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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 163 records · Page 9Linked to original sources

The effects of cytokines and growth factors on osteoblastic cells.

In this short review, some regulatory mechanisms that are involved in the control of normal bone formation are proposed, based on several in vivo and in vitro models our group has utilized recently to study osteoblast differentiation and mineralized bone matrix formation. Of course, these proposals must be assessed in the light of the limitations of the models, which probably represent a simplification of the complex and different ways in which normal mammalian bone is formed at different sites. Nevertheless, it is likely that the same general types of control mechanisms are active in each of the different types of bone formation. In adult humans, bone formation predominantly occurs by remodeling, the process by which bone which has recently been resorbed by osteoclasts is replaced by teams of osteoblasts. Other types of bone formation such as endochondral bone formation and appositional bone formation are also important, particularly during growth and adolescence. The end results of each of these processes are the same, namely a complex mineralized proteinaceous bone matrix. These processes are modulated by systemic hormonal influences, which are particularly important with respect to pituitary hormones and sex steroids during growth and adolescence, and by local cellular microenvironmental differences. The former will not be discussed here. Rather, we will concentrate on the local events and factors which are likely involved in the bone formation process occurring during normal bone remodeling.

Adult↗

The diagnosis and management of acute liver failure in dogs and cats.

Management of the small animal patient with a presumptive diagnosis of acute liver failure should aim to provide high quality supportive care aimed at the functional derangements that occur. A definitive histopathologic diagnosis should be pursued to allow evaluation of the reversibility of the underlying condition. With the current advances in veterinary critical care, improved medical and technical management should reduce both morbidity and mortality in the patient with potentially reversible liver failure.

Animals↗

Thrombosis of the straight sinus complicating hormone replacement therapy.

Oral contraceptives have been implicated in the pathogenesis of dural venous thrombosis. No similar association has been confirmed between postmenopausal hormone replacement therapy and cerebral venous thrombosis, although one previous report in the literature has identified such a case. We present a further case of thrombosis of the straight sinus in a patient on hormone replacement therapy (HRT) and suggest that dural sinus thrombosis is a rare, but dangerous complication of HRT.

Cerebral Angiography↗

Health care contracts in Britain and the United States: a case for technology transfer?

One unexpected point of convergence between the British and North American health care systems is the increased use of negotiated contracts to govern relationships between purchasers and providers. In Britain, the internal market reforms introduced a special regime of National Health Service (NHS) contracts; in the United States there has been a move from disorganization towards integration with the emergence of larger purchasing coalitions and provider organizations. While, in the past, US patients were simply billed for services or assigned claims to the provider, it is now common for payment to be made directly from purchaser to provider and for the terms of these transactions to be set out in contracts. This paper draws on the reading of contracts, interviews with contracting parties, and ongoing research on NHS contracting in Wales to compare contracting practice within the two systems. It examines how the very different environments of the public, hierarchically-regulated NHS and the private health care market of the US influence the detailed content of contract clauses. The analysis passes over similarities, different solutions to common problems, and fundamental differences of approach, before considering the possibilities for transfers of contracting 'technology'.

Contract Services↗

Use of hyperbaric oxygen in rheumatic diseases: case report and critical analysis.

Hyperbaric oxygen has been used in patients with rheumatic disease for many years without reports of untoward or unusual complications for a variety of non-rheumatic indications. Recent evidence that hyperbaric oxygen inhibits the actions of certain cytokines, acts as an immune modulator and may help cognitive dysfunction has resulted in a re-examination of its potential role in rheumatic diseases. A case report of a lupus/scleroderma crossover patient is presented whose cognitive dysfunction improved after hyperbaric oxygen therapy. The history of hyperbaric oxygen and its physiology are related, along with a focused review of its effects on the immune and central nervous systems. Areas which might warrant further consideration by rheumatologists are outlined, as well as areas of concern.

Cognition Disorders↗

The British health care reforms, the American health care revolution, and purchaser/provider contracts.

