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1.
Sci Total Environ ; 951: 175718, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39181251

RESUMO

The experiment was conducted in an Open Top Chamber facility located in the Mediterranean basin to investigate how nitrogen (N) fertilization affects the response of wheat to ozone (O3) exposure. The study considered the response of Artur Nick, a modern wheat cultivar commonly used in the area, to three O3 exposure levels (ambient and elevated ambient, +20 and +40 nL L-1 O3), and two N fertilization doses (100 and 200 kg ha-1). Measurements included leaf gas exchange, leaf chlorophyll content, leaf and grain N content, plant growth and yield parameters. Ozone × N interactive effects were studied and quantified based on accumulated O3 concentrations above a 40 nL L-1 threshold (AOT40) and phytotoxic O3 dose (POD) indices, which are used in O3-risk assessments, from which critical levels (CL) for a 5 % effect were derived. Results revealed that O3 impacts on growth and yield parameters were stronger under the highest N fertilization dose. In consequence, O3 Critical Levels (CL) were as much as 3-4 times lower for grain yield in the high-N compared to the low-N treatment. Interestingly, O3 limited the fertilizer stimulus, strongly reducing the N use efficiency for grain yield and the agronomic efficiency of N for protein yield. Another important aspect was that 71 % of the POD was accumulated before anthesis, stressing the potential importance of O3 exposure during the vegetative phase of wheat under Mediterranean conditions, which is usually considered less important than post-anthesis exposure. In conclusion, this study suggests the need to consider crop N management in the derivation of O3 CLs, due to its effect on dose-response relationships used for CL derivation, including the potential O3 effects in N use efficiency. Therefore, N modulation could be considered in the O3-risk assessment methodology to be applied in risk exercises when negotiating air pollution abatement policies.

2.
Arch Inst Pasteur Tunis ; 90(1-4): 61-7, 2013.
Artigo em Francês | MEDLINE | ID: mdl-26012212

RESUMO

Multiple myeloma (MM) is a still incurable adult's severe hematologic malignancy. It is characterized by deregulation of several cytokines and their receptors. Among these cytokines, Insulin growth factor 1 (IGF1) and its receptor (IGF1-R) are well documented as major factor of malignant plasma cells growth and survival in multiple myeloma. The objective of this study was to analyze the expression of IGF1-R in multiple myeloma at diagnosis in correlation with clinical and biological data. IGF1-R gene plasma cells expression was studied in 47 patients and 17 controls by Taqman technology RT-PCR. IGF1-R gene was down expressed in the malignant plasma cells of MM patients at diagnosis compared to normal plasma cells, isolated from healthy donors (p = 0.01). Expression decrease was accentuated in the disease advanced stage IIIB. A negative correlation was found between IGF1-R malignant plasma cells expression and the percentage of bone marrow invasion (p = 0.03). Bone marrow infiltration greater than 30% was significantly associated with a low level of IGF1-R gene expression (p = 0.04). Our results suggest that the decreased expression of IGF1-R by malignant plasma cells is a prognostic factor associated with severe disease. Understanding of mechanisms involved in IGF1-R expression negative regulation may contribute to the discovery of new targets therapy in myeloma. the discovery of new targets therapy in myeloma.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Receptor IGF Tipo 1/genética , Transcriptoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Tunis Med ; 89(2): 188-91, 2011 Feb.
Artigo em Francês | MEDLINE | ID: mdl-21308630

RESUMO

BACKGROUND: Ochronosis of alkaptonuria is a rare hereditary autosomal recessive disease in which there is an absence of homogentisic acid oxidase resulting in accumulation of homogentisic acid in tissues. AIM: To report a new case of alkaptonuria CASE REPORT: A 49-year-old man had been followed for 4 years for chronic lombalgia and arthropaty of two knees. He is married to his cousin and father of 4 girls. His parents are also cousins. The clinical examination has found a cutaneuous pigmentation and a lumbar stiffness. At biological checking, creatininemia was at 190 µmol/L and there are not inflammatory indicators. The radiography have shown a discal dorsolumbar calcifications, anterior inter somatic bridges and bilateral arthritis of knees without articular chondrocalcinosis. The diagnosis of ochronosis have been suspected and confirmed by the blackness of urine and the dosage of alkaptonuria. The patient has been treated symptomatiquely. Familial investigation have revealed that his daughter suffered from the same disease with the notion of blackness of urine. She is 12 year old and she's asymptomatic on the osteoarticular level. CONCLUSION: Alkaptonuria causes a degenerative arthropaty which can endanger functional prognosis. Early diagnosis and scanning of this innate error of metabolism by genetic study play a fundamental interest, especially for molecular and genetic advisement.


