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Biomedical subjects

J Adamson

Publications and source records attributed to J Adamson.

At least 19 recordsLinked to original sources
PubMed1994

Are cerebral aneurysms atherosclerotic?

BACKGROUND AND PURPOSE: The aim of our study was to investigate plasma and genetic risk factors for rupture of cerebral aneurysms. METHODS: In London, a case-control study was made of 56 consecutive patients admitted to a regional neurosurgical service for treatment of ruptured cerebral aneurysm and of 93 control subjects. A further 40 consecutive patients admitted in Arhus with ruptured cerebral aneurysm also were studied. RESULTS: The British case-control study showed that smoking was associated with an increased risk of ruptured cerebral aneurysm (odds ratio, 9.1; 95% confidence interval [CI], 3.4 to 23.8; P < .001 for a history of > 10 pack years). After age and sex adjustment, factors associated with ruptured cerebral aneurysm included a cholesterol concentration in the highest tertile (> or = 6.3 mmol/L; odds ratio, 10.2; 95% CI, 3.9 to 26.7; P < .001), an apolipoprotein B concentration in the highest tertile (> or = 0.84 g/L; odds ratio, 6.4; 95% CI, 2.5 to 16.3; P < .001), and concentrations of HDL cholesterol in the lowest tertile (< 1.1 mmol/L; odds ratio, 3.6; 95% CI, 1.4 to 8.2; P < .01). History of hypertension was of less importance (odds ratio, 4.0; 95% CI, 1.41 to 11.7; P < .01). Smoking history (P < .001) and increased concentrations of cholesterol (P < .0001) were the most important independent risk factors associated with ruptured cerebral aneurysm on multivariate analysis. The histories of hypertension and smoking, together with apolipoprotein B levels, in the Danish patients were similar to those in the British patients. In the entire patient group, the frequencies of two polymorphic variations in the type III collagen gene and polymorphisms at the apolipoprotein B, apolipoprotein C-III, and haptoglobin gene loci were not different from control subjects or the normal population; allele frequencies in British and Danish patients were similar. CONCLUSIONS: An atherosclerotic profile including increased total cholesterol concentration and a long smoking history may contribute to the rupture of cerebral aneurysms. This study provides no support for the hypothesis that inherited abnormalities of type III collagen are a common cause of cerebral aneurysms.

Adult↗
PubMed1993

Influence of type III collagen genotype on aortic diameter and disease.

Type III collagen contributes to the tensile strength of the aortic wall, and mutations in the type III collagen gene have been suggested as the basis for the familial tendency to abdominal aortic aneurysm (AAA). Variation in this gene was investigated in 153 patients with AAA, 87 with aortoiliac stenosis and 98 age-matched controls. The rare mutation at amino acid 619 of Gly-->Arg, previously associated with AAA in a single family, was not found in any of the patients with aneurysm. For the Ala-->Thr variation at amino acid 531, the frequency of the threonine allele was 0.25 in patients with AAA and stenosis, compared with 0.35 in controls. The frequency of the rare allele in the region 3' to the gene demonstrated by Ava II digestion (0.27 in the general population) was found to be 0.29 in the AAA group and 0.19 in the stenosis group (P = 0.023). In the AAA group the presence of the Ava II rare allele was associated with a significant increase in aneurysm diameter (P = 0.044). Non-invasive assessment of aortic distensibility was available in 25 patients: those carrying the Ava II rare allele had less distensible aortas than those not carrying this allele (median pressure-strain elastic modulus 42.0 and 23.9 N/cm2 respectively, P = 0.008). Variation in the type III collagen gene may influence the mechanical properties of the ageing aorta and hence its susceptibility to disease and dilatation. In contrast, there is no evidence for a single common founder mutation in type III collagen predisposing to AAA.

Aged↗
PubMed1993

Risk factors for atherosclerosis in men with stenosing or aneurysmal disease of the abdominal aorta.

