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Biomedical subjects

M K Hughes

Publications and source records attributed to M K Hughes.

At least 19 recordsLinked to original sources
PubMed2001

A large carbon sink in the woody biomass of Northern forests.

The terrestrial carbon sink, as of yet unidentified, represents 15-30% of annual global emissions of carbon from fossil fuels and industrial activities. Some of the missing carbon is sequestered in vegetation biomass and, under the Kyoto Protocol of the United Nations Framework Convention on Climate Change, industrialized nations can use certain forest biomass sinks to meet their greenhouse gas emissions reduction commitments. Therefore, we analyzed 19 years of data from remote-sensing spacecraft and forest inventories to identify the size and location of such sinks. The results, which cover the years 1981-1999, reveal a picture of biomass carbon gains in Eurasian boreal and North American temperate forests and losses in some Canadian boreal forests. For the 1.42 billion hectares of Northern forests, roughly above the 30th parallel, we estimate the biomass sink to be 0.68 +/- 0.34 billion tons carbon per year, of which nearly 70% is in Eurasia, in proportion to its forest area and in disproportion to its biomass carbon pool. The relatively high spatial resolution of these estimates permits direct validation with ground data and contributes to a monitoring program of forest biomass sinks under the Kyoto protocol.

Biomass↗
PubMed2000

Sexuality and the cancer survivor: a silent coexistence.

Human sexuality is an important aspect of well-being that can be altered significantly by cancer and cancer treatment. Because cancer was not considered a chronic illness until recently, this important quality of life issue usually is not addressed by nurses or other health care professionals. It is essential that nurses have the appropriate knowledge, skill, and attitudes to address the oncology patient's concerns about sexuality effectively. This article helps the nurse to become aware of the sexual changes that can occur as a result of cancer, its treatment, or both, and to recognize the importance of sexuality to patients. Using Annon's PLISSIT (permission, limited information, specific suggestions, and intensive therapy) model of sexual assessment, the nurse can learn how to assess a patient's sexual concerns. The model also can help the nurse to learn about interventions that assist patients with these concerns, thus breaking the silence.

Communication Barriers↗
PubMed1996

Psychiatric CNS consultation model in a medical setting.

A model for psychiatric CNS consultation services offered in a comprehensive cancer center is presented. The model combines inpatient and outpatient services; these services, described separately, are compared with and contrasted to those reported in the literature. Although many models of inpatient psychiatric CNS consultation-liaison activities have been published, the literature offers few descriptions of the psychiatric CNS in either independent or collaborative outpatient practice. CNSs, therefore, need to inform colleagues and consumers about the nature of their advanced practices. In the model described, the psychiatric CNSs receive direct referrals for both hospital and clinic patients as well as patients receiving cancer treatment outside the cancer center. CNSs evaluate patients independently, requesting medical psychiatric assessment and intervention when necessary. The independence with which the psychiatric CNSs function provides many patients with access to psychiatric services. The flexibility to follow patients in both in- and outpatient settings also offers continuity of care.

Adult↗
PubMed1995

Self peptides bound by HLA class I molecules are derived from highly conserved regions of a set of evolutionarily conserved proteins.

An evolutionary analysis of self peptides reported to be bound by HLA class I molecules showed that these peptides are largely derived from proteins that have been highly conserved in the history of mammals. These proteins also often have universal tissue expression and have a higher than average frequency of highly hydrophilic residues. The peptides themselves are generally still more highly conserved than the source proteins and have a higher frequency of highly hydrophobic residues, evidently often being derived from conserved hydrophobic cores of the source proteins. These results suggest that the mechanism by which peptides are derived for MHC presentation may preferentially select peptides from conserved protein regions. In the case of parasite-derived peptides, such a mechanism would be adaptive in that it would reduce the likelihood of escape mutants.

Animals↗
PubMed1995

Natural selection on Plasmodium surface proteins.