Assuntos
Alcaptonúria/diagnóstico , Alcaptonúria/genética , Calcinose/diagnóstico por imagem , Criança , Consanguinidade , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ocronose/diagnóstico , Ocronose/genética , Radiografia
4.
Ann Cardiol Angeiol (Paris) ; 68(5): 306-309, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31540700

RESUMO

BACKGROUND: Syncope or stroke remain frequently without any explained diagnosis. Long duration holter ECG is an available tool to diagnose arrhythmias. However, this tool is subject to availability of the recorders. AIM: Report a single center experience with long duration holter ECG in clinical practice, in the different cardiology and neurology indications, and to assess the different delays until achievement of a diagnosis. METHODS AND RESULTS: The device (Sorin Spiderflash) was used for 48 patients between January 2018 and June 2018. The holter was applied for a mean duration of 10±4days. The mean age was 55+19 years-old. 20 patients (42%) were explored for a stroke or transient ischemic attack (TIA), 18 (36%) for palpitations, 6 (12%) for syncope and 4 (8%) for evaluation of arrhythmias management. An abnormality has been recorded in 11 (22%) patients and a treatment has been administered in 5 patients (10%). Regarding, the timing of the exam, the mean time between the index event and the indication was 39 days. The mean time between the indication and the availability of the device was 32 days. 16 Days was the mean time for lecture and 23 days was the mean time between the result and the appointment with the cardiologist and neurologist. CONCLUSION: In this registry, the management of patients by non-invasive long duration holter ECG monitoring may be improved regarding the timing of the exams, their lecture and new appointments with the physicians.


Assuntos
Arritmias Cardíacas/diagnóstico , Eletrocardiografia Ambulatorial , Adulto , Idoso , Arritmias Cardíacas/complicações , Eletrocardiografia Ambulatorial/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
5.
Ann Biol Clin (Paris) ; 66(4): 471-4, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18725352

RESUMO

The authors report an 11-day-old exclusively breast-fed female, with a birth weight of 3 300 g, who had suffered from dehydration stage I, with acute renal failure and metabolic acidosis, with 170 mmol/L of serum sodium. Renal ultrasounds were normal but the rate of sodium in mother's milk was three times higher than controls (87 versus 21 mmol/L). Intravenous rehydration allowed the correction of hydroelectrolytic disorders.


Assuntos
Aleitamento Materno/efeitos adversos , Desidratação/etiologia , Hipernatremia/etiologia , Feminino , Humanos , Recém-Nascido
6.
Ann Biol Clin (Paris) ; 64(4): 319-26, 2006.
Artigo em Francês | MEDLINE | ID: mdl-16829474

RESUMO

INTRODUCTION: the measurement of plasma haemoglobin is utilized in the evaluation of various haemolytic phenomenons, especially at the time of sampling. Besides, the methods used to titrate plasmatic haemoglobin, an analysis which is of great interest to cardiac surgery, must be very accurate, because plasmatic levels are much lower than those found in whole blood. BACKGROUND: the purpose of this work is to present a new technique for direct determination of plasmatic haemoglobin. MATERIAL AND METHODS: this method was studied and adapted on a multiparametric analyzer Konelab 30 (Thermo Electron Corporation). The correlation was assessed with a Sigma Diagnostics spectrophotometric method, using the 3,3',5,5'-tetramethylbenzidine (TMB), a non carcinogenic reagent. The reaction of haemoglobin with TMB was studied with a SECOMAM S500P UV-Visible spectrometer. RESULTS AND DISCUSSION: the method demonstrates linearity, precision, and sensitivity suitable for clinical use and not affected by the presence of bilirubin, nor triglycerides. The method was precise (CV < 1,00%), accurate (CE < 5,00%) and showed excellent recovery of haemolysis (R > 0,95). The CV for the automated assay was less than 1%. Reference ranges were studied and lithium heparinate seems to be the best anticoagulant to use so as to minimize haemolysis. CONCLUSION: the studied technique is practical, specific, accurate, fast, reliable and inexpensive, and was adopted in emergency as in daily routine in our laboratory for plasmatic haemoglobin determination in various situations.


