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1.
J Laryngol Otol ; 131(1): 13-18, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27917727

RESUMO

OBJECTIVE: To determine the length and position of a thyroidectomy scar that is cosmetically most appealing to naïve raters. METHODS: Images of thyroidectomy scars were reproduced on male and female necks using digital imaging software. Surgical variables studied were scar position and length. Fifteen raters were presented with 56 scar pairings and asked to identify which was preferred cosmetically. Twenty duplicate pairings were included to assess rater reliability. Analysis of variance was used to determine preference. RESULTS: Raters preferred low, short scars, followed by high, short scars, with long scars in either position being less desirable (p < 0.05). Twelve of 15 raters had acceptable intra-rater and inter-rater reliability. CONCLUSION: Naïve raters preferred low, short scars over the alternatives. High, short scars were the next most favourably rated. If other factors influencing incision choice are considered equal, surgeons should consider these preferences in scar position and length when planning their thyroidectomy approach.


Assuntos
Cicatriz/psicologia , Preferência do Paciente/estatística & dados numéricos , Tireoidectomia/psicologia , Adulto , Cicatriz/etiologia , Estética/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/psicologia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Adulto Jovem
2.
South Med J ; 94(4): 429-31, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11332912

RESUMO

Streptococcus pneumoniae is a common cause of infection in the pediatric population, as well as an important cause of septic arthritis. The increased prevalence of drug-resistant S pneumoniae in North America has renewed interest in the use of pneumococcal vaccines. We describe the case of a child with isolated acute septic arthritis caused by infection with penicillin-resistant S pneumoniae.


Assuntos
Artrite Infecciosa/microbiologia , Resistência às Penicilinas , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae , Doença Aguda , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/terapia , Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Terapia Combinada , Desbridamento , Drenagem , Edema/microbiologia , Articulação do Cotovelo , Humanos , Lactente , Contagem de Leucócitos , Masculino , Testes de Sensibilidade Microbiana , Nafcilina/uso terapêutico , Dor/microbiologia , Penicilinas/uso terapêutico , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/terapia , Vacinas Pneumocócicas , Prevalência
3.
Clin Infect Dis ; 32(6): E107-10, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11247733

RESUMO

Chromobacterium violaceum sepsis, a rarely reported phenomenon, has a high mortality rate. We report a unique case of C. violaceum sepsis in an infant. A 4-month-old girl presented to our institution with fever, pustular skin lesions, and distended abdomen, as well as diminished activity and mental status. Radiological investigation revealed brain, lung, and hepatic abscesses. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.


Assuntos
Chromobacterium/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Sepse/diagnóstico , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Lactente , Sepse/tratamento farmacológico , Sepse/microbiologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
4.
Med Anthropol Q ; 15(4): 440-54, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11794869

RESUMO

Results of studies of the popular illness susto and the biomedical entity pulmonary tuberculosis are offered to illustrate how comparisons of sick and well people can elucidate societal processes in cultural anthropology.


Assuntos
Antropologia Cultural , Atitude Frente a Saúde/etnologia , Sociologia Médica , Tuberculose Pulmonar/etnologia , Adulto , Emprego , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , México , Pesquisa , Fatores Sexuais , Valores Sociais/etnologia , Estresse Psicológico/etnologia
5.
Eur J Pharmacol ; 401(3): 357-63, 2000 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-10936494

RESUMO

The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.


Assuntos
Autorreceptores/fisiologia , Dopamina/farmacocinética , Estrogênios/farmacologia , Piranos , Compostos de Espiro , Animais , Antifúngicos/farmacologia , Benzazepinas/farmacologia , Transporte Biológico/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Feminino , Haloperidol/farmacologia , Cinética , Ovariectomia , Fosfoproteínas Fosfatases/antagonistas & inibidores , Proteína Fosfatase 1 , Quimpirol/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inibidores , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Fatores de Tempo
6.
Proc Natl Acad Sci U S A ; 97(9): 5007-10, 2000 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-10781113

RESUMO

Two perceptual structures (based on colors) and one semantic structure (based on names) of eight basic chromatic colors were obtained from three judged similarity tasks for 41 Mandarin Chinese-speaking females in Taiwan and 35 English-speaking females in the United States. Major findings include the following: (i) there are robust and reliable individual differences among individuals, (ii) the structures for Chinese and English speakers are similar, and (iii) the semantic structure of color names is similar to the perceptual structures of colors. The results place strong constraints on theories relating to individual differences, linguistic relativity, and the relation of perceptual and semantic structures for colors.


