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3.
Sci Rep ; 9(1): 1627, 2019 02 07.
Article in English | MEDLINE | ID: mdl-30733569

ABSTRACT

The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450-1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate.

4.
J Biol Regul Homeost Agents ; 30(4): 1115-1123, 2016.
Article in English | MEDLINE | ID: mdl-28078862

ABSTRACT

There is an ever growing emergence in the popularity of patient-driven care. As this health and wellness model grows, inquiries into diet, lifestyle, and supplemental approaches will continue to become a focal point for the healthcare consumer. Because of this, the aim of this study is to determine the tolerability, and overall effectiveness of a proprietary multi-ingredient lipid-lowering supplement in subjects with dyslipidemia. Forty participants were recruited for a single-center, double-blind randomized, placebocontrolled trial. Study participants were recruited between December 2014 and March 2015. Initial screening included a physical examination, renal and hepatic function, serum lipid, serum electrolytes, complete blood counts, and urine analysis. The 40 participants were randomly assigned to receive either the proprietary multi-ingredient lipid-lowering supplement (PMILLS) n= 20 or placebo n= 20. The trial consisted of a screening visit, a two-week run-in, and a four-month treatment period. Samples were taken at baseline, one month and four months of treatment. Results from the trial showed that the PMILLS significantly reduced total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C), oxidized LDL (oxLDL), Apo-lipoprotein B, triglycerides (TG), LDL particle number (LDL-P), heart rate, and diastolic blood pressure compared to placebo at one month and four months. The PMILLS significantly increased high density lipoprotein (HDL) particle number (HDL-P), and low density lipoprotein (LDL) particle size from dense type III and IV to larger type I and II LDL particle, compared to placebo at one month and four months. In addition, the PMILLS significantly reduced high sensitivity C-reactive protein (hs-CRP), tumor necrosis alpha (TNF-α), and interleukin 6 (IL-6) within the treatment group from baseline. There were no adverse effects noted in the treatment group after four months of supplementation. The present study demonstrates this PMILLS improves all relevant lipid parameters, such as particle numbers and particles sizes, as well as showing a significant reduction in inflammatory markers linked to cardiovascular health. With such combined changes in lipids, lipid sub-fractions, and inflammation, which are considered among the most effective means of reducing coronary heart disease (CHD), this PMILLS represents a new addition to safe and effective lipid-modifying strategies.


Subject(s)
Dietary Supplements , Dyslipidemias/drug therapy , Adult , Aged , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Double-Blind Method , Female , Humans , Male , Middle Aged , Triglycerides/blood
5.
Mucosal Immunol ; 3(6): 537-44, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20811344

ABSTRACT

Inducible bronchus-associated lymphoid tissue (iBALT) is an organized tertiary lymphoid structure that is not pre-programmed but develops in response to infection or under chronic inflammatory conditions. Emerging research has shown that iBALT provides a niche for T-cell priming and B-cell education to assist in the clearance of infectious agents, highlighting the prospect that iBALT may be engineered and harnessed to enhance protective immunity against respiratory pathogens. Although iBALT formation is associated with several canonical factors of secondary lymphoid organogenesis such as lymphotoxin-α and the homeostatic chemokines, CXCL13, CCL19, and CCL21, these cytokines are not mandatory for its formation, even though they influence its organization and function. Similarly, lymphoid tissue-inducer cells are not a requisite of iBALT formation. In contrast, dendritic cells are emerging as pivotal players required to form and sustain the presence of iBALT. Regulatory T cells appear to be able to attenuate the development of iBALT, although the underlying mechanisms remain ill-defined. In this review, we discuss facets unique to iBALT induction, the cellular subsets, and molecular cues that govern this process, and the contribution of this ectopic structure toward the generation of immune responses in the pulmonary compartment.