Assuntos
Hemoglobinas/análise , Hemólise , Humanos , Indicadores e Reagentes , Plasma , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria/instrumentação , Espectrofotometria/métodos
7.
Exp Hematol ; 26(9): 903-9, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9694512

RESUMO

In the present study we investigated the effect of anti-CD3 stimulation on IL-3-induced histamine, IL-6, and IL-4 synthesis by murine hematopoietic precursor cells. These activities were strikingly decreased in splenocytes from mice that had received a single intravenous injection of 10 microg of anti-CD3 monoclonal antibody (mAb) 24 hours previously. A similar inhibition occurred after 24-hour in vitro stimulation of normal spleen cells with 1 microg/mL of anti-CD3 mAb. In both situations the inhibitory effect depended on T cell activation in that treatment with F(ab')2 fragments of anti-CD3 did not diminish secretion of histamine and cytokines. Cross-linking of Fas antigen on spleen cells mimicked the action of anti-CD3, provided that interferon (IFN)-gamma was present during the incubation period. Substantial amounts of this cytokine were detected in spleen cell supernatants, which were able to replace recombinant IFN-gamma during Fas receptor cross-linking. This effect was entirely mediated by IFN-gamma, as assessed by its neutralization in the presence of anti-IFN-gamma mAbs. In contrast to splenocytes, bone marrow cells responded normally to IL-3 after in vivo or in vitro stimulation with anti-CD3. They were also not affected by combined treatment with anti-Fas mAb and IFN-gamma. Together, our data support the notion that the decrease in IL-3-induced histamine and IL-6 production by splenocytes pretreated with anti-CD3 is mediated, at least in part, by Fas/FasL interactions, suggesting that the activity of extramedullary myeloid precursor cells can be modulated by molecules involved in apoptosis.


Assuntos
Basófilos/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Histamina/biossíntese , Interleucina-3/farmacologia , Interleucina-4/biossíntese , Interleucina-6/biossíntese , Muromonab-CD3/farmacologia , Baço/citologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Receptor fas/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Ensaio de Unidades Formadoras de Colônias , Feminino , Células-Tronco Hematopoéticas/citologia , Histamina/genética , Interferon gama/biossíntese , Interferon gama/fisiologia , Interleucina-4/genética , Interleucina-6/genética , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , Organismos Livres de Patógenos Específicos , Subpopulações de Linfócitos T/metabolismo
8.
Eur Cytokine Netw ; 6(4): 221-4, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8789286

RESUMO

In the present study, we demonstrate that unresponsive spleen T cells from mice injected with a low dose of anti-CD3 mAb (single 10 micrograms i.v. injection) significantly inhibit Con A-induced proliferation of normal spleen cells. The induction of this phenomenon requires in vivo activation since spleen cells from mice injected with the F(ab')2 fragment of anti-CD3 mAb fail to promote it. Suppression of normal T cell proliferation is concomitant with increased expression of IL-2 receptor on spleen cells from anti-CD3-treated mice. It disappears within 3 days when IL-2R has returned to background levels. A normal proliferative response to Con A can be restored when high concentrations of IL-2 are added together with the "suppressor" cells. Taken together, these data support the notion that activated spleen cells from anti-CD3-injected mice exert their inhibitory effect by competing for the IL-2 generated during culture.


Assuntos
Tolerância Imunológica , Receptores de Interleucina-2/imunologia , Baço/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Concanavalina A/farmacologia , Cricetinae , Feminino , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-2/antagonistas & inibidores , Baço/citologia , Linfócitos T/imunologia
9.
Ann Endocrinol (Paris) ; 64(6): 428-33, 2003 Dec.
Artigo em Francês | MEDLINE | ID: mdl-15067247

RESUMO

Craniopharyngioma, an intra- and suprasellar tumor generally observed in pediatric patients, can also occur in adults. We report three cases of histologically confirmed craniopharyngioma in three men aged 34 to 53 Years. Clinical manifestations were headache with visual and gonadic disorders associating impotence, infertiligy, and gynecomastia. Computed tomographic and magnetic resonance imaging revealed an intra- and suprasellar tumor with solid, hydric, and calcified components. Third ventricle compression was observed in two patients. Hormone test revealed gonadotrope insufficiency in two patients, associated with hyperprolactinemia in one of them, and pituitary insufficiency in the third patient. None of the patients had diabetes insipidus. The frontopterional approach was used for surgery. One patient died and the two others experienced persistent visual impairment with worsening pituitary insufficiency. Our observations suggest that these craniopharyngiomas were probably clinically latent congienital forms since endocrine features were lacking during childhood. Early diagnosis is required to achieve good outcome.


