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1.
Osteoarthritis Cartilage ; 27(3): 401-411, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30590194

RESUMO

PURPOSE: To provide a narrative review of the most relevant original research published in 2017/2018 on osteoarthritis imaging. METHODS: The PubMed database was used to recover all relevant articles pertaining to osteoarthritis and medical imaging published between 1 April 2017 and 31 March 2018. Review articles, case studies and in vitro or animal studies were excluded. The original publications were subjectively sorted based on relevance, novelty and impact. RESULTS AND CONCLUSIONS: The publication search yielded 1,155 references. In the assessed publications, the most common imaging modalities were radiography (N = 708) and magnetic resonance imaging (MRI) (355), followed by computed tomography (CT) (220), ultrasound (85) and nuclear medicine (17). An overview of the most important publications to the osteoarthritis (OA) research community is presented in this narrative review. Imaging studies play an increasingly important role in OA research, and have helped us to understand better the pathophysiology of OA. Radiography and MRI continue to be the most applied imaging modalities, while quantitative MRI methods and texture analysis are becoming more popular. The value of ultrasound in OA research has been demonstrated. Several multi-modality predictive models have been developed. Deep learning has potential for more automatic and standardized analyses in future OA imaging research.


Assuntos
Osteoartrite/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Radiografia , Tomografia Computadorizada por Raios X , Ultrassonografia
2.
Clin Radiol ; 71(6): 570-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27055743

RESUMO

AIM: To evaluate the prevalence of cervical facet oedema in patients referred for magnetic resonance imaging (MRI) to investigate neck pain and/or radiculopathy, and to investigate whether there is a correlation between the presence of oedema and patients' symptoms. MATERIALS AND METHODS: A retrospective report review of 1885 patients undergoing cervical spine MRI between July 2008 and June 2015 was performed. Exclusion criteria included acute trauma, surgery, neoplastic disease, or infection in the cervical spine. One hundred and seventy-three MRI studies with cervical facet oedema were evaluated by each of the two radiologists. In these patients, the grade of bone marrow oedema (BMO) and corresponding neuroforaminal narrowing at the cervical facets was assessed. Correlation with symptoms was performed based on pre-MRI questionnaire. RESULTS: The prevalence of cervical facet oedema was 9%; the most commonly affected levels were C3-4, C4-5, and C2-3. A total of 202 cervical facets were evaluated: mild BMO was seen in 35%, moderate in 41%, and severe in 24% of cases. Surrounding soft-tissue oedema was observed in 36%, 69%, and 92% of the BMO grades, respectively. The correlations between unilateral radiculopathy and ipsilateral facet BMO grades were 79%, 83%, and 73% (chi-square, p<0.001), respectively. Furthermore, neuroforaminal narrowing on the corresponding level was found in 35%, 38%, and 11% of cases, respectively. At follow-up imaging, facet oedema was most likely to remain unchanged or to decrease. CONCLUSION: The prevalence of cervical facet oedema is 9%. Cervical facet oedema is associated with ipsilateral radiculopathy. Neuroforaminal narrowing, however, is not associated with facet oedema.


Assuntos
Edema/diagnóstico , Edema/epidemiologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Radiculopatia/diagnóstico , Radiculopatia/epidemiologia , Doenças da Coluna Vertebral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebra Cervical Áxis/diagnóstico por imagem , Causalidade , Comorbidade , Feminino , Finlândia/epidemiologia , Humanos , Artropatias , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Doenças da Coluna Vertebral/epidemiologia , Estatística como Assunto , Avaliação de Sintomas/estatística & dados numéricos , Articulação Zigapofisária/diagnóstico por imagem
3.
Scand J Prim Health Care ; 33(3): 178-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26311207

