Biomedical subjects

J Hudson

Publications and source records attributed to J Hudson.

At least 19 recordsLinked to original sources

PubMed2004

Export of dissolved organic carbon from peatlands under elevated carbon dioxide levels.

Peatlands represent a vast store of global carbon. Observations of rapidly rising dissolved organic carbon concentrations in rivers draining peatlands have created concerns that those stores are beginning to destabilize. Three main factors have been put forward as potential causal mechanisms, but it appears that two alternatives--warming and increased river discharge--cannot offer satisfactory explanations. Here we show that the third proposed mechanism, namely shifting trends in the proportion of annual rainfall arriving in summer, is similarly unable to account for the trend. Instead we infer that a previously unrecognized mechanism--carbon dioxide mediated stimulation of primary productivity--is responsible. Under elevated carbon dioxide levels, the proportion of dissolved organic carbon derived from recently assimilated carbon dioxide was ten times higher than that of the control cases. Concentrations of dissolved organic carbon appear far more sensitive to environmental drivers that affect net primary productivity than those affecting decomposition alone.

Atmosphere↗

PubMed2003

Total knee arthroplasty for neglected permanent post-traumatic patellar dislocation--case report.

Permanent post-traumatic patellar dislocation is a rare entity resulting from recurrent trauma. This uncommon condition is often confused clinically with congenital dislocation of the patella. Treatment options, although not well defined, include observation, various soft tissue and bony procedures for realigning the patella and patellectomy. To our knowledge, this is the first case reporting the use of conventional non-constrained total knee arthroplasty with patellar resurfacing and soft tissue realignment procedure for long-standing patellar dislocation in a single stage. An interesting feature of this case was the patient's ability to function reasonably well for nearly 40 years with a dislocated patella until the development of secondary osteoarthritis, and the surprisingly good recovery after total knee replacement.

Arthrography↗

PubMed2002

Ultrastructural changes in malignant transformation of oral mucosa.

Transmission electron microscopy (EM) has been used to identify the ultrastructural details of normal and cancerous human oral mucosa. However, inconsistent reports of structural descriptions have rendered transmission EM valueless in the diagnosis of oral squamous cell carcinoma (SCC) or as a prognostic indicator. To identify features of dysplasia for diagnostic purposes, normal mucosa, severe dysplasia, oral SCC and normal margin adjacent to oral SCC were used to compare the ultrastructural features of normal and premalignant oral mucosa and oral SCC. The preparatory stages of dehydration, embedding, cutting and positive staining for transmission EM were modified and tested to improve ultrastructural definition. Thin and discontinuous basal laminas were found in mucosa with severe dysplasia and normal margin adjacent to oral SCC. No basal lamina was identified in oral SCC. This study has shown that there are some ultrastructural changes during malignant transformation of oral mucosa. Together with other laboratory investigative techniques, transmission EM may be helpful in detecting malignant changes in oral mucosa.

Acrylic Resins↗

PubMed2002

Antiviral activity of characterized extracts from echinacea spp. (Heliantheae: Asteraceae) against herpes simplex virus (HSV-I).

Extracts of 8 taxa of the genus Echinacea were found to have antiviral activity against Herpes simplex (HSV) virus Type I in vitro when exposed to visible and UV-A light. n-Hexane extracts of roots containing alkenes and amides were more active in general than ethyl acetate extracts containing caffeic acids. The most potent inhibitors of HSV were E. pallida var. sanguinea crude (70 % ethanol) inflorescence extract (MIC = 0.026 mg/mL), cichoric acid (MIC = 0.045 mg/mL) and Echinacea purpurea n-hexane root extract (MIC = 0.12 mg/mL).

Animals↗

PubMed2001

Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice.

Mutations in the human ectodysplasin-A (EDA) are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype, suggesting its vital role in the development of hair, sweat glands and teeth. Among several EDA splice isoforms, the most common and the longest EDA splice isoforms, EDA-A1 and EDA-A2, differing by only two amino acids, activate NF-kappaB-promoted transcription by binding to distinct receptors, EDAR and XEDAR. The extent to which any particular isoform is sufficient for the formation of hair, sweat glands or teeth has remained unclear. Here we report that transgenic expression of the mouse EDA-A1 isoform in tabby (EDA-less) males rescued development of several skin appendages. The transgenic tabby mice showed almost complete restoration of hair growth, dermal ridges, sweat glands and molars. The number of hair follicles in the transgenic mice is the same as in wild-type; though the development of follicles and associated glands varies from indistinguishable from wild-type to smaller and/or only partially formed. These results suggest that the other EDA isoforms may not be absolutely required for skin appendage formation, but consistent with distinctive temporal and spatial expression of the EDA-A2 isoform, are likely required for appropriate timing and completeness of development. Our data provide the first direct physiological evidence that EDA-A1 is a key regulator of hair follicle and sweat gland initiation; its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation.

