Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Child Care Health Dev ; 41(6): 1040-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26250608

RESUMO

BACKGROUND: Social and emotional development of infants and young children is largely based on the communicative interaction with their mother, or principal caretaker (Trevarthen ). The main modalities implied in this early communication are voice, facial expressions and gaze (Stern ). This study aims at analysing early mother-child interactions in the case of visually impaired mothers who do not have access to their children's gaze and facial expressions. METHODS: Spontaneous play interactions between seven visually impaired mothers and their sighted children aged between 6 months and 3 years were filmed. These dyads were compared with a control group of sighted mothers and children analysing four modalities of communication and interaction regulation: gaze, physical contacts, verbal productions and facial expressions. RESULTS: The visually impaired mothers' facial expressions differed from the ones of sighted mothers mainly with respect to forehead movements, leading to an impoverishment of conveyed meaning. Regarding the other communicative modalities, results suggest that visually impaired mothers and their children use compensatory strategies to guaranty harmonic interaction despite the mother's impairment: whereas gaze results the main factor of interaction regulation in sighted dyads, physical contacts and verbal productions assume a prevalent role in dyads with visually impaired mothers. Moreover, visually impaired mother's children seem to be able to differentiate between their mother and sighted interaction partners, adapting differential modes of communication. CONCLUSIONS: The results of this study show that, in spite of the obvious differences in the modes of communication, visual impairment does not prevent a harmonious interaction with the child.


Assuntos
Comunicação , Expressão Facial , Relações Mãe-Filho , Mães/psicologia , Pessoas com Deficiência Visual/psicologia , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
2.
Eur J Clin Microbiol Infect Dis ; 27(10): 907-13, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18470544

RESUMO

The reactivation of latent tuberculosis (TB) is a major complication of tumor necrosis factor (TNF)-alpha inhibitors. Screening for TB infection is recommended before anti-TNF therapy is initiated; however, the use of tuberculin skin testing (TST) is controversial, due to the high rate of false-negative results in patients receiving immunosuppressive treatment. To compare the performance of two commercial interferon (IFN)-gamma release assays (IGRA), T-SPOT.TB (TS-TB) and QuantiFERON-TB Gold "In-tube" (QFT-GIT), with TST for the detection of TB infection in patients due to start anti-TNF therapy, 69 human immunodeficiency virus (HIV)-negative Italian patients (mean age: 45.2 +/- 12.6 years; male=39) were enrolled between September 2005 to August 2006. Patients affected by rheumatoid arthritis (n = 18), psoriatic arthritis (n = 26), ulcerous rectocolitis (n = 6), and Crohn's disease (n = 19) were tested simultaneously with TST, TS-TB, and QFT-GIT. Overall, 26% of patients were positive by TST, 30.4% by TS-TB, and 31.8% by QFT-GIT. Agreement with TST was similar (kappa = 0.21, p = 0.0002 and kappa = 0.26, p < 0.001, respectively). In 11 TST-negative cases, IFN-gamma release assays were positive. In addition, in seven Mantoux-positive cases with no TB risk factors, TST result agreement was achieved with at least one blood test. Indeterminate results were detected in 5.8% and 2.8% of cases, respectively, with TS-TB and with QFT-GIT (p = not significant [ns]). In conclusion, our results suggest that IGRAs may be helpful for screening purposes in patient candidates for anti-TNF therapy to confirm positive TST results and in selected cases when false-negative results are suspected. The utility of blood tests in patients with low or no TB risk remains to be assessed.


Assuntos
Interferon gama/metabolismo , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Adulto , Feminino , Humanos , Imunoensaio/métodos , Itália , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Sensibilidade e Especificidade
3.
Int J Tuberc Lung Dis ; 9(4): 375-83, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15830742

