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1.
EMBO J ; 37(3): 321-336, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29311115

RESUMO

In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells. In contrast, we show that TRAK2-mediated retrograde mitochondrial transport is Miro1-dependent. Interestingly, we find that Miro is critical for recruiting and stabilising the mitochondrial myosin Myo19 on the mitochondria for coupling mitochondria to the actin cytoskeleton. Moreover, Miro depletion during PINK1/Parkin-dependent mitophagy can also drive a loss of mitochondrial Myo19 upon mitochondrial damage. Finally, aberrant positioning of mitochondria in Miro1/2 double-knockout cells leads to disruption of correct mitochondrial segregation during mitosis. Thus, Miro proteins can fine-tune actin- and tubulin-dependent mitochondrial motility and positioning, to regulate key cellular functions such as cell proliferation.


Assuntos
Dineínas/metabolismo , Cinesinas/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Miosinas/metabolismo , Proteínas rho de Ligação ao GTP/genética , Actinas/metabolismo , Proteínas Adaptadoras de Transporte Vesicular , Animais , Transporte Biológico , Proteínas de Transporte/metabolismo , Linhagem Celular Transformada , Proliferação de Células/genética , Desenvolvimento Embrionário/genética , Camundongos , Camundongos Knockout , Microtúbulos/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
2.
J Biol Chem ; 291(2): 613-29, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26553875

RESUMO

The DISC1 protein is implicated in major mental illnesses including schizophrenia, depression, bipolar disorder, and autism. Aberrant mitochondrial dynamics are also associated with major mental illness. DISC1 plays a role in mitochondrial transport in neuronal axons, but its effects in dendrites have yet to be studied. Further, the mechanisms of this regulation and its role in neuronal development and brain function are poorly understood. Here we have demonstrated that DISC1 couples to the mitochondrial transport and fusion machinery via interaction with the outer mitochondrial membrane GTPase proteins Miro1 and Miro2, the TRAK1 and TRAK2 mitochondrial trafficking adaptors, and the mitochondrial fusion proteins (mitofusins). Using live cell imaging, we show that disruption of the DISC1-Miro-TRAK complex inhibits mitochondrial transport in neurons. We also show that the fusion protein generated from the originally described DISC1 translocation (DISC1-Boymaw) localizes to the mitochondria, where it similarly disrupts mitochondrial dynamics. We also show by super resolution microscopy that DISC1 is localized to endoplasmic reticulum contact sites and that the DISC1-Boymaw fusion protein decreases the endoplasmic reticulum-mitochondria contact area. Moreover, disruption of mitochondrial dynamics by targeting the DISC1-Miro-TRAK complex or upon expression of the DISC1-Boymaw fusion protein impairs the correct development of neuronal dendrites. Thus, DISC1 acts as an important regulator of mitochondrial dynamics in both axons and dendrites to mediate the transport, fusion, and cross-talk of these organelles, and pathological DISC1 isoforms disrupt this critical function leading to abnormal neuronal development.


Assuntos
Dendritos/metabolismo , Dinâmica Mitocondrial , Morfogênese , Proteínas do Tecido Nervoso/metabolismo , Animais , Axônios/metabolismo , Transporte Biológico , Células COS , Chlorocebus aethiops , Retículo Endoplasmático/metabolismo , Humanos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas do Tecido Nervoso/química , Ligação Proteica , RNA Longo não Codificante , Proteínas Recombinantes de Fusão/metabolismo , Esquizofrenia/metabolismo , Relação Estrutura-Atividade
3.
J Neurochem ; 136(2): 388-402, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26509433

