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1.
Pediatr Hematol Oncol ; 33(2): 94-101, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26901768

RESUMO

The occurrence of congenital neuroblastoma presenting at birth with symptoms of epidural compression secondary to spinal canal invasion is rare. Almost all cases reported in the literature have survived from the tumor but suffer severe sequelae, with the exception of the 2 most recently described whose birth was anticipated. The 3 cases of this article have been followed for a minimum of 5 years with the aim to describe their definitive late complications. In none of these cases had the routine ultrasound scan performed in third trimester of pregnancy discovered a tumor mass, nor had it shown abnormal fetal movements. All had leg hypotonia detected on the first day of life. In all, both primary and intraspinal tumors responded well to chemotherapy. All survive with motor deficit and severe bladder dysfunction despite early physiotherapy. Scoliosis has developed in the case with the longest follow-up. The description of these patients enforces the importance of early diagnosis of tumor masses in late pregnancy. Neonatologists should be aware of this rare clinical entity and take it into account in the differential diagnosis with other conditions of early-onset hypotonia. On the other hand, obstetric sonologists should be aware of the possibility to detect such rare tumors in late pregnancy, as anticipation of delivery may reduce the risk of late sequelae.


Assuntos
Neuroblastoma/congênito , Neuroblastoma/complicações , Compressão da Medula Espinal/etiologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Neuroblastoma/diagnóstico por imagem , Ultrassonografia Pré-Natal
2.
Inhal Toxicol ; 26(11): 651-67, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25162719

RESUMO

The NERC Program conducted identically designed exposure-response studies of the respiratory and cardiovascular responses of rodents exposed by inhalation for up to 6 months to diesel and gasoline exhausts (DE, GE), wood smoke (WS) and simulated downwind coal emissions (CE). Concentrations of the four combustion-derived mixtures ranged from near upper bound plausible to common occupational and environmental hotspot levels. An "exposure effect" statistic was created to compare the strengths of exposure-response relationships and adjustments were made to minimize false positives among the large number of comparisons. All four exposures caused statistically significant effects. No exposure caused overt illness, neutrophilic lung inflammation, increased circulating micronuclei or histopathology of major organs visible by light microscopy. DE and GE caused the greatest lung cytotoxicity. WS elicited the most responses in lung lavage fluid. All exposures reduced oxidant production by unstimulated alveolar macrophages, but only GE suppressed stimulated macrophages. Only DE retarded clearance of bacteria from the lung. DE before antigen challenge suppressed responses of allergic mice. CE tended to amplify allergic responses regardless of exposure order. GE and DE induced oxidant stress and pro-atherosclerotic responses in aorta; WS and CE had no such effects. No overall ranking of toxicity was plausible. The ranking of exposures by number of significant responses varied among the response models, with each of the four causing the most responses for at least one model. Each exposure could also be deemed most or least toxic depending on the exposure metric used for comparison. The database is available for additional analyses.


Assuntos
Poluentes Atmosféricos/análise , Carvão Mineral/análise , Gasolina/análise , Fumaça/análise , Emissões de Veículos/análise , Madeira , Poluentes Atmosféricos/toxicidade , Animais , Gasolina/efeitos adversos , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Ratos , Fumaça/efeitos adversos , Estados Unidos , Emissões de Veículos/toxicidade
3.
Inhal Toxicol ; 20(13): 1125-43, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18800271

RESUMO

Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.


Assuntos
Gasolina/efeitos adversos , Nível de Saúde , Exposição por Inalação/efeitos adversos , Emissões de Veículos , Animais , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Material Particulado/administração & dosagem , Material Particulado/efeitos adversos , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos SHR
4.
Toxicol Ind Health ; 22(2): 65-85, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16716037

RESUMO

The U.S. Environmental Protection Agency's National Ambient Air Quality Standards for ozone and particulate matter (PM) require urban non-attainment areas to implement pollution-reduction strategies for anthropogenic source emissions. The type of fuel shown to decrease combustion emissions components versus traditional diesel fuel, is the diesel emulsion. The Lubrizol Corporation, in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories, recently conducted a health assessment of the combustion emissions of PuriNOx diesel fuel emulsion (diesel-water-methanol) in rodents. Combustion emissions from either of two, 2002 model Cummins 5.9L ISB engines, were diluted with charcoal-filtered air to exposure concentrations of 125, 250 and 500 microg total PM/m3. The engines were operated on a continuous, repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide (NO) and PM were reduced when engines were operated on PuriNOx versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, five days/week for the first 11 weeks and seven days/week thereafter. Exposures ranged from 61 to 73 days depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol in the 500-microg/m3 exposure group were observed. PM accumulation within alveolar macrophages was evident in all exposure groups. The latter findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups, but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol results, it can be concluded that the 250-microg/m3 exposure level was the no observed effect level. In general, biological findings in exposed rats and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.


