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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 451 records · Page 25Linked to original sources

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

Animals↗

[K-Lymphocyte cytotoxicity: role of human blood group ABO, rhesus and P alloantibodies].

Using human erythrocytes of known antigenic density, sensitized by ABO and Rhesus (D) alloantibodies, it is shown that K cell cytotoxicity mediated by peripheral blood lymphocytes is directly correlated with the number of IgG molecules specifically bound to the target cell surface. The lytic sensitivity of P1k but not P2 or p erythrocytes coated with anti-Tja (anti-P + P1 + Pk) antibodies, demonstrates that effector K cells are mainly triggered through the IgG ANTI-Pk component of such sera.

ABO Blood-Group System↗

[Development of antigens ABH and Ii in children between 0 to 16 years old].

The ABH and I, i erythrocyte antigens of 926 children from birth to sixteen years were tested in a semi-quantitative assay in order to follow their development. Results show that total activities of A, B and H erythrocyte antigens are reached within 13 and 24 months, the main modifications being observed within the first three months of life. However, these activities depend on the agglutinins used in the test; notably the results with anti-H lectins from Ulex europaeus and Laburnum alpinum are not totally identical. The decrease of i reactivity and the increase of I reactivity are simultaneous, but at birth the I reactivity of cord red cells is widely distributed, while that of i is more homogeneous. The increase in H activity tested with Laburnum alpinum is directly related to the decrease of foetal hemoglobin in the children's red cells.

ABO Blood-Group System↗

Activity of IgG and IgM ABO antibodies against some weak A (A3, Ax, Aend) and weak B (B3, Bx) red cells.

The IgG and IgM anti-A and anti-B activities from several immune and non-immune O, A and B sera were tested against a panel of weak (A (A3, AX, AND Aend) and weak B (B3 and Bx) red cells. In all cases it is the IgM which agglutinated optimally Ax (or Bx) cells, while IgG and IgM anti-A (or anti-B) reacted similarly with A3 and Aend (or B3) cells. The agglutinating activity of all these ABO antibodies was found straightly related to their association constant for the A (or the B) receptor.

ABO Blood-Group System↗

[A family with an "Hm" phenotype transmitted over 3 generations].

Hm phenotype represents a dissociation between a normal salivary expression of H substance and a very weakened expression of the antigen on red blood cells. Genetic analysis of the reported family reveals a dominant inheritance: Some members (Marie K..., Francette, Carmen) present a phenotype marked by a normal H enzyme but a deficient H antigen in erythrocyte membrane. Others Alice, Mathilde) have no expression of A1 antigen due to H substrate deficiency. H substance in salivary secretion is normal. In the other branch of this pedigree without consanguinity, Herbert presents an H substance deficiency, though quite different, as A1 antigen is expressed. In this family, Hm phenotype can be explained, without resorting to a Zm allele, by the expression of an exceptional allele at the H locus (like Am is an ABO allele). This hypothesis supports the possible polymorphism of H locus.

ABO Blood-Group System↗

The natural history of antitumour immunity in human breast cancer assayed by tube leucocyte adherence inhibition.

The specificity of the tube LAI in breast cancer was examined in a study with coded samples of PBL. In addition, 64 patients with breast cancer had their LAI reactivity monitored and correlated with their clinical status for up to 3 years after mastectomy. When patients were assayed by tube LAI, 83, 72, and 29% with Stage I, and II and III breast cancer respectively were positive. In Stage IV brest cancer, 88% of those with local recurrence and 15% of those with disseminated cancer were positive. By contrast, 3% of control subjects were LAI+. A select group of patients admitted to hospital with suspicious breast lumps that histopathologically proved to be benign breast disease (BBD) had a higher incidence of LAI+ (12%), whereas of outpatients with BBD only 2% were LAI+. Most breast cancer patients LAI reactivity became negative 2--4 months after mastectomy, even when some harboured micrometastases. LAI reactivity remained absent in those patients who remained clinically "cancer-free". In the follow-up patients, LAI activity returned about 4 months before local recurrence. LAI reactivity was observed in 7/8 patients in the coded study and 14/15 patients in the follow-up study preceding and/or at the time of local recurrence. A few patients (15%) progressed to widespread cancer without preceding positive LAI activity. The results suggest that tumour-specific immunity rapidly fades after surgery and may play no role in the rejection of micrometastases by 6 months after surgery. In addition, the present study has shown that the human hose manifests tumour-specific immunity when the cancer is small, and suggests that the early detection of human cancer would depend upon reliable methods to measure the tumour-specific immune response.