RESUMO

Impairment of the autophagy-lysosome pathway is implicated with the changes in α-synuclein and mitochondrial dysfunction observed in Parkinson's disease (PD). Damaged mitochondria accumulate PINK1, which then recruits parkin, resulting in ubiquitination of mitochondrial proteins. These can then be bound by the autophagic proteins p62/SQSTM1 and LC3, resulting in degradation of mitochondria by mitophagy. Mutations in PINK1 and parkin genes are a cause of familial PD. We found a significant increase in the expression of p62/SQSTM1 mRNA and protein following mitophagy induction in human neuroblastoma SH-SY5Y cells. p62 protein not only accumulated on mitochondria, but was also greatly increased in the cytosol. Increased p62/SQSMT1 expression was prevented in PINK1 knock-down cells, suggesting increased p62 expression was a consequence of mitophagy induction. The transcription factors Nrf2 and TFEB, which play roles in mitochondrial and lysosomal biogenesis, respectively, can regulate p62/SQSMT1. We report that both Nrf2 and TFEB translocate to the nucleus following mitophagy induction and that the increase in p62 mRNA levels was significantly impaired in cells with Nrf2 or TFEB knockdown. TFEB translocation also increased expression of itself and lysosomal proteins such as glucocerebrosidase and cathepsin D following mitophagy induction. We also report that cells with increased TFEB protein have significantly higher PGC-1α mRNA levels, a regulator of mitochondrial biogenesis, resulting in increased mitochondrial content. Our data suggests that TFEB is activated following mitophagy to maintain autophagy-lysosome pathway and mitochondrial biogenesis. Therefore, strategies to increase TFEB may improve both the clearance of α-synuclein and mitochondrial dysfunction in PD. Damaged mitochondria are degraded by the autophagy-lysosome pathway and is termed mitophagy. Following mitophagy induction, the transcription factors Nrf2 and TFEB translocate to the nucleus, inducing the transcription of genes encoding for autophagic proteins such as p62, as well as lysosomal and mitochondrial proteins. We propose that these events maintain autophagic flux, replenish lysosomes and replace mitochondria.


Assuntos
Lisossomos/metabolismo , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Mitofagia/genética , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Linhagem Celular Tumoral , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Lisossomos/efeitos dos fármacos , Proteínas de Membrana Transportadoras/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Neuroblastoma/patologia , Neuroblastoma/ultraestrutura , Ionóforos de Próton/farmacologia , RNA Interferente Pequeno/farmacologia , Receptores de Superfície Celular/metabolismo , Proteína Sequestossoma-1 , Fatores de Tempo , Transfecção , Tubulina (Proteína)/metabolismo
4.
Coll Antropol ; 36 Suppl 1: 139-46, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338763

RESUMO

The aim of this study was to determine socio economic, health status, nutritional and behavioral differences in obese, overweight and normal weight children attending first grade elementary school. In overweight group there is 13.8% of boys and 12.6% of girls, in obese group 8.3% of boys and 6.9% of girls. In factor analysis 12 factors was excluded with cumulative loading of 60% variability. Discriminant analysis was performed with 12 factors as predictive variables and discriminant variables were three BMI groups: normal weight, overweight and obese. Function 1 discriminate well normal weight group from overweight and obese group. Overweight and obese groups is described with lower number of children in the family and lower order of birth, higher education of parents, they eat less vegetables and fruits, spend more time playing computer games, have less physical activity, drink more alcohol with their meals, exactly opposite to normal weight group.


Assuntos
Comportamento Infantil , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Criança , Análise Discriminante , Análise Fatorial , Feminino , Humanos , Masculino
5.
Coll Antropol ; 36 Suppl 1: 9-13, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338741

RESUMO

Croatia has a long tradition of non-communicable disease prevention, but also obstacles to the implementation of preventive programs related to the general attenuation of public health and primary health care sector. The aim of this study was to determine trends in behavioral and biomedical risk factors and evaluate primary non-communicable disease and cardiovascular prevention. Physical inactivity was a leading risk factor with increasing trend and prevalence of 33.9% and 38.9% in men and women in 2008. In 2008, obesity was present in 26.1% and 34.1%, and hypertension in 65.8% and 59.7% of men and women. During the follow-up only smoking and alcohol consumption in men decreased significantly, while alcohol consumption and obesity in women, and hypertension in both sexes significantly increased. In the present situation, with the existing trends and environment it will not be possible to stop negative trends. Revitalization of public health activities and primary health care is essential.


