclear antigen and apoptosis in the resected livers were performed. RESULTS: Experimental study: The weight ratio of the non-embolized lobes to the total liver, 2 weeks after transcatheter portal embolization in the dogs with jaundice, was significantly lower than that of the normal dogs with transcatheter portal embolization (40.5 +/- 4.5% vs. 47.6 +/- 3.2%), but significantly larger than that of the dogs without transcatheter portal embolization. The cellular adenosine triphosphate content and tissue blood flow in the embolized lobes were significantly lower than those in the nonembolized lobes in the normal and cholestatic livers. Clinical study: The postoperative course in all patients was uneventful, with no serious complication or liver dysfunction. Extended right lobectomy with caudate lobectomy was equivalent to 65% before transcatheter portal embolization and to 56% after, transcatheter portal embolization owing to compensatory hypertrophy of the left lobe. However, there was no significant difference in liver volume in the patients with or without obstructive jaundice. Apoptosis was observed in the embolized lobe. CONCLUSIONS: Preoperative transcatheter portal embolization with percutaneous transhepatic biliary drainage for the purpose of liver regeneration would be useful for treating extended hepatectomy with obstructive jaundice.

HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans.

Antigens that produce an antibody response in some members of a species may fail to do so in others. The response to an antigen is controlled by a gene termed the immune response (Ir) gene, which is transmitted as a single dominant trait. We have provided evidence for similar immune suppression (Is) genes which control non-responsiveness through the antigen specific suppressor T cell. The non-responsiveness is also dominantly inherited and the Is genes are linked to the histocompatibility (HLA) antigen system. Here we report that the HLA-DR2 molecule from a non-responder haplotype (HLA-Dw12-DR2-DQwl) is required for the proliferative T cell response to schistosoma japonicum (Sj) antigen, as a restriction element, indicating that the HLA-DR2 is the product of the Ir gene, and that the HLA-DQwl molecule of the non-responder haplotype is important in the antigen-specific suppression of the response to this antigen, suggesting that it is the product of the Is gene. We therefore conclude that the HLA-DR and DQ molecules, which are controlled by the distinct genes in the MHC multigene family, regulate immune response and immune suppression and that the gene for HLA-DQ is epistatic to that for HLA-DR in controlling the immune response to schistosomal antigen in humans.

Evaluation of micro-ELISA for schistosomiasis japonica using crude egg antigen.

Procedures of micro-ELISA for detecting antibody of Schistosoma japonicum infection were improved by using crude egg antigen, peroxidase-labeled antibody and O-phenylenediamine on a micro-ELISA plate (M129A, Dynatech). Reactions were performed with 0.1 ml of reagents in 0.3 ml wells at each step and 0.3 ml of substrate was placed at the final procedure. The endpoint of reaction was defined as the upper limit of 99% critical range of absorbance in negative sera at 1:40 dilution which was approximately twice the absorbance of a pooled negative serum at 1:40. Using this endpoint, appropriate concentrations of antigen and conjugate were determined. Cross-reactions of egg antigen were observed with sera at 1:40 from the infections with other schistosomes, Trichobilharzia brevis, Fasciola hepatica, Echinococcus multilocularis and Trichinella spiralis were diminished at 1:200 serum dilutions except for other schistosomes. Among 177 egg positives, 171 (96.6%) showed the titer of 200 or higher while 67 old cases at Kofu, Japan showed low titers where 22 (31.9%) were lower than 40, 44 (63.7%) were between 40 and 160 and 3 (4.4%) were 320 or higher. The proven non-infected controls of 93 cases from Leyte and Manila, Philippines, Tokyo and Kofu, Japan were all negative. The result of ELISA for schistosomiasis japonica by crude egg antigen was satisfactory after standardization and stabilization of the procedures which were considered to be as important as using defined antigens.

Immunogenetic analysis of patients with post-schistosomal liver cirrhosis in man.

Immune responsiveness of 121 patients with post-schistosomal liver cirrhosis to schistosomal antigens was investigated. Out of 78 patients, only five (6.4%) showed low responsiveness to schistosomal adult worm antigen whereas 73 (93.6%) were high responders. Out of 57 healthy individuals with previous schistosomal infection, low responders were found in 17.5%. The frequency of low responders to schistosomal adult worm antigen was significantly decreased in the patients with post-schistosomal liver cirrhosis (P less than 0.05). Out of 121 patients, a significant increase in frequency of HLA-Bw44-DEn haplotype was observed (corrected P less than 0.02). On the other hand, HLA-Bw52-Dw12 haplotype which was reported to be in strong linkage disequilibrium with an immune suppression gene for schistosomal adult worm antigen was significantly decreased (corrected P less than 0.005). These observations suggested that an HLA-linked immune suppression gene controlled susceptibility or resistance to post-schistosomal liver cirrhosis through regulation of immune responsiveness of the hosts to schistosomal antigen in man.

Cross reactivity of schistosome antigens between Schistosoma mansoni and japonicum.

Fifty six patients with chronic Schistosomiasis japonica were given skin tests with preparations made of Schistosoma mansoni and Schistosoma japonicum. There was a high, significant positive correlation between the results of both antigens. Among 47 serum samples tested with indirect hemagglutination (IHA) 27 had the antibody titer 1:16 or higher, which was diagnostically significant in combination with positive skin test results. The results indicate a definite cross reactivity of japonicum and mansoni anitgens in patients with Schistosomiasis japonica.