ALLELOTYPE OF ADENOMA AND DIFFERENTIATED ADENOCARCINOMA OF THE STOMACH

The molecular mechanism of gastric tumourigenesis has not yet been clarified, although investigators have postulated that differentiated adenocarcinoma may arise from pre-existing adenoma, similarly to the colorectal adenoma–carcinoma sequence. An allelotype analysis has been performed to identify chromosomal regions which are frequently deleted in gastric tumours and to examine the significance of the adenoma–carcinoma sequence in gastric tumourigenesis. Forty-five gastric tumours, 20 adenomas, and 25 differentiated adenocarcinomas were examined for loss of heterozygosity (LOH) using 39 microsatellite markers covering each non-acrocentric chromosome arm. Frequent LOH in the adenocarcinomas was observed on chromosomes 2q (33 per cent), 4p (33 per cent), 5q (50 per cent), 6p (33 per cent), 7q (43 per cent), 11q (36 per cent), 14q (38 per cent), 17p (45 per cent), 18q (36 per cent), and 21q (40 per cent). In contrast, the incidence of LOH in adenomas did not exceed 10 per cent at any of the loci examined. In addition to the p53 gene on 17p and the DCC gene on 18q, which are known to be frequently deleted in differentiated adenocarcinomas of the stomach, other unknown tumour suppressor genes on the above-mentioned chromosomes may also be inactivated. These observations suggest that the adenoma–carcinoma sequence is not a major pathway in gastric tumourigenesis.     

RELATIONSHIP BETWEEN SYSTEMATIC BIOPSIES AND HISTOLOGICAL FEATURES OF 222 RADICAL PROSTATECTOMY SPECIMENS: LACK OF PREDICTION OF TUMOR SIGNIFICANCE FOR MEN WITH NONPALPABLE PROSTATE CANCER

PURPOSE: Because of the recent increase in nonpalpable prostate cancer (clinical stage T1c) in men, preoperative needle biopsy findings have had an important role for treatment decisions. We examine the correlation among histopathological features of 6 systematic biopsies and radical prostatectomy specimens in which 1 investigator reviewed all histological sections. MATERIALS AND METHODS: We studied a total of 450 men with clinical stage T1c prostate cancer from whom needle biopsies were matched with radical prostatectomy specimens, and selected 222 patient biopsies that were obtained from 6 or more separate regions of the prostate. The pretreatment parameters of serum prostate specific antigen (PSA), PSA density, number of positive needle biopsies, distribution of positive cores, linear cancer length, and percent Gleason grade 4/5 on the biopsy were determined and compared with histopathological features of prostate cancer in the radical prostatectomy specimens. All biopsies and radical prostatectomies were evaluated morphologically at the department of urology. RESULTS: Of the 222 men the largest cancer was clinically insignificant in 23 (10%), as measured by a cancer volume of less than 0.5 cc. Cancer volume in the prostatectomy specimen was significantly related to all parameters in the biopsy, with the surprising exception of cancer distribution in the positive biopsies. However, all of these correlations with cancer volume were weak, with Pearson's correlation squared (R(2)) multiplied by 100 less than 10%. Unfortunately, tumor grade on the biopsy agreed with the prostatectomy specimen in only 81 of 222 (36%) cases. Grade assessment with needle biopsy underestimated the tumor grade in 102 (46%) cases and overestimated it in 39 (18%). No single parameter in the biopsy was a predictor of tumor significance, as measured by a cancer volume of greater than 0.5 cc. However, the best model to predict a tumor less than 0.5 cc in volume was the combination of a single positive core with cancer length less than 3 mm. that contained no Gleason grade 4/5. The use of PSA or PSA density in combination with needle biopsy findings did not enhance prediction of tumor significance. CONCLUSIONS: These results indicate a weak and disappointing correlation among all pathological features of 6 systematic biopsies and radical prostatectomy specimens. The combination of 1 positive core with cancer length less than 3 mm. that contains no Gleason grade 4/5 is probably the best predictor of prostate cancer less than 0.5 cc in men with nonpalpable tumors, a cancer volume that occurred in only 10% of the 222 (23) men.     

