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1.
Environ Pollut ; 266(Pt 1): 115213, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32688110

ABSTRACT

Abundance, composition, and distribution of macro-litter found on the seafloor of the Strait of Sicily between 10 and 800 m depth has been studied using data collected by bottom trawl surveys MEDITS from 2015 to 2019. Three waste categories based on the items use were considered: single-use, fishing-related and generic-use. Over 600 sampling sites, just 14% of these were litter-free. The five-years average density of seafloor litter was 79.6 items/km2 and ranged between 46.8 in 2019 and 118.1 items/km2 in 2015. The predominant waste type was plastic (58% of all items). Regardless of material type, single-use items were a dominant (60% of items) and widespread (79% of hauls) fraction of litter with a mean density of 48.4 items/km2. Fishing-related items accounted for 12% of total litter items. Percentage of dirty hauls and litter density increased with depth. Analysis of the relation density-depth indicates a progressive increase of litter density beyond depth values situated within the interval 234-477 m depending on the litter category. A significant decrease in litter density by categories was observed over the period. Patterns of spatial distribution at the higher depths (200-80 0m) resulted stable over the years. Density hotspots of fishing-related items were found where the fishing activity that uses fish aggregating devices (FADs) is practised and in the proximity of rocky banks. Single-use and generic-use objects densities were greater on the seafloor along main maritime routes than other areas. Comparisons between the percentage of hauls littered with anthropic waste from the mid-1990s against those in 2018-19 highlighted an increase of about 10.8% and 15.3% for single-use items and fishing-related items respectively, and a decrease of 18.6% for generic-use items. This study provides a snapshot of the current situation of littering in the central Mediterranean Sea and represents a solid baseline against which the effectiveness of current and future mitigation strategies of the litter impact on marine environment can be measured.


Subject(s)
Environmental Monitoring , Waste Products/analysis , Animals , Mediterranean Sea , Plastics , Sicily
2.
Obes Sci Pract ; 5(4): 354-365, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31452920

ABSTRACT

OBJECTIVE: Harnessing social support from existing social ties represents a key weight control practice. This trial evaluated an intervention that provided health-promoting technologies for leveraging the influence of existing social ties. METHODS: Volunteers (N = 36) with a body mass index between 25 and 55 kg m-2 were randomized to a 16-week, in-person, technology-supported behavioural weight-loss treatment (standard behavioural treatment) or the same programme supplemented by providing self-selected members of participants' social networks with a digital body-weight scale and Fitbit Zip physical activity tracker (ENHANCED). RESULTS: Average weight losses from baseline to 16 weeks did not significantly differ between groups (standard behavioural treatment, 5.30%, SD =3.93%; ENHANCED, 5.96%, SD = 5.19%, p = 0.63). By the 1-year follow-up, standard behavioural treatment had lost 5.63%, SD = 8.14% of baseline weight versus 4.73%, SD = 9.43% for ENHANCED (p = 0.82). ENHANCED reported self-weighing on more days than did standard behavioural treatment (p = 0.03). Most participants reported high programme satisfaction. Similar improvements were observed in perceived social support for diet and exercise from baseline to 16 weeks in both groups (ps < 0.05) but regressed by 1 year (ps < 0.01). CONCLUSION: Although feasible to implement, this technology-based, social support approach failed to enhance outcomes of a face-to-face, group-based behavioural weight-loss treatment.

3.
Psychol Med ; 47(10): 1806-1815, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28290265

ABSTRACT

BACKGROUND: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder. METHOD: Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future. RESULTS: As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t 17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both). CONCLUSIONS: The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.


