This study was designed to investigate the role of duodenogastric reflux in the genesis of gastric carcinoma in rats. One hundred and two rats were subjected to one of following three surgical procedures: Antiperistaltic duodenogastric reflux (ADGR) was made for duodenal juice to reflux through the pylorus into the stomach. Isoperistaltic duodenogastric reflux (IDGR) was prepared for duodenal juice to reflux into the stomach through the gastrojejunostomy made at the greater curvature of the fundus. Simple laparotomy was employed as control. On the 50th postoperative week all surviving animals were killed and examined. No carcinoma was found in any of the 20 control animals. In seven of 17 animals (41%) with ADGR and five of 13(31%) with IDGR, carcinoma developed in the glandular stomach. The significant difference between ADGR and control group, and IDGR and control group was recognized at the incidence of occurrence of gastric cancer, respectively (P<0.01). The carcinomas were located at the prepyloric antrum in ADGR and at the fundus neighbouring gastrojejunal anastomosis in IDGR. The findings suggests that duodenogastric refulx may be an important factor in gastric carcinogenesis.
In order to reveal the effect of environmental factors to BromodeoxyUridine labelling index (BrdU L.I.) and its usefullness as clinicopathological information, 522 specimens obtained from 121 lesions of gastric cancer were studied. Five hundred twenty two specimens in which BrdU had been incorporated using an in vitro labelling method were devided into 3 groups according to their degree of necrosis and cell infiltration. The average L.I. of the specimens with no or slight necrosis was 23.3±8.7%, medium, 14.2±10.0%, and severe necrosis, 6.6±3.8%, with no or slight cell infiltration, 25.3±9.5%, medium, 21.0±7.1%, and severe cell infiltration, 21.2±6.1%, therefore L.I. correlated to necrosis and cell infiltration. Representive values for each lesion were adopted and compared using 3 methods. In method A, a representive value of the L.I. for each lesion was chosen using all biopsy specimens, method B using specimens without necrosis, and method C, specimens without necrosis and cell infiltration. L.I. correlated to stage and the lymphnode metastasis only using methods, B and C and more strictly using method C. Necrosis and cell infiltration should be considered in adopting a representive value of the L.I. for each lesion. Method C is considered to be a best among the three studied, and the L.I. of gastric cancer may be considered a clinicopathological marker.
The gastric epithelia of the rat after administrated with the minimal mixed bile acids and lysozyme for 9-weeks were studied using morphometric analysis and anti-Bromodeoxyuridine staining immuno-histochemistry. Our results show that the atrophic changes and increased anti-BrdU antibody staining positive and mitotic cells of the pyloric glands area in the group administration only bile acids. Lysozyme inhibited bile acids activation on these changes of this area.
It has been reported that mutations in the human ras gene family convert these genes into active oncogenes. In the present study using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the oligonucleotide hybridization assay, a total of 86 colorectal cancers were analyzed for the point mutations at codon 12 and 13 of K-ras genes. Mutations were present in 33 of the 86 colorectral cancers examined; 32 of the 33 mutations were at codon 12 of this gene and one of them was at colon 13. There was no apparent correlation between the presence of a ras gene mutation in a carcinoma and its anatomical location, level of differentiation, depth of invasion, degree of lymphnode metastasis or stage of progression, however, the high incidence of K-ras mutations was observed in early stage carcinomas (depth m and sm). This results suport the concept that the point mutation of K-ras gene is early event in tumorigenesis of colorectal cancer.
We analyzed the relationship between the presence of intrafamilial clustering of infection with hepatitis B virus (HBV) and the condition of the liver. Parents and siblings of subjects infected with HBV, some patients and some carriers, were tested for the presence of HBsAg, HBeAg, HBeAb, and liver damage. Then the original subjects with HBV were classified by the results into one of three groups. The subjects in the group without clustering had a higher rate of being seronegative for HBeAg than the groups with clustering, at all ages (P<0.01; test). Of the original subjects who were seronegative for HBeAg, the group without clustering had less damage of the liver than the groups with clustering. Of the subjects infected by horizontal transmission, the group without clustering had a higher rate of being seronegative for HBeAg and less damage of the liver than the groups with clustering. Subjects with HBV in a family with members who had normal liver function and who were seronegative for HBeAg were less likely to develop chronic hepatitis B than such subjects in a family with members having chronic liver damage. Thus the presence of intrafemilial clustering might affect the chance of subjects with HBV developing liver damage. The mode of infection and some genetic factors in the infected subjects seem to contribute to the condition of subjects with HBV infection.
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 intraaterial 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 neoplams 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.
Hepatic protein synthesis rate (HPS) in human livers were measured to evaluate hepatic functional reserve. HPS of 34 patients who underwent operations were studied and were divided into 4 groups. Normal liver (n=7), obstructive jaundice (n=9), liver cirrhosis (n=8) and other hepatic dysfunction (n=10). HPS in normal liver was 6.9±3.0nmol/mg wet wt./10min. HPS in obstructive jaundice liver was 17.1±10.3, and HPS in liver cirrhosis was 47.5±17.8. There were significant differences among these three groups. HPS correlated well with cholinesterase (r=-0.6533, P<0.01) and ICGR15 (r=0.7315, P<0.01). In 15 patients who received hepatectomy, relations between HPS and postoperative complication were studied. There were no complications in patients whose HPS were less than 20nmol/mg wet wt./10min. in major hepatic resection and in patient whose HPS were less than 40 in a segmentectomy. Even if HPS were elevated, the operations were safe in subsegmentectomy and partial hepatectomy. So HPS would be one of the good indices to evaluate hepatic functional reserve.
To analyze muscarinic receptors on rat pancreatic acini, we studied the binding of 125I-quinuclidinyl benzilate (125I-QNB) and N-[3H]-methylscopolamine ([3H]-NMS) to these acini. Binding of 125I-QNB and [3H]-NMS to acini was specific and reversible. 125I-QNB bound to low affinity site, which was not recognised by [3H]-NMS. However, nonspecific binding of 125I-QNB to acini was very high (46%), so 125I-QNB may be inadequate to analyze muscarinic receptor on pancreatic acini. Muscarinic receptors are classified in two groups, M1 and M2, according to affinity of pirenzepine which binds to M1 receptor selectively. Pirenzepine was 530 times less potent than atropine in inhibiting the binding of 125I-QNB, and 250 times less potent than atropine in inhibiting the binding of [3H]-NMS. These results suggest that muscarinic receptors on pancreatic acini are mainly M2 receptors.
Urinary excretions of hydroxyproline and fibronectin fragment (FN fragment) were serially investigated in the patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. While urinary excretion of FN fragment showed the maximal level on the first day of admission, high levels of urinary hydroxyproline were observed on the second to fifth day. As to the changes in the individuals, peak level of urinary FN fragment always preceded that of hydroxyproline. And it was assumed that the elevation of FN fragment excretion on the early phase of pancreatitis reflected tissue damages of pancreas itself and complicated organs, and following elevation of hydroxyproline showed enhanced collagen metabolism induced by acute inflammation and tissue damage. According to the severity of pancreatitis, urinary excretion of FN fragment on the first day increased, and it was therefore suggested that urinary FN fragment would be one of the parameters for the assessment of the severity of acute pancreatitis.