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1.
Ital J Pediatr ; 48(1): 22, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120570

RESUMO

The adverse effects of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are not limited to the related infectious disease. In children and adolescents, serious risks due to the coronavirus disease 2019 (COVID-19) pandemic are also related to its indirect effects. These include an unbalanced diet with an increased risk of weight excess or nutritional deficiencies, increased sedentary lifestyle, lack of schooling, social isolation, and impaired mental health.Pediatricians should be aware of the side effects of the COVID-19 pandemic on children's diet, physical mental health and advise the families according to their nutritional needs and financial resources. Moreover, the lack of a targeted therapy able to offer protection against the deleterious effects of SARS-CoV-2 infection should require a greater effort by scientific societies to find a more effective prevention strategy. In this context, much interest should be given to nutritional support, able to contrast malnutrition and to stimulate the immune system.


Assuntos
COVID-19 , Adolescente , Criança , Humanos , Estilo de Vida , Pandemias/prevenção & controle , SARS-CoV-2 , Isolamento Social
2.
BAG, J. basic appl. genet. (Online) ; 31(2): 39-44, Dec. 2020. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1345379

RESUMO

RESUMEN El higroma quístico es la malformación del sistema linfático que más frecuentemente se observa en el período prenatal y que se ubica principalmente en el cuello y/o la nuca. Su tasa de detección ha aumentado desde la implementación de la translucencia nucal fetal (TN) en el primer trimestre de embarazo, y su presencia se ha relacionado con anomalías congénitas, aneuploidías, pérdida del embarazo y trastornos en el desarrollo. El objetivo de la presentación de este caso es resaltar la importancia del diagnóstico antenatal del higroma quístico, con el fin de realizar una intervención precoz y evitar la muerte fetal. Se recibe para estudio anatomopatológico, feto de sexo indeterminado producto del primer embarazo de una madre de 19 años de edad sin previos controles prenatales, con presencia de una gran masa quística que se extiende desde el rostro hasta la nuca. Mediante el estudio histológico se confirma el diagnóstico de higroma quístico. Al carecer de análisis de cariotipo no fue posible establecer la preexistencia de alguna anomalía genética. El también conocido como linfangioma quístico, es un tumor vascular benigno cuyo diagnóstico antenatal mediante la ultrasonografía resulta fundamental en la evolución y pronóstico de la enfermedad. Desafortunadamente en nuestro caso, la falta de controles prenatales y la ausencia de estudios ultrasonográficos que permitieran conocer las características de este linfangioma, pudo impactar significativamente en el desenlace fatal.


ABSTRACT The cystic hygroma is the malformation of the lymphatic system that is most frequently observed in the prenatal period and is located mainly in the neck and/or the nape of the neck. Its detection rate has increased since the implementation of fetal nuchal translucency (NT) in the first trimester of pregnancy and its presence has been associated with congenital abnormalities, aneuploidies, pregnancy loss, and developmental disorders. The aim of this case is to highlight the importance of antenatal diagnosis of cystic hygroma in order to perform early intervention and avoid fetal death. It is received, for anatomopathological study, a fetus of undetermined sex product of the first pregnancy of a 19 year-old mother without previous prenatal controls, with the presence of a large cystic mass that extends from the face to the neck. The histological study confirms the diagnosis of cystic hygroma. As there was no karyotype analysis, it was not possible to establish the preexistence of any genetic abnormality. Also known as cystic lymphangioma, is a benign vascular tumor whose antenatal diagnosis by ultrasonography is essential in the evolution and prognosis of the disease. Unfortunately in our case, the lack of prenatal controls and the absence of ultrasonographic studies that would allow knowing the characteristics of this lymphangioma, could significantly impact in the fatal outcome.