Gigantic aneurysm in the thoraco-abdominal aorta of an infant

We report the case of a boy with a gigantic aneurysm in the thoraco-abdominal region which was detected by a chest X-ray taken prior to surgical correction of ptosis of the eyelids at 11 months of age. At 18 months, he successfully underwent aneurysm exclusion and bypass grafting. A biopsy from the thoracic aorta revealed medial degeneration with conspicuous smooth muscle cell involvement. Laboratory examination showed altered elastase activity in the granulocytes and whole blood. The present case may represent a unique form of aneurysm in infancy.     

Distribution of enzymes of nucleic acid metabolism in cow snout epidermis

Certain enzymes participating in the degradation of DNA have been measured in cow snout epidermis, liver, kidney and intestinal epithelium. High activities were found in epidermis compared to other tissues. The enzyme profile of the epidermis was investigated in relation to depth. Those enzymes directly concerned with DNA degradation occurred mainly in the upper (keratinizing) layer.     

Short communication: Fulminant hepatitis induced by cimetidine

Despite the widespread use of cimetidine, there have been only few reports of cimetidine-induced severe liver damage. This is an account of a 44 year old woman who developed, after a year of daily administration of cimetidine, fulminant hepatitis which was confirmed by unintentional rechallenge.     

The Reaction Specificity of Various Monoclonal Antibodies and Cellular Origin and Differentiation of Cultured Cell Lines Derived from Human Leukemias and Lymphomas

The specificity of 12 monoclonal antibodies was assessed byindirect immunofluorescence assay using 25 cultured cell linesderived from various human hemopoietic tumor cells.

1. The reactivity of these 12 monoclonal antibodies was highlyspecific. However, the titer of the antibody was found to differamong these cell lines. Therefore, titration of each monoclonalantibody requires the use of several cultured cell lines inorder to determine an appropriate concentration for clinicaluse.
2. Anti-Leu-1 and 10.2 (anti-human Lyt-2) antibodies reactedwithall T-cell lines of various stages of differentiation.Therefore,anti-Leu-1 and 10.2 are considered to react withpan T-ccllantigen (the so-called human T-lymphocyte antigen).
3. 9.6 (anti-human Lyt-3) antibody is considered to react withE-receptor-associated antigen.
4. All T-cell lines reactive withOKT4, OKT6 and OKT8 antibodiesare derived from thymic T-ALL,and they are considered to belongto the same stage of differentiationas normal cortical thymocytes.Anti-T monoclonal antibodiesdesignated as the OKT-series arevery useful for analysis ofthe differentiation of T-cell malignancies.
5. J5 antibody, whichwas reported to have the same reaction specificityas CALLA,reacted with cultured cell lines derived from commonALL, C/Thybrid type ALL, pre-B ALL and Burkitt's lymphoma.Therefore,J5 is considered to be a specific marker of lymphoidmalignanciesderived from lymphoid stem cells, some pre-T cells,pre-B cellsand some immature B-cells.
6. Anti-B1 antibody is consideredto be reactive with a part ofJ5-positive common ALL, immatureB-cell malignancy and matureB-cell malignancy, but unreactivewith immunoblast and plasmacell malignancy.
7. OK11 antibodyshowed almost the same reaction pattern as theheteroantiserumagainst Ia-like antigen.
8. OKM1 and anti-Mo1 antibodies werefound to react only with theP31/Fujioka monocytoid cell line.

The monoclonal antibodies specific for certain differentiationantigens will be very useful for elucidating the cellular origin,stage of differentiation and subset identification of humanhemopoietic tumor cells.     

