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Recombinant feline leukemia virus genes detected in naturally occurring feline lymphosarcomas.

Using a polymerase chain reaction strategy aimed at detecting recombinant feline leukemia virus (FeLV) genomes with 5' env sequences originating from an endogenous source and 3' env sequences resulting from FeLV subgroup A (FeLV-A), we detected recombinant proviruses in approximately three-fourths of naturally occurring thymic and alimentary feline lymphosarcomas (LSAs) and one-third of the multicentric LSAs from cats determined to be FeLV capsid antigen positive by immunofluorescence assay. In contrast, only 1 of 22 naturally arising FeLV-negative feline LSAs contained recombinant proviruses, and no recombinant env gene was detected in seven samples from normal tissues or tissues from FeLV-positive animals that died from other diseases. Four preferred structural motifs were identified in the recombinants; one is FeLV-B like (recognizing that FeLV-B itself is a product of recombination between FeLV-A and endogenous env genes), and three contain variable amounts of endogenous-like env gene before crossing over to FeLV-A-related sequences: (i) a combination of full-length and deleted env genes with recombination at sites in the middle of the surface glycoprotein (SU), (ii) the entire SU encoded by endogenous-like sequences, and (iii) the entire SU and approximately half of the transmembrane protein encoded by endogenous-like sequences. Additionally, three of the thymic tumors contained recombinant proviruses with mutations in the vicinity of the major neutralizing determinant for the SU protein. These molecular genetic analyses of the LSA DNAs correspond to our previous results in vitro and support the occurrence and association of viral recombinants and mutants in vivo in FeLV-induced leukemogenesis.

Amino Acid Sequence↗

Mechanism of 2-aminopurine mutagenesis in mouse T-lymphosarcoma cells.

We investigated the mechanism of action of 2-aminopurine (Apur) in eucaryotic cells. By analogy with studies in procaryotic systems, the base analog is presumed to incorporate into DNA predominantly opposite T where, upon subsequent DNA replication, it can mispair with C, inducing an A:T leads to G:C transition. This model predicts that Apur-induced mutagenesis will be enhanced by factors that favor formation of Apur-C mispairs, e.g., high levels of dCTP or low levels of TTP. We describe the use of a mutant T-lymphosarcoma cell line, AraC-6-1, which has an abnormally high dCTP pool and a low TTP pool, to test this prediction. AraC-6-1 cells were three- to fivefold more mutable by Apur than their parental cell line, NSU-1. This enhanced mutability by Apur could not be explained by altered incorporation of 3H-labeled Apur, by generally impaired ability to repair DNA damage, or by a direct effect of Apur on the endogenous deoxynucleotide pools. The addition of 10 microM thymidine to the growth medium of AraC-6-1 cells lowered their high dCTP pool (two- to threefold), raised the TTP pool (two- to threefold), and abolished their enhanced mutability by Apur. Further manipulation to produce an abnormally high TTP/dCTP ratio suppressed Apur-induced mutagenesis (8- to 10-fold) in both AraC-6-1 and NSU-1 cells. These observations support the hypothesis that Apur induces A:T leads to G:C transitions in mammalian cells by a mispairing mechanism.

2-Aminopurine↗

Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells.

When P1798 murine lymphosarcoma cells are exposed to 10(-7) M dexamethasone, there is a dramatic inhibition of rRNA synthesis, which is completely reversible when the hormone is withdrawn. In the present experiments we examined whether dexamethasone treatment causes any alteration in the accumulation or utilization of mRNAs that encode ribosomal proteins (rp mRNAs). No effect on the accumulation of six different rp mRNAs was detected. However, the translation of five of six rp mRNAs was selectively inhibited in the presence of the hormone, as judged by a substantial decrease in ribosomal loading. Normal translation of rp mRNA was resumed within a few hours after hormone withdrawal. In untreated or fully recovered cells, the distribution of rp mRNAs between polyribosomes and free ribonucleoprotein is distinctly bimodal, suggesting that rp mRNAs are subject to a particular form of translational control in which they are either translationally inactive or fully loaded with ribosomes. A possible relationship between this mode of translational control and the selective suppression of rp mRNA translation by glucocorticoids is discussed.

