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1.
Epidemiol Mikrobiol Imunol ; 72(2): 67-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37344219

RESUMO

OBJECTIVES: The aim of this work was to analyze the relationship between new cases of clinical tick-borne encephalitis (TBE) and various meteorological and seasonal predictors. MATERIAL AND METHODS: The modelling is based on national data from the Czech Republic for the period 2001-2016 in daily resolution, namely on average temperatures, average relative air humidity and the number of TBE cases classified according to the date of the first symptoms. Four variants of a negative binomial model from the generalized additive model class are used. The basic model relates the occurrence of TBE to the lagged ambient daily average temperature and daily average relative air humidity and their interaction with the lag reflecting the incubation period and other factors. The lag value was estimated via the optimization procedure based on Akaike information criterion. The model also includes the effect of the season and the effect of the day of the week. To increase the biological plausibility, the basic model has been expanded to account for possible time-varying effects of meteorological variables and to incorporate multiple lags. RESULTS: The most statistically significant effect is the within-year seasonality and then the interaction of the temperature and relative air humidity. The relationship of both meteorological factors and their interactions vary throughout the activities season of the hostquesting Ixodes ricinus. This also changes the conditions of occurrence of the new clinical cases of TBE. The time-varying effect of meteorological factors on the incidence of TBE shows non-trivial changes within a year. In the period before the middle of the calendar year (around the week 22) the effect decreases, then it is followed by an increase until the week 35. CONCLUSION: Flexible models were developed with quantitatively characterized effects of temperature, air humidity and their interaction, with the delay of the effect estimated through the optimization process. Performance of the model with multiple lags was checked using independent data to verify the possibility of using the results to improve the prediction of the risk of clinical cases of TBE uprise.


Assuntos
Encefalite Transmitida por Carrapatos , Ixodes , Animais , Humanos , Encefalite Transmitida por Carrapatos/epidemiologia , Conceitos Meteorológicos , Estações do Ano , República Tcheca/epidemiologia , Incidência
3.
Pediatr Endocrinol Rev ; 11(3): 341-53, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24716402

RESUMO

The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.


Assuntos
Comportamento do Adolescente/psicologia , Desenvolvimento do Adolescente/fisiologia , Estatura/genética , Hormônios/fisiologia , Adolescente , Peso Corporal , Criança , Feminino , Alemanha , Nível de Saúde , Hormônio do Crescimento Humano/fisiologia , Humanos , Hipotálamo , Masculino , Desnutrição , Estado Nutricional , Grupo Associado , Apoio Social , Fatores Socioeconômicos
4.
Radiat Prot Dosimetry ; 145(2-3): 133-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21460366

RESUMO

Two new single-family houses identified as insufficient with regard to existing radon barrier efficiency, have been selected for further examination. A complex set of radon diagnosis procedures has been applied in order to localise and quantify radon entry pathways into the indoor environment. Independent assessment of radon entry rate and air exchange rate has been carried out using the continuous indoor radon measurement and a specific tracer gas application. Simultaneous assessment of these key determining factors has turned out to be absolutely crucial in the context of major cause identification of elevated indoor radon concentration.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Contaminação Radioativa do Ar/prevenção & controle , Modelos Teóricos , Radônio , Habitação , Humanos , Software , Ventilação
5.
Homo ; 62(2): 144-58, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21236425

RESUMO

Possibilities of conducting longitudinal human growth studies are very limited, since it is necessary to monitor the probands for a long time. Another problem can be a loss of data currency, and the small size of the final sample. The solution can be a follow-up semi-longitudinal observation. This research is drawn up as a short longitudinal monitoring of 1925 children (990 boys, 935 girls), aged 6-15 years, at 20 elementary schools in four regions of the Czech Republic, which has been conducted at the same time. Data of repeatedly examined probands of a wide age range were acquired in a short time period. With the help of a linear regression model with mixed effect, the growth velocity curves of 12 somatic traits have been obtained. The timing, intensity and duration of separate growth spurts have been observed, as well as the mutual location of both points of growth velocity, local maxima and minima, and points of the maximal acceleration and deceleration. The results demonstrate that the velocity of characters with variable growth dynamics (skin-fold thicknesses, circumferences of limbs) - contrary to characters with regular growth velocity - have a higher number of partial growth spurts and an opposite course. In the period of separate growth velocity, peaks of somatic characters with regular growth dynamics reach points of partial local minima. In comparison to previous longitudinal studies of body height growth dynamics, the shift of both the beginning and the peak of boys' and girls' pubertal spurt, to a lower age can be found.


