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1.
J Fish Biol ; 84(5): 1490-502, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24773541

RESUMO

Using semi-natural enclosures, this study investigated (1) whether adult sea lamprey Petromyzon marinus show avoidance of damage-released conspecific cues, damage-released heterospecific cues and predator cues and (2) whether this is a general response to injured heterospecific fishes or a specific response to injured P. marinus. Ten replicate groups of 10 adult P. marinus, separated by sex, were exposed to one of the following nine stimuli: deionized water (control), extracts prepared from adult P. marinus, decayed adult P. marinus (conspecific stimuli), sympatric white sucker Catostomus commersonii, Amazon sailfin catfish Pterygoplichthys pardalis (heterospecific stimuli), 2-phenylethylamine (PEA HCl) solution, northern water snake Nerodia sipedon washing, human saliva (predator cues) and an adult P. marinus extract and human saliva combination (a damage-released conspecific cue and a predator cue). Adult P. marinus showed a significant avoidance response to the adult P. marinus extract as well as to C. commersonii, human saliva, PEA and the adult P. marinus extract and human saliva combination. For mobile P. marinus, the N. sipedon washing induced behaviour consistent with predator inspection. Exposure to the P. pardalis extract did not induce a significant avoidance response during the stimulus release period. Mobile adult female P. marinus showed a stronger avoidance behaviour than mobile adult male P. marinus in response to the adult P. marinus extract and the adult P. marinus extract and human saliva combination. The findings support the continued investigation of natural damage-released alarm cue and predator-based repellents for the behavioural manipulation of P. marinus populations in the Laurentian Great Lakes.


Assuntos
Comportamento Animal , Sinais (Psicologia) , Petromyzon/fisiologia , Animais , Reação de Fuga , Feminino , Masculino , Odorantes , Percepção Olfatória , Água/química
2.
Nat Genet ; 8(4): 392-8, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7894492

RESUMO

Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22-23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.


Assuntos
Neoplasias da Mama/genética , Mutação da Fase de Leitura , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Proteína BRCA1 , Sequência de Bases , Neoplasias da Mama/epidemiologia , Canadá/epidemiologia , Primers do DNA , Feminino , Haplótipos , Humanos , Masculino , Dados de Sequência Molecular , Neoplasias Ovarianas/epidemiologia , Linhagem
3.
Nat Genet ; 12(3): 333-7, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8589730

RESUMO

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.


Assuntos
Cromossomos Humanos Par 13 , Mutação , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética , Proteína BRCA2 , Sequência de Bases , Neoplasias da Mama Masculina/genética , Linhagem Celular , Clonagem Molecular , Primers do DNA , Éxons , Feminino , Expressão Gênica , Ligação Genética , Humanos , Masculino , Dados de Sequência Molecular , Neoplasias Ovarianas/genética , Reação em Cadeia da Polimerase , Polimorfismo Genético , Deleção de Sequência
4.
Encephale ; 38(3): 248-56, 2012 Jun.
Artigo em Francês | MEDLINE | ID: mdl-22726413