Assuntos
Doenças Cardiovasculares/epidemiologia , Adulto , Idoso , Estudos de Coortes , Croácia/epidemiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
6.
Coll Antropol ; 36 Suppl 1: 71-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338750

RESUMO

The objective of this paper was to evaluate the 5-year incidence of obesity on a sample of 3229 adults and investigate the potential effect of several sociodemographic and lifestyle habits on weight change and obesity incidence in these individuals. The average annual rate of increase in the prevalence of obese adults between 2003 and 2008 was 10.60% for men and 11.08% for women. Analysis showed that development of obesity in 5-year period in women in Croatia is significantly positively associated with frequent consumption of "hidden" fats of animal origin and significantly negative with each higher education level. No significant predictor of obesity has been found in men. Obesity remains a serious health problem for the Croatian population; the alarming rates of excess body weight continue to increase. Preventive measures should urgently be undertaken.


Assuntos
Obesidade/epidemiologia , Adulto , Estudos de Coortes , Croácia/epidemiologia , Feminino , Humanos , Incidência , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos
7.
Coll Antropol ; 36 Suppl 1: 77-81, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338751

RESUMO

Generalised obesity is increasing in prevalence globally, however trends in abdominal obesity are less well known. In 2003, 1,999 women of childbearing age participated in the Croatian Adult Health Survey, of whom 598 (29.9%) participated in the second cycle in 2008. For 2008, the prevalence of abdominal obesity using the International Diabetes Federation (IDF) criterion (waist circumference > or = 80 cm) was estimated at 70.3% (95% CI 61.8% to 75.7%), whereas the prevalence of abdominal obesity using the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) criterion (waist circumference > or = 88 cm) was estimated at 48.6% (42.6% to 54.7%). The preceding five-year cumulative incidence was 54.3% (44.5% to 64.2%) and 35.2% (28.0% to 42.4%) using the IDF and NCEP ATP III criteria, respectively. The burden of abdominal obesity is high and rapidly increasing in Croatian women of childbearing age, the key population subgroup for obesity control.


Assuntos
Obesidade Abdominal/epidemiologia , Adulto , Croácia/epidemiologia , Humanos , Incidência , Prevalência
8.
Coll Antropol ; 36 Suppl 1: 113-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338758

RESUMO

The aim of this study was to examine the association of weight gain and life expectancy at birth in Croatia. Mean body mass index was based on the data from the Croatian Adult Health Survey 2003. Birth rate and mortality data needed for life expectancy calculation were supplied by the Central Bureau of Statistics. The results suggest that the increase in mean body mass index value (1.31 kg m(-2) for women and 1.41 kg m(-2) for men) will shorten life expectancy at birth for one year. Obesity, if unchecked, might have a negative effect on life expectancy in Croatia. Despite widespread knowledge about how to reduce the severity of the problem, observed trends in obesity in Croatia continue to worsen. These trends threaten to diminish the health and life expectancy of current and future generations.


Assuntos
Longevidade , Obesidade/epidemiologia , Croácia/epidemiologia , Feminino , Humanos , Masculino , Obesidade/fisiopatologia , Aumento de Peso
9.
Coll Antropol ; 36 Suppl 1: 117-23, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22338759

RESUMO

The aim of this study was to examine the social conditioning of health behaviors of adults in Croatia, based on the data from Croatian Adult Health Survey 2003. This cross-sectional study on a representative random sample of 9070 Croatian adults showed that obesity was significantly and socially conditioned in women, whereas for men the indication of social conditioning has not reached a statistically significant level. Health behaviors were socially conditioned in both sexes. Men's living habits were more irregular than those of women. Compared with women, men consumed more cured meat products, consumed alcohol excessivelly and smoked cigarettes more often, whereas they ate less fruits and vegetables. Health promotion strategies based on the behavioral correlates of overweight and obesity are needed to prevent excess weight gain in the Croatian population. While for men a unique educational model is applicable, women require more specialized programs, adapted to their social background.


