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2.
Endocrine ; 66(2): 405-415, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31317524

RESUMO

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

3.
J Pediatr Surg ; 54(3): 608-611, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30409476

RESUMO

Transverse testicular ectopia is a rare condition in which both testicles occupy a single hemiscrotum. The aberrant positioning may lead to vascular compromise or impaired temperature regulation, which elevate the risks for torsion, infertility and testicular cancer. Definitive therapy consists of orchiectomy or orchiopexy. We report a case of a 10-month-old boy with an incarcerated inguinal hernia who was discovered to have transverse testicular ectopia following hernia reduction. The patient was treated with herniorrhaphy and open transseptal orchiopexy.


Assuntos
Criptorquidismo/cirurgia , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Orquidopexia/métodos , Criptorquidismo/complicações , Hérnia Inguinal/complicações , Humanos , Lactente , Laparoscopia/métodos , Masculino , Testículo/anormalidades , Testículo/cirurgia , Ultrassonografia Doppler/métodos
5.
Med. paliat ; 25(2): 83-94, abr.-jun. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-171707

RESUMO

Objetivo: Objetivo primario. Determinar la supervivencia y los factores predictores de supervivencia en pacientes con insuficiencia renal crónica avanzada (IRCA) desestimados para tratamiento renal sustitutivo (TRS). Objetivos secundarios. Describir: a) las características sociodemográficas de los pacientes y del cuidador principal; b) la etiología de la nefropatía y la comorbilidad asociada; c) variables clínicas de los pacientes cuando son incluidos en el programa; d) la evolución clínica en términos de tensión arterial (TA), número de episodios de sobrecarga hídrica, tratamientos recibidos, frecuencia de hospitalizaciones, causas de las mismas, lugar y causa del fallecimiento; e) la evolución de los parámetros analíticos; f) el grado de información del diagnóstico y del pronóstico del paciente y de la familia, y g) la actividad asistencial realizada por los equipos de soporte de atención paliativa domiciliaria (ESAPD) durante el seguimiento. Material y método: Diseño. Estudio descriptivo longitudinal de cohorte histórica. Ámbito. ESAPD áreas 1, 5 y 7 de Madrid. Sujetos a estudio. Pacientes con IRCA que han sido considerados y desestimados para TRS. Criterios de selección. 1) Pacientes con IRCA que han sido considerados y desestimados para depuración extrarrenal, y 2) el paciente y/o cuidador y/o familia acepta el seguimiento de la enfermedad por el ESAPD y/o por su médico de Atención Primaria. Tamaño de la muestra. Se seleccionaron todas las historias clínicas de los archivos desde la creación de los respectivos ESAPD, desde 1997 hasta diciembre del 2009. Variables analizadas. 1) Respuesta principal: tiempo de supervivencia; 2) variables secundarias: 2.1) sociodemográficas paciente y cuidador principal; edad, sexo; cuidador principal: estado civil, parentesco; 2.2) variables relacionadas con la enfermedad renal; etiología de la nefropatía, motivo de exclusión de TRS, comorbilidad; 2.3) variables clínicas; grado de control TA a lo largo de la evolución de la enfermedad; se recoge la TA en sucesivas visitas; presencia o ausencia de alguno de los siguientes síntomas al inicio del programa: edemas, dolor, estreñimiento, prurito, disnea, insomnio, ansiedad, tristeza y deterioro cognitivo; número de episodios sobrecarga hídrica; causa de salida del programa; lugar del fallecimiento; causa del fallecimiento y síntomas presentes en situación de últimos días; 2.4) variables terapéuticas; número de fármacos al inicio del programa; número de fármacos a la salida del programa de los pacientes cuyo motivo de salida era el exitus; tipo de fármacos; número de transfusiones realizadas; 2.5) variables de ingresos hospitalarios; número de ingresos hospitalarios; causas de hospitalización; 2.6) variables analíticas; grado de control a lo largo de la enfermedad de parámetros analíticos hasta el fallecimiento; 2.7) variables del grado de información del diagnóstico y del pronóstico; 2.8) variables de actividad asistencial; número de visitas domiciliarias realizadas al paciente. Resultados: N: 102 pacientes. Edad media: 79,62 (9,94) años. Etiología IRCA más frecuentes: vascular 37, no filiada 32, diabética 15. Comorbilidad: SCG riesgo bajo 17, SCG riesgo medio 35, SCG riesgo alto 50. Ponderación media del índice de Charlson: 6,88 (2,5).Causa desestimación TRS: comorbilidad 47,5%, edad 25,7%, decisión paciente 22,8%, otras 4%. Grado información diagnóstico paciente y cuidador 57,9 y 94,4%, respectivamente. Grado información pronóstica paciente y cuidador 11,8 y 90%, respectivamente. Síntomas más frecuentes en primera visita: disnea 33,3%, prurito 30,4%, insomnio 34,3%, tristeza 36,3 y edemas 43,1%. Mediana consumo fármacos al inicio: 10, al final de seguimiento: 11. Número de transfusiones: 5. Número de ingresos hospitalarios: 50, por sobrecarga hídrica: 35, comorbilidad: 12, oliguria: 3. Causa exitus: IRCA 72,9%, enfermedad intercurrente 27,1%. Localización exitus: domicilio 39, hospital agudos 31, unidad cuidados paliativos 13, urgencias 2. Media visitas por ESAPD: 11,32, mediana: 6,5. Mediana supervivencia: 4 meses, supervivencia al año: 25%. Factores predictores de supervivencia: creatinina primera visita HZ 1,106 (IC 95% 1,01-1,20), p=0,024; edad 71-80 años, HZ 4,42 (IC 95% 1,60-12,21), edad>81 años, HZ 2,97 (IC 95% 1,16-7,61). No se asoció a supervivencia niveles TA, volumen diuresis, niveles sodio, potasio, calcio, fósforo ni hemoglobina. Conclusiones: Los pacientes con IRCA en los que se desestimó TRS y que fueron seguidos en su domicilio por unidades de cuidados paliativos a domicilio tuvieron una mediana de supervivencia de 4 meses, siendo la edad y la función renal residual factores predictores de supervivencia, sin que la comorbilidad ni los niveles de electrólitos, TA ni el volumen de diuresis se asocien a supervivencia. Durante el seguimiento la causa más frecuente de ingreso hospitalario fue la sobrecarga hídrica. La mayoría de los pacientes fallecieron por la progresión de la IRCA, en su domicilio o en una unidad de cuidados paliativos de media-larga estancia