Assuntos
Craniofaringioma/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Adulto , Calcinose/etiologia , Terapia Combinada , Craniofaringioma/complicações , Craniofaringioma/congênito , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Disfunção Erétil/etiologia , Evolução Fatal , Cefaleia/etiologia , Humanos , Hiperprolactinemia/etiologia , Hipofisectomia , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Hormônios Adeno-Hipofisários/deficiência , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/congênito , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Radioterapia Adjuvante , Transtornos da Visão/etiologia
10.
Ann Urol (Paris) ; 37(4): 217-9, 2003 Aug.
Artigo em Francês | MEDLINE | ID: mdl-12951718

RESUMO

The purpose of our study is to compare the status of vitamin A and E enters a group of male patients aged 30-40 years and having idiopathic lithiasis in the other whose origin of the lithiasis is awarded to a hypercalciuria and/or hypercalciuria and/or hyperoxaluria. Reference values were established from a normal subjects aged 30-40 years and having no history of nephrolithiasis. Our results showed that the mean levels of vitamin A was significantly lower in idiopathic renal stone-formers than metabolic stone-formers (p < 0.001). Compared to control group, the status of vitamin A was found lower only in idiopathic renal stone patients (p < 0.05). On the contrary, the mean levels of vitamin E were found similar in the two patient groups, but significantly lower compared to control group. These results suggested that idiopathic renal stone genesis could be generated by vitamin A deficiency.


Assuntos
Cálculos Renais/etiologia , Deficiência de Vitamina A/complicações , Deficiência de Vitamina E/complicações , Adulto , Humanos , Masculino , Valores de Referência , Fatores de Risco
11.
Rev Laryngol Otol Rhinol (Bord) ; 123(4): 243-6, 2002.
Artigo em Francês | MEDLINE | ID: mdl-12723490

RESUMO

The thyroïd pseudo-nodules constitute cervical lesions that can simulating neoplastic thyroid lesions either by their size or by their "cold" character in scintigraphy. We describe 3 cases of thyroïd pseudo-nodules collected in 10 years: a thyroid hydatid cyst, a schwannoma of the recurrent nerve and a thyroglossal duct cyst. Throw these observations, the authors discuss the problems of differential diagnosis set out with these pseudo-nodules. Although the diagnosis in the 3 cases, was histological after post operative exam, the authors insist throw a review of the literature, on the place of fine needle aspiration cytology in the therapeutic strategy that can show specific signs for some lesions. For the other cases, surgery resection is effected to eliminate malignant lesions who are the principal differential diagnosis of thyroid pseudo-nodules.


Assuntos
Equinococose/diagnóstico , Neurilemoma/diagnóstico , Cisto Tireoglosso/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Adulto , Biópsia por Agulha , Diagnóstico Diferencial , Equinococose/patologia , Equinococose/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neurilemoma/patologia , Neurilemoma/cirurgia , Cisto Tireoglosso/patologia , Cisto Tireoglosso/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia
12.
Gynecol Obstet Fertil ; 42(6): 399-403, 2014 Jun.
Artigo em Francês | MEDLINE | ID: mdl-24411339

RESUMO

INTRODUCTION: The assessment of fetal head engagement by digital examination is highly subjective even though this method remains the gold standard. Ultrasound could be a new way to specify the fetal head engagement with objective and reproductible measurements. OBJECTIVE: To compare the clinical data and the transperineal ultrasound results for the diagnosis of fetal head engagement. PATIENTS AND METHODS: We conducted a prospective longitudinal study on a series of 70 patients and compared the clinical assessment of fetal engagement to the ultrasound measurements. Ultrasound examination was performed in the delivery room. The probe was placed on the ano-vulvar area. The measure used was: distance perineum-external table of fetal head bone. RESULTS: The ultrasound measures of the distance [perineum-external table of fetal head bone] went from 13 to 75 mm; and the measures of the distance [perineum-succedaneum bump] went from 22 to 68 mm. We tried to retain a value threshold of the distance [perineum-external table of fetal head bone] above which the diagnosis of engagement would be countered. The threshold so proposed is of 55 mm with a positive predictive value in 98%, a sensibility in 87% and specificity in 93%. DISCUSSION AND CONCLUSION: Transperineal ultrasound is a simple and easy method to define fetal head engagement by measuring the distance between perineum and fetal head. This new tool can be very useful in the delivery room when clinical examination is inconclusive hampered, for example, by the presence of a succedaneum bump.