Risk factors associated with atherosclerosis were compared in 2 groups of men: with aneurysmal dilatation (AAA) or stenosing disease (SAD) of the infrarenal aorta. In the AAA group (N = 114) the median aortic diameter was 6.9 cm and 89% of patients had undergone elective or emergency surgical repair. In the SAD group (N = 57) an equal proportion had had an aortobifemoral bypass, the median aortic diameter was 1.8 cm. Men with AAA were older (73 years vs 68 years; p < 0.001). There were no differences in total cholesterol and triglycerides between the two but men with AAA had a higher HDL-cholesterol concentration (1.22 mmol/l vs 1.08 mmol/l; p = 0.019). Tobacco consumption in the 2 groups was similar (36.5 pack years vs 35.0 pack years; p = 0.387). After correction for age, diastolic blood pressure was significantly higher in the AAA group. In both groups there is extensive aortic atherosclerosis but differences between the two groups indicate that stenosing and dilating disease are distinct pathological entities.

Age Factors↗
PubMed1993

Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7.

Erythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma-globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3).(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Northern↗
PubMed1992

Selection for screening for familial aortic aneurysms.

The reported familial clustering of abdominal aortic aneurysm (AAA) indicates the possible rewards of family-based screening programmes with respect both to the number of asymptomatic aneurysms detected and to identifying associated genes. Ultrasonographic screening of 28 families (25 brothers and 28 sisters) was carried out together with collecting a history and a blood sample for analysis of the cholesterol level and genetic markers. Among the screened siblings six (11 per cent), all > 60 years old, had an AAA > or = 3.0 cm in diameter. A further 11 siblings (21 per cent), six of whom were < 60 years old, had a wide (2.5-2.9 cm) aorta. The presence of an aneurysmal or wide aorta was significantly associated with smoking (P = 0.027), male sex (P = 0.008) and a proband age of < 60 years (P = 0.031). Polymorphic genetic markers for type III collagen and haptoglobin were not informative in these families. These results indicate that the efficiency of screening siblings of patients with AAA could be improved by limiting it to brothers with a smoking history and/or siblings of younger patients. The familial component appears to be greatest in these younger patients.

Adult↗
PubMed1991

Genetic variants of collagen III and abdominal aortic aneurysm.

Collagens provide the tensile strength of the aortic wall. Variations in collagen structure are recognised in Ehlers Danlos syndrome type IV and could also be associated with a predisposition to aortic aneurysm. The frequency of some minor genetic variants of type III collagen, present in the normal population, can be detected by restriction enzyme digestion of genomic DNA from peripheral leucocytes. The frequency of a minor collagen type III allele demonstrated with the restriction enzyme Ava II was compared in patients with abdominal aortic aneurysm (n = 70) and aortoiliac stenosis (n = 47). The frequency of the minor allele was significantly higher in aneurysm patients (0.30) compared with patients with aortoiliac stenosis (0.17), p less than 0.05. The presence of the minor allele was associated with a less elastic aneurysm wall (median pressure strain elastic modulus 4575, n = 7), compared with patients homozygous for the common allele (median pressure strain elastic modulus 1990, n = 6), p less than 0.05. These results indicate that genetic variants of type III collagen may influence the extensile properties of the aortic wall and that mutations in the type III collagen gene may be associated with aortic aneurysms.

Aged↗
PubMed1990

TonB protein of Salmonella typhimurium. A model for signal transduction between membranes.