3.
Eur J Obstet Gynecol Reprod Biol ; 248: 233-237, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32259737

RESUMO

OBJECTIVE: The aim of the present study is to investigate the correlation between pregnancies complicated by morphological or chromosomal fetal anomalies and an obstetric history of two or more pregnancy losses, analyzing the association with any maternal risk factor. STUDY DESIGN: Retrospective analysis of women who had access to the Day Hospital Clinic of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 2012 to 2018 for a pregnancy complicated by fetal malformation and/or abnormal karyotype, and who had an obstetric history of at least one pregnancy loss. Patients were divided into four groups depending on the number of miscarriages and the presence of a genetic anomaly: Group 0 included women with <2 miscarriages and fetal malformations, Group 1 included women with ≥2 miscarriages and fetal malformations, Group 2 included women with <2 abortion, fetal malformations and the presence of genetic anomalies; Group 3 included women with 2 ≥ abortions, fetal malformations and genetic anomalies. Statistical analysis was performed using the SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: A total of 466 patients were included in the present analysis. Out of these, 379 patients belonged to Group 0; 40 patients entered in Group 1; Group 2 included 42 patients, and 5 patients were part of Group 3. Pregnancies complicated by fetal congenital malformations in patients with two or more pregnancy losses were significantly associated with maternal trombophilic disease and previous birth defects. Recurrent miscarriage and fetal structural anomalies were also significantly correlated with advanced maternal age. CONCLUSIONS: An adequate periconceptional counseling regarding the risk of fetal congenital anomalies may be indicated in patients affected by thrombophilic disease, as well as in those of advanced maternal age and with a pregnancy history of fetal malformations. The screening for thrombophilia may be advisable in patients with an obstetric history of congenital birth defects.


Assuntos
Aborto Habitual/epidemiologia , Anormalidades Congênitas/epidemiologia , Aborto Habitual/etiologia , Adulto , Causalidade , Aberrações Cromossômicas/embriologia , Feminino , Humanos , Idade Materna , Gravidez , Estudos Retrospectivos
4.
Gynecol Endocrinol ; 34(1): 28-31, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28675713

RESUMO

The aim of our study is to identify - in a cohort of obese women - cardiovascular and clinical risk factors in women with previous complicated pregnancies and protective factors in women with previous physiological pregnancies. A total of 135 nonpregnant obese women referring to Policlinico Gemelli in Rome were prospectively collected in 2009-2010. Thirty-two women matched inclusion criteria: 16 reported a previous physiological pregnancy and 16 reported previous obstetric complications. A clinical, instrumental and laboratory evaluation has been performed for each patient. Statistical analysis was performed using StatView Software. Values are expressed as mean ± standard error (SEM). All tests were two-tailed with a confidence level of 95% (p < .05). Statistically significant reduced flow-mediated dilatation (p = .0338), increased serum values of vascular cell adhesion molecule (p = .0154) and higher systolic blood pressure values (p = .0427) have been detected in obese women with previous complicated pregnancies due to gestational diabetes and/or hypertension. In conclusion, obese patients with previous complicated pregnancies develop signs of endothelial dysfunction in the postpartum period. Future research should focus on the early identification of possible molecular mechanisms implicated in the development of glyco-metabolic and cardiovascular diseases in obese patients, since they are at higher risk of metabolic syndrome.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade/complicações , Complicações na Gravidez/epidemiologia , Adulto , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Diabetes Gestacional/fisiopatologia , Feminino , Hemodinâmica , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Itália/epidemiologia , Obesidade/epidemiologia , Obesidade/fisiopatologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Molécula 1 de Adesão de Célula Vascular/sangue
5.
PLoS One ; 9(9): e107106, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25202909

