Search PubMed⌕ Search

Biomedical subjects

J Woods

Publications and source records attributed to J Woods.

At least 19 recordsLinked to original sources
PubMed2006

Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia.

AIMS/HYPOTHESIS: Under normal physiological conditions, glucagon signalling is important in glucose homeostasis. Hyperglucagonaemia or altered insulin:glucagon ratio plays a role in maintaining hyperglycaemia in subjects with type 2 diabetes. It has been reported that glucagon receptor knockout (Gcgr (-/-)) mice develop normally and have lower plasma glucose on a normal diet. The goal of the current research was to further investigate the role of glucagon signalling in metabolic control and glucose homeostasis. METHODS: Gcgr (-/-) mice were challenged with a high-fat diet (HFD) and with streptozotocin, which induces beta cell damage. They were then analysed for whole-body and serum metabolic phenotypes as well as pancreatic islet morphology. RESULTS: In comparison with wild-type mice, Gcgr (-/-) mice exhibited decreased body weight and food intake, reduced plasma glucose levels, and improved oral and intraperitoneal glucose tolerance. Elevated glucagon-like peptide-1 levels and reduced gastric emptying were also observed in Gcgr (-/-) mice, which also had reduced HFD-induced hyperinsulinaemia and hyperleptinaemia, and were resistant to the development of hepatic steatosis. In addition, Gcgr (-/-) mice were resistant to STZ-induced hyperglycaemia and pancreatic beta cell destruction. CONCLUSIONS/INTERPRETATION: This study demonstrates that blocking glucagon signalling by targeted Gcgr gene deletion leads to an improvement in metabolic control in this mouse model.

Animals↗
PubMed2006

Clinical and research applications of photodynamic therapy in dermatology: experience of the Scottish PDT Centre.

BACKGROUND AND OBJECTIVES: The Scottish PDT Centre has carried out 3,442 treatments on 762 patients with superficial skin lesions, especially superficial basal cell carcinoma (sBCC), Bowen's disease (BD) and actinic keratosis (AK). STUDY DESIGN MATERIALS AND METHODS: The article reviews our experience of various light sources and associated dosimetry; thereafter we discuss clinical outcome followed by some of our research studies in clinically important areas. RESULTS: We show that improved dosimetry is required to ensure an optimal light dose is delivered to the tumour. We have shown that photosensitizers and proteins interact in such a way that their photophysical and photochemical properties are modified. We have also demonstrated the presence of DNA strand breaks with two different photosensitizers, but there is no evidence that PDT is significantly mutagenic in clinical practice. CONCLUSIONS: In our experience, topical PDT is generally well tolerated and is an effective treatment of sBCC, BD, AK, field change and lesions at sites of poor healing.

Aminolevulinic Acid↗
PubMed2004

Characterization of two outer membrane protein antigens of Porphyromonas gingivalis that are protective in a murine lesion model.

Porphyromonas gingivalis is a key periodontal pathogen that has been implicated in the aetiology of chronic adult periodontitis. The aim of this study was to characterize two potential vaccine candidates (PG32 and PG33) identified from a previous genomic sequence analysis. Gene knockout studies suggested that these proteins play an important role in bacterial growth and are transcriptionally linked. Analysis of 14 laboratory and clinical isolates of P. gingivalis found that in all strains, both genes were present with a high level of conservation and that the two proteins were also expressed in vitro. Truncated recombinant PG32 and PG33 proteins were produced in Escherichia coli in an attempt to increase the solubility of the proteins while retaining their native conformation. While most of the truncated proteins remained insoluble, two truncated proteins showed good solubility and high levels of protection in the P. gingivalis murine lesion model and may be considered as potential vaccine candidates for further testing in models of human periodontal disease.

Amino Acid Sequence↗
PubMed2003

The effect of passive heating and face cooling on perceived exertion during exercise in the heat.