Assuntos
Comportamentos Relacionados com a Saúde , Comportamento Social , Adolescente , Adulto , Idoso , Estudos de Coortes , Croácia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Lijec Vjesn ; 133(7-8): 284-7, 2011.
Artigo em Hr | MEDLINE | ID: mdl-22165197

RESUMO

Some studies indicate that visceral obesity may be a better predictor of morbidity and mortality related to cardiovascular diseases and type 2 diabetes than general obesity measured by the body mass index. A causal relationship seems to exist between the accumulation of visceral fat and occurence of cardiovascular diseases and type 2 diabetes. Assessment of cardiometabolic risk comprises information on intra-abdominal obesity, as well as traditional risk factors. Visceral fat acts as a large endocrine gland, excreting cytokines and adipokines which leads to insulin resistance and proinflammatory state, whereas subcutaneous fat may act as a protective metabolic sink. Of anthropometric measures, waist circumference seems to best correlate with visceral fat.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Obesidade Abdominal/complicações , Humanos , Fatores de Risco
11.
Acta Dermatovenerol Croat ; 28(2): 102-104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32876035

RESUMO

Certain regions of Bosnia and Herzegovina were prominent European sites of endemic syphilis. In 1934 and 1935 the School of Public Health in Zagreb, later the Andrija Stampar School of Public Health, conducted two surveys on endemic syphilis in Bosnia and Herzegovina. The surveys were well-described in the monograph published in 1939 by the School, under the title Endemic Syphilis in Bosnia: Survey by the School of Public Health in Zagreb ("Endemski sifilis u Bosni anketa Skole narodnog zdravlja u Zagrebu"). This paper provides a description of the publication for the first time, presents the most important data from it, and explores its significance from the historical perspective.


Assuntos
Doenças Endêmicas/história , Faculdades de Saúde Pública/história , Sífilis/história , Aniversários e Eventos Especiais , Bósnia e Herzegóvina/epidemiologia , História do Século XX , Humanos , Saúde Pública/história , Inquéritos e Questionários , Sífilis/epidemiologia
12.
Autophagy ; 16(3): 391-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31142229

RESUMO

Adaptor protein (AP) complexes mediate key sorting decisions in the cell through selective incorporation of transmembrane proteins into vesicles. Little is known of the roles of AP-4, despite its loss of function leading to a severe early onset neurological disorder, AP-4 deficiency syndrome. Here we demonstrate an AP-4 epsilon subunit knockout mouse model that recapitulates characteristic neuroanatomical phenotypes of AP-4 deficiency patients. We show that ATG9A, critical for autophagosome biogenesis, is an AP-4 cargo, which is retained within the trans-Golgi network (TGN) in vivo and in culture when AP-4 function is lost. TGN retention results in depletion of axonal ATG9A, leading to defective autophagosome generation and aberrant expansions of the distal axon. The reduction in the capacity to generate axonal autophagosomes leads to defective axonal extension and de novo generation of distal axonal swellings containing accumulated ER, underlying the impaired axonal integrity in AP-4 deficiency syndrome.Abbreviations: AP: adaptor protein; AP4B1: adaptor-related protein complex AP-4, beta 1; AP4E1: adaptor-related protein complex AP-4, epsilon 1; ATG: autophagy-related; EBSS: Earle's balanced salt solution; ER: endoplasmic reticulum; GFAP: glial fibrillary acidic protein; GOLGA1/Golgin-97/GOLG97: golgi autoantigen, golgin subfamily a, 1; GOLGA2/GM130: golgi autoantigen, golgin subfamily a, 2; HSP: hereditary spastic paraplegia; LC3/MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAP2: microtubule-associated protein 2; MAPK8IP1/JIP1: mitogen-acitvated protein kinase 8 interacting protein 1; NEFH/NF200: neurofilament, heavy polypeptide; RBFOX3/NeuN (RNA binding protein, fox-1 homolog [C. elegans] 3); SQSTM1/p62: sequestosome 1; TGN: trans-Golgi network; WIPI2: WD repeat domain, phosphoinositide interacting protein 2.


Assuntos
Complexo 4 de Proteínas Adaptadoras/metabolismo , Autofagossomos/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Axônios/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico , Síndrome , Rede trans-Golgi/metabolismo
13.
Coll Antropol ; 33 Suppl 1: 11-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19563140