Assuntos
Poluentes Atmosféricos/toxicidade , Emulsões , Gasolina , Metanol , Ratos Endogâmicos F344/fisiologia , Emissões de Veículos/toxicidade , Água/química , Administração por Inalação , Animais , Câmaras de Exposição Atmosférica , Bioensaio , Análise Química do Sangue , Peso Corporal , Emulsões/química , Emulsões/toxicidade , Feminino , Exposição por Inalação , Masculino , Testes para Micronúcleos , Óxidos de Nitrogênio/toxicidade , Material Particulado/toxicidade , Ratos
5.
Inhal Toxicol ; 18(8): 523-39, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16717024

RESUMO

Hardwood smoke is a contributor to both ambient and indoor air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center, a series of health assays was conducted on rodents exposed to environmentally relevant levels of hardwood smoke. This article summarizes the study design and exposures, and reports findings on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential. Hardwood smoke was generated from an uncertified wood stove, burning wood of mixed oak species. Animals were exposed to clean air (control) or dilutions of whole emissions based on particulate (30, 100, 300, and 1000 micromg/m3). F344 rats, SHR rats, strain A/J mice, and C57BL/6 mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Effects of exposure on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential were mild. Exposure-related effects included increases in platelets and decreases in blood urea nitrogen and serum alanine aminotransferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Pulmonary histopathology revealed very little accumulation of hardwood smoke particulate matter. Parallel studies demonstrated mild exposure effects on bronchoalveolar lavage parameters and in a mouse model of asthma. In summary, the results reported here show few and only modest health hazards from short-term to subchronic exposures to realistic concentrations of hardwood smoke.


Assuntos
Poluentes Atmosféricos/toxicidade , Fumaça/efeitos adversos , Madeira , Alanina Transaminase/sangue , Animais , Nitrogênio da Ureia Sanguínea , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Plaquetas , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos SHR , Testes de Toxicidade Crônica
6.
Inhal Toxicol ; 17(14): 851-70, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16282163

RESUMO

The U.S. Environmental Protection Agency (EPA) National Ambient Air Quality Standards for ozone and particulate matter are requiring urban nonattainment areas to implement pollution-reduction strategies for anthropogenic source emissions. A type of fuel shown to decrease combustion emissions components versus traditional diesel fuels is the diesel-water emulsion. The Lubrizol Corporation in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories recently conducted a rodent health assessment of inhaled combustion emissions of PuriNO(x) diesel fuel emulsion. Combustion emissions from either of two 2001 model Cummins 5.9-L ISB engines were diluted with charcoal-filtered air to exposure concentrations of 100, 200, and 400 microg total particulate matter/m(3). The engines were operated on a continuously repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide and particulate matter were reduced when engines were operated on PuriNO(x) versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, 5 days/wk for the first 11 wk and 7 days/wk threafter. Exposures ranged from 58 to 70 days, depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology, and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol and small increases in platelet values in some groups of exposed animals were observed. Particulate matter accumulation within alveolar macrophages was evident in all exposure groups. These findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol and platelet results, it can be concluded that the 100 microg/m(3) exposure level was the no-observed-effect level. In general, biological findings in diesel emulsion emission-exposed animals and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.


Assuntos
Poluentes Atmosféricos/toxicidade , Emulsões , Gasolina , Emissões de Veículos/toxicidade , Água/química , Administração por Inalação , Animais , Bioensaio , Análise Química do Sangue , Peso Corporal , Emulsões/química , Emulsões/toxicidade , Feminino , Humanos , Exposição por Inalação , Pulmão/citologia , Pulmão/patologia , Masculino , Testes para Micronúcleos , Ratos , Ratos Endogâmicos F344
7.
Inhal Toxicol ; 16(4): 177-93, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15204765

RESUMO

Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 microg/m(3)). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of contemporary diesel emissions.


