The immunophenotype, rearrangements of T cell receptor (TCR) gamma and delta chain genes as well as the immunoglobulin heavy chain (IgH) gene were studied in 37 cases of morphologically defined acute lymphoblastic leukemia (ALL). According to the expression of differentiation antigens, 8 cases were classified as T-ALL, 26 B lineage ALL, 2 acute undifferentiated leukemia (AUL) and myeloid phenotype. An order of TCR gene rearrangements was observed in T-ALL, with the rearrangement of delta gene preceding that of gamma gene. Both genes were also found frequently rearranged and/or deleted in high proportions of the ALL of B cell lineage. However, the patterns of gene rearrangements were somewhat different between the T and B lineage ALLs. In contrast, the IgH gene rearrangements were observed only in the B lineage ALL. The immunogenotype analysis of ALL proved to be a useful marker of the clonality and provided us with important information on early human lymphoid differentiation. We conclude that the determination of TCR gamma gene V-J junctional sequence can be used as clonal marker for detecting the minimal residual disease during clinical remission.

Adolescent↗

PubMed1994

Poor response to all-trans retinoic acid therapy in a t(11;17) PLZF/RAR alpha patient.

All-trans retinoic acid (ATRA) is a potent inducer of differentiation and cell death in malignant cells. Its effect is known to be mediated through binding to specific nuclear (RARs and RXRs) or cytoplasmic (CRABP) proteins. ATRA is strikingly effective in acute promyelocytic leukemia (the AML3 subtype) inducing a high incidence of complete remissions. Paradoxically, most AML3 cells harbor an abnormal retinoic acid receptor (PML/RAR alpha) resulting from the t(15;17) translocation. Though few AML3 patients do not respond to ATRA therapy, individualization of these cases is of practical importance. Recently the RAR alpha gene has been demonstrated to be involved in a novel fusion transcript (PLZF/RAR alpha) through a t(11;17) translocation. We describe here the second case of such a patient with a t(11;17)-PLZF/RAR alpha leukemic clone. Southern analysis revealed that the breakpoint in the RAR alpha gene was within the second intron (as for PML/RAR alpha) and the intron separating the second and third zinc finger of the PLZF gene. In vitro, the leukemic cells did not show increased NBT reduction or loss of self-renewal after incubation with ATRA. After therapy with ATRA, only partial remission was obtained. These results suggest that the t(11;17) (PLZF/RAR alpha) case of this study was less responsive to ATRA therapy than t(15;17) (PML/RAR alpha) cases and raises the question of the definition of this novel AML subtype.

Aged↗

PubMed1993

Active oxygen species in the induction of plant systemic acquired resistance by salicylic acid.

A complementary DNA encoding a salicylic acid (SA)-binding protein has been cloned. Its properties suggest involvement in SA-mediated induction of systemic acquired resistance (SAR) in plants. The sequence of the protein is similar to that of catalases and the protein exhibits catalase activity. Salicylic acid specifically inhibited the catalase activity in vitro and induced an increase in H2O2 concentrations in vivo. H2O2 or compounds, such as SA, that inhibit catalases or enhance the generation of H2O2, induced expression of defense-related genes associated with SAR. Thus, the action of SA in SAR is likely mediated by elevated amounts of H2O2.

Amino Acid Sequence↗

PubMed1993

The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains.

We show here that, in addition to generating an increase in DNA binding efficiency, heterodimerization of retinoid X receptor (RXR) with either retinoic acid receptor (RAR) or thyroid hormone receptor (TR) alters the binding site repertoires of RAR, RXR and TR homodimers. The binding site specificities of both homo- and heterodimers appear to be largely determined by their DNA binding domains (DBDs), and are dictated by (i) homocooperative DNA binding of the RXR DBD, (ii) heterocooperative DNA binding of RXR/RAR and RXR/TR DBDs, and (iii) steric hindrance. No homodimerization domain exists in the DBDs of TR and RAR. The dimerization function which is located in the ligand binding domain further stabilizes, but in general does not change, the repertoire dictated by the corresponding DBD(s). The binding repertoire can be further modified by the actual sequence of the binding site. We also provide evidence supporting the view that the cooperative binding of the RXR/RAR and RXR/TR DBDs to directly repeated elements is anisotropic, with interactions between the dimerization interfaces occurring only with RXR bound to the 5' located motif. This polarity, which appears to be maintained in the full-length receptor heterodimers, may constitute a novel parameter in promoter-specific transactivation.

