The murine Tcl1 oncogene: embryonic and lymphoid cell expression

In human leukemias and lymphomas nonrandom chromosomal rearrangements cause changes in cell growth and/or survival in such a way as to promote malignancy. The detailed study of the biochemical and genetic pathways altered in human cancer requires the identification or development of models to allow the study and manipulation of cancer gene function. Recently, the breakpoint gene TCL1, involved in chromosome translocations observed mostly in mature T-cell proliferations and chronic lymphocytic leukemias (CLL), was isolated and characterized, and showed to be part of a new gene family of proteins involved in these tumors. The murine Tcl1 gene, is similar in sequence to the murine and human MTCP1 gene also involved in T cell leukemias. The murine Tcl1 gene was shown to reside on mouse chromosome 12 in a region syntenic to human chromosome 14. Furthermore, we show that the murine Tcl1 gene is expressed early in mouse embryonic development and demonstrates expression in fetal hematopoietic organs as well as in immature T and B cells. Characterization of the murine Tcl1 gene will help in developing a mouse model of CLL and would provide the best opportunity to study and decipher the role of TCL1 in malignant transformation.     

Ovarian neoplasms in children

OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably.     

Acute effects of pentobarbital in a monkey operant behavioral test battery

The effects of acute pentobarbital treatment were assessed using a complex operant test battery containing five tasks in which correct performance is thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult, male rhesus monkeys were tested 15 min after IV injection of saline or pentobarbital (1, 3, 5.6, 10, or 15 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by PBT was TRD > IRA = DMTS = PR > CPR, in which sensitivity was defined as a significant disruption in any aspect of task performance. PBT slowed response rates at 10.0 and/or 15.0 mg/kg in all tasks. Accuracy was decreased in the TRD task at > or = 5.6 mg/kg but doses of > or = 10.0 mg/kg were required to decrease accuracy in the IRA, DMTS, and CPR tasks. Thus, behavior thought to model time perception (TRD) was more sensitive than behavior modeling learning (IRA), short-term memory and attention (DMTS), and motivation (PR). CPR was the least sensitive behavior. Because pentobarbital exerts its effects at least in part via GABA systems, the effects in the current study were compared with those of a previous study of the acute effects of diazepam. The two compounds exerted fundamentally different effects on operant test battery performance.     

Immunolocalization of natriuretic peptide receptor B in the rat kidney

The natriuretic peptide receptor (NPR) family consists of three receptor subtypes: two transmembrane forms that contain a guanylyl cyclase intracellular domain (NPR-A and NPR-B), and one truncated form (NPR-C). Because of the lack of specific agonists and antagonists for each receptor subtype and to the difficulty to detect the presence of small quantities of NPR-B by ligand binding studies, polyclonal antibodies against a peptide whose sequence was chosen from a region of the extracellular domain of rat NPR-B that is not homologous to sequences in NPR-A and NPR-C were developed. Western blotting with affinity-purified anti-NPR-B (413-426)-Tyr revealed a polypeptide of approximately 120 kD on COS-1 cell membranes transfected with rat NPR-B cDNA. The antibody recognized a second polypeptide, approximately 5 to 10 kD smaller, which probably represents the unglycosylated receptor. Anti-NPR-B (413-426)-Tyr did not show crossreactivity to any other NPR. Western blotting analysis with anti-NPR-B (413-426)-Tyr also identified a protein of appropriate size in renal vascular membranes. These results were supported by immunohistochemistry findings that demonstrated staining for NPR-B on papillary and medullary capillaries, glomeruli, and renal arteries. This study concludes that NPR-B is present in the rat kidney, although it was only detected in vascular structures.     

Phenotypic analysis of antigen-specific T lymphocytes

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.