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Biomedical subjects

L Young

Publications and source records attributed to L Young.

At least 37 records · Page 2Linked to original sources

Young AIDS migrants in Southern Africa: policy implications for empowering children.

Many AIDS-affected children in southern Africa engage in migration when household members fall sick or die from AIDS, or because they are sent to assist relatives. Despite this, little attention has been paid to the consequences of these movements for children's lives. Multi-method research, conducted in Lesotho and Malawi, revealed that children sent to live with kin commonly move over long distances and between urban and rural areas. They are generally not consulted or informed about these migrations and face a range of associated difficulties, particularly with integrating into new families and communities. Severed family ties exacerbate the difficulties faced by children who end up in institutions or on the streets. This paper advocates that policy approaches for those affected by AIDS should be children-centred and take into account the implications of migration at three levels. First, many of the difficulties children face could be overcome if they were familiar with the place and people they were moving to Second, children would be better able to cope with new situations if they were included in family discussions with decision-makers regarding their migration preferences. Third, maintaining ties with kin would ensure that children do not become distanced from their family and cultural heritage, which is essential for post-institutional support.

Acquired Immunodeficiency Syndrome↗

Gene expression in the developing embryo and fetus.

Determining the stage- and tissue-specific patterns of gene expression shown by the embryo and fetus will provide information about the control of normal development. Identification of alterations in these patterns associated with specific abnormal phenotypes will also be informative regarding the underlying molecular mechanisms. In addition, qualitative and quantitative changes in gene expression that deviate from the norm may provide a potential marker system for predicting future developmental defects, a system that would be particularly useful in preimplantation embryo technologies before recipient transfer. However, there are a number of important issues regarding the interpretation and relevance of many gene expression studies currently undertaken that are often not considered or are ignored. Even when rigorous methodology is applied to detect differences in gene expression, their functional significance is rarely defined. This review discusses the relevance of gene expression changes as diagnostic markers in relation to protein and epigenetic changes and indicates that gene expression studies should be rigorously designed and interpreted to yield meaningful results.

Animals↗

Interaction of atomic systems with X-ray free-electron lasers.

The planned construction of an X-ray free-electron laser (XFEL) will provide new opportunities for research in various areas of physics, chemistry and biology. The proposed design of the XFELs at DESY (Deutsches Elektronen-Synchrotron) and SLAC (Stanford Linear Accelerator Center) is built on the concept of a fourth-generation synchrotron source and will provide an intense pulse (I(0) approximately 10(16) W cm(-2), tau(gamma) approximately 100 fs) for photon wavelengths down to 1 A. Some guidelines for applications of these sources pertaining to atomic physics are presented here. Issues such as the onset of strong photon-field effects, multiple ionization and hollow-atom formation are analyzed. Attention is especially given to studying the interaction with rare-gas atoms, for which some numerical estimates are provided.

Journal Article↗

Genetic substructure in South African Bantu-speakers: evidence from autosomal DNA and Y-chromosome studies.

The extent of genetic differentiation between seven South African Bantu-speaking groups (Zulu, Xhosa, Tsonga/Shangaan, Southern Sotho, Pedi, Tswana, and Venda) was assessed from coancestry coefficients (F(ST)) estimated from autosomal serogenetic, DNA, and Y-chromosome DNA haplotypes. The overall F(ST) obtained from the autosomal data was 0.002, and that from the Y chromosome data was 0.014. The genetic relationships between groups examined were inferred from their cluster affinities in phylogenetic trees constructed from the genetic distances between them. Both autosomal and Y-chromosome DNA studies reveal that 6 of the 7 South African Bantu-speaking groups cluster according to their linguistic groupings, the exception being the Tsonga, who do not cluster with other Nguni language speakers, but rather with the Venda who live close to them. This suggests that the invading Shangaan-speakers, whose Nguni language was adopted by the Tsonga, did not have a major effect on the Tsonga gene pool, and that gene flow from the Venda into the Tsonga may have been considerable. Genetic distances were found to correlate with geographic distances between the regions where each group's apparent population density is the highest. Linguistic distances were also found to correlate with genetic distances, but linguistic and geographic distances showed no correlation. Together, these results suggest that linguistic and some genetic differentiation took place before the groups (or their forerunners) reached their present-day locations, and that further genetic change occurred after their arrival.