RESUMO

BACKGROUND: Emotional exhaustion is central in burnout syndrome and signals its development. General practitioners' (GP) work is emotionally challenging but research on these aspects is lacking. OBJECTIVE: To study the prevalence of emotional exhaustion among GPs and to evaluate how their characteristics and work experiences are associated with emotional exhaustion. DESIGN AND METHODS: A questionnaire survey was carried out among GPs in Finland in 2011 in which questions were posed regarding their experience of emotional exhaustion and items related to their work experiences and professional identity. A statement "I feel burnt out from my job" (never, seldom, sometimes, quite often, or often) enquired about emotional exhaustion. Those responding quite often or often were categorized as emotionally exhausted. RESULTS: Among the GPs, 68% responded (165/244). Of the respondents, 18% were emotionally exhausted. Emotional exhaustion was associated with older age, longer working history, experiences of having too much work, fear and reports of having committed a medical error, low tolerance of uncertainty in their work, and feeling alone at work. No differences in positive work experiences were found. In logistic regression analysis working experience > 5 years (OR 4.1, 95% CI 1.6-10.8; p = 0.0036) and feeling alone at work (OR 2.9, 95% CI 1.2-7.1; p = 0.020) predicted emotional exhaustion, having committed a medical error in the past three months predicted it marginally significantly (OR 2.4, 95% CI 1.0-5.9, p = 0.057), whereas tolerating uncertainty well protected against it (OR 0.2, 95% CI 0.09-0.7; p = 0.0098). CONCLUSIONS: Emotional exhaustion among GPs was common and associated with longer working history, having committed a medical error, and feelings of isolation at work. GPs should receive more support throughout their careers.


Assuntos
Atitude do Pessoal de Saúde , Esgotamento Profissional , Medicina Geral , Clínicos Gerais/psicologia , Satisfação no Emprego , Carga de Trabalho , Adulto , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/etiologia , Emoções , Feminino , Finlândia , Humanos , Modelos Logísticos , Masculino , Erros Médicos , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Incerteza
4.
Eur J Clin Microbiol Infect Dis ; 31(10): 2835-42, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22639174

RESUMO

A method for the rapid detection of methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) with a straightforward sample preparation protocol of blood cultures using an automated homogeneous polymerase chain reaction (PCR) assay, the GenomEra™ MRSA/SA (Abacus Diagnostica Oy, Turku, Finland), is presented. In total, 316 BacT/Alert (bioMérieux, Marcy l'Etoile, France) and 433 BACTEC (Becton Dickinson, Sparks, MD, USA) blood culture bottles were analyzed, including 725 positive cultures containing Gram-positive cocci in clusters (n = 419) and other Gram stain forms (n = 361), as well as 24 signal- and growth-negative bottles. Detection sensitivities for MSSA, MRSA, and MRCoNS were 99.4 % (158/159), 100.0 % (9/9), and 99.3 % (132/133), respectively. One false-positive MRSA result was detected from a non-staphylococci-containing bottle, yielding a specificity of 99.8 %. The lowest detectable amount of viable cells in the blood culture sample was 4 × 10(4) CFU/mL. The results were available within one hour after microbial growth detection and the two-step, time-resolved fluorometric (TRF) measurement mode employed by the GenomEra CDX™ instrument showed no interference from blood, charcoal, or culture media. The method described lacks all sample purification steps and allows reliable and simplified pathogen detection also in clinical microbiology laboratory settings without specialized molecular microbiology competence.


Assuntos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Proteínas de Bactérias/análise , Técnicas de Tipagem Bacteriana/métodos , Sobrevivência Celular , Coagulase , Fluorometria/instrumentação , Fluorometria/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/enzimologia , Proteínas de Ligação às Penicilinas , Reação em Cadeia da Polimerase/instrumentação , Kit de Reagentes para Diagnóstico/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Fatores de Tempo
5.
Scand J Prim Health Care ; 30(2): 121-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22339369

RESUMO

OBJECTIVE: To explore medical students' potential interest in family medicine in the future and their perceptions of a GP's work. DESIGN: A cross-sectional survey in 2008-2010. SETTING AND SUBJECTS: Fifth-year medical students prior to their main course in General Practice at the University of Helsinki. MAIN OUTCOME MEASURES: The students' opinions regarding the GP's work and their perceptions of the main aims of a GP's work. RESULTS: 309/359 medical students (mean age 25.7 years, 64% females) responded to the survey. Among the students, 76% considered the most attractive feature in the GP's work to be that it is versatile and challenging. The least attractive features included: too hasty, pressing work, too lonely work, and too many non-medical problems. The majority of the students considered the main aim of a GP's work as to identify serious diseases/disorders in order to refer those patients for specialized care (82%). Treatment of chronic diseases is an important responsibility of a GP's work according to 63% of the students. Only 38% considered health promotion to be an important aim. CONCLUSIONS: Medical students may have perceptions of the GP's work that influence their career choices to specialize in other fields.


