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L Lasky

Publications and source records attributed to L Lasky.

12 recordsLinked to original sources
PubMed1990

T cell depletion with anti-CD5 immunotoxin in histocompatible bone marrow transplantation. The correlation between residual CD5 negative T cells and subsequent graft-versus-host disease.

Twenty-nine patients with advanced leukemias (median age 34 years) received histocompatible sibling marrow that had been depleted of T cells by ex vivo incubation with anti-CD5 monoclonal antibody-ricin immunotoxin (T101-R) for the purpose of graft-versus-host disease prophylaxis. Donor cell engraftment was documented in 28/29 patients by DNA restriction fragment length polymorphisms. In this pilot study the dose of T101-R incubated with donor marrow was increased in a stepwise manner from 300 ng (10 patients) to 600 ng (5 patients) to 1000 ng immunotoxin (IT)/10(7) bone marrow mononuclear cells (14 patients) in an attempt to achieve more effective GvHD prophylaxis. A statistically significant reduction in acute GvHD was achieved for patients receiving marrow pretreated with 1000 ng of immunotoxin (34%) compared to recipients of BM treated with 300 ng immunotoxin (100%, P = 0.0004). T-depleted marrow samples were evaluated for residual T cell activity using several in vitro assays including proliferation to the purified mitogen PHA (HA-17) and in mixed lymphocyte culture (MLC), T cell cytotoxicity, a limiting dilution assay for detecting precursors of proliferating T cells (LDApPTL), and phenotypic analysis of viable T cells expanded in 16-day culture with interleukin 2. The extent of T cell depletion determined by LDA assay varied widely at each immunotoxin concentration used. Thus, there was no correlation between the dose of T cells infused and subsequent GvHD. Phenotyping of lymphocytes recovered from immunotoxin-treated marrow demonstrated that residual T cells were CD5 negative in all cases tested. The only in vitro parameter that predicted subsequent acute or chronic GvHD was the demonstration of viable CD5 negative lymphocytes with T cell phenotype (CD2, CD3, and/or CD7 positive) after 16-day culture with IL-2 of the T-depleted bone marrow. We observed that such CD5 negative cells expressing other T cell markers have cytotoxic function and speculate that these cells may be capable of mediating GvHD in allogeneic transplantation.

Antigens, CD↗
PubMed1990

Autologous transplantation for CML using marrow treated ex vivo with recombinant human interferon gamma.

Six chronic and four advanced patients with Ph1 positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using bone marrow treated ex vivo with recombinant human interferon gamma (rIFN gamma). In three cases 100% Ph1 negative bone marrow hematopoiesis was demonstrated 4 to 8 weeks after ABMT. In three additional cases, a maximum of 40-45% bone marrow metaphases were Ph1 negative 2 to 12 weeks following ABMT. In four cases, no or minimal evidence of Ph1 negative hematopoiesis could be demonstrated posttransplant. Seven patients survive in chronic phase at a median of 375 days (range 100-495 days). Five patients have not required therapy, while two patients receive low doses of rIFN alpha to control peripheral blood counts. Ex vivo treatment of CML bone marrow with rIFN gamma followed by ABMT in patients dependent upon or refractory to therapy prior to transplantation is associated with transient complete or partial Ph1 negative bone marrow hematopoiesis in the majority of patients post-transplant and with return of a chronic phase characterized by no need for therapy or by response to low doses of rIFN alpha. Modification of the ABMT procedure and efforts to maintain cytogenetic and hematologic remission following ABMT may lead to prolonged survival or cure.

Adult↗
PubMed1990

Bone marrow transplantation for acute lymphocytic leukemia utilizing total body irradiation followed by high doses of cytosine arabinoside: lack of superiority over cyclophosphamide-containing conditioning regimens.

The efficacy of a pre-bone marrow transplantation (BMT) preparative regimen consisting of single, high dose rate total body irradiation followed by 12 courses of high dose cytosine arabinoside (Ara-C) over 6 days with allogeneic or autologous rescue was studied in 68 consecutive patients with poor risk acute lymphocytic leukemia (ALL). Toxicity associated with the above preparative regimen included conjunctivitis in the majority of patients, severe gastrointestinal symptoms in seven patients (10%), skin desquamation in four patients (6%), and interstitial pneumonitis of unknown etiology in two patients (3%). One patient died from a 'capillary leak' syndrome that may have been attributable to Ara-C toxicity. With a follow-up of 1.1-4.3 years, the estimated survival is 21% (95% confidence interval, 10-32%), with a disease-free survival of 18% (8-28%) and an estimated relapse rate of 75% (62-88%) at 3 years. These results are not significantly different from overall outcome in 105 patients treated previously at this same institution with cyclophosphamide-containing preparative regimens (31% (22-40%) estimated survival, 29% (20-38%) disease-free survival, and an estimated relapse rate of 63% (52-74%) at 3 years), especially when results are stratified based on allogeneic versus autologous BMTs. Although efficacious for a minority of patients with poor risk ALL, a pre-BMT preparative regimen consisting of total body irradiation followed by high doses of Ara-C did not improve long-term survival over more conventional preparative regimens consisting of cyclophosphamide and total body irradiation. Future strategies may need to investigate novel approaches for reducing leukemic relapse rates in patients with ALL undergoing bone marrow transplantation.

