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Biomedical subjects

M A Baker

Publications and source records attributed to M A Baker.

At least 37 records · Page 2Linked to original sources
PubMed1994

Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

BACKGROUND: Plasma treatment has improved the outcomes in adults with thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome (HUS). We reviewed our experience in treating unselected patients to determine the clinical outcomes and to evaluate the treatments given in addition to plasma. METHODS: A chart review of all cases of TTP and HUS in adults treated at the Toronto (Ontario) Hospital, the largest treatment center for adults with TTP-HUS in the province of Ontario, was conducted. RESULTS: Sixty-seven episodes of TTP-HUS in 52 consecutive adult patients were treated during a 12-year period. Plasma was the primary form of therapy, and most patients received plasma exchange. A complete hematologic remission was achieved in 65 of 67 episodes; however, two patients in remission were brain-dead. The time to complete remission varied from 3 to 58 days (median, 13 days). The death rate during the acute illness was 8%. Long-term sequelae included relapses, persisting renal impairment, hepatitis, and transfusion-associated acquired immunodeficiency syndrome. Relapses occurred in 21% of patients during a median follow-up of 1.1 years (range, 0.1 to 18 years). Analyses of the treatment given in addition to plasma did not demonstrate a significant benefit in terms of reducing the illness duration, mortality, or long-term sequelae. CONCLUSION: While most patients recovered from TTP-HUS, deaths still occurred and many patients suffered long-term complications. The role of the treatments given in addition to plasma is uncertain.

Adolescent↗
PubMed1994

Inhibition of UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase from acute myeloid leukaemia cells by photoreactive nitrophenyl substrate derivatives.

Cells from patients with acute myeloid leukaemia (AML) contain an abnormally high UDP-GlcNAc: Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (core 2 beta 6-Gn-T) activity. Upon UV irradiation at 350 nm, the substrate Gal beta 1-3GalNAc alpha-p-nitrophenyl acted as an effective inhibitor for this enzyme but not for several other transferases. Preincubation with Gal beta 1-3GalNAc alpha-benzyl but not GalNAc alpha-benzyl protected core 2 beta 6-Gn-T from inhibition indicating that the inhibitor is specific for the substrate binding site of core 2 beta 6-Gn-T. A number of other nitrophenyl-sugar derivatives similarly acted as inhibitors for core 2 beta 6-Gn-T. GalNAc alpha-pnp at higher concentrations also inactivated UDP-Gal: GalNAc-R beta 3-galactosyltransferase from rat liver and AML cells and inhibition could be reduced by substrate protection. These results suggest that pnp-sugar derivatives may prove useful as specific inhibitors of glycosyltransferases and as affinity labels.

Acetylgalactosamine↗
PubMed1994

Effects of estrogen on thermoregulatory evaporation in rats exposed to heat.

The purpose of this study was to determine the effects of estrogen (E2) replacement on thermoregulation in ovariectomized rats exposed to heat. Female Sprague-Dawley rats were ovariectomized and splenectomized and implanted with a temperature-sensitive transmitter. Each rat was studied when E2 treated (after an E2 pellet implant) and untreated. Animals were divided into two groups with opposite order of treatment and were studied over a 9-wk period. Measurements of body core temperature (Tc) and evaporative water loss (EWL) were made on unrestrained animals resting at 38 degrees C air temperature. E2-treated animals increased EWL at all levels of Tc, reduced the threshold Tc for onset of saliva spreading, and regulated Tc at a lower level during heat exposure. E2 treatment elevated plasma E2 and reduced hematocrit but did not affect plasma osmolality. These effects of E2 on evaporative cooling and Tc in heat-stressed rats are similar to those that have been reported in human females. The mechanisms of the thermoregulatory effects of E2 remain to be studied.

Animals↗
PubMed1993

Anticancer efficacy of Magainin2 and analogue peptides.

