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1.
Int J Dent Hyg ; 14(4): 278-283, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27151435

RESUMO

OBJECTIVE: To determine whether multiple examiners can demonstrate consistent plaque removal advantages for an oscillating-rotating power toothbrush versus a manual toothbrush. METHODS: This was a replicate-use, single brushing, examiner-blind, randomized, two-treatment, four-period crossover clinical trial involving four examiners. Subjects were randomized to one of four treatment sequences involving two toothbrushes: an oscillating-rotating power toothbrush or a manual toothbrush. At each of the four visits, subjects arrived having abstained from oral hygiene for 24 h prior, and brushed with their assigned toothbrush and a marketed fluoride dentifrice under supervision unaided by a mirror. Plaque was assessed by each examiner using the Turesky-Modified Quigley-Hein Plaque Index at each study period before and after brushing. Data was analysed separately for each examiner using the analysis of covariance for crossover design. RESULTS: Ninety-five subjects between the ages of 18 and 70 met the entrance criteria and were enrolled in the study. Eighty-seven subjects completed all four periods of the study. Both brushes delivered a significant plaque reduction when compared to baseline. Significant treatment differences were observed for all four examiners - ranging from 0.10 to 0.16 - in favor of the oscillating-rotating brush (P < 0.001). There were no adverse events reported or observed for either brush. CONCLUSIONS: All four examiners demonstrated the power toothbrush removed significantly more plaque after a single brushing than the standard manual toothbrush. Both brushes were well tolerated.


Assuntos
Placa Dentária/prevenção & controle , Escovação Dentária/instrumentação , Adolescente , Adulto , Idoso , Estudos Cross-Over , Equipamentos Odontológicos , Placa Dentária/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Escovação Dentária/métodos , Adulto Jovem
2.
Herz ; 37(7): 804-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22773171

RESUMO

Left ventricular noncompaction (LNVC), first described in 1984, is a rare congenital cardiomyopathy that is thought to be caused by arrest of normal embryogenesis of the endocardium and the myocardium, and characterized by multiple prominent trabeculations with deep intertrabecular recesses. LVNC can be associated with other congenital cardiac abnormalities such as atrial septal defect and ventricular septal defect, but it can occur in isolation. The clinical manifestations of the disease are variable, ranging from no symptoms to signs of heart failure, systemic emboli, and ventricular arrhythmias. The diagnosis is established by two dimensional echocardiography or magnetic resonance imaging. We report the case of a 44-year-old man with LVNC and discuss the role of multimodal imaging in the diagnosis and assessment of the disease.


Assuntos
Ecocardiografia/métodos , Cardiopatias Congênitas/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Técnica de Subtração , Adulto , Humanos , Masculino
4.
Environ Entomol ; 39(5): 1532-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22546449

RESUMO

A greenhouse experiment was conducted to evaluate the effect of soil-dwelling larvae of the western corn rootworm, Diabrotica virgifera virgifera LeConte, on infection of maize roots by the mycotoxin-producing plant-pathogenic fungus, Fusarium verticillioides (Saccardo) Nirenberg (synonym=Fusarium moniliforme Sheldon). The time and order of application of F. verticillioides and western corn rootworm were varied in three different treatments to investigate the influence of timing on root colonization of F. verticillioides and western corn rootworm larval development. Root feeding by western corn rootworm larvae increased root colonization by F. verticillioides (as determined by real-time polymerase chain reaction) up to 50-fold when a high inoculum (10(7) spores/plant) of F. verticillioides was applied before western corn rootworm eggs were added. This effect was stronger the earlier F. verticillioides was applied relative to the time of western corn rootworm egg application but was only significant for the high F. verticillioides inoculum density treatment; F. verticillioides colonization was not increased when a low F. verticillioides inoculum density (10(6) spores/plant) was applied. F. verticillioides slightly suppressed larval development in that the ratio of second- to third-instar larvae was higher in treatments with F. verticillioides than without F. verticillioides. F. verticillioides reduced western corn rootworm head capsule width when applied before or simultaneously with western corn rootworm. The results of this study are discussed focusing on conditions that favor root colonization by F. verticillioides and its influence on western corn rootworm larval development.