Assuntos
Poluentes Atmosféricos , Pulmão/efeitos dos fármacos , Emissões de Veículos/toxicidade , Adenoma/induzido quimicamente , Adenoma/patologia , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Testes de Química Clínica , Relação Dose-Resposta a Droga , Feminino , Testes Hematológicos , Exposição por Inalação , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Testes para Micronúcleos , Ratos , Ratos Endogâmicos F344
8.
J Cell Biochem ; 82(3): 357-70, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11500913

RESUMO

CCAAT/Enhancer binding proteins (C/EBPs) play important roles in the regulation of cell growth and differentiation. This study investigated the expression and function of C/EBPbeta isoforms in the mouse mammary gland, mammary tumors, and a nontransformed mouse mammary epithelial cell line (HC11). C/EBPbeta mRNA levels are 2-5-fold higher in mouse mammary tumors derived from MMTV/c-neu transgenic mice compared with lactating and involuting mouse mammary gland. The "full-length" 38 kd C/EBPbeta LAP ("Liver-enriched Activator Protein") isoform is the predominant C/EBPbeta protein isoform in mammary tumor whole cell lysates, however, the truncated 20 kd C/EBPbeta LIP ("Liver-enriched Inhibitory Protein") isoform is also present at detectable levels (mean LAP:LIP ratio 5.3:1). The mammary tumor C/EBPbeta LAP:LIP ratio decreases 70% (from 5.3:1 to 1.6:1) when lysate preparation is switched from a rapid whole cell lysis protocol to a multistep nuclear/cytoplasmic fractionation protocol. In contrast to mammary tumors, only the C/EBPbeta LAP isoform is detectable in the mammary gland whole cell and nuclear lysates; the truncated "LIP" isoform is undetectable regardless of isolation protocol. Ectopic over expression of C/EBPbeta LIP or C/EBPbeta LAP did not alter HC11 growth rates. However, C/EBPbeta LIP over expressing HC11 cells (LAP:LIP ratio of approximately 1:1) exhibited a consistent 2-4 h delay in G(0)/S phase transition. C/EBPbeta LIP overexpressing HC11 cells did not express beta-casein mRNA (mammary epithelial cell differentiation marker) in response to lactogenic hormones. This defect in beta-casein expression was not corrected by carrying out the differentiation protocol in the presence of an artificial extracellular matrix. These results demonstrate that the "full-length" C/EBPbeta LAP isoform is the predominant C/EBPbeta protein isoform expressed in mouse mammary gland in vivo and mouse mammary epithelial cell cultures in vitro. C/EBPbeta LIP detected in mammary tumor lysates may result from in vivo production or ex vivo isolation-induced proteolysis of C/EBPbeta LAP. Ectopic overexpression of C/EBPbeta LIP (LAP:LIP ratio of approximately 1:1) inhibits mammary epithelial cell differentiation (beta-casein expression).


Assuntos
Mama/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Neoplasias Mamárias Animais/metabolismo , Animais , Mama/citologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Caseínas/genética , Ciclo Celular , Diferenciação Celular , Divisão Celular , Linhagem Celular , Feminino , Lactação , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Transgênicos , Gravidez , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição CHOP , Fatores de Transcrição/genética
9.
Breast Cancer Res Treat ; 58(1): 57-63, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10634518

RESUMO

The repeated lactation cycles in the mammary gland offer a unique environment for the study of cell growth, differentiation, and death. The CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors important in growth control and differentiation in many tissues. Our laboratory and others have shown that C/EBP-delta and C/EBP-beta mRNA expression is closely associated with normal mouse mammary gland involution. To examine the relative influence of local versus systemic factors in C/EBP expression and tissue remodeling, a gland sealing mouse model was used. Mice with unilateral sealing continue to lactate and nurse pups via nonsealed glands, while sealed glands initiate involution. The expression of C/EBP-alpha, beta and delta mRNA was investigated in sealed and nonsealed nursing glands. In situ apoptosis was documented and glandular morphology was also examined. C/EBP-delta mRNA levels are low in nonsealed glands, but are rapidly and transiently induced in sealed glands by 24 h. C/EBP-beta mRNA expression is also relatively low in nonsealed glands, but is induced in sealed glands within 72 h. Expression of the apoptosis-associated mRNAs encoding bax and TRPM-2 is also induced in sealed glands by 24-48 h. Apoptosis and a moderate degree of tissue remodeling occur within the sealed glands in spite of systemic hormone levels capable of sustaining lactation. These data demonstrate that local factors are sufficient to induce C/EBP-beta and C/EBP-delta in the mouse mammary gland. In addition, mammary epithelial apoptosis and glandular remodeling occur in sealed glands, confirming a critical role for local factors in mammary involution.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Lactação/metabolismo , Glândulas Mamárias Animais/fisiologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose , Northern Blotting , Proteínas Estimuladoras de Ligação a CCAAT , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Glândulas Mamárias Animais/metabolismo , Camundongos , Camundongos Endogâmicos , Proteínas Nucleares/genética , RNA Mensageiro/biossíntese , Fatores de Transcrição/genética
10.
Br J Cancer ; 78(8): 1102-7, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9792158