Subject(s)
Bronchi , Choristoma , Dendritic Cells/immunology , Lymphoid Tissue/immunology , Respiratory Tract Infections/immunology , Animals , Chemokines/immunology , Homeostasis/immunology , Humans , Immunity , Lymphoid Tissue/pathology , Organogenesis/genetics , Organogenesis/immunology , Respiratory Tract Infections/pathology , T-Lymphocytes, Regulatory/immunology , Transcriptional Activation
7.
Neuroscience ; 168(2): 551-63, 2010 Jun 30.
Article in English | MEDLINE | ID: mdl-20381591

ABSTRACT

Opioids have been discovered to have Toll-like receptor (TLR) activity, beyond actions at classical opioid receptors. This raises the question whether other pharmacotherapies for pain control may also possess TLR activity, contributing to or opposing their clinical effects. We document that tricyclics can alter TLR4 and TLR2 signaling. In silico simulations revealed that several tricyclics docked to the same binding pocket on the TLR accessory protein, myeloid differentiation protein 2 (MD-2), as do opioids. Eight tricyclics were tested for effects on TLR4 signaling in HEK293 cells over-expressing human TLR4. Six exhibited mild (desipramine), moderate (mianserin, cyclobenzaprine, imiprimine, ketotifen) or strong (amitriptyline) TLR4 inhibition, and no TLR4 activation. In contrast, carbamazepine and oxcarbazepine exhibited mild and strong TLR4 activation, respectively, and no TLR4 inhibition. Amitriptyline but not carbamazepine also significantly inhibited TLR2 signaling in a comparable cell line. Live imaging of TLR4 activation in RAW264.7 cells and TLR4-dependent interleukin-1 release from BV-2 microglia revealed that amitriptyline blocked TLR4 signaling. Lastly, tricyclics with no (carbamazepine), moderate (cyclobenzeprine), and strong (amitriptyline) TLR4 inhibition were tested intrathecally (rats) and amitriptyline tested systemically in wildtype and knockout mice (TLR4 or MyD88). While tricyclics had no effect on basal pain responsivity, they potentiated morphine analgesia in rank-order with their potency as TLR4 inhibitors. This occurred in a TLR4/MyD88-dependent manner as no potentiation of morphine analgesia by amitriptyline occurred in these knockout mice. This suggests that TLR2 and TLR4 inhibition, possibly by interactions with MD2, contributes to effects of tricyclics in vivo. These studies provide converging lines of evidence that several tricyclics or their active metabolites may exert their biological actions, in part, via modulation of TLR4 and TLR2 signaling and suggest that inhibition of TLR4 and TLR2 signaling may potentially contribute to the efficacy of tricyclics in treating chronic pain and enhancing the analgesic efficacy of opioids.


Subject(s)
Heterocyclic Compounds, 3-Ring/pharmacology , Lymphocyte Antigen 96/physiology , Toll-Like Receptors/physiology , Analgesics, Opioid/pharmacology , Animals , Cells, Cultured , Humans , Interleukin-1/metabolism , Ligands , Lymphocyte Antigen 96/chemistry , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Microglia/drug effects , Microglia/metabolism , Models, Molecular , Morphine/pharmacology , Myeloid Differentiation Factor 88/genetics , Pain Measurement , Protein Binding , Rats , Signal Transduction , Toll-Like Receptor 2/agonists , Toll-Like Receptor 2/antagonists & inhibitors , Toll-Like Receptor 2/physiology , Toll-Like Receptor 4/agonists , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/physiology , Toll-Like Receptors/agonists , Toll-Like Receptors/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis
8.
Clin Exp Allergy ; 39(12): 1920-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19735273

ABSTRACT

BACKGROUND: Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma. OBJECTIVE: Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent. METHODS: BALB/c mice were sensitized by intranasal administration of endotoxin(low) ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age. RESULTS: Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxin(low) OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxin(low) OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings. CONCLUSIONS: Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4(+) T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life.


Subject(s)
Hypersensitivity/etiology , Hypersensitivity/immunology , Membrane Glycoproteins/physiology , Toll-Like Receptor 7/physiology , Adjuvants, Immunologic/pharmacology , Animals , Animals, Newborn , Eosinophilia/pathology , Flagellin/pharmacology , Gene Expression/genetics , Gene Expression/immunology , Hyperplasia/pathology , Hypersensitivity/metabolism , Hypersensitivity/pathology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/metabolism , Interleukin-13/genetics , Interleukin-13/metabolism , Interleukin-4/metabolism , Interleukin-5/metabolism , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung/pathology , Lymph Nodes/immunology , Lymph Nodes/metabolism , Mice , Mice, Inbred BALB C , Mucous Membrane/pathology , Ovalbumin/administration & dosage , Ovalbumin/immunology , RNA, Viral/pharmacology , Teichoic Acids/pharmacology , Th2 Cells/immunology , Th2 Cells/metabolism , Toll-Like Receptor 2/physiology , Vaccination
9.
Allergy ; 64(7): 1014-22, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19187393