Assuntos
Cor , Idioma , Semântica , China/etnologia , Feminino , Humanos , Taiwan , Estados Unidos
7.
Radiology ; 214(2): 453-66, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10671594

RESUMO

PURPOSE: To present a database of systolic three-dimensional (3D) strain evolution throughout the normal left ventricle (LV) in humans. MATERIALS AND METHODS: In 31 healthy volunteers, magnetic resonance (MR) tissue tagging and breath-hold MR imaging were used to generate and then detect the motion of transient fiducial markers (ie, tags) in the heart every 32 msec. Strain and motion were calculated from a 3D displacement field that was fit to the tag data. Special indexes of contraction and thickening that were based on multiple strain components also were evaluated. RESULTS: The temporal evolution of local strains was linear during the first half of systole. The peak shortening and thickening strain components were typically greatest in the anterolateral wall, increased toward the apex, and increased toward the endocardium. Shears and displacements were more spatially variable. The two specialized indexes of contraction and thickening had higher measurement precision and tighter normal ranges than did the traditional strain components. CONCLUSION: In this study, the authors noninvasively characterized the normal systolic ranges of 3D displacement and strain evolution throughout the human LV. Comparison against this multidimensional database may permit sensitive detection of systolic LV dysfunction.


Assuntos
Imageamento por Ressonância Magnética , Função Ventricular Esquerda/fisiologia , Adulto , Algoritmos , Análise de Variância , Bases de Dados como Assunto , Endocárdio/anatomia & histologia , Endocárdio/fisiologia , Feminino , Septos Cardíacos/anatomia & histologia , Septos Cardíacos/fisiologia , Ventrículos do Coração/anatomia & histologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Rotação , Estresse Mecânico , Sístole
8.
Proc Natl Acad Sci U S A ; 97(1): 518-23, 2000 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-10618450

RESUMO

This paper describes a variety of statistical methods for obtaining precise quantitative estimates of the similarities and differences in the structures of semantic domains in different languages. The methods include comparing mean correlations within and between groups, principal components analysis of interspeaker correlations, and analysis of variance of speaker by question data. Methods for graphical displays of the results are also presented. The methods give convergent results that are mutually supportive and equivalent under suitable interpretation. The methods are illustrated on the semantic domain of emotion terms in a comparison of the semantic structures of native English and native Japanese speaking subjects. We suggest that, in comparative studies concerning the extent to which semantic structures are universally shared or culture-specific, both similarities and differences should be measured and compared rather than placing total emphasis on one or the other polar position.


Assuntos
Idioma , Semântica , Análise de Variância , Cultura , Emoções , Humanos
9.
Top Magn Reson Imaging ; 11(6): 359-71, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11153703

RESUMO

Magnetic resonance imaging with tissue tagging is a noninvasive technique for measuring three-dimensional motion and deformation in the human heart. Tags are regions of tissue whose longitudinal magnetization has been altered before imaging so that they appear dark in subsequent magnetic resonance images. They then move with the underlying tissue and serve as easily identifiable landmarks within the heart for the detailed detection of motion. Many different motion and strain parameters can be determined from tagged magnetic resonance imaging. Strain components that are based on a high density of tag data, such as circumferential and longitudinal shortening, or parameters that are combinations of multiple strain components, have highest measurement precision and tightest normal ranges. The pattern of three-dimensional motion and strain in the heart is important clinically, because it reflects the basic mechanical function of the myocardium at both local and global levels. Localized abnormalities can be detected and quantified if the pattern of deformation in a given heart is compared to the normal range for that region, because normal motion and strain in the left ventricle is spatially heterogeneous. Contraction strains typically are greatest in the anterior and lateral walls and increase toward the apex. The direction of greatest contraction lies along a counter clockwise helix from base to apex (viewed from the base) and approximates the epicardial muscle fiber direction. This fiber geometry also results in long-axis torsion during systole. Ejection is accomplished primarily by radially inward motion of the endocardium and by descent of the base toward the apex during systole.


