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Elizabeth A Jones, Yuanyuan Cheng, Katherine BelovFaculty of Veterinary Science, University of Sydney, NSW, AustraliaAbstract: Three transmissible cancers are known to have emerged naturally in the wild: canine transmissible venereal tumor (CTVT); Tasmanian devil facial tumor disease (DFTD); and a recently discovered leukemia-like cancer in soft-shell clams (Mya arenaria). These cancers have all acquired the ability to pass between individuals. DFTD emerged approximately 20 years ago and has decimated the Tasmanian devil population. CTVT arose over 10,000 years ago in an ancient breed of dog. The clam cancer is believed to have evolved at least 40 years ago. In this manuscript, we review CTVT and DFTD, the two transmissible mammalian cancers, and provide an overview of the leukemia-like cancer of clams. We showcase how genetics and genomics have enhanced our understanding of the unique biology, origins, and evolutionary histories of these rare cancers.Keywords: transmissible cancer, devil facial tumor disease, DFTD, canine transmissible venereal tumor, origin, evolution

Direct cytotoxicity and absorption analysis were used to detect HLA antigens on man/mouse somatic cell hybrids. Confirmation of the assignment of the Major Histocompatibility Complex to chromosome 6 was obtained. The same series of hybrids were used to study the interaction between HLA and β2m on the cell surface. Results obtained from a series of clones indicated that there was complete independence of expression of HLA and β2m. Human β2m was found to be unnecessary for the normal serological expression of HLA, suggesting that mouse β2m could possibly replace human β2m as a subunit of the HLA molecule. Evidence is presented demonstrating that this is in fact the case. Heteroantisera to human β2m and alloantiserum to HLA-A2 were used, together with complement, to selectively remove the chromosome coding for β2m and HLA from a hybrid clone. Manipulation of the karyotype in this way further confirmed the independence of HLA and β2m on somatic cell hybrids. © 1976 Plenum Publishing Corporation.

Although exacerbations of previously quiescent HBV infection, associated with chemotherapy, have been attributed to enhanced immunological responses to hepatocytes harboring reactivated HBV, the recommended treatment, prednisolone, is often unsuccessful. A young HBsAg-positive, anti-HBe-positive carrier, who received chemotherapy for choriocarcinoma, developed icteric hepatitis. The serum HBV DNA level was 34,000 x 10(6) genomic equivalents per milliliter serum. Treatment with prednisolone alone did not prevent progression to overt hepatic failure. By three days after initiating lamivudine therapy, however, there was reversal of stage III hepatic encephalopathy. With further lamivudine treatment, substantial further improvement in hepatocellular function occurred and HBV-DNA levels became undetectable. When an immunocompromised patient develops an exacerbation of hepatitis B associated with high HBV DNA levels, treatment with prednisolone seems inappropriate, as hepatocytotoxic HBV replication may be stimulated further. In this situation inhibition of HBV replication, eg, by administering lamivudine, may be life-saving

SELECTED CASE A year after being told that she had abnormal liver test results, a 52-year-old white woman presented with increasing fatigue, pruritus, diffuse abdominal pain, and jaundice. Although endoscopic retrograde cholangiopancreatography was indicated, a diagnostic laparotomy was undertaken. An intraoperative cholangiogram revealed beading and narrowing of intrahepatic and extrahepatic bile ducts characteristic of primary sclerosing cholangitis. Cholecystectomy, exploration of the common bile duct, and endoscopic dilation of large-duct biliary strictures were performed. During the ensuing 12 months the pruritus became severe. Her entire body itched; she slept poorly and felt like she was "on a cactus bed." She scratched until she bled, but scratching did not relieve the pruritus. Conventional doses and schedules of cholestyramine, hydroxyzine hydrochloride, and ursodeoxycholic acid had failed to provide her with relief and her pruritus was considered to be intractable. When referred to the National Institutes of Health, she was scratching continuously and was

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.

The amount of 125I-lgG which bound to membranes isolated from the human placenta was competitively inhibited by the presence of increasing amounts of unlabeled IgG but not by unlabeled albumin. The relationship between membrane-bound and free IgG indicated the presence of membrane receptors with an appreciable affinity for IgG. Incubation of membranes with collagenase or neuraminidase did not result in appreciable reduction of IgG-membrane binding, indicating that neither intact collagen nor sialic acid play an important role in the binding. Placental surface membranes isolated by salt extraction bound 3.79 ± 1.78 (SD) pmol IgG/μg membrane protein, whereas membranes isolated by differential centrifugation bound only 1.61 ± 0.24 pmol/μg (p 4, 4.5 × 104 and 6.0 × 104 daltons. These findings are consistent with the existence of a limited number of receptors for IgG on placental membranes, including IgG receptors on the microvillus membrane of the syncytial trophoblast. The latter, in accordance with Brambell’s hypothesis, could be of importance in the transplacental transport of maternal IgG.

SummaryThe testes of adult rats were exposed to 0–3000 r x-irradiation, and the animals were killed 6 hours to 21 days after treatment. The numbers of type-A, intermediate, and type-B spermatogonia, degenerating cells and mitotic figures were counted in fifty cross sections of seminiferous tubules in each testis.Statistical analyses showed that a curvilinear relationship exists between the number of type-A spermatogonia, and the number of intermediate and type-B spermatogonia, and (a) the dose administered and (b) the time after irradiation.The survival curves for type-A spermatogonia are indicative of a population of cells possessing a heterogeneity of radio-sensitivities. A comparison of the present results with corresponding data reported for the mouse by Oakberg reveals that for a given dose, the rate of depletion and subsequent recovery of spermatogonia is slower, and the incidence of degenerating cells lower, in the rat than in the mouse.The results suggest that the depletion of spermatogonia in the...

1. The enzymes glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, phosphoglucomutase, UDP-glucose pyrophosphorylase, phosphofructokinase, ATP-citrate lyase and acetyl-CoA carboxylase have been assayed in rat mammary glands in various stages of involution after hypophysectomy and weaning. 2. After hypophysectomy all seven enzymes decline in activity over a 12–16hr. period but the extent of the decline varies, with acetyl-CoA carboxylase becoming almost totally inactive, ATP-citrate lyase and phosphofructokinase showing a large decrease, and the remaining enzymes a less marked decline. 3. Within 24hr. of removing the litter a change in the pattern of enzyme activity is found very similar to that after hypophysectomy. 4. The significance of these results is discussed in relation to the endocrine control of mammary gland metabolism and the mechanisms of involution.

Primary biliary cirrhosis is a chronic liver disease of unknown cause that predominantly affects middleaged women.1 The syndrome of primary biliary cirrhosis arises as a consequence of a chronic nonsuppurative destructive cholangitis that involves the septal and larger interlobular bile ducts.2 The rate at which the bile-duct lesions evolve varies and is unpredictable. In asymptomatic patients the prognosis can be good (two decades), but once patients have symptoms attributable to the disease, its course is typically characterized by relentless destruction and loss of bile ducts, slowly progressive intrahepatic cholestasis, periportal piecemeal necrosis of hepatocytes, hepatic fibroplasia, and after a few . . .