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Older people have a high prevalence of falls and fractures, partly due to vitamin D deficiency. Sunlight is a major source of vitamin D, but many older people living in intermediate care facilities have inadequate sunlight exposure. The aim of this study was to determine the sun exposure practices and attitudes to sunlight in this population. Fifty-seven older residents of intermediate care facilities in Sydney, Australia were interviewed to determine their sun exposure practices, their views on sunlight and health and whether these have changed over their lives, factors affecting sunlight exposure and their knowledge of vitamin D. Sixty percent of the participants preferred to be outdoors, despite more than 92% believing that sunlight was healthy. In their youth however, almost 90% had preferred to be outdoors. Poor health, physical constraints and a sense of lack of ownership of outdoor spaces were barriers to sunlight exposure. Improved physical access, more outdoor leisure activities and promotion of greater autonomy may improve safe and appropriate sunlight exposure in this population., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The tumor suppressor Gadd45alpha was earlier shown to be a repressed target of sustained receptor-mediated ERK1/2 signaling. We have identified Gadd45alpha as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (GMR-V449E). GADD45A mRNA downregulation is also associated with FLT3-ITD(+) AML. Sustained ERK1/2 signaling contributes significantly to receptor-mediated downregulation of Gadd45alpha mRNA in FDB1 cells expressing activated receptor mutants, and in the FLT3-ITD(+) cell line MV4;11. Knockdown of Gadd45alpha with shRNA led to increased growth and survival of FDB1 cells and enforced expression of Gadd45alpha in FDB1 cells expressing FLT3-ITD or GMR-V449E resulted in reduced growth and viability. Gadd45alpha overexpression in FLT3-ITD(+) AML cell lines also resulted in reduced growth associated with increased apoptosis and G(1)/S cell cycle arrest. Overexpression of Gadd45alpha in FDB1 cells expressing GMR-V449E was sufficient to induce changes associated with myeloid differentiation suggesting Gadd45alpha downregulation contributes to the maintenance of receptor-induced myeloid differentiation block. Thus, we show that ERK1/2-mediated downregulation of Gadd45alpha by sustained receptor signaling contributes to growth, survival and arrested differentiation in AML.

Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.

We have previously demonstrated that concomitant activation of receptor tyrosine kinases and certain G protein-coupled receptors (GPCRs) can promote a synergistic increase in the rate of airway smooth muscle cell (ASM) proliferation. Here we clarify the role of p70S6 kinase (p70S6K) as an integrator of receptor tyrosine kinase and GPCR signaling that augments ASM DNA synthesis by demonstrating that specific p70S6K phosphorylation sites receive distinct regulatory input from GPCRs that promotes sustained kinase activity critical to mitogenesis. Prolonged stimulation of ASM cells with EGF and thrombin induced a greater than additive effect in levels of p70S6K phosphorylated at residue T389, whereas a significant but more modest increase in the level of T229 and T421/S424 phosphorylation was also observed. The augmenting effects of thrombin could be dissociated from p42/p44 MAPK activation, as selective inhibition of thrombin-stimulated p42/p44 failed to alter the profile of cooperative p70S6K T389 phosphorylation, p70S6K kinase activity, or ASM [(3)H]thymidine incorporation. Thrombin stimulated a sustained increase in the level of Akt phosphorylation and also augmented EGF-stimulated Akt phosphorylation. The cooperative effects of thrombin on Akt/p70S6K phosphorylation and [(3)H]thymidine incorporation were all attenuated by heterologous expression of Gbetagamma sequestrants. These data suggest that PI3K-dependent T389/T229 phosphorylation is limiting in late-phase p70S6K activation by EGF and contributes to the cooperative effect of GPCRs on p70S6K activity and cell growth.

Synthetic glucocorticoid dexamethasone suppressed interleukin-5 gene expression in PER-117 human T cells at the level of transcription. The conserved lymphokine element 0 in the interleukin-5 gene promoter context served as a target for dexamethasone.

Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele.

