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Biomedical subjects

M G Morales

Publications and source records attributed to M G Morales.

5 recordsLinked to original sources

Study of CYP2D6 gene in children with autoimmune hepatitis and P450 IID6 autoantibodies.

Cytochrome P450 IID6 is an autoantigen recognized by the sera of children affected with a subtype of autoimmune hepatitis. It was hypothesized that a mutation in the CYP2D6 gene could explain the autoimmune response in these patients. To examine this question, genomic DNA from peripheral lymphocytes (n = 9) and liver (n = 1) of 10 patients with anti-LKM-1 antibody was analysed by Southern blot for genetic association studies between a particular CYP2D6 haplotype and autoimmune hepatitis. In addition, a region of CYP2D6, from the same genomic DNA, was amplified by polymerase chain reaction (PCR) and digested by BstNI, in a search for the most prevalent 29B mutation, described in subjects who do not express the P450 IID6. Total RNA and proteins, prepared from the liver of an anti-LKM-1+ patient, were analysed by Northern and Western (immunoblot) blots respectively. Our results do not reveal any major structural change in the DNA of this patient at the CYP2D6 locus that could explain their autoimmune response. Corroborating this observation, no changes were noted either in P450 IID6 mRNA size or in the corresponding protein. However, these data do not exclude the possibility of subtle changes in the protein due to point mutations in critical regions that might trigger an autoimmune response.

Autoantibodies↗

[Study of lymphocyte subpopulations with monoclonal antibodies in acute hepatitis A and B].

Using monoclonal antibodies, it was determined the T3, T4 and T8 1ym phocyte populations in the blood samples of 40 patients with acute viral hepatitis (20 type A and 20 type B). al patients showed complete remission from it. The results of this study were compared with those of a control group of 20 healthy subjects. There was a non significant decreased of the total number of lymphocytes measured with the T3 monoclonal antibody in both types of hepatitis. The number of T8 lymphocytes was significantly increased (p less than 0.05) when the results were compared with those of the control group. The quotient T4/T8 was diminished in the initial phase of the disease (p less than 0.05). There were no other differences between hepatitis A and hepatitis B. In the follow up of the disease, the results tend to normal values in the whole group of patients.

Acute Disease↗

Evidences that fibroblasts and epithelial cells produce a specific type of macrophage and granulocyte inducer, also known as colony-stimulating factor, and that monocyte-macrophages can produce another factor with proliferative inducing activity on myeloid cells and differentiative activity on macrophages.

Molecules with the property to induce proliferation of bone marrow cells in liquid cultures, and with colony-stimulating activity, were found on media conditioned (MC) by lung fibroblasts and kidney epithelial cells. These factors presented an apparent mol wt of 70,000 and 22,000 d respectively. Also when MC by epithelial cells from lungs was tested for the induction of proliferation of bone marrow cells a molecule with 22,000 d was detected. These molecules are thought to be CSF because they induce colony formation, and they are also similar in mol wt to two of the already known CSF. In fact the GM-CSF obtained from endotoxic lungs with a large epithelial cell content has a mot wt of 22,000 d, and the CSF-1 produced by a fibroblast cell line had 70,000. When the MC by fibroblast was used to induce bone marrow cells to proliferate, three new molecules with colony-stimulating activity were secreted. These molecules with apparent mol wts of 45,000, 30,000 and 17,000 d were also found in the MC by bone marrow cells when induced to proliferate with MC by epithelial cells. When the 45,000-d molecules was used in induced bone marrow cells to proliferate, once again the 30,000- and the 17,000-d molecules were secreted. Evidence is also provided that the 45,000-d molecule is produced by the monocyte-macrophage cells, and that it can induce Fc receptors or resident and elicited peritoneal macrophages. The possibility that the production of CSF is cell specific is discussed together with two models to explain the way in which these molecules can participate as proliferative (MGI-1) and differentiative (MGI-2) function in normal myeloid cell differentiation. Finally, a new terminology is proposed to classify this family of molecules.

Animals↗

[Severe intoxication with verapamil].

Calcium channel blockers are currently widely used to treat many cardiological alterations; however, overdose and poisoning have been associated with morbidity and mortality mainly in those patients with suicidal attempts. We report a case and review the pathophysiology of overdose, treatment, and prognosis.

Adult↗

[Study of lymphocyte subpopulations by means of monoclonal antibodies in acute hepatitis A and B].

We studied T3, T4 and T8 lymphocyte populations in peripheral blood by monoclonal antibodies in 40 patients with acute viral hepatitis (Type A 20; Type B 20) who underwent outcome to complete recovery. We compared the results with 20 healthy subjects (control group). We found a decrease in total lymphocytes measured by T3 monoclonal antibodies and a significant increase in T8 lymphocyte populations compared with control groups. In the early stage the T4/T8 ratio was decreased. Lymphocyte populations and T4/T8 ratio was normal in 3-6 month follow-up for the acute A hepatitis group and 3.6 month to a year follow-up for the B hepatitis group. Results were related to the humoral and clinical outcome.

Adolescent↗