Linear helical channel-forming peptides structurally similar to the Xenopus-derived antibiotic, Magainin2-amide, were synthesized. Because activity resides in the physicochemical properties of the peptides, an all-D-amino acid as well as an all-L-amino acid sequence were tested for anticancer activity. In vitro activity against carcinoma cells and in vivo efficacy against four murine ascites tumors were determined. The novel peptides proved to have enhanced potency in vitro and in vivo as compared to the parent compound. The 50% inhibitory concentrations against A549 cells for the all-D, the all-L, and Magainin2 were 6, 10, and 110 micrograms/ml, respectively. All three peptides had activity against P388 leukemia, S180 ascites, and a spontaneous ovarian tumor when injected i.p. Increase in life span of over 100% was produced for the analogues in the latter two models. The maximally effective concentrations for the analogues were 20 to 25 mg/kg while Magainin2 required 50-60 mg/kg for in vivo efficacy. The all-D-amino acid peptide, MSI-238, proved as effective as doxorubicin at a more advanced stage of the ovarian tumor and this activity may be attributed to its resistance to proteolytic degradation. Therefore, this class of amphiphilic alpha-helical cationic peptides has potential in the peritoneal treatment of ovarian cancer.

Amino Acid Sequence↗
PubMed1993

Processing O-glycan core 1, Gal beta 1-3GalNAc alpha-R. Specificities of core 2, UDP-GlcNAc: Gal beta 1-3 GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase.

To elucidate control mechanisms of O-glycan biosynthesis in leukemia and to develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Gal beta 1-3GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (EC 2.4.1.102; core 2 beta 6-GlcNAc-T) and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase (EC 2.4.99.4; alpha 3-SA-T), two enzymes that are significantly increased in patients with chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic differences for the core 2 beta 6-GlcNAc-T activity; core 2 beta 6-GlcNAc-T from mucin secreting tissue (named core 2 beta 6-GlcNAc-T M) is accompanied by activities that synthesize core 4 [GlcNAc beta 1-6(GlcNAc beta 1-3)GalNAc-R] and blood group I [GlcNAc beta 1-6(GlcNAc beta 1-3)Gal beta-R] branches; core 2 beta 6-GlcNAc-T in leukemic cells (named core 2 beta-GlcNAc-T L) is not accompanied by these two activities and has a more restricted specificity. Core 2 beta 6-GlcNAc-T M and L both have an absolute requirement for the 4- and 6-hydroxyls of N-acetylgalactosamine and the 6-hydroxyl of galactose of the Gal beta 1-3GalNAc alpha-benzyl substrate but the recognition of other substituents of the sugar rings varies, depending on the tissue. alpha 3-sialyltransferase from human placenta and from AML cells also showed distinct specificity differences, although the enzymes from both tissues have an absolute requirement for the 3-hydroxyl of the galactose residue of Gal beta 1-3GalNAc alpha-Bn. Gal beta 1-3(6-deoxy)GalNAc alpha-Bn and 3-deoxy-Gal beta 1-3GalNAc alpha-Bn competitively inhibited core 2 beta 6-GlcNAc-T and alpha 3-sialyltransferase activities, respectively.

Animals↗
PubMed1993

The effects of noise and speech on cognitive task performance.

In the present study, which is based on Loeb's 1986 analysis, we used five levels of noise that varied in intermittency and meaningfulness, crossed with sex of subject and time of day. Memory tasks that differed in their reliance upon long-term, short-term free recall, and sequential short-term memory were used as dependent variables. A total of 160 subjects, 20 per block, participated in the 2 x 2 x 5 (Sexes x Time of Day x Noise Conditions) experimental design. Results support the prediction that white noise enhances performance on tasks with sequential short-term memory demands (anagrams: p < .05; random letter generation: p < .002). We found complex interactions by sex of subject, time of day, and type of noise for those tasks that placed a heavy demand on short-term working memory, i.e., complex sorting (Noise x Sex, p < .05) and random letter generation (Sex x Noise x Time of Day, p < .05). The predicted effects for anagrams were not supported. These results call into question previous generalizations about the effects of noise on performance (Broadbent, 1978; Dornic, Sarnelid, Larson, Svensson, & Fernaeus, 1982; Poulton, 1977), alternative interpretations are presented.