Assuntos
Cabeça/diagnóstico por imagem , Cabeça/embriologia , Apresentação no Trabalho de Parto , Trabalho de Parto , Ultrassonografia Pré-Natal , Adulto , Feminino , Humanos , Estudos Longitudinais , Palpação , Períneo/diagnóstico por imagem , Gravidez , Estudos Prospectivos , Tunísia
13.
Work ; 41 Suppl 1: 496-502, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22316772

RESUMO

The purpose of this paper is to present an ergonomic evaluation of a situation of co-exposure to solvents and noise in a flexible packaging printer. We discuss how such an approach carried out in the field of printing industry work has made it possible to highlight serious shortcomings in the effectiveness of the prevention actions that are supposed to protect workers from chemicals risks and noise. The ergonomic analysis identified a strain working conditions. Indeed, some jobs expose to noise and toxic risk. Lamination operations, winding and cutting are purveyors of noise. Some physical and spatial factors contribute to amplify the toxic risk. The not wearing of personal protective equipment (PPE) by the operators maybe explained by the fact that it doesn't any possibility to do "otherwise". Indeed, operators adopt a compromise to achieve the objectives of production to the detriment of their health and safety. These constraints are causing gene and psychosocial factors. The interviews revealed a state of psychosis in the workshop, which was accentuated by the reclassification of an operator which has created a climate of panic and anxiety especially for older operators who have more than 20 years exposed to handling of toxic and more exposure to high noise level.


Assuntos
Poluentes Ocupacionais do Ar/análise , Ergonomia , Ruído Ocupacional , Exposição Ocupacional/análise , Impressão , Solventes/análise , Adulto , Humanos , Masculino , Impressão/instrumentação , Embalagem de Produtos , Pesquisa Qualitativa , Inquéritos e Questionários , Tunísia , Adulto Jovem
16.
Neuroscience ; 154(4): 1607-18, 2008 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-18515016

RESUMO

Acetylcholine is released in the primary visual cortex during visual stimulation and may have a neuromodulatory role in visual processing. The present study uses both behavioral and functional neuroanatomy investigations to examine this role in the rat. In the first set of experiments the cholinergic system was lesioned with 192 immunoglobulin G (IgG) saporin and the visual acuity and performance in a visual water maze task were assessed. The cholinergic lesion did not affect the visual acuity measured pre- and post-lesion but it did reduce the efficiency to learn a novel orientation discrimination task measured post-lesion. In order to better understand the involvement of the cholinergic system in the neuronal activity in the visual cortex c-Fos expression induced by patterned visual stimulation was further investigated. Results obtained following lesion of the cholinergic fibers (192 IgG-saporin or quisqualic acid), muscarinic inhibition (scopolamine), or NMDA receptor inhibition (CPP) were compared with control conditions. Double and triple immunolabeling was used in order to determine the neurochemical nature of the activated cortical cells. The results demonstrated that patterned stimulation elicited a significant increase in c-Fos immunolabeled neurons in layer IV of the contralateral primary visual cortex to the stimulated eye which was completely abolished by cholinergic fibers lesion as well as scopolamine administration. This effect was independent of NMDA receptor transmission. The c-Fos activation was predominantly observed in the glutamatergic spiny stellate cells and less frequently in GABAergic interneurons. Altogether, these results demonstrate a strong involvement of the basal forebrain cholinergic system in the modulation of post-synaptic visual processing, which could be related to cognitive enhancement or attention during visual learning.


Assuntos
Acetilcolina/metabolismo , Córtex Visual/citologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Fibras Colinérgicas/metabolismo , Lateralidade Funcional/fisiologia , Imuno-Histoquímica , Masculino , Estimulação Luminosa , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Endogâmicos LEC
17.
Orthod Fr ; 74(4): 467-72, 2003 Dec.
Artigo em Francês | MEDLINE | ID: mdl-15301360

RESUMO

Over the course of time, an esthetic standard, molded by a certain number of rules, recognized virtually universally, has gained widespread recognition. Orthodontics, like the rest of the world, accepts this rule. So, we all try in our treatment objectives to conform to a set of standardized "norms" of facial and cephalometric esthetics. Still, one question must be asked: can these norms be the same throughout the four corners of the globe? Having pondered this matter carefully, we attempted to find an answer by undertaking a study of 53 patients with "normal dentitions", all students of dental medicine. On profile cephalograms and profile photographs of these patients, we carried out a variety of esthetic analyses. We then compared the results obtained with orthodontic averages and found that they differed in many points. Should this finding impel us to adopt different esthetic criteria? However, this question may be answered, we retain our essential conviction that we should endeavor to preserve the goal of achieving facial harmony for our patients and that we should know what its criteria are.