The tonB gene product is required for several outer membrane transport processes in bacteria. The tonB gene from Salmonella typhimurium was sequenced and found to be similar to that of Escherichia coli. The TonB protein is highly proline-rich and includes an unusual segment consisting of multiple X-Pro dipeptide repeats. A synthetic peptide corresponding to this segment has been used to raise anti-TonB antibodies. TonB was shown to be associated with the cytoplasmic membrane, apparently anchored via a single hydrophobic N-terminal segment. Protease accessibility studies, and the use of a series of TonB-beta-lactamase fusions, showed that the rest of the TonB protein is periplasmic. Unusually, export of TonB is not accompanied by cleavage of the N-terminal signal peptide. In the accompanying paper, we show that TonB interacts directly with the outer membrane FhuA (TonA) receptor. Thus, TonB must span the periplasm, providing a link between the cytoplasmic membrane and receptors in the outer membrane. On the basis of these data, and those published by other laboratories, we propose a model whereby TonB serves as a "mechanical" linkage that, by transmitting protein conformational changes from the cytoplasmic membrane across the periplasm, acts as a means of coupling energy to outer membrane transport processes. Such a mechanism has general implications for signal transduction within and between proteins.

Amino Acid Sequence↗
PubMed1989

An appraisal of the DSM-III system.

DSM-III is a major document in the history of psychiatry. The DSM-III system is here seen as an instrument that promotes the scientific development of psychiatry and the clarity of communication among psychiatrists. However a major theme of this review is that reliability does not ensure validity. While making this point it is recognized that the major defects in the DSM-III system result from scientific inadequacies inherent in present day psychiatry. This review also may be taken as an amplification of the statement in DSM-III-R that it is not a textbook. In particular the data required to arrive at diagnoses in the DSM-III system do not provide sufficient information to arrive at a comprehensive biopsychosocial case formulation, a shortcoming that has relevance for teaching and clinical practice.

Diagnosis, Differential↗
PubMed1988

Evidence for clonal development and stem cell origin of M7 megakaryocytic leukemia.

Previous studies have shown that acute nonlymphocytic leukemias are clonal diseases in which there is heterogeneity in the pattern of stem cell differentiative expression. To determine whether M7 megakaryocytic leukemia is a clonal disease and to evaluate the differentiative expression of the cells involved by the leukemia we studied a patient with megakaryocytic leukemia who was heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). The diagnosis of megakaryocytic leukemia was based on results obtained with the immunogold method and ultrastructural studies with the monoclonal anti-Gplla/IIIb antibody, 10E5. Direct testing of blood and marrow mononuclear cells and blood platelets demonstrated only A-type G6PD, whereas skin exhibited both B and A enzymes. The results indicate that the megakaryocytic leukemia in this patient was clonal at the time of study. To determine the differentiative expression of the stem cells, granulocyte/macrophage colony forming units and erythroid burst forming units were cultured and the resultant colonies were tested for G6PD. The results indicate that the stem cells involved by the leukemia exhibited differentiative expression multipotent for the megakaryocytic and granulocytic pathways, but no definitive conclusion could be made regarding the erythroid lineage.

Clone Cells↗
PubMed1988

Noncortical origins of the spinal motor evoked potential in rats.

Motor evoked potentials (MEPs) were recorded from the spinal cord, sciatic nerve, or both during transcortical electrical stimulation in the rat. Four peaks could be consistently identified in the spinal MEP. The latency and amplitude of the peaks varied differentially with intensity and polarity of stimulation. Conduction velocity for Peak 1 of the MEP was 43 m/sec. Bilateral sciatic nerve MEPs were present after unilateral cortical stimulation. The spinal MEP was elicited by stimulation of areas outside the motor cortex, and the response persisted during subcortical stimulation and after motor cortex ablation. We present evidence suggesting that components of the spinal MEP in rats arise from pathways outside the motor cortex.

Action Potentials↗
PubMed1987

An investigation of possible age-related changes in the inferior alveolar artery in man.

An histological examination of inferior alveolar arteries removed at post-mortem, from 16 human subjects failed to show significant age-related changes in luminal patency which would lead to narrowing and eventual obliteration of this structure. It is suggested that the artery continues, throughout life, to provide the major internal blood supply to the mandible.