Adult↗

Obturator hernia repair--a new technique.

Obturator hernia is a rare condition with few reports in the world literature. There appears to be no consensus on the ideal approach and repair for such a condition. We report a simple, quick technique via a lower midline incision using an autogenous peritoneal fold. It is ideal for the contaminated case and in settings where mesh is not readily available.

Aged↗

Reactivity and isotype profiling of monoclonal antibodies using multiple antigenic peptides.

The characterisation of monoclonal antibodies (MAbs) is essential for the development of assay systems particularly where antigens have been developed using synthetic peptides. Indeed some peptide-carrier conjugates fail to induce immune responses and may not generate antibodies that bind to native protein. As an alternative to peptide-carrier conjugates, multiple antigenic peptides (MAPs) have been used for immunization strategies, but with little regard to the characteristics of the MAbs produced. In this study, we used 3 MAPs of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) to immunise BALB/c mice. Overall, the polyclonal antibody responses from tail bleeds showed that MAPs evoked B-cell responses. However, on screening 144 hybridomas, 24 MAb supernatants exhibited weak to moderate reactivity in enzyme-linked immunosorbant assay (ELISA) and against cell cytospin preparations (B95.8 and AG876 LCL), respectively. Isotype profiling of hybridoma supernatants also showed that 11 out of 24 were IgM. Further characterization of 6 MAbs in Western blotting showed reactivity to recombinant LMP1 and only one MAb (B28D) showed weak reactivity to the malignant cells (Hodgkin/Reed-Sternberg; HRS cells) of an EBV+ Hodgkin's lymphoma using paraffin-embedded tissue. It is probable that these MAPs failed to augment T-cell help and contributed to the production of low affinity (IgM) antibodies. These observations may be of importance to future immunization strategies, where MAPs are used in the production of monoclonal reagents.

Animals↗

Bioinspired engineering of exploration systems for NASA and DoD.

A new approach called bioinspired engineering of exploration systems (BEES) and its value for solving pressing NASA and DoD needs are described. Insects (for example honeybees and dragonflies) cope remarkably well with their world, despite possessing a brain containing less than 0.01% as many neurons as the human brain. Although most insects have immobile eyes with fixed focus optics and lack stereo vision, they use a number of ingenious, computationally simple strategies for perceiving their world in three dimensions and navigating successfully within it. We are distilling selected insect-inspired strategies to obtain novel solutions for navigation, hazard avoidance, altitude hold, stable flight, terrain following, and gentle deployment of payload. Such functionality provides potential solutions for future autonomous robotic space and planetary explorers. A BEES approach to developing lightweight low-power autonomous flight systems should be useful for flight control of such biomorphic flyers for both NASA and DoD needs. Recent biological studies of mammalian retinas confirm that representations of multiple features of the visual world are systematically parsed and processed in parallel. Features are mapped to a stack of cellular strata within the retina. Each of these representations can be efficiently modeled in semiconductor cellular nonlinear network (CNN) chips. We describe recent breakthroughs in exploring the feasibility of the unique blending of insect strategies of navigation with mammalian visual search, pattern recognition, and image understanding into hybrid biomorphic flyers for future planetary and terrestrial applications. We describe a few future mission scenarios for Mars exploration, uniquely enabled by these newly developed biomorphic flyers.

Algorithms↗

Clinical analysis of families with heart, midline, and laterality defects.

Disturbances of the normal asymmetric placement of organs, such as polysplenia or situs inversus, have been defined traditionally as laterality defects. However, there is compelling evidence from vertebrate models and human birth defects to hypothesize that defects of the midline, isolated congenital heart defects, and laterality defects are etiologically related. We present the clinical characteristics of three families that exhibit a variety of midline defects and isolated heart defects in addition to laterality defects. These observations suggest that the phenotypic consequences of mutations causing laterality defects include defects of the midline as well as isolated heart defects. To further explore the relationship between midline, heart, and laterality defects, it is imperative that detailed phenotyping of individuals and families with laterality defects be done and a classification system created to facilitate identification of genes causing human laterality disorders.