Assuntos
Desenvolvimento Infantil , Crescimento , Adolescente , Antropometria , Estatura , Peso Corporal , Criança , República Tcheca , Extremidades , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores Sexuais , Dobras Cutâneas
6.
Rozhl Chir ; 90(10): 543-8, 2011 Oct.
Artigo em Tcheco | MEDLINE | ID: mdl-22324247

RESUMO

INTRODUCTION: Secondary peritonitis is a severe disease with high mortality and morbidity. In the last 20 years the results of treatment of this disease have improved markedly. AIM OF THE STUDY: To determine statistically significant risk factors for mortality in patients with severe secondary peritonitis. MATERIAL AND METHODS: We studied in retrospective analysis the cohort of patients treated at our clinic in the period 2005-2010. 65 patients (38 men and 27 women) with an average age of 60.7 years were included. 27 patients died (41.5%). The average age of the died patients was 72 years. The average value of APACHE II was 20.77, which corresponds to the prediction of lethality 41.8%. The average value of the SOFA score was 11.87. RESULTS: The performed statistical analysis showed age over 65 years, bronchopneumonia, obesity, ischemic heart disease, artificial ventilation over 6 days and circulatory support over 10 days as statistically significant independent factors for mortality. Patients older than 65 years had 8.9 times greater risk of death. In the case of bronchopneumonia was the risk 4.8 times higher. Obesity increased the risk of death 3.1 times and ischemic heart disease 2.4 times. In the case of mechanical ventilation for more than 6 days and circulatory support for more than 10 days, these increased the risk of death 4.1 times respectively 4.3 times. DISCUSSION: The benefit for determining the prognosis secondary peritonitis is the use of scoring systems. It was also shown that the basic clinical data may have the same benefit for predicting the prognosis of patients as a sophisticated scoring systems. CONCLUSION: The performed retrospective analysis age over 65 years, bronchopneumonia, obesity, artificial ventilation and circulatory support as statistically significant independent factors for prediction of poor survival. These basic clinical factors correlated with scoring systems APACHE II a SOFA.


Assuntos
Peritonite/mortalidade , APACHE , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite/etiologia , Peritonite/cirurgia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
7.
Rozhl Chir ; 89(7): 421-6, 2010 Aug.
Artigo em Tcheco | MEDLINE | ID: mdl-20925258

RESUMO

The authors performed a retrospective analysis in a group of consecutively treated patients with upper GIT fistules (ie. fistules with internal orifices in the esophageal, gastric and proximal small intestine region), hospitalized in the Plzen hospital Surgical Clinic Septic Intensive Care Unit, from January 1, 2006 to December 31, 2008. The author assessed the results using statistical methods and he studied any causative relationship between the characteristics of the fistules, the treatment methods and the patients morbidity/mortality rates.


Assuntos
Fístula Esofágica/cirurgia , Fístula Gástrica/cirurgia , Fístula Intestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Rozhl Chir ; 87(2): 65-7, 2008 Feb.
Artigo em Tcheco | MEDLINE | ID: mdl-18380156

RESUMO

The authors present a case review of a 30-year old patient, who developed central pleural effusion, a complication related to central venous catheterization and the consequent use of the central venous line. The authors aim to highlight potential complications of the method. The interesting feature of this case is the fact, that no apparent mistakes in the venous line introduction or its later use have been recorded.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Derrame Pleural/etiologia , Adulto , Humanos , Masculino
9.
Radiat Prot Dosimetry ; 130(1): 43-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18440962