Subject(s)
Anxiety Disorders/physiopathology , Anxiety/physiopathology , Caudate Nucleus/physiopathology , Optimism , Prefrontal Cortex/physiopathology , Adult , Anxiety/psychology , Anxiety Disorders/psychology , Caudate Nucleus/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Optimism/psychology , Phobia, Social/physiopathology , Phobia, Social/psychology , Prefrontal Cortex/diagnostic imaging , Young Adult
4.
Clin Transl Sci ; 9(6): 293-301, 2016 12.
Article in English | MEDLINE | ID: mdl-27766744

ABSTRACT

Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression. PTTG1 expression was correlated with proliferation, cell division, and mitosis in ovarian cancer tissues data sets. In sensitive cell lines, saracatinib treatment decreased PTTG1 and fibroblast growth factor 2 (FGF2) protein levels. Downregulating PTTG1 by siRNAs increased saracatinib sensitivity in two resistant cell lines. Our results indicate PTTG1 may be a valuable biomarker in ovarian cancer to predict sensitivity to saracatinib, and could form the basis of a targeted prospective saracatinib trial for ovarian cancer.


Subject(s)
Benzodioxoles/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Quinazolines/therapeutic use , Securin/metabolism , Benzodioxoles/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation/drug effects , Down-Regulation/genetics , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Female , Fibroblast Growth Factor 2/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Gene Silencing/drug effects , Humans , Models, Biological , Ovarian Neoplasms/pathology , Phosphorylation/drug effects , Quinazolines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Reproducibility of Results , Securin/genetics , src-Family Kinases/metabolism
5.
Psychol Med ; 46(14): 2943-2953, 2016 10.
Article in English | MEDLINE | ID: mdl-27476529

ABSTRACT

BACKGROUND: Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions? METHOD: A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others' fearful, angry, happy or neutral reactions. RESULTS: During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others' fearful reactions, and a trend towards decreased amygdala activation to objects associated with others' happy and neutral reactions. CONCLUSIONS: These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.


Subject(s)
Amygdala/physiopathology , Facial Expression , Facial Recognition/physiology , Fear/physiology , Phobia, Social/physiopathology , Prefrontal Cortex/physiopathology , Social Learning/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Young Adult
6.
Tech Coloproctol ; 19(8): 449-53, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25724967

ABSTRACT

BACKGROUND: Fistula-tract Laser Closure (FiLaC™) is a sphincter-saving technique for the treatment of anal fistulas that has been shown to be successful in the short and middle term. However, the long-term success rate is unknown. This study aimed to report long-term results in performing FiLaC™. METHODS: This study was performed as a retrospective observational study. Forty-five patients who underwent FiLaC™ between July 2010 and May 2014 were evaluated. In all cases, FiLaC™ was performed with a diode laser at a wavelength of 1470 nm by means of a radial fiber. Patients and fistula characteristics, previous treatments, healing rates, failures and postoperative incontinence were reviewed. RESULTS: Median follow-up time was 30 months (range 6-46 months). Thirty-five patients (78%) had a history of previous surgery for their fistulas. Primary healing was observed in 32 patients (71.1%), and the median healing time was 5 weeks (range 3-8 weeks). Eleven of the 13 failures (85%) were early failures (persistent symptoms). No patient reported postoperative incontinence. The best healing rate was observed in patients who had been previously treated with loose seton (19/24, 79%). CONCLUSIONS: Long-term follow-up after FiLaC™ seems to confirm the favorable short-term success rates reported for this procedure. Although sealing of chronic anal fistulas may be obtained with FiLaC™ in a single treatment, our current strategy consists of placing a loose seton into the fistula tract a few weeks prior to laser treatment. Seton treatment facilitates the following laser procedure and seems to have favorable effects on healing.


Subject(s)
Anal Canal/surgery , Laser Therapy/methods , Rectal Fistula/surgery , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Laser Therapy/adverse effects , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Survival Analysis , Treatment Outcome , Wound Healing , Young Adult
7.
Colorectal Dis ; 16(2): 110-5, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24119103

