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Biomedical subjects

M Grant

Publications and source records attributed to M Grant.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of livelihood security: a case study in the Kali-Khola watershed of Nepal.

This paper examines household livelihoods in highland and lowland communities of the Kali-Khola agricultural watershed in western Nepal on the basis of economic, ecological and social security indicators. Significant differences were found in soil fertility status, pests and diseases management, risk and uncertainties, use of agrochemicals and access to social services. No remarkable variations were found in crop diversification, annual agricultural income and food sufficiency. However, uncertainty and risk in agricultural production is relatively low in highland communities. The findings reveal that agriculture production alone is not a viable livelihood option for agricultural watershed communities in Nepal. The households growing crops with hired labour have relatively sustainable livelihoods in Nepal's agricultural watersheds. Insufficient agricultural land, insufficient working manpower within a family, and lack of access to ecological agricultural services are prime factors in being livelihood insecure in agricultural watershed communities. Therefore, long-term policies and plans need to be developed for the empowerment of local farmers and to support rural livelihoods with adaptable and flexible income-generating strategies, resilient resource management institutions and enhancement of knowledge, skills and social capital.

Agriculture↗
PubMed2006

Diffusive atomistic dynamics of edge dislocations in two dimensions.

The fundamental dislocation processes of glide, climb, and annihilation are studied on diffusive time scales within the framework of a continuum field theory, the phase field crystal model. Glide and climb are examined for single edge dislocations subjected to shear and compressive strain, respectively, in a two-dimensional hexagonal lattice. It is shown that the natural features of these processes are reproduced without any explicit consideration of elasticity theory or ad hoc construction of microscopic Peierls potentials. Particular attention is paid to the Peierls barrier for dislocation glide or climb and the ensuing dynamic behavior as functions of strain rate, temperature, and dislocation density. It is shown that the dynamics are accurately described by simple viscous motion equations for an overdamped point mass, where the dislocation mobility is the only adjustable parameter. The critical distance for the annihilation of two edge dislocations as a function of separation angle is also presented.

Journal Article↗
PubMed2006

Linkage to nodal osteoarthritis: quantitative and qualitative analyses of data from a whole-genome screen identify trait-dependent susceptibility loci.

OBJECTIVE: To identify susceptibility loci for nodal osteoarthritis. METHODS: A genome screen at an average marker spacing of 9.29 cM was carried out on 558 people from 202 families, of whom 491 had nodal osteoarthritis. All genotyped people were graded for the incidence and severity of distal interphalangeal (DIP) nodes, and radiographs from 354 people were graded for joint-space narrowing (JSN) and osteophytes (OSTs). Age-regressed indices for DIP nodes, JSN and OSTs were calculated using these phenotypic data. Affected sibling pair (ASP) and quantitative trait analyses were carried out using MERLIN. RESULTS: The data analysis identified suggestive linkage to loci on chromosomes 3 (for JSN and OST), 4 (for JSN), 8 (for DIP), 11 (for radiographic osteoarthritis) and 16 (for JSN). Both the ASP and quantitative analyses identified the loci on chromosomes 4 and 11. The loci on chromosomes 3 and 16 overlap with those previously identified for large-joint osteoarthritis. Of the loci identified by the quantitative analyses with the logarithm of the odds of linkage >1.5, two were linked to more than one trait, whereas nine were linked to single traits: one for DIP, six for JSN and two for OST. CONCLUSION: The ASP and quantitative analyses of the cohort with nodal osteoarthritis suggest that multiple susceptibility loci for osteoarthritis influence the traits, which combine to form the osteoarthritis phenotype, and that these loci may not act exclusively on the joints of the hand.

Cohort Studies↗
PubMed2006

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Adult↗
PubMed2005

Plant responses to potassium deficiencies: a role for potassium transport proteins.