RESUMO

Apoptosis is a physiological programmed cell death process whose dysregulation plays an important role in different human infectious diseases. An increasing number of intracellular pathogens are known to induce target cell apoptosis, while some other parasites inhibit it. Unlike necrosis, apoptosis is a silent immunological event occurring without inflammation. Infection-induced target cell apoptosis may be a successful strategy to eliminate pathogens and assure host survival. Conversely, apoptosis inhibition could represent an adaptive mechanism for pathogen survival, while it may be beneficial for the host to initiate an effective immune response. The worldwide increase in tuberculosis has stimulated more research aimed at defining the interaction between Mycobacterium tuberculosis and the immune system. M. tuberculosis possesses sophisticated strategies to circumvent its fate within target monocytic cells. Apoptosis of alveolar macrophages and monocytes has been described as a consequence of M. tuberculosis infection. Moreover, the observation that mycobacterial lipoproteins activate macrophages through Toll-like receptor (TLR) 2 suggests that innate immune receptors contribute to defence against M. tuberculosis. There is evidence that TLR-induced apoptosis modulates inflammation and immune activation during M. tuberculosis infection. Finally, the role of apoptotic-infected cells as a source of microbial antigens for cross-priming of effector T-cells is also discussed.


Assuntos
Apoptose/fisiologia , Macrófagos/imunologia , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Apresentação Cruzada/imunologia , Humanos , Glicoproteínas de Membrana/fisiologia , Receptores de Superfície Celular/fisiologia , Linfócitos T/imunologia , Receptor 2 Toll-Like , Receptores Toll-Like
4.
J Pers Soc Psychol ; 73(6): 1363-79, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9453990

RESUMO

The ability of congenitally blind persons to produce voluntarily facial expressions of a number of emotions was compared with that of normally sighted individuals using both objective facial measurement and observer recognition. Results revealed that there were almost no significant differences between blind and sighted participants with respect to the number and type of facial action units produced. The portrayals of the blind participants were significantly more poorly recognized by observers than were those of the sighted participants (except for happiness). Correspondence analyses of the data showed differences between sighted and blind participants in the dimensional structure of the expressions (as based on the similarity among emotions with respect to both objective measurement and judgments). Overall, the data relavitize earlier conclusions on the facial expression of blind as compared with sighted persons and suggest specific hypotheses and procedures for further work in this area.


Assuntos
Cegueira/psicologia , Emoções , Expressão Facial , Adolescente , Adulto , Idoso , Cegueira/congênito , Feminino , Humanos , Comportamento Imitativo , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Percepção Social , Socialização
5.
Vet Microbiol ; 61(1-2): 1-6, 1998 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9646460

RESUMO

Papillomatous lesions were isolated from the mammary skin of goats and examined for evidence of papillomavirus (PV) infection by various criteria, including gross morphology, histology and DNA hybridization. Although some lesions showed gross papillomatous morphological and histological features similar to those caused by papillomavirus in other species, no viral particles were detected. Reverse slot hybridization revealed cross-hybridization between DNA extracted from goat mammary papillomas and human papillomaviruses (HPV). Southern blot, using ovine papillomavirus (OPV) and bovine papillomavirus type 5 (BPV 5) DNA probes under conditions of reduced stringency (Tm -40 degrees C), detected homologous sequences in 40% of the biopsies. DNA fragments corresponding probably to a monomeric form (7000-8000 bp) of an unknown papillomavirus genome were detected. This study provides evidence for the existence of papillomavirus-like sequences in caprine mammary papillomas and suggests that a papillomavirus is likely to be involved in the development of precancerous lesions of goat mammary skin.


Assuntos
DNA Viral/isolamento & purificação , Doenças das Cabras , Papiloma/veterinária , Papillomaviridae/genética , Neoplasias Cutâneas/veterinária , Animais , Bovinos , Sondas de DNA , DNA Viral/genética , Feminino , Cabras , Humanos , Glândulas Mamárias Animais , Papiloma/patologia , Papiloma/virologia , Papillomaviridae/isolamento & purificação , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia
6.
J Toxicol Environ Health A ; 54(6): 459-66, 1998 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-9661911

RESUMO

The use of pesticides in agriculture has increased over the last decade. Their widespread, often uncontrolled use causes thousands of people to be daily exposed to environmental agricultural chemicals, resulting in acute and chronic health effects. At present there is a paucity of data on the potential adverse effects of exposure to low levels of mancozeb for prolonged periods. In order to investigate the effects of mancozeb exposure on pulmonary wildlife populations, tracheas and lungs of nine 1- to 7-yr-old nonmigratory pigeons raised near peach orchards and vineyards repeatedly sprayed with the fungicide were examined. The experimental situation allowed us to evaluate the long-term natural toxicity of mancozeb as a sentinel for human populations occupationally exposed to fungicides. The use of nonmigratory pigeons may serve as an important biological source from which helpful data may be obtained for assessing risks to human health and gaining new insight into pathogenetic mechanisms.


