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Biomedical subjects

A H Reid

Publications and source records attributed to A H Reid.

At least 19 recordsLinked to original sources

Initial genetic characterization of the 1918 "Spanish" influenza virus.

The "Spanish" influenza pandemic killed at least 20 million people in 1918-1919, making it the worst infectious pandemic in history. Understanding the origins of the 1918 virus and the basis for its exceptional virulence may aid in the prediction of future influenza pandemics. RNA from a victim of the 1918 pandemic was isolated from a formalin-fixed, paraffin-embedded, lung tissue sample. Nine fragments of viral RNA were sequenced from the coding regions of hemagglutinin, neuraminidase, nucleoprotein, matrix protein 1, and matrix protein 2. The sequences are consistent with a novel H1N1 influenza A virus that belongs to the subgroup of strains that infect humans and swine, not the avian subgroup.

Algorithms

Development and characterization of v-myc/v-raf-transformed murine fetal thymocyte cell lines.

Transformed murine fetal thymocyte cell lines were derived by incubating fetal thymic organ cultures with a v-myc/v-raf-containing retroviral construct in order to model developmental stages within the early triple negative (CD3-CD4-CD8-) thymocyte population. The resulting 10 cell lines had a lymphoid morphology, were all CD44+, CD90+, and were triple negative by surface antigen analysis. The cell lines, however, were distinguishable by differences in the expression of T cell-associated and T cell-specific genes. The CD3 genes were observed to be discoordinately expressed, in that CD3 gamma chain gene expression was detected in 2 cell lines in the absence of CD3 delta and epsilon expression. Expression of the CD3 gamma chain gene was observed in cell lines without the expression of other T cell-specific genes or T cell receptor rearrangement and may be one of the earliest T cell-specific genes to be expressed. The transcription factor Ikaros was expressed in all 10 cell lines, whereas the transcription factor TCF1 alpha was expressed only in the 2 most differentiated lines. In 8 cell lines, expression of partial TCR beta and/or TCR alpha transcripts was observed by Northern blot. In several lines, expression of rearranged TCR alpha transcripts in the absence of TCR beta transcripts was demonstrated; however, TCR beta DJ rearrangements were observed by Southern blot in all but 1 of these cell lines. Thus, these cell lines, ordered based on the general pattern of additive gene expression observed, may reflect various stages of triple-negative thymocyte differentiation and provide an in vitro mechanism to elucidate some of the molecular events involved in early thymocyte development.

Animals

MDM2 amplification, P53 mutation, and accumulation of the P53 gene product in malignant fibrous histiocytoma.

Fifty-two cases of malignant fibrous histiocytoma (MFH) were evaluated for amplification of the MDM2 gene, mutation of the P53 gene, accumulation of the P53 gene product, and their relation to disease-free and overall survival. All tests were carried out on formalin-fixed, paraffin-embedded tissue samples. Amplification of the MDM2 gene was detected in 15 of 52 cases (29%). Six of 52 cases (12%) demonstrated abnormalities of the P53 gene. Sequence analysis detected point mutations in four cases and a 1-base pair deletion in one case, whereas differential polymerase chain reaction (dPCR) indicated that the P53 gene had been entirely deleted in one case. Eight of 52 cases (15%) demonstrated staining for the P53 protein in >10% of tumor cells. The presence of MDM2 amplification did not have a significant effect on either disease-free or overall survival. Patients with accumulation of the P53 gene product did not differ in disease-free or overall survival from patients without P53 accumulation. Survival also was not significantly different in patients with genetic aberration in P53. However, when the patients were stratified by histologic grade, the results indicated that patients with alterations in the P53 gene may have shorter overall survival.

Gene Amplification

Behaviour symptoms among severely and profoundly mentally retarded patients. A 16-18 year follow-up study.

