Biomedical subjects
Publications and source records attributed to B Rodriguez.
A rabbit liver enzyme preparation oxidised racemic iminium ions 1 and 2 to optically active lactams 3 and 4 with enantiomer ratios ER/S = 5.5 and 0.14, respectively.
We have studied, by ultrastructural morphology and immunocytochemistry, the alterations that occur in cells from the HL60 leukaemia cell line and from patients with CGL following incubation in vitro with 1,25(OH)2D3 for 2-5 days. The main morphological changes observed were in the nuclear shape, the development of autophagic vacuoles and the appearance of a population of small granules in the cytoplasm. These changes were associated with a significant reduction in MPO activity and increased expression of membrane antigens detected by the monocyte-specific McAb FMC17 and FMC32, as shown by the IGM at EM level, and a decrease in granulocyte-specific antigens demonstrated by the McAb FMC10. These observations suggest that promyelocytes and myelocytes could transform into monocyte-like cells and that this remodelling of cells was associated with autophagic digestion of cellular structures.
A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.
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The expression of two membrane antigens identified by the monoclonal antibodies (McAb) My9 and 3C5 has been investigated in cells from 80 acute leukemias. My9 was positive in the blasts of 33 out of the 38 (87 per cent) cases of acute myeloid leukemia (AML) tested, regardless of FAB subtype, and in 13 of 18 (72 per cent) cases of chronic granulocytic leukemia (CGL) in myeloid blast crisis. The reactivity of 3C5 was confined to myeloblastic (M1) AML, 85 per cent of cases, and to lymphoblastic leukemia (ALL) of B-lineage, 70 per cent of cases, including CGL in lymphoid transformation. My9 was negative in ALL except for an unusual case. The phenotype My9+, 3C5+ was seen exclusively in M1 (69 per cent) and M2 (14 per cent) AML. Ultrastructural analysis with the immunogold method in combination with the myeloperoxidase (MPO) reaction showed that expression of My9 increased in parallel with MPO activity whereas 3C5 was expressed mainly in myeloblasts with little MPO content. We conclude that the use of these two McAb will contribute to the diagnosis and classification of AML and may throw some light to the pathogenesis of biphenotypic acute leukemias, including TdT + AML.
This multicenter, open study, carried out in 14 countries in Europe, Latin America, and Asia, recruited 4965 patients suffering from recurrent respiratory tract infections to investigate the safety and acceptability of the oral bacterial lysate immunomodulator LW 50020. Patients remained in the study for 4 months (two 4-week courses of LW 50020 separated by a 28-day treatment-free interval and follow-up). The incidence of all adverse events was 7.2%; that of adverse drug reactions was 0.6%. Adverse drug reactions were mild to moderate and not more frequent in the large subgroup of patients (77%) with a known history of allergies or underlying respiratory diseases; however, the incidence of adverse events in this subgroup was twofold higher than in the study population as a whole, probably indicating a generally increased vulnerability to disease. No clinically relevant changes in laboratory variables followed treatment. Comparison of the first study period (first course of LW 50020 and drug-free interval) with the second study period (second course of LW 50020 and follow-up) showed an overall reduction of at least 50% in the number, severity, and duration of respiratory tract infections, the number of antibiotic and symptomatic treatments, and the number of days absent from school or work. Tolerability and acceptability were assessed as good or very good in 99% of patients who completed the study.
The authors studied the association of cardiovascular risk variables with body fat distribution (BFD) in a cross-sectional sample of 743 Texas schoolchildren of both sexes ages 6-14 years. This association is well known in adults and several useful indices of BFD are available. Whether they are applicable to children remains a question of importance for epidemiological investigations in this age group. Canonical correlations between anthropometric (five skinfolds, four circumferences) and risk (blood pressures, cholesterol, pulse) variables ranged from 0.37 to 0.82 depending on sex/age group (p < 0.01). The skinfold vector suggested an association of risk with central fat at most but not all ages. The circumference vectors, on the other hand, suggest that size or fatness, not BFD, was related to risk. Partial correlation and stepwise regression of fatness and BFD indices with cardiovascular risk factors as dependent variables, showed that 'fatness' or 'size' was more clearly associated with risk factors than BFD. The variables most consistently entering the regression were hip circumference and sum of skinfolds. These results contrast with studies of adults or sexually mature adolescents, in which BFD is more clearly related to CV risk variables and the hip circumference is a 'low-risk' variable.
The Magainins, two antimicrobial peptides found in the skin of the frog Xenopus laevis, and 50 Magainin analogs were synthesized by the method of simultaneous multiple peptide synthesis (SMPS). This series of peptides was prepared in order to examine the effects of omitting individual amino acids on antimicrobial activity. The series consisted of 22 Magainin 1 omission analogs having a C-terminal carboxyl (M1-C) and 23 Magainin 2 omission analogs having a C-terminal amide (M2-A), as well as both the C-terminal amide and carboxyl forms of Magainin 1 and Magainin 2. These peptides were tested against E. coli (Gram negative), S. epidermis (Gram positive) and C. albicans (yeast). Amino acid omissions in the N-terminal region (residues 1-14) resulted in the complete loss of antimicrobial activity in both Magainin series. These analogs also had very low hemolytic activity against human erythrocytes. However, analogs with omissions in the C-terminal region, especially residues alanine-15, glycine-18 or glutamic acid-19, while having equal or increased antimicrobial activity relative to the original Magainin 1 or Magainin 2 forms, had variable hemolytic action. Thus, both Magainin 1 and Magainin 2 with the glutamic acid 19 omission had equal activity against E. coli and increased activity against S. epidermis, while having lower hemolytic activity than the original sequences. The amide form of Magainin 2 with glycine 18 omitted had equal antimicrobial activity, but significantly increased hemolytic activity. The C-terminal carboxyl form of Magainin 1, however, showed equal antimicrobial activity, but substantially decreased hemolytic action.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of dietary protein concentrations on the hepatic expression of phenylalanine hydroxylase (PAH) and tyrosine aminotransferase (TAT) mRNA concentrations was studied in rats adapted to consume diets (18 or 50% casein) in a restricted schedule of 7 h (0900 to 1600) for 5 days. After 6 hours of feeding, TAT mRNA concentrations of rats adapted to 18% casein diet and fed acutely 6, 18 and 50% casein diet were 0.15, 0.84 and 5.08 fold respectively higher than mRNA concentrations of rats before feeding. After 17 hours of fasting, TAT mRNA concentrations of rats previously fed 6, 18 or 50% casein diet were -0.45, 1.76 and 9.11 fold respectively higher than mRNA concentrations of rats before they were fed. PAH mRNA concentrations showed a similar pattern. There was a -0.68, 1.63 and 2.5 fold rise of PAH mRNA concentrations in rats fed 6,18 and 50% casein diet during the feeding period, and -0.86, 2.32 and 9.33 fold rise after 17 hours of fasting. TAT and PAH mRNA concentrations of rats adapted to consume 50% casein diet and then changed to 6% or kept on the 50% casein diet showed a maximum peak 6 hours after the rats began to consume the diet; however, they decreased 5 hours after fasting. These results suggest that increasing concentrations of protein in the diet were able to increase the concentration of TAT and PAH mRNA, possibly in order to eliminate the excess of amino acids consumed. The concentration of TAT and PAH mRNA depended more on the protein content of the diet to which the rats were previously adapted.