RESUMO

BACKGROUND: At the triple border Brazil/Paraguay/Argentina there is easy mobility from one city to another for economic and tourism activities. This constant and fast population mobility is mainly to visit Iguazu Falls, in the Iguazu River, on the border of the Brazilian state of Paraná and the Argentina. As the incidence of tuberculosis is high in this setting, our study aimed to establish a first baseline of circulating genotypic lineages of Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: This study included 120 patients from 10 cities in southwestern Paraná, Brazil with pulmonary symptoms, from July 2009 to July 2011. Information about sex, age, clinical features and address was collected by reviewing the national tuberculosis notification database. Of these, 96 (80%) isolates were identified as M. tuberculosis and 22 (22.9%) were drug resistant (20, 20.8% INH mono-resistant and 2, 2.1% multidrug-resistant). All isolates were subjected to genotyping by Spoligotyping and MIRU-VNTR typing. The distribution of the isolates analyzed by spoligotyping revealed 30 distinct patterns. The four mainly detected clades were Latin American and Mediterranean (LAM), ill-defined T, Haarlem (H) and S. The MIRU-VNTR showed 85 distinct patterns. Spoligotyping combined to MIRU-VNTR allowed 90 distinct patterns. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated that there is significant molecular diversity in circulating M. tuberculosis, with predominance of the LAM and T clades in cities of southwestern Paraná, Brazil, bordering Argentina and Paraguay.


Assuntos
Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Adolescente , Adulto , Idoso , Técnicas de Tipagem Bacteriana/métodos , DNA Bacteriano/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , América do Sul , Adulto Jovem
6.
Cell Death Dis ; 4: e821, 2013 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-24091664

RESUMO

Expansion of polyalanine tracts causes at least nine inherited human diseases. Among these, a polyalanine tract expansion in the poly (A)-binding protein nuclear 1 (expPABPN1) causes oculopharyngeal muscular dystrophy (OPMD). So far, there is no treatment for OPMD patients. Developing drugs that efficiently sustain muscle protection by activating key cell survival mechanisms is a major challenge in OPMD research. Proteins that belong to the Wnt family are known for their role in both human development and adult tissue homeostasis. A hallmark of the Wnt signaling pathway is the increased expression of its central effector, beta-catenin (ß-catenin) by inhibiting one of its upstream effector, glycogen synthase kinase (GSK)3ß. Here, we explored a pharmacological manipulation of a Wnt signaling pathway using lithium chloride (LiCl), a GSK-3ß inhibitor, and observed the enhanced expression of ß-catenin protein as well as the decreased cell death normally observed in an OPMD cell model of murine myoblast (C2C12) expressing the expanded and pathogenic form of the expPABPN1. Furthermore, this effect was also observed in primary cultures of mouse myoblasts expressing expPABPN1. A similar effect on ß-catenin was also observed when lymphoblastoid cells lines (LCLs) derived from OPMD patients were treated with LiCl. We believe manipulation of the Wnt/ß-catenin signaling pathway may represent an effective route for the development of future therapy for patients with OPMD.


Assuntos
Cloreto de Lítio/farmacologia , Cloreto de Lítio/uso terapêutico , Distrofia Muscular Oculofaríngea/tratamento farmacológico , Distrofia Muscular Oculofaríngea/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteínas de Fluorescência Verde/metabolismo , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Distrofia Muscular Oculofaríngea/metabolismo , Proteínas Mutantes/metabolismo , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Mioblastos/patologia , Proteína I de Ligação a Poli(A)/genética , Proteína I de Ligação a Poli(A)/metabolismo , Transporte Proteico/efeitos dos fármacos , Expansão das Repetições de Trinucleotídeos/genética , beta Catenina/metabolismo
7.
Rev Sci Instrum ; 84(3): 033505, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23556819

RESUMO

The non-intrusive density measurement of the thin plasma produced by a mini-helicon space thruster (HPH.com project) is a challenge, due to the broad density range (between 10(16) m(-3) and 10(19) m(-3)) and the small size of the plasma source (2 cm of diameter). A microwave interferometer has been developed for this purpose. Due to the small size of plasma, the probing beam wavelength must be small (λ = 4 mm), thus a very high sensitivity interferometer is required in order to observe the lower density values. A low noise digital phase detector with a phase noise of 0.02° has been used, corresponding to a density of 0.5 × 10(16) m(-3).