Assuntos
Besouros/crescimento & desenvolvimento , Fusarium/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Zea mays/microbiologia , Animais , DNA Fúngico/análise , Larva/crescimento & desenvolvimento , Óvulo/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Zea mays/crescimento & desenvolvimento
6.
J Neurogenet ; 15(3-4): 233-44, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12092906

RESUMO

In order to understand the level of complexity of the epileptic phenotype in the two strains of Genetically Epilepsy-Prone Rats (GEPRs), we determined two important measures of genetic complexity, penetrance and expressivity. Penetrance is the percentage of animals of a specific genotype who express the phenotype associated with that underlying genotype. Expressivity refers to the degree that a particular genotype is expressed as a phenotype within an individual. Incomplete penetrance and variable expressivity are caused by genetic and environmental variation. In this paper we have studied the epileptic phenotype for 20,373 rats. Animals were tested on three occasions for audiogenic seizure and given an audiogenic response score (on a scale of 0-9, 0 being no seizure and 9 being the most severe). The GEPR-3 and GEPR-9 animals both show incomplete penetrance and variable expressivity of the underlying genetic predisposition. The GEPR-9 strain has more animals that have variable levels of seizure predisposition (as measured by a scoring system that denotes the severity of generalized tonic/clonic seizures) and a greater percentage of animals that exhibit no susceptibility to such seizures induced by sound. Both strains have a number of animals that are not susceptible to sound-induced GTCSs and that exhibit some variability in seizure severity. The GEPR-9 males show greater differences in expressivity and penetrance compared to GEPR-9 females. The GEPR-3 animals also show sex-associated variable penetrance and expressivity of the epileptic phenotype, although the differences are much smaller. These findings are the first step toward the mapping of the underlying quantitative trait loci (QTL) for seizure in these animals.


Assuntos
Epilepsia/genética , Predisposição Genética para Doença , Penetrância , Animais , Feminino , Expressão Gênica , Masculino , Característica Quantitativa Herdável , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais , Especificidade da Espécie
7.
J Clin Microbiol ; 38(1): 279-81, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10618101

RESUMO

Current recommendations suggest that negative rapid Streptococcus pyogenes antigen tests be backed up with a culture, reflecting evidence that culture may have a higher sensitivity and also that testing of a second swab may yield a different (i.e., a positive) result because of variation in sample size or distribution. If the latter is common, the sensitivities of current antigen detection tests might be improved by simply increasing the amount of sample tested. The present study assessed the effect of antigen testing of two swabs extracted together compared to independent testing of each swab extracted separately for children with clinical pharyngitis. S. pyogenes grew from one or both swabs for 198 (37%) of 537 children. The combined culture was significantly (P < 0.05) more sensitive than culture of either swab alone. Compared to combined culture, antigen testing of two swabs extracted and tested together was significantly more sensitive than two single swab extractions (94.1 versus 80%; P = 0.03); however, the specificity was decreased (81.5 versus 89.8 to 92.7%; P < 0.05). This study suggests that sample size and/or uneven sample distribution may have influenced the apparent sensitivities of prior studies that compared antigen tests to a single plate culture. A strategy, such as the one used in the present study, that increases the sample size available for antigen testing (i.e., extraction of samples from both swabs) may improve detection rates to a level that will better approximate true disease status and obviate the need for backup cultures if specificity can be improved.


Assuntos
Antígenos de Bactérias/isolamento & purificação , Faringite/microbiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/imunologia , Adolescente , Carboidratos/imunologia , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Humanos , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de Espécimes
8.
Image J Nurs Sch ; 31(1): 83-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10081218

