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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 397 records · Page 22Linked to original sources

Basidiomycete allergy: what is the best source of antigen?

Skin prick test activity and antigenicity of extracts of in vitro growth of the Basidiomycete Pleurotus ostreatus (PO) were compared to extracts of spores from PO growing in the wild. Patients demonstrated significant differences in skin test reactivity to the PO extracts. Some reacted only to in vitro growth extracts, others only to the spore extracts and 1 patient to all extracts. Further studies analyzed antigens present in all extracts with rabbit antisera to PO. Common as well as unique antigens were present in the spore extracts as compared to those from in vitro preparations. The fact that spores contain unique antigens suggests that basidiospores may be the best source of relevant allergens for clinical studies.

Antigens, Fungal↗

Impairment of cellular immunity and OKT4 lymphocytes in symptom-free hemophiliacs with antibodies to human T leukemia virus III (HTLV III).

Antibodies against the human T-leukemia virus III (HTLV III) were detected by immunofluorescence in the sera of 17 out of 48 hemophiliacs (35.4%) without AIDS or ARC, frozen in 1983-84. Immunological data collected at that time were re-evaluated by separating HTLV III-positive and negative subjects. HTLV III positive patients had significantly reduced OKT4 cells (both in %: 26.1 +/- 10.9 vs 41.2 +/- 15.2; P less than 0.01; and in absolute numbers: 469 +/- 291 vs 1,038 +/- 541; P less than 0.005) and OKT3 lymphocytes (in absolute numbers: 1,234 +/- 550 vs 2,050 +/- 1,067; P less than 0.01). Subpopulations identified by other monoclonal reagents (OKT8, Leu 7, OKM1, anti-Tac) showed no significant differences between the two groups. Patients subsequently found to be seropositive had significantly more frequent anergy to skin tests to recall antigens and often an impairment of in vitro response to phytohemagglutinin A. Despite these relevant defects of some tests of cell-mediated immunity, in HTLV III-positive cases no clinical progression toward AIDS-related complex was observed in a mean period of follow-up of more than 1.5 years.

Acquired Immunodeficiency Syndrome↗

Relevance of 3A1 monoclonal antibody in the diagnosis of T-cell acute lymphoblastic leukemia.

Two childhood and three adult patients with acute lymphoblastic leukemia (ALL) are described. The identification of the T-cell nature of their ALL-cells was based on the positivity of their blasts with 3A1 monoclonal antibody which recognizes immature and mature T-cells. Four tested cases showed a terminal deoxynucleotidyl transferase (TdT) positivity, and four out of five were acid phosphatase (AcP)-positive. Cells from all cases were characterized with a panel of 15 monoclonal antibodies: 3A1 was constantly positive; J5, BA-1, OKT6, Leu-7, and other monoclonal antibodies reactive with T-cells (OKT3, OKT4, OKT8, OKT11, Leu-1, T65) were negative; only two cases had weak positivity with OKT11 and Leu-1, respectively; cells from all cases were surface immunoglobulin (SIg)-negative; three out of the five cases were OKT10-positive and three OKT9-positive; none of the cases reacted with OKM1 and anti-HLA-DR. Our findings indicate that the use of 3A1 monoclonal antibody was helpful in the recognition of individual cases of T-ALL otherwise considered as unclassified-ALL (U-ALL). 3A1 and an anti-common ALL Antigen (CALLA) reagent may represent the essential monoclonal antibodies to be used for screening ALL cells.

Adult↗

Evidence for absence of toxicity of T101 immunotoxin on human hematopoietic progenitor cells prior to bone marrow transplantation.

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show that conditions previously defined to produce high tumor cell killing, i.e., a 20-hr incubation at 37 degrees in the presence of T101-ricin A-chain immunotoxin up to 10(-7) M in a 10 mM ammonium chloride solution, do not affect the in vitro proliferative capacity of human hematopoietic stem cells studied by means of semisolid medium cultures (granulocyte-macrophage progenitors, burst-forming units-erythrocyte) and continuous liquid cultures (pre-granulocyte-macrophage progenitors). Therefore, autologous bone marrow transplantation with T101-ricin A-chain immunotoxin-treated graft should be feasible.

Antibodies, Monoclonal↗

Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T 101 in the treatment of leukemia and lymphoma: first clinical observations.

Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.

Adolescent↗

Septic arthritis of the hip joint: sonographic and CT findings.

Two patients with acute bacterial arthritis of the hip joint were suspected clinically to have a psoas abscess. For this reason a computed tomographic scan of the abdomen and pelvis (two patients) and ultrasonography (one patient) were requested. These scans showed no evidence of an abscess in the abdominal cavity nor retroperitoneum but did demonstrate a hip joint effusion which was compatible with septic arthritis.

Adolescent↗

Termination sites of the in vitro DNA synthesis on single-stranded DNA photosensitized by promazines.

Bacteriophage phi X174 and M13 mp9 single-stranded DNA molecules were primed either with restriction fragments or synthetic primers and irradiated with near UV light in the presence of promazine derivatives. These DNAs were used as template for in vitro complementary chain synthesis by Escherichia coli DNA polymerase I large fragment. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis of the synthesis products and localized by comparison with a standard dideoxy sequencing pattern. More than 90% of the chain terminations were mapped exactly one nucleotide before a guanine residue. In addition, photoreaction was shown to occur more predominantly with guanine residues localized in single-stranded parts of the genome. The same guanine residues could also be damaged when the reaction was performed, in the dark, in the presence of the artificially generated promazine cation radicals. Using the BamHI-SmaI adaptor (5'GATCCCCGGG-3'), it was shown that the guanine alteration was a covalent addition of the promazine, or of a cation radical photodegradation product, on the guanine moiety. Kinetics of chlorpromazine photoaddition on single-stranded and double-stranded DNAs were determined.