Objective: Primary objective. To determine survival and survival predictive factors in advanced chronic renal failure (ACRF) patients not considered candidates for renal replacement therapy (RRT). Secondary objectives. To describe: a) the sociodemographic characteristics of the patients and the main caregiver; b) the aetiology and associated comorbidity of the nephropathy; c) the clinical variables of patients when they are included in the programme; d) the clinical outcome in terms of blood pressure (BP), episodes of fluid overload, treatments received, frequency of hospitalisation, causes of hospitalisation, place and cause of death; e) the evolution of analytical parameters; f) the degree of information about diagnosis and prognosis given to the patient and family, and g) care activity provided by the domiciliary palliative care support team (DPCST) during follow-up. Material and method: Design. Longitudinal descriptive study of a historical cohort. Scope. DPCST of Madrid areas 1, 5 and 7. Study subjects. Patients with ACRF not considered candidates for RRT. Selection criteria. 1) patients with ACRF considered and rejected for extra-renal depuration, and 2) the patient and/or caregiver and/or family had accepted follow-up by the DPCST and/or his or her Primary Care physician. Sample size. All clinical histories from the archives of the DPCSTs were selected, from 1997 up to December 2009. Variables analysed. 1) Main answer: time of survival; 2) secondary variables: 2.1) sociodemographic characteristics of patient and caregiver: age and gender; main caregiver: marital status, kinship; 2.2) variables related to the renal disease: the aetiology of the nephropathy, reason for exclusion from RRT, comorbidity; 2.3) clinical variables: degree of BP control during evolution of disease; measurements from several visits were collected; at initiation of programme, the presence or absence of the following was recorded: oedema, pain, constipation, pruritus, dyspnoea, insomnia, anxiety, sadness and cognitive deterioration; number of episodes of fluid overload; cause for exiting the programme; place of death; cause of death and symptoms observed in last days situation; 2.4) therapeutic variables: number of medications at beginning of programme, number of medications at time of exiting the programme, when cause of exit was death; type of medications; number of transfusions received; 2.5) variables of hospital admission: number of admissions; causes of admission; 2.6) analytical variables: degree of control of analytical parameters during illness until death; 2.7) variables on the degree of information about diagnosis and prognosis; 2.8) variables of care activity: number of domiciliary visits to the patient. Results: N: 102 patients. Mean age: 76.92 (9.94) years. Aetiology ACRF: vascular 37, unknown origin 32, diabetic 15. Comorbidity: low risk SCG 17; medium risk SCG 35; high risk SCG 50. Median Charlson comorbidity index: 6.88 (2.5). Cause for rejection for RRT: comorbidity 47.5%, age 25.7%, patient's decision 22.8%, others 4%. Degree of information about diagnosis to patient and caregiver: 57.9 and 94.4%, respectively. Degree of information about prognosis to patient and caregiver: 11.8 and 90%, respectively. Symptoms on first visit: dyspnoea 33.3%, pruritus 30.4%, insomnia 34.3%, sadness 36.3%, oedema 43.1%. Average medications at beginning of follow-up: 10. At the end: 11. Number of transfusions: 5. Number of hospital admissions: 50; caused by fluid overload: 35, comorbidity: 12, oliguria: 3. Cause of death: ACRF 72.9%, intercurrent illness 27.1%. Place of death: home 39, acute hospitalization ward 31, palliative care ward 13, emergency room 2. Average of visits by DPCST: 11.32, median 6.5. Average survival: 4 months, survival at one year: 25%. Predictive survival factors: creatinine on first visit HZ 1.106 (95% CI 1.01-1.20), p=.024; age 71-80 years, HZ 4.42 (95% CI 1.60-12.21), age>81 years, HZ 2.97 (95% CI 1.16-7.61). The following were not associated with survival rates: BP, volume of diuresis, levels of sodium, potassium, calcium, phosphorus and haemoglobin. Conclusions: ACRF patients rejected for RRT receiving domiciliary follow-up by palliative care teams had an average survival of 4 months; age and residual renal function were predictive factors for survival, whereas comorbidity, electrolyte levels, BP and diuresis were not. During follow-up, the most frequent cause of hospital admission was fluid overload. Most patients died because of disease progression, at home or in a palliative care medium-long term hospital ward