RESUMO

To subserve the institutional research and tasks coming out from the Czech National Radon Programme, a new QA programme to calibrate all the known types of devices that measure radon and its short-lived progeny was developed at the Department of Radon mobile group of the National Radiation Protection Institute (NRPI) at Prague. The programme also included calibration of instruments measuring a unique quantity of unattached and attached fractions of short- lived radon progeny Generally, NRPI declares estimation of radon concentration during all routine calibration measurements with an overall uncertainty <5% (one sigma) and of equilibrium-equivalent radon concentration with an overall uncertainty <10% (one sigma). The results of the comparative measurements of the unattached and attached fractions of each short-lived radon progeny carried out with a comparing continuous monitor Fritra 4 in the German reference radon chamber at PTB Braunschweig indicated an acceptable level of agreement, up to 10%.


Assuntos
Programas Governamentais/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Monitoramento de Radiação/instrumentação , Monitoramento de Radiação/normas , Proteção Radiológica/instrumentação , Proteção Radiológica/normas , Radônio/análise , República Tcheca , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Toxicol In Vitro ; 21(7): 1268-75, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17945463

RESUMO

The efficacy of sunscreen products has been recognized as an important public health issue. Adequate methods for assessment of the level of protection should be developed and standardised. While the SPF COLIPA testing method in vivo has been used for years, preference should be given to in vitro testing methods as in vivo methods raise ethical concern. The present study aims to assess possible in vitro approaches based on diffuse transmission spectroscopy, published previously by Diffey, and two methods based on measurements of UVB transmission through a defined layer of a sunscreen product applied on various UV-transparent substrates. The attenuated UVB intensity, using different UV light sources, is detected radiometrically and transformed to real SPF value by means of a calibration curve, which is based on an extensive number of measurements performed using both in vivo and in vitro method The outcome of the three in vitro methods employed in the study showed great differences in the obtained SPF values in comparison with reference SPF determined by means of the COLIPA method in vivo. The high variability of in vitro results suggests that main attention should be focused on substrate selection simulating the human skin surface and homogenous product application. The in vitro screening methods may represent a fast and reasonable tool reducing the number of in vivo experiments and risks related to UV exposure of human subjects, when the technical test parameters are adjusted and optimized.


Assuntos
Proteção Radiológica , Análise Espectral/métodos , Protetores Solares/farmacologia , Raios Ultravioleta , Adolescente , Adulto , Calibragem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Queimadura Solar/prevenção & controle
11.
Econ Hum Biol ; 5(3): 409-25, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17766203

RESUMO

The Czech Republic has undergone rapid political, social, and economic transformation since the late 1980s. While obesity rates among children and adolescents in the Czech Republic have been previously relatively low, this has changed in recent years. Across the past 50 years, body weight, body mass index (BMI)-for-age, and adiposity rebound (AR) (the time when a child reaches the lowest BMI before their BMI gradually begins to increase until adulthood) occurs earlier. The most dramatic changes have been observed among school-aged children, where BMI values have increased at the 50th, 90th, and 97th percentiles. In contrast, adolescent girls appear to be thinner than in the past. The analyses of weight-for-height percentiles indicated that the 50th percentile of the body weight among boys and girls remained similar in nearly all age categories across the past 50 years. Although the growth pattern of children at the 50th percentile has not changed, the 10th and 90th percentiles have expanded. Our findings suggest that the secular trend of increased height, accelerated growth, and earlier maturation is responsible for Czech children experiencing adiposity rebound at earlier ages compared to the past.


Assuntos
Adiposidade , Estatura , Índice de Massa Corporal , Peso Corporal , Estado Nutricional , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Imagem Corporal , Criança , Pré-Escolar , República Tcheca , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Atividade Motora , Apoio Nutricional , Percepção , Prevalência , Fatores de Tempo
12.
Econ Hum Biol ; 4(2): 237-52, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16371255

RESUMO

The trend of increasing height can be interpreted as a reflection of the unfolding progress of civilization. Height changes among children and adolescents are good markers of this trend. We analyze the secular trend in the heights of children and adolescents in the Czech Republic on the basis of data from anthropological surveys. The earliest height data pertain to Czech youths who attended the Military Schools in Austria in 1800-1809. Data also exist for 1895 and continue in 1951 and at 10-year intervals thereafter. Growth curves were obtained for separate age groups by fitting mean values via third-order polynomial smoothing splines. Between 1951 and 2001, the mean heights of boys and girls aged 2.5 years increased by 2.7 and 3 cm, respectively. Since 1895, the mean height of 13-year-old boys has increased by 19.4 cm, and the mean height of girls has increased by 18.3 cm.


Assuntos
Antropologia Física/história , Estatura , Adolescente , Criança , República Tcheca , Coleta de Dados , Feminino , História do Século XIX , História do Século XX , Humanos , Masculino
13.
Placenta ; 27(8): 799-811, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16229888

RESUMO

The human neonatal Fcgamma-receptor (hFcRn) involved in overall maternal-fetal IgG transmission is expressed in placental villous syncytiotrophoblast. However, the role of hFcRn in IgG transport and trafficking across this cell layer is poorly characterized. To gain insight into this mechanism we have overexpressed functional hFcRn in trophoblast-derived BeWo cells (BeWo/hFcRn cells) [Ellinger I, Reischer H, Lehner C, Leitner K, Hunziker W, Fuchs R. Placenta 2005;26:171-82] since parental BeWo cells endogenously express low levels of the receptor. We now demonstrate that hFcRn overexpression differentially affected apical-to-basolateral transcytosis and apical recycling: whereas IgG transcytosis was reduced by 35%, IgG recycling was stimulated by 100% as compared to parental cells, indicating that hFcRn plays a role in both processes. The endosomal compartments involved in hFcRn/IgG transport after apical IgG internalization were then analyzed by confocal immunofluorescence microscopy using compartment specific markers. hFcRn/IgG were found in apical early endosomes, in transferrin recycling compartments and in vesicles near the basolateral plasma membrane, presumably transcytotic vesicles. Neither hFcRn nor IgG was routed to the degradative pathway to lysosomes. These transport and localization data are in accordance with efficient hFcRn-mediated apical IgG recycling and basolateral directed IgG transcytosis in placental trophoblasts.


Assuntos
Imunoglobulina G/metabolismo , Receptores de IgG/fisiologia , Trofoblastos/ultraestrutura , Membrana Celular/química , Núcleo Celular/química , Células Cultivadas , Retículo Endoplasmático/química , Retículo Endoplasmático/metabolismo , Endossomos/metabolismo , Feminino , Humanos , Imunoglobulina G/análise , Lisossomos/metabolismo , Microscopia Confocal , Placenta/citologia , Placenta/metabolismo , Transporte Proteico , Receptores de IgG/análise , Receptores de IgG/genética , Trofoblastos/metabolismo
14.
Zentralbl Chir ; 130(2): 128-31, 2005 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-15849656

RESUMO

AIM: Evaluating the importance of intraabdominal pressure measurement in cases of severe acute pancreatitis and its use in determining indication for surgery. METHODS: A retrospective evaluation of the treatment of patients with severe acute pancreatitis hospitalised at the Department of Surgery or the Department of Anaesthesiology and Resuscitation of the Charles University hospital in Pilsen during the last two years (from January 1 (st), 2002 to December 31 (st), 2003) was performed. RESULTS: During this period, 63 patients with severe acute pancreatitis were hospitalised at both departments, among which 18 patients underwent an operation (28.6 %), eight of them died (12.7 %). In four of the 18 patients who underwent an operation the surgery was indicated due to progression of abdominal compartment syndrome (ACS) and all of these patients survived. CONCLUSIONS: At present, basic treatment of severe acute pancreatitis is considered to be conservative. The only generally accepted indication for surgery is an established infection of the necrotic tissue. In our presentation, we draw attention to those cases where the general condition of the patient deteriorates combined with a progression of ACS and where a decompressive laparotomy can improve the prognosis of the disease.