8.
J Biol Regul Homeost Agents ; 26(3 Suppl): 43-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23158514

RESUMO

Postnatal growth restriction and failure to thrive still remain a major problem in Extremely Low Birth Weight (ELBW) infants . The goal for the nutritional care of these infants is to achieve rate of growth similar to those of the fetus in utero at the equivalent gestational age. Human milk fortified remains the best food for all these preterms. Two groups of preterm of weight 580-1250 g and gestational age 23-32 wk, were fed with different protein intake in the human/maternal milk fortified ( 3,5 g Kg-1 per day and 4,8 g Kg-1 per day in the control and intervention group respectively).The feeding tolerance, intrahospital growth, neurological outcome and anthropometric data until 12 months of corrected age, were evaluated. The protein supplemented group (PSG) showed an intrahospital highter growth rate ( mostly in head circumference, p 0,02, and length growth, p 0,04) only in the preterms with 580-980 g and 23-30 wk. In the same preterms, Griffith Development Mental Score at 3 and 12 months corrected age showed higher score than in the control group in the Performance (p 0,04) and Hearing/Language (p 0,03) items. The auxological evaluation in the postdischarge period showed in the PSG group mean z-score values for length higher than those in the control group at 9 (p 0,04) months of corrected age.


Assuntos
Insuficiência de Crescimento/dietoterapia , Alimentos Fortificados , Recém-Nascido de Peso Extremamente Baixo ao Nascer/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leite Humano/química , Proteínas/administração & dosagem , Peso ao Nascer/efeitos dos fármacos , Estatura/efeitos dos fármacos , Aleitamento Materno , Estudos de Casos e Controles , Nutrição Enteral , Feminino , Idade Gestacional , Audição/efeitos dos fármacos , Audição/fisiologia , Humanos , Alimentos Infantis , Recém-Nascido de Peso Extremamente Baixo ao Nascer/psicologia , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Lactação , Idioma , Leite Humano/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Testes Neuropsicológicos , Proteínas/química
9.
Minerva Ginecol ; 61(2): 89-95, 2009 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-19255556

RESUMO

AIM: Urinary incontinence is a classical sign of childbirth-related perineal trauma, the prevalence of which is estimated, depending on age, at between 10% and 50%. Pelviperineal rehabilitation offers an excellent opportunity to prevent pelviperineal disorders. The aim of the present study was to evaluate the prevalence of urinary incontinence and pelviperineal disorders in the local context, and also that of pelviperineal rehabilitation. METHODS: Of the 1793 women who gave birth in Udine in 2006, 900 primipara and secondipara Caucasians with single term pregnancies dated ultrasonically to be within 20 weeks of gestation, were selected. A total of 602 of them were contacted by telephone and two questionnaires were administered. RESULTS: The prevalence of pelviperineal rehabilitation in our population was 4.49%, while that of pelviperineal disorders was much higher, at around 40.20%. The prevalence of urinary incontinence was due in 27.57% of cases to stress and in 14.45% to urgency, with an overlap in 9.8% of cases and a story of prior incontinence in 9.97%. The prevalence of urinary urgency in women subjected to rehabilitation is significantly lower than in those not treated (P=0.004). Dyspareunia represents 16.11% of cases, coital incontinence 0.33%. One case of gas incontinence emerged but there was no case of faecal incontinence. CONCLUSIONS: Pelviperineal rehabilitation in the observed population has a very low prevalence, especially if compared with the high prevalence of disturbances related to dysfunctions of the pelvic floor during postpartum.