Adolescent↗
PubMed1985

Platelet-derived growth factor enhances in vitro erythropoiesis via stimulation of mesenchymal cells.

The growth of erythroid colonies (from erythroid colony-forming cells) and erythroid bursts (from burst-forming cells [BFU-E]) is enhanced in the presence of serum as compared with plasma. A significant proportion of the enhanced growth is due to the platelet release product, platelet-derived growth factor (PDGF). Colony growth in cultures of whole marrow cells in platelet-poor plasma-derived serum (PDS) and erythropoietin was enhanced in a dose-dependent fashion by increasing concentrations of purified human PDGF with optimal enhancement at 12.5 ng/ml. However, no effect of platelet-release products or PDGF was observed on nonadherent human marrow cells or peripheral blood BFU-E, suggesting that an accessory cell population was required for the effect of PDGF on hematopoietic progenitors. In a two-layer culture system, pure populations of fibroblasts or smooth muscle cells, known to be present in the marrow microenvironment, restored the response of nonadherent marrow cells in the overlayer to PDGF and also conferred responsiveness to peripheral blood BFU-E. Endothelial cells in the two-layer culture system and macrophages, in contrast, lacked the ability to restore the enhancing effect of PDGF. Because other platelet-release mitogenic products are also found in serum, a monospecific anti-PDGF IgG preparation was added to cultures grown in platelet rich plasma-derived serum. Only partial reduction in colony and burst growth was seen, suggesting that other platelet-release products were acting in this system. These results demonstrate that PDGF enhancement of human hematopoietic progenitor cell growth requires mesenchymal cells, and provide an example and mechanism by which growth factors may influence hematopoietic progenitors via cells of the marrow microenvironment.

Bone Marrow↗
PubMed1984

Recovery of the ipsilateral oculotectal projection following nerve crush in the frog: evidence that retinal afferents make synapses at abnormal tectal locations.

The ipsilateral oculotectal projection in the frog is a topographic mapping of the binocular part of the visual field of one eye on the ipsilateral tectal lobe. The underlying neuronal circuitry consists of the topographic, crossed retinotectal projection and an intertectal pathway which relays information from a given point in one tectal lobe to the visually corresponding point in the other. During optic nerve regeneration, there is a period when the terminals of retinotectal afferents are found at abnormal locations in the opposite tectal lobe. Whether they form functional synapses at this time is not known. If so, one would expect to observe correlated abnormalities in the ipsilateral oculotectal projection. To determine whether such abnormalities exist, we have made parallel electrophysiological studies of the recovery of the retinotectal and ipsilateral oculotectal projections following crush of one optic nerve. The earliest stage of recovery was characterized by a lack of significant topographic order in the retinotectal projection and by the absence of a physiologically observable ipsilateral projection. Within a short time, the retinotectal projection became topographically organized and a similarly organized ipsilateral projection appeared. While topographic, the retinotectal projection at intermediate times was abnormal in that the multiunit receptive fields recorded at individual tectal loci were greatly enlarged. Multiunit receptive fields were similarly enlarged in the ipsilateral projection. In addition, some ipsilateral fields included areas of visual space not normally represented in the projection. The abnormalities in both projections subsequently disappeared over the same time course. Throughout recovery there was a high correlation between multiunit receptive field sizes in the contralateral tectal lobe and those at visually corresponding points in the ipsilateral tectal lobe. Enlarged multiunit receptive fields in the contralateral tectal lobe could not be accounted for in terms of optical or retinal abnormalities since single unit receptive field sizes were normal. Nor could they be accounted for in terms of changes in recording characteristics since simultaneously recorded fields activated by the undisturbed eye were normally sized. We conclude that the enlarged fields in the contralateral tectal lobe indicate the presence at individual tectal loci of afferents from wider than normal retinal regions. Similar considerations ruled out optical, retinal, and recording abnormalities as the explanation for the enlarged multiunit receptive fields in the ipsilateral tectal lobe.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