Blood Vessels↗

Eukaryotic-like adenylyl cyclases in Mycobacterium tuberculosis H37Rv: cloning and characterization.

Screening the Mycobacterium tuberculosis H37Rv genomic library for complementation of catabolic defect for cAMP-dependent expression of maltose operon produced the adenylyl cyclase gene (Mtb cya, (1997)) annotated later as Rv1625c (Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., III, et al. (1998) Nature 393, 537-544). The deduced amino acid (aa) sequence (443 aa) encoded by Mtb cya contains a single hydrophobic domain of six transmembrane helices (152 aa) in the amino-terminal half of the protein. Flanking this domain are an arginine-rich (17%) amino-terminal cytoplasmic tail (46 aa) and a carboxyl-terminal cytoplasmic domain (245 aa) with extensive homology to the catalytic core of eukaryotic adenylyl cyclases. Site-directed mutagenesis of Arg(43) and Arg(44) to alanine/glycine showed a loss of adenylyl cyclase activity, whereas mutagenesis to lysine restored the activity. Hence it is proposed that the formation of the catalytic site in Mtb adenylyl cyclase requires an interaction between Arg(43) and Arg(44) residues in the distal cytoplasmic tail and the carboxyl-terminal cytoplasmic domain. Mtb adenylyl cyclase activity at the physiological concentration of ATP (1 mm) was 475 nmol of cAMP/min/mg of membrane protein in the presence of Mn(2+) but only 10 nmol of cAMP/min/mg of membrane protein in the presence of Mg(2+). The physiological significance of the activation of Mtb adenylyl cyclase by Mn(2+) is discussed in view of the presence of manganese transporter protein in mycobacteria and macrophages wherein mycobacteria reside.

Adenosine Triphosphate↗

Augmentation in expression of activation-induced genes differentiates memory from naive CD4+ T cells and is a molecular mechanism for enhanced cellular response of memory CD4+ T cells.

In an attempt to understand the molecular basis for the immunological memory response, we have used cDNA microarrays to measure gene expression of human memory and naive CD4+ T cells at rest and after activation. Our analysis of 54,768 cDNA clones provides the first glimpse into gene expression patterns of memory and naive CD4+ T cells at the genome-scale and reveals several novel findings. First, memory and naive CD4+ T cells expressed similar numbers of genes at rest and after activation. Second, we have identified 14 cDNA clones that expressed higher levels of transcripts in memory cells than in naive cells. Third, we have identified 135 (130 known genes and 5 expressed sequence tags) up-regulated and 68 (42 known genes and 26 expressed sequence tags) down-regulated cDNA clones in memory CD4+ T after in vitro stimulation with anti-CD3 plus anti-CD28. Interestingly, the increase in mRNA levels of up-regulated genes was greater in memory than in naive CD4+ T cells after in vitro stimulation and was higher with anti-CD3 plus anti-CD28 than with anti-CD3 alone in both memory and naive CD4+ T cells. Finally, the changes in expression of actin and cytokine genes identified by cDNA microarrays were confirmed by Northern and protein analyses. Together, we have identified approximately 200 cDNA clones whose expression levels changed after activation and suggest that the level of expression of up-regulated genes is a molecular mechanism that differentiates the response of memory from naive CD4+ T cells.