BACKGROUND: Little is known about the natural history and evolution of behaviour symptoms and patterns in severely and profoundly mentally retarded adults. This paper reports a cohort study of 100 such adults. METHOD: Abnormal behaviour symptoms and patterns have been followed, using a carer rating scale and the modified Manifest Abnormality Scale of Goldberg's Clinical Interview Schedule (1970) by the same two consultant psychiatrists in 1975, 1981 and 1992. RESULTS: Emotional withdrawal, stereotypes and eye avoidance are particularly persistent. Carer ratings of noisiness and social withdrawal, and psychiatrist ratings of suspiciousness, overactivity and hostile irritability, are also persistent but to a lesser degree. Overall ratings of psychiatric disorder are persistent and act against successful community placement. CONCLUSIONS: Abnormal behaviour patterns in severely and profoundly mentally retarded adults show only a modest degree of abatement over time. Care staff need a good understanding of clinical psychiatric and behaviour management techniques.

Activities of Daily Living

Irregular distortion of the erythrocytes (acanthocytes, spur cells) in senile dementia.

An excess of irregularly distorted red cells with spiked forms (acanthocytes, spur cells) has been found in a substantial minority of patients with senile dementia of Alzheimer type (7 of 50 patients, 3 of 21 men and 4 of 29 women). Of 100 control patients, 42 men and 58 women), 5 (3 men and 2 women) showed comparable distortion, but, of these, one man may well have incipient dementia and the others had serious organic diseases which may be associated with comparable erythrocytic changes. The cause of the distortion is not yet clear, but the presence of occasional giant erythrocytes in the absence of general macrocytosis suggests a possible abnormality of cell-membrane synthesis. This distortion may be a useful marker in patients with loss of memory. Whether it is a manifestation of a haemopoietic clone or a constitutional anomaly associated with Alzheimer's disease remains to be seen.

ABO Blood-Group System

A cryptic peptide from the preprothyrotropin-releasing hormone precursor stimulates thyrotropin gene expression.

The precursor peptide of TRH (prepro-TRH) contains five copes of pro-TRH linked by other peptide sequences. These peptides are coprocessed with TRH in the median eminence of the hypothalamus and released into the portal circulation, rendering this family of peptides available to act at the level of the anterior pituitary. Therefore, we tested the potential bioactivity of one cryptic peptide, prepro-TRH amino acids 160-169 [prepro-TRH-(160-169)], in a TRH-responsive pituitary cell line (GH3). In a heterologous TSH expression assay, we found that prepro-TRH-(160-169) stimulated TSH beta gene promoter activity in a time- and dose-dependent manner; moreover, the effect of prepro-TRH-(160-169) was more rapid and of greater magnitude than that of TRH on TSH beta-directed chloramphenicol acetyltransferase synthesis. In the same cells, we found that prepro-TRH-(160-169) stimulated PRL synthesis and secretion, but the effect was similar in magnitude and duration to that of TRH. The effect of prepro-TRH-(160-169) appears to be additive to that of TRH, suggesting that prepro-TRH-(160-169) may act through a mechanism separate from that of TRH. Thus, prepro-TRH-(160-169) has potent endocrinological effects at the level of the genome.

Amino Acid Sequence

bcl-2 rearrangement in Hodgkin's disease. Results of polymerase chain reaction, flow cytometry, and sequencing on formalin-fixed, paraffin-embedded tissue.

We examined 81 cases of Hodgkin's disease for evidence of the t(14;18) translocation, using the polymerase chain reaction assay on lysates of formalin-fixed, paraffin-embedded tissue. Seven of 74 amplifiable cases (9%) were positive for the translocation, which involves the bcl-2 oncogene and the immunoglobulin heavy chain gene. Two of these cases were sequenced and the breakpoints had the same pattern found in follicular lymphoma. The nuclei from one of the cases were sorted into large and small subpopulations. The t(14;18) signal was more intense in the large nucleus subpopulation, which contained a greater proportion of Reed-Sternberg-like nuclei. These results are consistent with the hypothesis that Reed-Sternberg cells carry the translocation, but they do not exclude the possibility that the translocation is found in cells representing the reactive component of Hodgkin's disease. The results also demonstrate that routinely processed material is suitable for polymerase chain reaction-based analysis of translocations, although the sensitivity is reduced 10- to 100-fold, compared with fresh tissue.