Increased body temperature is thought to be an important component of the higher perception of exertion that is a feature of fatigue during exercise in the heat but a causal relationship has yet to be demonstrated. We have investigated the effect of passive heating on the perception of exertion during a standard bout of exercise and also assessed the effect of cooling the head on compensating for the increased body temperature on the feelings of exertion. Ten male subjects performed a 14-min cycling exercise [average power approximately 63% of maximum power output ( W(max))] at an ambient temperature of 35 degrees C at resting rectal temperature [mean (SD): 37.49 (0.27) degrees C; control (CON) trial] on one occasion, and after sitting in a sauna to raise rectal temperature [mean (SD): 38.95(0.13) degrees C; sauna (SAU) trial]. During the exercise, subjects reported their ratings of overall perceived exertion (RPE), perceived exertion of the legs (RPE(legs)) and thermal comfort (TC). A blood sample was collected by the end of the exercise for determination of plasma glucose, lactate and prolactin and haematocrit. RPE values were significantly elevated after passive heating [mean (SE): 14.5 (0.7) units in CON and 17.2 (0.5) units in SAU, at the end of exercise; P<0.001] as were the RPE(legs) ( P<0.01), while ratings of TC were similar in CON and SAU trials. Passive heating increased blood glucose ( P<0.05) but had no effect on lactate at the end of the exercise. Plasma prolactin was markedly elevated as a result of the sauna exposure [mean (SE): 1598 (152) versus 225 (31) mU l(-1) in SAU and CON trials, respectively; P<0.001]. Six of the subjects repeated the two trials but with the face cooled during exercise (trials CON(FAN) and SAU(FAN)) that was achieved by combining face fanning and spraying the face with a mist of cooled water. Face cooling decreased RPE values after sauna to a point that no differences between the two conditions existed. RPE(legs) scores and heart rate, however, remained higher in SAU(FAN) compared with CON(FAN) ( P<0.05). We conclude that hyperthermia is a causative element of the increased perception of exertion during submaximal exercise in the heat and that the effect of increased core temperature on the feelings of exertion is modulated by face cooling.

Adult↗
PubMed2001

Reinforcing and discriminative-stimulus effects of ephedrine isomers in rhesus monkeys.

Ephedrine is a sympathomimetic drug that is currently found in many over-the-counter preparations. This compound exists as four isomers which, in addition to a racemic mixture, were evaluated for their positive reinforcing effects and for their similarity to (+)-amphetamine as a discriminative stimulus. Rhesus monkeys (N=3) with intravenous cocaine (0.1 mg/kg/inj) or saline as a consequence for lever pressing were shown to self-administer all of the ephedrine compounds (range tested: 0.03-3.0 mg/kg/inj), with the exception of (-)-pseudoephedrine, when each drug/dose was substituted for cocaine or saline during test sessions. However, the (-)-pseudoephedrine isomer was evaluated within a limited dose range due to solubility limitations. Systematically increasing the number of responses required for an injection indicated that these isomers were not as effective as reinforcers as was cocaine. Rhesus monkeys (N=3) trained to discriminate intragastric 1.0 mg/kg (+)-amphetamine from saline were given substitution tests with the ephedrine isomers and the racemic mixture. When given intragastrically, at least one dose of all the ephedrine isomers substituted for the (+)-amphetamine discriminative stimulus in at least one of the subjects tested. However, (+)-amphetamine-like effects were not systematically related to dose. When the discriminative-stimulus effects of (-)-ephedrine were also compared with those of (+)-amphetamine across three different routes of administration, full, dose-related, (+)-amphetamine-like responding was observed with both the intramuscular and intravenous routes. Taken together, these results suggest that the ephedrines have psychomotor stimulant-like abuse potential, lower than that of cocaine. Parenteral administration may enhance psychomotor-stimulant-like effects.

Animals↗
PubMed2001

Extreme diversity, conservation, and convergence of spider silk fibroin sequences.

