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Biomedical subjects

F Rosa

Publications and source records attributed to F Rosa.

At least 55 records · Page 3Linked to original sources

Gene expression in amphibian embryogenesis.

The study of molecular events during the embryogenesis of Xenopus laevis has advanced as a result of the availability of molecular markers, i.e., nucleic acid and antibody probes for genes that are expressed in a temporally and spatially regulated fashion during development. In this article we summarize results on the localized expression of keratin genes and on the reconstruction of regulated transcription of the gastrula/neurula-specific DG42 gene. Furthermore, we discuss experiments that investigate molecular events during mesoderm induction and provide information on the nature of the inducing principle.

Animals↗

Tau microheterogeneity: an immunological approach with monoclonal antibodies.

The family of tau polypeptides purified from mammalian brain exhibit both extensive heterogeneity and large similarities in their chemical, physical, and functional properties. All the tau isoforms generated at a transcriptional or posttranscriptional level share the property of interacting with tubulin dimers in a specific manner. They strengthen longitudinal interactions between tubulin dimers and thus may stabilize microtubules once they are formed. Mild proteolysis or phosphorylation does not remove but only modulates the tau specific function that is probably related to the conserved sequences of the molecules. Monoclonal antibodies raised against tau were found to recognize epitopes conserved not only between species but also in different tissues. Using indirect immunofluorescence, a specific staining pattern was observed on rat neuronal cells and also on human skin fibroblasts. The same antibodies did not recognize glial cells, suggesting that these cells either do not contain detectable levels of tau or contain tau molecules different from the neuronal ones. These data suggest that tau protein is widely distributed, highly conserved, and may be preferentially associated with special subclasses of microtubules.

Aging↗

Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate.

Using sodium butyrate and alpha, beta, and gamma interferons as inducing agents it has been possible to demonstrate the triggering of HLA class I antigen synthesis in the K562 cell line. This cell line, widely used to study hemopoietic differentiation, does not naturally express HLA antigens. This effect was confirmed by the detection of HLA class I antigens on the cell membrane with specific monoclonal antibodies, by immuneprecipitation, and by isolation of specific HLA ABC messenger RNA, in the induced cells. No synthesis of HLA class II antigens was observed. Because leukemic cells can be considered as a model representing certain stages of normal hemopoietic differentiation, the expression of HLA antigens on K562 cells induced to differentiate could be interpreted as an event related to the process of differentiation itself. The lack of expression of DR antigens may result from a genetic defect as observed for beta 2-microglobin in Daudi cells.

Antibodies, Monoclonal↗

Control of protein synthesis in human reticulocytes by heme-regulated and double-stranded RNA dependent eIF-2 alpha kinases.

Heme-deficiency and double-stranded RNA (dsRNA) activate distinct cyclic 3':5'-AMP independent protein kinases (HRI and dsI, respectively) in rabbit reticulocyte lysates. These kinases inhibit protein synthesis by phosphorylating the 38,000 daltons (38K) subunit of the initiation factor eIF-2 (eIF-2 alpha). Using separation techniques to obtain a reticulocyte enriched fraction and reticulocyte-free erythrocytes, we have prepared lysates of these fractions from normal human whole blood. Human reticulocyte-enriched lysates contain the hemin-regulated and dsRNA-dependent protein kinases which inhibit protein synthesis and which phosphorylate rabbit eIF-2 alpha. An endogenous 38K polypeptide which co-migrates with rabbit eIF-2 alpha is also phosphorylated. In contrast, human mature erythrocytes contain little or no heme-regulated or dsRNA-dependent eIF-2 alpha kinase activities which are inhibitory of protein synthesis.

Blood Proteins↗

Transformation of LMTK- cells with purified HLA class I gene. VI. Serological characterization of HLA-B7 and AW24 molecules.

Serological characterization of HLA-B7 and HLA-AW24 class I molecules following transfection of murine LMTK- cells with purified HLA class I genes was performed using human alloantisera. Induction by murine alpha interferon of the expression of class I molecules was required to obtain unambiguous identification of these molecules which appear serologically identical to the HLA-B7 and HLA-AW24 molecules expressed at the surface of human peripheral blood lymphocytes of 20 unrelated individuals. Analysis of the transformed cells with 8 different anti-HLA class I monoclonal antibodies results in the definition of 3 separate clusters of antigenic determinants shared by all HLA class I molecules. These studies further suggest the existence of locus-specific serological reactivities associated either with the HLA-A or with the HLA-B and C gene products.

Animals↗

Isotretinoin and pregnancy.

Approximately 120,000 women of childbearing age used isotretinoin in the first 16 months after its release for the treatment of cystic acne. In September, 1983, the American Academy of Dermatology requested its members to relate the outcome of pregnancies of women inadvertently exposed to isotretinoin ( Accutane ) during pregnancy to its Adverse Drug Reaction Reporting System ( ADRRS ). Of nine pregnancies reported, seven ended in spontaneous abortion or the birth of an infant with birth defects. Of thirty-five pregnancies with isotretinoin exposure reported to the ADRRS or the U.S. Food and Drug Administration, twenty-nine (83%) resulted in spontaneous abortion or infants with birth defects. The most frequently reported severe birth defects involved the central nervous system (microcephaly or hydrocephalus) and the cardiovascular system (anomalies of the great vessels). Microtia or absence of external ears were also noted in a majority of cases. These findings illustrate the usefulness of specialty-based reporting of adverse drug effects and emphasize the teratogenic risk of isotretinoin in humans. Physicians need to fully and carefully inform women of childbearing age of these risks.

