Human carcinoma cell lines xenografted in athymic mice: biological and antigenic characteristics of an intraabdominal model

Summary In order to investigate in vivo clinical applications of murine monoclonal antibodies directed against human ovarian carcinoma a preclinical in vivo model was developed using BALB/c athymic mice. Three human carcinoma cell lines (MCF7, HT29, and SW626) were injected into the peritoneal cavity of pristane-primed animals and the biological and antigenic characteristics of the i.p. grown tumors were studied. The animals were killed when moribund or 6–8 weeks after tumor injection. At autopsy tumor take was observed in 85% of the injected animals, whereas palpable nodules were evident in only 83%. Examination of the peritoneal cavity revealed intraabdominal carcinomatosis with tumor masses varying in size between 0.2 and 0.5 cm in diameter and tumor sheets. The most frequently affected organs were the diaphragm, the liver, and the reproductive system. Ascitic fluid formation was rare and no animal developed tumors outside the peritoneal cavity. To determine whether the in vivo tumors retained the same antigenic characteristics as the in vitro cell lines, four monoclonal antibodies (MBrl, MOv2, MOv8, and MOv15) directed against ovarian carcinoma-associated antigens and two different experimental approaches (immunofluorescence and immunoblotting) were used. Variations at either a quantitative or a qualitative level were observed for some antigens, whereas no evident changes were apparent for others. In particular, the antigens detected by MBr1 and MOv15 on the MCF7 line both maintained high levels of expression and immunoblotting staining pattern, whereas the antigens detected by MOv2 on the HT29 and SW626 lines, although present at a high level, clearly changed their staining pattern. As regards the antigens recognized by MOv8 and MOv15 on the HT29 and SW626 lines, we observed a drastic decrease in the level of their expression and in many cases a drop below the threshold of detectability of the test. The intraabdominal carcinomatosis described partially mimics the growth characteristics of human ovarian cancer and maintains the expression of some antigenic markers associated with epithelial tumors of the ovary and may therefore be useful in devising immunodiagnostic and/or immunotherapeutic strategies for ovarian carcinoma.     

Ultrastructural immuno-localization of tropoelastin in the chick eye

Summary Immuno-gold labeling at the electron-microscopy level was used to investigate the distribution of tropoelastin in the chick eye. Intense staining was found in the amorphous part of mature elastic fibers in different regions of the organ. In elaunin fibers, both the amorphous core and the surrounding microfibrils were clearly labeled. In addition, reactive sites were detected in the oxitalan fibers of the stroma of the cornea and in Descemet's membrane, which showed a gradient of reactive sites increasing from the center toward the periphery. Oxitalan fibers of the stroma often fused with Descemet's membrane; the pattern of immunological staining suggested a continuity between the two structures. In the ciliary zonule, labeling for tropoelastin was observed in discrete areas on the bundles of microfibrils. The results show a complex structural organization of elastic tissue; this may be important in endowing the various parts of the eye with different mechanical properties.     

Diagnosis of abdominal masses with percutaneous biopsy guided by ultrasound.

OBJECTIVE--To assess the accuracy and safety of percutaneous biopsy of abdominal masses guided by ultrasound. DESIGN--Prospective study. SETTING--Combined gastroenterology service, Scarborough Hospital. PATIENTS--108 Consecutive patients identified as having a discrete mass on diagnostic ultrasound examination of the abdomen. INTERVENTION--A sample of tissue was obtained with an aseptic technique under local anaesthesia: an 18 steel wire gauge needle (Tru-Cut) was mounted in a spring loaded firing device (Biopty gun) that was advanced under simultaneous ultrasound scanning, permitting precise localisation of the target organ. MAIN OUTCOME MEASURE--Results of histological examination of tissue specimens. RESULTS--Biopsy failed in four patients. Adequate histological specimens were obtained in 104 patients with masses in the liver (31), pancreas (37), kidney (10), and adrenal glands (six) and in 20 undiagnosed abdominal and retroperitoneal masses. Follow up was until death or confirmation of the diagnosis. Three complications but no deaths occurred. Malignancy was suspected in 84 patients before biopsy. This was confirmed in 70 patients, in 26 of whom confirmation of dissemination obviated the need for further investigation. In 10 patients biopsy indicated a previously unsuspected primary tumour, and in 12 it showed only a benign lesion. Among 24 patients considered to have benign disease biopsy showed an unsuspected neoplasm in seven. Use of biopsy thus had a major effect on clinical management in 55 patients. Four false negative but no false positive diagnoses resulted from the procedure. CONCLUSION--Percutaneous biopsy of abdominal and retroperitoneal masses under ultrasound guidance is a safe and accurate method of obtaining a histological diagnosis. The results obtained have a considerable effect on clinical management.     