Spiders (Araneae) spin high-performance silks from liquid fibroin proteins. Fibroin sequences from basal spider lineages reveal mosaics of amino acid motifs that differ radically from previously described spider silk sequences. The silk fibers of Araneae are constructed from many protein designs. Yet, the repetitive sequences of fibroins from orb-weaving spiders have been maintained, presumably by stabilizing selection, over 125 million years of evolutionary history. The retention of these conserved motifs since the Mesozoic and their convergent evolution in other structural superproteins imply that these sequences are central to understanding the exceptional mechanical properties of orb weaver silks.

Amino Acid Motifs↗
PubMed2001

Expression of expanded repeat androgen receptor produces neurologic disease in transgenic mice.

Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by the expansion of a polyglutamine tract within the androgen receptor. This disease is unusual among the polyglutamine diseases in that it involves lower motor and sensory neurons, with relative sparing of other brain structures. We describe the development of transgenic mice, created with a truncated, highly expanded androgen receptor driven by the neurofilament light chain promoter, which develop many of the motor symptoms of SBMA. In addition, transgenic mice created with the prion protein promoter develop widespread neurologic disease, reminiscent of juvenile forms of other polyglutamine diseases. Thus, in these experiments, the distribution of neurologic symptoms depends on the expression level and pattern of the promoter used, rather than on specific characteristics of androgen receptor metabolism or function. The transgenic mice described here develop neuronal intranuclear inclusions (NIIs), a hallmark of SBMA and the other polyglutamine diseases. We have shown these inclusions to be ubiquitinated and to sequester molecular chaperones, components of the 26S proteasome and the transcriptional activator CREB-binding protein. Apart from the presence of NIIs, evidence of neuropathology or neurogenic muscle atrophy was absent, suggesting that the neurologic phenotypes observed in these mice were the result of neuronal dysfunction rather than neuronal degeneration. These mice will provide a useful resource for characterizing specific aspects of motor neuron dysfunction, and for testing therapeutic strategies for this and other polyglutamine diseases.

Animals↗
PubMed2001

Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma: a molecular genetic and clinicopathological study.

PURPOSE: Cholangiocarcinoma (CC) is the second most common malignant tumor in the liver and the molecular genetic alterations involved in the tumorigenesis of CC have not been well studied. PATIENTS AND METHODS: The authors analyzed the loss of heterozygosity (LOH) in four tumor suppressor genes, including the adenomatous polyposis coli (APC) gene, the deleted in colon cancer (DCC) gene, the 8-hydroguanine-specific DNA glycosylase (OGG1) gene, and the p53 gene in 22 surgically resected primary CCs by using microdissection-based PCR amplification and direct DNA sequencing. RESULTS: A total of 19 (86.4%) out of 22 CCs exhibited genetic alterations, of which 11 (57.9%) and eight (42.1%) cases showed one and more than one gene alterations, respectively. The frequency of genetic alterations of the four genes studied ranged in order from high to low as APC (68.8%) > DCC (46.2%) > OGG1 (41.7%) > p53 (37.5%). Based on the pattern of altered genes and their correlation with clinical and pathological parameters, the genetic alterations were classified into three groups: group I: no detectable genetic alterations (n = 3, 13.6%); group II: LOH in APC and/or DCC (n = 9, 40.9%); and group III: LOH in OGG1 and/or p53 occurred separately or combined with LOH in APC and/or DCC (n = 10, 45.5%). The > or = 3-year survival rates between group II and group III are 88.9% and 30%, respectively (P < 0.05). No significant differences were found between genetic alterations and tumor size, tumor type, tumor invasion, TNM staging, and tumor differentiation (P > 0.05). CONCLUSION: Accumulation of multiple genetic alterations are involved in the tumorigenesis of CC, of which genetic alterations of APC and DCC occur at a relatively early stage, and of OGG1 and p53 occur at a relatively late stage during development of CC.

Aged↗
PubMed2001

Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers.