Actins↗

Thymosin alpha-1.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of thymosin alpha-1 (TA1) are reviewed. TA1 is a synthetic polypeptide. The drug is in Phase III trials for the treatment of hepatitis C and in Phase II trials for hepatitis B. Additional possible indications are malignant melanoma, hepatocellular carcinoma, drug-resistant tuberculosis, and DiGeorge's syndrome. TA1 is thought to modulate the immune system by augmenting T-cell function. TA1 may affect thymocytes by stimulating their differentiation or by converting them to active T cells. TA1 is rapidly absorbed, achieving peak serum concentrations within two hours. Blood levels return to baseline within 24 hours, and the serum half-life is approximately 2 hours. TA1's efficacy in hepatitis B has been evaluated in 195 patients in four clinical trials. One study found hepatitis B virus (HBV) DNA clearance at six months in 9 of 17 patients receiving TA1, compared with 10 of 16 patients treated with interferon alfa-2b (IFN-alpha 2b) and 4 of 15 historical controls. An open-label trial found HBV DNA clearance in 53% of patients at six months. A randomized, controlled trial found HBV DNA clearance in 40.6% and 25.6% of patients treated with TA1 for 6 and 12 months, respectively, compared with 9.4% of untreated controls. Efficacy for hepatitis C has been evaluated in 162 patients in three clinical trials. In one trial, the number of patients who achieved normal serum alanine aminotransferase (ALT) levels did not differ significantly between TA1 and placebo. In the other two trials, combination TA1 and IFN-alpha 2b was compared with IFN-alpha 2b alone. One trial found a normal serum ALT level at six months in 71% of patients receiving combination therapy, versus 35% of patients receiving IFN-alpha 2b alone. Hepatitis C virus RNA clearance occurred in 65% of patients treated with combination therapy and 29% of patients treated with IFN-alpha 2b alone. The third trial, comparing combination TA1 and IFN-alpha 2b with IFN-alpha 2b alone and with placebo, found normalization of ALT levels at six months in 37.1% of patients receiving combination therapy, 16.2% of patients receiving IFN-alpha 2b alone, and 2.7% of patients receiving placebo. TA1 is well tolerated. Most studies observed only local irritation at the injection site. For hepatitis B and C, TA1 1.6 mg (900 micrograms/m2) should be administered subcutaneously twice a week. Clinical trials of TA1 for chronic hepatitis B or C have had mixed results. TA1 may be useful as monotherapy for hepatitis B or in combination with IFN-alpha 2b for hepatitis C, but its effects on morbidity and mortality remain to be seen.

Adjuvants, Immunologic↗

Role of the ABC transporter Mdl1 in peptide export from mitochondria.

ATP-binding cassette (ABC) adenosine triphosphatases actively transport a wide variety of compounds across biological membranes. Here, the ABC protein Mdl1 was identified as an intracellular peptide transporter localized in the inner membrane of yeast mitochondria. Mdl1 was required for mitochondrial export of peptides with molecular masses of approximately 2100 to 600 daltons generated by proteolysis of inner-membrane proteins by the m-AAA protease in the mitochondrial matrix. Proteolysis by the i-AAA protease in the intermembrane space led to the release of similar-sized peptides independent of Mdl1. Thus, two pathways of peptide efflux from mitochondria exist that may allow communication between mitochondria and their cellular environment.

ATP-Binding Cassette Transporters↗

Effects of intraarticular glucocorticoids on macrophage infiltration and mediators of joint damage in osteoarthritis synovial membranes: findings in a double-blind, placebo-controlled study.

OBJECTIVE: To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration, the expression of the chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha), and the expression of matrix metalloproteinases 1 and 3 (MMPs 1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases 1 and 2 (TIMPs 1 and 2), in osteoarthritis (OA) synovial membranes. METHODS: Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids. Twenty-one patients received 120 mg of methylprednisolone acetate (Depo-Medrol; Upjohn, Kalamazoo, MI), and 20 patients received placebo (1 patient received placebo in 1 knee and methylprednisolone acetate in the other). Immunoperoxidase staining for the expression of CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 was performed, and the immunostaining was quantified by color video image analysis. RESULTS: CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining was observed in all synovial membranes. Intraarticular glucocorticoid treatment was associated with a small (30%) but statistically significant (P = 0.048) reduction in CD68+ macrophage staining in the synovial lining layer, but there was no change in the CD68 expression in the synovial sublining layer. No significant differences were observed for MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining in the synovial lining or sublining layers. CONCLUSION: Intraarticular glucocorticoids may reduce CD68+ macrophage infiltration into the synovial lining layer, but not the expression of MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 in the synovial membrane, in patients with OA.