RESUMO

Circulating neuron-specific enolase (NSE) and chromogranin A (CgA) were measured in 128 patients with neuroendocrine tumours (NET) to compare their sensitivity and specificity, to investigate factors associated with elevated serum levels and to determine the usefulness of these markers in the follow-up of NET patients. NSE (Cispack NSE, Cis Bio International, Gif-sur-Yvette, France; normal <12.5 microg l(-1)), and chromogranin A (CgA-Riact, Cis Bio International, normal <100 microg l(-1)) were measured in 128 patients without renal insufficiency. There were 99 patients with gastroenteropancreatic (GEP) NET, 19 with medullary thyroid carcinoma and ten with phaeochromocytoma. Fifty-three patients with non-NET were studied as controls. Serum NSE and CgA levels were elevated in 48 (38%) and 76 (59%) of the 128 NET patients respectively. In all groups of NET patients, CgA proved to be more sensitive than NSE. NSE and CgA had a specificity of 73% and 68% respectively. Immunostaining for NSE was positive in three out of eight controls with elevated CgA levels, whereas immunostaining for CgA and synaptophysin was negative in all cases. Elevated CgA levels were significantly associated with two independent parameters, namely the presence of other secretions (P = 0.0001) and a heavy tumour burden (P = 0.001). Elevated NSE levels were exclusively associated with poor tumour differentiation (P = 0.01). Among six patients with NET followed for 11-37 months, CgA appeared to be a better marker of tumour evolution than NSE. We suggest that CgA ought to be the only general marker screened in NET patients.


Assuntos
Biomarcadores Tumorais/sangue , Cromograninas/sangue , Neurônios/química , Fosfopiruvato Hidratase/sangue , Adolescente , Adulto , Idoso , Carcinoma/sangue , Carcinoma Medular/sangue , Cromogranina A , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos , Neoplasias Pancreáticas/sangue , Feocromocitoma/sangue , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue , Neoplasias da Glândula Tireoide/sangue
11.
Br J Cancer ; 78(4): 546-9, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9716042

RESUMO

Adrenocortical carcinoma (ACC) is a rare tumour with a poor prognosis. Cisplatin is the most widely tested cytotoxic agent in this disease. A total of 18 patients with advanced ACC were enrolled. Cytotoxic therapy consisted of etoposide (VP16) (100 mg m(-2) day(-1) on days 1-3) and cisplatin (100 mg m(-2) day(-1) on day 1) every 4 weeks. Mitotane treatment was maintained during chemotherapy in 14 patients. A complete response was observed in three cases and a partial response in three cases, giving an overall response rate of 33%. Tumour response was observed in three of the six patients with progressive disease during treatment with mitotane given at an effective dosage, as shown by serum levels >14 mg l(-1). Toxic effects were as expected and were non-life-threatening; no treatment interruption was required.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Adulto , Idoso , Cisplatino/efeitos adversos , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitotano/uso terapêutico , Resultado do Tratamento
12.
J Cell Physiol ; 174(2): 232-9, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9428809

RESUMO

The CCAAT/enhancer binding proteins (C/EBPs) are a highly conserved family of DNA binding proteins implicated in the transcriptional control of genes involved in cell growth and differentiation in a variety of tissues. The expression of C/EBP-alpha, beta, and delta mRNA in the normal mouse mammary gland was investigated during pregnancy, lactation, and involution via Northern blotting and in situ hybridization. Mammary gland C/EBP-alpha mRNA is detectable at low levels during pregnancy and postlactational involution. C/EBP-beta mRNA levels are elevated during pregnancy, decline slightly in midlactation, and are induced within 48 hours of the onset of involution. C/EBP-delta mRNA content is low throughout pregnancy and lactation, but increases dramatically (>100-fold) within 12 hours after the onset of postlactational involution. In situ hybridization demonstrates that mammary epithelial cells are responsible for the expression of C/EBP-delta mRNA during involution. In contrast to mammary gland, C/EBP-alpha is the predominate isoform expressed in liver with relatively low expression of C/EBP-beta and C/EBP-delta mRNA. Liver C/EBP isoform mRNA levels are unaffected by lactation status. These results demonstrate the tissue-specific regulation of C/EBPs. The pronounced sequential induction of C/EBP-delta and C/EBP-beta during postlactational involution is consistent with a role for C/EBPs in the regulation of mammary epithelial cell apoptosis.