Acoustic Stimulation↗
PubMed1993

Selective brain cooling in goats: effects of exercise and dehydration.

1. Measurements of brain and central blood temperature (Tbr and Tbl), metabolic rate (MR) and respiratory evaporative heat loss (REHL) were made in trained goats walking on a treadmill at 4.8 km h-1 at treadmill inclines of 0, 5, 10, 15 and 20% when they were fully hydrated and at 0% when they had been deprived of water for 72 h. 2. In hydrated goats, exercise MR increased progressively with increasing treadmill incline. Both Tbl and Tbr rose during exercise, but Tbl always rose more than Tbr, and selective brain cooling (SBC = Tbl - Tbr) increased linearly with Tbl. Significant linear relationships were also present between REHL and Tbl and between SBC and REHL. Neither the slope of the regression relating SBC to Tbl nor the threshold Tbl for onset of SBC was affected by exercise intensity. Manual occlusion of the angularis oculi veins decreased SBC in a walking goat, while occlusion of the facial veins increased SBC. 3. Dehydrated goats had higher levels of Tbl, Tbr and SBC during exercise, but the relationship between SBC and Tbl was the same in hydrated and dehydrated animals. In dehydrated animals, REHL at a given Tbl was lower and SBC was thus maintained at reduced rates of REHL. 4. It is concluded that SBC is a linear function of body core temperature in exercising goats and REHL appears to be a major factor underlying SBC in exercise. The maintenance of SBC in spite of reduced REHL in dehydrated animals could be a consequence of increased vascular resistance in the facial vein and increased flow of cool nasal venous blood into the cranial cavity.

Animals↗
PubMed1993

Extensive cutaneous plasmacytomas.

An unusual case of extensive cutaneous and subcutaneous plasmacytomas is reported. Breast involvement was also a feature in this individual. The relevant literature relating to this unusual presentation of myeloma is reviewed.

Breast Neoplasms↗
PubMed1992

Effects of hydration state on exercise thermoregulation in goats.

In this study we asked how exercise affects sweating and panting and how dehydration affects exercise thermoregulation in goats. Six goats exercised (4.8 km/h, +10% slope) for 45 min at an ambient temperature of 35 degrees C when hydrated and after 48 h without drinking water. Hematocrit (Hct), plasma protein concentration (PP), and plasma osmolality were elevated by dehydration (P less than or equal to 0.05). Hct and plasma osmolality increased further during exercise in hydrated and dehydrated animals (P less than or equal to 0.05), but PP rose only in hydrated goats (P less than or equal to 0.05). The increase in central blood temperature (Tbl) during exercise was greater in dehydrated than in hydrated animals (P less than or equal to 0.001). Evaporation by panting (Eresp) and sweating were linearly related to Tbl during exercise. The relationship between Eresp and Tbl was not affected by dehydration, but dehydrated animals showed an increased Tbl threshold for sweating. We postulate that the elevation in threshold for sweating may be due primarily to increased body fluid osmolality, and that hypovolemia may not play a significant role in the thermoregulatory adjustments to exercise in dehydrated goats.

Animals↗
PubMed1992

Activated protein kinase C directly phosphorylates the CD34 antigen in acute lymphoblastic leukemia cells.

The precursors of all blood cell lineages are contained within the 1-3% of bone marrow cells which express the CD34 antigen, and this population can reconstitute the hematopoietic system of lethally irradiated animals and humans. A potential regulatory role for the CD34 antigen in progenitor cell function and differentiation was indicated by our recent findings that the CD34 antigen can be phosphorylated in vivo to high stoichiometry in primitive CD34+ cell-lines by activated protein kinase C. To exclude the possibility that these effects were restricted to cell-lines, we have performed similar experiments on fresh cells from a patient with drug-resistant acute lymphoblastic leukemia. Similar to our previous findings, we found the CD34 antigen to be hyperphosphorylated in lymphoblasts labeled in the presence of active phorbols. The same peptides which were hyperphosphorylated in phorbol-stimulated cell-lines were also phosphorylated in phorbol-stimulated lymphoblasts. These data indicate that CD34 is a substrate molecule for PKC in fresh CD34+ lymphoblasts and underline the role of modulators of PKC activity in the biology of primitive leucocytes.