Infection of Locusta migratoria with entomopoxviruses from Arphia conspersa and Melanoplus sanguinipes grasshoppers

Entomopoxvirus (EPV) occlusion bodies isolated from Arphia conspersa and Melanoplus sanguinipes grasshoppers were fed to 3rd and 4th instar Locusta migratoria nymphs. Locus mortality induced by A. conspersa EPV was first detected 18 days after addition of virus to the diet, and reached a level of approximately 68% of the colony population by 60 days after virus inoculation. In a similar population of L. migratoria nymphs, mortality induced by M. sanguinipes virus reached 90% 60 days after virus inoculation. Entomopoxvirus was isolated from M. sanguinipes EPV infected locust nymphs and the viral DNA was cleaved with several restriction endonucleases. The DNA fragment patterns obtained after agarose gel electrophoresis were compared with the fragment patterns from the original sample of M. sanguinipes EPV DNA cleaved with the same restriction endonucleases. No differences in the cleavage patterns were detected between the two virus DNA samples. Virus structural proteins of M. sanguinipes EPV purified from infected locust nymphs were compared by polyacrylamide gel electrophoresis with virus proteins isolated from the original sample of M. sanguinipes EPV. A total of six different virus protein bands were detected between the two poxvirus preparations.     

Cause of death in 1144 patients with diabetes mellitus: an autopsy study.

The pathological reports for all patients over 13 years of age who had had an autopsy at one of three university-affiliated hospitals between 1967 and 1976 were reviewed to determine the principal cause of death. The clinical records of the patients with diabetes were reviewed to verify the diagnosis and to determine the known duration of diabetes. There were 1144 patients with diabetes mellitus and 5674 without. The sex distribution was similar in the two groups. The patients with diabetes were slightly older, males by 2.2 years and females by 3.2 years. Disease of the circulatory system was the principal cause of death in males (53.7%) and females (58.9%) with diabetes. The rates in the corresponding patients without diabetes were 37.6% and 35.2%. Neoplasms accounted for 18.9% of deaths in males with diabetes, compared with 35.7% in males without diabetes; the corresponding figures in females were 16.0% and 39.4%. Renal disease accounted for 5.9% of deaths in patients with diabetes.     

Moisture as a factor influencing the distributions of two species of terrestrial salamanders

Summary Plethodon richmondi shenandoah occurs in at least three geographically isolated talus slopes in Shenandoah National Park, Virginia, U.S.A., each surrounded by a continuous population of Plethodon c. cinereus in the soil outside the talus. Distributions are contiguous but largely non-overlapping. The talus presents a much drier habitat than does the surrounding soil. Four experiments were designed to test the responses of the two species to moisture and substrate. Although shenandoah lives in a habitat generally drier than that of cinereus, both species choose the wet end of a moisture gradient and do not differ significantly in moisture preference. When given choices between a substrate of rock or soil, the two species respond similarly: neither expresses a preference when both substrates are moist and both choose soil over rock as the substrates dry, showing that substrate preference is based on moisture content and not texture. A third experiment demonstrates that cinereus suffers significantly greater mortality and loss of body water when subjected to a drying rock substrate than when subjected to a soil substrate, since the latter holds moisture longer. Thus the talus most likely presents a greater stress of dehydration to salamanders than does the soil. A fourth experiment shows that when forced to dehydrate, shenandoah survives longer, loses significantly less body water per hour, and withstands a greater loss of body water before death than does cinereus.The conclusions drawn are that cinereus inhabits areas of deep soil not due to a preference for that substrate but due to the requirement of a moist substrate, and it cannot enter the talus due to the dry conditions there. P. r. shenandoah, on the other hand, neither prefers the rocky nor the dry conditions of the talus and is probably excluded from the soil by the presence of cinereus. The survival of shenandoah in the talus is due, at least in part, to its ability to withstand the stress of dehydration for a longer period than can cinereus.