ABSTRACT

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7Ralpha) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4(+) T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. METHODS: Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR(+) DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. RESULTS: Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR(+) and CD11c(+) cells infiltrated relatively late (24-48 h). The majority of TSLPR(+) cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7Ralpha chains. Maturation and stimulation with TSLP or polyriboinosinic-polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7Ralpha chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells(+) CD4(+) T cells. CONCLUSION: The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cytokines/biosynthesis , Dendritic Cells/immunology , Hypersensitivity/immunology , Receptors, Cytokine/metabolism , Receptors, Interleukin-7/metabolism , Adolescent , Adult , Allergens/immunology , Antigens, CD1 , Antigens, Surface/immunology , Antigens, Surface/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cytokines/immunology , Cytokines/pharmacology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Glycoproteins , Humans , Hypersensitivity/metabolism , Interferon Inducers/pharmacology , Interleukin-15/pharmacology , Interleukin-7/pharmacology , Lectins, C-Type/immunology , Lectins, C-Type/metabolism , Membrane Glycoproteins/immunology , Membrane Glycoproteins/metabolism , Middle Aged , Poly I-C/pharmacology , Receptors, Cytokine/agonists , Receptors, Cytokine/immunology , Receptors, Immunologic/immunology , Receptors, Immunologic/metabolism , Receptors, Interleukin-7/agonists , Receptors, Interleukin-7/immunology , Skin/immunology , Skin/pathology , Young Adult , Thymic Stromal Lymphopoietin
10.
Br Dent J ; 203(1): E2; discussion 40-1, 2007 Jul 14.
Article in English | MEDLINE | ID: mdl-17546060

ABSTRACT

AIM: To retrospectively evaluate the performance of reinforced glass ionomer restorations placed in load-bearing surfaces of posterior teeth in three UK general dental practices. METHODS: Inclusion criteria for the participating practitioners were that they would be able to find, in their regularly attending patients' mouths, a minimum of 30 Fuji IX restorations placed in load-bearing cavities in posterior teeth. The three practitioners who agreed to participate were given training in the methods of assessment of restorations. Presence/absence of the restoration, presence of secondary caries, anatomic form, margin adaptation, margin discolouration, surface roughness and colour match were recorded. RESULTS: Three general dental practitioners and 169 restorations in 116 patients were included in the study. Seventy-eight percent of restorations were placed in molar teeth, the remainder in premolar teeth, with 67 being Class I and 102 Class II. The mean age of restorations at examination was 25 months, ranging from five months to 56 months. Of the restorations examined, 98% (n = 166) were found to be present and intact. No secondary caries was detected clinically. Three restorations were found to have fractured. CONCLUSION: Reinforced glass ionomer restorations placed in load-bearing situations in patients attending three dental practices in the UK were found to be performing satisfactorily at two years. Further investigations, of improved rigour, may now be indicated to more fully assess the performance of such restorations in the long term.


Subject(s)
Dental Restoration, Permanent/methods , Glass Ionomer Cements , Adolescent , Adult , Aged , Bicuspid , Dental Restoration Failure , Dental Restoration, Permanent/statistics & numerical data , Female , Humans , Male , Middle Aged , Molar , Retrospective Studies , United Kingdom
11.
Technol Health Care ; 14(4-5): 281-96, 2006.
Article in English | MEDLINE | ID: mdl-17065751