Assuntos
Paridade , Período Pós-Parto , Incontinência Urinária/epidemiologia , Incontinência Urinária/reabilitação , Adulto , Estudos de Coortes , Terapia por Exercício , Feminino , Humanos , Itália/epidemiologia , Diafragma da Pelve , Períneo/lesões , Gravidez , Prevalência , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários , População Branca/estatística & dados numéricos
10.
Reumatismo ; 60(1): 35-40, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-18432323

RESUMO

The term undifferentiated connective tissue diseases (UCTD) is used to identify systemic autoimmune diseases not fulfilling classificative criteria for defined connective tissue diseases (CTD). Aim of the present study was to evaluate the evolution to defined CTD of an historical cohort of 91 UCTD patients followed at our Unit and to describe clinical and serological characteristics of stable UCTD patients with a disease duration of more than 5 years. Patients, previously described, were selected for having an undifferentiated profile after 1 year of follow up. These patients have been regularly followed at our Unit and their diagnosis has been reassessed annually based on the existing classificative criteria. Seven UCTD patients with a follow up of less than 5 years have been excluded from the study, therefore 84 patients (F: 81, M: 3) have been analysed. During the follow up 28 patients (33%) developed a defined CTD. In particular 22 patients developed systemic lupus erythematosus (SLE), while the remaining 6 patients developed other CTDs (2 primary Sjögren's syndrome, 2 overlap syndromes, 1 Systemic Sclerosis, 1 rheumatoid arthritis). The evolution to a defined CTD occurred after a mean disease duration of 80.6+/- 66.8 months (min 14, max 336, median 72); the evolution to SLE occurred after a mean disease duration of 66.8+/-43.3 months (min 17, max 216, median 57). Anti-cardiolipin antibodies were the only variable correlated with the evolution to SLE (p<0.05). Stable UCTD were characterized by a simplified clinical picture with no major organ involvement and by a simplified autoantibody profile (anti-Ro/SSA antibodies and anti-RNP antibodies were the single antibody specificities observed in 22% and 13% of patients respectively). These results confirm previous data showing that about 30% of UCTD patients will develop a defined CTD, the predictive role of anti-cardiolipin antibodies for the evolution to SLE, and the existence of stable UCTD, distinct clinical entities with a simplified clinico-serological profile. The early identification of stable UCTD is very important both from a clinical and a research point of view. Future research is needed to define a new set of classification criteria.


Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Autoimmun Rev ; 6(1): 1-4, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17110308

RESUMO

The term undifferentiated connective tissue diseases is used to define conditions characterized by the presence of signs and symptoms suggestive of a systemic autoimmune disease that do not satisfy the classificative criteria for defined connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA) and others. A small percentage of patients presenting with an undifferentiated profile will develop during the first year follow up of a full blown CTD, however an average of 75% will maintain an undifferentiated clinical course. These patients may be defined as having a stable undifferentiated connective tissue diseases (UCTD). The most characteristic symptoms of UCTD are represented by arthritis and arthralgias, Raynaud's phenomenon, leukopenia, while neurological and kidney involvement are virtually absent. Eighty percent of these patients have a single autoantibody specificity, more frequently anti-Ro and anti-RNP antibodies. Stable UCTD are considered as distinct clinical entities and therefore it has been proposed to define those conditions as UCTD. Classificative criteria have also been proposed and a work to better define them is still under way.


Assuntos
Autoimunidade/fisiologia , Doenças do Tecido Conjuntivo/fisiopatologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/imunologia , Humanos
12.
Mol Hum Reprod ; 12(9): 587-91, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16820404

RESUMO

Cell-free fetal DNA in maternal plasma or serum is at present widely investigated as a source of fetal genetic material, both in studies of pregnancy-related disorders and in planning strategies for non-invasive prenatal diagnosis. Despite the number of trials already performed on the quantitation of fetal DNA, data about the amount of DNA at the beginning of pregnancy, in particular in the first trimester, remain limited. A new probe mapping on the deleted in azoospermia (DAZ) repetitive region of the Yq chromosome was designed for an early assessment of fetal DNA concentration in maternal serum. Among 57 pregnant women prospectively studied in their first trimester, fetal DNA was detected already by the 5th gestational week, with the analysis becoming reliable by the 8th week of gestation when a 100% accuracy in fetal sex determination was achieved. Moreover, in the three cases of pregnancy ending in fetal loss, the amount of fetal DNA apparently decreased before the abortion was diagnosed, whereas it consistently showed an increasing trend in normal pregnancies. Real-time PCR with the use of DAZ multilocus probe can efficiently quantitate free fetal DNA in the maternal serum at the beginning of pregnancy.


