[The intracellular pH of the peripheral blood lymphocytes in cattle during the development of leukemia]. / Vnutrikletochnyi pH limfotsitov perifericheskoi krovi krupnogo rogatogo skota pri razvitii leikoza.

The intracellular pH distribution of peripheral cattle lymphocytes has been studied in normal state and at six stages of the development of bovine leukosis by the dye microfluorimetry of single cells. It has been shown that the increase of mean intracellular pH value occurs as well some distribution parameters, such as pH range and asymmetry change during the disease process. Probable reasons responsible for the observed modification of the distribution pattern are discussed.

Properties of tumor infiltrated cells induced by N-CWS.

Analysis of surface marker of cells after intratumor injection with Nocardia rubra cell wall skeleton (N-CWS) resulted in gradually increasing percentage of macrophage, Pan T and BoCD4+ cells. Proportion of BoCD8+ cells gradually increased from 4th day and then decreased from 8th day after the injection. Fresh tumor infiltrated cells obtained from lymphatic nodule at 8 days after injection of N-CWS showed cytotoxic activity against bovine leukemia cell line, but this activity decreased with the time of cultivation and no activity could be detected after 14 days cultivation. These cultured cells were injected twice to lymphatic nodule at one week interval for adoptive immunotherapy and found to induce complete regression of nodule after 5 weeks from first injection.

Chemotherapy and immunotherapy of bovine leukosis.

To prevent the progression of the disease, we treated leukemic or preleukemic cows with (1) adriamycin (ADM) entrapped in liposomes conjugated with monoclonal antibody, c143, against tumor-associated antigens (TAA) of bovine leukemic cells and (2) an immunotherapy using an immunopotentiator consisting of the cell wall skeleton of Nocardia rubra (N-CWS). Five leukemic or preleukemic cows with TAA-positive peripheral blood lymphocytes (PBL) received four injections of ADM alone (0.4 mg/kg body weight) or c143-conjugated liposomes containing the same dose of ADM (L-ADM-c143) through the jugular vein at about 4-day intervals. In three animals treated with L-ADM-c143, the TAA-positive cells gradually decreased with treatment and finally two animals became TAA-negative during a 6-week period and a 14-week period after treatment, respectively. About 6 weeks later, however, TAA-positive cells gradually increased. In the control, two animals treated with ADM alone showed no decrease of TAA-positive cells. Five TAA-positive animals with enlarged subcutaneous lymphatic nodules, each nodule estimated to be from 1 to 4 cm3 in size, were treated by injection of N-CWS into the tumors. Complete regression of tumor was observed in seven out of ten tumors treated in five animals. Decrease of TAA-positive cells was also observed in PBL for all five treated animals. In one animal, the TAA-positive cells remained low for at least 280 days after treatment. This study documents that ADM treatment and intralesionally administered N-CWS are effective in the treatment of bovine leukosis.

Hematologic abnormalities similar to the preleukemic state of adult T-cell leukemia in African green monkeys naturally infected with simian T-cell leukemia virus.

Studies were made of the hematologic features of 23 adult African green monkeys (Cercopithecus aethiops) naturally infected with simian T-cell leukemia virus (STLV), which is closely related to human T-cell leukemia virus type I. None of the STLV-infected monkeys showed any clinical signs, but their absolute lymphocyte count and percentage of atypical lymphocytes were significantly higher than those of uninfected monkeys. Three STLV-infected monkeys had especially high percentages of atypical lymphocytes. Most of the atypical lymphocytes were small- or medium-sized lymphocytes with a lobulate or convoluted nucleus, and were very similar to the leukemic cells in human cases of adult T-cell leukemia (ATL), while other atypical cells were large lymphoblastoid cells. Both types of atypical cells were positive for Leu2a and Tac antigens, and expressed STLV antigen after short-term culture. These findings suggested the presence of a preleukemic state in these STLV-infected monkeys similar to that seen in human ATL, and indicated the value of this natural infection system as an animal model of ATL in humans.

Dysmyelopoiesis in the cat: a hematological disorder resembling refractory anemia with excess blasts in man.

Clinical and pathological findings in three cats affected with a myelodysplastic disorder are presented. This hematological disorder resembles that of refractory anemia with excess of blasts as seen in man. The hematological profile in man is one of peripheral cytopenia in one or all of the marrow cell lines which occurs despite a normal to hypercellular bone marrow. Quantitatively, the marrow has a preponderance of blasts (up to 20%). Qualitative abnormalities consist of dysthrombopoiesis and/or dyserythropoiesis and/or dysgranulopoiesis. Myelodysplastic disorders in the cat are a form of marrow failure often associated with infection with feline leukemia virus. The use of the term refractory anemia with excess of blasts appears to be applicable to the cat and should be considered in evaluating dysplastic disorders of the feline bone marrow.

Feline preleukemia: an animal model of human disease.

In man, hematologic abnormalities precede the development of acute myeloblastic leukemia in about one-third of individuals. This preleukemic state may represent a stage of adult leukemia wherein small numbers of leukemic cells are present and the normal marrow stem cell compartment has not been seriously compromised. A syndrome resembling human preleukemia occurs in cats infected with feline leukemia virus (FeLV). This disorder is characterized by anemia, leukopenia or thrombocytopenia occurring weeks or months prior to the development of feline acute leukemia. The natural occurrence of this syndrome in this domestic animal population makes it a potential model of human preleukemia. Initial poor results of therapy of human preleukemia presently prohibit one from carrying out controlled trials with chemotherapeutic agents in such a group of patients. Preliminary trials with chemo- and/or immunotherapy may be more easily attempted with FeLV infected preleukemic cats.

[Studies on the virus demonstration in enzootic bovine leukosis using the revertase test]. / Untersuchungen zum Nachweis des Virus der enzootischen Rinderleukose mit Hilfe eines Revertasetestes.

This exogenic test for the detection of enzyme activities (revertase) is helpful in differentiating between leucocytes of leukaemic cattle, on the one hand, and those of intact animals, on the other. The mechanism of such identification is based on differences in enzyme activity in the presence of poly rA/oligo dT and poly dA/oligo dT. The best results were obtained from short-time cultured leucocytes which gave ten times higher margins of incorporation by comparison between intact and preleucotic cattle. The morphological findings obtained by electron microscopy confirmed the results by other authors and enlarged them by determination, for the first time, of RNA filaments and protein rings.