Biomedical subjects
Publications and source records attributed to M Prendergast.
Two cases of autism and autosomal chromosome abnormalities are reported: a 14-year-old boy with interstitial deletion of chromosome 17 and a 19-year-old man with an unbalanced translocation of chromosome 5, resulting in monosomy for part of the short arm (5pter-->5p15.3). The possible implications for research into the aetiology of autism are discussed.
A 13 year old Asian girl presenting with apparent hysterical paralysis and subsequent rapid cycling bipolar mood disorder was found to have biochemical evidence of pseudohypoparathyroidism type II. The mood disorder responded to treatment of the pseudohypoparathyroidism with a vitamin D analogue. Investigation of her parents and siblings showed phenotypes consistent with two distinct types of pseudohypoparathyroidism (type I and type II) in different family members.
Four children presented to child psychiatric clinics with a variety of symptoms. They were all later recognised as having Crohn's disease. There was a significant delay between the onset of symptoms and diagnosis, compared with a control group of patients with Crohn's disease whose presentation was with predominantly gastrointestinal symptoms, which was associated with evidence of increased morbidity. Children with abdominal and psychiatric symptoms occurring in combination need serial assessments of physical status, including height and weight, and measurements of inflammatory and nutritional status.
Substantial numbers of both alpha/beta and gamma/delta T cells are present in human fetal liver, which suggests a role of the fetal liver in T cell development. The diversity of fetal liver T cell receptor (TCR) gamma and delta chain rearrangements was examined among both CD4+CD8- and CD4-CD8- gamma/delta T cell clones. In addition, TCR delta chain transcripts from three fetal livers were sequenced after polymerase chain reaction amplification of TCR delta chains with V delta 1 or V delta 2 rearrangements. Five of six fetal liver gamma/delta T cell clones had a V delta 2-D delta 3-J delta 3 gene rearrangement with limited junctional diversity; three of these clones had an unusual CD4+CD8- phenotype. V delta 2-D delta 3-J delta 3 gene rearrangements were also common among both in-frame and out-of-frame transcripts from three fetal livers, indicating that they are the result of an ordered rearrangement process. TCR gamma chain sequences of the fetal liver gamma/delta T cell clones revealed V gamma 1-J gamma 2.3, V gamma 2-J gamma 1.2, and V gamma 3-J gamma 1.1 rearrangements with minimal incorporation of template-independent N region nucleotides. TCR gamma chain rearrangements found in these fetal liver T cell clones were different from those that have been observed among early thymic gamma/delta T cell populations, while similar TCR delta chain rearrangements are found among gamma/delta T cells from both sites. These data demonstrate that the fetal liver harbors gamma/delta T cell populations distinct from those found in the fetal thymus, suggesting that the fetal liver is a site of gamma/delta T cell development in humans. These unusual T cell populations may serve a specific function in the fetal immune system.
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A long-term CD4-CD8- TCR alpha beta human T-cell line, as well as similar CD4-CD8- TCR gamma delta T-cell lines for comparison, were generated from various tissues by negative selection using anti-CD4 and anti-CD8 monoclonal antibodies (MAbs) followed by positive selection with specific anti-TCR MAb and then repeated in vitro stimulation with interleukin-enriched media and lectin. These cell lines all demonstrated non-MHC-restricted cytolysis on a variety of human tumor cell lines. However, removal of lymphokines from the culture media for 24 hr abrogated most of the non-MHC-restricted target-cell lysis without affecting TCR alpha beta or TCR gamma delta cell viability or TCR function as determined by antibody-triggered redirected target-cell lysis. Subsequent re-exposure to lymphokines reconstituted non-MHC-restricted cytolysis by these cell lines. Thus, much of the non-specific, non-MHC-restricted cytolytic activity generated by CD4-CD8- TCR alpha beta or TCR gamma delta cells is secondary to lymphokine-activated killing (LAK) activity. These cells have potent LAK activity and may be prominent in LAK-cell populations. In addition, after lymphokine deprivation, both CD4-CD8- TCR alpha beta and TCR gamma delta cells showed residual activity against some tumor-cell targets, the nature of which remains to be defined.
Tics are relatively common in childhood, especially between the ages of six to 12 years. While eye-blinking and eye-winking tics are well recognised, eye-movement tics are not. Three children with conjugate eye-movement tics, occurring alone or in combination with other tics, are described and the differential diagnosis is discussed. Treatment of tics in the first instance comprises reassurance and explanation. Detailed further investigation is not indicated, but follow-up is desirable while tics persist, since some children may go on to develop Tourette syndrome or chronic tic disorder.
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Two patients with Gilles de la Tourette syndrome (GTS) showed tics triggered by external stimuli. This unusual feature is of significance to the aetiology of GTS and in particular the relationship between GTS and the startle response.
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Aesthetic malar augmentation is described to improve the appearance of patients with flattening of the malar eminence, to create a more youthful appearance of the face, to make the face more oval in appearance, and to de-emphasize prominent nasal or mental profiles. Detailed preoperative analysis of surgical candidates has not been reported. Twenty models studied by photogrammetry of frontal, lateral, and oblique views were analyzed to synthesize ideal measurements of an aesthetic face with particular attention to points describing the malar mound. Photographs of patients operated on were analyzed using computer graphics to compare the synthesized ideal and surgical results. Ideal candidates are defined as those patients with ptotic malar mounds with adequate soft tissue to create a balanced and harmonious result. Examples of candidates and potential pitfalls are presented.
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The unequal prevalence of hyperactivity in Britain and the U.S. was investigated with a cross-national diagnostic study. Case histories of 6-11-yr-old boys were evaluated by British and American research teams as well as British and American clinician panels using both ICD-9 and DSM-III. Interrater agreement was acceptably high only for the specially trained research teams. ICD-9 generated fewer diagnoses of Hyperkinetic Syndrome than did DSM-III of Attention Deficit Disorder with Hyperactivity. The difference was greatest for U.K. clinicians. Diagnostic scheme and clinician training both contribute to the difference in reported rates.
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Two monoclonal antibodies suitable for leukemia cell purging of remission bone marrow from patients with common acute lymphoblastic leukemia (common-ALL) are described. WM-21, reacting with the gp 100 common-ALL associated antigen (CALLA), and FMC-8, reactive with a p24 surface antigen, both bind to the majority of leukemic blast cells from cases of common ALL, and promote complement-mediated lysis of CALLA+ leukemias and cell lines. After initial dye exclusion studies to standardize antibody and rabbit complement concentrations and incubation times, an in vitro plating assay using CALLA+ p24+ cell lines was used to investigate the lytic ability of monoclonal antibody treatment. Incubation with WM-21, FMC-8, and complement produced up to 5 logs inhibition of growth in this system. Under similar conditions, no inhibition of in vitro growth of normal bone marrow myeloid progenitor cells was seen. These antibodies therefore appear to be useful therapeutic reagents for removing residual common ALL blast cells from bone marrow prior to autologous marrow transplantation.