RESUMO

The objective of this study was to investigate regional gradient of a synthetic cardiovascular burden (CVRB) in Croatia. Analysis was based on a multistage stratified sample representative of general adult population in six regions of Croatia (Croatian Adult Health Survey). Synthetic CVRB was defined by incidents (heart attack, stroke), blood pressure, overweight/obesity (BMI, waist circumference), and risky behaviours (smoking, physical inactivity, high alcohol consumption, inadequate nutrition). Total CVRB in Croatia was 44.7% for men and 50.3% for women. Combining both high and moderate CVRB, men were found to be under more risk than women (72.8% vs. 61.7%, respectively). The result showed an east-north-west gradient in continental Croatia, with high CVRB in Eastern (40.2%) and Central region (44.3%), City of Zagreb (45.7%) and Northern region (53.1%). Mountainous region had the lowest prevalence of respondents with high CVRB (39.2%). Coastal region with the prevalence of 46.3% of high CVRB was nearly the same as the City of Zagreb. The results suggest the presence of substantial regional differences in the cardiovascular risk burden.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Adolescente , Adulto , Distribuição por Idade , Idoso , Croácia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Características de Residência , Risco , Distribuição por Sexo , Fatores Socioeconômicos
14.
Nat Commun ; 10(1): 4399, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562315

RESUMO

Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and Endoplasmic Reticulum-Mitochondria Contacts Sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.


Assuntos
Retículo Endoplasmático/metabolismo , Fibroblastos/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Sítios de Ligação , Transporte Biológico , Células Cultivadas , Embrião de Mamíferos/citologia , Retículo Endoplasmático/ultraestrutura , Fibroblastos/citologia , Células HeLa , Humanos , Camundongos Knockout , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Membranas Mitocondriais/ultraestrutura , Proteínas Mitocondriais/genética , Ligação Proteica , Ratos , Proteínas rho de Ligação ao GTP/genética
15.
Eur J Hum Genet ; 16(9): 1097-102, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18322453

RESUMO

The human population is undergoing a major transition from a historical metapopulation structure of relatively isolated small communities to an outbred structure. This process is predicted to increase average individual genome-wide heterozygosity (h) and could have effects on health. We attempted to quantify this increase in mean h. We initially sampled 1001 examinees from a metapopulation of nine isolated villages on five Dalmatian islands (Croatia). Village populations had high levels of genetic differentiation, endogamy and consanguinity. We then selected 166 individuals with highly specific personal genetic histories to form six subsamples, which could be ranked a priori by their predicted level of outbreeding. The measure h was then estimated in the 166 examinees by genotyping 1184 STR/indel markers and using two different computation methods. Compared to the value of mean h in the least outbred sample, values of h in the remaining samples increased successively with predicted outbreeding by 0.023, 0.038, 0.058, 0.067 and 0.079 (P<0.0001), where these values are measured on the same scale as the inbreeding coefficient (but opposite sign). We have shown that urbanisation was associated with an average increase in h of up to 0.08-0.10 in this Croatian metapopulation, regardless of the method used. Similar levels of differentiation have been described in many populations. Therefore, changes in the level of heterozygosity across the genome of this magnitude may be common during isolate break-up in humans and could have significant health effects through the established genetic mechanism of hybrid vigour/heterosis.


Assuntos
Triagem de Portadores Genéticos , Urbanização , Consanguinidade , Croácia , Marcadores Genéticos , Variação Genética , Genética Populacional , Humanos , População Rural , População Urbana
16.
Croat Med J ; 49(5): 625-35, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18925696

RESUMO

AIM: To define prognostic significance of B-cell differentiation genes encoding proteins and BCL2 and BCL6 gene abnormalities in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. METHODS: In 53 patients with diffuse large B-cell lymphoma and 20 patients with follicular lymphoma grade 3 with >75% follicular growth pattern the following was performed: 1) determination of protein expression of BCL6, CD10, MUM1/IRF4, CD138, and BCL2 by immunohistochemistry; 2) subclassification into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) groups according to the results of protein expression; 3) detection of t(14;18)(q32;q21)/IgH-BCL2 and BCL6 abnormalities by fluorescent in situ hybridization in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern as well as in GCB and ABC groups; and 4) assessment of the influence of the analyzed characteristics and clinical prognostic factors on overall survival. RESULTS: Only BCL6 expression was more frequently found in follicular lymphoma grade 3 with >75% follicular growth pattern than in diffuse large B-cell lymphoma (P=0.030). There were no differences in BCL2 and BCL6 gene abnormalities between diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients were equally distributed in GCB and ABC groups. t(14;18)(q32;q21) was more frequently recorded in GCB group, and t(14;18)(q32;q21) with BCL2 additional signals or only BCL2 and IgH additional signals in ABC group (P=0.004). The GCB and ABC groups showed no difference in BCL6 gene abnormalities. There was no overall survival difference between the diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients, however, GCB group had longer overall survival than ABC group (P=0.047). Multivariate analysis showed that BCL6, CD10, and BCL2 expression, BCL2 and BCL6 abnormalities, and International Prognostic Index were not significantly related to overall survival. CONCLUSION: Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients have very similar characteristics and their prognosis is more influenced by protein expression of B-cell differentiation stage genes than by tumor cells growth pattern, BCL2 and BCL6 abnormalities, and International Prognostic Index.


Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Interleucina-6/genética , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Interleucina-6/análise , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neprilisina/genética , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-6 , Sindecana-1/genética
17.
Clin Neurol Neurosurg ; 172: 99-104, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986205

RESUMO

OBJECTIVES: Tentorial alignment and dimensions of posterior fossa cisterns are measurements whose variability can decrease surgical freedom if not taken into account when choosing the approach to the pineal region. The aim is to provide quantitative anatomical information regarding these dimensions, and to discuss their relevance in two most commonly used approaches to this region: the occipital transtentorial and supracerebellar-infratentorial approach. PATIENTS AND METHODS: A retrospective study of midsagittal T1-weighted MRI images of 410 randomly selected healthy subjects was performed. The clivus-tentorium (C-T) angle was measured to assess tentorial alignment. The following distances were used as craniocaudal cisternal measurements: quadrigeminal cistern = superior colliculi - inferior part of the splenium of corpus callosum (SC-ISCC), and superior cerebellar cistern = vermis - inferior part of the splenium of corpus callosum (VER-ISCC). RESULTS: Median C-T angle value was 19 ±â€¯7°, the quadrigeminal cistern height 6.7 ±â€¯1.6 cm, and the superior cerebellar cistern height 10.4 ±â€¯2.6 cm. The C-T angle was negatively correlated with the SC-ISCC distance (r = -0.271; p <  0.001) and the VER-ISCC distance (r = -0.052, p >  0.001). The SC-ISCC distance was positively correlated with the VER-ISCC distance (r = 0.282; p < 0.001). CONCLUSION: Our new method of measuring tentorial alignment provides a simple and effective aid in preoperative planning. For the first time, we present data on craniocaudal dimensions of posterior fossa cisterns, their relationship with tentorial alignment, and discuss their relevance in SCIT and OT approaches.


Assuntos
Encéfalo/cirurgia , Imageamento por Ressonância Magnética , Glândula Pineal/cirurgia , Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fossa Craniana Posterior/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Adulto Jovem
18.
Acta Med Croatica ; 61(3): 239-43, 2007 Jun.
Artigo em Hr | MEDLINE | ID: mdl-17629097

RESUMO

OBJECTIVES: To estimate the regional prevalence of metabolic syndrome, and potential implication of socioeconomic characteristics to it. METHODS: Assessment was performed in a sample representative of the Croatian population (N=9070). The metabolic syndrome was defined as "waist circumference greater than 102 cm for male and 88 cm for female, and at least two of the following criteria: arterial blood pressure > or =140/90 mm Hg (regulated hypertonic was considered as normal blood pressure person), elevated blood lipids, and elevated blood sugar (self reported). Statistically, the prevalence and confidence intervals, and comparative figure for the prevalence of metabolic syndrome (according to Julious et al. 2001) were applied. RESULTS AND DISCUSSION: The prevalence of metabolic syndrome in young adults (aged < or =34) was less than 1%. In older population groups the prevalence was greater. In the > or =65 age group, the prevalence (male 7.7, 95%CI 8.6-9.2; female 9.9, 95%CI 8.6. 11.1) was twofold that recorded in the 35-64 age group (male 15.2, 95%CI 12.4-17.9; female 22.5, 95%CI 20.1-24.8). The prevalence of metabolic syndrome was higher in female population in all age groups. There were no regional statistically significant differences. Socioeconomically, the metabolic syndrome population showed lower economic status, lower education level, and unfavorable health perception. As socioeconomic characteristics are not independent of age and sex, adjustment was made by calculating comparative figure for the prevalence of metabolic syndrome. Results showed no statistically significant differences between different socioeconomic groups, however, the groups with poor health perception showed a higher rate of metabolic syndrome than other groups. Comparative prevalence of the metabolic syndrome was 126.5, 95%CI 121.7-131.5 in the group with poor health perception, and 70.7, 95%CI 70.6-70.9 in well being groups. CONCLUSION: The prevalence of metabolic syndrome in the Croatian population is not region dependent. Socioeconomic status does not cause significant differences in the prevalence of metabolic syndrome, whereas poor health perception is associated with a higher prevalence of the syndrome.