Assuntos
Ventrículos do Coração/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Marcadores de Spin , Feminino , Humanos , Masculino , Valores de Referência , Sensibilidade e Especificidade
11.
Circulation ; 99(2): 284-91, 1999 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-9892596

RESUMO

BACKGROUND: To limit ischemic myocardial injury, it is important to differentiate viable from infarcted myocardium. Three dimensional (3D) tagged MRI has the ability to quantify myocardial 3D deformation and strain (noninvasively and precisely), and can achieve a true comparison of contraction not only from region to region, but also at different levels of function. In this study, we investigated whether regional strain mapping obtained by 3D-tagged MRI can differentiate between viable but stunned myocardium and nonviable myocardium. METHODS AND RESULTS: We examined 7 dogs 2 days after a 90-minute closed-chest left anterior descending coronary artery occlusion followed by 48 hours of reperfusion. 3D-tagged MR images spanning the entire left ventricle were acquired both at rest and during dobutamine infusion (5 microg. kg-1. min-1 IV). Regional blood flow was measured with radioactive microspheres and used to define risk regions. Infarcted regions were defined as 2,3,5 triphenyltetrazolium chloride negative regions. Strains in infarcted regions were greatly impaired compared with remote regions (P<0.001) and remained unchanged during dobutamine stress. Risk regions showed a dysfunction at rest, with improved function during dobutamine infusion. Receiver operating characteristics analysis showed that radial strain was more accurate for identifying viable regions. CONCLUSIONS: When coupled with a stress test, 3D strain mapping by the use of tagged MRI is a sensitive and noninvasive method for characterizing ischemic injury. Regional strain can be used to differentiate between viable but stunned and nonviable myocardium within the postischemic injured myocardium.


Assuntos
Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Animais , Circulação Coronária , Cães , Infarto do Miocárdio/patologia , Miocárdio Atordoado , Fatores de Tempo , Sobrevivência de Tecidos
12.
J Cardiovasc Magn Reson ; 1(3): 207-22, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-11550355

RESUMO

The purpose of this study was to investigate the relationship between three-dimensional (3D) deformation patterns in the canine left ventricle and localized graded reductions in perfusion. Magnetic resonance (MR) tissue tagging in a clinical scanner was used to determine systolic 3D deformation throughout the left ventricle with 32-msec time resolution. Six dogs were studied at normal and reduced left anterior descending coronary artery flow levels, for a total of 14 studies. Deformation was calculated by fitting a 3D displacement field to tag displacement data from three orthogonal sets of tags and taking spatial derivatives. A novel index of 3D radial mechanical function, calculated from the 3D strain tensor components and the tissue incompressibility constraint, had a higher correlation (R = 0.94) with perfusion (colored microspheres) than any of the 3D Lagrangian finite strain tensor components or wall thickening. As a function of the fraction of baseline perfusion, it was well fit by a linear relationship for subnormal perfusion with a slope of 0.46 +/- 0.05 and an intercept of -0.156 +/- 0.026. Longitudinal strain was lost first with decreasing perfusion (48%), followed by circumferential (40%) and finally radial function (35%). The strain method detected perfusion drops as small as 20%, and early paradoxical strain transients lasting 100 msec were seen only with ischemia. 3D strain changes can be noninvasively measured throughout the left ventricle with MR tissue tagging. MR imaging-derived strain indices, unique to 3D analysis, correlate most sensitively with regional perfusion in the canine left ventricle.