Assuntos
Atitude do Pessoal de Saúde , Medicina de Família e Comunidade , Estudantes de Medicina/psicologia , Adulto , Escolha da Profissão , Feminino , Finlândia , Humanos , Masculino , Papel do Médico , Inquéritos e Questionários , Adulto Jovem
6.
Eur J Clin Microbiol Infect Dis ; 31(8): 1961-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22278292

RESUMO

A new automated closed tube PCR assay, the GenomEra(™) MRSA/SA Diagnose (Abacus Diagnostica Oy, Finland) was evaluated for rapid confirmation of methicillin-resistant Staphylococcus aureus (MRSA) from cultured screening specimens. The ability of the assay to detect genotypically different MRSA strains was studied with a collection of 304 MRSA isolates covering 68 spa types. The specificity was investigated with a collection of 146 non-MRSA staphylococcus isolates. The usefulness of the assay for clinical purposes was assessed by a sequential combination of MRSA screening culture and confirmation of the colonies with the GenomEra MRSA/SA Diagnose assay. A total of 145 suspected MRSA colonies on chromogenic plates were analyzed this way. All MRSA isolates from the culture collection and from the clinical screening specimens were confirmed as MRSA with the GenomEra MRSA/SA Diagnose assay and none of the non-MRSA staphylococci caused false-positive results, which indicates both sensitivity and specificity of 100%. The combination of GenomEra MRSA/SA Diagnose with preceding culture on selective MRSA agar permitted MRSA confirmation within 24 h. This practice offers a reliable and quick detection of MRSA that is also suitable in areas where several strain types cause epidemics.


Assuntos
Meios de Cultura/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Infecções Estafilocócicas/microbiologia , Ágar , Compostos Cromogênicos/metabolismo , Humanos , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e Especificidade
7.
Patient Educ Couns ; 78(2): 218-23, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19767167

RESUMO

OBJECTIVE: Tolerance of uncertainty related to the complex work is a major dimension of general practitioner's (GP) profession. Strategies for managing uncertainty have been studied among GPs but less is known about how medical students develop tolerance of uncertainty during their studies. The aim of this study was to investigate how the medical students experience uncertainty during their first clinical years and how their feelings develop with time as they progress from the 3rd year to the 4th year. METHODS: The material consisted of 22 students' reflective learning diaries and writings on specific themes collected during the 3rd and 4th year of their medical studies. The analysis was performed using thematic content analysis. In this article we present the results related to the theme of uncertainty. RESULTS: Uncertainty is a major cause of mental strain for medical students, particularly fear of making mistakes. Main themes related to facing uncertainty and found in the diaries and writings were insecurity of professional skills, own credibility, facing with the inexactness of medicine, fear of making mistakes, coping with responsibility, and tolerating oneself as incomplete and accepting oneself as a good-enough doctor-to-be. Common steps of development towards tolerance of uncertainty were found in diaries over a one-year time period as the students progressed in their clinical studies. CONCLUSIONS: Reflective writing showed to be an effective means for the students of both expressing and dealing with uncertainty, both with the difficult and the pleasant feelings and the experiences the students had with their first patient contacts. It also gave some of them the means of self-reflection which they afterwards found worthwhile. PRACTICE IMPLICATIONS: Reflective writing is powerful tool which medical students could use to facilitate their maturation process what comes to uncertainty during their first clinical year.


Assuntos
Tomada de Decisões , Educação de Graduação em Medicina/métodos , Medicina de Família e Comunidade/educação , Estudantes de Medicina/psicologia , Incerteza , Redação , Adulto , Diversidade Cultural , Feminino , Humanos , Masculino , Narração , Pesquisa Qualitativa , Inquéritos e Questionários
8.
Endocrinology ; 148(3): 989-1008, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17138649

RESUMO

To identify cell populations directly responsive to prolactin (PRL), GH, erythropoietin, or granulocyte-colony stimulating factor within the physiological setting of an intact mammal, we combined in situ detection of hormone-activated signal transducer and activator of transcription (Stat)-5 in rats with high-throughput tissue array analysis using cutting-edge matrix assembly (CEMA). Inducible activation of Stat5a/b, as judged by levels of nuclear-localized, phosphoTyr694/699-Stat5a/b, served as an immediate and sensitive in situ marker of receptor signaling in rat tissues after injection into male and female rats of a single, receptor-saturating dose of hormone for maximal receptor activation. CEMA tissue arrays facilitated analysis of most tissues, including architecturally complex, thin-walled, and stratified tissues such as gut and skin. In 40 tissues analyzed, 35 PRL-responsive and 32 GH-responsive cell types were detected, of which 22 cell types were responsive to both hormones. Interestingly, PRL but not GH activated Stat5 in nearly all of the endocrine glands. In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells. Finally, the organism-wide screening revealed a yet-to-be identified erythropoietin-responsive cell type in connective tissue. CEMA tissue arrays provide cost-effective in situ analysis of large numbers of tissues. Biomarker-based identification of cell populations responsive to individual hormones may shed new light on endocrine disease as well as improve understanding of effects and side effects of hormones and drugs.


