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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 757 records · Page 42Linked to original sources
PubMed1993

HIV-related respiratory disease.

The lungs are a primary target for the opportunistic infections and malignancies affecting those with HIV infection. In the patient whose HIV infection is undiagnosed, PCP is the commonest clue to its presence. Early diagnosis prevents morbidity and mortality. Less commonly, interstitial lung disease and tuberculosis, often "primary" or clinically atypical, will be the clue to underlying HIV infection. Other pulmonary complications are usually a late manifestation of HIV infection, which has usually (but not always) already been diagnosed.

AIDS-Related Opportunistic Infections↗
PubMed1993

Evidence for the localization of haemopexin immunoreactivity in neurones in the human brain.

Haemopexin is a 60 kDa serum glycoprotein responsible for the transport of haem to tissues such as liver, by receptor-mediated endocytosis, in an analogous manner to the iron transport protein transferrin, with recycling of intact haemopexin. The immunocytochemical distribution of haemopexin has been investigated, using a monospecific polyclonal antiserum to human haemopexin, in human brain. Neurones in all the brain regions studied showed immunostaining of the soma, axons and dendrites. A few scattered glial cells exhibited positive immunostaining. Oligodendrocytes and choroid plexus epithelial cells lacked haemopexin immunoreactivity. Thus, haemopexin is present within neurones and we propose that this protein may play an important role in haem transport for neuronal iron homeostasis.

Aged↗
PubMed1993

Crystallization of the C-terminal domain of rabbit serum hemopexin.

The C-terminal domain of rabbit serum hemopexin, comprising residues 215 to 435, has been crystallized following removal of the attached carbohydrate using the endoglycosidase Endo F. The crystals, grown by vapour diffusion from solutions containing polyethylene glycol 1500, are orthorhombic, with cell dimensions a = 41.0 A, b = 64.2 A, c = 85.2 A, space group P2(1)2(1)2(1), and one molecule in the asymmetric unit. The crystals diffract to 2.4 A resolution and are suitable for X-ray structure analysis.

Animals↗
PubMed1993

The MAPI as a treatment outcome measure for adolescent inpatients.

The Millon Adolescent Personality Inventory (MAPI; Millon, Green, & Meagher, 1982) was administered at admission and discharge to 215 hospitalized adolescents. Significant mean score differences were found for both internalizing (affective disorder) and externalizing (disruptive behavior disorder) adolescents. Consistent with theory, internalizing adolescents reported significantly greater distress at both admission and discharge than externalizing adolescents. Finally, test-retest reliability coefficients were somewhat lower than those reported previously (Millon et al., 1982) for hospitalized adolescents.

Adolescent↗
PubMed1993

Expression of alternative forms of differentiation inhibiting activity (DIA/LIF) during murine embryogenesis and in neonatal and adult tissues.

Differentiation inhibiting activity/leukaemia inhibitory factor (DIA/LIF) is a pleiotropic cytokine which has been implicated in a variety of developmental and physiological processes in mammals due to its broad range of biological activities in vitro. A role in very early development is suggested by the requirement for DIA/LIF to support the self-renewal of cultured embryonic stem (ES) cells. Other data point to potential roles in the establishment and maintenance of primordial germ cells, in osteogenesis and in haematopoiesis, and possibly in neuronal specification. DIA/LIF may also act as a mediator of the hepatic acute phase response. In the present study the expression of DIA/LIF transcripts during murine development and in adult mice has been determined using a highly sensitive ribonuclease protection analysis. In contrast to previous reports, it is apparent that DIA/LIF transcripts are present at low levels in many adult mouse tissues. Higher levels of expression are observed in skin, lung, intestine, and uterus. Elevated amounts of mRNA are also found in certain foetal tissue during late gestation and neonatally. In earlier embryogenesis, however, DIA/LIF mRNA is produced primarily in extraembryonic tissues. The alternative transcripts which produce either soluble or matrix-associated DIA/LIF exhibit overlapping but non-identical patterns of expression, consistent with the proposition that the two isoforms may have distinct biological functions. These findings are suggestive of widespread roles for DIA/LIF in vivo and are discussed in the light of available data on the phenotype of homozygous DIA/LIF-deficient mice.

Aging↗
PubMed1993

Analysis of the synergistic stimulation of mouse macrophage proliferation by macrophage colony-stimulating factor (CSF-1) and tumor necrosis factor alpha (TNF-alpha).