Assuntos
Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Isquemia Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Estimulação Cardíaca Artificial , Circulação Coronária , Cães , Processamento de Imagem Assistida por Computador , Sístole/fisiologia
13.
Proc Natl Acad Sci U S A ; 94(10): 5489-94, 1997 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-9144265

RESUMO

Research is presented on the semantic structure of 15 emotion terms as measured by judged-similarity tasks for monolingual English-speaking and monolingual and bilingual Japanese subjects. A major question is the relative explanatory power of a single shared model for English and Japanese versus culture-specific models for each language. The data support a shared model for the semantic structure of emotion terms even though some robust and significant differences are found between English and Japanese structures. The Japanese bilingual subjects use a model more like English when performing tasks in English than when performing the same task in Japanese.


Assuntos
Emoções , Multilinguismo , Semântica , Intervalos de Confiança , Inglaterra , Humanos , Japão , Modelos Psicológicos , Estados Unidos
14.
Proc Natl Acad Sci U S A ; 93(10): 4699-705, 1996 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-11607678

RESUMO

Culture consists of shared cognitive representations in the minds of individuals. This paper investigates the extent to which English speakers share the "same" semantic structure of English kinship terms. The semantic structure is defined as the arrangement of the terms relative to each other as represented in a metric space in which items judged more similar are placed closer to each other than items judged as less similar. The cognitive representation of the semantic structure, residing in the mind of an individual, is measured by judged similarity tasks involving comparisons among terms. Using six independent measurements, from each of 122 individuals, correspondence analysis represents the data in a common multidimensional spatial representation. Judged by a variety of statistical procedures, the individuals in our sample share virtually identical cognitive representations of the semantic structure of kinship terms. This model of culture accounts for 70-90% of the total variability in these data. We argue that our findings on kinship should generalize to all semantic domains--e.g., animals, emotions, etc. The investigation of semantic domains is important because they may reside in localized functional units in the brain, because they relate to a variety of cognitive processes, and because they have the potential to provide methods for diagnosing individual breakdowns in the structure of cognitive representations typical of such ailments as Alzheimer disease.

15.
Radiology ; 195(3): 829-35, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7754016

RESUMO

PURPOSE: To reconstruct three-dimensional (3D) myocardial deformations from orthogonal sets of parallel-tagged magnetic resonance (MR) images. MATERIALS AND METHODS: Displacement information in the direction normal to the undeformed tag planes was obtained at points along tag lines. Three independent sets of one-dimensional displacement data were used to fit an analytical series expression to describe 3D displacement as a function of deformed position. The technique was demonstrated with computer-generated models of the deformed left ventricle with data from healthy human volunteers. RESULTS: Model deformations were reconstructed with a 3D tracking error of less than 0.3 mm. Error between estimated and observed one-dimensional displacements along the tags in 10 human subjects was 0.00 mm +/- 0.36 (mean +/- standard deviation). Robustness to noise in the tag displacement data was demonstrated by using a Monte Carlo simulation. CONCLUSION: The combination of rapidly acquired parallel-tagged MR images and field-fitting analysis is a valuable tool in cardiac mechanics research and in the clinical assessment of cardiac mechanical function.


Assuntos
Coração/anatomia & histologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Simulação por Computador , Coração/fisiologia , Humanos , Modelos Cardiovasculares , Contração Miocárdica
16.
Ann Thorac Surg ; 57(6): 1605-11, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8010809

RESUMO

The imaging modalities used to study the mechanism of cardiomyoplasty, such as echocardiography and radionuclide scintigraphy, are seriously limited by their two-dimensional format. Radiofrequency-pulse-tagged magnetic resonance imaging was used to generate three-dimensional reconstructions of the left ventricle throughout the cardiac cycle after cardiomyoplasty. In 2 dogs that had undergone conditioned, right anterior cardiomyoplasty, wrap stimulation with alternating heartbeats was found to produce marked translation of the left ventricle in the short-axis plane, rotation around the long axis, and displacement along the long axis with net long-axis compression; there was no augmentation of radial squeeze. The findings from this study suggest that any systolic augmentation produced by the right anterior wrap is due primarily to long-axis compression. Our study demonstrates a new, more accurate technique of assessing the mechanical effects of cardiomyoplasty in three dimensions, thus permitting a more rational optimization of wrap configurations, and emphasizes the perils of using standard two-dimensional imaging modalities in this setting of exaggerated three-dimensional motion.