Adult↗
PubMed1992

Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica glycoprotease: implications for purification of CD34-positive progenitor cells.

Our previous studies have shown that a unique glycoprotease from Pasteurella haemolytica specifically cleaves only proteins containing sialylated O-linked glycans. The hematopoietic progenitor cell antigen, CD34, which is heavily glycosylated with both N- and O-linked glycans, is readily cleaved by this protease. In this study, we demonstrate that the epitopes detected by five of the seven CD34 monoclonal antibodies are removed by the glycoprotease. The differential sensitivity of the CD34 epitopes to cleavage with either neuraminidase and/or glycoprotease establishes three classes of epitopes: 1) (class I) those identified by MY10, B1.3C5, 12.8, and ICH3 that are differentially affected by neuraminidase and removed by the glycoprotease; 2) (class II) the epitope detected by QBEND 10 that is removed only by the glycoprotease; and 3) (class III) those identified by TUK3 and 115.2 that are not removed by either enzyme. Cleavage of the 110-kd CD34 structure by the glycoprotease generates a major cell-bound fragment of about 75 kd, identified by the class III antibodies. We have also used the enzyme to improve the rapid recovery of CD34+ cells selected by immunomagnetic affinity techniques. In a preclinical model, we separated CD34+ KG1 cells with high yield (90%-95%) and high purity (94%-98%) from sham mixtures containing 50% CD34- cells. We also separated CD34+ blast cells from a patient in megakaryoblastic crisis of chronic myelogenous leukemia. In this case, the purity and yield were 93% and 94%, respectively. Enzyme treatment had no detrimental effect on cell viability, and the treated cells showed a normal quantitative expression and distribution of CD34 antigen as assessed with class III antibodies. We conclude that the P. haemolytica glycoprotease has potential to improve the isolation, from human bone marrow, of primitive hematopoietic cells that carry the CD34 antigen.

Antigens, CD↗
PubMed1991

Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy.

Four well defined multidrug-resistant cell lines and their drug-sensitive counterparts were examined for intracellular distribution of daunorubicin (DNR) by laser-assisted confocal fluorescence microscopy: P-glycoprotein-negative HL-60/AR cells, and P-glycoprotein-positive P388/ADR, KBV-1, and MCF-7/ADR cells. Both drug sensitive cell lines (HL-60/S, P388/S, KB3-1, and MCF-7/S) and drug-resistant cell lines (HL-60/AR, P388/ADR, KBV-1, and MCF-7/ADR) exposed to DNR showed a similar rapid distribution of drug from the plasma membrane to the perinuclear region within the first 2 min. From 2-10 min, the drug sensitive HL-60/S, P388/S, and MCF-7/S cells redistributed drug to the nucleus and to the cytoplasm in a diffuse pattern. In contrast, drug-resistant HL-60/AR, P388/ADR, and MCF-7/ADR redistributed DNR from the perinuclear region into vesicles distinct from nuclear structures, thereby assuming a "punctate" pattern. This latter redistribution could be inhibited by glucose deprivation (indicating energy dependence), or by lowering the temperature of the medium below 18 degrees C. The differences in distribution between sensitive and resistant cells did not appear to be a function of intracellular DNR content, nor the result of drug cytotoxicity. Drug-sensitive KB3-1 and -resistant KBV-1 cells did not fully follow this pattern in that they demonstrated an intracellular DNR distribution intermediate between HL-60/S and HL-60/AR cells with both "punctate" and nuclear/cytoplasmic uptake sometimes in the same cell. These data indicate that the intracellular distribution of DNR is an important determinant of drug resistance regardless of the overexpression of P-glycoprotein. The intracellular movement of drug requires the presence of glucose and a temperature above 18 degrees C, implicating energy-dependent processes and vesicle fusion in the distribution process. This intracellular transport of DNR away from the nucleus in multidrug-resistant cells may protect putative cell targets such as DNA against drug toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Biosynthesis of O-glycans in leukocytes from normal donors and from patients with leukemia: increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3 GalNAc alpha-R (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells.