Assuntos
Proteínas de Ligação a DNA/genética , Lactação , Glândulas Mamárias Animais/fisiologia , Proteínas Nucleares/genética , RNA Mensageiro/genética , Animais , Proteínas Estimuladoras de Ligação a CCAAT , Proteínas de Ligação a DNA/biossíntese , Feminino , Hibridização In Situ , Camundongos , Proteínas Nucleares/biossíntese , Gravidez , RNA Mensageiro/biossíntese
14.
Pediatr Med Chir ; 18(3): 279-81, 1996.
Artigo em Italiano | MEDLINE | ID: mdl-8966129

RESUMO

Great changes have occurred in the adolescent behaviour in the last twenty years; this has caused a great increase in the number of the transmitted by sexual intercourse diseases. These, along with the adolescent habits changing, have so widely spread among young people, that one third of the recorded case are actually referred to this group of age. So, a matter of great social interest, which would require a common effort by the adolescents' families, the teachers and by the adolescents themselves, to be faced in the most proper way, has arisen. But the greatest commitment is asked for to the specialized in infectious diseases pediatricians, who are called to state the best strategy to efficaciously fight adolescents' STD. Pediatricians' specific competence and experience can build up the major security to face the prevention and diagnostic matters and their therapy as well.


Assuntos
Comportamento do Adolescente , Comportamento Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Feminino , Humanos , Itália , Masculino , Educação Sexual , Infecções Sexualmente Transmissíveis/etiologia
15.
J Clin Endocrinol Metab ; 81(3): 990-4, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8772562

RESUMO

The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found among ER, PR status, and the presence of serum thyroid antibodies. In conclusion, 1) the present study provides evidence that the overall prevalence of thyroid disorders is increased in patients with breast cancer, and 2) thyroid autoimmune disorders, especially Hashimoto's thyroiditis, account to a large extent for the increased prevalence of thyroid disease in patients with breast cancer. This feature is independent from the ER and PR status of the primary tumor. The present findings call attention to the usefulness of screening for thyroid disease in any patient with breast cancer.


Assuntos
Doenças Autoimunes/complicações , Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/complicações , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Prevalência , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Valores de Referência , Tireoidite Autoimune/complicações , Tireoidite Autoimune/epidemiologia
16.
J Endocrinol Invest ; 19(3): 159-64, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8743281

RESUMO

Several authors have demonstrated the presence of estrogen receptors (ER) and progesterone receptors (PR) in thyroid tissue, generally using dextran coated charcoal method (DCCA). The aim of the study was to measure ER and PR in thyroid specimens using an immunoenzymatic method, and to evaluate the meaning of different prevalence of ER and PR in malignant and benign thyroid disease, as compared with normal thyroid tissue. We have measured ER and PR in thyroid tissue from 28 benign and 20 malignant thyroid lesions, and in 38 samples of surrounding normal thyroid tissues. The sensitivity of ER-EIA and PR-EIA was 1.0 and 1.5 fmol/mg protein, respectively. In thyroid carcinoma the frequency of ER positivity (ER+) was 7/20 (35%); it was significantly higher in the surrounding normal tissue (15/20; 71%) (p = 0.03). In benign thyroid disease, the prevalence of ER+ was 11/28 (39%) and in the surrounding normal tissue it was 11/18 (61%) (p = not significant). PR+ was detected in 7/20 (35%) thyroid cancers and in 15/28 (53%) benign lesions without significant difference with the frequency detected in the surrounding normal tissues. ER and PR concentrations (mean +/- SD) in thyroid cancer was 2.2 +/- 2.2 and 2.2 +/- 2.9 respectively, similarly to that detected in benign thyroid disease and in normal tissue. The simultaneous presence of ER and PR (ER+PR+) was also evaluated. We have found that the frequency of ER+ PR+ was significantly higher in benign lesions (8/28; 28.6%) as compared with malignant samples (1/20; 5%) (p < 0.05); the frequency of ER+PR+ was significantly higher in normal tissue surrounding the malignant lesions (9/20; 45) (p = 0.003). Our data indicate i) EIA method is appropriate to detect ER and PR in thyroid tissue. ii) The frequency of ER+ and ER+PR+ specimens is significantly higher in normal thyroid tissue than in pathologic tissues. This indicates that ER and PR immunoassays may be useful tools to evaluate the normal biological activity of thyroid cells.