The health care systems of the United States and the United Kingdom are changing rapidly. After the Thatcher government's 1989 white paper, the formerly unified British National Health Service (NHS) was split into purchaser and provider sides, with the NHS District Health Authorities becoming purchasers, and the NHS hospitals, now reconstructed as independent NHS trusts, becoming providers. The U.S. health care system, driven by market forces rather than government fiat, has been moving rapidly toward integration, with increasingly formalized purchaser and provider relationships. Contracts are found at the purchaser/provider interface in both systems. We reviewed American and British purchaser/provider contracts. The contracts address similar issues but often take disparate approaches. These dissimilarities illuminate the profound, continuing differences between the two systems. They also, however, offer possibilities to transfer contracting "technology" between the two contracting cultures.

Competitive Bidding↗

The role of social change in preventing low birth weight.

The authors of this article examine the relationship between social factors and low birth weight and the ways in which disparities in socioeconomic status have been addressed over time. The evidence regarding the effectiveness of various efforts to influence birth weight by mitigating the consequences of disadvantage are also assessed. Low socioeconomic status has been shown to influence low birth weight through its various correlates. Historically and today, most programs and policies directed at low birth weight prevention attempt to address the individual health consequences of economic and social disadvantage. By and large, these efforts have produced mixed results. Efforts to affect low birth weight by addressing the underlying causes of social and economic disadvantage have been similarly inconclusive, reflecting the paucity of research on the subject, as well as the historical and ongoing failure to make the research link between health and social policy. The authors argue that reducing persistent disparities in low birth weight requires several steps, including embracing a broader definition of health which incorporates social dimensions, recasting the focus of research and interventions from pregnancy outcomes and infant health exclusively to include the notion of women's health more globally, expanding the research agenda to unravel the paradox of socioeconomic factors and health, and pursuing a dedicated, national commitment to assuring adequate support to individuals and families, including both adequate income and health care.

Female↗

Effects of age, sex, reproductive status, and hospitalization on serum alpha 1-antitrypsin concentration in dogs.

We performed a study to determine a reference range for serum alpha 1-antitrypsin (alpha 1AT) in dogs by specific immunoassay; to evaluate whether serum alpha 1AT concentration varied with age, sex, or reproductive status in healthy dogs; and to investigate whether the serum alpha 1AT concentration in hospitalized dogs differed from that of healthy, nonhospitalized dogs. Serum alpha 1AT was quantitated by radial gel immuno-diffusion for 60 healthy dogs and 311 hospitalized dogs. In healthy dogs, serum alpha 1AT concentration was 2.33 +/- 0.41 mg/ml (mean +/- SD), yielding a reference range (mean +/- 2 SD) of 1.51 to 3.15 mg/ml. A correlation was not found between serum alpha 1AT concentration and age in healthy dogs. The serum alpha 1AT concentration (mean +/- SEM mg/ml) was significantly higher in healthy, sexually intact females (2.64 +/- 0.1) than in healthy, spayed females (2.22 +/- 0.12; P < 0.004); healthy, sexually intact males (2.14 +/- 0.1; P < 0.0006); and healthy, and castrated males (2.25 +/- 0.14; P < 0.02). Hospitalized, sexually intact females had a lower serum alpha 1AT concentration (1.93 +/- 0.07) than healthy, sexually intact females (2.64 +/- 0.1; P < 0.0002). Likewise, the serum alpha 1AT concentration in hospitalized, sexually intact males (1.92 +/- 0.04) was less than in healthy, sexually intact males (2.14 +/- 0.1; P < 0.04). A difference in alpha 1AT concentration was not found between healthy and hospitalized, neutered dogs.

Age Factors↗

The effectiveness of the Masterson curette in sampling the endometrial cavity.

The Masterson curette was used to sample the endometrial cavity of 25 women prior to scheduled hysterectomy for benign or malignant pathology. Adequate amount of tissue was obtained in 20 (87%) of 23 patients who did not have endometrial atrophy. The Masterson curettage detected all seven cases of endometrial hyperplasia or adenocarcinoma for a sensitivity of 100%. However, the Masterson curette does not sample the entire endometrial cavity. If abnormal uterine bleeding persists despite normal histology on curettings obtained with the Masterson or other endometrial sampling device, hysteroscopy is recommended.

Adenocarcinoma↗

Birth and the moon.

Explore the source record for details and available documents.

Circadian Rhythm↗

Human IMR-32 neuroblastoma cells as a model cell line in Alzheimer's disease research.

