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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 199 records · Page 11Linked to original sources

Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family.

For a better understanding of genes that potentially function in B lymphocyte cell signaling, we isolated the human genomic counterpart of the murine pp52 or LSP1 gene. We unexpectedly found that the human pp52 gene is one of four closely related loci. Representative cosmids from each of the four family members were isolated and chromosomally localized by fluorescence in situ hybridization. Nucleotide sequence was obtained from an exon common to each locus and demonstrated very close similarity among all four loci. Two of the four loci harbored dysfunctional frameshift mutations or premature translation stop sites. The exon of one locus was flanked by an 80-bp perfect inverted repeat, suggesting that it may have originated through a looped intermediate DNA structure. Through a series of cDNA hybridization studies and nucleotide sequence analyses we were able to unambiguously link the lymphocyte-expressed gene to the locus mapped to chromosome 11p15.5. This same chromosomal band has been involved in tumor-related chromosomal translocations found in chronic lymphocytic leukemia.

Animals↗

A comparison of speech audiometry and pure tone audiometry in patients with secretory otitis media.

Speech audiometry was performed on 15 children with secretory otitis media pre- and post-operatively and the findings compared with the pre- and post-operative pure tone audiograms. The results showed that in 30 per cent of cases pre-operatively the speech audiogram suggested a significantly worse hearing ability than that suggested by the pure tone audiogram (PTA). Where a PTA gives a borderline threshold disproportionate parental concern should be taken seriously as the hearing ability may well be worse than the PTA suggests.

Audiometry, Pure-Tone↗

A pathological and microbiological evaluation of omphalophlebitis in very young calves slaughtered in New Zealand.

Omphalophlebitis, generally referred to as navel ill, is a common post-mortem meat inspection finding in very young calves slaughtered in New Zealand, and a gross pathological, histopathological and bacteriological evaluation of 147 carcasses condemned for this condition at routine post-mortem meat inspection was undertaken. Localised lesions restricted to the umbilicus alone were present in 29.9% of cases. The majority of cases included gross pathological change in the umbilical vessels and other tissue sites beyond the umbilicus. Most hepatic nodes were grossly normal but histological examination revealed that 61.5% of nodes from other than localised cases of navel ill were hyperplastic. However, there was little difference in the prevalence of hyperplastic hepatic nodes from cases of localised navel ill (21.4%) compared with normal calves (15.9%). Despite the wide range of bacteria isolated from umbilical lesions, Salmonella typhimurium recovered from the navel, liver and hepatic nodes of a single extended case of navel ill was the only isolation of known public health importance. Given the separation of cases of navel ill into different gross pathological, histopathological and microbiological categories, current meat inspection judgments whereby all calves with navel ill are condemned should be revised. In particular, routine condemnation of the carcass and viscera in all cases of localised navel ill (lesions restricted to the umbilicus alone) should be reassessed.

Journal Article↗

A serial study of psychometric and magnetic resonance imaging changes in multiple sclerosis.

Over a 6-month period, five patients with early relapsing--remitting multiple sclerosis and five with long-standing, benign multiple sclerosis underwent serial psychometric testing and contrast enhanced magnetic resonance imaging of the brain at 2-weekly or monthly intervals, respectively. All patients were individually matched with healthy controls who completed the same psychometric battery at the same time intervals. As a group, multiple sclerosis patients either made more errors or performed slower on all psychometric tasks than controls. In the control subjects and those patients with a stable brain lesion score, no consistent deterioration occurred in any test and the overall pattern was one of improvement over time commensurate with practice effects. However, patients with a deteriorating lesion score either showed a fall-off in performance on some psychometric tasks (patients 2, 3) or else an impaired ability to improve with practice on certain tests of attention and information-processing speed (patient 10).

Adult↗

Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes.

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjögren-Vogt, or Batten, disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci.

Alleles↗

Is mammographic microcalcification of biological significance?

Mammographic microcalcification is a feature of a proportion of breast cancers. Its occurrence does not appear to be significantly associated with age or primary tumour size. Lymph node involvement by tumour is present in 50% of patients with mammographic microcalcification in relation to the primary tumour, but only 24% of patients without microcalcification. A significantly larger number of lymph nodes (61 of 241 nodes) are involved with tumour in patients with, in comparison to those without (59 of 476 nodes) microcalcification (P < 0.001, chi 2 test). These differences suggest a biologically significant role for the deposition of calcium in microcalcifications, which may relate to the process of tumour cell metastasis. This may be of importance in the assessment of patients with cancers which demonstrate microcalcification on mammography.

Breast Neoplasms↗

Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit.

Purified bovine brain phosphatidylinositol 3-kinase (Pl3-kinase) is composed of 85 kd and 110 kd subunits. The 85 kd subunit (p85 alpha) lacks Pl3-kinase activity and acts as an adaptor, coupling the 110 kd subunit (p110) to activated protein tyrosine kinases. Here the characterization of the p110 subunit is presented. cDNA cloning reveals p110 to be a 1068 aa protein related to Vps34p, a S. cerevisiae protein involved in the sorting of proteins to the vacuole. p110 expressed in insect cells possesses Pl3-kinase activity and associates with p85 alpha into an active p85 alpha-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85 alpha.

Amino Acid Sequence↗

Immunoglobulin kappa light chain germ-line transcripts in human precursor B lymphocytes.