RESUMO

PURPOSE: To describe the rationale maternity patients use in determining whether to accept care by a male student nurse. Information about the activities that women are comfortable having male nursing students perform is inconsistent and the reasons for women's comfort or discomfort are unclear. Furthermore, little is known about what factors patients consider when assigned a male nursing student. Yet, knowledge of such factors can enhance understanding and guide the selection of students in maternity units. DESIGN: Focused ethnography using a purposive convenience sample of 32 women, aged 20 to 40 years, who spoke English, and who had given birth to normal newborns in one small community hospital in the mid-Atlantic region of the United States. Patients were excluded if they or their infants were in an unstable physical or mental condition. The study was conducted in 1995. METHODS: The women were interviewed using a semi-structured format. FINDINGS: Data from participants pertained to personal and contextual factors. Personal factors were perception of postpartum self and personal feelings. Contextual factors were student characteristics, establishment of relationships, nursing care activities, and partner viewpoint. CONCLUSIONS: Women during and after giving birth have definite thoughts about male student nurses caring for them. Nurse educators should consider these when assigning men. Educators should encourage professionalism and competence in their students.


Assuntos
Mães/psicologia , Relações Enfermeiro-Paciente , Enfermeiros/psicologia , Enfermagem Obstétrica , Estudantes de Enfermagem/psicologia , Adulto , Antropologia Cultural , Feminino , Humanos , Entrevista Psicológica/métodos , Masculino , Mid-Atlantic Region , Gravidez
9.
Hum Mol Genet ; 7(9): 1393-8, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9700192

RESUMO

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.


Assuntos
Asma/genética , Efeito Fundador , Genoma Humano , Adolescente , Adulto , Alelos , Hiper-Reatividade Brônquica/genética , Pré-Escolar , Mapeamento Cromossômico , Consanguinidade , Feminino , Ligação Genética , Marcadores Genéticos , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético
10.
Genomics ; 49(3): 452-7, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9615232

RESUMO

SM22 is a 22-kDa protein identified variously as SM22, transgelin, WS3-10, or mouse p27. Though its precise function is unknown, it is abundant in smooth muscle and so may contribute to the physiology of this widespread tissue. We found that cosmid 16b6 contains the entire 5.4-kb, five-exon human SM22 gene (HGMW-approved symbol, TAGLN), and we cytogenetically localized the gene to chromosome 11q23.2. Northern analysis of human adult tissues showed that SM22 mRNA is most prevalent in smooth muscle-containing tissues, but is also found at lower levels in heart. The human SM22 promoter contains nuclear factor-binding motifs known to regulate transcription in smooth muscle, and human SM22 promoter-luciferase reporter constructs exhibited high transcriptional activity in A7r5 or primary canine aortic smooth muscle cells, but show little activity in nonmuscle COS7 cells. In addition, human SM22 promoter activity increased by two- to threefold upon serum stimulation of nonmuscle cells.


Assuntos
Cromossomos Humanos Par 11 , Proteínas dos Microfilamentos , Proteínas Musculares/genética , Regiões Promotoras Genéticas , Adulto , Animais , Células COS , Mapeamento Cromossômico , Cães , Humanos , Hibridização In Situ , Luciferases/biossíntese , Linfócitos/metabolismo , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas Musculares/biossíntese , Músculo Liso/metabolismo , Músculo Liso Vascular/metabolismo , Especificidade de Órgãos , Proteínas Recombinantes/biossíntese , Transcrição Gênica , Transfecção
11.
Int Immunol ; 9(3): 415-26, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9088980

RESUMO

B cell development is a complex process involving interactions between B cell precursors, stroma, and known and unknown ligands and cytokines. In order to more fully understand the requirements for Ig in that development we have created transgenic mice that carry a gamma 2b transgene and express it early in B cell development. Previously it was believed that these B cells arrested in their development prior to the pro- to pre-B cell transition. We show here that in conventional gamma 2b mice, B cell development actually arrests later, at the pre-B cell stage. This shows for the first time that a constant region different from mu can allow signaling through the pre-B cell receptor, but cannot promote complete development. The pro- and pre-B cells in the conventional gamma 2b transgenics are not fully functional since they cannot grow in IL-7 without stromal cells. This is a novel phenotype, separating development from stroma independence. The few, mature B cells that do develop in these mice express both mu and gamma 2b simultaneously, and are CD5+. Expression of a Bcl-2 transgene allows survival of gamma 2b transgenic immature B cells, but does not promote full maturation, indicating that normally mu provides both an anti-apoptotic signal and a differentiation signal. One line of gamma 2b mice, the C line, does not have this phenotype. B cell development is accelerated in this unconventional line, and the developing B cells have a very different phenotype from both normal mice and conventional gamma 2b mouse lines, but are very similar to mu transgenics. Mature B cells are largely CD5-, gamma 2b-only expressing. This unique phenotype is apparently due to the activation in B cell precursors of a gene at the insertion site of the transgene, circumventing the need for mu. Comparison of conventional gamma 2b transgenics with the C line and mu transgenics reveals the multiple signals required throughout B cell development.