ABSTRACT

AIM: Fistula laser closure (FiLaC™) is a novel sphincter-saving procedure for the treatment of anal fistula. Primary closure of the track is achieved using laser energy emitted by a radial fibre connected to a diode laser. The energy causes shrinkage of the tissue around the radial fibre with the aim being to close the track. This pilot study was designed to investigate the safety and effectiveness of this new technique in the treatment of anal fistula. METHOD: Thirty-five patients with anal fistula underwent the FiLaC™ procedure. They had either a primary or a recurrent trans-sphincteric anal fistula, a previously placed seton or a fistula involving a significant portion of the sphincter with a potential risk of postoperative incontinence on fistulotomy. The surgical procedure consisted of 'sealing' the fistula by laser energy. The primary end-point was cure of the disease and evaluation of morbidity. The secondary end-point was an assessment of the degree of postoperative continence using the Cleveland Clinic Florida (CCF) Fecal Incontinence Score. RESULTS: The median operation time was 20 (6-35) min. No intra-operative complications were reported. Median duration of follow up was 20 (3-36) months. Primary healing was observed in 25 (71.4%) patients. There were eight (23%) failures and two recurrences at 3 and 6 months after the operation. No patient reported incontinence postoperatively. CONCLUSION: The laser FiLaC™ procedure for fistula-in-ano is a safe, relatively simple, minimally invasive, sphincter-saving procedure with a high chance of success.


Subject(s)
Fecal Incontinence/surgery , Lasers, Semiconductor/therapeutic use , Rectal Fistula/surgery , Adult , Aged , Anal Canal , Fecal Incontinence/etiology , Female , Humans , Laser Therapy , Male , Middle Aged , Organ Sparing Treatments , Rectal Fistula/complications , Treatment Outcome
8.
Br J Cancer ; 105(1): 177-84, 2011 Jun 28.
Article in English | MEDLINE | ID: mdl-21654675

ABSTRACT

BACKGROUND: In England, cervical cancer is the second most common cancer in women aged under 35 years. Overall incidence of cervical cancer has decreased since the introduction of the national screening programme in 1988 but recent trends of incidence in young women have not been studied in detail. METHODS: Information on 71,511 incident cases of cervical cancer in England, 1982-2006, in 20-79-year-olds was extracted from a national cancer registration database. Changes in incidence were analysed by age group, time period and birth cohort. Poisson regression was used to estimate annual percentage change (APC). RESULTS: Overall incidence, during 1982-2006, fell significantly from 213 to 112 per million person years. However, in 20-29-year-olds, after an initial fall, incidence increased significantly during 1992-2006, (APC 2.16). In 30-39-year-olds incidence stabilised during the latter part of the study period. The pattern was most marked in the North East, Yorkshire and the Humber and East Midlands regions. Birth cohorts that were initially called for screening between 60-64 and 35-39 years of age show an incidence peak soon after the age of presumed first screen, whereas younger birth cohorts show a peak at about 35 years of age. Incidence in the 1977-1981 birth cohort has increased relative to that among women born between 1962 and 1976. CONCLUSION: These results have implications for cervical screening, human papilloma virus vaccination and other public health interventions targeting young people.


Subject(s)
Mass Screening/statistics & numerical data , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Age Factors , Aged , England , Female , Humans , Incidence , Middle Aged , Time Factors , Uterine Cervical Neoplasms/epidemiology , Young Adult , Uterine Cervical Dysplasia/epidemiology
9.
Br J Cancer ; 101(11): 1939-45, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19888224

ABSTRACT

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.


Subject(s)
Neoplasms/mortality , Adolescent , Adult , England/epidemiology , Humans , Population Dynamics , Survival Rate , Young Adult
10.
Psychol Med ; 39(7): 1153-61, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19102795

ABSTRACT

BACKGROUND: Generalized social phobia (GSP) involves the fear/avoidance of social situations whereas generalized anxiety disorder (GAD) involves an intrusive worry about everyday life circumstances. It remains unclear whether these, highly co-morbid, conditions represent distinct disorders or alternative presentations of a single underlying pathology. In this study, we examined stimulus-reinforcement-based decision making in GSP and GAD. METHOD: Twenty unmedicated patients with GSP, 16 unmedicated patients with GAD and 19 age-, IQ- and gender-matched healthy comparison (HC) individuals completed the Differential Reward/Punishment Learning Task (DRPLT). In this task, the subject chooses between two objects associated with different levels of reward or punishment. Thus, response choice indexes not only reward/punishment sensitivity but also sensitivity to reward/punishment level according to between-object reinforcement distance. RESULTS: We found that patients with GAD committed a significantly greater number of errors than both the patients with GSP and the HC individuals. By contrast, the patients with GSP and the HC individuals did not differ in performance on this task. CONCLUSIONS: These results link GAD with anomalous non-affective-based decision making. They also indicate that GSP and GAD are associated with distinct pathophysiologies.