Assuntos
Técnicas Imunoenzimáticas , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Glândula Tireoide/química , Neoplasias da Glândula Tireoide/química , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual
17.
J Comp Physiol B ; 166(2): 138-43, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8766911

RESUMO

The effect of dehydration in the presence or absence of continued food intake on renal function was evaluated in chickens. In addition, renal transport of organic anions and cations under these conditions was assessed in vitro by uptake of 14C-para-aminohippuric acid and 14C-tetraethylammonium bromide by renal slices. Water restriction with continued food intake resulted in increases in serum osmolality and serum concentrations of sodium, uric acid, calcium and total protein. If food was restricted in addition to water, only serum osmolality and sodium concentration were significantly increased after 48 hours. Dehydration with continued access to food resulted in marked decreases in extracellular fluid volume, glomerular filtration rate and effective renal plasma flow. If food was restricted during dehydration, the decrease in effective renal plasma flow was attenuated despite reductions in glomerular filtration rate and extracellular fluid comparable to that seen in dehydrated birds allowed free access to food. Transport of organic anions was significantly increased after 24 and 48 hours of water restriction, regardless of whether food was withheld. Enhanced transport of organic anions in the presence of decreased glomerular filtration rate and effective renal plasma flow during dehydration may promote precipitation of urates and nephrosis in chickens.


Assuntos
Galinhas/fisiologia , Desidratação , Privação de Alimentos , Transporte de Íons/fisiologia , Rim/fisiologia , Animais , Análise Química do Sangue , Peso Corporal , Galinhas/metabolismo , Desidratação/metabolismo , Espaço Extracelular , Taxa de Filtração Glomerular/fisiologia , Histocitoquímica , Inulina/farmacocinética , Rim/metabolismo , Testes de Função Renal , Fluxo Plasmático Renal Efetivo/fisiologia , Tetraetilamônio , Compostos de Tetraetilamônio/metabolismo , Ácido p-Aminoipúrico/farmacocinética
18.
Pediatr Med Chir ; 17(6): 567-71, 1995.
Artigo em Italiano | MEDLINE | ID: mdl-8668595

RESUMO

Our experiences at the "Centro di Profilassi Antirabbica" of the "Dipartimento di Pediatria" suggest to us some thoughts: though the seriousness of the lesions is important also for the patient's aestethics, mostly for girls, the physician must always take into consideration the infectious consequences of the bite itself. Among these bacterial infections mostly frequent enough are those overlapping the deepest wounds as the bites of cates are. Therefore adequate early preventive attendances (within the 24 hours) are necessary. The importance of prevention against rabies, luckily very rare in our country, but to be always afraid of and to be always taken into consideration because of its emotional impact, is to be highlighted.


Assuntos
Mordeduras e Picadas , Fatores Etários , Animais , Mordeduras e Picadas/epidemiologia , Mordeduras e Picadas/terapia , Gatos , Criança , Cães , Feminino , Humanos , Masculino , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Estações do Ano , Espanha/epidemiologia , Infecção dos Ferimentos/prevenção & controle
20.
Am J Vet Res ; 54(3): 415-9, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8498745

RESUMO

Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii antigen-containing IgM immune complexes (T gondii-specific IgM-IC) and IgG immune complexes (T gondii-specific IgG-IC) in the serum of cats were developed. Serum from clinically ill, naturally infected cats; healthy, naturally infected cats; and healthy cats experimentally inoculated with T gondii was assayed. All combinations of T gondii-specific IgM, IgG, antigens, IgM-IC, and IgG-IC were detected in naturally infected and experimentally infected cats. Clinically ill cats and cats with ocular signs of toxoplasmosis were more likely than healthy cats to have T gondii-specific IC in serum. It was concluded that T gondii-specific IC form in the serum of cats, may play a role in clinical disease development, and affect the results of T gondii-specific IgM, IgG, and antigen serologic assays.


Assuntos
Anticorpos Antibacterianos/sangue , Complexo Antígeno-Anticorpo/sangue , Antígenos de Bactérias/sangue , Doenças do Gato , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Animais , Gatos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Fatores de Tempo , Toxoplasmose Animal/sangue
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