Assuntos
Linfócitos B/citologia , Hematopoese/fisiologia , Imunoglobulina G/imunologia , Transdução de Sinais/fisiologia , Animais , Medula Óssea/patologia , Diferenciação Celular , Células Cultivadas , Cruzamentos Genéticos , Citometria de Fluxo , Regulação da Expressão Gênica , Genes bcl-2 , Imunoglobulina G/genética , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Cadeias gama de Imunoglobulina/genética , Cadeias gama de Imunoglobulina/fisiologia , Cadeias mu de Imunoglobulina/genética , Cadeias mu de Imunoglobulina/fisiologia , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/patologia , Imunofenotipagem , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Baço/patologia
12.
Rofo ; 165(4): 359-63, 1996 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-8963048

RESUMO

PURPOSE: To evaluate MR-imaging for the differentiation of fatty necrosis (FN) of the breast. MATERIAL AND METHODS: In 1016 MR mammographies FN was found in 13 patients aged 44 to 69 years. In all studies we used a proton-weighted fat suppressed sequence (STIR) and serial T1-weighted gradient echo sequences before and after bolus injection of Gd-DTPA, MRI was correlated to ultrasound and in 8 cases to mammographic findings. RESULTS: All 15 FN displayed fat-isointense signal on T1-weighted and on proton-weighted, fat-suppressed sequences. They were delineated by a more or less wide rim of low signal intensity with sharp border to the center. After intravenous injection of gadopentetate dimeglumine they showed no increase of signal intensity in the centre and no increase, or only a minor increase, of the rim. Ultrasound could not distinguish FN from recurrent tumour in 6 cases. 7 FN looked like atypical cysts. CONCLUSION: MR-mammography is very promising in the diagnosis of FN.


Assuntos
Doenças Mamárias/diagnóstico , Necrose Gordurosa/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Combinação de Medicamentos , Estudos de Avaliação como Assunto , Feminino , Gadolínio , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética/métodos , Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos , Ácido Pentético/análogos & derivados , Estudos Retrospectivos , Ultrassonografia Mamária
13.
Rofo ; 164(6): 469-74, 1996 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-8688503

RESUMO

PURPOSE: We investigated the role of magnetic resonance mammography in monitoring tumour response of locally advanced breast cancer (LABC) after neoadjuvant radiochemotherapy. MATERIAL AND METHODS: 17 patients with LABS had a magnetic resonance mammography and ultrasonography before and after neoadjuvant radiochemotherapy. RESULTS: After neoadjuvant radiochemotherapy 14 patients showed in MR-mammography less pronounced and prolonged enhancement without washout. After treatment three patients had signal intensity-time curves still characteristic for tumour. Ultrasonography was true negative in two patients, true positive in 12 and false positive in three patients. CONCLUSION: Magnetic resonance mammography is suitable for monitoring tumour response after radiochemotherapy of LABC. However, a negative MRI does not exclude a residual tumour. Ultrasonography is of limited value in monitoring therapy of LABC.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Ultrassonografia
14.
Rofo ; 164(4): 295-300, 1996 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-8645862

RESUMO

PURPOSE: To demonstrate typical MR mammographic findings after plastic surgery of breast cancer. PATIENTS AND METHODS: Postoperative (7-38 months, median 13) MR mammographic examinations of 25 patients operated for breast cancer (11 latissimus dorsi-flaps (LAT), 14 rectus abdominis myocutaneous-flaps (TRAM)), were reevaluated. The examinations were performed with a breast coil at 1 T. The sequences applied were a fat-suppressed 2-D turbo IR-sequence proton-weighted and a T1-weighted FLASH 3-D sequence as dynamic series. RESULTS: Scars between the myocutaneous flap and the remaining breast tissue always appeared in form of a ligament or septum. Signal and perfusion characteristics of scar tissue and muscle stalk in this investigation were clearly different from those of tumour. One tumour recurrence and one fat necrosis was found and rectified by biopsy. CONCLUSION: MR mammography is a very valuable diagnostic method for postoperative evaluation of myocutaneous flap-based therapy of breast cancer.


Assuntos
Neoplasias da Mama/cirurgia , Imageamento por Ressonância Magnética , Mamoplastia , Recidiva Local de Neoplasia/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Retalhos Cirúrgicos/patologia , Adulto , Idoso , Artefatos , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Microcirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias
15.
J Med ; 27(3-4): 205-10, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8982968

RESUMO

Lesions of the anterior mediastinum typically include neoplasms of the thymus or thyroid, hemangioma, germ cell neoplasms, lymphoma and others. Renal cell carcinoma often presents with flank pain, hematuria, abdominal pain and/or fever. Chest cavity involvement by renal cell carcinoma typically manifests as pulmonary parenchymal disease with or without hilar lymph node involvement. We report an unusual presentation of renal cell carcinoma in a patient who presented with symptoms secondary to a large anterior mediastinal mass. A 64-year-old woman came to the hospital complaining of malaise, cough, dyspnea, weight loss and night sweats. Chest roentgenogram and computed tomography revealed a large anterior superior mediastinal mass without significant pulmonary parenchymal disease. She was also noted to have microscopic hematuria and a renal mass was found. Histology of both masses revealed renal cell carcinoma. This case suggests that renal cell carcinoma may merit consideration in the differential diagnosis of an anterior mediastinal mass and illustrates an unusual manner by which this lesion may present.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias do Mediastino/patologia , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/secundário , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada por Raios X
16.
J Vet Pharmacol Ther ; 18(5): 346-51, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8587152

RESUMO

A 20% solution of apramycin was administered intravenously (i.v.) and intramuscularly (i.m.) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i.v. to lactating goats with normal udders. The i.v. disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26-1.45 L/kg. The absorption rate of the drug from the i.m. injection site was rapid, the i.m. bioavailability was 60-70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%). Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUCmilk/AUCserum was < 0.32. Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk Cmax values were more than tenfold greater than the Cmax in normal milk. On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.


Assuntos
Antibacterianos/farmacocinética , Bovinos/metabolismo , Cabras/metabolismo , Leite/química , Nebramicina/análogos & derivados , Ovinos/metabolismo , Animais , Antibacterianos/análise , Antibacterianos/sangue , Bovinos/sangue , Feminino , Cabras/sangue , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Lactação/metabolismo , Modelos Lineares , Glândulas Mamárias Animais/metabolismo , Mastite/metabolismo , Mastite/veterinária , Mastite Bovina/metabolismo , Nebramicina/análise , Nebramicina/sangue , Nebramicina/farmacocinética , Ovinos/sangue , Doenças dos Ovinos/metabolismo , Especificidade da Espécie
17.
J Exp Med ; 181(3): 1059-70, 1995 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-7869028

RESUMO

gamma 2b transgenic mice have a severe B cell defect, apparently caused by strong feedback inhibition of endogenous H-gene rearrangement coupled with an inability of gamma 2b to provide the survival/maturation functions of mu. A unique gamma 2b transgenic line, named the C line, was found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b+ B cells develop in the homozygous knockout. In contrast, a transgenic line representative of all the other gamma 2b lines is completely B cell deficient when mu-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b transgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C line are identical to that of the original transgene. These results have led to the conclusion that in the C line the transgene integration constitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C line is expressed, C mice were crossed onto a lambda 5 knockout background. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combination with an unknown factor and the sL, gamma 2b can provide these nurturing functions.


