BCL1, a murine model of prolymphocytic leukemia. I. Effect of splenectomy on growth kinetics and organ distribution.

BCL1 is a transplantable murine B-cell leukemia that closely resembles human prolymphocytic leukemia (PLL). Syngeneic mice injected with BCL1 cells develop massively enlarged spleens followed by leukemia. Splenectomy performed either prior to BCL1 transplantation or prior to the leukemic phase of transplanted BCL1 results in a markedly altered clinical syndrome: the onset of leukemia is delayed by about 2 months; the leukemia is low-grade; and the lymph nodes, which are not prominently involved in leukemic animals with intact spleens, are massively infiltrated in the splenectomized transplant recipient. The immunologic phenotype of the BCL1 cell is not altered by splenectomy and thus does not appear to account for the altered tissue distribution of BCL1 in the splenectomized host. However, the results indicate a striking dependence of BCL1 on microenvironmental influences of the host lymphoid tissues.     

Cytogenetic studies in a case of T-cell prolymphocytic leukemia

The authors describe cytogenetic aberrations observed in a case of T prolymphocytic leukemia. C11 deletion (q14) B5 deletion (pter), D14q⁺, E20 trisomy, and two markers are the main anomalies of the complement.     

Immunopathogenicity and oncogenicity of murine leukemia viruses. II. Infection of mice and rats with Scripps leukemia virus.

The pathologic consequences of infection of newborn mice and rats with MuLV (Scripps leukemia virus--SLV) were observed. Serum MuLV p30 concentrations of most strains were elevated 20 to 100 times that of controls while MuLV gp70 levels were elevated only 1.1 to 14.8 times, probably reflecting in part the higher concentrations of gp70 in control sera but also indicating the lack of parallelism in regulation of synthesis of these two viral antigens. Infected mice of most strains developed immunologic diseases, including antinuclear antibody and glomerulonephritis, but not Coombs' antibodies. The nature and severity of the immunologic disease varied considerably, depending upon the genetic character of the host. Most infected animals developed lymphatic leukemias, but four strains showed partial to complete resistance to SLV oncogenesis: BALB/c (nude); C57 Bl/6; (NZB times NZW) F1, and (NZW times BALB/c) F1.     

Clonal evolution of T-cell prolymphocytic leukemia to a T-large-cell lymphoma. A morphologic and immunologic study

We describe a patient with T-cell prolymphocytic leukemia who developed a large-cell lymphoma of the T-cell type. The neoplastic cells of the large-cell lymphoma demonstrated the same immunologic phenotype (ER+, Leu-3+, Leu-2-, and HLA ABC+) as the cells of the prolymphocytic leukemia, which indicated a clonal evolution of a T-cell prolymphocytic leukemia into a large-cell lymphoma of the T-cell phenotype.     

An acquired Robertsonian translocation in prolymphocytic leukemia: a case presentation and review

Robertsonian translocations between the acrocentric autosomes are the most common type of constitutional chromosome rearrangement in humans. However, Robertsonian translocations are very rarely acquired in cancer cells. We report a patient with prolymphocytic leukemia and an acquired Robertsonian translocation in the leukemic cells. The translocation was between chromosomes #13 and #15; t(13;15)(q11;p12). Two other cases of malignancy with an acquired Robertsonian translocation have been found, one being of the t(13;15) type, which accounts for only 1% of constitutional Robertsonian translocations. We propose, therefore, that although Robertsonian translocations are occasionally observed in cancer cells, they are very rarely acquired.     

The ultrastructure of transmissible murine colonic hyperplasia.

Transmissible murine colonic hyperplasia was examined ultrastructurally by sequential sampling after inoculation with the etiologic agent, Citobacter freundii. Light-microscopic changes in the descending colon of inoculated mice were correlated with scanning and transmission electron-microsopic findings. Bacteria were attached to the surface of the mucosa between 4 and 10 days after inoculation. Hyperplasia was most severe at 16 days and thereafter underwent regression. Regression was preceded by extrusion of infected cells from the surface mucosa and replacement by immature hyperplasia epithelium. Hyperplastic epithelium throughtout the crypt resembled undifferentiated crypt cells of controls. By 45 days, the mucosa had reverted to near normal structure. The results suggest that severe mucosal proliferation with minimal inflammatory change resulted from attachment of bacteria to the surface mucosal epithelium. The hyperplastic response appeared to be a defense mechanism of replacing infected cells with newly migrated, uninfected epithelium.     