Subject(s)
Anxiety Disorders/psychology , Decision Making , Motivation , Phobic Disorders/psychology , Adult , Anxiety Disorders/diagnosis , Arousal , Choice Behavior , Comorbidity , Depression/diagnosis , Depression/psychology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pattern Recognition, Visual , Personality Inventory/statistics & numerical data , Phobic Disorders/diagnosis , Psychometrics , Punishment , Reward , Young Adult
11.
Br J Cancer ; 99(5): 830-5, 2008 Sep 02.
Article in English | MEDLINE | ID: mdl-18728673

ABSTRACT

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13-24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30,000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996-2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.


Subject(s)
Neoplasms/pathology , Survival Analysis , Adolescent , Adult , England , Humans , Neoplasms/classification , Socioeconomic Factors
12.
Br J Cancer ; 97(11): 1588-94, 2007 Dec 03.
Article in English | MEDLINE | ID: mdl-17987032

ABSTRACT

We examined cancer mortality at ages 13-29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkin's lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval -2.09 to -1.62). Cancer groups with the highest mortality differed from those with the highest incidence.


Subject(s)
Mortality/trends , Neoplasms/mortality , Adolescent , Adult , England/epidemiology , Female , Humans , Male , Registries/statistics & numerical data , Wales/epidemiology
13.
G Chir ; 26(8-9): 311-3, 2005.
Article in Italian | MEDLINE | ID: mdl-16329773

ABSTRACT

Appendiceal mucocele is an uncommon disorder caused by accumulation of mucus within the appendiceal lumen. Mucoceles represent a heterogeneous group comprising various histopathologic lesions including mucosal hyperplasia, cystoadenomas, and cystoadenocarcinomas and prognosis is related to these subtypes. The most common symptom is pain or a palpable mass in the right lower quadrant on physical examination. The preoperative diagnosis is performed with abdominal U.S. and confirmed with CT scan; typical CT scan image is a capsulated cystic mass with calcification of the wall while U.S. pattern shows cystic lesion with the onion skin sign considered a specific sonographic marker for appendiceal mucocele. In conclusion a cystic mass sonographically detected with onion skin sign, in the presence of normal female reproductive organs, suggest the diagnosis of appendiceal mucocele.


Subject(s)
Appendix , Mucocele , Adult , Cecal Diseases/diagnosis , Cecal Diseases/surgery , Humans , Male , Mucocele/diagnosis , Mucocele/surgery
14.
Eur Respir J ; 22(3): 403-7, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14516126

ABSTRACT

Primary pulmonary hypertension (PPH) and Castleman's disease (CD) are rare conditions infrequently encountered in clinical practice. In this paper, two patients diagnosed with both of these diseases are reported. The authors speculate that rather than being a chance occurrence, these conditions are linked by a common angio-proliferative mechanism. Therefore, an association between infection with the human herpesvirus-8 and the diseases of PPH and CD was sought. Evidence of human herpesvirus-8 infection was found in the lung tissue and, specifically, in the plexiform lesions from one of the patients.


