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Biomedical subjects

J Noble

Publications and source records attributed to J Noble.

At least 19 recordsLinked to original sources
PubMed2006

Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease.

The major susceptibility locus for type 1 diabetes mellitus (T1D) maps to the human lymphocyte antigen (HLA) class II region in the major histocompatibility complex on chromosome 6p21. In southern European populations, like the Basques, the greatest risk to T1D is associated with DR3 homo- and heterozygosity and is comparable to that of DR3/DR4, the highest risk genotype in northern European populations. Celiac disease (CD) is another DR3-associated autoimmune disorder showing certain overlap with T1D that has been explained by the involvement of common genetic determinants, a situation more frequent in DR3-rich populations, like the Basques. As both T1D- and CD-associated HLA alleles are part of conserved extended haplotypes (CEH), we compared DR3-homozygous T1D and CD patients to determine whether CEHs were equally distributed between both disorders or there was a differential contribution of different haplotypes. We observed a very pronounced distribution bias (P<10(-5)) of the two major DR3 CEHs, with DR3-B18 predominating in T1D and DR3-B8 in CD. Additionally, high-density single nucleotide polymorphism (SNP) analysis of the complete CEH [A*30-B*18-MICA*4-F1C30-DRB1*0301-DQB1*0201-DPB1*0202] revealed extraordinary conservation throughout the 4.9 Mbp analyzed supporting the existence of additional diabetogenic variants (other than HLA-DRB1*0301-DQB1*0201), conserved within the DR3-B18 CEH (but not in other DR3 haplotypes) that could explain its enhanced diabetogenicity.

Celiac Disease↗
PubMed2004

Morphological measurements of the proximal interphalangeal joint.

The morphology of the proximal interphalangeal joint was determined using a photographic technique. The head of the proximal phalanx, viewed end on, has a complex trapezoid appearance characteristic for each named digit. The asymmetric condyles diverge from one another and are separated by an intercondylar groove that increases in depth from the dorsal to the palmar surface. Saggital sections of the head of the proximal phalanx are not circular, but, sections taken in the plane of maximum dimensions of the condyle are circular with a radius of curvature of approximately one half of the height of the condyles. The articular surface of the base of the middle phalanx is not circular in outline in either the saggital or coronal plane. In coronal sections the articular surface is biconcave convex with a prominent median ridge separating the two adjacent concave articular surfaces. The implications of this varied morphology on implant design are discussed.

Anatomy, Cross-Sectional↗
PubMed2004

The effect of alpha-ketoglutaric acid on amino acid utilization by nonstarter Lactobacillus spp. isolated from Cheddar cheese.

AIMS: To examine the effect of alpha-ketoglutaric acid (alpha-KG) on the utilization and catabolism of amino acids by strains of nonstarter lactobacilli isolated from Cheddar cheese. METHODS AND RESULTS: The effect of alpha-KG in the growth medium of nonstarter lactobacilli on amino acid metabolism, catabolite levels, peptide hydrolase and aminotransferase activities was examined. The pattern of amino acid utilization, catabolite formation and aminotransferase activity was affected by keto acid. CONCLUSIONS: Amino acid conversion into cheese aroma and flavour compounds by nonstarter lactobacilli is enhanced in the presence of alpha-ketoglutarate. SIGNIFICANCE AND IMPACT OF THE STUDY: Increasing the availability of alpha-ketoglutarate in cheese offers a possible method of reducing the maturation period by accelerating the rate of character compound formation from amino acids by the nonstarter lactobacilli.

Amino Acids↗
PubMed2003

Prevention. Part 7: professionally applied topical fluorides for caries prevention.

This paper reviews the use of professionally applied topical fluorides (PATF) in caries prevention. PATFs are indicated for children and adults with one or more decayed smooth surfaces and/or those who are at high caries risk. Frequency of administration depends on the patient's caries risk, and is usually every 6 months. The effectiveness of fluoride varnish and gel applications has been well established in caries prevention trials involving permanent teeth. Although both types are effective, varnish may be preferred because it is easier to apply, reduces the risk of fluoride over-ingestion, and has greater patient acceptance. Fluoride foams are similar products to gels, but have not been tested clinically. The use of in-office two-part rinses is not recommended because they have not been proven effective. A cleaning, or prophylaxis, is not necessary before the application of topical fluoride for caries prevention. In conclusion, when used appropriately, PATFs are a safe, effective means of reducing caries risk among high-risk populations.