Assuntos
Cefalometria/normas , Estética Dentária , Face/anatomia & histologia , Adulto , Beleza , Humanos , Tunísia
18.
Stem Cells ; 15(2): 154-60, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9090792

RESUMO

The present study evaluates hematopoietic modifications consecutive to in vivo treatment of mice with anti-CD3 monoclonal antibodies (mAb). The hamster mAb 145-2C11, administered in a single i.v. injection of 10 micrograms, induced the release of both interleukin 3 (IL-3) and GM-CSF into the circulation. IL-3 could be detected in the serum within 1 h, attained maximal levels after 4 h and had disappeared after 24 h. Three days later, treated mice exhibited a two- to threefold rise in blood neutrophil levels and increased spleen cell counts. Concomitantly, the incidence of nucleated erythroid cells in these spleens increased around 10-fold, relative to controls having received hamster Ig. At the same time point, clonogenic progenitor frequencies were 10-fold higher in spleens from treated mice than in those from control mice. Furthermore, the responsiveness of these splenocytes to IL-3, in terms of histamine synthesis, was enhanced. In contrast, bone marrow cell populations were only slightly affected by anti-CD3 injection. All hematopoietic changes required multivalent crosslinking of the mAb for induction, since F(ab')2 fragments lacked this activity. A return to normal occurred 7-10 days after treatment. Two i.v. injections of recombinant murine IL-3 together with recombinant murine GM-CSF on a single day had a less pronounced effect on progenitor cell frequencies in the spleen than treatment with anti-CD3. This difference is probably due to the amplification of growth factor-induced hematopoiesis by the interaction with other cytokines generated in response to anti-CD3.


Assuntos
Complexo CD3/imunologia , Hematopoese/imunologia , Muromonab-CD3/farmacologia , Animais , Células da Medula Óssea , Complexo CD3/efeitos dos fármacos , Complexo CD3/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Hematopoese/efeitos dos fármacos , Injeções Intravenosas , Interleucina-3/biossíntese , Interleucina-3/metabolismo , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Muromonab-CD3/administração & dosagem , Muromonab-CD3/metabolismo , Baço/citologia
19.
Clin Exp Immunol ; 103(3): 491-8, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8608651

RESUMO

Anti-CD3 MoAb treatment is widely used as an immunosuppressive therapy. In the present study we examined the in vitro T cell response in mice having received 24 h before a single i.v. injection of 10 microgram of anti-CD3 MoAb. We found that splenocytes from these mice displayed a dramatically decreased proliferative response to the T cell mitogens concanavalin A (Con A), anti-CD3, phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) + calcium ionophore, while the effect of lipopolysaccharide (LPS) was not impaired. T cell suppression persisted for about 10 days after anti-CD3 injection, returning to normal within 15 days. The F(ab')2 fragment of anti-CD3 had no such effect, indicating the requirement for in vivo activation. At the dose used, anti-CD3 resulted neither in T cell depletion nor in down-modulation of the CD3/T cell receptor (TCR) complex. The low proliferation was also not explained by apoptosis, following secondary challenge with Con A. Splenocytes from anti-CD3-injected mice were highly responsive to IL-2, but generated little or no IL-2, IL-3, IL-4 and interferon-gamma (IFN-gamma) when exposed to Con A. Normal cytokine production could not be restored by the addition of optimal doses of IL-2 during Con A stimulation. Transforming growth factor-beta (TGF-beta) was the only cytokine whose mRNA expression was not modified in stimulated splenocytes from anti-CD3-injected mice. Furthermore, anti-TGF-beta antibodies increased Con A-induced T cell proliferation, but not cytokine production.


Assuntos
Anticorpos Monoclonais/farmacologia , Complexo CD3/imunologia , Linfócitos T/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Concanavalina A/farmacologia , Cricetinae , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Interleucina-2/farmacologia , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Coelhos , Baço/citologia , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/farmacologia
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