Acepromazine↗

Induction of breaks in deoxyribonucleic acid by photoexcited promazine derivatives.

Near-u.v. photoexcited promazine and three of its derivatives are shown to induce single-strand breaks in phi X174-DNA replicative form. The mechanisms of this DNA breakage depend upon the various photochemical properties of the promazine derivatives. Chlorpromazine is shown to act predominantly via the photodechlorination reaction both in aerobic and anaerobic conditions. The three other promazine derivatives (promazine, trifluopromazine and methoxypromazine) display two mechanisms for DNA breakage. One of them occurs through the cation radical, which is formed during near-u.v. irradiation of promazine derivatives. The second mechanism is demonstrated to act via an hydroxyl radical-dependent pathway. Acepromazine is without photoactivated action. EPR-spin-trapping studies of irradiated mixtures, containing the drugs and 5,5-dimethyl-1-pyrroline-N-oxide (as spin trap), suggest the production of superoxide radical by photoexcited promazines. When DNA is present in the irradiation mixture, this superoxide radical is converted into hydroxyl radical probably via a Haber Weiss-type reaction, catalysed by DNA-iron complexes.

DNA↗

Terminations of DNA synthesis on 'proflavine and light'-treated phi X174 single-stranded DNA.

Bacteriophage phi X174 single-stranded DNA molecules were primed with five different restriction fragments and irradiated with visible light in the presence of proflavine. This photodamaged DNA was used as template for the in vitro complementary chain synthesis by E. coli DNA polymerase I (Klenow fragment). Chain terminations were observed by polyacrylamide gel electrophoresis of the synthesized products and localized by comparison with standard sequencing performed simultaneously on the untreated template. 90% of the chain terminations occurred one nucleotide before a guanine residue in the template strand. More than 80% of the sequenced guanine residues were blocking lesions demonstrating the absence of 'hot-spots' for the photodamaging effect of proflavine. At a defined position, the chain termination frequency increased linearly with the irradiation time and was directly influenced by the proflavine concentration present. An important part of lesions resulted from the action of singlet oxygen produced by excited proflavine as shown by the effect that both NaN3 and 2H2O exerted on the reaction. The induced blocking lesions must be important in vivo since no complete replicative forms could be extracted from cell infected with bacteriophages inactivated by 'proflavine and light' treatment.

Acridines↗

Phase II study of epirubicin in advanced malignant melanoma.

Twenty patients with advanced malignant melanoma refractory to conventional chemotherapy, were entered into a Phase II study of epirubicin, one of the new doxorubicin analogues. The drug was given at a dose of 90 mg/m2 IV every 3 weeks. One partial response and three disease stabilizations were observed. Nausea and vomiting and alopecia were common. Mild to moderate leukopenia occurred in 6 patients. Three cases of reversible ST-T changes were recorded. The observed response rate of 5% with a 39.2% probability of a true response rate greater than or equal to 10%, does not suggest that epirubicin, in the dose and schedule chosen, is active in metastatic malignant melanoma.

Adolescent↗

Controlled study of DTIC versus DTIC plus epirubicin in metastatic malignant melanoma.

Forty-two previously untreated patients with metastatic malignant melanoma were randomized to receive DTIC at a dose of 250 mg/m2/day 4 IV on days 1-5 or the same drug plus epirubicin (Epi-DX) at a dose of 90 mg/m2 on day 1. Cycles were repeated every 3 weeks. Partial responses were observed in two out of 22 patients (9.1%) treated with DTIC, and in four out of 19 evaluable patients (21.1%) treated with Epi-DX + DTIC. Overall, Epi-DX + DTIC combination was well tolerated, thus permitting administration after a 3-week interval of the full drug dosages in all but two patients. No major cardiotoxicity was observed. Although patients in the Epi-DX + DTIC group had a better response rate than those in the DTIC group, the difference was not statistically significant, and the 21.1% response rate observed with the two-drug combination does not differ from that reported with DTIC used alone.

Adolescent↗

ASTA Z 7557 (INN mafosfamide) for the in vitro treatment of human leukemic bone marrows.

The in vitro treatment of leukemic bone marrows, collected during complete remission, aims at eliminating residual blast cells prior to freezing and preservation, while sparing normal hematopoietic stem cells. We report our experience on the activity of ASTA Z 7557 on human leukemic (CFU-L) and normal hematopoietic stem cells. The sensitivity of human leukemic and normal progenitor cells (CFU-c), detected in semi-solid media cultures, is similar. However, pre-CFUc progenitors detected in long term marrow cultures are much less sensitive to ASTA Z 7557. Therefore autologous bone marrow transplantation can successfully be done with pretreated marrows containing 5 +/- 5% residual CFUc. The wide range of stem cells sensitivity to ASTA Z 7557 justify the predetermination of the optimal dose of drug for incubation prior to marrow collection for each individual patient. Our preliminary clinical experience is exposed.

Bone Marrow Transplantation↗