Karyotypic findings in a case of prolymphocytic leukemia with a history of radiation exposure

Cytogenetic examination, utilizing B- and T-cell mitogens, of the peripheral blood lymphocytes of a patient with the prolymphocytic variant of chronic lymphocytic leukemia (CLL) and a history of radiation exposure revealed two abnormal clones. One clone with 48 chromosomes (+t(6;12),6q-, +12,14q+) may be derived from CLL cells, whereas the clone with 46 chromosomes and a ring #11 possibly originated from normal T and/or B cells affected by past irradiation.     

Temporal lymphoreticular changes caused by ts1, a paralytogenic mutant of Moloney murine leukemia virus TB.

Inoculation of newborn FVB/N mice with ts1, a mutant of Moloney murine leukemia virus TB, induced severe thymic atrophy, spongiform polioencephalomyelopathy, and fatal posterior paralysis of the affected mice 35-40 days after inoculation. During the early course of infection viral replication was found in the spleen and, more importantly, within the thymus. Of these organs, the thymus was affected most severely by ts1-infection. Thymic weights of infected mice decreased markedly during disease progression, culminating in severe atrophy at the time of paralysis. During the first 10 days after inoculation, the virus replicated within the endothelial lining of splenic and thymic capillaries and was released albuminally into the basement membrane before spreading outwardly into perithelial, epithelial, and reticuloendothelial cells. Within these cells there was productive viral replication and subsequent dissemination of the virus to the thymic T cell population. Early infection (up to 10 days after inoculation) of the thymus induced an increase in thymocytic mitosis, followed by a progressive increase in thymocytic death between 15 and 35 days after inoculation. Thymuses from paralyzed mice killed 30-39 days after inoculation, demonstrated pronounced involution, characterized by loss of lobular architecture, effacement of the cortex and medulla, severe depletion of thymocytes, and partial or complete loss of Hassall's corpuscles. Immunohistochemistry for viral antigens showed positive labeling of splenic megakaryocytes, reticuloendothelial cells, and thymocytes in mitosis, and reticulo-epithelial-endothelial cells of the thymus. The thymic phase of viral replication appeared to be crucial for development of neurological lesions and posterior paralysis.     

Morphology of lysosomes in different phases of growth of lymphoblasts of L5178Y murine leukemia.

Parallel studies were carried out on the morphology of lysosomes, activity of DNA synthesis measured by the rate of 3 H-thymidine incorporation, and proliferative activity on the basis of values of the mitotic index of leukemia L5178Y lymphoblasts under varying growth conditions. Morphology of lysosomes was studied by the method of intravital staining with euchrysine. Observations were made on cells growing from the logarithmic phase to saturation density and synchronized by double blocking of DNA synthesis by hydroxyurea. The results showed some variation of the morphology of lysosomes related to growth phase of the cells.     

Morphology and ultrastructure of fungi in extended-wear soft contact lenses.

Filamentous fungi of the genera Acremonium, Aspergillus, Alternaria, Cladosporium, Curvularia, and Fusarium penetrated the matrix of soft contact lenses both during normal usage and in laboratory studies. Growth of the fungi within the lens matrix increased with increasing water content of the lens. Hyphae within the lens were coiled. Some species penetrated completely through the lens within 96 h. More frequent cleaning and disinfection of extended-wear soft contact lenses is recommended.     

Morphology and ultrastructure of Lymphocystis disease virus, a fish iridovirus, grown in tissue culture

The morphology and the ultrastructure of the Lymphocystis disease virus (LDV) strain Leetown , a fish iridovirus , was studied by electron microscopy. The virus was grown on bluegill fry (BF-2) cells at 21 degrees. LDV showed an icosahedral shape by ultrathin sections and negative staining, with a diameter of about 200 nm. The shell of the virion seemed to be composed of two unitary membranes with a total diameter of 16 nm. The outer membrane demonstrated swelling in negative staining, exhibiting a central core and the presence of globular subunits at its external surface organized in geometrical arrays of 60 and 90 degrees. Glutaraldehyde fixation preserved very effectively the icosahedral structure with the subunits remaining invisible. The internal structure of the virions was composed of osmiophilic threads or granules of 6 to 8 nm in diameter surrounded by an amorphous material of 10 to 20 nm in thickness. External filaments were observed at the surface of the particles in ultrathin sections, giving the appearance of a halo surrounding the shell. In negative staining these filaments were rarely observed; in one virus preparation, they appeared in bundles.     

