Distribution of a novel nuclear protein in normal and regenerating liver cells.

Monoclonal antibodies to a rat liver nuclear protein (B2, 68 kda, pI: 6.5-8.2) have been established and characterized to localize the distribution of this antigen in nuclear organization. It was demonstrated that this nuclear protein B2 is associated with actively transcribed nucleosomes and the nuclear matrix as revealed by immunogold labelling. In the regenerating liver cell, the immunogold particles are predominantly in the euchromatin as compared to the resting liver cells which are mainly in nuclear matrix and heterochromatin. It was also demonstrated that the incorporation of 32P into the nuclear protein B2 is increased 6-fold in the actively transcribed nucleosomes as compared to the nuclear matrix, as analyzed by two-dimensional polyacrylamide gel electrophoresis. We hypothesize that this nuclear protein may act as an anchorage point either for actively transcribed RNA or for DNA replication. Once this protein is highly phosphorylated, it dissociates from the nuclear envelope and can then dynamically interact with active nucleosomes within the nucleus.

Translocation (14;19) in acute biphenotypic leukemia.

Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.

Isochromosome 7q as the sole abnormality in an unusual case of T-cell lineage malignancy.

We present a case of large cell lymphoma in a 20-year-old Oriental male who presented with massive splenomegaly and mild anemia. Surface marker and molecular genetic analyses of lymphomatous cells obtained from the spleen indicated a T-cell origin. Chromosomal analysis identified an isochromosome 7q as the sole abnormality. This is the first report of isochromosome 7q as the sole cytogenetic abnormality in a T-lineage malignant clonal expansion.

Selected ultrastructural aspects of urothelial and prostatic tumors.

Ultrastructural techniques have been widely applied in the study of urothelial and prostatic tumors. In the common proliferative diseases affecting the lower urogenital tract, electron microscopy has provided us with a greater understanding of the pathobiology and morphology of these disease processes. Specific diagnostic application, however, has been limited. In the unusual tumors affecting urothelium and prostate such as neuroendocrine carcinoma, carcinosarcoma, and sarcomas, electron microscopy has provided some practical diagnostic information of value in patient management. This paper provides a survey of the fundamental and practical contributions of ultrastructural studies in the prostatic and urothelial areas.

Acute inclusion-body leukemia. Case report and review of literature.

An unusual case of acute leukemia with basophilic cytoplasmic inclusion bodies in a child is described. Certain aspects of the case suggested a lymphoblastic phenotype and others a myeloid origin. The inclusions stained positively for acid phosphatase and toluidine blue. Too few patients have been reported to determine the prognostic significance of acute leukemia with inclusion bodies.

Mallory body-like abnormalities in carcinomas induced by cultured transformed rat liver cells.

Hepatoma cells isolated from rats after administration of a carcinogen, diethylnitrosamine, and propagated in culture, contained a genetically stable cytoskeletal abnormality resembling Mallory bodies. These juxtanuclear aggregates of intermediate-sized filaments were maintained in carcinomas produced in nude mice after inoculation of uncloned mass cultures and a cloned subculture. Paraffin and frozen sections of these tumors revealed acentric nuclei and a glassy hyalin-type cytoplasmic lesion which stained pink with hematoxylin-eosin and blue with Mallory's aniline blue stain. The cells in culture and in the tumor sections were strongly positive for gamma-glutamyl transpeptidase. Cryostat sections examined by indirect immunofluorescence microscopy with antisera to purified bovine hoof prekeratin, desmosome-associated tonofilaments from bovine muzzle, and murine vimentin, as well as transmission electron microscopy revealed the presence of juxtanuclear aggregates of intermediate-sized filaments. All characteristics previously reported for the tissue culture cell line were stably maintained in the tumor tissue. These results suggest that the Mallory body-containing cells frequently observed in man in alcoholic hepatitis and other degenerative liver diseases could, under appropriate environmental "promoting" conditions, be precursor cells in focal hepatocellular carcinoma formation.

Ultrastructural demonstration of terminal deoxynucleotidyl transferase (TdT).

Using an electronmicroscopic peroxidase-antiperoxidase technique in combination with a three-step fixation procedure according to Willingham, the ultrastructural site of terminal deoxynucleotidyl transferase (TdT) could be shown in cells of a human lymphoblastic leukemia cell line (MOLT 4). TdT appeared in the cytoplasm of the cells associated with large membrane bound granules from 150 to 600 nm in diameter usually arranged in aggregates. TdT-positive spaces were completely segregated form the rest of the cytoplasm and seemed to be interconnected by a tubular system. No TdT was detected in the nuclei.

Tumorigenicity, immunogenicity, and virus production in mouse melanoma cells treated with 5-bromodeoxyuridine.

Bromodeoxyuridine (BrdU), whether administered in a 30-hr pulse of 30 mug/ml or continuously in low concentrations (1-3 mug/ml), significantly increased production of particles with the morphology of murine leukemia virus in a mouse melanoma (B16) cell line. Particles were very rare in control cells, detectable only by electron microscopy. By contrast, in many experiments with BrdU-treated cells the numbers of virus particles counted by electron microscopy increased over 100-fold, and other tests for murine leukemia virus (plaque assay and tests for group-specific antigens 1 and 3 and for Gross cell-surface antigens) became positive. All BrdU-treated cells, regardless of drug concentration or length of treatment, in addition to showing loss of both pigment and of piled-up morphology, were suppressed in tumorigenicity compared with the control cells. These effects were all reversible. A significant percentage of mice injected with BrdU-treated cells were protected against subsequent tumor formation when challenged with malignant control cells. The degree of protection conferred on the mice correlated well with the number of virus particles counted in the injected cells. There was also good correlation between the amount of cell-associated virus and the degree of suppression of malignancy for cells treated continuously with 1 mug of BrdU per ml, but not as good for cells treated for short periods with higher concentrations of BrdU.

Theta particles: a structure found in hamster sarcoma virus.

Hamster sarcoma virus (HaSV), a ribonucleic acid tumor virus, pelleted from tissue culture fluid manifests type C morphology by electron microscopy. However, if virus is first concentrated by polyethylene glycol or ammonium sulfate followed by density gradient banding, the virus shows a dramatically atypical barred core structure, termed "theta particles." This structure suggests a condensation of the ribonucleoprotein into a flat disc. Atypical particles are found with HaSV and not in similarly treated feline leukemia virus or Rauscher-murine leukemia virus. Differences in the composition of HaSV as compared with these other viruses may be responsible for the production of such particles.