Base Sequence

Epstein-Barr virus in Hodgkin's disease from patients with human immunodeficiency virus infection.

The polymerase chain reaction (PCR) technique was used to detect the presence of Epstein-Barr virus (EBV) DNA sequences in Hodgkin's disease specimens from 10 patients who were also positive for the human immunodeficiency virus (HIV). Eight of 10 specimens were positive for EBV, compared to 23 of 57 Hodgkin's disease specimens from patients without HIV infection, suggesting a closer association between Epstein-Barr virus infection and Hodgkin's disease in patients with HIV infection than in the general population.

Adult

Thyrotropin-releasing hormone regulation of thyrotropin beta-subunit gene expression involves intracellular calcium and protein kinase C.

Our previous studies demonstrated TRH stimulation of TSH beta gene expression in rat pituitary cell cultures and GH3 tumor cells in a transient expression assay. To begin to characterize the gene-proximal elements of the pathways involved in TRH stimulation of TSH beta gene transcription, we examined the effects of factors that increase intracellular calcium concentration, [Ca2+]i, or activate protein kinase C on TSH beta promoter activity in transfected GH3 cells. TPA, a tumor-promoting phorbol ester, stimulated a dose-dependent increase in TSH beta promoter activity at 8 h similar to TRH (2-3-fold). TPA did stimulate protein kinase C activation without [Ca2+] mobilization. The calcium ionophore ionomycin increased cytoplasmic free [Ca2+] by stimulating both calcium influx and release from internal stores without affecting protein kinase C. Ionomycin also stimulated a dose-dependent increase (2-fold) in TSH beta promoter activity at 8 h. However, the voltage-dependent Ca2+ channel agonist Bay K 8644, which increased influx of extracellular calcium, had little or no effect on TSH beta gene expression until 48 h (5-fold). Similar effects on prolactin/mRNA levels were observed in these cells. Effects of these factors were not additive, suggesting a common pathway(s) to stimulate gene expression. Inhibition of intracellular calcium mobilization by treatment with 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) inhibited ionomycin effects on gene expression without affecting phorbol ester activity, and, conversely, inhibition of protein kinase C activity by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) or TPA desensitization blocked TPA effects without affecting ionomycin activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

The psychiatric symptoms, diagnoses and care needs of 100 mentally handicapped patients.

One hundred randomly selected residents of a mental handicap hospital originating from Dundee were interviewed using a standardised assessment based on the modified Standardised Clinical Interview Schedule. Information on certain behavioural items and self-care skills was obtained from nursing staff and case records. An ICD-9 diagnosis could be made for 80 individuals, including diagnoses usually reserved for children. Thirty subjects were regarded as needing long-term psychiatric mental handicap hospital care. All but one of the remaining 70 subjects required a staffed residential placement and all but 15 some form of out-patient or short-term in-patient provision from specialist health services. The findings indicate a need for approximately 30 psychiatric mental handicap beds per 100,000 population.

Adult

Detection of Epstein-Barr virus sequences in Hodgkin's disease by the polymerase chain reaction.

The authors examined paraffin-embedded lymph node biopsies from 65 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, using the highly sensitive polymerase chain reaction technique. Overall 40% of the cases were positive for EBV DNA; there were no statistically significant differences in the frequency of EBV positivity among the different subtypes of Hodgkin's disease. These results are in agreement with those of previous studies that employed less sensitive detection techniques and suggest that EBV either is present in pathologic tissues only in some phases of the evolution of Hodgkin's disease or is a pathogenetic factor involved in only a portion of cases.

Biopsy

Schizophrenia in mental retardation: clinical features.

Schizophrenia is a small but important aspect of the psychiatry of mental retardation. In this article the literature is reviewed and the clinical features, symptomatology, and diagnostic parameters are discussed. Data are presented about prevalence rates, degree of mental retardation, male: female distribution, and age of onset. There appears to be no specific relationship with epilepsy or chromosomal abnormalities, although paranoid syndromes are often associated with disorders of hearing and vision. Differential diagnosis is considered and treatment approaches outlined.

Adolescent