Assuntos
Síndrome Metabólica/epidemiologia , Adulto , Idoso , Croácia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
19.
Croat Med J ; 47(4): 619-26, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16909460

RESUMO

AIM: To investigate the relationships between body mass index (BMI), dietary habits, and cardiovascular risk factors in isolated Adriatic island populations of Croatia. METHODS: Random sample of subjects (n=1001) was interviewed, using a validated questionnaire developed for this research program. Dietary habits were assessed on the basis of applied Food Frequency Questionnaire (FFQ). Biochemical analyses of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, and blood glucose were performed. Blood pressure (mm Hg), height (m), and weight (kg) were measured following standard procedures. RESULTS: Out of 1001 study participants, 507 (50.7%) were overweight (247 [48.7%] men and 260 [51.3%] women), whereas 268 (26.8%) were obese (122 [45.5%] men and 146 [54.5%] women). In both genders, there was a positive correlation between body mass index (BMI) and levels of triglycerides (P<0.001), glucose (P<0.001), diastolic blood pressure (P<0.001), and systolic blood pressure (male: P=0.002, female: P<0.001). Logistic regression showed that female gender (OR, 2.31; 95% CI, 1.61-3.31), overweight (OR, 1.97; 95% CI, 1.34-2.88), obesity (OR, 1.90; 95% CI, 1.22-2.96), more frequent consumption of meat (OR 1.17; 95% CI, 1.06-1.30) and beer (OR 1.14; 95% CI, 1.03-1.27), and less frequent consumption of potatoes (OR 0.91; 95% CI, 0.83-0.99) were predictive for the presence of cardiovascular risk factors. CONCLUSION: Prevalence of obesity and related health outcomes was surprisingly high for the studied population. We found a correlation between BMI, dietary habits, and cardiovascular risk factors.


Assuntos
Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Dieta , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Croácia , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações
20.
Coll Antropol ; 30 Suppl 2: 85-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17508480

RESUMO

The aim of the study was to assess the prevalence of depression among Croatian patients infected with human immunodeficiency virus (HIV) and to make a comparison with patients with other acute and chronic infectious diseases. We assessed the depressive disorder using the Beck Depression Inventory questionnaire (BDI), without clinical confirmation. The BDI scores were examined in 80 HIV-infected persons and compared to 80 persons with chronic viral hepatitis and 78 with acute infectious diarrhea. All examinees were treated as outpatients at the University Hospital for Infectious Diseases in Zagreb in March and April of 2003. Prevalence of moderate and severe depression among HIV-infected was 16/80 (20%) with a 95% confidence interval 11% to 29%. Male patients with HIV or chronic viral hepatitis had a significantly higher BDI scores than males with acute infectious diarrhea (p = 0.017, Kruskall-Wallis, d.f. 2). Female patients with HIV infection tended to have a lower BDI score than females with chronic viral hepatitis or acute infectious diarrhea (p = 0.087, Kruskall-Wallis, d.f. 2). Prevalence of moderate and severe depression among Croatian HIV-positive patients is higher than the upper estimate for general population. Croatian males with chronic infectious disease have higher rate of depression than those with acute infectious disease.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Disenteria/psicologia , Infecções por HIV/psicologia , Hepatite Crônica/psicologia , Adulto , Distribuição por Idade , Croácia/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/etiologia , Disenteria/complicações , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite Crônica/complicações , Humanos , Masculino , Prevalência , Distribuição por Sexo , Inquéritos e Questionários
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