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1.
Ann Plast Surg ; 77(6): 623-625, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27404475

RESUMO

BACKGROUND: Distal radius fractures are common, accounting for approximately 18% of all fractures in adults. Operative management is common, and there are numerous variants of plates used. However, data on safety and complication rates for different plates are limited. OBJECTIVE: To determine whether the rate of complications differed between two distinct types of volar plate design for distal radius fracture fixation, one using predetermined fixed angles for the locking screws or pegs and the other using a variable angle locking design for the locking screws or pegs. Our null hypothesis was that the rate of complications would be the same in each group. MATERIALS AND METHODS: A retrospective chart review was performed on patients with unstable distal radius fractures treated operatively between 2008 and 2011. Patients treated with external fixation or small fragment plates were excluded; all remaining patients underwent internal fixation with 1 of 3 plate designs: Stryker Universal Distal Radius Plate, Acumed Acu-Loc, or Trimed Volar Bearing Plate. RESULTS: A total of 189 patients underwent surgical treatment for an unstable distal radius fracture with a volar plate. Fixed angle plates were used in 60 patients and polyaxial locking plates using a rotatable bearing were used in 148 patients. In the fixed angle plate group, 11 required a second operation on the affected limb for a total of 18 procedures. In 7 of 11 patients, secondary surgery was directly related to complications from the hardware (symptomatic hardware, loose hardware and tendon rupture). All 7 of these patients were in the fixed angle plate group, for a rate of hardware related complications of 12% (7/60). No hardware related complications occurred in patients in the group treated with a polyaxial locking plate (0/129). The complication rate in the fixed angle plate group is significantly different than 0, the rate observed in the polyaxial locking plate group (z score = 3.95, P < 0.001). CONCLUSIONS: Our data suggest that treatment of unstable distal radius fractures with a volar bearing variable angle plate fixation is safe and effective. In our series, there was a significant reduction in the rate of hardware-related complications with the polyaxial locking plate as compared with a fixed angle plate.Therapeutic, Level III, retrospective comparative study.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Complicações Pós-Operatórias/epidemiologia , Fraturas do Rádio/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Cleft Palate Craniofac J ; 53(3): 302-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26575966

RESUMO

OBJECTIVE: To analyze indications and outcomes for primary premaxillary setback. DESIGN: Retrospective. SETTING: Academic children's hospital. PATIENTS: All children with bilateral complete cleft lip age ≤2 years of age who had premaxillary setback by one surgeon (1992 to 2011). RESULTS: Twenty-five patients with bilateral complete cleft lip underwent primary premaxillary setback at an average age of 9 months; the mean follow-up was 47 months. There were three indications: failed dentofacial orthopedics (n = 9), delayed referral precluding manipulation (n = 10), and intact secondary alate (n = 6). Of 19 patients with bilateral complete cleft lip/palate, primary setback was combined with nasolabial repair (n = 11), adhesions (n = 2), or palatoplasty (n = 6). Patients who had nasolabial closure and setback were significantly younger than those who had combined palatal closure and setback (6.5 versus 16 months, P = .01). No patient exhibited postoperative premaxillary instability. Serial anthropometry showed similar growth of nasolabial features after both primary setback (n = 9) and active dentofacial orthopedics (n = 35). CONCLUSIONS: Primary premaxillary ostectomy and setback permits synchronous bilateral nasolabial-alveolar closure or alveolar-palatal repair in a child with intact secondary palate. This procedure should be considered whenever dentofacial orthopedics cannot be accomplished. Speech is paramount in an older child; setback with palatal closure is scheduled before nasolabial repair. Disturbance of midfacial growth is likely following primary premaxillary ostectomy and setback in patients with bilateral complete cleft lip/palate; however, most already need maxillary advancement. Furthermore, premaxillary setback permits proper primary nasolabial design and construction in appreciation of expected changes with growth.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Maxila , Procedimentos de Cirurgia Plástica , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos
3.
Ann Plast Surg ; 74(6): 672-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24317242