Assuntos
Eritropoetina/farmacologia , Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Hormônio do Crescimento/farmacologia , Prolactina/farmacologia , Análise Serial de Tecidos , Animais , Glândulas Endócrinas/citologia , Glândulas Endócrinas/efeitos dos fármacos , Glândulas Endócrinas/metabolismo , Feminino , Gônadas/citologia , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Hibridização In Situ , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
J Oral Rehabil ; 31(7): 647-52, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15210024

RESUMO

In 1990, 364 elderly (76-86 years) inhabitants of Helsinki, Finland, attended a dental and oral examination study that was conducted as part of the Helsinki Aging Study. In spring 1996, these subjects were recalled for a 5-year follow-up. Between the baseline and follow-up examinations, 114 (31%) subjects had deceased (86 women and 28 men), whereas 134 had either moved, were too ill, or refused to participate in the follow-up. Follow-up examination was conducted for 113 subjects (79 women and 34 men), with the participating rate being 46%. Five subjects became edentulous during the follow-up. Of the subjects, 61% had 1-32 teeth at follow-up. In these subjects, the mean number of teeth decreased from 14.9 (+/-8.3) to 13.5 (+/-8.6) (P < 0.0001). Prosthetic status changed in 40% of the elderly dentate people: 25% received new prostheses whereas 15% lost prostheses that were not replaced. New fixed partial dentures were made in five maxillae and in nine mandibles during the follow-up. Acrylic removable partial dentures (ARPD) were most frequently used: 35% of dentate subjects had an ARPD. Subjects with removable prostheses had higher levels of salivary microbes and higher root caries incidence than those with natural teeth. Furthermore, the presence of removable prostheses at baseline, together with the male gender, was clearly associated with tooth loss during follow-up. This study indicates that fixed rather than removable prostheses should be used in elderly patients. The need for a removable denture ought to be carefully considered.


Assuntos
Prótese Parcial Fixa/estatística & dados numéricos , Prótese Parcial Removível/estatística & dados numéricos , Perda de Dente/reabilitação , Idoso , Idoso de 80 Anos ou mais , Prótese Parcial Removível/efeitos adversos , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Masculino , Fatores de Risco , Cárie Radicular/etiologia , Saliva/microbiologia , Fatores Sexuais , Perda de Dente/epidemiologia , Perda de Dente/etiologia
10.
Equine Vet J Suppl ; (34): 186-90, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12405684

RESUMO

Iron is of key importance for aerobic metabolism, and natural feeds of the horse are fairly rich sources of iron. Accordingly, the known incidence of iron deficiency anaemia is apparently rare in performance horses; despite this, iron deficiency in performance horses continues to be of concern to trainers and veterinarians. Effects of exercise on plasma ferritin concentrations were therefore studied in Standardbreds, Finnhorses and half-bred riding horses. Blood samples were taken after a moderate exercise test on a racetrack, a competition exercise test on a treadmill and a race. Even moderate exercise caused an increase in plasma ferritin concentration, with the increase being greater as the intensity and duration of exercise increased. Return to the basal level was slower after maximal-intensity exercise than after moderate exercise. In conclusion, although ferritin is a useful marker of low iron stores, samples should be taken only after at least 2 days rest following strenuous exercise.


Assuntos
Anemia Ferropriva/veterinária , Ferritinas/sangue , Doenças dos Cavalos/sangue , Ferro/metabolismo , Condicionamento Físico Animal/fisiologia , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Animais , Teste de Esforço/veterinária , Feminino , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/epidemiologia , Cavalos , Deficiências de Ferro , L-Lactato Desidrogenase/metabolismo , Masculino , Esforço Físico/fisiologia , Fatores de Tempo , gama-Glutamiltransferase/metabolismo
11.
Equine Vet J ; 34(2): 150-5, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11902757