Acidulated Phosphate Fluoride↗
PubMed2003

Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease.

Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone and 17beta-estradiol are synthesized by cytochrome P450s from endogenous cholesterol. We previously reported a new cytochrome P450 enzyme, CYP7B, highly expressed in rat and mouse brain that metabolizes DHEA and related steroids by hydroxylation at the 7alpha position. Such 7-hydroxylation can enhance DHEA bioactivity in vivo. Here we show that the reaction is conserved across mammalian species: in addition to mouse and rat, DHEA hydroxylation activity was present in brain extracts from sheep, marmoset and human. Northern blotting using a human CYP7B complementary deoxyribonucleic acid (cDNA) probe confirmed the presence of CYP7B mRNA in marmoset and human hippocampus; CYP7B mRNA was present in marmoset cerebellum and brainstem, with lower levels in hypothalamus and cortex. In situ hybridization to human brain revealed higher levels of CYP7B mRNA in the hippocampus than in cerebellum, cortex, or other brain regions. We also measured CYP7B expression in Alzheimer's disease (AD). CYP7B mRNA was significantly decreased (approximately 50% decline; P<0.05) in dentate neurons from AD subjects compared with controls. A decline in CYP7B activity may contribute the loss of effects of DHEA with ageing and perhaps to the pathophysiology of AD.

Adipates↗
PubMed2002

The osteodystrophy of mucolipidosis type III and the effects of intravenous pamidronate treatment.

Mucolipidosis type III (ML III; McKusick 252600) is a rare lysosomal storage disease in which skeletal involvement is prominent, in particular the destruction of vertebral bodies and the femoral heads. We describe studies in two siblings with ML III that suggest the presence of a distinct metabolic bone disorder. Biochemical indices of bone turnover were increased, and transiliac bone biopsy demonstrated both trabecular osteopenia and marked subperiosteal bone resorption. Intravenous pamidronate treatment given monthly for a year was well tolerated and produced dramatic clinical effects, with reduction in bone pain and improvements in mobility, despite incomplete suppression of bone resorption as assessed by biochemical, radiographic and histological criteria. Bisphosphonate therapy may have an important role in the management of bone pain in ML III, as it does in the related lysosomal disorder of Gaucher disease.

Absorptiometry, Photon↗
PubMed2002

Rapid assessment of antimould efficacies of pressure-treated southern pine.

A membrane-screening method was developed in conjunction with flow cytometric (FC) analysis for determining the efficacies of antimould pressure-treatment formulations for mould species of cosmetic significance on southern pine. Fusarium subglutinans, Aspergillus flavus, Penicillium chrysogenum, and Paecilomyces spp. were the predominant moulds colonizing surfaces of the variously treated pine stored in sealed plastic bags over 3- to 6-month periods. Nylon membranes placed directly on pressure-treated pine and membranes saturated with the various formulations were inoculated with the conidia of selected moulds. FC analysis of conidia stained with propidium iodide (PI) before and after exposure to the pressure-treatment formulations permitted a rapid assessment of the inocula and selection of those pressure-treatment formulations with probable inhibitory activity versus probable nonactive preparations. Recoveries of the fungi from the membranes over 9-14 days were in general agreement with the emergence of colonizing fungi on the similarly preserved uninoculated pine stored in sealed plastic bags for 6 months. This combination of procedures provided for a relatively rapid assessment of preservative formulations designed to provide enhanced efficacy against surface mould growth on lumber during storage and retail display.

Antifungal Agents↗
PubMed2001

Acute restraint stress increases 5-HT7 receptor mRNA expression in the rat hippocampus.