Prostate cancer is one of the leading causes of cancer-related deaths for men in the United States. Like other malignancies, prostate cancer is underscored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently identified among prostate cancers, few genes have been identified thus far as critical to the development of invasive prostate cancers. In this report, we used the recently developed technology, the "differential subtraction chain," to perform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence was deleted in >50% of prostate cancers we tested. We mapped this sequence to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 cases, or 80%). Statistical analysis indicates that deletion of myopodin is highly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers.

Amino Acid Sequence↗
PubMed2001

Frequent allelic imbalance and loss of protein expression of the DNA repair gene hOGG1 in head and neck squamous cell carcinoma.

Reactive oxygen species produced by aerobic cellular metabolism or through exposure to environmental carcinogens can cause oxidative DNA damage by generating DNA base lesions and strand breakage. Prime among these base lesions is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DNA base lesions, 8-oxoguanine is the most abundant and is critical in terms of mutagenesis because it is capable of mispairing with adenine, which, if not sufficiently repaired, may lead to G:C to T:A transversion upon DNA replication. The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), capable of excision repair of 8-oxoguanine, has been recently cloned, characterized, and mapped to the short arm of chromosome 3 (3p25-26), a region showing frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the present study, we developed a tissue microdissection approach designed for use with formalin-fixed, paraffin-embedded specimens which is capable of detecting and characterizing the hOGG1 allelic loss using two highly informative, intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases were informative. We analyzed these 18 cases and found that 11 showed evidence of hOGG1 allelic loss. By immunohistochemical staining on a total of 71 HNSCC cases using a commercially available anti-hOGG1 antibody, we showed that hOGG1 gene expression was markedly suppressed in up to 38% of the cases. The frequent allelic imbalance and suppression of the hOGG1 gene thus imply that repair for oxidative DNA damages may be relevant in future studies on head and neck squamous carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed2001

Methadone advocacy: the voice of the patient.

This decade will see great strides in the acceptance of methadone treatment for heroin addiction, as a result of clear scientific and clinical evidence of its efficacy, and strong methadone advocacy. The new proposal for rule making (NPRM) will help the medical profession accept methadone treatment as beneficial for opiate addiction and realize that it should be more accessible to patients from trained physicians in the community. This will be the first step in reducing the stigma and prejudice that continue to hinder the availability of this lifesaving medication to all who need it. Methadone advocacy has grown into a powerful network of groups working toward the same major goals. As the premier methadone advocacy organization and the voice for methadone patients, the National Alliance of Methadone Advocates (NAMA) will promote the view that methadone patients are to be judged by the contributions they make to their families and communities.

Heroin Dependence↗
PubMed2000

The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis.

5-Hydroxytryptamine 2A (5-HT2A) receptors, a major site of action of clozapine and other atypical antipsychotic medications, are, paradoxically, internalized in vitro and in vivo by antagonists and agonists. The mechanisms responsible for this paradoxical regulation of 5-HT2A receptors are unknown. In this study, the arrestin and dynamin dependences of agonist- and antagonist-mediated internalization were investigated in live cells using green fluorescent protein (GFP)-tagged 5-HT2A receptors (SR2-GFP). Preliminary experiments indicated that GFP tagging of 5-HT2A receptors had no effect on either the binding affinities of several ligands or agonist efficacy. Likewise, both the native receptor and SR2-GFP were internalized via endosomes in vitro. Experiments with a dynamin dominant-negative mutant (dynamin K44A) demonstrated that both agonist- and antagonist-induced internalization were dynamin-dependent. By contrast, both the agonist- and antagonist-induced internalization of SR2-GFP were insensitive to three different arrestin (Arr) dominant-negative mutants (Arr-2 V53D, Arr-2-(319-418), and Arr-3-(284-409)). Interestingly, 5-HT2A receptor activation by agonists, but not antagonists, induced greater Arr-3 than Arr-2 translocation to the plasma membrane. Importantly, the agonist-induced internalization of 5-HT2A receptors was accompanied by differential sorting of Arr-2, Arr-3, and 5-HT2A receptors into distinct plasma membrane and intracellular compartments. The agonist-induced redistribution of Arr-2 and Arr-3 into intracellular vesicles and plasma membrane compartments distinct from those involved in 5-HT2A receptor internalization implies novel roles for Arr-2 and Arr-3 independent of 5-HT2A receptor internalization and desensitization.