Assuntos
Circulação Assistida , Procedimentos Cirúrgicos Cardíacos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Músculos/transplante , Retalhos Cirúrgicos , Animais , Cães , Estimulação Elétrica , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Movimento , Contração Miocárdica/fisiologia , Marca-Passo Artificial , Rotação , Função Ventricular Esquerda/fisiologia , Pressão Ventricular/fisiologia
17.
Cell ; 77(5): 651-61, 1994 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-8205615

RESUMO

Normal male sex differentiation requires that Sertoli cells in the embryonic testes produce müllerian inhibiting substance (MIS), a TGF beta-like hormone that causes müllerian duct regression. In primary Sertoli cells, the orphan nuclear receptor, steroidogenic factor 1 (SF-1), regulates the MIS gene by binding to a conserved upstream regulatory element. In heterologous (HeLa) cells, MIS gene activation by SF-1 requires removal of the SF-1 ligand-binding domain, implicating a Sertoli cell-specific ligand or cofactor. Finally, the sexually dimorphic expression of SF-1 during development coincides with MIS expression and müllerian duct regression. We propose that SF-1 regulates MIS in vivo and participates directly in the process of mammalian sex determination.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Glicoproteínas , Inibidores do Crescimento/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Diferenciação Sexual/genética , Diferenciação Sexual/fisiologia , Hormônios Testiculares/genética , Fatores de Transcrição/metabolismo , Animais , Hormônio Antimülleriano , Sequência de Bases , Sítios de Ligação , Núcleo Celular/metabolismo , DNA/genética , Feminino , Fatores de Transcrição Fushi Tarazu , Regulação da Expressão Gênica , Proteínas de Homeodomínio , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/metabolismo , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , Células de Sertoli/metabolismo , Caracteres Sexuais , Fator Esteroidogênico 1 , Testículo/embriologia , Ativação Transcricional
18.
Radiology ; 190(3): 765-9, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8115625

RESUMO

PURPOSE: To validate cine magnetic resonance (MR) image tagging measurements of a deforming object by means of a precise photographic method. MATERIALS AND METHODS: A piece of silicone rubber that acted as a phantom was stretched in a cyclical fashion inside a plastic clamp driven by a respirator pump. Deformation as a function of time was measured with a rapid gradient-echo cine tagging sequence and with sequential stroboscopic photographs. Deformations from 1.0 to 1.2 (0% to 20% stretch) in the readout direction were measured over a 7-cm region of the phantom, which had a maximum standard error of +/- 0.001 with photography and a maximum standard error of +/- 0.003 with MR imaging. RESULTS: The deformation versus time values measured with MR imaging had a standard error of 0.002 about a straight line fit to the photographic deformation versus time data. These results demonstrate that the MR imaging deformation estimates were accurate and precise. CONCLUSION: The validated tagging method can now be used to evaluate MR imaging motion estimation techniques.


Assuntos
Artefatos , Imageamento por Ressonância Magnética/métodos , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/normas , Modelos Estruturais , Movimento (Física) , Fotografação , Elastômeros de Silicone
19.
Mol Endocrinol ; 8(1): 97-108, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8152434