RESUMO

We report the effects of mouldy hay/straw exposure, inhaled hay dust suspension (HDS) and inhaled lipopolysaccharide (LPS) on bronchoalveolar lavage fluid (BALF) gelatinolytic matrix metalloproteinase (MMP) levels and degree of activation in healthy (n = 6) and heaves- (previously termed chronic obstructive pulmonary disease) affected (n = 6 or 7) horses. Gelatinolytic MMPs in BALF were quantified by zymography, and gelatinases were shown by Western immunoblotting to be MMP-2 and MMP-9. Hay/straw and HDS challenges increased BALF total gelatinolytic activity only in heaves horses, with the majority of gelatinolytic activity comprising pro- and active MMP-9. The 5 h duration hay/straw challenge increased BALF gelatinolytic MMP activity in heaves horses at 5 and 24 h after the start of this challenge, with activity returning to baseline by Day 4. In contrast to hay/straw and HDS challenges, LPS inhalation increased BALF gelatinolytic MMP activity in both groups. For all challenges, absolute BALF neutrophil counts were highly significantly correlated (P<0.0001) with levels of proMMP-9 and active MMP-9, but not with levels of MMP-2 (P>0.05). As gelatinolytic MMPs are pro-inflammatory agents, they may contribute to lung dysfunction and tissue destruction in heaves horses exposed to airborne organic stable dusts.


Assuntos
Poeira/efeitos adversos , Doenças dos Cavalos/enzimologia , Lipopolissacarídeos/efeitos adversos , Pulmão/enzimologia , Metaloproteinases da Matriz/metabolismo , Doença Pulmonar Obstrutiva Crônica/veterinária , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/patologia , Cavalos , Pulmão/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/patologia
12.
Mol Cell Endocrinol ; 183(1-2): 151-63, 2001 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-11604235

RESUMO

Milk production remains suppressed in mammals during late pregnancy despite high levels of lactogenic polypeptide hormones. At parturition, associated with a precipitous fall in circulating progesterone, rising glucocorticoid levels synergize with prolactin to initiate copious milk production. This synergy is mediated at least in part through the coordinated activation of glucocorticoid receptors and transcription factor Stat5, particularly Stat5a. Here we show that two proline-juxtaposed serine residues within the transactivation domain of Stat5a are phosphorylated in the mammary gland during late gestation and lactation, and that these phosphorylation sites inhibit the transcriptional activity of Stat5a in the absence of glucocorticoid receptor costimulation. Specifically, transfection assays revealed that phosphorylation of residues S725 and S779 of Stat5a cooperatively suppressed prolactin-stimulated transcription from the beta-casein promoter in both COS-7 kidney and MCF-7 mammary cells. This suppression was associated with shortened duration and reduced amplitude of nuclear DNA binding activity of wild type Stat5a relative to that of the serine phosphorylation-defective Stat5 mutant. However, costimulation of glucocorticoid receptors completely reversed the suppressive effect of Stat5a serine phosphorylation on beta-casein gene transcription. We propose that serine phosphorylation within the transactivation domain may limit the activity of Stat5a in the absence of proper coactivation by glucocorticoid receptors.


Assuntos
Caseínas/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Proteínas do Leite , Fosfosserina/metabolismo , Prolactina/farmacologia , Transativadores/metabolismo , Sequência de Aminoácidos , Animais , Caseínas/metabolismo , Bovinos , Linhagem Celular , Meios de Cultura Livres de Soro , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Immunoblotting , Lactação/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fosforilação , Gravidez , Receptores de Glucocorticoides/metabolismo , Fator de Transcrição STAT5 , Alinhamento de Sequência , Transativadores/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor
13.
Lab Invest ; 81(6): 815-26, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11406643