Tumor necrosis factor alpha (TNF-alpha) more than doubles tritiated thymidine ([3H]TdR) uptake in mouse macrophages stimulated by macrophage colony-stimulating factor (CSF-1). However, nothing is known of how TNF-alpha affects this increase or even whether it is manifested by increased cellular proliferation. Here we characterize the effects of TNF-alpha on CSF-1-stimulated proliferation of both primary cells (bone marrow-derived macrophages, BMMs) and a cloned growth factor-dependent macrophage cell line (S1). We show that the TNF-alpha-induced increase in [3H]TdR uptake of CSF-1-stimulated macrophages is directly proportional to an increase in the DNA content of the culture and that the effects of TNF-alpha are direct and independent of cell number. TNF-alpha decreases the population doubling time of log-phase growing macrophages having quite different growth rates to the same (approximately 30%) extent: the doubling time of BMMs decreases from 24 to 17 h and that of S1 cells from 17 to 13 h. TNF-alpha exerts its effects on log-phase growth by increasing to the same proportion CSF-1-stimulated proliferation at all concentrations of CSF-1; that is, TNF-alpha does not shift, but rather amplifies, the CSF-1 dose-response curve. Although TNF-alpha alone does not stimulate macrophage proliferation, its presence in S1 cell cultures coming to quiescence after withdrawal of CSF-1 greatly increases subsequent CSF-1-stimulated [3H]TdR uptake as the cells reenter the cycle. Finally, we show that both human and mouse TNF-alpha increase CSF-1-stimulated log-phase growth and reentry of quiescent cells into the cycle equally on a molar basis (half-maximal stimulation of approximately 0.3 nM). The latter observation argues that the growth-stimulatory effects of TNF-alpha are mediated via the 55-60-kd TNF receptor. We conclude that TNF-alpha acts directly on growth-competent macrophages to decrease significantly the population doubling time in a manner that enhances the mitogenic effects of CSF-1.

Animals↗
PubMed1993

The importance of starch biosynthesis in the wrinkled seed shape character of peas studied by Mendel.

The wrinkled-seed mutant (rr) of pea (Pisum sativum L.) arose through mutation of the gene encoding starch-branching enzyme isoform I (SBE1) by insertion of a transposon-like element into the coding sequence. Two isoforms of starch-branching enzyme have been documented in the developing pea embryo. The second isoform, SBEII, is expressed towards the later stages of embryo development while SBEI is expressed highly in the early stages. Due to mutation of SBEI the total amount of starch and the proportion of amylopectin, a branched starch polymer, are greatly reduced in the wrinkled (rr) line as compared to that in the wild-type, round (RR) line. Consequently, the level of sucrose in the rr line is nearly two fold that of the RR line. Increased sucrose concentration in the developing embryos of this mutant line causes increased uptake of water and thereby increases the cell size and fresh weight. During seed maturation in these mutant seeds a greater loss of water occurs. As a result, the wrinkled seed phenotype develops. Besides this morphological variation, the mutation also causes changes in the amount of lipid and of one storage protein, legumin. This review article discusses the role of the SBEI enzyme in causing such metabolic changes in the developing embryos with the implication that metabolism can play a central role in plant development.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1993

Stable continuous constitutive expression of a heterologous protein in Saccharomyces cerevisiae without selection pressure.

The stability of heterologous protein expression in Saccharomyces cerevisiae during continuous culture without selection for plasmid-containing cells was investigated. The protein chosen was the leech thrombin inhibitor desulphato-hirudin, which is tolerated well by S. cerevisiae when over-expressed. Expression was from a 2-mu derived multicopy vector containing a synthetic hirudin gene under control of the constitutive glyceraldehyde-3-phosphate dehydrogenase derived GAPFL promoter. The behaviour of the system was studied at three dilution rates (D) corresponding to approximately 30% (0.06 h-1), 60% (0.12 h-1) and 90% (0.17 h-1) of the estimated maximum D. The level of plasmid loss was low at all Ds, with only 5-10% plasmid-free cells observed at 75 generations. The plasmid was most stably maintained at the intermediate D of 0.12 h-1, where the rate of loss was comparable to the loss of the native 2-mu plasmid. Hirudin expression was also highest at D = 0.12 h-1, possibly as a result of cell lysis at D = 0.06 h-1 and D = 0.17 h-1, leading to the release of vacuolar proteases and subsequent proteolysis of hirudin. Differences in expression levels were not a result of changes in plasmid copy number, which was in the range 40-60 throughout all three experiments. The high stability of this system at all Ds investigated shows that heterologous protein expression is not a burden to S. cerevisiae when the protein expressed is tolerated well.

Animals↗
PubMed1993

Evaluation of a behavioral medicine consultative treatment for chronic, ruminative vomiting.

This case study evaluated a multicomponent behavioral medicine treatment package for chronic ruminating and vomiting in a 13-year-old child with multiple disabilities. Treatment incorporated dietary and medication manipulations combined with behavioral intervention. The treatment package was designed and evaluated via a consultative model in a residential-care setting. The child's ruminative vomiting decreased steadily with implementation of treatment and reduced rates were maintained 2 years later. This case illustrates collaboration between physicians and psychologists in developing comprehensive behavioral medicine interventions for health-threatening clinical disorders.