Assuntos
Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Diálise Renal/métodos , Diálise Peritoneal/métodos , Cuidados Paliativos na Terminalidade da Vida/métodos , Análise de Sobrevida , Estudos Longitudinais , Análise de Dados/métodos , Insuficiência Renal Crônica/etiologia , Comorbidade
6.
Mediators Inflamm ; 2015: 347965, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25977599

RESUMO

Clinical treatment with glucocorticoids (GC) can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR), a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR-) driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1ß exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1ß and afterwards challenged with GC. After a GC challenge, sustained IL-1ß exposure reduced the cytoplasmic GR level, GR(Ser203) and GR(Ser211) phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1ß, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1ß dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the "split GCR" model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.


Assuntos
Glucocorticoides/metabolismo , Interleucina-1beta/farmacologia , Receptores de Glucocorticoides/metabolismo , Western Blotting , Linhagem Celular , Imunofluorescência , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fatores Reguladores de Interferon/genética , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas de Ligação a Tacrolimo/genética , Tristetraprolina/genética
7.
Proc Natl Acad Sci U S A ; 107(13): 5925-30, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20231472

RESUMO

Studies here respond to two long-standing questions: Are human "pre/pro-B" CD34(+)CD10(-)CD19(+) and "common lymphoid progenitor (CLP)/early-B" CD34(+)CD10(+)CD19(-) alternate precursors to "pro-B" CD34(+)CD19(+)CD10(+) cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig V(H)-D-J(H) sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34(high)Lineage(-) pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34(+)CD45RA(+)CD10(-)CD19(-)) directly generate an initial wave of Pax5(+)TdT(-) "unilineage" pre/pro-B cells and a later wave of "multilineage" CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the V(H)-D-J(H) Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway.