Role of endogenous murine leukemia virus in immunologically triggered lymphoreticular tumors II. Isolation of B-tropic mink cell focus-inducing (MCF) murine leukemia virus

Previous work has shown that (BALB/c x A)F, (CAF₁) mice with an immunological disorder, the graft-versus-host reaction (GVHR), express an oncogenic murine leukemia virus (MuLV) which appears to be responsible for the subsequent development of lymphoreticular tumors. A mink cell focus-inducing (MCF) virus has been isolated from a reticulum cell neoplasm induced in a BALB/c mouse by serially passaged B-tropic MuLV originating in a CAF, GVHR mouse. The cloned MCF virus has a dual host range. It grows both in mouse cells where it is XC negative, B tropic, and in mink lung cells where it induces characteristic foci. It is partially neutralized by xenotropic MuLV antiserum and it partially competes in a homologous ecotropic gp70 radioimmunocompetition assay. Both ecotropic and xenotropic MuLV interfere with its infectivity. In these biological properties, the GVHR MCF virus closely resembles recombinant AKR MCF virus. We discuss the possible origin and significance of a presumptive recombinant MuLV in a low virus model where lymphoreticular tumors are triggered by an immunological disturbance.     

Morphology and ultrastructure of oral strains of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus.

Selected human oral and nonoral strains of the genera Actinobacillus and Haemophilus were examined by transmission and scanning electron microscopy. The strains examined were morphologically identical to recognized Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and Haemophilus paraphrophilus. By transmission electron microscopy, the cells were typically gram negative in morphology, with several strains possessing some extracellular ruthenium red-staining polymeric material. Numerous vesicular structures, morphologically identical to lipopolysaccharide vesicles, were seen to originate from and be continuous with the surface of the outer membrane. Large numbers of these vesicles were also found in the external environment. Scanning electron microscopic observations revealed that both actinobacilli and haemophili possessed surface projections and an amorphous surface material which connected and covered adjacent cells.     

Transfer factor: a murine model.

Transfer factor has been studied extensively in humans, but a satisfactory subprimate model has not been established. Using BALB/c mice immunized with complete Freund adjuvant, we show that a low-molecular-weight substance derived from disrupted spleen cells transferred sensitivity to purified protein derivative (PPD) to recipient nonimmunized BALB/c mice. Transfer was confirmed by footpad swelling to PPD in vivo and by splenic lymphocyte transformation to PPD in vitro. In recipients of transfer factor, an inverse correlation was noted between the splenic lymphocyte response to PPD and to concanavalin A. Material obtained from spleens of saline-treated BALB/c mice did not transfer sensitivity to PPD to recipient mice.     

T, not B, lymphocytes are required for immunodeficiency and paralysis induced by ts1, a mutant of Moloney murine leukemia virus-TB.

BALB/c mice when injected as newborn with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus-TB, developed a fatal hindlimb paralysis and immunodeficiency. This disease induction was prevented, to a great extent, by transient depletion of the peripheral T lymphocytes during the early course of infection by using anti-Thy 1.2 antibody. FVB/N mice, which are highly susceptible to ts1, but express Thy 1.1 instead of Thy 1.2 on their T lymphocytes, did not show any difference in the disease profile when treated similarly with anti-Thy 1.2 antibody. Transient depletion of the peripheral B lymphocytes in BALB/c mice in the early course of ts1 infection had no effect on the disease induction. In the T cell depleted BALB/c mice, virus replication was reduced, survival of the mice was increased and viral specific antibodies were produced, whereas, in the B cell depleted mice the disease process went on in a fashion similar to untreated mice infected with ts1. Thus, this study demonstrates that the disease syndrome induced by ts1 in BALB/c mice is dependent upon the presence of T lymphocytes during the early course of infection, and that presence of B lymphocytes have little or no effect on the disease outcome.