Adolescent↗
PubMed1993

Effects of sleep deprivation, lunch, and personality on performance, mood, and cardiovascular function.

The present study examined the effects of sleep deprivation on performance, mood, and cardiovascular functioning in the late morning and early afternoon. The results showed that the sleep-deprived subjects felt less alert and detected fewer targets in a cognitive vigilance task. Selective impairments due to sleep deprivation were also observed in a logical reasoning task. There was little evidence to suggest that consumption of lunch altered these effects of sleep deprivation. However, individual differences in the effects of sleep deprivation were apparent, with trait anxiety being related to the changes in subjective alertness produced by sleep deprivation, and sleep-deprived extraverts showing greater performance impairments than the sleep-deprived introverts.

Adolescent↗
PubMed1993

Development of the collagen network of the human fetal myocardium: an immunohistochemical study.

We have studied the development of the collagen network within the ventricular myocardium of sixteen human fetuses of gestational age 12 weeks to 22 weeks. Using the technique of indirect immunohistochemistry with antibodies raised against collagen Types I and III, we have demonstrated that the 12 week old heart has a rudimentary endomysial collagen structure which coexpresses both collagen types. Perimysial structures evolve with the onset of the second trimester and are collagen III positive before expressing collagen Type I. No differences in collagen deposition were detected between the right and left ventricular free walls, but collagen content of the interventricular septum appeared relatively high and expressed in thick highly organised fibrils. Transventricular gradients of collagen distribution were seen for both collagen isoforms which persisted with increased age. Intraventricular differences in collagen deposition were marked due to the insertion of the atrioventricular valves and tension apparatus. These findings suggest that the collagen network of the fetal myocardium is composed of copolymer fibrils, possibly rich in collagen type III which evolve at a time when the mechanical efficiency of the fetal heart must improve to keep pace with the escalating demands of a rapidly growing body.

Collagen↗
PubMed1993

Autopsy: consent, completion and communication in Alzheimer's disease research.

The definitive diagnosis of Alzheimer's disease remains histopathological. To date many published studies have been limited by being based on clinical diagnosis alone, which has a significant false positive rate. In a prospective, longitudinal, clinicopathological study which aims to develop an antemortem diagnostic test for Alzheimer's disease, we have achieved 96% (250/260) consent and 97% (59/61) completion rates. We here describe some of the factors we believe are responsible for these high rates and which may be relevant to other studies requiring autopsy to verify clinical diagnoses.

Alzheimer Disease↗
PubMed1993

Studies of cardiopulmonary bypass in children: implications for the regulation of brain natriuretic peptide.

OBJECTIVE: The aim was to examine the influence of cardiopulmonary bypass on brain natriuretic peptide (BNP) and on hormones of importance in the control of sodium and water balance and blood volume. METHODS: Nine patients (mean age 4 years, range 2-9) undergoing cardiac surgery were studied. Blood samples were taken before, during, and up to 24 h after bypass. Plasma levels of BNP, atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity, aldosterone, and catecholamines were measured. RESULTS: Preoperative concentrations of plasma BNP [573(SEM 68) pg.ml-1] and ANP [332(74) pg.ml-1] were greatly increased (p < 0.05) before bypass in all patients when compared to normal levels in children [BNP = 31(4) pg.ml-1; ANP = 27(3) pg.ml-1, n = 28]. With general anaesthetic and sternotomy, there were large reductions (p < 0.05) in both plasma BNP [180(62) pg.ml-1] and plasma ANP [163(59) pg.ml-1]. During bypass, there were no further significant decreases in plasma ANP or BNP concentrations compared with preoperative levels. Postoperatively, plasma BNP gradually increased for 12 h, to 170(28) pg.ml-1, whereas plasma ANP showed a further small decrease, to 107(20) pg.ml-1. However, postoperative plasma levels of both ANP and BNP remained well below preoperative values (p < 0.01). Plasma AVP increased rapidly within 15 min of the onset of bypass, reaching a peak value of 153(5) pg.ml-1 after 45 min. Off bypass, plasma AVP decreased slowly and was still almost 10-fold above preoperative levels 12 h after end of bypass [137(11) pg.ml-1]. Mean central venous pressure decreased during the onset of bypass, from 4.3(1.9) to 0.4(1.1) mm Hg (p < 0.05), and increased again at the end of bypass, to 9.0(3.3) mm Hg (p < 0.05); there was little further change during the postoperative period. CONCLUSIONS: The major source of plasma BNP in patients with congenital heart disease is the cardiac ventricle. The lower plasma ANP and BNP levels and the narrow band of change in central venous pressure following surgical repair of cardiac abnormalities may be a response to improved cardiac function.

Aldosterone↗