Animals↗
PubMed2000

Randomised comparison of the effectiveness and costs of community and hospital based mental health services for children with behavioural disorders.

OBJECTIVE: To test the hypothesis that a community based intervention by secondary child and adolescent mental health services would be significantly more effective and less costly than a hospital based intervention. DESIGN: Open study with two randomised parallel groups. SETTING: Two health districts in the north of England. PARTICIPANTS: Parents of 3 to 10 year old children with behavioural disorder who had been referred to child and adolescent mental health services. INTERVENTION: Parental education groups. MAIN OUTCOME MEASURES: Parents' and teachers' reports of the child's behaviour, parental depression, parental criticism of the child, impact of the child's behaviour on the family. RESULTS: 141 subjects were randomised to community (n=72) or hospital (n=69) treatment. Primary outcome data were obtained on 115 (82%) cases a year later. Intention to treat analyses showed no significant differences between the community and hospital based groups on any of the outcome measures, or on costs. Parental depression was common and predicted the child's outcome. CONCLUSIONS: Location of child mental health services may be less important than the range of services that they provide, which should include effective treatment for parents' mental health problems.

Child↗
PubMed2000

Electronic versus paper instruments for daily data collection.

PURPOSE: Collecting daily information on a series of similar, recurring events such as menstrual bleeding, headaches, or insulin levels using paper instruments is subject to problems such as missing or incorrectly recorded data, and retrospective data entry. The authors are developing and evaluating electronic data collection using hand-held personal computers (H/PC) for a variety of health-related applications, including tracking premenstrual syndrome (PMS), fertility awareness, and headaches, to improve accuracy and timeliness of data collection.METHODS: ProCycle is a prototype electronic diary for collection of daily data on menstrual bleeding, medications, and health symptoms. In a 3-month pilot test in 25 regularly cycling women, we compared its performance with a paper calendar regarding missing and incorrect data, data entry lag, data cleaning time, and users' preferences with respect to factors such as remembering to enter data, convenience, and overall preference. Additional programs for PMS, fertility, and headaches are being field tested on subjects from the Boston and New York areas, comparing performance with paper versions.RESULTS: In the pilot test, missing data occurred less frequently with ProCycle than with paper, particularly for any days with missing symptoms (4% vs. 35%, p < 0.05). ProCycle did not permit any data recording mistakes such as circling contradictory responses (e.g., bleeding and no bleeding), compared with incorrect data on 13% of paper calendars. Data entry/cleaning time was 81% lower for ProCycle. 70% of users preferred ProCycle overall, compared with 9% preferring paper (p < 0.01).CONCLUSIONS: Although the initial cost of the H/PC is significantly higher than paper, there are no recurring charges for printing or data entry, and data cleaning is minimal. Electronic instruments on an H/PC provide an efficient, accurate method of data collection, applicable to a number of areas of health-related research involving daily data collection.

Journal Article↗
PubMed2000

A PPARgamma mutant serves as a dominant negative inhibitor of PPAR signaling and is localized in the nucleus.