Assuntos
Columbidae , Exposição Ambiental/efeitos adversos , Fungicidas Industriais/efeitos adversos , Pulmão/efeitos dos fármacos , Maneb/efeitos adversos , Traqueia/efeitos dos fármacos , Zineb/efeitos adversos , Animais , Microanálise por Sonda Eletrônica , Epitélio/efeitos dos fármacos , Epitélio/patologia , Pulmão/ultraestrutura , Microscopia Eletrônica de Varredura , Modelos Biológicos , Vigilância de Evento Sentinela , Traqueia/ultraestrutura
7.
Drugs Exp Clin Res ; 16(10): 543-50, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2151628

RESUMO

The effect of a 60 day administration of 200 mg heparan sulfate (Hemovasal 100 b.i.d.) or 100 mg mesoglycan (50 mg b.i.d.) was assessed under double blind design in forty patients (thirty-six males and four females) with peripheral occlusive arterial disease with respect to pain-free walking distance and various haemorheological and haemostasiological variables, platelet aggregation and blood chemistry. The pain-free walking distance significantly improved with heparan sulfate (up 67% from baseline 200.0 +/- 22.5 m and up 34%, with mesoglycan from baseline 207.7 +/- 23.4 m). Heparan sulfate significantly stimulated fibrinolysis and reduced platelet aggregability: these findings suggest an action of heparan sulfate on the endothelial cells, thus reducing their thrombogenicity. The results of the study thus confirm the activity of heparan sulfate in peripheral vascular disease, correcting the conditions which constitute the basis of increased thrombotic risk.


Assuntos
Arteriopatias Oclusivas/sangue , Hemostasia/efeitos dos fármacos , Heparitina Sulfato/uso terapêutico , Idoso , Arteriopatias Oclusivas/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Fibrinólise/efeitos dos fármacos , Glicosaminoglicanos/uso terapêutico , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Caminhada
8.
Int Angiol ; 14(4): 400-3, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8708436

RESUMO

The authors studied 200 consecutive outpatients with symptoms due to venous disease of the lower limbs. All the patients underwent anamnestic, clinical and instrumental evaluation (c.w. Doppler velocimetry and strain-gauge plethysmography). The results of this study showed that some anamnestic and clinical data are significantly related to venous disease detected by instrumental techniques. The superficial and deep vein hypertension were, instead, correlated to oral contraceptive use.


Assuntos
Pacientes Ambulatoriais , Flebite/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Anticoncepcionais Orais/efeitos adversos , Feminino , Humanos , Hipertensão/induzido quimicamente , Fluxometria por Laser-Doppler , Perna (Membro)/irrigação sanguínea , Masculino , Anamnese , Pessoa de Meia-Idade , Morbidade , Flebite/diagnóstico , Flebite/epidemiologia , Pletismografia , Gravidez , Estudos Retrospectivos , Fatores de Risco
9.
Int Angiol ; 4(2): 229-34, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2870124

RESUMO

This paper summarizes the results of two studies carried out to evaluate the effects of the cardioselective betablockers atenolol, acebutolol and metoprolol on peripheral circulation of the lower limbs. The 1st study was a double dummy double blind cross over placebo controlled trial carried out for 13 weeks to evaluate the effects of acebutolol (600 mg/die) and metoprolol (300 mg/die), two cardioselective betablockers, on peripheral haemodynamics in patients suffering from mild to moderate hypertension. The 2nd study was a placebo controlled trial on the effects of atenolol (100 mg/day) on haemodynamics at the calf carried out for 8 weeks in patients suffering from essential to severe moderate hypertension, part of which aged over 65 years and affected by arteriosclerosis obliterans of the lower limbs, stage I and II according to Fontaine's classification. Calf blood flow in basal condition (R.F.) and after ischemic stimulus (P.F.) was evaluated by strain gauge plethysmography; basal (B.V.R.) and minimal (M.V.R.) vascular resistances at the calf by the ratio between M.B.P./R.F. and M.B.P./P.F. respectively, Windsor's index (W.I.) by ultrasound. Neither the patients with hypertension only nor the elderly hypertensive suffering from arteriosclerosis obliterans of the lower limbs showed changes in R.F. and P.F., in B.V.R. and M.V.R. and in W.I. after chronic treatment with cardioselective beta-blockers. Many patients--about 17% of all patients, and 40% of arteriopathics--in the two trials had cold hands and feet. These studies suggest that chronic administration of selective beta-blockers does not exert unfavourable effects on muscular blood flow at the calf in patients with hypertension with or without arteriosclerosis obliterans of the lower limbs at I and II stage.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Hipertensão/fisiopatologia , Perna (Membro)/irrigação sanguínea , Adulto , Idoso , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos
10.
J Comp Pathol ; 110(3): 227-36, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8040388