Dominantly inherited sensory neuropathy (HSNI) is a degenerative disorder of sensory neurons characterized predominantly by sensory loss with mild motor impairment. Recently our group identified a locus on chromosome 3p for a new form of HSNI associated with cough and gastroesophageal reflux (GER). Haplotype analysis in a second family refined the interval to a 3.4-cM region that includes the candidate genes TOP2B and SLC4A7. The genes TOP2B and SLC4A7 and five other characterized genes that map within the critical interval have been investigated and excluded from having a pathogenic role in HSNI with cough and GER. Two novel single nucleotide polymorphisms were identified; however both changes were observed in affected and non-affected individuals, suggesting that they have no relation to the disease. We have used the resources of the Human Genome Project to report a transcript map of the region on chromosome 3p24 containing the HSNI with cough and GER locus.

Hereditary sensory neuropathy type I (HSN I) is a group of dominantly inherited degenerative disorders of peripheral nerve in which sensory features are more prominent than motor involvement. We have described a new form of HSN I that is associated with cough and gastroesophageal reflux. To map the chromosomal location of the gene causing the disorder, a 10-cM genome screen was undertaken in a large Australian family. Two-point analysis showed linkage to chromosome 3p22-p24 (Zmax=3.51 at recombination fraction (theta) 0.0 for marker D3S2338). A second family with a similar phenotype shares a different disease haplotype but segregates at the same locus. Extended haplotype analysis has refined the region to a 3.42-cM interval, flanked by markers D3S2336 and D3S1266.

Objective: To evaluate the extent to which the guideline to perform laparoscopic cholecystectomy in day care was followed in the institute where the guideline was developed and in the other hospitals in the Netherlands., Design: Retrospective, descriptive., Method: For the patients who underwent a laparoscopic cholecystectomy in the Amsterdam University Medical Centre (AMC) during the period 1 January 1998-31 December 2000, data were collected from medical records on how the intervention was performed: in day care or during a hospital admission. The national figures were obtained from SIG Zorginformatie in Utrecht., Results: A total of 262 patients underwent a laparoscopic cholecystectomy at the AMC: 60 men and 202 women, with an average age of 43 years (range: 2-86). A total of 163 (62%) patients were eligible for treatment in day care. Laparoscopic cholecystectomy was performed in day care in the years 1998, 1999 and 2000 in 80%, 92% and 93% of patients respectively (n = 144). Of these 144 patients, 129 (90%) were discharged to home the same day. For the same years, these figures for the whole of the Netherlands were 0.8%, 1.3% and 1.7% respectively., Conclusion: The clinical guideline for performing laparoscopic cholecystectomy in day care has been implemented to a large extent in the AMC but has scarcely been implemented at the national level. At the AMC, day care treatment could be carried out for 90% of the patients for whom this had been planned.

Interleukin-5 (IL-5) is a T-cell cytokine involved in Type 2 diseases and is commonly described as being coordinately regulated with other Type 2 cytokines, such as IL-4 and IL-13. Considering the unique control of eosinophilia by IL-5, such coordinate regulation would be surprising. In fact, the biological specificity of eosinophilia and its control by IL-5 suggests a unique and independent control of IL-5 regulation. In this report we show the binding of GATA-3 to three sites in the human IL-5 promoter in the human T-cell line PER117. The previously identified -70 site and another site at position -152 are shown to positively regulate IL-5 transcription. More importantly, the site located at -400 acts as a powerful repressor of IL-5 transcription with mutagenesis of this site allowing a high level expression of IL-5 without the activation of other factors normally required for IL-5 expression. Whereas GATA-3 has been proposed to be involved in the regulation of the IL-4/IL-5/IL-13 locus, we show here that it has another function in controlling IL-5 transcription that supports the observed unique biological function of this cytokine.

Inclusion body myositis (IBM) is a form of idiopathic inflammatory myopathy of unknown aetiology. A strong association with HLA class II (HLA-DR3) suggested a role for genes in the human major histocompatibility complex (MHC) in the predisposition to this disease. In this study, we have taken advantage of the ancestral haplotype (AH) concept and historical recombinations to map for a possible susceptibility gene(s) in the MHC. We performed detailed typing of three MHC-related HSP70 genes and defined allelic combinations in the context of MHC AH. We also modified existing methods to give a simple and accurate method for typing two TNF microsatellites. Using the HSP70 and TNF markers and HLA-DR, -B, and C4 typing of our patients with IBM, we defined a potential site for the MHC-associated susceptibility gene(s) in the region between HLA-DR and C4.

An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.