The availability of potassium to the plant is highly variable, due to complex soil dynamics, which are strongly influenced by root-soil interactions. A low plant potassium status triggers expression of high affinity K+ transporters, up-regulates some K+ channels, and activates signalling cascades, some of which are similar to those involved in wounding and other stress responses. The molecules that signal low K+ status in plants include reactive oxygen species and phytohormones, such as auxin, ethylene and jasmonic acid. Apart from up-regulation of transport proteins and adjustment of metabolic processes, potassium deprivation triggers developmental responses in roots. All these acclimation strategies enable plants to survive and compete for nutrients in a dynamic environment with a variable availability of potassium.

Acclimatization↗
PubMed2005

Cyclosporine-induced coronary endothelial dysfunction: is tetrahydrobiopterin the solution?

BACKGROUND: Coronary endothelial dysfunction after heart transplantation is predictive of cardiac allograft vasculopathy. Immunosuppressive drugs, particularly cyclosporine may contribute to this dysfunction by a direct effect. Tetrahydrobiopterin (BH(4)) is a potent antioxidant and an essential cofactor of nitric oxide biosynthesis. The purpose of this study was to investigate whether BH(4) could reverse the endothelial dysfunction induced by cyclosporine. METHODS: A previously described in vitro model of drug incubation in Krebs-bicarbonate solution (4 degrees C, 48 hours) of porcine epicardial coronary arteries was used. Coronary endothelial function studies were performed in organ chamber experiments after incubation with cyclosporine (10(-4) mol/L) in the presence or absence of 6-methyltetrahydropterin (MH(4) [0.1 mol/L], a BH(4) analog) to assess its effect on the cyclosporine-induced endothelial dysfunction. RESULTS: The average doses of PGF2(alpha) required to attain 50% of the maximal contraction to KCl was significantly lower (P < .001) in the cyclosporine group (8.6 +/- 1.94 x 10(-6) mol/L) compared to the control group (24.8 +/- 5.2 x 10(-6) mol/L). Exposure to cyclosporine induced a significant decrease in endothelium-dependent relaxations to serotonin (5HT) (% E(max) [5HT]: 77% +/- 4%; P < .05). Addition of MH(4) significantly reversed this impaired response (% E(max) [5HT]: 62% +/- 4%; P < .05). No alterations of relaxation were observed with bradykinin in both groups. Endothelium-independent relaxations to sodium nitroprussiate were fully preserved. CONCLUSIONS: These results suggest a significant protective role of BH(4) on coronary endothelial function following exposure to cyclosporine, which could reduce the incidence of endothelial dysfunction and cardiac allograft vasculopathy following cardiac transplantation.

Animals↗
PubMed2005

Synthesis and biologic activity of conformationally constrained analogs of L-363,301.

We report the synthesis, biological activity and conformational analysis of analogs of the cyclic hexapeptide L-363,301, c[Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11] (numbering as in the native hormone somatostatin-14). The d-Trp in position 8 was replaced with (2R,3S)- and (2R,3R)-beta-MeTrp respectively, with an added methyl group in the beta position of Trp. The objective of our study was to determine the potency and selectivity generated by the added constraint in the beta position of the d-Trp upon binding to human somatostatin receptors hsst1-5. We synthesized the building blocks enantioselectively and incorporated them into the peptides by SPPS. Competition binding assays revealed that both compounds 2 and 3 were selective for hsst2 over hsst5. The (2R,3S) analog 2 was approximately 30 times more potent at hsst2 than the (2R,3R) analog 3. Interestingly, the (2R,3R) compound showed no binding affinity at hsst5.

Amino Acids↗
PubMed2004

Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas.