RESUMO

SUMMARY: Fibroblast growth factor 8 (FGF-8) is implicated in growth of prostate cancer. Alternative splicing of the human FGF-8 gene potentially allows coding for four protein isoforms (a, b, e, and f). These isoforms differ in their binding to FGF receptors (FGFR) and in their mitogenic and transforming capacity in transfection assays. Here, we used RT-PCR and immunohistochemistry to study the expression of FGF-8 and FGFR isoforms in human prostate cancer (n = 31). Nonmalignant prostate specimens from cystoprostatectomies (n = 24) were examined as controls. Most prostate cancer samples and some control prostates also contained prostatic intraepithelial neoplasia (PIN) lesions. FGF-8a and e were expressed at significantly higher frequencies in prostate cancer (FGF-8a, 55%; FGF-8e, 45%) than in control samples (FGF-8a, 17%, p = 0.0052; FGF-8e, 8%, p = 0.0031). On the contrary, FGF-8b was found at an equal frequency in prostate cancer (55%) and in control prostates (50%). Furthermore, a combination of two or three FGF-8 isoforms (a, b, and/or e) was also expressed at a higher frequency in prostate cancer than in control samples (45% and 8%, respectively, p = 0.0031). Immunohistochemistry with an antibody recognizing all FGF-8 isoforms was more strongly immunoreactive in prostate cancer cells and PIN lesions than in normal-type epithelium. The receptor splicing variants FGFR1IIIc and FGFR2IIIc, which are activated by FGF-8, were found both in prostate cancer and control samples. Interestingly, immunoreactivity for FGFR1 and FGFR2 was much stronger in prostate cancer cells and PIN than in normal epithelium. These results demonstrate, for the first time, that FGF-8 isoforms and their receptors FGFR1IIIc and FGFR2IIIc are expressed at an increased level not only in prostate cancer but also in premalignant PIN lesions. These data suggest that FGF-8 may have an important autocrine role in the development of human prostate cancer. In addition to FGF-8b, the FGF-8 isoforms a and e may be involved in this process.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Lesões Pré-Cancerosas/metabolismo , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Idoso , Fator 8 de Crescimento de Fibroblasto , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Próstata/metabolismo , Isoformas de Proteínas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Valores de Referência , Distribuição Tecidual
14.
J Org Chem ; 66(6): 2061-6, 2001 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-11300901

RESUMO

Fmoc-protected trans-4-methylproline was synthesized starting from D-serine. The chiral scaffold of serine in the form of olefinated Garner's aldehyde 3 was used to control the diastereoselective formation of the new stereocenter on the hydrogenation of allylic alcohol 4. The diastereoselectivity (syn/anti ratio) of the process was 86:14, attained with Raney nickel. Hydrogen migration seems not to be the sole factor lowering the diastereoselectivity, as nickel is known not to promote double-bond migration. Instead, the moderate stereocontrol is attributed to the mobility of the side chain of 4, which allows the attack of hydrogen on both faces of the olefin (open transition state). A series of transformations led to ring precursor 8, which after recrystallization afforded the syn diastereoisomer in dr = 95:5. Protected trans-4-methylproline 11 was obtained from 8 in a straightforward fashion.


Assuntos
Aminoácidos/química , Fluorenos/química , Prolina/síntese química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Prolina/análogos & derivados , Prolina/química , Análise Espectral
15.
Urol Res ; 29(1): 23-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11310211

RESUMO

Cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) each have an important role in angiogenesis. The expression of these genes was investigated in human prostate cancer by immunohistochemistry, the expression of COX-1 and COX-2 being confirmed by mRNA analysis. Prostate cancer specimens from 12 patients were compared to control prostates from 13 patients operated on for bladder carcinoma. The intensity of COX-2 and NOS-2 immunostaining was significantly stronger in prostate cancer cells than in the non-malignant glandular epithelium of the control prostates. COX-2 and NOS-2 were clearly also expressed in the lesions of prostatic intraepithelial neoplasia (PIN) in control prostates. COX-2 was detected in the muscle fibres of the hyperplastic stroma of some control prostates. No significant difference was detected in COX-1 expression between control and cancer prostates. These results indicate that the expression of COX-2 and NOS-2 is elevated in prostatic adenocarcinoma and in PIN.


Assuntos
Isoenzimas/genética , Óxido Nítrico Sintase/genética , Prostaglandina-Endoperóxido Sintases/genética , Neoplasia Prostática Intraepitelial/enzimologia , Neoplasias da Próstata/enzimologia , Idoso , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Isoenzimas/análise , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase Tipo II , Prostaglandina-Endoperóxido Sintases/análise , RNA Mensageiro/análise
16.
Lab Invest ; 80(7): 993-1006, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10908145

RESUMO

The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. PRL also stimulates growth and differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We therefore investigated the importance of Stat5a for prostate development and function by examining Stat5a-null mice. The absence of Stat5a in mice was associated with a distinct prostate morphology characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates. Affected acini were typically filled with desquamated, granular epithelial cells that had become embedded in dense, coagulated secretory material. These features were reminiscent of acinar cyst formation and degeneration frequently observed in human benign prostate hyperplasia, however, cystic changes in prostate acini of Stat5a-deficient mice were not associated with increased prostate size or morphologic hallmarks of epithelial hyperplasia. Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice. Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers the first evidence for a direct role of Stat5a in the maintenance of normal tissue architecture and function of the mouse prostate.