Subject(s)
Castleman Disease/virology , Herpesviridae Infections/complications , Herpesvirus 8, Human/isolation & purification , Hypertension, Pulmonary/virology , Adult , Cardiac Catheterization , Castleman Disease/pathology , Female , Herpesviridae Infections/pathology , Humans , Hypertension, Pulmonary/pathology , Immunohistochemistry , Lung/pathology , Lymph Nodes/pathology , Male , Polymerase Chain Reaction
15.
Ann Readapt Med Phys ; 46(4): 184-90, 2003 May.
Article in French | MEDLINE | ID: mdl-12787975

ABSTRACT

OBJECTIVE: The purpose of this work was to define the influence of obesity on static postural control of teenagers. SUBJECTS AND METHOD: Nine obese subjects and seven non-obese subjects were characterised with stabilometric data of surface, of lengths and spontaneous sway in the lateral (X) and antero-posterior (Y) axis with open eyes and closed eyes in two conditions on firm floor and foam floor condition. RESULTS: For length data, significative differences were observed between the two groups for the opened eyes condition (p < 0.02) and eyes closed (p < 0.03) during foam floor condition. CONCLUSION: During experimental solicitations, obesity influences significatively the postural control of teenagers. Instead of systematic statistic differences, we observed a decrease in balance capacities of obese subjects. The effects of fat tissue distributions were not verified.


Subject(s)
Obesity/complications , Postural Balance , Posture , Adolescent , Biomechanical Phenomena , Body Composition , Female , Humans , Male
16.
Respir Res ; 2(4): 210-5, 2001.
Article in English | MEDLINE | ID: mdl-11686886

ABSTRACT

Genomics, or the study of genes and their function, is a burgeoning field with many new technologies. In the present review, we explore the application of genomic approaches to the study of pulmonary hypertension (PH). Candidate genes, important to the pathobiology of the disease, have been investigated. Rodent models enable the manipulation of selected genes, either by transgenesis or targeted disruption. Mutational analysis of genes in the transforming growth factor-beta family have proven pivotal in both familial and sporadic forms of primary PH. Finally, microarray gene expression analysis is a robust molecular tool to aid in delineating the pathobiology of this disease.


Subject(s)
Hypertension, Pulmonary/genetics , Animals , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Mutation , Oligonucleotide Array Sequence Analysis
17.
J Pathol ; 195(3): 367-74, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11673836

ABSTRACT

Pulmonary arteries of patients with severe pulmonary hypertension (SPH) presenting in an idiopathic form (primary PH-PPH) or associated with congenital heart malformations or collagen vascular diseases show plexiform lesions. It is postulated that in lungs with SPH, endothelial cells in plexiform lesions express genes encoding for proteins involved in angiogenesis, in particular, vascular endothelial growth factor (VEGF) and those involved in VEGF receptor-2 (VEGFR-2) signalling. On immunohistochemistry and in situ hybridization, endothelial cells in the plexiform lesions expressed VEGF mRNA and protein and overexpressed the mRNA and protein of VEGFR-2, and the transcription factor subunits HIF-1alpha and HIF-1beta of hypoxia inducible factor, which are responsible for the hypoxia-dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and src, which, together with Akt, relay the signal transduction downstream of VEGFR-2. Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis.


Subject(s)
DNA-Binding Proteins , Endothelial Growth Factors/analysis , Hypertension, Pulmonary/metabolism , Lymphokines/analysis , Pulmonary Artery/metabolism , Receptor Protein-Tyrosine Kinases/analysis , Receptors, Aryl Hydrocarbon , Receptors, Growth Factor/analysis , Aryl Hydrocarbon Receptor Nuclear Translocator , Biomarkers/analysis , Case-Control Studies , Endothelial Growth Factors/genetics , Humans , Hypertension, Pulmonary/pathology , Hypoxia-Inducible Factor 1, alpha Subunit , In Situ Hybridization/methods , Lymphokines/genetics , Neovascularization, Pathologic , Oligopeptides/analysis , Phosphatidylinositol 3-Kinases/analysis , Pulmonary Artery/pathology , RNA, Messenger/analysis , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor , Transcription Factors/analysis , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
18.
Phys Rev Lett ; 87(10): 102701, 2001 Sep 03.
Article in English | MEDLINE | ID: mdl-11531477

ABSTRACT

Experimental information has been derived from the neutron-proton correlation function in order to deduce the time sequence of neutrons and protons emitted at 45 degrees in the E/A = 45 MeV 58Ni + 27Al reaction.