Animals↗

PubMed2001

HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study.

BACKGROUND: Lipodystrophy, dyslipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. The aims of this study were to determine if these are reversible with continued HIV suppression following protease inhibitor substitution. METHODS: Eighty-one HIV protease inhibitor recipients (78 male; mean antiretroviral therapy, 55 months) with predominant peripheral lipoatrophy, HIV RNA < 400 copies/ml plasma for at least the preceding 6 months, and no prior abacavir, non-nucleoside analogue or adefovir therapy were randomized 3 : 2 to continue nucleoside analogues and substitute protease inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to continue all therapy (n = 32) with an option to switch at week 24. The primary endpoints were total body fat and HIV RNA at week 24. Other assessments were regimen safety, regional body composition, metabolic parameters, quality of life, and CD4 T-lymphocyte counts to week 48. RESULTS: There was a greater decline in total body fat in the switch group than in the continue group (-1.6 and -0.4 kg, respectively at week 24; P = 0.006). This comprised greater declines in limb and subcutaneous abdominal fat, and in intra-abdominal fat of patients with moderate or severe abdominal fat accumulation. Viral suppression was similar, despite 18 (37%) switch group patients ceasing at least one study drug by week 24 because of adverse events. Total cholesterol and triglycerides declined more in the switch group (both P < 0.002). High density lipoprotein cholesterol increased significantly in both groups at week 48 (P < 0.02). There was no change for any glycaemic parameter. CONCLUSIONS: In predominantly lipoatrophic patients, switching from HIV protease inhibitor therapy lead to improved lipids and less intra-abdominal fat, but also to less peripheral fat, and had minimal effect on insulin resistance. Virological control in these heavily pretreated patients was unaffected, despite frequent switch drug cessations.

Adenine↗

PubMed2001

Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors.

This study details the profile of 13 cell surface cluster differentiation markers on human reserve stem cells derived from connective tissues. Stem cells were isolated from the connective tissues of dermis and skeletal muscle derived from fetal, mature, and geriatric humans. An insulin/dexamethasone phenotypic bioassay was used to determine the identity of the stem cells from each population. All populations contained lineage-committed myogenic, adipogenic, chondrogenic, and osteogenic progenitor stem cells as well as lineage-uncommitted pluripotent stem cells capable of forming muscle, adipocytes, cartilage, bone, fibroblasts, and endothelial cells. Flow cytometric analysis of adult stem cell populations revealed positive staining for CD34 and CD90 and negative staining for CD3, CD4, CD8, CD11c, CD33, CD36, CD38, CD45, CD117, Glycophorin-A, and HLA DR-II.

Aged↗

PubMed2001

Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells.

Clonal populations of lineage-uncommitted pluripotent mesenchymal stem cells have been identified in prenatal avians and rodents. These cells reside in the connective tissue matrices of many organs and tissues. They demonstrate extended capabilities for self-renewal and the ability to differentiate into multiple separate tissues within the mesodermal germ line. This study was designed to determine whether such cells are present in the connective tissues of postnatal mammals. This report describes a cell clone derived by isolation from postnatal rat connective tissues, cryopreservation, extended propagation, and serial dilution clonogenic analysis. In the undifferentiated state, this clone demonstrates a high nuclear-to-cytoplasmic ratio and extended capacity for self-renewal. Subsequent morphological, histochemical, and immunochemical analysis after the induction of differentiation revealed phenotypic markers characteristic of multiple cell types of mesodermal origin, such as skeletal muscle, smooth muscle, fat cells, cartilage, and bone. These results indicate that this clone consists of pluripotent mesenchymal stem cells. This report demonstrates that clonal populations of reserve stem cells are present in mammals after birth. Potential roles for such cells in the maintenance, repair, and regeneration of mesodermal tissues are discussed.

Animals↗

PubMed2001

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗

PubMed2001

Extent of linkage disequilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk.

While studies have implicated alleles at the CAG and GGC trinucleotide repeats of the androgen receptor gene with high-grade, aggressive prostate cancer disease, little is known about the normal range of variation for these two loci, which are separated by about 1.1 kb. More importantly, few data exist on the extent of linkage disequilibrium (LD) between the two loci in different human populations. Here we present data on CAG and GGC allelic variation and LD in six diverse populations. Alleles at the CAG and GGC repeat loci of the androgen receptor were typed in over 1000 chromosomes from Africa, Asia, and North America. Levels of linkage disequilibrium between the two loci were compared between populations. Haplotype variation and diversity were estimated for each population. Our results reveal that populations of African descent possess significantly shorter alleles for the two loci than non-African populations (P<0.0001). Allelic diversity for both markers was higher among African Americans than any other population, including indigenous Africans from Sierra Leone and Nigeria. Analysis of molecular variance revealed that approx. 20% of CAG and GGC repeat variance could be attributed to differences between the populations. All non-African populations possessed the same common haplotype while the three populations of African descent possessed three divergent common haplotypes. Significant LD was observed in our sample of healthy African Americans. The LD observed in the African American population may be due to several reasons; recent migration of African Americans from diverse rural communities following urbanization, recurrent gene flow from diverse West African populations, and admixture with European Americans. This study represents the largest genotyping effort to be performed on the two androgen receptor trinucleotide repeat loci in diverse human populations.