Assuntos
Proteínas de Ligação a DNA/deficiência , Proteínas do Leite , Próstata/patologia , Doenças Prostáticas/etiologia , Doenças Prostáticas/patologia , Transativadores/deficiência , Animais , Apoptose , Divisão Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Células Epiteliais/patologia , Células Epiteliais/fisiologia , Epitélio/metabolismo , Epitélio/patologia , Masculino , Camundongos , Camundongos Knockout/genética , Prolactina/sangue , Prolactina/fisiologia , Próstata/metabolismo , Próstata/fisiopatologia , Doenças Prostáticas/genética , Doenças Prostáticas/metabolismo , Receptores da Prolactina/metabolismo , Valores de Referência , Fator de Transcrição STAT5 , Transdução de Sinais , Testosterona/sangue , Transativadores/genética , Transativadores/metabolismo
17.
Endocrinology ; 140(11): 5412-21, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10537173

RESUMO

PRL is one of several polypeptide factors that regulate growth and differentiation of prostate epithelium besides steroid hormones. This hormone may also participate in the development of pathologic changes of the prostate, as evidenced by marked prostate hyperplasia in hyperprolactinemic mice. We have previously demonstrated expression of PRL receptors and androgen-dependent local production of PRL in rat and human prostate epithelium, suggesting the existence of an autocrine loop. We now show that PRL acts as a survival factor for epithelial cells of rat dorsal and lateral prostate but not ventral prostate, using long-term organ cultures as an in vitro model. Culture of prostate explants in androgen-free medium was associated with a transient surge of apoptosis during the first 2-4 days of culture in rat ventral, dorsal, and lateral prostate tissues, as quantified by either nuclear morphology or in situ DNA fragmentation analysis. PRL significantly inhibited apoptosis in androgen-deprived dorsal and lateral prostate cultures, by 40-60%, as determined by the two methods. The present study has established conditions and methodology for analysis of apoptosis in organ cultures of rat prostate and suggests a physiological role for PRL as a survival factor for prostate epithelium.


Assuntos
Androgênios/administração & dosagem , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Prolactina/farmacologia , Próstata/citologia , Animais , Meios de Cultura , Fragmentação do DNA , Células Epiteliais/citologia , Masculino , Mitose , Ratos , Ratos Sprague-Dawley
18.
Prostate ; 35(4): 263-72, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9609549

RESUMO

BACKGROUND: Group II phospholipase A2 (PLA2) is a lipolytic enzyme suggested to play a role in inflammation and antibacterial defence. In seminal fluid, the concentration of PLA2 is exceedingly high under normal circumstances (about 1,000 times the concentration in blood plasma of healthy humans). To elucidate the origin of the enzyme present in seminal plasma, we investigated the expression of group II PLA2 in male reproductive organs both at protein and mRNA levels. In addition, the presence of the enzyme was studied in common male genital tumors. METHODS: The methods used were immunocytochemistry, in situ hybridization, and Northern blotting. RESULTS: Northern blotting gave positive results for group II PLA2 mRNA in normal prostate, whereas other normal genital tissues gave negative results. Immunohistochemistry and in situ hybridization of group II PLA2 gave identical results. The enzyme was produced exclusively by the secretory epithelial cells of the prostatic gland. Surprisingly, expression was restricted to the posterior lobe and paraurethral glands of the prostate. Cells of prostatic adenocarcinoma expressed group II PLA2, whereas cells of other male genital tumors contained neither the enzyme protein nor the mRNA of group II PLA2. In some cases prostatic cancer cell seemed to express group II PLA2 at a higher rate than normal prostatic gland cells. CONCLUSIONS: The high content of group II PLA2 in seminal plasma is due to the local production and secretion of the enzyme by the epithelial cells of the prostatic glands. Group II PLA2 is expressed focally, suggesting that specialized prostatic glands secrete this enzyme. All prostatic adenocarcinomas tested expressed group II PLA2 in variable amounts.