19.
Am J Physiol Heart Circ Physiol ; 281(3): H1005-14, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11514265

ABSTRACT

Prolonged infusions of 17beta-estradiol reduce fetal pulmonary vascular resistance (PVR), but the effects of endogenous estrogens in the fetal pulmonary circulation are unknown. To test the hypothesis that endogenous estrogen promotes pulmonary vasodilation at birth, we studied the hemodynamic effects of prolonged estrogen-receptor blockade during late gestation and at birth in fetal lambs. We treated chronically prepared fetal lambs with ICI-182,780 (ICI, a specific estrogen-receptor blocker, n = 5) or 1% DMSO (CTRL, n = 5) for 7 days and then measured pulmonary hemodynamic responses to ventilation with low- and high-fraction inspired oxygen (FI(O(2))). Treatment with ICI did not change basal fetal PVR or arterial blood gas tensions. However, treatment with ICI abolished the vasodilator response to ventilation with low FI(O(2)) [change in PVR -30 +/- 6% (CTRL) vs. +10 +/- 13%, (ICI), P < 0.05] without reducing the vasodilator response to ventilation with high FI(O(2)) [change in PVR, -73 +/- 3% (CTRL) vs. -77 +/- 4%, (ICI); P = not significant]. ICI treatment reduced prostacyclin synthase (PGIS) expression by 33% (P < 0.05) without altering expression of endothelial nitric oxide synthase or cyclooxygenase-1 and -2. In situ hybridization and immunohistochemistry revealed that PGIS is predominantly expressed in the airway epithelium of late gestation fetal lambs. We conclude that prolonged estrogen-receptor blockade inhibits the pulmonary vasodilator response at birth and that this effect may be mediated by downregulation of PGIS. We speculate that estrogen exposure during late gestation prepares the pulmonary circulation for postnatal adaptation.


Subject(s)
Estradiol/administration & dosage , Estrogen Antagonists/administration & dosage , Prenatal Exposure Delayed Effects , Pulmonary Circulation/drug effects , Receptors, Estrogen/antagonists & inhibitors , Animals , Animals, Newborn , Blotting, Western , Cyclooxygenase 1 , Cyclooxygenase 2 , Cytochrome P-450 Enzyme System/metabolism , Drug Administration Schedule , Estradiol/analogs & derivatives , Female , Fetus/blood supply , Fetus/drug effects , Fetus/physiology , Fulvestrant , Hemodynamics/drug effects , Infusions, Intra-Arterial/methods , Intramolecular Oxidoreductases/metabolism , Isoenzymes/metabolism , Lung/drug effects , Lung/embryology , Lung/enzymology , Nitric Oxide/metabolism , Nitric Oxide/pharmacology , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Organ Specificity , Pregnancy , Prostaglandin-Endoperoxide Synthases/metabolism , Pulmonary Artery/embryology , Pulmonary Artery/physiology , Pulmonary Circulation/physiology , Pulmonary Ventilation/drug effects , Sheep , Vasodilation/drug effects , Vasodilation/physiology
20.
Eur Respir J ; 17(6): 1065-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11491145

ABSTRACT

The recent discoveries of the familial primary pulmonary hypertension gene and somatic mutations in key cell growth and cell death regulatory genes in primary pulmonary hypertension have added a new dimension to severe pulmonary hypertension research. These findings have already impacted on how the disease is viewed, and ultimately, how severe pulmonary hypertension is diagnosed and treated. However, this new information raises several fundamental questions related to the role of bone morphogenetic protein receptor signalling in the control of lung vascular cell function. Furthermore, additional genes and gene products may also be involved in the pathogenesis of the disease. The way severe pulmonary hypertension is viewed and studied is on the verge of shifting from a vasoconstrictive to a cell growth paradigm.


Subject(s)
Hypertension, Pulmonary/genetics , Bone Morphogenetic Protein Receptors, Type II , DNA Mutational Analysis , Endothelium, Vascular/physiopathology , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Protein Serine-Threonine Kinases/genetics , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/genetics , Signal Transduction/physiology
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