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D Straus

Publications and source records attributed to D Straus.

45 records · Page 3Linked to original sources

Cell marker analysis in acute monocytic leukemias.

Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.

Esterases↗

Enhancement of carrier-mediated transport after immunologic activation of peritoneal macrophages.

Immunologically activated peritoneal macrophages from inbred mice and Hartley strain guinea pigs demonstrate a markedly greater than normal transport of 2-deoxy-D-glucose and L-leucine. The degree of nutrilite transport enhancement was greatest when animals were injected with the appropriate eliciting antigens before harvesting and also, if antigen was included in the tissue culture medium during the initial hours of in vitro culture. Enhanced hexose and amino acid uptake could also be achieved by exposure of macrophages from nonimmunized animals for 48 hr to supernatants of sensitized splenic lymphocyte cultures incubated with specific antigens. The animal systems in which this phenomenon was observed included CBA/J and C57BL/6J mice immunized with Staphylococcus aureus or sub-lethal doses of Listeria monocytogens, and the Hartley strain, albino guinea pig immunized with S. aureus or BCG. In all cases, immunization resulted in a state of delayed hypersensitivity as measured by skin testing or footpad swelling. Splenic cell supernatants contained lymphokines as detected by the presence of macrophage inhibitory factor (MIF), and by the supernatants' capacity to stimulate incorporation of 14C-glucosamine by macrophages in vitro. No increase of glucose or leucine transport by macrophages was observed in the absence of appropriate antigen stimulation in vivo or in vitro. We previously showed that a phagocytic stimulus results in a significant increase in hexose transport by normal macrophages; leucine transport by these same cells was unaltered after phagocytosis. In contrast, immunologically activated macrophages do not transport measurably more 2-deoxy-C-glucose after particle ingestion; activation or the phagocytic stimulus enhance 2-deoxy-C-glucose uptake to approximately the same extent. Analysis of nutrilite transport kinetics revealed that immunologic activation of macrophages increases the initial velocity (V1) and Vmax but does not change the Km values of hexose or amino acid transport. The kinetics of transport by the immunologically activated macrophages do not change measurably after phagocytosis. We conclude that either immunological activation or phagocytosis results in augmented 2-deoxy-D-glucose transport via identical or related mechanisms and that transport of the sugar can't be increased above that level induced by either event. The reasons why immunologic activation increases both glucose and leucine transport but phagocytosis increases only the former are not yet understood.

Animals↗

Uptake of diphtheria toxin and its fragment A moiety by mammalian cells in culture.

Evidence suggesting that diphtheria toxin reaches the cytoplasm of susceptible mammalian cells by two independent mechanisms is presented. A schematic model describing the two processes of toxin entry into the cell is developed. One process of toxin uptake considered to by physiologically significant is passage of the protein toxin through the plasma membrane. This most likely happens by binding of fragment B to receptors on the membrane and by subsequent toxin-membrane interaction so that ultimately fragment A, the enzymatically active moiety, is transported tothe cell interior. This process, which ultimately leads to cessation of protein synthesis and cell death, involves a comparatively small number of toxin molecules. A second mechanism of toxin uptake is by classical pinocytosis. The majority of toxin taken into the cell is accomplished by this process. The fate of toxin taken into HEp-2 cells via pinocytosis is proteolysis by lysosomal enzymes. Thus, such vesicle-bound toxin is ordinarily not expressed biologically. Evidence suggesting that ammonium chloride provides total protection to diphtheria toxin-susceptible cells by preventing entry of toxin by the specific receptor-associated process is also provided; data showing that the ammonium salt immobilizes bound toxin on the plasma membrane of HEp-2 cells are presented. Finally, it is suggested that actively endocytic cells such as guinea pig macrophages interact with toxin in a significantly different manner than do nonphagocytic cells.

Ammonium Chloride↗

Enriched selection of dominant mutations: histidine operator mutations.