The peroxisomal proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that act as ligand-activated transcription factors. PPARgamma plays a critical role in regulating adipocyte differentiation and lipid metabolism. Recently, thiazolidinedione (TZD) and select non-TZD antidiabetic agents have been identified as PPARgamma agonists. To further characterize this receptor subclass, a mutant hPPARgamma lacking five carboxyl-terminal amino acids was produced (hPPARgamma2Delta500). In COS-1 cells transfected with PPAR-responsive reporter constructs, the mutant receptor could not be activated by a potent PPARgamma agonist. When cotransfected with hPPARgamma2 or hPPARalpha, hPPARgamma2Delta500 abrogated wild-type receptor activity in a dose-responsive manner. hPPARgamma2Delta500 was also impaired with respect to binding of a high-affinity radioligand. In addition, its conformation was unaffected by normally saturating concentrations of PPARgamma agonist as determined by protease protection experiments. Electrophoretic mobility shift assays demonstrated that hPPARgamma2Delta500 and hPPARgamma2 both formed heterodimeric complexes with human retinoidxreceptor alpha (hRXRalpha) and could bind a peroxisome proliferator-responsive element (PPRE) with similar affinity. Therefore, hPPARgamma2Delta500 appears to repress PPAR activity by competing with wild type receptor to dimerize with RXR and bind the PPRE. In addition, the mutant receptor may titrate out factors required for PPAR-regulated transcriptional activation. Both hPPARgamma2 and hPPARgamma2Delta500 localized to the nucleus of transiently transfected COS-1 cells as determined by immunofluorescence using a PPARgamma-specific antibody. Thus, nuclear localization of PPARgamma occurs independently of its activation state. The dominant negative mutant, hPPARgamma2Delta500, may prove useful in further studies to characterize PPAR functions both in vitro and in vivo

Animals↗
PubMed2000

Effect of intrauterine treatment with prostaglandin E2 prior to insemination of mares in the uterine horn or body.

Two trials were conducted to investigate the effects of intrauterine infusion of PGE2 and uterine horn insemination on pregnancy rates in mares achieved by breeding with a suboptimal number of normal spermatozoa. Estrus was synchronized and mares were teased daily with a stallion to detect estrus. Mares in estrus were examined by transrectal palpation and ultrasonography to monitor follicular status. On the first day a 35-mm diameter follicle was present, hCG (1500 IU, iv) was administered and the mares were bred the next day. Mares (Trial 1, n = 34; Trial 2, n = 28) were inseminated with 25 million total spermatozoa from either a stallion with good semen quality (Trial 1) or poor semen quality (Trial 2). In each trial, mares were assigned to 1 of 4 treatment groups as follows: Group PGE-HI - infusion of 0.25 mg PGE2 into the proximal end of the uterine horn ipsilateral to the dominant follicle 2 h prior to insemination in the proximal end of the same uterine horn; Group PGE-BI - infusion of 0.25 mg PGE2 into the proximal end of the uterine horn ipsilateral to the dominant follicle 2 h prior to insemination in the uterine body; Group SAL-HI - infusion of 1 mL sterile saline into the proximal end of the uterine horn ipsilateral to the dominant follicle 2 h prior to insemination in the proximal end of the same uterine horn; or Group SAL-BI - infusion of 1 mL sterile saline into the proximal end of the uterine horn ipsilateral to the dominant follicle 2 h prior to insemination in the uterine body. After breeding, mares were examined daily by transrectal ultrasonography to confirm ovulation, and were re-examined 14 to 16 d after ovulation for pregnancy status. Data were analyzed by Chi-square. Overall pregnancy rates were 59% for stallion 1 and 29% for stallion 2. Group pregnancy rates did not differ for mares bred by either stallion (P > 0.10). Pregnancy rates were not altered by horn insemination for either stallion (P > 0.10). Intrauterine infusion of PGE2 improved pregnancy rate in mares bred by the stallion with good quality semen (P < 0.05), but did not alter pregnancy rate in mares bred by the stallion with poor quality semen (P > 0.10). Further research is warranted to determine if intrauterine infusion of PGE2 will enhance spermatozoal colonization of the oviduct and pregnancy rates in mares, and if PGE-treatment will improve pregnancy rates achieved by subfertile stallions.

Animals↗