The brain serotonin (5-HT) system interacts closely with the hypothalamic-pituitary-adrenal axis. We examined the effects of stress on hippocampal 5-HT7 receptor and corticosteroid receptor (mineralocorticoid receptor (MR) and glucocorticoid receptor (GR)) mRNA expression measured by in situ hybridisation histochemistry. Acute restraint stress increased 5-HT7 receptor mRNA in CA2 and CA3 hippocampal subregions (32% increase) and had a small effect on GR but not MR mRNA (19% fall in GR in CA1). In contrast, chronic stress (1 week of variable stressors) had little effect on hippocampal 5-HT7 receptor mRNA (9% rise in CA3) but decreased MR mRNA (e.g. 34% decrease in CA2) and GR mRNA expression selectively in the dentate gyrus (26% decrease). The rise in 5-HT7 receptor mRNA expression following restraint stress parallels our previously reported increase in expression after inhibiting the synthesis of adrenal steroids. These data suggest that acute but not chronic stress regulates 5-HT7 receptor mRNA expression in a manner that is likely to be independent of its glucocorticoid actions.

Animals↗
PubMed2001

Short-term administration of fluoxetine and venlafaxine decreases corticosteroid receptor mRNA expression in the rat hippocampus.

Chronic treatment with antidepressant drugs (2 weeks or longer) increases corticosteroid receptor mRNA expression in the hippocampus and reduces hypothalamic-pituitary-adrenal axis activity in parallel with improving mood and neuroendocrine function. Earlier effects are less well documented. We examined the effects of short term (9 days) treatment with fluoxetine (10 mg/kg) and venlafaxine (10 mg/kg) on hippocampal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression and spatial memory in adult rats. In situ hybridization histochemistry showed that the antidepressants decreased MR mRNA expression in all hippocampal subregions (e.g. 45% decrease in CA1 with venlafaxine, P<0.001), while GR mRNA expression was selectively reduced in the CA3 subregion. There was a trend for decreased plasma corticosterone levels following fluoxetine (50% fall, P=0.07) and venlafaxine (30% fall, P=0.18) but neither antidepressants affected spatial memory in the watermaze. Thus antidepressants can have complex and opposing actions on hippocampal corticosteroid receptor expression depending on the duration of treatment.

Animals↗
PubMed2001

Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments.

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11beta-HSD-1 acts as a functional 11beta-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11beta-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11beta-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11beta-HSD-1 inhibitors may protect against hippocampal function decline with age.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Explaining social learning of food preferences without aversions: an evolutionary simulation model of Norway rats.

Norway rats (Rattus norvegicus) transmit preferences for novel foods socially by smelling each other's breath. However, rats fail to learn aversions, acquiring a preference even if the rat whose breath they smell has been poisoned. Rats can distinguish between sick and healthy conspecifics and social learning of both preferences and aversions is present in other species - hence it is unclear why rats cannot learn aversions socially. We constructed an evolutionary simulation in which a population of rats foraged from a central location, exploiting food sites that could contain edible or toxic foodstuffs. We examined the relationship between toxin lethality and selection for individual versus social learning and discrimination between sick and healthy conspecifics in order to allow learning of both preferences and aversions. At low lethality levels individual learning was selected for and at intermediate levels we found social learning of both preferences and aversions. Finally, given high lethality levels the simulated rats would employ social learning but failed to learn aversions, matching the behaviour of real rats. We argue that Norway rats do not learn aversions socially because their environment may contain only highly lethal toxins which make interaction with a sick conspecific an extremely rare event.

Animals↗
PubMed2001

Meniscal tearing and rheumatoid arthritis.

We report five cases of meniscal tears in patients who were subsequently found to have rheumatoid arthritis (RA) and discuss the management priorities with regard to symptom relief.

Arthritis, Rheumatoid↗
PubMed2001

Prospective analysis of relationships of outcome measures for ulnar neuropathy at the elbow.