B lymphoblastoid cell lines (BLCL), established from bone marrow and peripheral blood mononuclear cells from two severe combined immunodeficiency (SCID) patients, manifested a complete absence of genomic rearrangements of the immunoglobulin (Ig) heavy (H) and light (L) chain loci. The BLCL contained germ-line transcripts of the Ig kappa region locus of approximately 1.2 kilobase (kb). By cDNA cloning and sequence analysis the transcripts were shown to consist of a C kappa segment, a J kappa 1 gene segment, 160 base pairs (bp) of J kappa 1 5' intervening sequence, containing the heptamer/nonamer recombination recognition sequences and at the 5' end a 523-bp segment designated human kappa zero, The first 206 bp of this 5' segment were homologous to the reported murine kappa zero region. Genomic restriction mapping and DNA sequence analysis demonstrated that the human kappa zero segment is located approximately 4 kb upstream of J kappa 1. The kappa zero segment contains a putative promoter region with an OCT2 binding site, and has a splice donor site to accomplish splicing to an acceptor site 160 bp upstream of J kappa 1. Expression of the kappa zero gene segment was found in BLCL derived from normal fetal bone marrow, in which both Ig kappa loci were in the germ-line configuration. These findings indicate that the described transcripts are not only present in SCID, but also in normal developing pre-B lymphocytes. The expression of germ-line Ig kappa L chain transcripts may be associated with the locus becoming accessible to gene rearrangement.

B-Lymphocytes↗

Acute exercise: buffering psychosocial stress responses in women.

We evaluated the experimental hypothesis that an acute bout of aerobic exercise (AE) serves as a buffer to psychosocial stress responses in low to moderate physically fit women. Forty-eight (24 White, 24 Black) 25- to 40-year-old women participated in two counterbalanced experimental conditions: an attention control and a 40-min bout of AE at 70% heart rate (HR) reserve. The attention control and AE treatments were followed by (a) 30 min of quiet rest, (b) exposure to mental and interpersonal threat, and (c) 5 min of recovery. Blood pressure (BP) and HR were monitored at baseline, during the stressors, and throughout recovery. Self-reported distress was assessed before each stressor and upon completion of the recovery period. The results provided clear evidence that exercise dampens BP reactivity to psychosocial stress. Additionally, compared with the attention placebo control, AE reduced both the frequency and intensity of anxiety-related thoughts that occur in anticipation of interpersonal threat and challenge.

Adaptation, Psychological↗

Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase.

Affinity-purified bovine brain phosphatidylinositol 3-kinase (PI3-kinase) contains two major proteins of 85 and 110 kd. Amino acid sequence analysis and cDNA cloning reveals two related 85 kd proteins (p85 alpha and p85 beta), which both contain one SH3 and two SH2 regions (src homology regions). When expressed, these 85 kd proteins bind to and are substrates for tyrosine-phosphorylated receptor kinases and the polyoma virus middle-T antigen/pp60c-src complex, but lack PI3-kinase activity. However, an antiserum raised against p85 beta immunoprecipitates PI3-kinase activity. The active PI3-kinase complex containing p85 alpha or p85 beta and the 110 kd protein binds to PDGF but not EGF receptors. p85 alpha and p85 beta may mediate specific PI3-kinase interactions with a subset of tyrosine kinases.

Animals↗

Carnitine in dried blood spots: a method suitable for neonatal screening.

A method is described which enables the quantitative determination of both free and total carnitine levels in dried blood spots. This method is suitable for neonatal screening for either primary or secondary carnitine deficiency. The 95% confidence interval for free carnitine was 26-76 mumol/l (median = 44) and for total carnitine was 35-102 mumol/l (median = 60).

Carnitine↗

Full-length chicken parathyroid hormone. Biosynthesis in Escherichia coli and analysis of biologic activity.

Chicken parathyroid hormone (cPTH) has been reported to stimulate adrenal steroidogenesis and to have unusual potency on traditional PTH target tissues. To evaluate these properties, chicken PTH-(1-88) has been expressed in Escherichia coli using a plasmid encoding a fusion protein which links together growth hormone, a factor Xa recognition site, and chicken PTH-(1-88). The growth hormone-cPTH fusion protein required the presence of 0.02% sodium dodecyl sulfate to remain in solution and be cleaved by factor Xa. The high performance liquid chromatography-purified recombinant cPTH-(1-88) and chemically synthesized cPTH-(1-34) had similar potency in rat osteosarcoma (ROS 17/2.8) cells, opossum kidney (OK) cells, and dispersed primary chicken kidney cells. The biologic potencies of cPTH-(1-34) and cPTH-(1-88) in radioreceptor binding and cAMP generation in both bone- and kidney-derived cell lines were less than those of human (h)PTH-(1-34). In dispersed chicken kidney cells, cAMP production by cPTH-(1-34) and cPTH-(1-88) was similar to that stimulated by human PTH-(1-34). No stimulation of steroidogenesis could be detected when recombinant chicken PTH-(1-88) was added to dispersed chicken adrenal cells. The biologic activity of recombinant chicken PTH-(1-88) purified from E. coli was comparable with that of chicken PTH-(1-88) expressed by mammalian COS cells. Thus, the full-length chicken PTH did not exhibit enhanced potency, when compared with human PTH in ROS 17/2.8, OK cell lines, and dispersed chicken kidney cells and did not demonstrate the novel steroidogenic action previously reported in adrenal cells. The successful production of chicken PTH-(1-88) will enhance our understanding of the structure-activity relationships for PTH, particularly the sequence-dependent metabolism of the hormone.

Animals↗