The actions of somatostatin (SST) are mediated through five somatostatin receptor subtypes, termed SSTR1-5. Although SSTRs commonly display an overlapping pattern of tissue distribution, subtype-selective responses have been shown to occur in the same tissue. In the present study, we have investigated the changes in SSTR subtypes at the cellular and molecular level in both the brain and the pancreatic islets of mice deficient in SSTR5 (SSTR5KO). Expression levels of insulin and glucagon were also determined in the pancreas of these mice. Semi-quantitative RT-PCR and Western blot analysis showed significant increases in the expression of SSTR2 and 3 with a corresponding reduction in SSTR4 in the brains of female SSTR5KOs, while no changes were observed in male KOs. Strikingly, SST mRNA and SST-like immunoreactivity (SST-LI) were reduced in the brain of male KO animals but not in their female counterparts. In male SSTR5KO islets, there was an increase in the number of cells immunoreactive for SSTR1-3, whereas in female islets only SSTR3 expression was increased. Pancreatic SST-LI and SST mRNA, as well as immunoreactivity for insulin were reduced in male but not in female KO mice. These data indicate that deficiency of SSTR5 leads to subtype-selective sexually dimorphic changes in the expression of both brain and pancreatic SSTRs.

Animals↗
PubMed2004

Community involvement in medical practitioner recruitment and retention: reflections on experience.

The provision of health services to rural and remote communities has been the source of much concern and debate in recent times. One aspect of this is the universal problem of insufficient medical practitioners in rural areas and the associated issues of recruitment and retention. Rural communities can play an important role in the recruitment and retention of health professionals, particularly in terms of aiding the integration of health professionals and their families into the community. Community 'involvement' is not community 'development' in the usual sense of that term. Community involvement is about engaging and facilitating active community participation and leadership in the process at hand. This article reflects on experience gained through working with rural and remote communities in Queensland, Australia, with the key purpose of facilitating active community involvement in the recruitment and retention of medical practitioners. This article raises and discusses a number of issues arising from these experiences, with particular focus on barriers and opportunities to community involvement, and working with other agencies. Communities and agencies that attempt to increase rural community involvement in health service planning, provision, recruitment and retention should consider the following. For communities: Involvement must be real--active participation; Expectations need to be achievable (short and long term); Outcomes should be sustainable; Resources and capacity should remain in the community. For agencies: Avoid creating unrealistic community expectations; Be aware of time and resource requirements and constraints; Be consistent, forthright and honest in all dealings with communities; Keep communities informed of pending policy changes; See the process through to whatever conclusion.

Journal Article↗
PubMed2004

Biphasic effect of daidzein on cell growth of human colon cancer cells.

Colorectal cancer is one of the most common cancers in the world, poorly responding to available chemotherapeutic agents. To investigate whether natural molecules can inhibit colon cancer progression, we investigated a principle phytoestrogen found in soybean known as daidzein, and determined its effects on the human colon cancer cell line LoVo. LoVo cells were treated with 0.1, 1, 5, 10, 50 and 100 microM daidzein for 2, 3, 4 or 5 d. The results indicated that daidzein stimulated the growth of LoVo cells at 0.1 and 1 microM whereas at higher concentrations (10, 50 and 100 microM) cell growth was inhibited in a dose-dependent manner. Treatment of daidzein at 10, 50 and 100 microM resulted in cell cycle arrest at G0/G1 phase, DNA fragmentation and increases in caspase-3 activity. There were no changes in alkaline phosphatase activity (ALP), an indicator of cell differentiation, upon treatment with daidzein when compared to controls. These results indicate that daidzein has a biphasic effect on LoVo cell growth and its tumor suppressive effect is by means of cell cycle arrest and apoptosis but not through cell differentiation.

Alkaline Phosphatase↗
PubMed2004

Effects of a cancer genetics education programme on clinician knowledge and practice.

BACKGROUND: Many clinicians lack adequate knowledge about emerging standards of care related to genetic cancer risk assessment and the features of hereditary cancer needed to identify patients at risk. OBJECTIVE: To determine how a clinical cancer genetics education programme for community based clinicians affected participant knowledge and changed clinical practice. METHODS: The effects of the programme on participant knowledge and changes in clinical practice were measured through pre and post session knowledge questionnaires completed by 710 participants and practice impact surveys completed after one year by 69 out of 114 eligible annual conference participants sampled. RESULTS: Respondents showed a 40% average increase in specific cancer genetics knowledge. Respondents to the post course survey reported that they used course information and materials to counsel and refer patients for hereditary cancer risk assessment (77%), shared course information with other clinicians (83%), and wanted additional cancer genetics education (80%). CONCLUSIONS: There was a significant immediate gain in cancer genetics knowledge among participants in a targeted outreach programme, and subset analysis indicated a positive long term effect on clinical practice. Clinician education that incorporates evidence based content and case based learning should lead to better identification and care of individuals with increased cancer risk.