Amino Acid Sequence↗

PubMed1993

Health risk in hospitals through airborne allergens for patients presensitised to latex.

Two nurses had to stop practicing because of severe work-related allergic respiratory or systemic symptoms. Both developed similar symptoms within a short time when they attended hospitals as outpatients or visitors or consulted a doctor or dentist, even when they had no direct contact with latex articles. The airborne latex allergen concentration in one room that induced symptoms was 128 ng per m3. In skinprick tests both women showed positive reactions to the phosphated cornstarch powder used to prevent latex gloves sticking together, but only when the powder had been in contact with latex. This powder seems a likely vehicle for the airborne latex allergen.

Adult↗

PubMed1993

Identification of masked and variant Ph (complex type) translocations in CML and classic Ph in AML and ALL by fluorescence in situ hybridization with the use of bcr/abl cosmid probes.

In the present study, three chronic myelogenous leukemia (CML) patients with variant Philadelphia (Ph) chromosomes (complex types), two CML patients with a masked Ph, one case with Ph positive acute lymphocytic leukemia (ALL), and one with Ph positive acute myelocytic leukemia (AML) were analyzed by standard cytogenetic techniques (G-banding), Southern blot studies, and fluorescence in situ hybridization (FISH) procedures using probes from portions of the bcr and abl genes. It has been previously shown that this FISH approach could detect the bcr/abl fusion event in CML patients with classic or variant (simple type) Ph. Our results demonstrate that this FISH assay can also detect the bcr/abl fusion status in CML patients with masked or variant (complex type) Ph chromosomes and in some patients with Ph positive ALL or AML.

Adult↗

PubMed1993

t(8;21) prior to acute leukemia.

A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.

Chromosomes, Human, Pair 21↗

PubMed1993

Purification and characterization of a soluble salicylic acid-binding protein from tobacco.

Previously, we identified a soluble salicylic acid (SA)-binding protein (SABP) in tobacco whose properties suggest that it may play a role in transmitting the SA signal during plant defense responses. This SA-binding activity has been purified 250-fold by conventional chromatography and was found to copurify with a 280-kDa protein. Monoclonal antibodies capable of immunoprecipitating the SA-binding activity also immunoprecipitated the 280-kDa protein, indicating that it was responsible for binding SA. These antibodies also recognized the 280-kDa protein in immunoblots of the partially purified SABP fraction or the crude extract. However, when the crude extract was prepared in the presence of antioxidants, only a 57-kDa protein was recognized. Since the SABP has a native molecular mass of 240 kDa, it appears that the SABP is a complex which contains a 57-kDa subunit and perhaps one or more additional proteins which are covalently crosslinked in the absence of antioxidants. The ability of a variety of phenolic compounds to compete with SA for binding to the SABP was both qualitatively and quantitatively correlated with their biological activity in inducing defense-related genes. Moreover, the inducibility of the pathogenesis-related (PR)-1 genes by SA was proportional to the abundance of the SABP in different organs. These correlations are consistent with a role for the SABP in perceiving and transducing the SA signal in plant defense.

Antibodies, Monoclonal↗

PubMed1993

Crystallization and preliminary crystallographic studies of human beta-glucuronidase.

Crystals of human beta-glucuronidase have been obtained by the vapor diffusion method, using 2-methyl-2,4-pentanediol as a precipitant. The crystals belong to the orthorhombic space group P222(1), with cell dimensions a = 134.5 A, b = 95.1 A, c = 124.4 A. The unit cell contains two copies of the tetrameric enzyme. Complete native data have been collected to a resolution of 2.6 A.

Glucuronidase↗

PubMed1993

Identification of a scavenger receptor in rat luteal cells which recognizes chemically modified lipoproteins and mediates the uptake of cholesterol for steroidogenesis.

