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Biomedical subjects

A Cooper

Publications and source records attributed to A Cooper.

At least 199 records · Page 11Linked to original sources

Human immunodeficiency virus and acquired immunodeficiency syndrome: recent developments and their implications for pediatric surgeons.

Advances in medical management have enhanced both the quality and the quantity of life currently enjoyed by HIV-infected infants and children. Advances in surgical treatment have complemented these advances and contributed to the improving prognosis of HIV disease in the pediatric population. The resultant "aging" of the pediatric HIV population means that pediatric surgeons can expect to encounter HIV-infected patients on an ever-increasing basis. This article reviews the new advances in diagnosis and treatment of pediatric HIV disease most relevant to pediatric surgical practice.

Acquired Immunodeficiency Syndrome↗

Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages.

Despite the potential role of the macrophage in the eradication of invading microbes, Mycobacterium species have evolved mechanisms to ensure their survival and replication inside the macrophage. Particles phagocytosed by macrophages normally will be delivered into acid lysosomal compartments for degradation. Mycobacterium must, in some way, avoid this fate by modulation of their phagosome. Immunoelectron microscopy of macrophages infected with Mycobacterium avium or Mycobacterium tuberculosis indicates that the vacuolar membrane surrounding the bacilli possesses the late endosomal/lysosomal marker, LAMP-1 (lysosomal-associated membrane protein-1), but lacks the vesicular proton-ATPase. Analysis of the intersection of the bacteria-containing vacuoles with the endocytic network of the macrophage supports previous studies indicating that these bacilli restrict the fusion capability of their intracellular compartments. The occurrence of vesicles containing lipoarabinomannan, discrete from those containing Mycobacterium, indicate that material does traffic out from the mycobacterial vacuole. To compensate for this loss of membrane, the vacuole must remain dynamic and fuse with LAMP-1-containing vesicles to maintain the density of this marker.

Animals↗

Independent folding of the domains in the hydrophilic subunit IIABman of the mannose transporter of Escherichia coli.

The active form of the hydrophilic subunit (IIABman) of the mannose transporter of Escherichia coli is a homodimer of two 35-kDa subunits. Each subunit consists of two distinct domains, IIA and IIB, which can be separated by limited trypsin digestion. Separation of tryptic fragments yields monomers of IIB and dimers of IIA, which are active and stable. To test whether the domains fold as independent units, the effects of guanidine hydrochloride (GuHCl) and temperature on the structural stability of the intact IIABman were compared with those of the isolated fragments. Equilibrium GuHCl-induced reversible unfolding, measured by circular dichroism and tryptophan fluorescence, showed a biphasic transition for intact IIABman and monophasic transitions for each isolated fragment. The midpoint transitions of the isolated IIB and IIA fragments (at 1.0 and 2.3 M GuHCl) coincide with the first and second transitions of intact IIABman. Analytical ultracentrifugation studies suggested that dissociation precedes the unfolding of IIA. Thermal unfolding of IIABman, monitored by differential scanning calorimetry, showed two well-separated transitions near 52 and 95 degrees C which corresponded to the midpoint transitions of the isolated IIB and IIA fragments. The combined results demonstrate an independent stepwise unfolding of the domains in IIABman as well as the absence of stabilizing interdomain interactions. The lack of interdomain interactions suggests an unrestricted domain motion. This may play an important role in the phosphoryl transfer reaction which is catalyzed by the binding of IIABman to a phosphoryl carrier protein HPr (via the IIA domain) and to the transmembrane subunits of the mannose transporter (via the IIB domain).

Calorimetry, Differential Scanning↗

Calorimetric studies of the energetics of protein-DNA interactions in the E. coli methionine repressor (MetJ) system.

Calorimetric measurements of binding of a specific DNA fragment and S-adenosyl methionine (SAM) co-repressor molecules to the E. coli methionine repressor (MetJ) show significant differences in the energetics of binary and ternary protein-DNA complexes. Formation of the MetJ:SAM:DNA ternary complex is significantly more exothermic (delta H congruent to -99 kJ.mol-1) than either MetJ:DNA or MetJ:SAM binary complexes alone (delta H congruent to -10 kJ.mol-1 each). The protein is also significantly more stable to unfolding (delta Tm congruent to 5.4 degrees C) when bound to DNA. These observations suggest that binding of SAM to the protein-DNA complex leads to a significant reduction in dynamic flexibility of the ternary complex, with considerable entropy-enthalpy compensation, not necessarily involving any overall conformational change.

Bacterial Proteins↗

Ancient DNA sequences reveal unsuspected phylogenetic relationships within New Zealand wrens (Acanthisittidae).

Ancient DNA sequences from preserved specimens are increasingly being used for the investigation of Pacific Island ecosystems prior to the large scale modification and extinction of endemic biota associated with human colonization. However, many difficulties are associated with the use of ancient DNA sequences in studies of genetically close taxa. In this paper, these difficulties are discussed as they relate to a study involving extinct and extant members of an ancient New Zealand avian family, the New Zealand wrens (Acanthisittidae). Sequences of the mitochondrial small ribosomal subunit RNA gene (12S) were obtained from museum specimens of several wren taxa in order to investigate their phylogenetic relationships and the taxonomic status of a rock wren (Xenicus gilviventris) subspecies. Limitations due to sample size and 12S sequence variability as well as the difficulties in authenticating ancient DNA sequences prevent firm conclusions but the data suggest unsuspected phylogenetic relationships exist and raise the possibility that conservation management of rock wren populations is required.

Animals↗

Unfolding studies of the protease domain of urokinase-type plasminogen activator: the existence of partly folded states and stable subdomains.