X‐ray Radiation Causes Electromagnetic Interference in Implantable Cardiac Pacemakers

Background: X‐rays are not thought to cause electromagnetic interference (EMI) in implantable cardiac pacemakers. However, x‐ray radiation during computed tomography (CT) scanning has been reported to cause EMI in some implantable cardiac pacemakers. The objectives of this study were to identify the location within the pacemakers where x‐ray radiation causes EMI and to investigate the association of EMI with the x‐ray radiation conditions. Methods: We verified the location where x‐ray radiation caused EMI using a CT scanner and conventional radiographic x‐ray equipment. An inhibition test and an asynchronous test were performed using five types of implantable cardiac pacemakers. Results: X‐ray radiation inhibited the pacing pulses of four types of implantable cardiac pacemakers when the body of each implantable cardiac pacemaker, containing a complementary metal‐oxide semiconductor (CMOS), was scanned using a CT scanner. We confirmed that x‐ray‐induced EMI depends on the x‐ray radiation conditions, that is, the tube voltage, tube current, x‐ray dose, and direction of x‐ray radiation, as well as the sensing thresholds of the implantable cardiac pacemakers. Conclusions: X‐ray radiation caused EMI in some implantable cardiac pacemakers, probably because the CMOS component was irradiated. The occurrence of EMI depended on the pacemaker model, sensing threshold of the pacemaker, and x‐ray radiation conditions. (PACE 2010; 33:1174–1181)     

Long-Term Survival in Patients with Small Cell Lung Cancer

Of the 66 patients with small cell lung cancer (SCLC) who weretreated by combination chemotherapy with or without radiationtherapy from July 1978 to December 1983 at the National CancerCenter Hospital, Tokyo, 12 (18%) sur vived over two years andnine (14%) have remained disease-free over three years. Thetwo-year survival rates were compared according to the patientcharacteristics of sex, performance status (PS), extent of disease,histologic subtype, regimen of the initial chemotherapy andresponse to treatment. Sex, extent of disease and response tothe initial chemotherapy were the most important prognosticfactors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patientswho were treated by surgical resection after chemotherapy, achievedcomplete response (CR) with chemotherapy with or without radiationtherapy. Eleven of the 12 two-year survivors achieved CR. Becauseof the small number of patients in our study, it will be necessaryto evaluate further the influence of prognostic factors in patientswith SCLC in future studies.     

Effects of endoscopic variceal sclerotherapy on azygos vein blood flow and systemic haemodynamics*

The present study was designed to determine the systemic haemodynamic effects of obliterating oesophageal varices by endoscopic sclerotherapy. We evaluated systemic and splanchnic haemodynamics before and after the first course of sclerotherapy in cirrhotic patients. The baseline cardiac index was significantly correlated with baseline azygos vein blood flow (r = 0.64; P< 0.01) and the azygos vein blood flow and cardiac index significantly decreased (-33% and -16%, respectively; P< 0.01) following sclerotherapy. The systemic vascular resistance index was also increased significantly (+20%; P<0.01) in these patients. Moreover, the per cent change in azygos vein blood flow was directly correlated with that of the cardiac index (r=0.51; P< 0.03). We conclude from these findings that the obliteration of portosystemic collaterals by sclerotherapy significantly reverses hyperdynamic circulation in such patients via a decrease in cardiac preload. The blood flow of the portosystemic shunt per se is a leading contributor to the hyperdynamic circulation observed in patients with well-developed portal systemic collateral vessels.     

CARDIOVASCULAR ACTIVITY OF 14-DEOXY-11, 12-DIDEHYDROANDROGRAPHOLIDE IN THE ANAESTHETISED RAT AND ISOLATED RIGHT ATRIA

The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) fromAndrographis paniculata(Burm.f.) Nees (Acanthaceae) was elucidated in anaesthetised Sprague–Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced significant falls in mean arterial blood pressure (MAP) and heart rate in a dose-dependent manner with the maximum decrease of 37.6±2.6% and 18.1±4.8%, respectively. The ED₅₀value for MAP was 3.43 mmol kg⁻¹. Pharmacological antagonist studies were done using this dose. The hypotensive action of DDA was not mediated through effects on the α-adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it was not affected by phentolamine, atropine as well as pyrilamine and cimetidine. However, it seems to work via adrenoceptors, autonomic ganglia receptor and angiotensin-converting enzyme, since the hypotensive effect of DDA was negated or attenuated in the presence of propranolol, hexamethonium and captopril. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose-dependent manner. These results further supported the bradycardia-inducing and β-adrenoceptor antagonistic properties of DDAin vivo.