The present study evaluated the presence of DSM-IV personality disorders among young adults from a nonclinical setting who produced an MMPI 2-7-8 profile in comparison to a group of MMPI-defined controls. Categorical and dimensional analyses of personality disorders were evaluated. Participants in the 2-7-8 group (n = 20) received significantly more personality disorder diagnoses than did controls (n = 29), and 85% of these individuals received at least one Cluster A (Paranoid, Schizoid, Schizotypal) diagnosis in contrast to only 6.9% of controls (categorical analysis). The 2-7-8 group also received significantly more Cluster A diagnoses than Cluster B or C diagnoses. When dimensional analyses were applied (subclinical diagnoses), 95% of the 2-7-8 group evidenced Cluster A features. Comorbidity patterns were also evaluated; the most frequent comorbid diagnosis for the 2-7-8 group was Avoidant Personality Disorder (n = 8), consistent with Meehl s (1962, 1989, 1990) conceptualization of schizotypy. These results support the use of the MMPI 2-7-8 profile as an indicator of schizophrenia-related pathology within nonclinical samples of young adults.

Revision arthroplasty of the hip is often complicated by infection, bone loss, and perioperative fracture of the femur. A simple, inexpensive spacer that keeps tissue planes intact and prevents soft tissue contracture during the interoperative period of a 2-stage revision is described. This can provide intramedullary support to a fractured or weak femur and enable local antibiotic delivery, as well as permit limited mobilization of the patient. It can be easily fabricated during surgery using universally available materials and can be tailored for specific requirements. Such a spacer was used in 5 cases. The experience is presented, and the technique and pitfalls are discussed.

Researchers in the language and social-cognitive fields have suggested that social mores and the use of masculine generic grammatical terms such as he and man have resulted in a people = male bias. This information processing bias causes most people to attribute male gender to a gender-unspecified person. Male gender appears to be prototypic of the person construct or category. These research findings have implications for the interpretation of the Draw-A-Person Test (Machover, 1949).

With the increase in the number of orthopaedic surgeons and the aggressive marketing by manufacturing companies, high technology orthopaedic surgery is being more frequently carried out in Malaysia. Post-operative sepsis complicating this type of surgery can have disastrous consequences. No data is available in this country on the incidence of post-operative infection in Orthopaedic Surgery. The aim of this study was to determine the incidence of post-operative infection. A retrospective survey of 703 patients undergoing elective Orthopaedic Surgery in the year 1991 was carried out. We found an overall post-operative infection rate of 6.8% and a deep infection rate of 3.3%. This figure of 3.3% is higher than the internationally accepted figure of less than 2%. A need for ongoing surveillance and concerned effort to reduce the infection rate is stressed.

We analysed data from a case-control study in the Netherlands in order to investigate whether reproductive events and hormonal factors are similarly related to colon cancer risk in men and women after adjustment for dietary factors. In total, 232 colon cancer cases (102 women, 130 men) and 259 controls (123 women, 136 men) were interviewed about life style, medical conditions and usual dietary patterns, using a structured dietary history technique. In women, age at first childbirth was positively associated with colon cancer risk (odds ratio (OR) age > or = 26 vs < 26 years, 1.7; 95% confidence interval (CI), 0.9-3.3). Women with three or more children were at reduced risk compared with women with one or two children (OR, 0.6; 95% CI, 0.3-1.1). When women had had their first child after the age of 26 years, parity was observed to be important (for one or two children vs > or = three children: OR, 2.8; 95% CI, 1.1-7.0). For men, opposite but non-significant associations were found. Adjustment for dietary patterns and other risk factors did not change the estimates markedly. Of the hormonal factors, late age at menarche decreased risk (OR, 0.5; 95% CI, 0.3-0.9) while late age at natural menopause slightly increased risk. Our study provides additional support for the role of reproductive status in the aetiology of colon cancer in women, independently of dietary factors.

Senescent floating leaf material of Nymphaea alba L., collected in an acidified moorland pool, was used in decomposition studies in two aquatic systems that differed greatly in pH, alkalinity and nutrient concentration. Concentrations of extractable protein and phenolics in the decomposing leaf material were measured during the incubation period. Protein levels were not significantly different in the leaf material from the two study sites, whereas the concentrations of phenolics in the degrading leaf blades from the acid site remained higher than in the material from the alkaline site. The resource quality of the decomposing leaf material was estimated by feeding tests using Asellus aquaticus (L.) in the laboratory. The effect of an artificially increased level of tannin on the feeding activity of A. aquaticus was also studied. Material from the acid system was consumed at a lower rate than material from the other system. The phenolic content of the material was found to be the most important feeding cue. The protein level of the leaf blade detritus seems to be of less importance. The structure of the decomposing leaf blades may have influenced the resource quality in the later stages of the experiment.

