Prognostic significance of proliferating cell nuclear antigen-positive growth fraction in gastric adenomas.

The proliferative activity of gastric adenomas from 18 patients (42 endoscopic procedures) was compared with follow-up results. These cases were gastric adenomas proven by follow-up with repeated endoscopic procedures for more than 2 years, or were confirmed as gastric adenocarcinoma thereafter by histopathologic examination. Among the eighteen cases, nine showed carcinoma in the subsequent biopsies (group 1) and the remaining nine did not result in carcinoma (group 2). The proliferating cell nuclear antigen (PCNA) positivity rates of the two groups were significantly different (P < 0.01). The average PCNA positivity in group 1 was 33.1%, while it was 10.0% in group 2. The risk of developing carcinoma increased as the PCNA positivity increased: 0% in the low PCNA positivity group, 41% in the mid-positivity group and 89% in the high positivity group. We concluded that growth fraction could be taken into account as one of the most important prognostic factors for gastric adenoma, and accordingly repeated endoscopic biopsies with close follow-up should be carried out especially in the high PCNA positivity group.     

Determination of beta-adrenoceptor subtype on rat isolated ventricular myocytes by use of highly selective beta-antagonists.

1. The relative proportions of beta 1- and beta 2-adrenoceptors were determined by radioligand binding studies in three different rat myocardial preparations: membranes prepared from rat ventricle (ventricular membranes), membranes prepared from rat isolated ventricular myocytes (myocyte membranes), and myocytes isolated from rat ventricle (myocytes). 2. Competition experiments using CGP 20712A or ICI 118,551 with [125I]-iodocyanopindolol ([125I]-ICYP) revealed high- and low-affinity binding sites in ventricular membranes. The concentration at which each beta-antagonist occupied 100% of its high-affinity binding sites was 300 nM for CGP 20712A (beta 1-adrenoceptor) and 50 nM for ICI 118,551 (beta 2-adrenoceptor). 3. The density of high-affinity (beta 1-adrenoceptor) and low-affinity (beta 2-adrenoceptor) binding sites for CGP 20712A was measured by a saturation experiment using [125I]-ICYP in the presence and absence of 300 nM CGP 20712A. In ventricular membranes, the proportions of high-affinity and low-affinity binding sites for CGP 20712A were 73% and 27%, respectively, whereas in myocyte membranes, the corresponding figures were 90% and 10%, respectively. The density of low-affinity binding sites for CGP 20712A in ventricular membranes, defined as [125I]-ICYP-specific binding in the presence of 300 nM CGP 20712A, was decreased by addition of 50 nM ICI 118,551, whereas that in myocyte membranes was not affected. 4. In myocytes, specific binding of [125I]-ICYP and [3H]-CGP 12177 was not detected by saturation experiments performed in the presence of 300 nM CGP 20712A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical treatment of acquired tricuspid stenosis]

There is no definitive surgical procedure for acquired lesions of the tricuspid valve (TV). From Feb, 1978, through March, 1990, the surgical treatment for the organic lesions of TV was performed in 10 patients, repair in 6 and TV replacement in 4. TV was repaired by commissurotomy, annuloplasty or valvuloplasty, or combination of them. When residual significant tricuspid regurgitation (TR) and/or stenosis (TS) was detected by intraoperative pulsed Doppler echocardiography after reparative procedures, TV was replaced. Follow-up periods ranged from 1 to 12 years (mean, 45.3 months). There was no early death, and late death was noted in one patient 32 months after operation. Preoperatively, 7 patients were in NYHA class IV and 3 in class III. Out of survivors, 7 are in class I and 2 in class II because of progression of mitral stenosis or coronary artery disease. Following surgery, the patients exhibited significant decrease in the cardiothoracic ratio (69.3 +/- 7.2 to 56.9 +/- 6.4%; p less than 0.01) and in the mean right atrial pressure (11.4 +/- 3.6 to 8.6 +/- 3.1 mmHg; p less than 0.05). The postoperative right ventriculography showed mild to moderate TR in 3 of 6 patients who underwent TV repair. In conclusion, TV repair could be a reasonable procedure for the organic TV lesions, although careful follow-up is recommended for residual TR.     