ABSTRACT

In vitro macro- and micro-indentation test systems have been designed to measure the dynamic micro-mechanical properties of human prostate tissues at actuation frequencies between 5 Hz and 30 Hz, and 0.5 Hz and 20 Hz, respectively. The development of in vitro test systems was aimed at assessing the capacity of such an in vivo medical probe to provide information useful for the diagnosis of various prostate diseases. The macro-indentation test system is an established one, which we have used to determine structure-property relationships in human and canine prostate tissues and here we use it to validate a newly-developed micro-indentation test system using a tissue phantom. Mechanical testing was also carried out on sections of prostate tissue harvested from cystectomy and radical prostatectomy, diagnosed with bladder cancer and benign prostatic hyperplasia. Dynamic probing under displacement control was carried at pre-strains between 5% and 8% for macro-probing and at 5% pre-strain for micro-probing, and the general effect of pre-strain on the dynamic mechanical properties (described by the amplitude ratio between stress and strain, and the phase lag between strain and stress) of phantom and prostate tissues is presented. Specific point probing on epithelial and stromal histological components was also carried out showing a significant difference between the amplitude ratios of epithelial and stromal components for actuation frequencies exceeding 5 Hz. However, no significant difference was found between phase lags for epithelial and stromal tissues.


Subject(s)
Biomechanical Phenomena , Prostatic Hyperplasia/physiopathology , Prostatic Neoplasms/physiopathology , Silicones/analysis , Compressive Strength , Diagnosis, Differential , Epithelial Cells/pathology , Humans , Immunohistochemistry , Male , Phantoms, Imaging , Prostate/chemistry , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Stromal Cells/pathology , Tissue Engineering
12.
Cochrane Database Syst Rev ; (2): CD004374, 2006 Apr 19.
Article in English | MEDLINE | ID: mdl-16625600

ABSTRACT

BACKGROUND: Urinary catheterisation (by the urethral or suprapubic routes) is common following urogenital surgery. There is no consensus on how to minimize complications and practice varies. OBJECTIVES: To establish the optimal way to manage urinary catheters following urogenital surgery in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (searched 30 May 2005) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials were identified. Studies were excluded if they were not randomised or quasi-randomised trials of adults being catheterised following urogenital surgery. DATA COLLECTION AND ANALYSIS: Data collection was performed independently by two of the review authors and cross-checked. Where data might have been collected but not reported, clarification was sought from the trialists. MAIN RESULTS: Thirty nine randomised trials were identified for inclusion in the review. They were generally small and of poor or moderate quality reporting data on only few outcomes. Confidence intervals were all wide. USING A URINARY CATHETER VERSUS NOT USING ONE: The data from five trials were heterogeneous but tended to indicate a higher risk of (re)catheterisation if a catheter was not used postoperatively. The data gave only an imprecise estimate of any difference in urinary tract infection. URETHRAL CATHETERISATION VERSUS SUPRAPUBIC CATHETERISATION: In six trials, a greater number of people needed to be recatheterised if a urethral catheter rather than a suprapubic one was used following surgery (RR 3.66, 95% CI 1.41 to 9.49). SHORTER POSTOPERATIVE DURATION OF CATHETER USE VERSUS LONGER DURATION: In 11 trials, the seven trials with data suggested fewer urinary tract infections when a catheter was removed earlier (for example 1 versus 3 days, RR 0.50, 95% CI 0.29 to 0.87) with no pattern in respect of catheterisation. CLAMP AND RELEASE POLICIES BEFORE CATHETER REMOVAL VERSUS IMMEDIATE CATHETER REMOVAL: In a single small trial, the clamp-and-release group showed a significantly greater incidence of urinary tract infections (RR 4.00, 95% 1.55 to 10.29) and a delay in return to normal voiding (RR 2.50, 95% CI 1.16 to 5.39). AUTHORS' CONCLUSIONS: Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.


Subject(s)
Urinary Catheterization/standards , Urogenital Surgical Procedures , Adult , Humans , Randomized Controlled Trials as Topic , Urinary Catheterization/methods
13.
Obes Rev ; 7(1): 5-12, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16436098

ABSTRACT

The goal of this paper is to compare the extent of child obesity in Canada, Norway and the United States. As child poverty is an important correlate of child obesity, we wish to examine the potential role of international differences in child poverty in explaining international differences in the extent of child obesity. We use three representative microdata surveys containing parental reports of child height and weight collected in the mid-1990s in Canada, Norway and the US. We calculate both the prevalence and proportional severity of child obesity for 6-11-year-old children in each country, and represent the 'extent' of obesity diagrammatically. Differences in patterns of child poverty are similarly depicted. Obesity extent is also compared for poor and non-poor children in Canada and the US. Finally, child obesity in the three countries is compared using only non-poor children where we find that the extent of child obesity is much lower in Norway than in Canada or the US. The pattern apparent for obesity is remarkably similar to that found for child poverty. In Canada and especially in the US, we find a much greater extent of obesity for poor than non-poor children. However, when we compare only non-poor children in the three countries, although the magnitude of difference is smaller, it remains clear that Norwegian children are much less likely to be obese. Policy and research directed towards reducing the extent of child obesity in both Canada and the US should pay particular attention to issues of child poverty.