Numbers of synonymous (ds) and nonsynonymous (dN) nucleotide substitutions per site were analysed in eight polymorphic Plasmodium genes: circumsporozoite protein gene (CSP), sporozoite surface protein 2 (thrombospondin related anonymous protein, TRAP), merozoite surface antigen 2 (MSA-2), apical membrane antigen 1 (PF83), liver-stage antigen-1 (LSA-1), knob-associated histidine-rich protein (KAHRP), ring-infected erythrocyte surface antigen (RESA) and S-antigen. In certain regions of genes coding for proteins of the sporozoite and merozoite surface (CSP, TRAP, MSA-2 and PF83), dN was significantly greater than dS. This unusual pattern of nucleotide substitution is indicative of positive Darwinian selection acting to promote diversity at the amino-acid level; thus our results suggest that the sporozoite and merozoite surface proteins are under positive selection, presumably exerted by the host immune system. No such pattern of substitution was observed on LSA-1, KAHRP, RESA, or S-antigen. Observed patterns of nucleotide substitution were not explicable by nucleotide content bias. G + C content in the 5' nonrepeat region of CSP in nine Plasmodium species was positively correlated with that in the 3' nonrepeat region; however, there was no relationship between G + C content and the ratio dS/dN in either CSP or a larger sample of all regions of all genes analysed.

Animals↗
PubMed1995

Natural selection on the gag, pol, and env genes of human immunodeficiency virus 1 (HIV-1).

Natural selection on polymorphic protein-coding loci of human immunodeficiency virus-1 (HIV-1), the more geographically widespread of the two viruses causing human acquired immune deficiency syndrome (AIDS), was studied by estimating the rates of nucleotide substitution per site in comparisons among alleles classified in families of related alleles on the basis of a phylogenetic analysis. In the case of gag, pol, and gp41, the rate of synonymous substitution generally exceeded that of nonsynonymous substitution, indicating that these genes are subject to purifying selection. However, in the case of several of the variable (V) regions of the gp120 gene, especially V2 and V3, comparisons within and between families often showed a significantly higher rate of nonsynonymous than of synonymous nucleotide substitution. This pattern of nucleotide substitution indicates that positive Darwinian selection has acted to diversify these regions at the amino acid level. The V regions have been identified as probable epitopes for antibody recognition; therefore, avoidance of such recognition seems likely to be the basis for positive selection on these regions. By contrast, regions of HIV-1 proteins identified as epitopes for T cell recognition show no evidence of positive selection and are often highly conserved at the amino acid level. These results suggest that selection favoring avoidance of T cell recognition has not been a major factor in the history of HIV-1 and thus that avoidance of T cell recognition is not likely to be a major factor in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Natural selection at the class II major histocompatibility complex loci of mammals.

The role of natural selection at major histocompatibility complex (MHC) loci was studied by analysis of molecular sequence data from mammalian class II MHC loci. As found previously for the class I MHC molecule and a hypothetical model of the class II molecule, the rate of non-synonymous nucleotide substitution exceeded that of synonymous substitution in the codons encoding the antigen recognition site of polymorphic class II molecules. This pattern is evidence that the polymorphism at these loci is maintained by a form of balancing selection, such as overdominant selection. By contrast, in the case of monomorphic class II loci, no such enhancement of the rate of non-synonymous substitution was observed. Phylogenetic analysis indicates that, in contrast to monomorphic ('non-classical') class I MHC loci, some monomorphic class II loci of mammals are quite ancient. The DMA and DMB loci, for example, diverged before all other known mammalian class II loci, possibly before the divergence of tetrapods from bony fishes. Analysis of the patterns of sharing of polymorphic residues at class II MHC loci by mammals of different species revealed that extensive convergent evolution has occurred at these loci; but no support was found for the hypothesis that MHC polymorphisms have been maintained since before the divergence of orders of eutherian mammals.

Animals↗
PubMed1994

Allelic variation in the circumsporozoite protein of Plasmodium falciparum from Thai field isolates.