BACKGROUND: We undertook a prospective study to investigate relationships between outcome measures of ulnar neuropathy at the elbow. METHODS: Thirty-one patients (mean age 52.6, range 20-80), with clinically and electrically verified ulnar neuropathy at the elbow, were seen independently by a neurosurgeon and a physiotherapist. All tests were administered to all patients on each visit. Data collected included measures of sensory (monofilament, two-point discrimination, vibration) and motor function (grip, key-pinch, muscle atrophy), pain (visual analogue scale (VAS)) and impact on lifestyle (Levine's questionnaires (function status score--FSS, symptom severity score--SSS)), disability of the arm, shoulder and hand module (DASH) and patient-specific measures (PSM). Parametric and non-parametric correlation and factor analysis were done. RESULTS: Outcome analysis was available for 63 patient visits, with follow-up obtained for 20 patients (mean 8.5 months). Lifestyle and pain instruments (FSS, SSS, DASH, PSM and VAS) all correlated well with each other (r > 0.6, p < .01). DASH was moderately to highly correlated to nine of the 11 measures. Some tests correlated poorly, for example, Semmes-Weinstein monofilament with other sensory measures and muscle atrophy with almost all measures. Factor analysis revealed that there are two principal factors, accounting for 77% of the variance. Factor 1 relates to impact on lifestyle and pain while Factor 2 relates to strength and function. DISCUSSION/CONCLUSIONS: Intraclass measures, particularly ones assessing lifestyle and pain instruments are strongly correlated. Factor analysis revealed two principal factors that account for the majority of the variance; future studies with a larger sample size are needed to validate this analysis.

Adult↗
PubMed2001

Autoantibodies and human leucocyte antigen class II in first-degree family members of Mexican-American type 1 diabetic patients.

As part of a genetic study of type 1 diabetes in Mexican-Americans, 360 first-degree relatives of 108 type 1 diabetic probands were studied. Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD(65)), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. ICA was positive in 37% of the probands and 5.8% of the relatives. A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD(65) and was found positive. 4/14 ICA+ first-degree relatives were GAD(65) positive. Four relatives, positive for two antibodies, subsequently developed type 1 diabetes. Life-Table analysis of first-degree relatives with autoantibodies indicated an 80% disease-free survival at 3.5 yr. HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands. These results suggest that autoimmunity occurs in type 1 diabetes families of Mexican descent in similar frequencies to that of non-Hispanic, Caucasian families. The presence of autoantibodies appears to be regulated in part by HLA class II genes, even in the absence of overt diabetes.

Adolescent↗
PubMed2001

Comparison of active and passive recovery of blood lactate and subsequent performance of repeated work bouts in ice hockey players.

This study examined the effect of active and passive recovery on lactate concentration and subsequent performance of repeated work bouts in 18 male NCAA Division I ice hockey players. Using a repeated measures design, subjects performed a series of skating tests before and after a 15-minute recovery. The skating test consisted of skating a course for 7 shifts, which lasted 40 seconds per shift with 90 seconds rest between shifts. Active recovery (low-intensity cycling) and passive recovery (sitting) lasted for 15 minutes and were followed by an identical 7-shift skating test. Passive vs. active recovery showed no statistically significant differences for distance skated, heart rate, or lactate. There appeared to be a trend for greater skating distance in period 2 when active recovery was used, but the difference was not significant (p > 0.05). It was concluded that active recovery did not enhance lactate removal or subsequent performance of repeated work bouts in simulated hockey play.

Adult↗
PubMed2000

Should the patella be resurfaced at total knee replacement?

Total knee replacement (TKR) presumably is replacement of the total knee articular surface. Sometimes it is and sometimes it is not. It is this author's firm conviction that the patella should be resurfaced in the vast majority of cases. Such advocacy must be critically justified and the potential drawbacks and alternatives examined.

Journal Article↗
PubMed2000

Infected knee treated by total knee arthroplasty.

The perceived wisdom in orthopaedics precludes insertion of implants in cases of post-recent active joint sepsis. However, revision knee surgery after infected arthroplasty has now been recognised to be safe and efficacious in specialised centres. We illustrate the concept of using principles of revision surgery to successfully treat knees destroyed by primary staphylococcal septic arthritis.

Journal Article↗