In the course of selection of bacteria with derepressed levels of histidine biosynthetic enzymes, it was found that when mutagen-treated cells were spread on a selective medium without allowing intervening growth to occur, the frequency of operator mutants obtained was dramatically increased. This may be useful as a general enrichment for operator or other dominant mutations.

Alanine↗

Specific dimerization of the light chains of human immunoglobulin.

1. The light chains of human immunoglobulin were allowed to dimerize in vitro on removal of the dispersing agents acetic acid or urea. 2. On electrophoresis in polyacrylamide gel at pH8.8 the dimers yielded up to nine regularly spaced bands. This approximates to the number of electrophoretic components known to occur among the monomers. 3. Single electrophoretic components of the dimers were isolated from the gel, dissociated into monomers, and subjected as such to electrophoresis in urea-containing gels. Each gave two adjacent bands. 4. Similarly, after all the light chains as monomers had been subjected to electrophoresis in urea-containing gels, single electrophoretic components were isolated and allowed to dimerize. When examined now as dimers in the absence of urea, each component gave two adjacent bands. 5. These findings are explicable on the following basis. (a) The dimerization of the light chains is specific, at least inasmuch as it occurs between monomers of the same electrophoretic mobilities. (b) With the buffer constant, different light chains undergo different changes in net charge on being transferred from urea-containing to urea-free solution; in this way two different chains of the same initial charge can acquire a charge difference of 1. 6. Experiments with Bence-Jones proteins and other homogeneous light chains gave results substantiating the conclusions (a) and (b).

Blood Protein Electrophoresis↗

Cyclophosphamide/fludarabine (CF) is active in the treatment of mantle cell lymphoma.

The purpose of this study was to determine the efficacy and toxicity of the cyclophosphamide and fludarabine (CF) regimen in patients with newly diagnosed and relapsed/refractory mantle cell lymphoma (MCL). Thirty patients with pathologically confirmed MCL were treated with the CF regimen. Ten (33%) had no prior therapy, six (20%) had one previous regimen, and 14 (47%) received two or more prior regimens. Ninety cycles of CF with a median of 3 cycles/patient (range, 1-5 cycles) were administered to patients with MCL. Nine patients (30%) had a complete response (CR) and 10 (33%) had a partial response (PR) for an overall response rate (RR) of 63%. The median failure-free survival (FFS) and overall survival (OS) was 4.8 months and 17.5 months, respectively. When patients were analyzed based upon the number of previous treatments (0, 1, or 2 or more), those with no previous treatment (n=10) had an overall response of 100%, with 70% CR. The median FFS was 28.1 months and the median OS for this group has not been reached at 42.3+ months. Hematologic and infectious toxicity were the major toxicities encountered with the CF regimen. Grade 3-4 neutropenia, thrombocytopenia and anemia were seen in 50%, 37%, and 36% of patients, respectively. There were 13 episodes of grade 3 infections. There was no treatment related mortality, In conclusion, the high response rate associated with the CF regimen merits further investigation in previously untreated patients with MCL, particularly in those who are not candidates for aggressive therapy.

Aged↗

Cell-specific induction of hsp72-mediated protection by glutamine against oxidant injury in IEC18 cells.

Glutamine is a major metabolic fuel and trophic agent for intestinal epithelial cells that can enhance intestinal epithelial cell survival against oxidant and thermal stress, possibly through the induction of heat shock protein 72 (hsp72). In this study, we examined the possibility of a direct causal relationship and tissue specificity of glutamine-induced hsp72. Glutamine treatment of intestinal (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production of hsp72 in a concentration-dependent fashion, without affecting the expression of the constitutively expressed heat shock protein, hsc73. To determine the specific role that hsp72 induction by glutamine plays in resistance of IEC18 cells to oxidant injury, stable transfected cells expressing an hsp72 antisense construct were established. Although thermal induction of hsp72 was blocked only partially by the antisense construct, glutamine induction of hsp72 was completely inhibited. This was associated with a loss of the protective effects of glutamine against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in intestinal epithelial cells, which mediates cell protection against inflammation-induced stress such as oxidants.

Animals↗