Animals↗

Translational initiation factor expression and ribosomal protein gene expression are repressed coordinately but by different mechanisms in murine lymphosarcoma cells treated with glucocorticoids.

P1798 murine lymphosarcoma cells cease to proliferate upon exposure to 10(-7) M dexamethasone and exhibit a dramatic inhibition of rRNA and ribosomal protein synthesis (O. Meyuhas, E. Thompson, Jr., and R. P. Perry, Mol. Cell Biol. 7:2691-2699, 1987). These workers demonstrated that ribosomal protein synthesis is regulated primarily at the level of translation, since dexamethasone did not alter mRNA levels but shifted the mRNAs from active polysomes into inactive messenger ribonucleoproteins. We have examined the effects of dexamethasone on the biosynthesis of initiation factor proteins in the same cell line. The relative protein synthesis rates of eIF-4A and eIF-2 alpha were inhibited by about 70% by the hormone, a reduction comparable to that for ribosomal proteins. The mRNA levels of eIF-4A, eIF-4D, and eIF-2 alpha also were reduced by 60 to 70%, indicating that synthesis rates are proportional to mRNA concentrations. Analysis of polysome profiles showed that the average number of ribosomes per initiation factor polysome was only slightly reduced by dexamethasone, and little or no mRNA was present in messenger ribonucleoproteins. The results indicate that initiation factor gene expression is coordinately regulated with ribosomal protein synthesis but is controlled primarily by modulating mRNA levels rather than mRNA efficiency.

Animals↗

Folic acid and other absorption tests in lymphosarcoma, chronic lymphocytic leukaemia, and some related conditions.

An improved folic acid absorption test is described in detail. Using the folic acid and other absorption tests, a study of intestinal function has been made in eight patients with lymphosarcoma, eight with chronic lymphocytic leukaemia, two with Hodgkin's disease, and one each with reticulum cell sarcoma, Whipple's disease, and macroglobulinaemia. It was found that laboratory evidence of intestinal malabsorption was extremely common in patients with this group of diseases. The folic acid absorption test was the most sensitive single index of malabsorption of the tests used in this study. Correlation between the different absorption tests was poor, and there does not appear to be a characteristic biochemical profile of intestinal function in these patients.

Animals↗

Hypercalcaemic stupor as a presentation of lymphosarcoma.

A case is reported of a 32 year old woman with a two year history suggestive of schizophrenia who presented in stupor. This proved to be due to hypercalcaemia with a concomitant high cerebrospinal fluid calcium concentration associated with previously unsuspected lymphosarcoma. Necropsy revealed no significant intracranial abnormality, and mechanisms that may have been involved in the production of the impaired consciousness are discussed.

Adult↗

Malabsorption in relation to abdominal irradiation and quadruple chemotherapy for lymphosarcoma.

A case of severe diarrhoea and steatorrhoea following chemotherapy and abdominal irradiation for lymphosarcoma, is described. Investigations demonstrated bile acid malabsorption, and treatment with cholesytramine and a low fat diet was successful. A questionnaire was sent to thirty-two subjects who had undergone similar treatment for similar pathology and failed to demonstrate any sustained alteration of bowel function. Additionally, nine of these subjects underwent a 14C-glycocholic acid test and no evidence of interruption of the enterohepatic circulation of bile acids was found.

Abdomen↗

Bovine leucosis (lymphosarcoma): a clinical study of 60 pathologically confirmed cases.

The clinical features of 60 pathologically confirmed cases of bovine leucosis (lymphosarcoma) are described. The majority of cases could be classified into one of four distinct clinical forms, ie, juvenile multicentric, thymic, skin and adult multicentric. Diagnosis of leucosis in animals with these forms was possible on clinical grounds alone. Five animals, four of which were adult, could not be thus classified and diagnosis required haematological and, or, pathological examinations. The clinical, epidemiological and serological findings would suggest that the cases were examples of sporadic bovine leucosis.

Animals↗

Lymphosarcoma in experimentally induced feline immunodeficiency virus infection [corrected].