The domain structure and the stability against thermal and chemical denaturation of urokinase-type plasminogen activator (u-PA) have been investigated by NMR spectroscopy and differential scanning calorimetry (DSC). At least five structurally autonomous regions of this three-domain protein have been found to exist. Two of these are the EGF-like and the kringle domains; the others are all within the third domain, which is a serine protease. The latter undergoes three unfolding transitions in its enzymatically active form. Reaction with a specific affinity label (L-Glu-L-Gly-L-Arg-chloromethyl ketone) to produce an inactivated protein results in a stabilization of the structure involved in two of these transitions, and an increase in cooperativity to give a domain which unfolds in two, not three, distinct steps. These are attributed to the denaturation of the two major subdomains of the protease structure. One of the subdomains has exceptional stability, being unfolded only under extreme conditions such as 75 degrees C at pH 2.5 or 4 M GuDCl at pH 4.5 and 29 degrees C. This region has been identified by isolation and characterization of a fragment (residues Ile-159 to Thr-277) obtained by limited proteolysis with thermolysin under conditions where the protease domain was partly unfolded. The NMR data are consistent with this stable region being at the N-terminus of the protein and indicate that its structure and stability are similar to those of the corresponding region of the native protein. These results support the idea that the u-PA protease domain has structural resemblance to the digestive serine proteases, but that stabilizing interactions within the structure can differ significantly between a group of homologous proteins.

Affinity Labels↗

Oligonucleotide probe design--a new approach.

The use of oligonucleotides for gene amplification, as diagnostic probes or antisense-based drugs can be optimized by minimizing the possibility of nonspecific hybridization.

Base Sequence↗

Mortality and truncal injury: the pediatric perspective.

To determine the extent and consequences of major truncal injury in children, we analyzed data collected prospectively by the National Pediatric Trauma Registry (NPTR) from 1985 to 1991. Of the 25,301 patients entered into the study, 1,553 (6%) had thoracic injuries (T); 2,047 (8%) had abdominal injuries (A). Blunt mechanisms predominated for both groups (86% T, 83% A), with the automobile being the most frequent blunt agent (74% T, 59% A); gunshot wounds were responsible for the majority of penetrating injuries (60% T, 56% A). Fifteen percent (195) of those with blunt thoracic injuries died; however, in only 14% of these cases (27) was thoracic injury the cause of death. Fourteen percent (33) of those with penetrating thoracic injuries died, with thoracic injury the cause of death in 97% of these cases (32). Only 9% (161) of those with blunt abdominal injuries died; in 22% (35) abdominal injury was the cause of death. Likewise, only 6% (15) of those with penetrating abdominal injuries died, but abdominal injury was the cause of death in 67% (10). The pleural space, lung, and ribs were the most frequently damaged thoracic organs; with the exception of lung contusion, injuries to these structures were associated with fatality rates in excess of 50%. The liver, spleen, kidneys, and gastrointestinal tract were the most frequently damaged abdominal organs; injuries to these structures were associated with fatality rates of 15% or less, except for injuries involving major blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

Pulmonary embolism and lupus anticoagulant in a woman with renal cell carcinoma.

We report on a woman in whom pulmonary embolism and positive lupus anticoagulant occurred 9 months before the diagnosis of renal cell carcinoma. To our knowledge this association has been described previously with other malignant neoplasms but not with a renal tumor, and it may represent an autoimmune paraneoplastic event.

Carcinoma, Renal Cell↗

The NHS R&D Information Systems Strategy (ISS).

Following a strategy study which reported in August 1992 the NHS R&D Information Systems Strategy (ISS), a strategic framework for information systems, has been developed to support research and development in the NHS. This paper summarizes its main features, illustrates the benefits which specific information systems will bring, and outlines how the products of the programme are disseminated and accessed.

Cost-Benefit Analysis↗

Cyclosporin treatment of atopic dermatitis: five case studies and literature review.

This study reports on five adult patients with severe atopic dermatitis who were treated in our department with a three month course of cyclosporin. All patients demonstrated significant clinical improvement with minimal side effects. We conclude that provided safety guidelines are observed, cyclosporin can be used with good effect in those patients where conventional treatment is unsatisfactory. This paper also reviews the use of cyclosporin in atopic dermatitis and includes a brief discussion of how it may alter pathophysiologic mechanisms.

Adolescent↗

Myocardial depressant effect of nitrous oxide after valve surgery.

We have studied the cardiovascular effects of 50% nitrous oxide after cardiopulmonary bypass in 14 patients undergoing valve surgery. All patients received morphine as the principal anaesthetic. Nitrous oxide administration for 5 min caused a decrease in mean arterial pressure from 82 +/- 10 to 71 +/- 12.7 mmHg (P < 0.001), cardiac index (2.8 +/- 0.5 to 2.4 +/- 0.5 litres min-1 m-2, P < 0.01), heart rate (104 +/- 17 to 99 +/- 18 beats min-1, P < 0.05), left ventricular stroke work index (29.4 +/- 8.1 to 22 +/- 8.7 gm-m beat-1 mm-1, P < 0.001), stroke volume (45.3 +/- 11.6 to 40 +/- 12.8 ml beat-1, P < 0.05) and an increase in pulmonary vascular resistance from 106.4 +/- 53.9 to 143.9 +/- 81.0 dynes s cm-5 (P < 0.01) and right atrial pressure (1.42 +/- 2.09 to 1.71 +/- 2.21 mmHg, P < 0.05). There was no change in systemic vascular resistance. When nitrous oxide was discontinued all the parameters started to recover within 3 min. Mean arterial pressure returned to control value in 5 min, but cardiac index and pulmonary vascular resistance returned to control value in 10 min. Our results suggest a direct myocardial depression and that the use of nitrous oxide is not recommended immediately after valve surgery and cardiopulmonary bypass.

Adult↗