RESUMO

Studies of adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y-1 cells. We sought to make new, alternative mouse steroidogenic cell lines by genetically targeted tumorigenesis. Transgenic mice were constructed expressing both the SV40 T-antigen and a bacterial neomycin-resistance gene under the control of the promoter for the human P450 cholesterol side-chain cleavage (P450scc) gene, which encodes the first and rate-limiting enzyme in steroidogenesis. Two female transgenic mice expressed T-antigen in various nonsteroidogenic tissues but generated tumors only in the adrenals, suggesting adrenal tumor formation was an early event. Ovarian tissues, which, unlike the adrenal, do not make steroids in fetal or early postnatal life, did not develop tumors. Cell lines derived from the adrenal tumors were resistant to the neomycin analog G418. Clonal sublines are stable, growing easily in monolayers with a doubling time of 24-60 h. The cell lines secrete progesterone and 11-deoxycorticosterone, indicating these cells express the P450scc system, 3 beta-hydroxysteroid dehydrogenase, and 21-hydroxylase activity. However the 21-hydroxylase activity was not mediated by P450c21, as the cells lacked P450c21 mRNA. The cells did not secrete any 11-hydroxylated steroids, although they contained P450c11 beta mRNA. Both the secretion of progesterone and the abundance of P450scc mRNA increase in response to 8-bromo-cAMP, but not to ACTH or angiotensin II. In addition to expression of steroidogenic enzyme mRNAs, one cell line also expresses mouse renin-1 mRNA, making these cells useful for studies of the role of adrenal renin in regulating adrenal steroidogenesis. These findings represent an approach in transgenic mice to develop highly differentiated adrenal cell lines.


Assuntos
Corticosteroides/biossíntese , Córtex Suprarrenal/metabolismo , Neoplasias das Glândulas Suprarrenais/genética , 3-Hidroxiesteroide Desidrogenases/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Linhagem Celular , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Desoxicorticosterona/biossíntese , Resistência a Medicamentos/genética , Feminino , Expressão Gênica , Camundongos , Camundongos Transgênicos , Neomicina , Progesterona/biossíntese , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Renina/genética , Esteroide 21-Hidroxilase/genética
20.
Endocrinology ; 133(1): 368-75, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8319583

RESUMO

Both cortisol and aldosterone bind to and activate the mineralocorticoid receptor. Cortisol concentrations are generally 100- to 200-fold higher than aldosterone concentrations, yet mineralocorticoids clearly exert effects different from glucocorticoids. One hypothesis is that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts cortisol to biologically inactive cortisone, protects the mineralocorticoid receptor from cortisol. The circulating concentrations of cortisol in the squirrel monkey are 20- to 50-fold higher than human cortisol concentrations, yet this animal has no evidence of glucocorticoid or mineralocorticoid excess. We used this experiment of nature to test the hypotheses that the known (hepatic) form of 11 beta-HSD protects renal mineralocorticoid receptors from the action of cortisol and that it modulates glucocorticoid concentrations in target tissues. Using a long oligonucleotide based on the rat sequence, we cloned the squirrel monkey 11 beta-HSD complementary DNA and gene. The encoded monkey amino acid sequence is 75% and 91% identical to the corresponding rat and human sequences, respectively. The tissue abundance of the messenger RNA for the monkey enzyme was similar to or less than that seen for the rat and human enzymes. Both the monkey and human 11 beta-HSD complementary DNAs were cloned into an expression vector and used to transfect cultures of Chinese hamster ovary cells. Both vectors were transcribed and translated into equivalent amounts of 11 beta-HSD enzyme. The monkey enzyme was slightly more efficient than the human enzyme in converting [3H]cortisol to cortisone, and estimates of the Michaelis-Menten constant and maximum velocity of both enzymes are similar. These data indicate that the abundance and activity of the hepatic form of 11 beta-HSD are insufficient to inactivate the very high concentrations of cortisol in the squirrel monkey, suggesting that this form of 11 beta-HSD does not defend the mineralocorticoid receptor or protect tissues from high cortisol concentrations. Rather, this enzyme appears to favor conversion of cortisone to cortisol, thus maximizing tissue concentrations of cortisol to overcome glucocorticoid resistance associated with a 50% reduction in glucococorticoid receptors.


Assuntos
Glucocorticoides/farmacologia , Hidroxiesteroide Desidrogenases/química , Hidroxiesteroide Desidrogenases/metabolismo , Fígado/enzimologia , 11-beta-Hidroxiesteroide Desidrogenases , Sequência de Aminoácidos , Animais , Sequência de Bases , Células CHO , Clonagem Molecular , Cricetinae , DNA/química , DNA/genética , Resistência a Medicamentos , Humanos , Hidroxiesteroide Desidrogenases/genética , Dados de Sequência Molecular , RNA Mensageiro/análise , Saimiri , Distribuição Tecidual , Transfecção
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