Africa↗

PubMed2001

Isolation and characterization of canine hematopoietic progenitor cells.

The purpose of this study was to purify and characterize canine hematopoietic progenitor cells for surface antigen phenotype and reconstitution ability. Canine hematopoietic progenitor cells were isolated by density gradient sedimentation, lineage depletion with monoclonal antibodies, and fluorescence-activated cell sorting (FACS) for selection of cells with low-forward and right-angle scatter that were rhodamine 123 (Rh-123)(dull). Isolated cells were characterized for expression of CD34, c-kit, and Flt-3. A canine/murine xenograft model and a mixed-chimerism assay were used to examine the in vivo proliferative potential of isolated cells. The lineage-positive (Lin(+)) cells represented 80 +/- 11% (n = 22) of the input mononuclear cells. Lineage depletion resulted in a fourfold increase in colony-forming unit granulocyte/monocyte (CFU-GM), a 2.5-fold increase in burst-forming unit-erythroid (BFU-E), and a twofold increase in the number of Rh-123(dull) cells over nonlineage-depleted bone marrow mononuclear cells (BMMCs). Lineage depletion led to a 2.7-fold enrichment of CD34 cells, a 10.4-fold enrichment of c-kit cells, and a 10.8-fold enrichment of CD34/c-kit(+1) cells over total BMMCs. Nineteen percent of lineage-negative (Lin(-)) cells were positive for Flt-3. Injection of canine cells into irradiated (400 rads) NOD/SCID mice resulted in the detection of canine CD45(+) cells with BMMCs, Lin(-) cells, or Rh-123(dull) cells. Transplantation of purified Lin(-) cells in dog leukocyte antigen-matched littermates resulted in low-level engraftment for at least 10 weeks. The development of methods for purification and characterization of canine hematopoietic progenitor cells should enhance the utilization of the canine model for a variety of experimental and therapeutic purposes.

Animals↗

PubMed2001

Gender differences, physiological arousal and the role of winning in fruit machine gamblers.

AIMS: To examine gender differences in changes in physiological arousal as indexed by heart rate during fruit machine gambling while controlling for the confounding effect of movement and as a function of winning and losing, and to examine relationships between sensation-seeking, self-reported arousal during gambling, heart rate during gambling and loss of control of gambling behaviour. SAMPLE, DESIGN AND MEASUREMENTS: Heart rate and subjective arousal were recorded in a sample of 22 male and 20 female fruit machine players before, during and after the gambling process. At baseline measures were taken of sensation seeking, self-reported arousal during gambling and loss of control of gambling. A simulation of the behaviour used to operate fruit machines was used during baseline measurement. FINDINGS: Significant increases in heart-rate over movement controlled baselines were observed within participants during gambling. However, for the losing group these differences were slight compared to the increases found when participants won during play. Furthermore, winning/losing was the only variable among a range of variables which was a significant predictor of heart-rate increase during play over a baseline control. Additionally HR levels of males and females behaved the same way in relation to the manipulations. Significant correlations between HR during play and the measures of both subjective arousal and sensation seeking were also present. CONCLUSIONS: Winning during gambling is essential in order to maintain increased HR levels over baseline after play. Subjective arousal and sensation seeking may be predictors of levels of arousal experienced during play.

Adult↗

PubMed2000

A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 study.

