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Biomedical subjects

D Beatty

Publications and source records attributed to D Beatty.

At least 19 recordsLinked to original sources
PubMed1996

Expression of either the TCL1 oncogene, or transcripts from its homologue MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients.

Patients with the recessively inherited disorder ataxia telangiectasia (A-T) have a high level of specific chromosome translocations which can be easily observed in peripheral T cells and show a greatly increased predisposition to leukaemia/lymphoma, mainly of T cell origin. Some translocation cells proliferate into a large clone and may develop into T cell prolymphocytic leukaemia (T-PLL). By the time of diagnosis of T-PLL, the clone contains many more genetic changes in the form of additional translocations. T-PLL is also seen in non-A-T individuals where expression of either TCL1 (at 14q32) or the c6.1B/MTCP1 A1 transcript (at-Xq28) has been demonstrated in just a few instances. We show here, that expression of TCL1 occurs in leukaemic T cells from A-T patients with chromosome 14 rearrangements. Expression of TCL1 also occurs in the preleukaemic clone cells of A-T patients containing the primary translocation alone. Some expression of TCL1 could also be detected in randomly selected A-T patients without large cytogenetic clones and without any evidence of leukaemic change. We also show that expression of the B1 transcript from a second gene, MTCP1, occurred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocations whereas the MTCP1/A1 transcript is much more widely expressed in both tumour and non tumour cells of A-T and non-A-T individuals.

Ataxia Telangiectasia↗
PubMed1996

Changes within T cell receptor V beta subsets in infants following measles vaccination.

Measles produces immune suppression which contributes to an increased susceptibility to other infections. Recently, high titered measles vaccines have been linked to increased long-term mortality among some female recipients. Because the mechanisms by which wild-type or attenuated live-vaccine strains of measles virus alter subsequent immune responses are not fully understood, this prompted an examination of the changes within the peripheral blood T cell receptor V beta repertoire following measles immunization. Twenty-four 6- and 9-month-old infants were studied at 2 weeks and 3 months following immunization by semiquantitative reverse transcription-polymerase chain reaction. There was a significant increase in V beta 2 expression (P less than 0.05), and a decrease in the V beta 4 subset (P less than 0.03) 2 weeks following vaccination with subsequent return to baselines at 3 months in vaccine recipients who seroconverted. These data suggest that measles virus may affect immune responses in part by altering the T cell receptor repertoire.

Base Sequence↗
PubMed1996

The effect of Edmonston-Zagreb and Schwarz measles vaccines on immune response in infants.

The effects of measles immunization on immune responses in infants and the roles of vaccine strain and age of immunization are not known. Eighty-eight children were immunized at 6 or 9 months of age with the Edmonston-Zagreb (EZ) or Schwarz (SW6, SW9) strain of measles vaccine. Children were studied before and 2 weeks and 3 months after immunization. Seroconversion was similar, but geometric mean neutralizing titers at 3 months differed by vaccine group: SW9, 1367 mIU/mL; SW6, 982; and EZ, 303 (P = .003). Mitogen-induced lymphoproliferation was decreased at 2 weeks in the SW9 group and at 3 months in all groups and was negatively correlated with measles antibody level at 3 months (r = -.387, P = .003). CD8 T cells, soluble CD8, neopterin, and beta2-microglobulin were increased at 2 weeks in the SW9 group, and soluble CD8 and beta2-microglobulin remained elevated at 3 months. Therefore, measles immunization resulted in suppression of lymphoproliferation, which was most evident in infants with the highest antibody responses and most immune activation.

Age Factors↗
PubMed1994

A gene on chromosome Xq28 associated with T-cell prolymphocytic leukemia in two patients with ataxia telangiectasia.

A t(X;14)(q28;q11) translocation was present for many years in T cells in two patients with ataxia telangiectasia (A-T), who subsequently developed T-prolymphocytic leukemia. We describe here the relationship between the translocation breakpoints in these patients with respect to two recently described genes, c6.1A and c6.1B, on Xq28 which are transcribed in opposite directions from the same CpG island. In our first patient, the Xq28 breakpoint disrupts the c6.1A gene which is consequently transcribed as a fusion mRNA with the TCR C alpha chain gene. In the second case, the Xq28 breakpoint lies within the adjacent gene c6.1B, and c6.1A is not transcribed. We show that the c6.1B gene is transcribed in both of our patients. c6.1B may be important in the initial clonal proliferation of T lymphocytes which commonly precedes transformation to T-PLL in ataxia telangiectasia patients. The same gene may also be involved in the development of T-PLL in the non-A-T population.

Adult↗
PubMed1992

Infections in severely traumatized children.

To study the incidence and types of infection among severely traumatized children, we reviewed the medical charts of 212 children, hospitalized following traumatic injury, who received antibiotics at sometime during their hospitalization. Infection occurred in 19%. Eleven children had trauma-related infections, whereas 29 (71% of those infected) had 36 nosocomial infections. Tracheitis, sepsis, and urinary tract infections were the most common nosocomial infections and were diagnosed in the second week (10 +/- 3 days) following injury. Nosocomial infections were more likely to develop in children who were more severely injured and who had a greater number of invasive procedures. Severe head injury (cerebral edema or subarachnoid hemorrhage) was more common in those with nosocomial infection (P < .0002, odds ratio 6.8, 95% confidence interval 2.2 to 21.3). Those without these injuries were much less likely to develop nosocomial infections (specificity 97% and negative predictive value 86%). Finally, the development of any nosocomial infection prolonged the hospitalization by a mean of 16 +/- 6 days when comparing children with the same degree of traumatic injury. Prevention of nosocomial infection in children with severe trauma will significantly reduce length of hospitalization.

Accidents, Traffic↗
PubMed1992

Development of T-cell leukaemia in an ataxia telangiectasia patient following clonal selection in t(X;14)-containing lymphocytes.

Ataxia telangiectasia is a rare inherited and progressive neurological disorder in which patients show an unusual predisposition to T-cell leukaemia. We report here observations on a patient with a large cytogenetically abnormal clone showing a single t(X;14)(q28;q11) translocation which conferred a proliferative advantage on the cells. The further evolution of this clone to cytogenetically more complex clones of lymphocytes was seen in the patient. She subsequently developed a rapidly progressing T-cell leukaemia, with a CD4+CD8+ T-cell phenotype, about five years after the first appearance of additional chromosome translocations in the clone cells.

Ataxia Telangiectasia↗
PubMed1990

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