A cat experimentally infected with feline immunodeficiency virus (FIV) but known to be free of feline leukaemia virus (FeLV) developed lymphosarcoma. The lesions in the liver and kidneys were present nine months after infection, when the cat was 21 months old. The cat had no overt signs of immunodeficiency and it is suggested that the B cell activation induced shortly after FIV infection produced a large pool of proliferating lymphocytes from which the malignant cells emerged.

Animals↗

Ultrasound-guided biopsy as a diagnostic aid in three horses with a cranial mediastinal lymphosarcoma.

An ultrasound examination of the thorax of three horses which were performing poorly or had mild signs of colic showed that they had a cranial mediastinal mass and a pleural effusion. A cytological examination of the pleural fluid showed that it did not contain neoplastic cells. A histological examination of an ultrasound-guided core biopsy of the cranial mediastinal mass showed that in each of the three horses it was a lymphosarcoma.

Animals↗

A comparison of the electrokinetic properties of metastasizing and non-metastasizing forms of a hamster lymphosarcoma.

Metastasizing (ML) and non-metastasizing (NML) forms of a hamster lymphosarcoma were investigated for possible differences in the cell surface properties using isoelectric equilibrium analysis and cytopherometry. ML cells were found to have a higher isoelectric point (pI) and therefore a lower net negative charge density on their surface than the NML cells. On the contrary, ML cells showed a greater electrophoretic mobility than NML cells. When pH mobility curves were constructed for the two tumour types, the curves crossed over at pH 4.8. The isoelectrophoretic points (pIE) extrapolated from these curves gave a pIE for ML cells which was higher than that of NML cells; thus, consistent with their true pI values. Furthermore, the isoelectric data showed that the two tumour types possessed similar negative charge densities at pH 4.8 which confirmed the crossover phenomenon noticed with the pH mobility curves. It is suggested that the contradictory observations may be due to differences in the depths of the zones of the cell surface probed by the two electrokinetic methods, and that in ML cells a greater proportion of a cationic groups occur at a depth of between 30 and 60 Angstrom zone adjacent to this plane. The isoelectric data also suggest that the cationic groups of NML cells are more basic than those of the ML cells.

Animals↗

Acute disseminated lymphosarcoma with B cell markers in a child.

A case of a 4-year-old child with disseminated lymphosarcoma with meningeal involvement is described. Immunological investigations of the blast cells in the cerebrospinal fluid were carried out and in most of them Ig determinants and no response to PHA stimulation were found. So the B-dependent nature of these cells was ascertained. This observation is a contribution to the diagnosis of lymphoid malignancies through the evaluation of the immunological nature of the blast cells. The data of the literature are still scarce and inconclusive.

B-Lymphocytes↗

Primary lymphosarcoma of the lungs- a review of 121 cases.

Lymphosarcomas are the most frequent forms of primary pulmonary sarcomas. A comparison has been made between a total of 121 primary lymphatic sarcomas of the lungs and 314 other histomorphological forms of primary sarcomas of the lungs found in the literature in 15 years, out of which 7 are our own cases. Our results are summarized in a table, which shows the differences. Histomorphology, clinic and prognosis are discussed with special emphasis. The average are is 52 years, the age period 4-80 years, the sex distribution 1:1, the localization of the right side of the lungs 71%, the rate of recidives 4%, the general metastasizing 23%, the number of patients who survived the 5-years limit postoperatively 26.5%. An attempt is made to explain the postoperatively often unusually favorable development of these primarily malignant tumors by the histomorphological and pathophysiological characteristics.

Adolescent↗

Differential growth characteristics of low and high metastatic variant RAW117 murine lymphosarcoma cells.

The Abelson-virus-induced murine lymphosarcoma cell line RAW117-P and its in vivo selected highly malignant and metastatic variant RAW117-H10 have been studied for their growth in vivo, in vitro and in semi-solid agar. The highly malignant metastatic variant RAW117-H10 cells killed syngeneic Balb/c mice rapidly and formed 100-200 times more gross liver tumor nodules than the less malignant parental RAW117-P cells. On the other hand, there were no differences between the in vitro growth kinetics of these cells as measured by various parameters such as metaphase arrest or cells in DNA synthetic phase on various days after the initiation of the culture. These cells could be grown in semi-solid agar and formed characteristic colonies. The parental cells formed many very small colonies, whereas the highly malignant cells formed fewer, but very large colonies in soft agar. These results suggest that differential interactions of highly malignant RAW117-H10 cells with the host, particularly the host immune system, are much more important for regulating the number of metastases than any intrinsic growth advantages. It appears that growth differences, potentially based on lack of response to feedback inhibition rather than on kinetic parameters, are responsible for highly malignant RAW117-H10 cells forming larger colonies both in agar in vitro and in the liver in vivo.

