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C Bartholomew

Publications and source records attributed to C Bartholomew.

At least 55 records · Page 3Linked to original sources
PubMed1990

Phenotypes and mechanisms in the transformation of hematopoietic cells.

Interleukin 3 (IL-3) is a growth factor that supports the proliferation of early hematopoietic stem cells, as well as cells that are committed to a variety of the myeloid lineages. The mechanisms by which IL-3 functions have been studied through the use of a series of IL-3-dependent cell lines isolated from myeloid leukemias or long-term bone marrow cultures. A variety of studies have implicated tyrosine phosphorylation in IL-3 signal transduction. One of the substrates of phosphorylation is a 140 kDa, IL-3-binding protein that is speculated to be the biologically relevant IL-3 receptor. IL-3, through tyrosine phosphorylation, supports viability and growth through the regulation of transcription of a series of genes including c-myc and c-pim-1. The c-myc gene contributes to viability, in part, by regulating the transcription of the ornithine decarboxylase gene. The role of growth factors in differentiation is less clear. By studying IL-3-dependent myeloid leukemia cell lines, two genes have been identified whose altered expression is associated with blocking the ability of the cells to differentiate. The c-myb gene is a nuclear DNA binding protein that has been implicated in myeloid transformation in a number of systems. The Evi-1 gene is a novel gene of the zinc finger family of transcriptional activators. Possible mechanisms by which these genes interfere with normal differentiation are discussed.

Animals↗
PubMed1990

The human Evi-1 gene is located on chromosome 3q24-q28 but is not rearranged in three cases of acute nonlymphocytic leukemias containing t(3;5)(q25;q34) translocations.

The murine Evi-1 gene encodes a protein that has multiple 28-amino acid repeats containing the consensus sequence found in the zinc finger domains of many transcriptional regulatory proteins. Activation of the expression of the Evi-1 gene is frequently found in murine myeloid leukemias and leukemia cell lines and is due to retroviral insertions in the 5' region of the gene in either the Evi-1 or the CB-1/FIM3 common sites of viral integrations. To examine the role of the Evi-1 gene in human leukemias we have cloned regions of the human locus corresponding to the coding region of the gene and regions corresponding to the Evi-1 and CB-1/FIM3 common sites of integrations. Using these probes we demonstrate that the human Evi-1 gene maps to chromosome 3q24-q28 in a region that is translocated in acute nonlymphocytic leukemias with a t(3;5)(q25;q34). By in situ hybridization with metaphase chromosomes from one patient with a 3;5 translocation, the Evi-1 gene was found to be translocated to the derivative 5 chromosome. However, no rearrangements were detected by Southern blot analysis with DNAs from three patients with a t(3;5) using probes from the Evi-1 or CB-1/FIM3 loci. No Evi-1 transcripts were detected with RNA from leukemic blasts of one patient with a t(3;5).

Blotting, Northern↗
PubMed1990

Insertional mutagenesis and transformation of hematopoietic stem cells.

The mechanisms that are involved in the control of the normal differentiation of hematopoietic progenitor cells are largely unknown. Moreover, little is known concerning the types of genes that can alter the ability of hematopoietic progenitors to differentiate and cause transformation. One approach to the latter has been to use retroviral induced IL-3-dependent myeloid leukemia cell lines to identify transforming genes by their activation through insertional mutagenesis. This approach has implicated alterations in c-myb in transformation and has identified a novel transcriptional factor of the zinc finger family that is frequently activated in murine myeloid leukemias and in some cases of human AML. Using this approach it should be possible to identify additional myeloid transforming genes. The identification and characterization of the genes will provide important information and approaches to the study of the regulation of differentiation in normal hematopoiesis.

Acute Disease↗
PubMed1990

A study of HTLV-I and its associated risk factors in Trinidad and Tobago.

Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection.

Adult↗
PubMed1989

Identification of a functional allele of a human interferon-alpha gene previously characterized as a pseudogene.

Three recombinant phage lambda L47 clones containing 4 alpha interferon (IFN) genes have been isolated from a newly constructed human genomic library. Each gene is an allele of a previously described IFN gene, three being only minor variants. The fourth gene SMTIII.1A is a functional allele of the psi LeIF-L gene which previously has been described only as a pseudogene. Therefore, it appears likely that other variant alleles may remain to be described and that the IFN system may be able to tolerate some degeneracy as a consequence of the large number of members of the family.

Alleles↗
PubMed1989

Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene.

A common retroviral integration site (CB-1) was identified in two IL-3-dependent myeloid leukemia cell lines (DA-3, DA-34). The CB-1 locus was mapped to murine chromosome 3 and was shown to be closely linked to another myeloid common site of viral integrations in myeloid leukemias, Evi-1. A comparison of the CB-1 restriction map with published restriction maps for other common integration sites demonstrated that it was nearly identical to the restriction map of a common site of Friend MuLV integration in myeloid tumors termed Fim-3 (Bordereaux et al. 1987). Genomic clones representing approximately 110 kb of the CB-1 locus and 80 kb of the 5' region of the Evi-1 locus demonstrate no physical overlap of these viral integration sites. Previous studies (Morishita et al. 1988) have shown that retroviral insertions in the Evi-1 locus activate the expression of a gene potentially encoding a 120 kd zinc finger protein. Evi-1 expression is also activated in cell lines with viral integrations in the CB-1 locus. These results demonstrate that the CB-1/Fim-3 and Evi-1 loci constitute a large genomic region in which viral integrations activate the transcription of a new potential myeloid transforming gene.

Animals↗
PubMed1989

Retroviruses in the Caribbean.

Transmission of HIV in many Caribbean countries has followed the pattern of initial predominance among homosexual and bisexual males, with the infection subsequently spreading into the heterosexual community. However, on Saint Lucia the epidemic began among heterosexual contacts of Saint Lucian laborers from Florida; in Bermuda 58% of AIDS cases have been in intravenous drug abusers; and in the Bahamas 59% of the AIDS patients have been heterosexuals and 19% children infected via the perinatal route. Seroprevalence of the human T-lymphotropic virus, type 1 (HTLV-I), whose modes of transmission resemble those of HIV, has been found to range from 2.3% in Trinidad and Tobago to 5.4% in Jamaica. In a study of HIV and HTLV-1 infection patterns in homosexual males in Trinidad and Tobago, the cohort was too small for confirmation that coinfection with these two viruses hastened progression in AIDS, but further investigation is warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cutaneous histoplasmosis in the acquired immune deficiency syndrome--a report of three cases from Trinidad.

Three cases are reported of patients with the Acquired Immune Deficiency Syndrome (AIDS) and cutaneous histoplasmosis. Their initial presentation was that of a generalised maculopapular rash. Two patients were bisexual males and the third was an unmarried female. The range of opportunistic infections seen in AIDS patients in Trinidad is mentioned and clinicians are alerted to the fact that in areas endemic for Histoplasma capsulatum maculopapular rash in patients with AIDS may suggest disseminated histoplasmosis. The value of skin biopsy is mentioned.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Transmission of HTLV-I and HIV among homosexual men in Trinidad.

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Racial and other characteristics of human T cell leukemia/lymphoma (HTLV-I) and AIDS (HTLV-III) in Trinidad.

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-I) is causally related to adult T cell leukaemia/lymphoma. A subgroup of HTLV, designated HTLV-III, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe 12 cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40% of the population. West Indians of African descent may have increased susceptibility to infection with both HTLV-I and HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMed1984

AIDS on Trinidad.

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Acquired Immunodeficiency Syndrome↗