The present study investigated expression and processing of amyloid precursor protein by neuronally differentiated IMR-32 neuroblastoma cells. APP mRNA in these cells was found to consist of approximately 58% APP695, 38% APP751, and < 4% APP770. APP-immunoreactive bands detected in western blots of cellular protein extracts were only detected by anti-APP antibodies to peptides with strong homology to APLP2, suggesting that these bands represent APP-like proteins and not APP itself. This result suggests that previous studies claiming immunodetection of cellular forms of APP may have to be re-evaluated. Four main species of C-terminal truncated, secreted APP were detected in blots of protein extracts from medium conditioned by these cells. The immunoreactive profile of these bands suggested a cleavage site N-terminal to the Lys16-Leu17 bond of alpha-secretase. This, together with differences in number and molecular mass of APP-immunoreactive bands between secreted APP from IMR-32 cells and that from the commonly used PC-12 cells, suggests differences in APP processing between these two neuronally differentiated cell lines. In theory, IMR-32 cells being of human neuronal origin may be a more appropriate cell line to study APP-processing in relation to Alzheimer's disease than the rat phaeochromocytoma PC-12 cell line. Therefore, these detected differences warrant further investigation. Additionally IMR-32 cells under certain tissue culture conditions can form intracellular fibrillary material that reacts with anti-PHF specific antibodies. Neuronally differentiated IMR-32 cells could therefore be used as a model system to investigate possible interactions between APP-processing and PHF formation.

Alzheimer Disease↗

Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP.

The antibiotic kirromycin inhibits protein synthesis by binding to EF-Tu and preventing its release from the ribosome after GTP hydrolysis. We have isolated and sequenced a collection of kirromycin resistant tuf mutations and identified thirteen single amino acid substitutions at seven different sites in EF-Tu. These have been mapped onto the 3D structures of EF-Tu.GTP and EF-Tu.GDP. In the active GTP form of EF-Tu the mutations cluster on each side of the interface between domains I and III. We propose that this domain interface is the binding site for kirromycin.

Amino Acids↗

Use of surface molecules and receptors for studying macrophages and mononuclear phagocytes.

Members of the mononuclear phagocyte system use their extensive repertoire of cell surface receptors to interact with their external environment. A number of different assays are available for the study of these molecules and their many functions. In this paper we describe how monoclonal antibodies may be generated against macrophage molecules, and discuss how screening strategies aimed at producing functionally active reagents may be devised. Using the macrophage mannose and scavenger receptors as examples, we describe assays for determining macrophage adhesion to culture plastic surfaces, endocytosis of soluble ligands and phagocytosis of particles in vitro. These assays may be used in the production of inhibitory monoclonal antibodies, as well as in studies of the regulation of macrophage phenotype and activity.

Animals↗

Fusidic acid-resistant mutants define three regions in elongation factor G of Salmonella typhimurium.

We have sequenced fusA, the gene coding for elongation factor G (EF-G), in 18 different mutants of Salmonella typhimurium selected as fusidic acid resistant (FuR). In addition, we have sequenced two previously described FuR mutants from Escherichia coli. In all cases, the resistance is due to a mutation in one of three separate regions in fusA. The three clusters of mutant sites superimpose on regions that are well conserved, suggesting that they are of a more general functional importance. To further classify the mutants, we have measured the minimal inhibitory concentration (MIC) for Fu and for two other antibiotics which interfere with translocation on the ribosome, kanamycin (Km) and spectinomycin (Sp). The levels of resistance to Fu for each of the mutants are significantly higher than in the wild type (wt), and vary by about one order of magnitude between the highest and the lowest. Most of the mutants are also more resistant to Km than the wt, although the level of resistance is low and the variation small. In contrast, about half of the mutants are more sensitive to Sp than the wt, with only one being more resistant. Only three of the twenty mutants behave like the wt with respect to the non-selected phenotypes, KmR and SpR.

Bacterial Proteins↗

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗

Successful treatment of sinusitis caused by Cunninghamella bertholletiae.

Seventeen cases of infections due to Cunninghamella species have been reported worldwide in humans, and there have been only three survivors. We report a case of paranasal sinusitis due to Cunninghamella bertholletiae in an elderly patient who had diabetes mellitus and myelodysplasia. After receiving 7 weeks of therapy with deoxycholate amphotericin B (44 mg/kg or a total of 3 g) and rifampin, the patient was cured and did not have to undergo radical surgery.

Aged↗