Assuntos
Abdome , Síndromes Compartimentais/etiologia , Descompressão Cirúrgica , Pancreatite/diagnóstico , Pancreatite/cirurgia , Abdome/fisiopatologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Drenagem , Feminino , Seguimentos , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Pancreatite/mortalidade , Pancreatite/terapia , Pressão/efeitos adversos , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
15.
Toxicol In Vitro ; 17(5-6): 791-6, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14599479

RESUMO

We have introduced the 3T3 NRU cytotoxicity test for methodological, economical and ethical reasons as a regular part of tier pre-marketing testing to assess local tolerance of raw materials for cosmetics, household chemicals and final cosmetic products. Using the 3T3 cell line according to the standard INVITTOX protocol No.64 (NRU Assay) the borderline concentration, relevant to the highest tolerated dose, is determined for each material. The toxic effect is reached at different concentration levels specific for individual cosmetics categories, depending on their chemical characteristics. Typical ranges of cytotoxicity for specific categories of cosmetics were established after testing of hundreds of materials. The range lies between 1 microg/ml (anti-dandruff shampoos), up to 2000 microg/ml (toothpastes and mouthwashes). The 3T3 NRU cytotoxicity test is a sensitive tool able to identify more aggressive products, that are also more likely to evoke irritation in human skin. It was even possible to detect protective effects of one natural herbal ingredient. The comparative study of cytotoxicity test results and human patch test results from a group of essential oils is presented. Cytotoxicity tests represent a highly ethical approach for estimation of irritancy. On the basis of in vitro test results suggesting low risk we can proceed to confirmatory tests in human volunteers.


Assuntos
Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Cosméticos/toxicidade , Fibroblastos/efeitos dos fármacos , Irritantes/toxicidade , Testes de Toxicidade/métodos , Células 3T3 , Animais , Sobrevivência Celular/efeitos dos fármacos , Qualidade de Produtos para o Consumidor/normas , Cosméticos/classificação , República Tcheca , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Humanos , Indicadores e Reagentes/metabolismo , Irritantes/classificação , Camundongos , Vermelho Neutro/metabolismo , Testes do Emplastro
16.
Cell Biol Toxicol ; 19(2): 107-19, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12776928

RESUMO

In this study we test the hypothesis that immortalized adult rat Sertoli cells respond to known testicular toxins in a similar manner to Sertoli cells tested in vivo and in primary culture. This cell line was developed by immortalizing adult rat Sertoli cells with the temperature-sensitive mutant of SV40, ts255, such that the cells proliferate at the permissive temperature of 33 degrees C but express differentiated characteristics at the nonpermissive temperature of 40 degrees C. Confluent monolayers, grown at 33 degrees C or 40 degrees C, were exposed to a range of concentrations of dinitrobenzene (DNB) or dinitrotoluene (DNT) isomers or to cadmium chloride. Cellular response was assessed by neutral-red cell viability assay and ultrastructural changes. Cells grown at 40 degrees C were sensitive to lower concentrations of each toxicant than were cells grown at 33 degrees C. 1,2-DNB was more toxic than 1,3-DNB, and 3,4-DNT was more toxic than 2,4-DNT, as judged by the neutral-red cell viability assay. Ultrastructurally, cells treated with 1,2-DNB or 2,4-DNT showed increased numbers of autophagic vesicles compared to controls. Intercellular penetration of ruthenium red demonstrated breached tight junctions in 1,2-DNB and cadmium-treated cells. From these observations, we conclude that this cell line can serve as a model for studying toxic mechanisms in adult Sertoli cells.


Assuntos
Cloreto de Cádmio/toxicidade , Dinitrobenzenos/toxicidade , Células de Sertoli/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Viral , Masculino , Microscopia Eletrônica , Ratos , Células de Sertoli/ultraestrutura , Vírus 40 dos Símios/genética , Temperatura
17.
Horm Res ; 58(2): 71-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12207165

RESUMO

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.


Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Crescimento/efeitos dos fármacos , Antropometria , Estatura/efeitos dos fármacos , Criança , Feminino , Transtornos do Crescimento/etiologia , Hormônio do Crescimento Humano/deficiência , Humanos , Perna (Membro)/anatomia & histologia , Perna (Membro)/crescimento & desenvolvimento , Masculino , Modelos Biológicos , Valor Preditivo dos Testes , Análise de Regressão , Caracteres Sexuais , Fatores de Tempo
18.
Traffic ; 2(10): 727-36, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11576449

RESUMO

Many viruses gain access to the cell via the endosomal route and require low endosomal pH for infectivity. The GTPase dynamin is essential for clathrin-dependent endocytosis, and in HeLa cells overexpressing the nonfunctional dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a human minor group rhinovirus, is internalized by members of the low-density lipoprotein receptor family in a clathrin-independent manner. The low endosomal pH then leads to conversion of the capsid to C-antigen, which is required for release (uncoating) and transfer of the viral RNA into the cytosol and de novo synthesis of infectious virus. We here demonstrate that overexpression of dynaminK44A reduces this antigenic conversion and results in diminished viral synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence, HRV2 uncoating is diminished early after internalization but attains control levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in addition to trafficking defects, results in an elevated endosomal pH and thereby affects virus infection and most likely endosomal sorting and processing.


Assuntos
Endossomos/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Células HeLa/metabolismo , Células HeLa/virologia , Rhinovirus/patogenicidade , Sítios de Ligação/fisiologia , Dinaminas , Imunofluorescência/métodos , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Mutação Puntual/genética , Mutação Puntual/fisiologia , Infecções por Vírus de RNA/metabolismo , Rhinovirus/metabolismo , Regulação para Cima/genética , Regulação para Cima/fisiologia
19.
Environ Health Perspect ; 109(1): 41-5, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11171523

RESUMO

We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals.


Assuntos
Carcinógenos Ambientais/efeitos adversos , Aberrações Cromossômicas , Transtornos Cromossômicos , Neoplasias/etiologia , Exposição Ocupacional , Radônio/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Citogenética , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , Medição de Risco
20.
Cell Stress Chaperones ; 6(4): 306-15, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11795467

RESUMO

Fever has been associated with shortened duration and improved survival in infectious disease. The mechanism of this beneficial response is still poorly understood. The heat-inducible 70-kDa heat shock protein (Hsp70) has been associated with protection of leukocytes against the cytotoxicity of inflammatory mediators and with improved survival of severe infections. This study characterizes the induction of Hsp70 by feverlike temperatures in human leukocytes in vitro and in vivo. Using flow cytometry, Hsp70 expression was determined in whole blood samples. This approach eliminated cell isolation procedures that would greatly affect the results. Heat treatment of whole blood in vitro for 2 hours at different temperatures revealed that Hsp70 expression depends on temperature and cell type; up to 41 degrees C, Hsp70 increased only slightly in lymphocytes and polymorphonuclear leukocytes. However, in monocytes a strong induction was already seen at 39 degrees C, and Hsp70 levels at 41 degrees C were 10-fold higher than in the 37 degrees C control. To be as close as possible to the physiological situation during fever, we immersed healthy volunteers in a hot water bath, inducing whole body hyperthermia (39 degrees C), and measured leukocyte Hsp70 expression. Hsp70 was induced in all leukocytes with comparable but less pronounced cell type-specific variations as observed in vitro. Thus, a systemic increase of body temperature as triggered by fever stimulates Hsp70 expression in peripheral leukocytes, especially in monocytes. This fever-induced Hsp70 expression may protect monocytes when confronted with cytotoxic inflammatory mediators, thereby improving the course of the disease.


Assuntos
Febre/metabolismo , Proteínas de Choque Térmico HSP70/biossíntese , Resposta ao Choque Térmico , Leucócitos/metabolismo , Adulto , Células Cultivadas , Estudos Cross-Over , Feminino , Proteínas de Choque Térmico HSP70/sangue , Temperatura Alta , Humanos , Imersão , Leucócitos Mononucleares/metabolismo , Linfócitos/metabolismo , Masculino , Monócitos/metabolismo , Temperatura , Fatores de Tempo
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