Breast Neoplasms↗

[Quantitative and thermodynamic study of B antigen in a family including individuals with phenotypes B 3 and AB 3].

Four B3 and one A1B3 erythrocyte samples belonging to the same family were studied using several series of quantitative measurements: percentage of agglutination, agglutination kinetics and thermodynamic methods. For this last assay the erythrocytes were used fresh and after treatment by formalin. From the obtained results evidence was given that while B antigen density was lower in A1B3 than in B3O cells, the reactive structure is qualitatively the same in these two kinds of cells. The enthalpy change of the reaction of this B3 antigen with a non stimulated anti-B from A1O individual was -- 5,000 cal/mole, i.e. weaker than when normal B cells were concerned (-- 16,000 cal/mole).

ABO Blood-Group System↗

Inheritance of cis-AB in three generations (family Lam.).

In a case of disputed paternity genetic incompatibility was observed in the ABO blood group system between mother (O) and child (AB). From biostatistical evaluation of 21 genetic markers, including HLA phenotypes, a high value of probability for paternity, maternity and parentage was found between the child, the child's mother, the accused man and his mother. Substitution of the newborn was thereby excluded. The serostatistical evaluation of maternity and paternity could be supported by anthropological opinion. In serological investigations of the ABH system the A and B antigens of the 'A2B' cells were found to be abnormal in the child, the child's father, and the father's mother: the A was weaker than normal A1 but stronger than normal A2; the B was found to be abnormal which in addition was documented through occurrence of irregular anti-B antibodies in the child. In comparison to normal controls (A1, A2, B, A1B, A2B) diminished activity of alpha-D-N-acetylgalactosamine and alpha-D-galactosyltransferase were observed in the three 'A2B' propositi. These facts confirmed the existence of a cis-AB gene in the Lam. family which the child inherited from her father and the child's father from his mother. Assuming a population frequency of 1.1 X 10(-5) for the cis-AB gene, the probability for paternity was calculated from all genetic markers to be W = 99.9999985%.

ABO Blood-Group System↗

Pipazethate--acute childhood poisoning.

A previously healthy child who who had accidentally ingested an unknown quantity of 20-mg tablets of pipazethate developed severe acute poisoning with neurologic, metabolic, and cardiovascular disturbances. She recovered with symptomatic and supportive therapy.

Acidosis↗

An unusual case of leukemia with high fetal hemoglobin: demonstration of abnormal hemoglobin synthesis localized in a red cell clone.

A high level of fetal hemoglobin was found in an 8-yr-old boy without any hematologic disorders except for a moderate anemia. The absence of hemoglobin abnormalities in the parents led us to suspect a latent malignant disease that, on follow-up, was confirmed to be myelomonocytic leukemia. Hemoglobin biosynthetic studies provided evidence of unbalanced synthesis of globin subunits by reticulocytes, while the production of non-alpha chains was equal to that of alpha chains in bone marrow cells. The expression of red cell antigen i was increased, while those of I, A, and A1 antigens were found to decrease progressively. Two populations of erythrocytes, A-positive and A-negative, were distinguished and could be separated by differential agglutination. Unbalanced globin chain synthesis, increased fetal hemoglobin, and antigenic changes of the membrane were shown to be restricted to the A-negative population. The biologic data were not entirely consistent with a genuine reversion to fetal erythropoiesis. The question remains of a polychromosomal lesion of either quiescent F cells or adult stem cells.

ABO Blood-Group System↗