Allelic variation in the Plasmodium falciparum circumsporozoite (CS) protein gene has been examined by sequencing the entire gene in 15 isolates from an endemic area of Thailand. The isolates contain a total of six new allelic forms of the tetrapeptide repeats and eight variants of the T cell epitope (TCE) region of the CS gene. All nucleotide substitutions in the TCE are nonsynonymous. There is no apparent association between the sequence patterns in the repeats and in the TCE. Comparison of the TCE with published sequences has shown that most variants of our isolates are not identical to those found in different geographic areas, suggesting geographic variation in genetic diversity of the CS protein. In a phylogenetic tree, the new Thai alleles did not cluster together, suggesting a considerable heterogeneity within some geographic areas. Furthermore, analyses of tetrapeptide repeats from a number of isolates and strains showed evidence of three genetic mechanisms for the generation of variation in the repeats of the CS gene: point mutation, duplication of one or more repeat units, and intragenic recombination.

Alleles↗
PubMed1993

Tissue response and in vivo degradation of selected polyhydroxyacids: polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA).

The tissue response and in vivo molecular stability of injection-molded polyhydroxyacids--polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA, 5-22% VA content)--were studied. Polymers were implanted subcutaneously in mice and extirpated at 1, 3, and 6 months in order to study tissue response and polymer degradation. All polymers were well tolerated by the tissue. No acute inflammation, abscess formation, or tissue necrosis was observed in tissues adjacent to the implanted materials. Furthermore, no tissue reactivity or cellular mobilization was evident remote from the implant site. Mononuclear macrophages, proliferating fibroblasts, and mature vascularized fibrous capsules were typical of the tissue response. Degradation of the polymers was accompanied by an increase in collagen deposition. For the polylactide series, the inflammatory response after 1 month of implantation was less for materials containing the D-unit in the polymer chain, whereas in the case of the polyhydroxybutyrate/valerates, the number of inflammatory cells increased with increasing content of the valerate unit in the polymer chain. Between 1-3 months, there was slightly more tissue response to the PHB and PHB/VA polymers than to PLA. This response is attributed to the presence of leachable impurities and a low molecular weight soluble component in the polyhydroxybutyrate/valerates. At 6 months, the extent of tissue reaction was similar for both types of polymers. All polylactides degraded significantly (56-99%) by 6 months. For a poly(L-lactide) series, degradation rate in vivo decreased with increasing initial molecular weight of the injection-molded polymer. Several samples showed pronounced bimodal molecular weight distributions (MWD), which may be due to differences in degradation rate, resulting from variability in distribution of crystalline and amorphous regions within the samples. This may also be the result of two different mechanisms, i.e., nonenzymatic and enzymatic, which are involved in the degradation process, the latter being more extensive at the later stage of partially hydrolyzed polymer. The PHB and PHB/VA polymers degraded less (15-43%) than the polylactides following 6 months of implantation. Generally, the polymer with higher valerate content (19%, 22%) degraded most. The decrease in molecular weight was accompanied by a narrowing of the MWD for PHB and copolymers; there was no evidence of a bimodal MWD, possibly indicating that the critical molecular weight that would permit enzyme/polymer interaction had not been reached. Weight loss during implantation ranged from 0-50% for the polylactides, whereas for the PHB polymers weight loss ranged from 0-1.6%.

Absorption↗
PubMed1993

Adaptive evolution in the rat olfactory receptor gene family.

Comparison of DNA sequences of the rat (Rattus norvegicus) olfactory receptor gene family revealed an unusual pattern of nucleotide substitution in the gene region encoding the second extracellular domain (E2) of the protein. In this domain, nonsynonymous nucleotide differences between members of this subfamily that caused a change in amino acid residue polarity were over four times more frequent than nonsynonymous differences that did not cause a polarity change. This nonrandom pattern of nucleotide substitution is evidence of past directional selection favoring diversification of the E2 domain among members of this subfamily. This in turn suggests that E2 may play some important role in the functions unique to each member of the olfactory receptor family, and that it may perhaps be an odorant binding domain.

Amino Acids↗
PubMed1993

Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci.

A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large-scale recombination events (involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small-scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus.

Alleles↗
PubMed1993

Evolution of duplicate genes in a tetraploid animal, Xenopus laevis.