Adolescent↗
PubMed1988

Epitope mapping of the human immunodeficiency virus type 1 gp120 with monoclonal antibodies.

A soluble form of recombinant gp120 of human immunodeficiency virus type 1 was used as an immunogen for production of murine monoclonal antibodies. These monoclonal antibodies were characterized for their ability to block the interaction between gp120 and the acquired immunodeficiency syndrome virus receptor, CD4. Three of the monoclonal antibodies were found to inhibit this interaction, whereas the other antibodies were found to be ineffective at blocking binding. The gp120 epitopes which are recognized by these monoclonal antibodies were mapped by using a combination of Western blot (immunoblot) analysis of gp120 proteolytic fragments, immunoaffinity purification of fragments of gp120, and antibody screening of a random gp120 gene fragment expression library produced in the lambda gt11 expression system. Two monoclonal antibodies which blocked gp120-CD4 interaction were found to map to adjacent sites in the carboxy-terminal region of the glycoprotein, suggesting that this area is important in the interaction between gp120 and CD4. One nonblocking antibody was found to map to a position that was C terminal to this CD4 blocking region. Interestingly, the other nonblocking monoclonal antibodies were found to map either to a highly conserved region in the central part of the gp120 polypeptide or to a highly conserved region near the N terminus of the glycoprotein. N-terminal deletion mutants of the soluble envelope glycoprotein which lack these highly conserved domains but maintain the C-terminal CD4 interaction sites were unable to bind tightly to the CD4 receptor. These results suggest that although the N-terminal and central conserved domains of intact gp120 do not appear to be directly required for CD4 binding, they may contain information that allows other parts of the molecule to form the appropriate structure for CD4 interaction.

Animals↗
PubMed1979

Transcriptional regulation in avian erythroid cells.

Both the translational and transcriptional repertoires of nearly mature avian erythroid cells appear to be highly restricted: molecular hybridization experiments demonstrate the presence of about 4000 species of poly(A)+ nRNA and fewer than 100 species of poly(A)+ mRNA. This paper addresses the question of whether the nRNA of erythroid cells contains sequences which, although not expressed in the erythroid cells, are found on polysomes in another cell type. We have prepared cDNA from liver mRNA and have determined the representation of liver mRNA sequences in the erythroid cell nRNA. Liver mRNA consists of about 14 000 species of poly(A)+ RNA. Of these only about 100 species are detectable in erythroid cell nRNA. The vast majority of liver mRNA species is undetectable in erythroid cells; i.e., they are present at less than 0.03 copies per cell. The few species of liver mRNA that are detectable in erythroid cells are present in both the nuclear and polysomal RNA at concentrations less than 0.1 copies per cell. These data suggest that gene expression in avian erythroid cells is highly regulated at the transcriptional level.

Animals↗
PubMed1978

Lysine-rich histones and the selective digestion of the globin gene in avian red blood cells.

Deoxyribonuclease I (DNase I) is known to preferentially digest the adult globin gene sequences in avian red blood cells. We have investigated the contribution of histones H1 and H5 in maintaining the nuclease-sensitive structure about the globin genes. When the lysine-rich histones H1 and H5 were selectively removed from avian red blood cell nuclei, the rate of digestion with DNase I increased several fold. However, the globin genes in H1-and H5-depleted nuclei were still selectively digested. Since histone H1 is necessary for the higher order folding of the nucleosomes, these data suggest that DNase I recognizes an aspect of structural heterogeneity within each core particle rather than some higher order packaging of the nucleosome cores.

Animals↗
PubMed1977

Bleomycin: effects upon mammalian epidermal DNA synthesis.

The effects of bleomycin upon epithelial DNA synthesis have been evaluated in a keratinizing tissue culture line and following topical application on intact mouse epidermis. In both models, bleomycin inhibited epithelial DNA synthesis after prolonged exposure of the tissue to large doses of the polypeptide antibiotic. The effect is probably limited by the penetration of bleomycin through epithelial cell membranes. Inhibition of epidermal DNA synthesis was also observed in non-treated animals subjected to restraint and/or partial starvation. These conditions, which are commonly associated with studies of topical therapeutic agents, must, therefore, be carefully controlled.

Animals↗