RESUMO

Four cases of silicate pneumoconiosis are described in pigs raised near several chalk quarries and two cement works. The pulmonary changes were characterized by thickened alveolar septa, resulting in distorted airspaces, and small foci of initial fibrosis. In the bronchiolar and alveolar sites, as in the interstitium, free and intracytoplasmic dust was detected. An energy dispersive X-ray microanalysis coupled with a scanning electron microscope revealed that this dust was composed mainly of silicon, calcium, potassium, sulphur, aluminium and iron. In lung-associated lymph nodes, severe lymphoid cell depletion and dilatation of peritrabecular and subcapsular sinuses were constant findings. The inorganic material found in the lymph nodes contained the elements listed above. Air samples from the same geographical area revealed particulate pollutants, the qualitative features of which were similar to those found in lung and lymph nodal tissue. It is concluded that domestic animals raised in polluted environmental conditions represent an important biological source from which helpful data may be obtained for assessing risks to human health.


Assuntos
Silicose/veterinária , Doenças dos Suínos/patologia , Animais , Microanálise por Sonda Eletrônica/veterinária , Pulmão/patologia , Pulmão/ultraestrutura , Microscopia Eletrônica de Varredura/veterinária , Silicose/patologia , Suínos
11.
Angiology ; 48(9): 805-11, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9313630

RESUMO

Thirty adult patients with distal, monolateral deep vein thrombosis of the lower limbs were randomly treated for sixty days either with subcutaneous Ca-Heparin or with Sulodexide, administered IM for ten days and orally for fifty days. The thrombus accretion above the knee, the venous pressures of the affected leg, the clinical symptomatology, and some laboratory coagulative tests were monitored throughout the administration period. Local tolerability of the two treatments was also evaluated. The two applied treatments evidenced a net antithrombotic activity, preventing thrombus accretion above the knee, improving with the same efficacy the venous pressures in the affected legs, and similarly reducing clinical symptoms, with a quick and statistically significant trend toward normalization. Blood fibrinogen was significantly lowered by both drugs, while only Ca-heparin yielded a prolongation of activated partial thromboplastin time. Local tolerability of treatments was better for the mainly oral Sulodexide administrations, while subcutaneous Ca-heparin often induced small, though transient, hematomas.


Assuntos
Fibrinolíticos/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Heparina/uso terapêutico , Tromboflebite/tratamento farmacológico , Adulto , Idoso , Feminino , Fibrinolíticos/administração & dosagem , Glicosaminoglicanos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
12.
Clin Ter ; 161(1): 35-7, 2010.
Artigo em Italiano | MEDLINE | ID: mdl-20393676

RESUMO

OBJECTIVE: To reveal a possible reduction of the aorto-mesenteric angle and to diagnose suspected cases of superior mesenteric artery (SMA) syndrome. It was controlled, prospective study in which, in order to reveal a possible reduction of aorto-mesenteric angle, the following techniques. MATERIALS AND METHODS: In a cohort of patients referred to our department by their general practitioners for unexplained dyspepsia and/or abdominal pain an abdominal ultrasonography with power colour Doppler was performed; patients with reduced SMA angle were screened by gastroduodenoscopy, hypotonic duodenography, contrast-enhanced spiral computerized tomography. RESULTS: In a cohort of 1468 patients, 460 subjects were taken into consideration, specifi cally the patients where US and power colour Doppler had been adequately performed. US detected a signifi cant reduction of the SMA angle in 20 of those patients; in these 20 subjects, gastroscopy showed duodenal compressive pulsation in 5 of the 20 patients under examination, and X-ray revealed a compression of the third segment of the duodenum in 18 of them. The following CT examination confi rmed the presence of a reduced angle and various degrees of duodenal compression in all patients. US and CT examinations gave overlapping results (p>0.05) in diagnosing pathological aorta-mesenteric angle. CONCLUSIONS: The analysis of data led the authors to believe that the incidence of reduced aorto-mesenteric angle and SMA syndrome might be underrated. US power colour Doppler imaging that is a rapid, repeatable, and non invasive, low cost and easy to perform diagnostic procedure, is useful in epidemiological screening of reduced aorto-mesenteric angle to diagnose suspected cases of SMA syndrome in patients with inexplicable abdominal pain.