Subject(s)
Obesity/epidemiology , Poverty , Body Height , Body Mass Index , Body Weight , Canada/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Male , Norway/epidemiology , Obesity/economics , United States/epidemiology
14.
Urology ; 66(2): 447-50, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16098374

ABSTRACT

OBJECTIVES: To investigate the relationship between the morphology and mechanical properties of benign and malignant prostatic tissues measured in vitro. METHODS: Fresh tissue specimens were collected from patients undergoing transurethral resection of the prostate (TURP) for benign or malignant prostatic enlargement. Individual TURP chippings underwent immediate mechanical testing by applying a dynamic compressive strain to the samples. The amplitude ratio (E*) and phase difference (tan delta), measures of tissue elastic and viscous components respectively, were derived. Individual sections from the processed specimens underwent immunohistochemical staining and computerized image analysis was used to measure the morphologic characteristics of each TURP chipping. Linear regression analysis was used to assess correlations between morphologic and mechanical measurements, and the unpaired t test, assuming equal variances, was used to compare the mechanical and morphologic characteristics of benign and malignant prostates. RESULTS: Significant differences were noted between the morphology of the benign and malignant prostates. Tan delta was significantly smaller within the malignant prostates (P = 001). No difference was found between the benign and malignant prostates with respect to E*. Within the malignant prostates, a strong negative correlation was found between the epithelial tissue content and tan delta (R2 = 0.50, P = 0.031). CONCLUSIONS: The results of this study showed that measurable differences exist between the mechanical characteristics of benign and malignant prostatic tissue and provide further evidence that significant correlations exist between prostatic tissue morphology and mechanical characteristics. We believe that the ability to quantify prostatic tissue mechanical characteristics in vivo may be of clinical benefit in the future assessment of prostatic diseases, both benign and malignant.


Subject(s)
Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/physiopathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/physiopathology , Aged , Aged, 80 and over , Biomechanical Phenomena , Diagnosis, Differential , Elasticity , Humans , Male , Middle Aged , Viscosity
15.
Urology ; 65(5): 1024-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15882757

ABSTRACT

OBJECTIVES: To investigate the relationship between the morphology and the mechanical properties of benign prostatic tissues measured in vitro. METHODS: Fresh tissue specimens were collected from 17 patients undergoing transurethral resection of the prostate for benign prostatic obstruction. Individual tissue specimens underwent immediate mechanical testing, by applying a dynamic compressive strain to the samples. The amplitude ratio (E*) and phase difference (tan delta), measures of tissue elastic and viscous components, were derived. Individual sections from the processed specimens underwent immunohistochemical staining and computerized image analysis to measure the morphologic characteristics of each transurethral resection of the prostate chipping. Correlations between the morphologic and mechanical measurements were assessed. RESULTS: A strong positive correlation was found between prostatic smooth muscle content and (E*) (R2 = 0.58, P = 0.009). CONCLUSIONS: The results of this study have demonstrated that strong correlations exist between prostatic tissue morphology and mechanical characteristics. We believe that the ability to quantify prostatic tissue mechanical characteristics in vivo may be of clinical benefit in the future assessment and treatment of benign prostatic disease.


Subject(s)
Prostate/physiopathology , Prostatic Hyperplasia/physiopathology , Aged , Aged, 80 and over , Biomechanical Phenomena , Elasticity , Humans , Immunohistochemistry , In Vitro Techniques , Male , Middle Aged , Muscle, Smooth/metabolism , Muscle, Smooth/pathology , Prostate/chemistry , Prostate/pathology , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Viscosity
16.
Clin Exp Allergy ; 34(8): 1276-82, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15298570