Assuntos
Cromossomos Humanos Y/genética , Sondas de DNA , DNA/sangue , Troca Materno-Fetal , Gravidez/sangue , Proteínas de Ligação a RNA/genética , Proteína 1 Suprimida em Azoospermia , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Processos de Determinação Sexual
14.
J Neurochem ; 80(2): 271-7, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11902117

RESUMO

The endogenous synthesis of morphine has been clearly demonstrated throughout the phylogenesis of the nervous system of mammals and lower animals. Endogenous morphine, serving as either a neurotransmitter or neurohormone, has been demonstrated in the nervous system of both vertebrates and invertebrates. As one of the effects of exogenous morphine is the modulation of pain perception, we investigated the effects that the depletion of endogenous morphine had on nociceptive transmission. The immunoneutralization of endogenous morphine from brain extracellular spaces was obtained through the intracerebroventricular administration of affinity purified anti-morphine IgG to mice, which then underwent the hot plate test. Endogenous morphine immunoneutralization decreased thermal response latency and attenuated the anti-nociceptive effect of the mu selective agonist DAMGO in hot plate test suggesting that endogenous morphine is involved in pain modulation.


Assuntos
Hiperalgesia/metabolismo , Morfina/metabolismo , Peptídeos Opioides/metabolismo , Doença Aguda , Analgésicos Opioides/farmacologia , Animais , Soluções Tampão , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , D-Penicilina (2,5)-Encefalina/farmacologia , Etilcetociclazocina/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Hiperalgesia/tratamento farmacológico , Imunoglobulina G/análise , Imunoglobulina G/farmacologia , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos , Morfina/análise , Morfina/imunologia , Atividade Motora , Nociceptores/metabolismo , Peptídeos Opioides/análise , Peptídeos Opioides/imunologia , Temperatura Cutânea
15.
Proc Natl Acad Sci U S A ; 98(23): 13318-23, 2001 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-11687635

RESUMO

Huntington's disease (HD) is a dominant neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt). HD pathogenesis appears to involve the production of mutated N-terminal htt, cytoplasmic and nuclear aggregation of htt, and abnormal activity of htt interactor proteins essential to neuronal survival. Before cell death, neuronal dysfunction may be an important step of HD pathogenesis. To explore polyQ-mediated neuronal toxicity, we expressed the first 57 amino acids of human htt containing normal [19 Gln residues (Glns)] and expanded (88 or 128 Glns) polyQ fused to fluorescent marker proteins in the six touch receptor neurons of Caenorhabditis elegans. Expanded polyQ produced touch insensitivity in young adults. Noticeably, only 28 +/- 6% of animals with 128 Glns were touch sensitive in the tail, as mediated by the PLM neurons. Similar perinuclear deposits and faint nuclear accumulation of fusion proteins with 19, 88, and 128 Glns were observed. In contrast, significant deposits and morphological abnormalities in PLM cell axons were observed with expanded polyQ (128 Glns) and partially correlated with touch insensitivity. PLM cell death was not detected in young or old adults. These animals indicate that significant neuronal dysfunction without cell death may be induced by expanded polyQ and may correlate with axonal insults, and not cell body aggregates. These animals also provide a suitable model to perform in vivo suppression of polyQ-mediated neuronal dysfunction.