Aged↗

Review of effects of water pollution on the breeding success of waterbirds, with particular reference to ardeids in Hong Kong.

Predatory waterbirds, such as ardeids, are susceptible to bioaccumulation of pollutants through the ingestion of contaminated food sources. High body burdens of contaminants, including PCBs, PAHs, cadmium, mercury, lead, copper, zinc and arsenic have been detected in many bird species worldwide. There is a paucity of literature, however, linking contaminant body burden and effects on reproductive success in waterbirds. This review is a synthesis of pertinent literature on this topic, with specific reference to contaminant residues in various tissue types, relationship between body burden and reproductive success, and the use of biomarkers to predict more serious adverse affects. The impetus for this review was the development of a conservation strategy and management plan (commissioned by the Agriculture, Fisheries and Conservation Department of Hong Kong Special Administrative Region (SAR)) for an important wetland in Hong Kong that supports many threatened waterbirds, including ardeids.

Animals↗

Quality of health services and early postpartum discharge: results from a sample of non-English-speaking women.

Few studies have explored the knowledge, perceptions and satisfaction of ethnic women in relation to early obstetric discharge. The aim of this study was to form a profile of Vietnamese mothers who opt for early postpartum discharge, and to identify factors associated with those decisions. Focus group discussions, in-depth interviews and survey questionnaires were utilized to collect information from a sample of 160 mothers. Sixty mothers (38%) opted for early discharge (< 48 h). Factors strongly associated with early discharge were poor comprehension of English (OR=6.58, 95% CI=1.81, 24.02), very low level of education (OR=3.10, 95% CI=1.55, 6.20) and first time mother (OR=2.70, 95% CI=1.15, 4.27). The in-depth interviews identified further factors driving early discharge, including fear and anxiety when having to approach staff for assistance, and perceptions of disempowerment within culturally unfamiliar hospital surroundings. The findings in this study ought to alert administrators and clinicians to possible negative drivers for the choice of early postpartum discharge by Vietnamese mothers.

Adult↗

The non-peptidyl fungal metabolite L-783,281 activates TRK neurotrophin receptors.

Neurotrophin binding to the extracellular surface of the Trk family of tyrosine kinase receptors leads to the activation of multiple signalling cascades, culminating in neuroregenerative effects, including neuronal survival and neurite outgrowth. Since neurotrophins themselves are not ideal drug candidates due to their poor pharmacokinetic behaviour and bioavailability, small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present study demonstrates that L-783,281, a non-peptidyl fungal metabolite, is capable of stimulating TrkA, B and C phosphorylation to various extents in CHO cells stably expressing human Trk receptors. L-783,281 also stimulated Trk phosphorylation in a number of rat and human primary neuronal cultures, whereas the highly similar compound, L-767,827, was without effect. Mechanistic studies utilizing transiently transfected PDGF/TrkA and TrkA/PDGF chimeras, demonstrated that L-783,281 is likely to interact with the intracellular domain of the TrkA receptor. Further investigations suggested that L-783,281 was nevertheless able to instigate receptor dimerization by binding in a non-covalent manner. Although the cytotoxicity of the compound was shown to preclude its effects in neuronal survival and neurite outgrowth assays, it is a prototype for a small molecule neurotrophin mimetic that activates Trk by interacting at a site different from the neurotrophin-binding site.

Animals↗

Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease.

BACKGROUND & AIMS: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors. We addressed this in a prospective, double blind, randomized, controlled trial. METHODS: H. pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited. Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos. A second concurrently recruited control group of H. pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week. All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks. Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months. A relapse was defined as moderate or severe reflux symptoms. H. pylori eradication was determined by 13C-urea breath test. RESULTS: The H. pylori-positive cases were randomized to antibiotics (n = 93) or placebo (n = 97). Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H. pylori-negative groups during the 12-month study period. Life tables revealed no statistical difference between the 2 H. pylori-positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse. Two patients in each group developed grade B esophagitis at 12 months. CONCLUSIONS: H. pylori eradication therapy does not seem to influence relapse rates in GERD patients.

Adult↗