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Biomedical subjects

J R Seale

Publications and source records attributed to J R Seale.

13 recordsLinked to original sources
PubMed2000

'Catastrophic' antiphospholipid syndrome.

When 'catastrophic' is applied as an adjective to the antiphospholipid syndrome, it implies a characteristic presentation due to predominantly small blood vessel thrombosis leading to rapidly progressive failure of multiple organs and a frequently fatal outcome. We present the case of a 48-year-old woman who presented with the 'catastrophic' antiphospholipid syndrome without previous history of coagulation disorder or connective tissue disease that illustrates the difficulties in diagnosing and managing this disorder. We also review the factors that have been reported to have a role in the development of this condition and show how this case throws light on its pathogenesis.

Anti-Inflammatory Agents↗
PubMed1996

Interferon augments PML and PML/RAR alpha expression in normal myeloid and acute promyelocytic cells and cooperates with all-trans retinoic acid to induce maturation of a retinoid-resistant promyelocytic cell line.

The PML gene is fused to the retinoic acid receptor alpha gene (RAR alpha) in the acute promyelocytic leukemia (APL) 15; 17 translocation. PML is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern. In the bone marrow, it is preferentially expressed in myeloid cells. PML appears to be transcriptionally regulated by class I and II interferons, which raises the possibility that interferons modulate the function and growth and differentiation potential of normal myeloid cells and precursors by activating PML-dependent pathways. Similarly, interferons could act on APL cells, alone or in combination with all-trans retinoic acid (RA), especially if the PML/RAR alpha fusion transcript that results from the t(15; 17) is induced by interferon. We report here that PML is expressed at low levels or not expressed in normal circulating human monocytes, lymphocytes, and polymorphonucleate cells, but is markedly induced by interferon; that PML and PML/RAR alpha expression is augmented by interferon in the NB4 APL cell line, which carries the t(15; 17), and in APL blasts from patients; that interferon inhibits growth and survival of NB4 APL cells in cooperation with RA; that interferons alone have minimal maturation effect on NB4 cells; and, finally, that interferon gamma, but not alpha or beta, induces maturation and growth suppression of NB4 cells with de novo retinoid resistance, and partially restores RA response.

Cell Differentiation↗
PubMed1996

Quantification of PML-RAR alpha transcripts in acute promyelocytic leukaemia: explanation for the lack of sensitivity of RT-PCR for the detection of minimal residual disease and induction of the leukaemia-specific mRNA by alpha interferon.

The RT-PCR technique for the identification of the PML-RAR alpha fusion mRNA is widely used for the detection of minimal residual in acute promyelocytic leukaemia (APL). A positive result after remission induction is highly predictive of early relapse, but the vast majority of patients have no detectable disease by this technique after chemotherapy consolidation, despite the fact that many later relapse. We report a quantitative PCR technique for the PML-RAR alpha cDNA which was used to show that less than 1000 PML-RAR alpha molecules are obtained from 1 microgram of diagnostic bone marrow RNA derived from approximately 1 million APL blasts. The lack of sensitivity of currently employed RT-PCR methods may therefore be explained by their poor yield of PML-RAR alpha cDNA. Minor modifications to the reverse transcription procedure improved this yield 3 fold. Furthermore, expression of the leukaemia-specific transcript increased by approximately one order of magnitude after incubation of the patient's cells for 24 h in vitro with 100 iu/ml alpha interferon.

DNA, Neoplasm↗
PubMed1987

Pathogenesis and transmission of AIDS.

AIDS is a slow virus disease caused by a lentivirus. The silent incubation period following infection usually lasts many years, during which the infected person is potentially infectious to others. Pathological changes accumulate imperceptibly. When major symptomatic disease develops it is eventually fatal. The epidemic spread of the virus is new in Africa, as well as in North America and Europe. Twenty-five per cent of people infected with the virus die within seven years of infection. The ultimate mortality 20 years after infection cannot yet be known, but it may turn out to be close to 100 per cent. It is already apparent that AIDS is the most lethal epidemic viral disease of humans known to medical science. Flaws in the generally accepted hypothesis that AIDS is a sexually transmitted infection are exposed. It has been, characteristically, a blood-borne infection in the early years of the epidemic. However, the AIDS virus is exceptionally unstable genetically and it is probable that means of transmission more efficient than through blood have already developed.

Acquired Immunodeficiency Syndrome↗