The presence of the acetyl low density lipoprotein (acetyl-LDL), or scavenger receptor, which binds modified forms of LDL, was examined in rat luteal cells. Acetyl-LDL supported progesterone production by dispersed rat luteal cells at least equal to that of the native LDL under basal conditions and in the presence of human chorionic gonadotropin (hCG). The acetyl-LDL-supported progesterone production was stimulated by hCG and dibutyryl cAMP in a concentration-dependent manner. Studies on acetyl-LDL binding to ovarian plasma membranes revealed a single class of binding sites with high affinity. The binding is specific in that unlabeled acetyl-LDL and fucoidin, a known competitor for binding to scavenger receptor, were effective competitors, while native LDL was not. Furthermore, degradation of 125I-acetyl-LDL by cultured luteal cells was inhibited by unlabeled acetyl-LDL and fucoidin but not native LDL. The experiments on cross-competition between acetyl-LDL and tetranitromethane-modified high density lipoprotein (TNM-HDL) indicated that TNM-HDL is also recognized as a ligand by this receptor. In addition, in vivo pretreatment of rats with hCG resulted in induction of acetyl-LDL binding activity of ovarian plasma membranes in a time-dependent manner when compared to saline injected controls. The increase in binding activity was due to an increase in the number of binding sites rather than to a change in the binding affinity. In conclusion, this study demonstrates that, in addition to receptor-mediated LDL and HDL pathways, rat luteal cells possess a scavenger receptor pathway, which recognizes TNM-HDL as well as acetyl-LDL. This receptor may play an important role in the uptake and utilization of modified lipoprotein-associated cholesterol by luteal cells.

Animals↗

PubMed1993

Local heating in mesoscopic systems.

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Journal Article↗

PubMed1993

[Chemofiltration for locally advanced cancer].

In chemofiltration a large dose of a cytotoxic drug is infused into an artery supplying a cancerous area, thus limiting systemic toxicity. The venous return from the area is pumped into a chemofiltration unit at 750 ml/min and the drug is filtered out of the blood, which is then returned to the systemic circulation. Of 22 patients with locally advanced cancer, systemic chemotherapy had failed in 63%. 9 of them underwent chemofiltration of the liver for advanced metastatic cancer of the colon (4 cases), rectum (2), breast (2) and ovaries (1); and 13 underwent chemofiltration of the pelvis for advanced cancer of the rectum (5), malignant melanoma (5), ovaries (1), cervix uteri (1) and vulva (1). The following drugs were used: 5-FU (750 mg/m2/10 min) and mitomycin-C (30 mg/m2/10 min) for colorectal, ovarian and breast carcinomas; melphelan (1 mg/kg/20 min) or cisplatinum (200 mg/m2/30 min) for malignant melanoma or ovarian carcinoma; mitomycin-C or bleomycin (50 mg/m2/10 min) for carcinoma of the cervix or vulva. 1 patient with extensive liver metastases died of respiratory failure 28 days after the procedure. Surgically related complications occurred in 16% and included wound hematoma (2 cases), infection (1) and venous thrombosis (1). Drug-related complications occurred in 50%, and included transient leukopenia (9), mild renal failure (1), hair loss (2) and prolonged paralytic ileus (1). Partial remission was observed in 10/20 patients who had measurable disease. Time to progression was 5.4 months (range: 4 weeks to 20 months). Stabilization of disease occurred in 7/20 (35%), while in 3 the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

PubMed1993

Energies of quark-antiquark systems, the Cornell potential, and the spinless Salpeter equation.

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Journal Article↗

PubMed1993

Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis.

Amino acid sequence comparisons reveal that tyrosine-152 and lysine-156 of Drosophila alcohol dehydrogenase (ADH) are conserved in homologous dehydrogenases, suggesting that these residues are important in catalysis. To test this hypothesis, we used site-directed mutagenesis to substitute tyrosine-152 with phenylalanine, histidine, or glutamic acid or to substitute lysine-156 with isoleucine. All of these mutants are catalytically inactive. Two mutants were active: A cysteine mutation of tyrosine-152 has 0.25% of wild-type ADH activity, while an arginine substitution of lysine-156 retains 2.2% of wild-type ADH activity. Kinetic analysis shows that the cysteine mutant increases Km(ethanol) 56-fold and Km(propan-2-ol) 100-fold, while Km(NAD) values are essentially unaltered. The arginine mutant also shows the significant enlargement of Km(ethanol), but not of Km(NAD). Furthermore, the cysteine mutant and arginine mutant have different substrate specificity and behave differently on competitive inhibition than wild-type ADH. These results suggest that both tyrosine-152 and lysine-156 have essential roles in catalysis by Drosophila ADH.

1-Propanol↗