Effects of preoperative transcatheter portal embolization (TPE) on prevention of hepatic failure after massive hepatectomy]

Effects of TPE on prevention of hepatic failure after massive hepatectomy were studied experimentally using dogs. A 70% or 85% hepatectomy (Hx) was performed two weeks after TPE. All of the 70%Hx groups with(+)/without(-) TPE were alive for over two weeks after hepatectomy. While all of the 85%Hx group without TPE died, eight of ten in the 85%Hx group with TPE survived. Without TPE, total bilirubin levels in sera were elevated markedly in the 85%Hx group and moderately in the 70%Hx group after hepatectomy. The levels of escaped enzymes in sera, such as GOT or GPT, were also elevated remarkably in the TPE(-) groups. Although the levels of these enzymes were also high in the 85%Hx.TPE(+) group, these values were as same as those of 70%Hx.TPE(-) group. In the 85%Hx.TPE(-) group, critical diminution of functional hepatic cell mass and severe portal hypertension occurred after hepatectomy and coagulopathy and death followed to these phenomena. TPE might prevent the onset of these critical phenomena, and diminish the damage caused by massive hepatectomy. These results suggest that TPE is useful for prevention of postoperative hepatic failure so that we could perform massive hepatectomy safely, and extend the operative indication.     

Interleukin-1 alpha gene-transcription in murine keratinocytes is inhibited by HSV-1 infection

The effect of in vitro infection with herpes simplex virus 1 (HSV-1) on the Interleukin-1 (IL-1) activity of murine keratinocytes was investigated. IL-1 alpha mRNA synthesis was measured by the Northern blot technique, and the IL-1 protein production was measured in terms of the ability of dialysed supernatants from cultures of uninfected and HSV-1 infected keratinocytes to enhance mitogen-induced murine thymocyte proliferation. IL-1 alpha mRNA-synthesis in uninfected keratinocytes was detected 24 h and 48 h after isolation of the keratinocytes. IL-1 protein secretion by these keratinocytes was measureable at 18 h and reached a peak of 73 h, whereas intracellular and membrane-bound IL-1 protein production reached a maximum after 25 h. Keratinocytes, which had been cultured in vitro for 18 h, were infected with HSV-1 for 2 h and further cultured for an additional 4 h or 22 h before IL-1 measurements. A marked reduction of IL-1 alpha gene-expression was noted 6 hours after HSV-1-infection of keratinocytes, and nearly total shut-off was detected after infection for 24 h. Reduced gene-expression was paralleled by a reduction in the IL-1 protein secretion from the HSV-1 infected keratinocytes.     

Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis.

Using the polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis, we have examined the highly conserved regions of the p53 gene in 58 biopsy samples of head and neck tumors. Mutations were found in 13/58 (23%) tumor specimens, but not in 6 normal tissues. Ten of 13 mutations were due to single base changes and the remaining 3 were 1- or 8-base deletion mutants. These mutations were clustered in exons 5 and 7 and resulted in amino acid changes. Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies. The relationship of Epstein-Barr virus or human papillomavirus and p53 gene mutations in this group of cancers was also analyzed and discussed.     

Phenotypic heterogeneity associated with defective apolipoprotein B-100 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred

Of 163 individuals with a diagnosis of heterozygous familial hypercholesterolemia (FH), only one subject was found to be positive for familial defective apo B-100 (FDB). The eight-member kindred ascertained through this subject who presented with both a clinical phenotype of FH and the FDB apo B-100 (Arg₃₅₀₀→-Gln) mutation was studied. Plasma lipid and lipoprotein profiles, apo E phenotypes, apo B gene markers at the 3′ hypervariable region and LDL-receptor haplotypes (ApaLI, PvuII, NcoI), were determined, together with LDL-receptor activity on freshly isolated blood lymphocytes. The FDB mutation, present in four relatives, was associated with three different phenotypes: FH and severe hypercholesterolemia, moderate hypercholesterolemia and normolipidemia. The FH phenotype occurred in the absence of any functional LDL-receptor defect. In homozygotes for the absence of the PvuII cutting site who had the apo B mutation, LDL-cholesterol levels were low in the presence of the apo E3/2 phenotype and high in the presence of the apo E4/4 phenotype. None of the major known environmental influences accounted for the wide range of variation in LDL-cholesterol among the affected members. Further observations in the spouse and offspring of the normolipidemic FDB subject confirmed the association of apo E4, the FDB mutation and the PvuH(-/-) genotype with high cholesterol levels. It is concluded that the phenotypic expression of the FDB mutation may vary widely as a function of the genetic environment within a family. The presence of phenotypic heterogeneity among individuals with the same apo B mutation may result from epistatic interaction of the apo B locus with genetic factors regulating cholesterol homeostasis, including possible involvement of the apo E and the LDL-receptor gene loci. This study also confirms that the clinical diagnosis of FH is not necessarily associated with an LDL-receptor defect.