We have studied the effects of gonadectomy and testoterone supplementation on the development of the vasopressin- and oxytocin-containing nucleus (VON) of the pig hypothalamus that shows a decrease in neuron number during the first weeks postnatally, followed by an increase during puberty. Neonatal gonadectomy caused a 2.5-fold increase in VON volume and neuron number in males and 3-fold in females at the age of 16 weeks, the onset of puberty. However, the difference between gonadectomized and nongonadectomized animals disappeared after puberty (38 weeks). Testosterone replacement from 16 weeks onwards induced a decrease in neuron number and volume of the VON. The present study indicates that the development of the VON is influenced by gonadal steroids although it seems improbable that these hormones affect the VON directly.

A chemostat study was conducted to investigate the influence of water quality parameters related to acidification processes on the decomposition of floating leaves of Nymphaea alba L. HCO inf3 sup- and total Al concentration and pH influenced the decay rate. The activity of four cell-wall decaying exoenzymes was measured in the detritus. The activity of two types of pectic enzyme and xylanase was low under acid conditions. Cellulase activity was little affected. The exoenzyme activity seemed to be influenced by the pH of the water within the detritus. Inhibition of pectic enzymes under acid conditions may be an important factor causing the slow decay of macrophyte remains in acid waters.

A farmer underwent disarticulation at the right shoulder followed by numerous skin grafts. After one of these grafts a phantom hand cramp developed, which disappeared on treatment of trigger points under a split thickness grafted, scarred area on the chest wall. Each phantom finger relaxed on injection of a definite area: i.e. the 'fingers' could be mapped out on the chest wall which was devoid of normal epicritic sensibility. The discussion points out the error of central versus peripheral theories of etiology and an approach toward understanding the patient as a psychophysic entity is stressed. The special characteristics of phantom limb pain are outlined, with emphasis on its remarkable response to psychic and physical factors.

Four of the five veterinary E. coli strains, which were unable to transfer their antibiotic resistance by conjugation, were found to harbour plasmids. Evidence from transformation, agarose gel electrophoresis and curing experiments showed that in strains KE-3, KE-4 and KE-14 a nonconjugative R plasmid carried the gene for resistance to tetracycline. The plasmids in KE-9 were cryptic.

Testes of foetal pigs between 26 to 35 days post coitum (p.c.) were investigated histochemically and ultrastructurally. Diaphorase and delta 5-3 beta-hydroxysteroid dehydrogenase activities were studied using, respectively, NADH and pregnenolone and dihydroxy androsterone as substrates. Ultrastructurally, attention was focused on the development of mesenchymal cells and on the sustentacular cells in the primitive sex cords in an attempt to detect the origin of Leydig cells. Histochemically there is a concentration of activity toward the interstitium with increasing age. Also the reactions increase in intensity. Ultrastructurally no evidence for Leydig cell development from Sertoli cells could be observed. Mesenchymal cells between the sex cords show a development toward Leydig cells. This is absent in mesenchymal cells in the future tunica albuginea. Before 30 days p.c. no 'true' Leydig cells can be observed morphologically. The role of the rough endoplasmic reticulum/mitochondrial complex, which is present in many mesenchymal and sustentacular cells, is discussed.

Fifteen independent E. coli strains of avian, bovine and porcine origin in Peninsular Malaysia were tested for antibiotic resistance and conjugative R plasmids. Eight (53%) isolates were found to be antibiotic resistant. Among them, 37.5% were mono-resistant and 62.5% were resistant to three or more antibiotics, i.e., multi-resistant. All of them were resistant to Tc and sensitive to Gm and Nx. Three of the eight antibiotic resistant strains were able to transfer all or part of their resistance to an E. coli K12 recipient by conjugation. The transfer frequencies of Km, Sm and Tc resistance of the three donors varied between 4.5 X 10(-8) to 6.8 X 10(-7). Analysis of the plasmid profiles of all the three donors and their respective transconjugants after agarose gel electrophoresis provided conclusive evidence that the transferable resistance traits were plasmid-mediated.