Animals↗

Primary lymphosarcoma of the larynx in a child.

A 4 7/12-year-old Caucasian female with a history of "croup-like symptoms" and persistent airway obstruction, was found to have a primary lymphosarcoma by biopsy at the time of laryngoscopy and bronchoscopy. No metastatic disease was found. After an induction course of vincristine, prednisone and local irradiation, she received CNS prophylaxis with intrathecal methotrexate and cranial irradiation. Maintenance therapy, administered over a 2 3/4 year period, consisted of cyclophosphamide, methotrexate, and 6-mercaptopurine. Excluding the diagnostic evaluation, she was hospitalized only once for the management of suspected sepsis, gastrointestinal ulceration and severe bone marrow depression. Since discontinuing treatment 27 months ago, she has remained free of disease.

Child, Preschool↗

Analysis of rabbit and guinea pig complement efficiency in cytotoxicity tests against fibrosarcoma and lymphosarcoma cells.

In a complement-dependent 51Cr cytotoxicity assay, using as target murine fibrosarcoma or lymphosarcoma cells, the rabbit complement (RC) was more efficient than guinea pig complement (GPC) when tested either with strong antisera, such as antihistocompatibility sera, or with weak sera, such as wera from normal mice shown previously to posses a natural antitumor response. The high efficiency of RC was not due to activation by antibodies of a different class or specificity than those activating GPC. In fact, both 2-mercaptoethanol (2-Me)-sensitive or-resistant immunoglobulins could activate both RC and GPC, and the results of absorption tests indicated that the antibodies detected using either of the 2 complements were directed against the same specificities. In addition, the results of tests searching for cooperative antibodies excluded that a cooperative effect might be responsible for the high efficiency of RC. With weak antisera, sera of different rabbits were found to have different complement activity.

Animals↗

Histiolymphocytic lymphosarcoma in the subcutis of two horses.

Two aged mares with histiolymphocytic lymphosarcoma had multiple rapidly proliferating tumours in the subcutis. Consistent haematological changes were absent. One mare had lymph node involvement but no neoplastic lesions in the viscera. Microbiological examination of tumour tissue showed coryneform bacteria; there was no evidence of C-type or lytic viruses or of reverse transcriptase. Prominent intramitochondrial crystalline inclusions were in histiocytic tumour cells.

Animals↗

Ultrastructure and lectin histochemistry of equine cutaneous histiolymphocytic lymphosarcomas.

Tissues from subcutaneous lymphosarcomas and regional lymph nodes were examined by light and electron microscopy and by lectin histochemistry. Tumors were composed of two major cell types: small lymphocytes with few organelles and pleomorphic histiocytic cells with undulant surfaces, large numbers of cytoplasmic vacuoles, and many mitochondria with large crystalline inclusions. A large gram-positive coryneform bacterium was isolated from tumor nodules but was not identified morphologically in tumor tissues. Evaluation of sections of tumors with lectins as histochemical probes revealed three staining patterns: 1) lectin labeling histiocytic cells only (wheat germ, succinylated-wheat germ, Phaseolus vulgaris and soybean agglutinins); 2) lectins labeling histiocytic, interstitial and some lymphoid cells (concanavalin A, and Pisum sativum, Lens culinaris, and Ricinus communis I agglutinins); and 3) lectins failing to label any cell (peanut, Sophora japonica, and Ulex europaeus I agglutinins). In the lymph node, macrophages were labeled by lectins of groups 1 and 2; interdigitating reticular cells were labeled by group 2 lectins. Lectin staining of histiocytic cells in tumor tissues suggested that these were reactive cells and that lymphoid cells were the primary neoplastic component.

Animals↗