ABSTRACT

BACKGROUND: The mechanism whereby allergen induces eotaxin expression at the site of allergic inflammation is incompletely understood. Structural cells, including endothelial cells, are a major source of eotaxin. OBJECTIVE: We have investigated, in vivo and in vitro, the relationship between mast cell activation and the expression of eotaxin (eotaxin 1) by endothelial cells. METHODS: The effects of intradermal allergen challenge and histamine injection on eotaxin mRNA and protein generation were studied in atopic subjects using immunofluorescence, immunohistochemistry and in situ hybridization. Histamine-induced expression of eotaxin mRNA and protein by endothelial cells was also measured, as was histamine-induced eosinophil adhesion to cultured endothelial cells. RESULTS: A rapid increase in degranulating cutaneous mast cells, together with a concomitant increase in eosinophils, was observed 60 min after allergen challenge. This was accompanied by the appearance of immunoreactive eotaxin that peaked at 1 h around blood vessels and at 3 h within the tissue. Intradermal histamine injection produced an increase in the number of eotaxin+ cells in the tissues, which was maximal at the 3-h time-point. In vitro, endothelial cells produced eotaxin mRNA and protein product in a dose- and time-dependent fashion following incubation with histamine, an effect that was blocked by levocetirizine. Pre-incubation of endothelial cells with histamine also induced a significant increase in eosinophil adherence, an effect that was inhibited with an anti-eotaxin blocking monoclonal antibody. CONCLUSION: The antigen-induced expression of eotaxin by endothelial cells and the adherence and subsequent migration of eosinophils from the microvasculature to the tissues are rapid events partially under the control of histamine released from degranulating mast cells.


Subject(s)
Chemokines, CC/metabolism , Chemotaxis, Leukocyte , Dermatitis, Atopic/immunology , Mast Cells/metabolism , Adult , Cell Adhesion , Cell Line , Cetirizine/pharmacology , Chemokine CCL11 , Chemokines, CC/genetics , Endothelial Cells/immunology , Eosinophils/pathology , Female , Gene Expression/drug effects , Histamine/metabolism , Histamine H1 Antagonists/pharmacology , Humans , Irritants/metabolism , Male , Piperazines/pharmacology , RNA, Messenger/analysis , Statistics, Nonparametric
17.
Soc Sci Med ; 58(10): 1917-27, 2004 May.
Article in English | MEDLINE | ID: mdl-15020008

ABSTRACT

In this paper, we use the Canadian National Longitudinal Survey of Children and Youth data to examine the links between child well-being and neighbourhood 'quality.' This study adds to the literature by (i) investigating the relationship between neighbourhood quality and child health, (ii) by utilizing subjective assessments by individuals familiar with the neighbourhood (i.e., the survey respondent and interviewer), and (iii) by utilizing multiple assessments of neighbourhood quality, and (iv) by investigating several measures of health. Other work has found that controlling for family level characteristics reduces or eliminates the apparent association between neighbourhood quality and health. We find, measuring both child well-being and neighbourhood quality multi-dimensionally, that even after controlling for family level characteristics neighbourhood quality has strong associations with child well-being.


Subject(s)
Child Welfare/statistics & numerical data , Health Status , Residence Characteristics/classification , Social Environment , Adult , Canada/epidemiology , Child , Child Behavior Disorders/epidemiology , Child, Preschool , Family Characteristics , Female , Housing , Humans , Infant , Infant, Newborn , Interviews as Topic , Longitudinal Studies , Male , Multivariate Analysis , Residence Characteristics/statistics & numerical data , Socioeconomic Factors , Sociology, Medical
18.
Bone Marrow Transplant ; 29(5): 425-34, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11919733

ABSTRACT

There has been little empirical documentation of the acute effects of bone marrow or stem cell transplant (BMT) on children. In the present study, the responses of 153 children undergoing BMT were assessed in a prospective, longitudinal design. Children were assessed at the time of admission for transplant, then underwent weekly assessments to week +6, followed by monthly assessment to month +6. Data were obtained both by parent report and patient report (for patients age 5 and up) using the BASES scales. The major findings are: (1) children undergoing BMT enter the hospital with an already heightened level of distress (defined by high levels of somatic symptoms and mood disturbance, and low levels of activity) that increases dramatically following conditioning, reaching a peak approximately 1 week following transplant; (2) this increased distress is transient, declining rapidly back to admission levels by week +4 to week +5, followed by a further decline to presumed basal levels by months 4-6; and (3) the trajectories of distress depicted by both parent and child report are remarkably similar, each providing confirmatory support for the validity of the findings. These findings confirm a number of widely held clinical impressions that had not previously been documented empirically, and point to the need for new interventions or more intensive approaches to supportive care aimed at reducing levels of distress during the acute phase of transplant.