BACKGROUND: Highly active antiretroviral therapy (HAART) including two nucleoside analogues and a potent protease inhibitor is standard of care initial therapy for HIV-infected adults. The best-tolerated and most potent initial HAART regimen is unknown and was investigated in this study. METHODS: One hundred and nine HIV-infected adults with no prior antiretroviral therapy, and CD4 lymphocyte counts < 500 x 10(6) cells/l or plasma HIV RNA > 30,000 copies/ml were randomized to zidovudine-lamivudine-indinavir (ZDV-3TC-IDV), stavudine-lamivudine-indinavir (d4T-3TC-IDV) or stavudine-didanosine-indinavir (d4T-ddI-IDV) for 52 weeks. The primary endpoints were plasma HIV RNA and drug-related adverse events. Other assessments were overall safety, adherence and adverse events, CD4 lymphocyte counts, cutaneous delayed type hypersensitivity (DTH) responses and quality of life (Euroqol). RESULTS: Only 58% patients had HIV RNA < 50 copies/ml plasma at 12 months, with no significant difference between the three regimes (P = 0.34). Drug-related adverse events sufficiently severe to warrant drug discontinuation were less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who remained on their assigned therapy with plasma HIV RNA < 50 copies/ml at 52 weeks were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV. Virological failure at 52 weeks was more likely in those whose adherence was estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in those who developed grade 3 or 4 drug-related adverse events. At 52 weeks, the mean CD4 lymphocyte count increase was 200 x 10(6) cells/l with only 7% of patients having counts lower than at baseline; DTH responses improved but remained clinically impaired in most patients. Quality of life improved significantly in all groups. CONCLUSIONS: Initial HAART regimens including IDV failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only 12 months of therapy although there was significant overall improvement immunologically and in quality of life. The type of dual nucleoside combination used was less important in predicting virological failure than was imperfect adherence early in therapy. Consideration should be given to modifying a HAART regimen relatively early in non-adherent patients.

Adult↗

PubMed2000

Suppression of microtubule dynamic instability and treadmilling by deuterium oxide.

Deuterium oxide (D(2)O) is known to promote the assembly of tubulin into microtubules in vitro, to increase the volume of mitotic spindles and the number and length of spindle microtubules, and to inhibit mitosis. Reasoning that its actions on cellular microtubules could be due to modulation of microtubule dynamics, we examined the effects of replacing H(2)O with D(2)O on microtubule dynamic instability, treadmilling, and steady-state GTPase activity. We found that replacing 50% or more of the H(2)O with D(2)O promoted microtubule polymerization and stabilized microtubules against dilution-induced disassembly. Using steady-state axoneme-seeded microtubules composed of pure tubulin and video microscopy, we found that 84% D(2)O decreased the catastrophe frequency by 89%, the shortening rate by 80%, the growing rate by 50%, and the dynamicity by 93%. Sixty percent D(2)O decreased the treadmilling rate of microtubules composed of tubulin and microtubule-associated proteins by 42%, and 89% D(2)O decreased the steady-state GTP hydrolysis rate by 90%. The mechanism responsible for the ability of D(2)O to stabilize microtubule dynamics may involve enhancement of hydrophobic interactions in the microtubule lattice and/or the substitution of deuterium bonds for hydrogen bonds.

Animals↗

PubMed2000

Low HDL cholesterol, aggression and altered central serotonergic activity.

Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

Adult↗

PubMed2000

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

Adult↗

PubMed2000

Femoral morphology and cross-sectional geometry of adult myostatin-deficient mice.

GDF-8, also known as myostatin, is a member of the transforming growth factor-beta (TGF-beta) superfamily of secreted growth and differentiation factors that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared with normal mice. We examined femoral morphology of adult myostatin-deficient mice to assess the effects of muscle fiber hypertrophy and hyperplasia on bone shape and cross-sectional geometry. Femora of age- and weight-matched adult mice homozygous for the disrupted myostatin sequence were compared with those of wild-type controls (n = 8 per group). Results show that, as was the case in previous studies, myostatin null mice have hindlimb muscle masses that are approximately double those of controls. Myostatin-deficient mice exhibit third trochanters that are significantly larger than those of controls, whereas the femoral midshafts of the control and experimental mice do not differ significantly from one another in cortical area, bending moment of inertia, and polar moment of inertia. Our findings indicate that the increased muscle mass of myostatin-deficient mice primarily affects sites of muscle insertion, but does not induce additional cortical bone deposition in the diaphysis relative to controls. We therefore conclude that the expanded third trochanters of myostatin-deficient subjects result from tendon and Sharpey fiber expansion associated with muscle growth rather than cortical bone deposition in response to increased levels of mechanical stress.

Animals↗

PubMed2000

Effects of a medicine review and education programme for older people in general practice.

AIMS: To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice. METHODS: Older people taking at least three medicines were randomly allocated to a control or intervention group. Both groups received three visits from a clinical pharmacist: Visit 1: Assessment and patients' medicines rationalized in intervention group. Visit 2: Intervention group given medicines education. Visit 3: Knowledge and compliance in both groups assessed by structured questionnaire RESULTS: Compliance in the intervention group was 91.3%, compared with 79.5% in the control group (P < 0.0001). The number of intervention group patients correctly understanding the purpose of their medicines increased from 58% to 88% on the second visit, compared with 67% to 70% in the control group (P < 0.0005). CONCLUSIONS: A general practice based medication review and education programme improved medicine compliance and knowledge of older people in the short term.

Aged↗