To understand the evolution of duplicate genes, we compared rates of nucleotide substitution between 17 pairs of nonallelic duplicated genes in the tetraploid frog Xenopus laevis with rates between the orthologous loci of human and rodent. For all duplicated X. laevis genes, the number of synonymous substitutions per site (dS) was greater than the number of nonsynonymous substitutions per site (dN), indicating that these genes are subject to purifying selection. There was also a significant positive correlation (r = 0.915) between dN for the X. laevis genes and dN for the mammalian genes, suggesting that, at the amino acid level, the X. laevis genes and the mammalian genes are under similar constraints. Results of relative-rate tests showed nearly equal rates of nonsynonymous substitution in each copy of the X. laevis genes; apparently there are similar constraints on both copies. No correlation was found between dS for the X. laevis genes and dS for the mammalian genes. There was a significant positive correlation both between members of pairs of duplicated X. laevis genes (r = 0.951) and between human and rodent orthologues (r = 0.854) with respect to third-position G+C content but no such relationship between the X. laevis genes and either of their mammalian orthologues. The results indicate that both copies of a duplicate gene can be subject to purifying selection and thus support the hypothesis of selection against all genotypes containing a null allele at either of two duplicate loci.

Animals↗
PubMed1992

Degradation of five polyurethane gastric bubbles following in vivo use: SEC, ATR-IR and DSC studies.

Five Garren-Edwards Gastric Bubbles were characterized, following up to 4 months use in vivo, using size exclusion chromatography, differential scanning calorimetry and attenuated total reflectance infrared spectroscopy. These techniques show that the material used to construct the bubble is probably an aromatic polyester urethane and revealed a 39-55% decrease in number average molecular weight, a 9 degrees C decrease in glass transition temperature, the disappearance of soft segment crystallinity and a broadening of the hard segment melting region after exposure to highly acidic (approximately pH 1.2) gastric fluid. The results indicate that significant chemical and morphological changes have taken place in the bubble material, including loss in chemical functionality, phase separation and increased hard segment aggregation. A comparison of the decrease in glass transition temperature as a function of molecular weight suggests that glass transition temperature is a sensitive predictor of this material's stability. Additionally, evidence is provided that the broad infrared absorption at 1077-1067 cm-1 normally assigned to C-O-C hard segment may represent two types of C-O-C stretching: (1) C-O-C stretching of the free urethane carbonyl, and (2) C-O-C stretching of the hydrogen bonded urethane carbonyl.

Biodegradation, Environmental↗
PubMed1991

Determination of cholesterol and cortisone absorption in polyurethane. I. Methodology using size-exclusion chromatography and dual detection.

A size-exclusion chromatographic method is described for measuring the absorption of the steroid-based lipids cholesterol and cortisone into Pellethane 2363, a polyurethane used in biomedical implants. The method uses refractometry and ultraviolet diode-array detection, with tetrahydrofuran as the mobile phase. Using an injection volume of 150 microliters, the lower limit of accurate measurement for cholesterol (refractive index detection) was 6 micrograms/ml with a lower limit of detection, based on a 2:1 signal-to-noise ratio, of 0.15 micrograms (1 microgram/ml). For cortisone (ultraviolet detection), the lower accurate limit was 0.6 micrograms/ml with a lower limit of 0.015 micrograms (0.1 micrograms/ml). The results show that after 44 h, 2037 micrograms/g cholesterol and 3131 micrograms/g cortisone were absorbed by the polyurethane. The method eliminates extensive sample manipulation and is sensitive to low levels of lipid in the presence of a high-molecular-mass synthetic polymer.

Absorption↗
PubMed1981

A comparative study of low-vision patients: Their ocular disease and preference for one specific series of light transmission filters.

One hundred low-vision patients who complained of sensitivity to light were permitted to select any one of five filters (Recreational Innovations Co.) The results show that patients with certain types of pathology prefer to use specific filters to control the light reaching their eyes. Patients with albinism chose amber filters. Patients with glaucoma of diabetes both selected the same filter. Most patients with retinitis pigmentosa found most help from a filter which allowed only 2% light transmission.

Adolescent↗