Subject(s)
Quality of Life , Stem Cell Transplantation/psychology , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/psychology , Child , Child, Preschool , Female , Humans , Infant , Male , Mood Disorders/etiology , Neoplasms/therapy , Parents , Patient Compliance , Prospective Studies , Stem Cell Transplantation/adverse effects , Treatment Outcome
19.
Bone Marrow Transplant ; 29(5): 435-42, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11919734

ABSTRACT

Medical and demographic variables were examined as predictors of acute health-related quality of life (HRQL), specifically, somatic distress, mood disturbance and activity levels, during the period of bone marrow transplant (BMT) hospitalization, and the transition phase in the months following hospital discharge. The responses of 153 children undergoing BMT were assessed by both parent report and patient self-report in a prospective longitudinal design. Type of transplant, diagnosis, age, gender, and socio-economic status (SES) were examined as predictor variables of patient outcome. Type of transplant, patient age, and SES emerged as significant determinants of patient response. Children undergoing unrelated donor (MUD) transplants experiencing the highest levels of distress, followed by those undergoing matched-sibling BMT, while those undergoing autologous transplant experienced the lowest levels of distress. Younger patients experienced lower levels of distress and better HRQL than older children and adolescents. Although patients from different SES backgrounds appeared very similar at the time of hospital admission, those from lower SES backgrounds demonstrated greater distress and disturbance in HRQL subsequently, and throughout the first 6 months post BMT. These findings help to target specific subgroups of patients that may be in greater need of preventive interventions or more aggressive supportive care.


Subject(s)
Quality of Life , Stem Cell Transplantation/psychology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Evaluation Studies as Topic , Female , Humans , Infant , Male , Middle Aged , Mood Disorders/etiology , Parents , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors , Social Class , Stem Cell Transplantation/adverse effects , Stress, Physiological/etiology , Time Factors
20.
Am J Respir Cell Mol Biol ; 25(4): 425-33, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11694447

ABSTRACT

The increase in eosinophils at the site of antigen challenge has been used as evidence to suggest that this cell type plays a role in the pathophysiology of asthma. Aberrant production of several different cytokines, particularly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 influences the development and maturation of eosinophils in a number of different ways. Of note is the ability of IL-5 to act as a survival factor for eosinophils specifically inhibiting apoptosis. The precise mechanism by which IL-5 exerts its effect remains obscure. We used microarray technologies to investigate the changes in the messenger RNA expression profile of eosinophils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total of 80 genes were observed to be regulated by 2-fold or greater. Many of the genes previously identified as regulated by IL-5 were regulated in our microarray experiments. Of the 73 genes found to be upregulated, many were shown to play a role in adhesion, migration, activation, or survival of eosinophils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survivability of eosinophils, we used an alternative cellular model, TF1.8 cells, whose survival was also dependent on IL-5. Comparison of these models identified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regulation was similarly coordinated in both systems. Identification of Pim-1 and SLP-76 as regulated by IL-5 led us to suggest a direct role for these proteins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restricted to the eosinophil compared with their expression in brain, bone marrow, kidney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiquitous in their expression by microarray.


Subject(s)
Apoptosis/genetics , Eosinophils/cytology , Eosinophils/physiology , Immediate-Early Proteins , Interleukin-5/metabolism , Membrane Glycoproteins , Oligonucleotide Array Sequence Analysis , Adaptor Proteins, Signal Transducing , Antigens, CD/genetics , Antigens, Differentiation, T-Lymphocyte/genetics , CD24 Antigen , Cell Survival/genetics , Cells, Cultured , DNA-Binding Proteins/genetics , Dual-Specificity Phosphatases , Early Growth Response Protein 1 , Humans , Interleukin-5/pharmacology , Lectins, C-Type , Molecular Sequence Data , Phosphoproteins/genetics , Protein Serine-Threonine Kinases/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-pim-1 , Transcription Factors/genetics
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