Assuntos
Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Adulto , Estudos de Coortes , Duodenoscopia , Feminino , Gastroscopia , Humanos , Incidência , Masculino , Programas de Rastreamento , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Síndrome da Artéria Mesentérica Superior/complicações , Tomografia Computadorizada Espiral
16.
J Cardiovasc Pharmacol ; 8 Suppl 5: S122-4, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-2427870

RESUMO

A significant reduction of maximal vasodilation capacity at the calf in relation to the severity of the hypertensive state has been demonstrated in essential hypertension. The aim of this study was to evaluate the behavior of calf blood flow and vascular resistance in borderline hypertensives (BH) in comparison with normotensive control subjects (CS). We studied 32 BH, with average age of 47.31 +/- 16.78 years and blood pressure 140-160/90-95 mm/Hg, in comparison with 20 CS, with average age of 47.24 +/- 11.75 years and blood pressure values below 140/85 mm Hg. Calf rest flow (RF) and peak flow (PF) were evaluated by strain-gauge plethysmography, and basal vascular resistance (BVR) and minimal vascular resistance (MVR) were calculated by the ratio between mean blood pressure and RF and PF, respectively. Mean blood pressure was significantly higher in BH in comparison with CS. RF and PF did not differ significantly in BH in comparison with CS. BVR did not differ in BHs in comparison with CS. In contrast, MVR were significantly higher in BH in comparison with CS. These results show that in BH, arterial flow at the calf is normal, whereas MVR are higher, indicating an impairment of maximal vasodilation capacity despite the modest blood pressure elevation.


Assuntos
Hipertensão/fisiopatologia , Perna (Membro)/irrigação sanguínea , Resistência Vascular , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional
17.
Eur Heart J ; 16(11): 1692-7, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8881866

RESUMO

This study was designed to analyse the relationship between arterial hypertension and changes in arterial blood flow and vascular wall damage of the lower limbs in hypertensive patients with various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 males and 233 females) aged 35 to 70 years and 88 healthy subjects (63 males and 25 females) aged 39 to 60 years were studied. Strain-gauge plethysmography of the lower limbs was used to calculate arterial calf blood flow (RF), arterial calf blood flow after post-ischaemic hyperaemia (PF), basal and minimal vascular resistances (BVR and MVR), time to reach peak flow (tPF), time until 50% reduction of peak flow (tT1/2) and total recovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients, a morphological study by echo-Doppler duplex scanning of the popliteal artery was performed to measure medial-intimal thickening and popliteal lumen diameter. Our results indicate that regional haemodynamics of the lower limbs worsened in hypertensives in comparison with control subjects. In addition, the change in peripheral haemodynamics was related to the degree of hypertension. Moreover, medial--intimal thickening was significantly (P < 0.05) higher in severe hypertensives than mild hypertensives. Popliteal lumen diameter was significantly (P < 0.05) lower in severe hypertensives than moderate and mild hypertensives. In all these subjects mean blood pressure was correlated directly (r = 0.31; P < 0.001) with medial-intimal thickening and inversely (r = -0.37; P < 0.001) with popliteal lumen diameter. Multiple regression analysis indicated that mean blood pressure, age and serum cholesterol were independently correlated to medial-intimal thickening. This relationship was not influenced by the diabetic patients and smokers among the groups. Our results indicate that hypertension impairs peripheral flow and encourages the development of medial-intimal thickening.