RESUMO

BACKGROUND: Process management within a health care setting is poorly understood and often leads to an incomplete understanding of the true costs of patient care. Using time-driven activity-based costing methods, we evaluated the high-volume, low-complexity diagnosis of plagiocephaly to increase value within our clinic. METHODS: A total of 59 plagiocephaly patients were evaluated in phase 1 (n = 31) and phase 2 (n = 28) of this study. During phase 1, a process map was created, encompassing each of the 5 clinicians and administrative personnel delivering 23 unique activities. After analysis of the phase 1 process maps, average times as well as costs of these activities were evaluated for potential modifications in workflow. These modifications were implemented in phase 2 to determine overall impact on visit-time and costs of care. RESULTS: Improvements in patient education, workflow coordination, and examination room allocation were implemented during phase 2, resulting in a reduced patient visit-time of 13:25 (19.9% improvement) and an increased cost of $8.22 per patient (7.7% increase) due to changes in physician process times. However, this increased cost was directly offset by the availability of 2 additional appointments per day, potentially generating $7904 of additional annual revenue. Quantifying the impact of a 19.9% reduction in patient visit-time at an increased cost of 7.7% resulted in an increased value ratio of 1.113. CONCLUSIONS: This pilot study effectively demonstrates the novel use of time-driven activity-based costing in combination with the value equation as a metric for continuous process improvement programs within the health care setting.


Assuntos
Redução de Custos/métodos , Custos Hospitalares/estatística & dados numéricos , Plagiocefalia/terapia , Melhoria de Qualidade/organização & administração , Boston , Redução de Custos/estatística & dados numéricos , Humanos , Satisfação do Paciente/estatística & dados numéricos , Projetos Piloto , Plagiocefalia/diagnóstico , Plagiocefalia/economia , Avaliação de Processos em Cuidados de Saúde , Melhoria de Qualidade/estatística & dados numéricos , Fatores de Tempo
4.
Ann Plast Surg ; 73(2): 156-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23407261

RESUMO

PURPOSE: This study aimed to introduce the technique and results of a forearm Bier block for upper extremity surgery. INTRODUCTION: Various techniques of anesthesia are used for hand surgery. Intravenous regional anesthesia, the Bier block, is an effective anesthetic technique. However, there exist several disadvantages and potential complications. We present our technique and results using the forearm Bier block. MATERIALS AND METHOD: A retrospective review was performed studying our experience using forearm Bier block from May to December of 2010. The technique involves exsanguination of the forearm and inflation of a pneumatic tourniquet placed distal to the elbow joint. Twenty-five milliliter of 0.5% lidocaine is injected intravenously. One hundred five patients underwent hand surgery using this technique. There were 53 females and 52 males with a median age of 56 years. In total, 121 procedures were performed. Patients were interviewed by telephone 24 hours postoperatively. RESULTS: All patients received adequate anesthesia from the block. There were no intraoperative and no postoperative complications. There were no mechanical or tourniquet problems. Average tourniquet time was 10.1 minutes. Total operating time was less than 30 minutes. DISCUSSION: Forearm Bier block presents several advantages over standard upper arm technique. Conventional Bier block involves a double tourniquet and a significant amount of lidocaine, which has potential cardiac and neurologic toxicity. Consequently, minimum tourniquet inflation time is 30 minutes. The dosage of lidocaine needed to provide analgesia using the forearm Bier block is significantly reduced, thereby minimizing the potential for these complications. This lower dose allows for shorter tourniquet time rather than the standard 30 minutes. This shorter tourniquet time in itself presents several advantages. Tourniquet pain and risk of ischemic problems are minimized, and efficiency is increased. This efficiency has practical and financial implications such as decreased total operating and recovery room times, decreased cost of medicines, and decreased operating time for the surgeon. Lastly, this technique might also be used for lower extremity surgeries. CONCLUSIONS: Forearm Bier block is a safe and efficient method for upper extremity surgery. It significantly reduces the risk of complications and increases the efficiency of the surgeon and surgery facility.


Assuntos
Anestésicos Locais/administração & dosagem , Antebraço , Mãos/cirurgia , Lidocaína/administração & dosagem , Bloqueio Nervoso/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Intravenosa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Torniquetes , Adulto Jovem
5.
Ann Otol Rhinol Laryngol ; 117(5): 327-34, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18564528

RESUMO

OBJECTIVES: Acquired subglottic stenosis in a newborn is often associated with prolonged endotracheal intubation. This condition is generally diagnosed during operative endoscopy after airway injury has occurred. Unfortunately, endoscopy is unable to characterize the submucosal changes observed in such airway injuries. Other modalities, such as magnetic resonance imaging, computed tomography, and ultrasound, do not possess the necessary level of resolution to differentiate scar, neocartilage, and edema. Optical coherence tomography (OCT) is an imaging modality that produces high-resolution, cross-sectional images of living tissue (8 to 20 microm). We examined the ability of this noninvasive technique to characterize the newborn airway in a prospective clinical trial. METHODS: Twelve newborn patients who required ventilatory support underwent OCT airway imaging. Comparative analysis of intubated and non-intubated states was performed. RESULTS: Imaging of the supraglottis, glottis, subglottis, and trachea was performed in 12 patients, revealing unique tissue characteristics as related to turbidity, signal backscattering, and architecture. Multiple structures were identified, including the vocal folds, cricoid cartilage, tracheal rings, ducts, glands, and vessels. CONCLUSIONS: Optical coherence tomography clearly identifies in vivo tissue layers and regional architecture while offering detailed information concerning tissue microstructures. The diagnostic potential of this technology makes OCT a promising modality in the study and surveillance of the neonatal airway.


Assuntos
Laringoestenose/diagnóstico , Laringe/patologia , Tomografia de Coerência Óptica/instrumentação , Diagnóstico Diferencial , Desenho de Equipamento , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Laringoscopia/métodos , Reprodutibilidade dos Testes
6.
Tech Hand Up Extrem Surg ; 11(3): 204-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17805158

RESUMO

This article will review the basic principles and techniques of managing axillary burn contractures in both industrialized and developing nations. Surgeons specializing in hand and upper extremity surgery should be adept in treating axillary soft tissue deficits secondary to burn contractures. The focus of this article will be to provide suggestions for performing skin grafts and latissimus dorsi musculocutaneous flaps, as well as illustrate guidelines for postoperative rehabilitation.


Assuntos
Queimaduras/complicações , Contratura/etiologia , Contratura/cirurgia , Transplante de Pele/métodos , Retalhos Cirúrgicos , Axila , Humanos
7.
Plast Reconstr Surg ; 140(2): 326e-332e, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28746287

RESUMO

BACKGROUND: Repair of bilateral complete cleft lip requires more than following a design in a textbook. The operative strategy should incorporate knowledge of anticipated nasolabial changes with growth. METHODS: Direct nasolabial anthropometry was recorded in 174 children with bilateral complete cleft lip before and immediately after primary repair. Serial measurements were taken in 66 Caucasian patients between the ages of 6 months and 15 years and compared to Farkas' normal values. Data for upper philtral width were unavailable; therefore, this dimension was measured in 454 nonsyndromic Caucasian male and female subjects aged 1 year to adulthood. Rates and types of revision were also documented. RESULTS: Inter-medial canthal width stayed above the mean and within normal limits throughout puberty. Interalar width was initially narrowed and hovered in the high normal range throughout adolescence. Columellar height and nasal projection were constructed slightly long and paralleled normal growth. Available cutaneous philtral length was used in the primary repair; however, this dimension remained short. The philtrum was made narrow and matched normal values throughout adolescence. Normal inferior/superior philtral width ratio was 1.60 for female subjects and 1.59 for male subjects. A full median tubercle was built at primary repair but, sometimes in late childhood, necessitated secondary augmentation with a dermal graft in 31 of 174 patients (18 percent), usually performed in late childhood or adolescence. CONCLUSIONS: Serial anthropometry documented postoperative changes in nasolabial dimensions compared to normal growth curves. Repair of bilateral complete cleft lip requires primary correction of nasal and labial features based on their differential growth, with special attention to nasal width, philtral height and proportions, and size of the median tubercle. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Fenda Labial/cirurgia , Lábio/anatomia & histologia , Nariz/anatomia & histologia , Adolescente , Pesos e Medidas Corporais , Criança , Pré-Escolar , Fenda Labial/patologia , Feminino , Humanos , Lactente , Masculino , Valores de Referência , Estudos Retrospectivos , Fatores de Tempo
8.
Cancer Res ; 62(3): 747-55, 2002 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11830529

RESUMO

We examined the ability of recombinant murine interleukin-12 (rmIL-12) to inhibit the vasculature and growth of mammary carcinomas arising in situ in mouse mammary tumor virus (MMTV)-infected female C3H/HeN mice. Although it is a potent antiangiogenic and antitumor agent in many transplanted murine tumor models, rmIL-12 failed to inhibit the vascularity, reduce the perfusion, or alter the growth of these autochthonous carcinomas. Factors intrinsic to these tumor cells were unlikely to be responsible for therapy failure. This is because primary cells derived from these carcinomas responded to IFN-gamma, and rmIL-12 was effective against transplanted tumors arising from Mm5MT cells, a line established from a MMTV-induced mammary carcinoma in C3H mice. Factors intrinsic to the mice that host the autochthonous mammary carcinomas were also not responsible for failure, because they sponsored rmIL-12 antiangiogenic and antitumor effects against transplanted K1735 murine melanoma tumors. Instead, the autochthonous nature of the mammary carcinomas and their possession of a high percentage of mature, pericyte-covered vessels that are resistant to therapeutic regression may be responsible. This is supported by the observation that transplanted Mm5MT tumors had a lower proportion of pericyte-covered vessels and responded to rmIL-12 therapy. These results point to significant differences between the vasculature of transplanted and autochthonous murine tumors and indicate that their susceptibility to antivascular therapy may differ substantially.


Assuntos
Interleucina-12/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/virologia , Vírus do Tumor Mamário do Camundongo , Neovascularização Patológica/prevenção & controle , Animais , Divisão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Proteínas Recombinantes/farmacologia
9.
Plast Reconstr Surg ; 132(4): 923-932, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23783057

RESUMO

BACKGROUND: Primary repair of bilateral incomplete cleft lip appears to be uncomplicated but requires attention to technical details in the third dimension in anticipation of changes in the fourth dimension. METHODS: Direct anthropometry was used to document nasolabial dimensions before and immediately after repair in 51 infants with bilateral incomplete cleft lip. Technical details were analyzed in 48 patients; serial anthropometry was plotted in 22 male patients aged 2 to 20 years and compared to Farkas's normal growth lines. Revisions were also documented (n = 46). RESULTS: Nasal width was made narrow and widened to normal by adolescence. Nasal tip protrusion was elongated and grew parallel to normal. Columellar length was constructed above normal, lengthened slowly in childhood, and was slightly short by adulthood. The Cupid's bow was designed narrow, widened slightly, and maintained normal dimension in adulthood. The upper philtrum was tapered and remained less wide than the lower philtrum. Although maximum available cutaneous prolabium was used in repair, it was short postoperatively and philtral height failed to exhibit catchup growth. The median tubercle was constructed overly full, but growth frequently fell behind in adolescence; 39 percent of patients required secondary augmentation. Total upper labial height closely followed the normal growth curve. CONCLUSIONS: Serial anthropometry documented postoperative changes in nasolabial dimensions compared with normal growth lines. Repair of bilateral incomplete cleft lip requires primary correction of nasal and labial features based on their differential growth. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Fenda Labial/cirurgia , Lábio/cirurgia , Nariz/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Fatores Etários , Antropometria , Criança , Pré-Escolar , Bases de Dados Factuais , Humanos , Lábio/crescimento & desenvolvimento , Masculino , Nariz/crescimento & desenvolvimento , Resultado do Tratamento , Adulto Jovem
10.
Plast Reconstr Surg ; 128(6): 1257-1262, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22094745

RESUMO

BACKGROUND: The most common clinical presentation of thoracic outlet syndrome stems from compression of the lower trunk of the brachial plexus or ulnar nerve. A plethora of anatomical variations have been implicated in the cause of thoracic outlet syndrome. Roos' identification and classification of scalene muscle and fibrous bands have added an additional dimension to understanding its cause and subsequent treatment. Understanding the anatomy and relationship of this band with the lower trunk of the brachial plexus is of paramount importance. METHODS: As part of the authors' long-term study of the type 3 band in relation to the brachial plexus, 70 embalmed cadavers were dissected to yield 100 first thoracic ribs. Fibrous bands, when present, were studied in relation to the brachial plexus. RESULTS: A fibrous band consistent with Roos' type 3 was identified and found to occur in 35 percent of first ribs and 41 percent of cadavers. The mean size was 3.45 × 0.27 cm. Origins and insertions are described. Contrary to Roos' own description, however, the authors observed that Roos' type 3 band was anterior to the T1 nerve root, creating a tunnel through which the T1 nerve root must pass before joining the C8 nerve root. CONCLUSIONS: The authors believe that the type 3 band, when present, can create a tunnel that compresses the T1 nerve root against the first rib, potentially predisposing susceptible individuals to thoracic outlet syndrome. Clinical studies are needed to determine whether correlations between type 3 bands and thoracic outlet syndrome exist.


Assuntos
Plexo Braquial/patologia , Costela Cervical/anormalidades , Fáscia/anormalidades , Músculos do Pescoço/anormalidades , Músculos do Pescoço/patologia , Síndromes de Compressão Nervosa/patologia , Raízes Nervosas Espinhais/anormalidades , Raízes Nervosas Espinhais/patologia , Síndrome do Desfiladeiro Torácico/patologia , Adolescente , Adulto , Idoso , Costela Cervical/patologia , Dissecação , Fáscia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
11.
J Pharmacol Toxicol Methods ; 62(2): 107-18, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20601018

RESUMO

INTRODUCTION: The cardiac Na+ current (I(Na)) underlies the rapid depolarization of the cardiac myocyte, and block of the current slows cardiac conduction and increases the risk of ventricular arrhythmia. A feature of Na+ channel block termed use-dependence is important to the assessment of blocking potency. We developed a robust automated patch clamp assay to rapidly and routinely assess the use-dependent block of I(Na) by drug candidates. The assay clarifies whether drug candidates block more potently at increased heart rates and provides a quantitative score of use-dependence. METHODS: A use-dependent cardiac I(Na) assay was implemented on the PatchXpress 7000A, an automated whole-cell patch clamp device, using a HEK cell line stably expressing the human cardiac Na+ channel, Na(V)1.5. Stable recordings lasting up to 30 minutes were achieved by selection of holding potential (-100 mV) as well as an appropriate osmotic gradient to prevent time-dependent loss of cell capacitance and current. The final protocol allows evaluation of I(Na) inhibition at three pulsing rates at three test concentrations for each recorded cell. RESULTS: IC(50) values obtained for three standard I(Na) blockers lidocaine, mexiletine, and flecainide, at pulsing frequencies of 0.2 Hz, 1 Hz, and 3 Hz, were compared to IC(50) values obtained with conventional pipette patch clamp of the Na(V)1.5 cell line and of guinea pig cardiac myocytes using matched voltage protocols and pulsing rates. Absolute potencies were well correlated only under conditions of matched holding potential and fell within an approximately three-fold window. While absolute potencies could vary widely with holding potential, the fold increases in potency with increases in pulsing rates were less prone to variation of the holding potential. DISCUSSION: Use-dependence of cardiac Na+ channel block can be rapidly assessed in the PatchXpress platform and quantified at early stages of drug development to guide lead optimization.