We have studied the biosynthesis of altered O-glycan structures on leukocytes from patients with chronic myelogenous leukemia and with acute myeloblastic leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Gal beta 1-3GalNAc alpha-R (sialic acid to galactose) alpha(2-3)-sialytransferase (EC 2.4.99.4) is increased in leukocytes from patients with chronic myelogenous leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg, and R. N. Taub, Cancer Res., 47: 2763-2766, 1987) and with AML (A. Kanani, D. R. Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R. N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003-5007, 1990). This increased activity may in part be responsible for the hypersialylation observed in leukemic leukocytes; however, hypersialylation may also be due to changes in underlying O-glycan structures. To test this hypothesis, we have assayed in normal human granulocytes and leukemic leukocytes several glycosyltransferases involved in the synthesis and elongation of the four common O-glycan cores. UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta(1-6)-GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAc beta 1-6[Gal beta 1-3]GalNAc alpha), is significantly elevated in chronic myelogenous leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human granulocytes. Neither normal nor leukemic cells show detectable activities of GlcNAc transferases which synthesize O-glycan core 3 (GlcNAc beta 1-3GalNAc-R) and core 4 (GlcNAc beta 1-6[GlcNAc beta 1-3] GalNAc-R) or the blood group I structure. The beta 3-GlcNAc transferase which elongates core 1 and core 2 was found at low levels in normal granulocytes but was not detectable in leukemic cells. The beta 3-GlcNAc transferase and beta 4-Gal transferase involved in poly-N-acetyllactosamine synthesis, as well as the beta 3-Gal transferase synthesizing core 1 (Gal beta 3 GalNAc), were present in all samples but were significantly increased in patients with AML. The observed changes are consistent with hypersialylation in leukemia.

Chromatography, High Pressure Liquid↗
PubMed1991

Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets.

We have identified and biochemically characterized an antigen, 8A3, which is expressed on activated T lymphoblasts and activated platelets. Monoclonal antibodies to 8A3 were raised against the primitive lymphoid/myeloid cell line KG1a and additionally bound to the erythroleukemia-derived cell line HEL, whilst exhibiting little or no reactivity with a panel of other hematopoietic cell lines. The 8A3 antigen was expressed on poorly differentiated T-cell leukemias and on phytohemagglutinin-activated T-cells maintained in interleukin-2 (7,000 sites/cell). This antigen, though not detected on resting platelets, was expressed on thrombin-activated platelets (2,000 sites/platelet). Antibodies to 8A3 identified polypeptides of Mr 170,000 and 150,000 in lysates of surface-iodinated KG1a cells, T lymphoblasts, and activated platelets under both reducing and nonreducing conditions. However, peptide mapping and susceptibily to glycosidases indicated that the 8A3 antigen was a monomeric glycoprotein of Mr 170,000 which contained two N-linked endoglycosidase H-sensitive glycans, and that the Mr 150,000 structure was derived from it by proteolytic degradation. The 8A3 antigen was not detectably phosphorylated in KG1a cells in vivo, nor did immune complexes containing it exhibit kinase activity in vitro. Structural and serologic characteristics of the 8A3 antigen indicate that it is different from other previously described leukocyte activation antigens including transferrin receptors, interleukin-2 receptors, members of the integrin family of adhesion molecules, or "restricted" members of the leukocyte-common antigen/CD45 cluster. Furthermore, the 8A3 antigen does not appear to be related to the other previously described activation-specific platelet molecule, GMP140/PADGEM. This antibody may be useful in monitoring T-cell activation status in some clinical situations and in characterizing clinically relevant activation-associated platelet membrane alterations.

Animals↗
PubMed1991

Genotoxic effects of gossypol acetic acid on cultured murine erythroleukemia cells.

Gossypol acetic acid, a male anti-fertility drug, was evaluated for its effects on cell multiplication, chromosomes, scheduled and unscheduled DNA synthesis, and the surface ultrastructure in cultured murine erythroleukemia cells (clone 6A11A). Gossypol treatments inhibited cell multiplication at 10 and 20 micrograms/ml concentrations and this inhibitory effect increased with elevated dosage and prolonged treatment. Gossypol significantly depressed the mitotic index but did not alter chromosome numbers or increase the frequency of chromosomal structural abnormalities. Cell fraction techniques revealed that gossypol induced a negative effect on cellular DNA synthesis at concentrations as low as 3.3 micrograms/ml after 24 hr of treatment. The number of cells undergoing DNA synthesis decreased with increasing dosages and durations of drug exposure. An unscheduled DNA synthesis assay (UDS) found gossypol to be an active UDS-inducing agent at certain dose levels and treatment times, as measured by increase in net nuclear gain and percentage of UDS cells (ANOVA, Bonferroni test, P less than 0.05). A scanning electron microscope study revealed that 10 micrograms/ml treatment with gossypol caused changes in mouse erythroleukemia cell surface ultrastructure characterized by general balding and the appearance of holes, often after 48 hr of treatment.

Animals↗
PubMed1991

Membrane glycoprotein changes associated with anthracycline resistance in HL-60 cells.

The glycoproteins on the surface of HL-60/S wild-type, drug-sensitive human leukemia cells and HL-60/AR anthracycline-resistant cells which do not overexpress the P-glycoprotein, were characterized by labeling with [35S]-methionine, NaB[3H4], phosphorus 32, or sodium iodide I 125. HL-60/S and HL-60/AR cell lysates and membrane fractions tagged with [35S]-methionine or phosphorus 32 showed no significant differences in their protein patterns as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by autoradiography. HL-60/S cells labeled with NaB[3H4] yielded glycoproteins that were smeared predominantly in the molecular-weight range of 210,000 and 160,000 Da, with pI values ranging between pH 4 and pH 4.4. In contrast, NaB[3H4]-labeled HL-60/AR cells showed 7-8 discrete glycoproteins within a molecular-weight range of 170,000 and 140,000 Da, with pI values also ranging between pH 4 and pH 4.4. In addition, [3H]-glucosamine incorporation into HL-60/S and HL-60/AR cells revealed that the latter showed lower uptake of [3H]-glucosamine than did the former. Following treatment with tunicamycin, [3H]-glucosamine uptake in HL-60/S cells decreased, whereas that in HL-60/AR cells remained unchanged. Surface-membrane radioiodination of HL-60/S and HL-60/AR cells showed two distinct protein electrophoretic patterns, with differences being observed in both the high-(220-95 kDa) and low-molecular-weight ranges (21 kDa). Flow cytometric analysis of HL-60/S and HL-60/AR cells using myeloid and lymphoid antigen-specific antibodies demonstrated no antigenic differences between HL-60/S and HL-60/AR cells. HL-60/S cells incubated in the presence of tunicamycin, an inhibitor of N-linked glycosylation, or the protein kinase C agonist phorbol 12-myristate 13-acetate (PMA) developed a glycoprotein pattern similar to that observed in HL-60/AR cells. In addition, tunicamycin treatment of HL-60/S cells decreased daunorubicin (DNR) retention and altered its intracellular distribution as compared with that in HL-60/AR cells. These data indicate that HL-60/AR cells do not possess either de novo or amplified high-molecular-weight surface-membrane proteins; instead, existing proteins are hypoglycosylated. These results also show that HL-60/AR cells exhibit the multidrug-resistant phenotype in association with altered membrane glycoproteins of both high (220-95 kDa) and low molecular weight (21 kDa), but without overexpression of the P-glycoprotein. Furthermore, in HL-60/S cells, the multidrug-resistant phenotype is partially inducible by inhibition of N-linked glycosylation of cell-surface proteins.

Antibiotics, Antineoplastic↗