Assuntos
Regulação Enzimológica da Expressão Gênica , Neoplasias dos Genitais Masculinos/enzimologia , Genitália Masculina/enzimologia , Fosfolipases A/biossíntese , Próstata/enzimologia , Hiperplasia Prostática/enzimologia , Neoplasias da Próstata/enzimologia , Epididimo/enzimologia , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/cirurgia , Genitália Masculina/citologia , Genitália Masculina/patologia , Humanos , Masculino , Fosfolipases A2 , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , RNA Mensageiro/biossíntese , Valores de Referência , Sêmen/enzimologia , Glândulas Seminais/enzimologia , Neoplasias Testiculares/enzimologia , Testículo/enzimologia , Transcrição Gênica , Uretra/enzimologia
19.
FASEB J ; 11(14): 1297-307, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9409549

RESUMO

Peptide hormones and growth factors are involved in the regulation of prostatic cell proliferation, differentiation, and programmed cell death, which functions are primarily controlled by androgen. In carcinogenesis, prostatic cancer cells often lose androgen dependence and become largely dependent on local growth factors. The prostatic cancer cells able to respond to factors other than androgen by proliferation and inhibition of apoptosis are possibly able to survive. We demonstrate that prostatic epithelium expresses prolactin mRNA and protein in a characteristic manner. By using in situ hybridization, an overall distribution of prolactin mRNA was demonstrated in the epithelium of rat dorsal and lateral prostate, whereas a very specific localization of prolactin protein to single cells was observed by immunohistochemistry in the same tissues. In these cells, immunoelectron microscopy showed that prolactin was primarily localized to the secretory granules. These data demonstrate a selective regulation of prostatic prolactin at least at the level of transcript processing/translation and/or protein accumulation and secretion. In addition, the expression of prolactin protein in rat dorsal and lateral prostate was found to be androgen dependent in vivo in castrated and in castrated, testosterone-treated rats, as well as in vitro in organ cultures. Our results support the concept of an autocrine/paracrine loop of prolactin action in prostate where it could mediate some of androgen actions. Also, locally synthesized prolactin might belong to the factors that take over androgen regulation of prostatic cancer cells during the development of androgen-independent growth.


Assuntos
Androgênios/metabolismo , Prolactina/metabolismo , Próstata/metabolismo , Animais , Grânulos Citoplasmáticos/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/ultraestrutura , Regulação da Expressão Gênica/efeitos dos fármacos , Hibridização In Situ , Masculino , Microscopia Imunoeletrônica , Orquiectomia , Técnicas de Cultura de Órgãos , Prolactina/genética , Próstata/efeitos dos fármacos , Próstata/ultraestrutura , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Testículo/fisiologia , Testosterona/farmacologia
20.
J Oral Rehabil ; 24(5): 332-7, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9183025

RESUMO

A large epidemiological health investigation, the Helsinki Ageing Study (HAS), was performed in 1989-1991 in Helsinki, Finland. We report here the prevalence of oral mucosal lesions in 338 76-, 81- and 86-year-old home-living elderly people, who completed the oral health investigation at the Institute of Dentistry, University of Helsinki. One or more lesions were found in 128 subjects (38%). Fifty-one per cent of the edentulous complete-denture wearers and 31% of the elderly with some natural teeth had mucosal lesions. The most common finding was inflammation under the denture, which occurred alone or combined with other lesions in 25% of the denture wearers. The three most common mucosal changes not related to denture wearing were coated changes of the tongue (7%), angular cheilitis (6%) and varicose veins under the tongue (4%). No differences were found in the number of mucosal lesions among the three age groups. Angular cheilitis and inflammation under removable dentures were more frequent in women than in men. However, no other differences were found in the presence of mucosal lesions between sexes. The total number of mucosal lesions correlated positively with the number of medications used daily. Ninety-six per cent of the subjects with complete dentures, and 98% of those with some natural teeth reported cleaning their dentures at least once a day. Of the denture wearers, 88% reported cleaning their oral mucosa also, as part of their oral hygiene routine. The presence of mucosal lesions was related to self-reported cleaning of the denture-bearing mucosa. However, no association was observed between cleaning frequency and presence of mucosal changes.


Assuntos
Doenças da Boca/epidemiologia , Higiene Bucal/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Queilite/epidemiologia , Higienizadores de Dentadura , Prótese Total/estatística & dados numéricos , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Finlândia/epidemiologia , Humanos , Arcada Parcialmente Edêntula/epidemiologia , Masculino , Mucosa Bucal/patologia , Boca Edêntula/epidemiologia , Prevalência , Fatores Sexuais , Estomatite sob Prótese/epidemiologia , Língua/irrigação sanguínea , Doenças da Língua/epidemiologia , Escovação Dentária/estatística & dados numéricos , Varizes/epidemiologia
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