Assuntos
Linfócitos B/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Cadeias gama de Imunoglobulina/fisiologia , Cadeias lambda de Imunoglobulina/fisiologia , Cadeias mu de Imunoglobulina/fisiologia , Alelos , Animais , Sequência de Bases , Mapeamento Cromossômico , Genes de Imunoglobulinas , Imunoglobulina M/biossíntese , Cadeias mu de Imunoglobulina/genética , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , RNA Mensageiro/análise , Receptores de Antígenos de Linfócitos B/fisiologia
19.
EMBO J ; 13(4): 827-34, 1994 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-8112297

RESUMO

Mice of the SJL strain produce approximately 50 times less serum lambda 1 immunoglobulin light chains than other mouse strains. The defect is genetically linked to the lambda locus, but it is unknown whether it is due to regulatory alterations or known structural changes. We find no mutation in the SJL lambda 3-1 enhancer which regulates both lambda 1 and lambda 3. To investigate the defect further, the production of lambda light chains was amplified by crossing SJL with kappa-knockout mice. In kappa-knockout mice with the wildtype lambda locus (kappa -/- lambda +/+), the majority of serum light chains are lambda 1. In contrast, kappa-knockout mice with the SJL lambda locus (kappa -/- lambda s/s) show a pronounced expression of lambda 2 and lambda 3, with only some expression of lambda 1. The results show that the SJL defect is lambda 1 specific, since the linked lambda 3 expression is normal. As the transcription and rearrangement of lambda 1 appear normal in SJL, the defective lambda 1 synthesis is most likely due to a point mutation in the lambda 1 constant region resulting in a glycine to valine substitution. At the cellular level, in kappa-knockout mice with the SJL lambda locus there are fewer immature, and especially mature, lambda 1 B cells and the production of lambda 1 plasma cells is strongly inhibited. The lambda 1 specificity of the defect suggests that the point mutation in SJL C lambda 1 creates an immunoglobulin receptor complex which is dysfunctional in B cell differentiation.


Assuntos
Linfócitos B/citologia , Cadeias lambda de Imunoglobulina/genética , Receptores Imunológicos/genética , Animais , Linfócitos B/metabolismo , Sequência de Bases , Células da Medula Óssea , Diferenciação Celular/imunologia , Separação Celular , Mapeamento Cromossômico , Cruzamentos Genéticos , Primers do DNA , Elementos Facilitadores Genéticos , Citometria de Fluxo , Rearranjo Gênico de Cadeia Leve de Linfócito B , Homozigoto , Hibridomas , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Mutação Puntual , RNA Mensageiro/metabolismo , Receptores Imunológicos/fisiologia , Baço/citologia
20.
Immunol Res ; 13(4): 291-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7616056

RESUMO

The development of B lymphocytes is tightly linked to the expression of immunoglobulins (Igs). Pro/preB cells which do not correctly rearrange heavy/light chain genes are aborted. Correctly rearranged Ig transgenes are apparently recognized by the developing B cells and can prevent the rearrangement of endogenous Ig genes. Both mu and gamma 2b heavy chain genes cause this feedback inhibition of heavy chain gene rearrangement. Mu transgenes can in addition replace endogenous MU in its preB cell survival/maturation function. However, several different transgenic lines have shown that gamma 2b transgenes do not provide the nurturing functions of mu, except for one unique gamma 2b transgenic line, the C line. In this line mature B cells express gamma 2b only. Presumably, an unknown gene has been activated at the transgene integration site whose product overcomes the need for mu. The function of this gene depends of the presence of the surrogate light chain (sL), and thus must operate in combination with the preB cell receptor or in a downstream signaling/antiapoptosis event requiring the gamma 2b/sL receptor. The analysis of the two types of gamma 2b transgenic mice shows that the signals for preB cell development are highly complex and promises to reveal new insights into the molecular and cellular mechanisms of B cell maturation.


Assuntos
Linfócitos B/imunologia , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Imunoglobulinas/genética , Animais , Diferenciação Celular/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/imunologia , Células-Tronco Hematopoéticas/fisiologia , Região de Troca de Imunoglobulinas/genética , Região de Troca de Imunoglobulinas/imunologia , Camundongos , Camundongos Transgênicos , Transdução de Sinais/genética
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