Assuntos
Axônios , Caenorhabditis elegans/metabolismo , Neurônios Aferentes/fisiologia , Peptídeos/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/citologia , Morte Celular , Proteínas de Fluorescência Verde , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência
17.
Proc Natl Acad Sci U S A ; 98(4): 1811-6, 2001 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-11172033

RESUMO

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the protein huntingtin (htt). Pathogenesis in HD appears to involve the formation of ubiquitinated neuronal intranuclear inclusions containing N-terminal mutated htt, abnormal protein interactions, and the aggregate sequestration of a variety of proteins (noticeably, transcription factors). To identify novel htt-interacting proteins in a simple model system, we used a yeast two-hybrid screen with a Caenorhabditis elegans activation domain library. We found a predicted WW domain protein (ZK1127.9) that interacts with N-terminal fragments of htt in two-hybrid tests. A human homologue of ZK1127.9 is CA150, a transcriptional coactivator with a N-terminal insertion that contains an imperfect (Gln-Ala)(38) tract encoded by a polymorphic repeat DNA. CA150 interacted in vitro with full-length htt from lymphoblastoid cells. The expression of CA150, measured immunohistochemically, was markedly increased in human HD brain tissue compared with normal age-matched human brain tissue, and CA150 showed aggregate formation with partial colocalization to ubiquitin-positive aggregates. In 432 HD patients, the CA150 repeat length explains a small, but statistically significant, amount of the variability in the onset age. Our data suggest that abnormal expression of CA150, mediated by interaction with polyglutamine-expanded htt, may alter transcription and have a role in HD pathogenesis.


Assuntos
Alanina , Encéfalo/patologia , Repetições de Dinucleotídeos , Glutamina , Doença de Huntington/patologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/fisiologia , Idade de Início , Animais , Encéfalo/metabolismo , Caenorhabditis elegans , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Proteína Huntingtina , Doença de Huntington/genética , Doença de Huntington/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/fisiologia , Transativadores/genética , Transativadores/metabolismo , Fatores de Elongação da Transcrição
20.
Am J Obstet Gynecol ; 181(3): 675-80, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10486483

RESUMO

OBJECTIVES: We investigated whether the number of weeks of gestation influences the accuracy of first-trimester fetal sex prediction by analysis of deoxyribonucleic acid extracted from whole maternal blood. A comparison was also made to determine whether a difference exists between this approach and the deoxyribonucleic acid analysis of transcervical cells performed on the same group of subjects. STUDY DESIGN: Deoxyribonucleic acid was isolated from 50 maternal blood samples taken between gestational weeks 7 and 11. The sex of the fetus was assessed by nested polymerase chain reaction specific for the amelogenin gene. A receiver-operating characteristic curve analysis was used to correlate the accuracy of fetal gender prediction with the gestational age and also to compare the goodness of the 2 methods under investigation. RESULTS: Analysis of the receiver-operating characteristic curve provided a cutoff value of 9 weeks 4 days of gestation for both tests, indicating that a higher degree of accuracy in the sex assignment was obtained in those samples taken before or at this time. However, this difference was statistically significant only for analysis of deoxyribonucleic acid from maternal blood. The comparison between tests of deoxyribonucleic acid from maternal blood and from transcervical cells showed that the first approach is better, although a statistically significant difference was not found. CONCLUSION: Analysis of maternal blood deoxyribonucleic acid is a better approach than analysis of trans-cervical cell deoxyribonucleic acid in fetal sex prediction. The highest degree of accuracy is obtained when blood is drawn before 10 weeks of gestation. This can be important when sampling of chorionic villi should be avoided because of the risk of an X-linked disease when the fetal sex is female.


Assuntos
DNA/sangue , Idade Gestacional , Análise para Determinação do Sexo/métodos , Amelogenina , Colo do Útero/citologia , Proteínas do Esmalte Dentário/genética , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez , Primeiro Trimestre da Gravidez , Curva ROC , Sensibilidade e Especificidade
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