Assuntos
Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Perna (Membro)/irrigação sanguínea , Adulto , Idoso , Artérias/diagnóstico por imagem , Feminino , Hemodinâmica , Humanos , Joelho/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia , Resistência Vascular
18.
J Virol ; 75(22): 10843-55, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11602725

RESUMO

Human immunodeficiency virus (HIV)-induced immunodeficiency is characterized by progressive loss of CD4(+) T cells associated with functional abnormalities of the surviving lymphocytes. Increased susceptibility to apoptosis and loss of proper cell cycle control can be observed in lymphocytes from HIV-infected individuals and may contribute to the lymphocyte dysfunction of AIDS patients. To better understand the relation between T-cell activation, apoptosis, and cell cycle perturbation, we studied the effect of exogenous interleukin-2 (IL-2) administration on the intracellular turnover of phase-dependent proteins. Circulating T cells from HIV-infected patients display a marked discrepancy between a metabolic profile typical of G(0) and a pattern of expression of phase-dependent proteins that indicates a more-advanced position within the cell cycle. This discrepancy is enhanced by in vitro activation with ConA and ultimately results in a marked increase of apoptotic events. Conversely, treatment of lymphocytes with IL-2 alone restores the phase-specific pattern of expression of cell cycle-dependent proteins and is associated with low levels of apoptosis. Interestingly, exogenous IL-2 administration normalizes the overall intracellular protein turnover, as measured by protein synthesis, half-life of newly synthesised proteins, and total protein ubiquitination, thus providing a possible explanation for the effect of IL-2 on the intracellular kinetics of cell cycle-dependent proteins. The beneficial effect of IL-2 administration is consistent with the possibility of defective IL-2 function in vivo, which is confirmed by the observation that lymphocytes from HIV-infected patients show abnormal endogenous IL-2 paracrine/autocrine function upon in vitro mitogen stimulation. Overall these results confirm that perturbation of cell cycle control contributes to HIV-related lymphocyte dysfunction and, by showing that IL-2 administration can revert this perturbation, suggest a new mechanism of action of IL-2 therapy in HIV-infected patients.


Assuntos
Ciclo Celular/efeitos dos fármacos , Infecções por HIV/imunologia , Interleucina-2/farmacologia , Linfócitos/efeitos dos fármacos , Terapia Antirretroviral de Alta Atividade , Nucléolo Celular , Cisteína Endopeptidases/biossíntese , Infecções por HIV/tratamento farmacológico , Humanos , Interleucina-2/biossíntese , Linfócitos/fisiologia , Complexos Multienzimáticos/biossíntese , Ornitina Descarboxilase/biossíntese , Complexo de Endopeptidases do Proteassoma
19.
Blood ; 97(6): 1756-64, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11238118

RESUMO

Human immunodeficiency virus (HIV)-infection is characterized by loss of CD4+ T cells associated with high levels of immune activation, T-cell proliferation, and lymphocyte apoptosis. To investigate the role of intrinsic perturbations of cell-cycle control in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS), we studied the expression of cell-cycle-dependent proteins in lymphocytes from HIV-infected patients. Cyclin B1 expression, Nucleolar Organizer Regions (NORs) number, and NORs area of distribution were all consistently increased in HIV-infected patients, but returned to normal after effective antiretroviral therapy, suggesting that viral replication is directly implicated in the genesis of the observed changes. Analysis of cyclin B1 intracellular turnover showed that the increased cyclin B1 expression is (1) caused by defective degradation in the presence of normal rates of synthesis, and (2) is temporally associated with decreased levels of ubiquitination. After in vitro activation of lymphocytes from healthy individuals, cyclin B1 and cdc25 expression and ubiquitination, p34 cdc2 activity, NORs morphology, and C23/nucleolin localization showed a 72- to 96-hour cyclic pattern that led to a biologic state similar to baseline. On the contrary, complex but consistent changes of the same indices followed activation of T lymphocytes from HIV-infected patients, resulting in a 5-fold increase in apoptosis. Overall, our data indicate that a profound dysregulation of cell-cycle control is present in lymphocytes from HIV-infected patients. This finding may provide a novel biologic link between immune activation, accelerated lymphocyte turnover, and increased apoptosis during HIV infection.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Infecções por HIV/patologia , Linfócitos/patologia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Apoptose , Proteína Quinase CDC28 de Saccharomyces cerevisiae/metabolismo , Ciclo Celular , Ciclina B/efeitos dos fármacos , Ciclina B/metabolismo , Ciclina B1 , Infecções por HIV/tratamento farmacológico , Humanos , Cinética , Região Organizadora do Nucléolo/efeitos dos fármacos , Fosfoproteínas/metabolismo , Fosfatases cdc25/metabolismo
20.
Stor Crit Psicol ; 1(1): 79-91, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-11615990
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA