Detection of t(14; 18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease

The most frequent nonrandom chromosome rearrangements in B-cell non-Hodgkin lymphoma (NHL) is the t(14;18)(q32;q21) found in follicular lymphomas. The t(14;18) in Hodgkin disease (HD) was rarely observed using cytogenetic techniques. Although Southern blot analysis failed to demonstrate the t(14;18), there have been conflicting reports concerning the occurrence of the translocation using polymerase chain reaction (PCR) methods in HD. In some HD tissues, the translocation might be derived from background lymphocytes rather than Hodgkin and Reed-Sternberg (HRS) cells, because B-cells with t(14;18) are regularly generated in normal individuals. However, the cells bearing the translocation have remained unidentified. We describe a patient with HD who showed t(14;18) in hyperdiploid cells using fluorescence in situ hybridization (FISH) and HRS cells which were strongly positive for BCL2 by immunohistochemistry. These findings suggest that HRS cells may have a t(14;18).     

Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo

Long-term potentiation (LTP) is thought to be particularly important in the acquisition of hippocampus-associated memory, in part because it develops quickly and persists for indefinite periods. Extracellular proteolysis has been hypothesized to contribute to LTP by modifying adhesive relations of synapses and thus the morphology of excitatory synapses. Here we report that neuropsin (NP), an extracellular serine protease, is critically involved in the formation of both the potentiation effect and hippocampus-dependent forms of memory. NP-knockout mice were significantly impaired in the Morris water maze and Y-mazes and failed to exhibit early phase LTP induced by a single tetanus. Potentiation was also impaired or completely blocked by in vivo application of a specific inhibitor or a neutralizing monoclonal antibody for NP. Intriguingly, recombinant (r-) NP alone, without tetanic stimulation, elicited either long-lasting potentiation or depression, depending on the applied dose. The r-NP-elicited potentiation was occluded by prior induction of LTP, while theta-burst-elicited LTP was occluded by application of r-NP alone, suggesting that the two forms of plasticity have a common signalling pathway. r-NP-elicited potentiation and depression increased phosphorylation at different sites on the GluR1 subunit of the AMPA receptor that had previously been associated with LTP or long-term depression. Thus, we conclude that NP is necessary for establishment of LTP and has a significant role in memory acquisition.     

Thymosin alpha 1 exerts protective effect against the 5-FU induced bone marrow toxicity

Thymosin alpha 1 was shown to prevent the 5-fluorouracil(5-FU)-induced bone marrow toxicity in BDF1 mice, as determined by the cellularity, haemopoietic stem cells (CFU-s) and granulocyte-macrophage colony forming unit (GM-CFU). Furthermore, thymosin alpha 1 increased the levels of colony stimulating factor (CSF) in sera or in culture media of spleen cells derived from 5-FU-treated mice. The treatment of spleen cells with anti-Thy 1,2 antibody plus complement abolished completely the CSF production. The in vivo treatment of donor mice with anti-Thy 1,2 antibody following 5-FU abolished completely the capability of their bone marrow cells to save lethally irradiated recipients. Thymosin alpha 1 treatment prevented the damage by such combined treatment. The present study indicates that thymosin alpha 1 exerts its protective effect against the 5-FU-induced bone marrow toxicity, at least partially, through its effect on the maturation of immature T cells to functional T cells which produce various kinds of lymphokines including CSF.     

Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations

Adhesion formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. adhesion formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose- dependent reduction in the area of the sidewall injury that was involved in adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of adhesion formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced adhesion formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of adhesion formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation and reformation of postoperative adhesions in three animal models.      

Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer's lung, ventilation pneumonitis, and bird fancier's lung: report of a nationwide epidemiologic study in Japan

We performed a nationwide epidemiologic study of hypersensitivity pneumonitis (HP) in Japan by questionnaire and found that 835 cases of HP were recognized during the 1980s; 74.4% were summer-type HP, 8.1% farmer's lung, 4.3% ventilation pneumonitis, 4.1% bird fancier's lung, 2.3% other types, such as chemical worker's lung, and 6.8% of unknown causative agent. It was found that the CD4/CD8 ratios of bronchoalveolar lavage (BAL) lymphocytes were significantly different with the type of disease. The ratio was 0.6 +/- 0.1 (mean +/- SEM) in summer-type HP (N = 271), 4.4 +/- 0.7 in farmer's lung (N = 22), 1.6 +/- 0.3 in ventilation pneumonitis (N = 19), and 2.0 +/- 0.5 in bird fancier's lung (N = 19). In farmer's lung, the CD4/CD8 ratio in smokers was 6.2 +/- 1.9 (N = 6) in contrast with 3.4 +/- 0.7 for nonsmokers (N = 16) (p less than 0.05). It has been generally considered that the phenotypes of BAL lymphocytes in patients with HP are predominately CD8 cells. Our present results, however, indicate that the phenotypes of BAL lymphocytes vary with the type of HP, probably depending on factors such as causative agent, smoking, or staging of the disease.     

Identification of complex phenotype (OKT4+/OKT8+) on adult T-cell leukemia cells by sequential application of indirect rosette assay with protein A-coated ox red blood cells and immunoperoxidase technic

The specific immunophenotypic characterization of the hematologic malignant diseases has been obtained most commonly by the immunofluorescent technic. It requires a microscope with illuminator or the expensive flow cytometer that usually precludes morphologic assessment. It was compared with the indirect rosette assay and the immunoperoxidase study, which allowed both immunologic and morphologic assessment. These three technics appeared to be comparable quantitatively, and the latter two technics utilizing cytospin preparations were applied sequentially to the leukemic cells of adult T-cell leukemia with a complex phenotype (OKT4+/OKT8+) and successfully displayed the double markers on each leukemic cell.     

Comparison of inhibition of the action of C1 on C4 by two synthetic substrates of C1 esterase, TAMe and ATEe

Two synthetic substrates, TAMe and ATEe, were tested for their abilities to inhibit the formation of SAC14 and SAC142 and found to act as inhibitors in different ways. In addition to inhibition of the formation of SAC142 from SAC14 and C2, TAMe inhibited the formation of SAC14 from SAC1 and C4 and the inactivation of C4 by C1 and EAC1. ATEe inhibited the formation of SAC14, but only slightly inhibited the inactivation of C4 by C1 and EAC1 and further did not interfere with the formation of SAC142. ATEe could be entirely replaced by acetyl-L-tyrosine in these effects on the action of C1 on C4. The possible mechanism of inhibitions by these compounds was discussed.     

Transitional cell carcinoma with sarcomatous elements in the urinary tract. Six cases examined by immunohistochemistry.

We report six cases of carcinoma showing sarcomatous change in the urinary tract examined by conventional histochemistry and immunohistochemistry. All of the cases were transitional cell carcinoma with or without focal squamous cell carcinoma. Sarcomatous components resembling spindle cell sarcoma with a marked myxoid stroma or chondrosarcomatous element were also observed in all cases. The sarcomatous elements were closely associated with the areas of squamous cell carcinoma in three cases. Various histochemical staining procedures demonstrated mesenchymal features in the stroma of sarcomatous areas. By immunohistochemical examination, the epithelial components showed positive reactions for keratin, epithelial membrane antigen and, focally, carcinoembryonic antigen. The sarcomatous components revealed a positive immunoreaction for keratin but lacked other epithelial markers in all cases. Chondrosarcomatous elements in two cases were positive for both keratin and S-100 protein. These findings indicate that sarcomatous elements in carcinoma may represent mesenchymal metaplasia with partial or complete loss of epithelial features. However, further study will be necessary in order to determine whether heterogeneous elements, such as chondrosarcomatous areas, are epithelial or truly mesenchymal in origin.