Assuntos
Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/imunologia , Linfopoese/imunologia , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/imunologia , Animais , Antígenos CD19/metabolismo , Antígenos CD34/metabolismo , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/imunologia , Sequência de Bases , Células da Medula Óssea/citologia , Diferenciação Celular/imunologia , Proliferação de Células , Técnicas de Cocultura , DNA/genética , Sangue Fetal/citologia , Sangue Fetal/imunologia , Perfilação da Expressão Gênica , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Recém-Nascido , Leucemia de Células B/genética , Leucemia de Células B/imunologia , Camundongos , Modelos Imunológicos , Neprilisina/metabolismo , Células Estromais/citologia
8.
Colomb. med ; 41(1): 10-16, jan.-mar. 2010. tab, ilus, graf
Artigo em Inglês | LILACS | ID: lil-572987

RESUMO

Introduction: This study shows the relaxant effect induced by ayanin in aorta rings from Wistar rats linked to nitric oxide/cyclic-GMP pathway. This flavonoid is the prevalent compound obtained from Croton schiedeanus Schlecht (Euphorbiaceae), specie used in Colombian folk medicine for the treatment of arterial hypertension. Objectives: To identify possible action mechanisms of vascular relaxation induced by ayanin (quercetin 3,4',7-trimethyl ether).Methodology: Isolated aorta rings from Wistar rats obtained at the Animal House of the University of Salamanca were contracted with KCl (80 mM) or phenylephrine (PE, 10-6 M) and exposed to ayanin (10-6-10-4 M). Then, the effect of ayanin was assessed in deendothelized rings contracted with PE and in intact rings contracted with PE previously incubated with: ODQ (10-6 M), L-NAME (10-4 M), L-NAME plus D- and L-arginine (10-4 M), indomethacin (5x10-6 M), dipyridamole (3x10-7 M), glibenclamide (10-6 M), propranolol (10-6 M), verapamil (10-7 M) or atropine (3x10-5 M). In addition, the relaxant effect of acetylcholine (Ach, 10-8-3x10-4 M), and sodium nitroprusside (SNP, 10-9-3x10-5 M) was assessed in the presence and absence of ayanin (10-6 M).Results: Ayanin induced a greater concentration-dependent relaxation in vessels contracted with phenylephrine (pEC50: 5.84±0.05), an effect significantly reduced by deendothelization and by both ODQ and L-NAME. L-arginine was able to reverse the effect of L-NAME. Indomethacin weakly inhibited ayanin response. Dipyridamole, glibenclamide, propranolol, verapamil, and atropine did not affect ayanin relaxation. Ayanin did not have any effect on the relaxation elicited by acetylcholine (ACh), while weakly decreasing the relaxation induced by sodium nitroprusside (SNP).Conclusion: Ayanin induces endothelium-dependent relaxation in the rat aorta mainly related to nitric oxide/cGMP pathway, according to the response observed in the presence of L-NAME, L-arginine and ODQ.


Introdución: Este estudio muestra el efecto vasodilatador inducido por ayanina en anillos de aorta de ratas Wistar vinculado con la vía óxido nítrico/GMP-cíclico. Este flavonoide es el compuesto mayoritario aislado de Croton schiedeanus Schlecht (Euphorbiaceae), especie utilizada en la medicina popular colombiana para el tratamiento de la hipertensión arterial. Objetivos: Identificar los posibles mecanismos vasodilatadores inducidos por la ayanina (quercetin 3,4',7-trimetileter). Metodología: Se adicionó ayanina (10-6 - 10-4 M) a anillos aislados de aorta procedentes de ratas Wistar contraídos con KCl (80 mM) o fenilefrina (10-6 M). Luego se evaluó el efecto de la ayanina en anillos sin endotelio contraídos con fenilefrina y en anillos íntegros, contraídos con fenilefrina, previamente incubados con: ODQ (10-6 M), L-NAME (10-4 M), L-NAME más L- o D-arginina (10-4 M), indometacina (5x10-6 M), dipiridamol (3x10-7 M), glibenclamida (10-6 M), propranolol (10-6 M), verapamilo (10-7 M) o atropina (3x10-5 M). Además se examinó la relajación inducida por acetilcolina (Ach, 10-8-3x10-4 M) y nitroprusiato de sodio (SNP, 10-9-3x10-5 M) en presencia y ausencia de ayanina (10-6 M). Resultados: La ayanina produjo una mayor relajación en los anillos contraídos con fenilefrina (pEC50: 5.84±0.05), efecto que se redujo en anillos sin endotelio o en anillos íntegros preincubados con ODQ y L-NAME. L-arginina fue capaz de revertir la respuesta inducida por L-NAME. La indometacina inhibió discretamente la relajación generada por la ayanina. El dipyridamol, la glibenclamida, el propranolol, el verapamilo y la atropina no modificaron el efecto de la ayanina. La ayanina no afectó la relajación inducida por la acetilcolina y débilmente disminuyó la inducida por el nitroprusiato de sodio...