Abnormalities, Drug-Induced↗

Medicaid drug-event data: an emerging tool for evaluation of drug risk.

Post-marketing surveillance (PMS) of drugs requires access to multiple data resources covering the spectrum of drug exposures and drug-associated events. In the U.S., the Federal/State third party payment system for medical care to welfare recipients, Medicaid, maintains drug-event data by date of service. The FDA has explored this data for drug utilization studies, generation of signals of drug risk, and strengthening of hypotheses of drug associated problems. Thus far, studies suggest the data from Michigan and Minnesota, covering 1.5 million patients for 18 months, can be a useful, multifunctional tool for PMS studies. Examples of use to date are presented.

Adolescent↗

HLA class I genes integrated into murine cells are inducible by interferon.

In human cells treated with interferon, there is an increase in the amount of HLA-A, B, C mRNA and, to a lower extent, membrane-bound antigen. However, the mechanism of this mRNA enhancement is still unknown. Using mouse L cells transfected with a unique class I HLA gene, we were able to show that both the related HLA mRNA and protein are increased after murine but not human interferon treatment. Moreover, the discrepancy between interferon-directed HLA mRNA and protein enhancement is also observed. The mouse transfected cells allowed us to study more precisely the origin of this discrepancy.

Animals↗

The beta2-microglobulin mRNA in human Daudi cells has a mutated initiation codon but is still inducible by interferon.

The human Burkitt lymphoma cell line Daudi does not synthesize beta2-microglobulin (beta2m) and lacks the cell surface histocompatibility antigens. The cells, however, contain RNA hybridizing to a cloned human beta2m cDNA probe. cDNA from this Daudi beta2m RNA, was cloned and sequenced. By comparison with cDNA prepared from Ramos cells, which synthesized microglobulin, we determined the sequence of the 20 amino acid long leader peptide of pre-beta2m and show that in Daudi cells the initiator ATG has been mutated to ATC. Although Daudi beta2m RNA cannot be translated, interferon induces the beta2m RNA in Daudi cells as well as in normal human cells.

Amino Acid Sequence↗

Differential regulation of HLA-DR mRNAs and cell surface antigens by interferon.

Human interferons-alpha, -beta and -gamma enhance HLA-DR mRNAs in all the human lymphoblastoid and melanoma cell lines studied. The increase concerns both alpha and beta chain mRNAs. Moreover, we show that immune interferon-gamma preferentially enhances class II MHC mRNA. This effect of IFN-gamma on the synthesis of alpha and beta HLA-DR chains has been also analysed by immunoprecipitation. It is abolished by a monoclonal antibody directed against human IFN-gamma. The effect of interferon on the cell surface level of HLA-DR molecules does not always correspond to the enhancement of HLA-DR mRNA. Our experiments suggest that this discrepancy between the enhancement of HLA-DR mRNA and cell surface antigen might be due to a constitutively high level of the corresponding antigens on several of the human cells studied.

B-Lymphocytes↗

Presence of an abnormal beta 2-microglobulin mRNA in Daudi cells: induction by interferon.

Human alpha and beta interferons increase the amount of class I human histocompatibility messenger RNA HLA-A, B, C and beta 2-microglobulin in most human cells studied to date. This report concerns the effect of interferons on the Burkitt lymphoma-derived cell line Daudi, which does not express HLA-A, B, C antigens or beta 2-microglobulin on its membrane. HLA-A, B, C messenger RNA present in Daudi cells is increased by both alpha and beta interferons. Furthermore, we have shown that although it was not possible to detect mature beta 2-microglobulin protein in the cytoplasm or on the cell membrane of Daudi cells, a poly A+ messenger RNA is present in Daudi cells, which hybridizes with a cDNA clone specific for human beta 2-microglobulin. This abnormal messenger RNA is, however, increased normally by interferon. These effects were also observed with human interferon beta on a variant of Daudi cells characterized by a markedly reduced sensitivity to anti-proliferative and anti-cellular effects of human interferon alpha.

Beta-Globulins↗

[Effect of interferon on human cell lines which do not express class I transplantation antigens: K 562 and Daudi. Presence of a pseudo-messenger RNA of beta 2-microglobulin in Daudi cell line].

Human alpha and beta interferons increase the rate of class I human MHC antigens mRNA HLA-A, B, C and beta 2-microglobulin (beta 2m) in most human cells studied so far. The present work studies the effect of those interferons upon cell lines which do not express class I antigen on their membrane: K 562 et Daudi. If beta 2m mRNA is enhanced in K 562 cell by both alpha and beta interferons, those interferons are not able to promote the de novo synthesis of HLA-A, B, c mRNA, which is not detectable in this cell line. On the other hand, HLA-A, B, C mRNA, which is present in Daudi cell, is amplified by both alpha and beta interferons. Furthermore, we could show that, if it has not been possible to detect mature beta 2m protein either in the cytoplasm or on Daudi membrane, there is a poly A+ RNA in it, which hybridizes with a cDNA probe specific for beta 2m.

Beta-Globulins↗

A new Epstein-Barr virus negative Burkitt's lymphoma derived cell-line. I. Analysis of cell surface markers and abnormal expression of HLA antigens.

CHEV, a new Epstein-Barr virus negative Burkitt's lymphoma derived cell line has been studied. Karyotype analyses demonstrated the t (8; 14) characteristic translocation. Cell surface characterisation of this line showed the presence of mu and chi immunoglobulin chains and beta 2-microglobulin and the absence of the complement receptor. We are unable to detect HLA--A, B alloantigens on the cell surface which was in contrast with an apparently normal expression of these antigens in the cytoplasm.

Antigens, Neoplasm↗