Assuntos
Proteínas Musculares/antagonistas & inibidores , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Sódio/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Flecainida/farmacologia , Cobaias , Células HEK293 , Humanos , Lidocaína/farmacologia , Mexiletina/farmacologia , Proteínas Musculares/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5 , Canais de Sódio/metabolismo
12.
Plast Reconstr Surg ; 113(4): 1296-7, 2004 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15083054
13.
Eur J Immunol ; 32(4): 945-56, 2002 04.
Artigo em Inglês | MEDLINE | ID: mdl-11920560

RESUMO

Mouse mammary tumor virus (MMTV) is acquired by neonates through milk and first infects lymphocytes in Peyer's patches. We show here that newborn mice lacking beta7 integrin or L-selectin were infected with MMTV at wild-type levels in both their lymphoid and mammary tissues. Superantigen-mediated activation and cognate T cell deletion were also unimpaired in both types of null mice. A large proportion of neonatal Peyer's patch lymphocytes in wild-type mice were beta7 and beta1 integrin low and both populations increased in response to MMTV infection. These results suggest that adhesion molecules other than beta7 integrin or L-selectin play a role in lymphocyte homing in the gut, peripheral lymph nodes and mammary gland in response to MMTV infection.


Assuntos
Cadeias beta de Integrinas , Integrinas/fisiologia , Selectina L/fisiologia , Subpopulações de Linfócitos/imunologia , Vírus do Tumor Mamário do Camundongo/fisiologia , Infecções por Retroviridae/imunologia , Infecções Tumorais por Vírus/imunologia , Animais , Animais Recém-Nascidos , Antígenos Virais/imunologia , Linfócitos B/imunologia , Linfócitos B/virologia , Caderinas/fisiologia , Adesão Celular , Moléculas de Adesão Celular , Movimento Celular , Citocinas/fisiologia , Feminino , Imunoglobulinas/fisiologia , Integrinas/deficiência , Integrinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Selectina L/genética , Lactação , Cooperação Linfocítica , Subpopulações de Linfócitos/citologia , Subpopulações de Linfócitos/virologia , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Leite/virologia , Mucinas/fisiologia , Mucoproteínas/fisiologia , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/virologia , Superantígenos/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia
14.
Proc Natl Acad Sci U S A ; 99(5): 2860-5, 2002 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-11854457

RESUMO

BCL6, a gene on chromosome 3 band q27, encodes a Kruppel-type zinc finger transcriptional repressor. Rearrangements of this gene are frequent in various kinds of lymphomas, particularly of the large-cell B-cell type. The BCL6 nuclear phosphoprotein is expressed in a variety of tissues and is up-regulated particularly in lymph node germinal centers. The zinc fingers of BCL6 bind DNA in a sequence-specific manner. To identify targets of the BCL6 repressive effects, we used a VP16-BCL6 fusion protein containing the zinc fingers but devoid of the repressor domains to compete with the binding of endogenous BCL6 in a transiently transfected B-cell line and then performed subtractive hybridization by using a method to selectively amplify sequences that are differentially expressed. We found that the programmed cell death-2 (PDCD2) gene is a target of BCL6 repression. This gene is the human homolog of Rp8, a rat gene associated with programmed cell death in thymocytes. Immunohistochemistry reveals the anticipated inverse relationship between BCL6 and PDCD2 expression in human tonsil. PDCD2 is detectable in cells of the germinal center in areas where there is less BCL6 expression as well as in the mantle zone, where there is little or no BCL6 expression. These results raise the possibility that BCL6 may regulate apoptosis by means of its repressive effects on PDCD2. BCL6 deregulation may lead to persistent down-regulation of PDCD2, reduced apoptosis, and, as a consequence, accumulation of BCL6-containing lymphoma cells.


Assuntos
Apoptose , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Proteínas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Dedos de Zinco , Animais , Especificidade de Anticorpos , Proteínas Reguladoras de Apoptose , Linfócitos B , Sítios de Ligação , Northern Blotting/métodos , Linhagem Celular , Sequência Consenso , Proteínas de Ligação a DNA/genética , Expressão Gênica , Perfilação da Expressão Gênica , Genes Reporter , Proteína Vmw65 do Vírus do Herpes Simples/genética , Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Humanos , Técnicas Imunoenzimáticas , Luciferases/genética , Camundongos , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Coelhos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Análise de Sequência de DNA , Fatores de Transcrição/genética
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