Assuntos
Ratos , Aorta , Croton , Fatores Relaxantes Dependentes do Endotélio , Flavonoides , Ratos Wistar , Vasodilatadores
9.
Hepatology ; 42(2): 411-9, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16025514

RESUMO

A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl(4)-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-alpha (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.


Assuntos
Inflamação/etiologia , Cirrose Hepática Experimental/imunologia , Mesentério/imunologia , Monócitos/imunologia , Células Th1/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Polaridade Celular , Inflamação/imunologia , Interferon gama/biossíntese , Linfonodos/imunologia , Masculino , Ratos , Ratos Sprague-Dawley
10.
J Hepatol ; 40(4): 624-31, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15030978

RESUMO

BACKGROUND/AIMS: To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. METHODS: Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. RESULTS: Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. CONCLUSIONS: In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.


Assuntos
Anti-Infecciosos/uso terapêutico , Cirrose Hepática Alcoólica/tratamento farmacológico , Cirrose Hepática Alcoólica/imunologia , Norfloxacino/uso terapêutico , Fator de Necrose Tumoral alfa/biossíntese , Proteínas da Fase Aguda , Ascite/tratamento farmacológico , Ascite/imunologia , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Enterobacteriaceae/imunologia , Enterobacteriaceae/patogenicidade , Feminino , Homeostase , Humanos , Imunidade Celular , Lipopolissacarídeos/sangue , Cirrose Hepática Alcoólica/microbiologia , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Estudos Prospectivos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
11.
Blood ; 101(9): 3424-30, 2003 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-12446447

RESUMO

Circulating CD34(+) cells are used in reparative medicine as a stem cell source, but they contain cells already committed to different lineages. Many think that B-cell progenitors (BCPs) are confined to bone marrow (BM) niches until they differentiate into B cells and that they do not circulate in blood. The prevailing convention is that BCP transit a CD34(+)CD19(-)10(+) early-B-->CD34(+)CD19(+)CD10(+) B-cell progenitor (pro-B)-->CD34(-)CD19(+)CD10(+) B-cell precursor (pre-B) differentiation pathway within BM. However, populations of CD34(+)CD10(+) and CD34(+)CD19(+) cells circulate in adult peripheral blood and neonatal umbilical cord blood (CB) that are operationally taken as BCPs on the basis of their phenotypes, although they have not been submitted to a systematic characterization of their gene expression profiles. Here, conventional CD34(+)CD19(+)CD10(+) and novel CD34(+)CD19(+)CD10(-) BCP populations are characterized in CB by single-cell sorting and multiplex analyses of gene expression patterns. Circulating BCP are Pax-5(+) cells that span the early-B, pro-B, and pre-B developmental stages, defined by the profiles of rearranged V-D-J(H), CD79, VpreB, recombination activating gene (RAG), and terminal deoxynucleotidyl transferase (TdT) expression. Contrary to the expectation, circulating CD34(+)CD19(-)CD10(+) cells are essentially devoid of Pax-5(+) BCP. Interestingly, the novel CD34(+)CD19(+)CD10(-) BCP appears to be the normal counterpart of circulating preleukemic BCPs that undergo chromosomal translocations in utero months or years before their promotion into infant acute lymphoblastic B-cell leukemia after secondary postnatal mutations. The results underscore the power of single-cell analyses to characterize the gene expression profiles in a minor population of rare cells, which has broad implications in biomedicine.


Assuntos
Linfócitos B/citologia , Perfilação da Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Antígenos CD19/análise , Diferenciação Celular , Linhagem da Célula , Proteínas de Ligação a DNA/análise , Células-Tronco Hematopoéticas/classificação , Células-Tronco Hematopoéticas/metabolismo , Humanos , Recém-Nascido , Neprilisina/análise , Fator de Transcrição PAX5 , Receptores de Complemento 3b/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/análise
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