Curriculum↗
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2001

Thermal effects on atomic friction.

We model friction acting on the tip of an atomic force microscope as it is dragged across a surface at nonzero temperatures. We find that stick-slip motion occurs and that the average frictional force follows (absolute value lnv)(2/3), where v is the tip velocity. This compares well to recent experimental work, permitting the quantitative extraction of all microscopic parameters. We calculate the scaled form of the average frictional force's dependence on both temperature and tip speed as well as the form of the friction-force distribution function.

Journal Article↗
PubMed2001

Sharp interface limits of phase-field models.

The use of continuum phase-field models to describe the motion of well-defined interfaces is discussed for a class of phenomena that includes order-disorder transitions, spinodal decomposition and Ostwald ripening, dendritic growth, and the solidification of eutectic alloys. The projection operator method is used to extract the "sharp-interface limit" from phase-field models which have interfaces that are diffuse on a length scale xi. In particular, phase-field equations are mapped onto sharp-interface equations in the limits xi(kappa)<<1 and xi(v)/D<<1, where kappa and v are, respectively, the interface curvature and velocity and D is the diffusion constant in the bulk. The calculations provide one general set of sharp-interface equations that incorporate the Gibbs-Thomson condition, the Allen-Cahn equation, and the Kardar-Parisi-Zhang equation.

Journal Article↗
PubMed2001

Curved tails in polymerization-based bacterial motility.

The curved actin "comet-tail" of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.

Actins↗
PubMed2001

Solidification of a supercooled liquid in a narrow channel.

We simulate solidification in a narrow channel through the use of a phase-field model with an adaptive grid. In different regimes, we find that the solid can grow in fingerlike steady-state shapes, or become unstable, exhibiting unsteady growth. At low melt undercoolings, we find good agreement between our results, theoretical predictions, and experiment. For high undercoolings, we report evidence for a new stable steady-state finger shape which exists in experimentally accessible ranges for typical materials.

Journal Article↗
PubMed2001

Neuromodulatory effect of propentofylline on rat brain under acute and long-term hypoperfusion.

1. The effects of propentofylline (PPF, 25 mg kg(-1) body weight per day) on rat cerebral energy state and cytokine expression as well as on behaviour and histopathology were studied after acute and long-term permanent bilateral common carotid artery occlusion (BCCAO). 2. In the absence of PPF, acute ischaemia led to a decrease in energy-rich phosphates in parietotemporal cortex and hippocampus which correlated with an increase in AMP and adenosine concentrations measured by high-performance liquid chromatography technique. The concentrations of cortical cytokines TNF alpha and IL1 beta were increased 12 and 19 fold, respectively. 3. PPF had a neuroprotective action after 20 min of BCCAO, reducing the deleterious effect of acute ischaemia on rat brain energy state and microglial reaction. Simultaneously, PPF treatment increased cyclic-AMP 3 fold. 4. Three weeks of permanent BCCAO did not significantly disturb brain energy metabolism, microglial reaction or histopathology. However, a significant reduction of 30 -- 50% in rat memory capacities and a locomotor hyperactivity were obtained. 5. Continuous PPF-application, however, led to a marked increase in rat working memory and to reduced locomotor activity, which were returned nearly to control levels by 1 week after permanent BCCAO. In summary, PPF showed a clear neuroprotective effect on cerebral energy state and pro-inflammatory cytokines under conditions of acute global ischaemia. Continuous administration of PPF led to memory improvement during permanent BCCAO. 6. These results underscore the benefit of treatment with PPF in clinical practice, particularly during stroke, but also in cerebrovascular and neurodegenerative disorders.

Adenosine↗