RESUMO

INTRODUCTION: Space and motion discomfort (SMD) refers to various symptoms that occur in environments with unreliable visual and kinesthetic information that do not permit adequate spatial orientation. Some studies have demonstrated that there is a stable and predictable relationship between vestibular dysfunction and anxiety disorders. Further, vestibular dysfunction can predispose or trigger the development of panic disorder with or without agoraphobia (PD/A) or reinforce phobic avoidance. It therefore seems clinically useful to develop and validate instruments for evaluating SMD in various populations. Measuring SMD could facilitate identification of individuals with PD/A who present comorbid vestibular dysfunction. Jacob et al. developed and validated such a questionnaire: the Situational characteristics questionnaire (SitQ). This questionnaire evaluates the presence of symptoms such as dizziness, vertigo, and instability under specific conditions. The SitQ comprises two subscales that measure SMD and one subscale (agoraphobia) that measures agoraphobic avoidance behaviours. The instrument has two sections. The first section is composed of the SMD-I and agoraphobia subscales, containing 19 and seven items, respectively. Each item consists of two contrasting descriptors of a specific situation or environment. The respondent is required to indicate to what extent the two described situations or environments cause discomfort. Each item includes a "criterion" descriptor for the situation (i.e., a descriptor that is presumed to engender SMD) and an alternative (non-criterion) descriptor. The second section comprises the SMD-II scale; this scale is composed of nine criterion situations, for which non-criterion situations are not supplied. The instrument takes approximately 20 minutes to complete. OBJECTIVE: The present study focuses on the validation of the French-language version of the SitQ: the questionnaire des caractéristiques situationnelles (QCS). METHOD: The sample was composed of French Canadians recruited across Quebec from an anxiety disorders treatment clinic, general psychiatric care clinics, a community organization for individuals with anxiety disorders, advertisements in local newspapers, and ads posted in various public locations. The sample included 141 participants who met the criteria for lifetime PD/A. Participants reported current PD/A (n=73) or PD/A in remission (n=68). The control sample was recruited from undergraduate courses in various disciplines. Two hundred and thirty-five (n=235) students completed the questionnaires. Data from 63 (26.8%) participants were excluded from the analyses due to failure to complete all of the research questionnaires. RESULTS: Analysis of the global descriptive data and the descriptive data for each dependent variable revealed that the data were independent of sociodemographic variables and respected the assumptions of normal distribution (skewness and kurtosis). Parametric tests were subsequently conducted. Using the combined data from the control and clinical groups, the internal consistency of the scales was analyzed using Cronbach's alpha. The SMD-I and SMD-II scales demonstrated good homogeneity. The results were comparable or superior to those obtained with the English-language version of the questionnaire. The agoraphobia scale demonstrated weaker internal consistency and corresponding weaker homogeneity. This result was consistent with that of the original version of the agoraphobia scale; this scale was eliminated for the subsequent analyses. Construct validity was analyzed via t-tests comparing clinical and control groups. Effect sizes were estimated using percentage of variance explained. The SMD-I scale demonstrated weak construct validity and was also eliminated from subsequent analyses. The SMD-II scale demonstrated good construct validity and provided an adequate measure of the theoretical construct of SMD. This scale permitted discrimination of participants according to the presence or absence of PD/A. It is therefore possible to identify participants with PD/A by their level of SMD. This result is comparable to that of Jacob et al. CONCLUSION: The results of the present study are generally consistent with the results of the validation of the original version of the questionnaire. However, the SMD-I and agoraphobia scales in the French-language version of the measure did not achieve a level of significance sufficient to definitively establish validity.


Assuntos
Agorafobia/psicologia , Cinestesia , Enjoo devido ao Movimento/psicologia , Orientação , Transtorno de Pânico/psicologia , Percepção Espacial , Inquéritos e Questionários , Adulto , Agorafobia/diagnóstico , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Enjoo devido ao Movimento/diagnóstico , Transtorno de Pânico/diagnóstico , Psicometria/estatística & dados numéricos , Quebeque , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Tradução
5.
J Vet Cardiol ; 26: 19-28, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31794914

RESUMO

INTRODUCTION/OBJECTIVES: We sought to determine the prevalence and clinical significance of right heart remodeling and right ventricular (RV) dysfunction in dogs with pulmonary valve stenosis (PS). We also sought to evaluate repeatability of several measurements of severity of PS, right heart size, and RV function in dogs with PS. ANIMALS, MATERIALS AND METHODS: Several indices of right atrial (RA) size and RV size and function were prospectively evaluated in 48 dogs with PS. Regression analysis was used to determine if indices of right heart size and function were independently associated with maximum transpulmonary pressure gradient (max PG) and adverse clinical findings (exercise intolerance, syncope, or right heart failure). Eight dogs underwent a second echocardiogram performed by the same operator to assess repeatability of the echocardiographic indices, which was quantified by coefficient of variation (CV) and repeatability coefficient. RESULTS: Increased RA size (81%), increased RV wall thickness (83%), and decreased tricuspid annular plane systolic excursion (TAPSE [81%]) were common. Right atrial size, end-diastolic RV area, and RV wall thickness were independently associated with max PG. Decreased TAPSE was independently associated with adverse clinical findings. All indices except RA area (18.6%) and RV systolic velocity (20.7%) had CVs <15%. Repeatability coefficients are available to help distinguish a true change versus measurement variability during serially obtained exams. CONCLUSIONS: Right heart remodeling and RV dysfunction are common in dogs with PS and are associated with echocardiographic and clinical severity. Results support the quantitative assessment of right heart size and function in dogs with PS.


Assuntos
Doenças do Cão/diagnóstico por imagem , Ecocardiografia/veterinária , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Estenose da Valva Pulmonar/veterinária , Disfunção Ventricular Direita/veterinária , Animais , Cães , Feminino , Átrios do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Masculino , Estenose da Valva Pulmonar/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem
6.
J Clin Invest ; 50(12): 2660-7, 1971 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-5001960

RESUMO

A radioimmunoassay for monkey placental lactogen (MPL) was developed to study the factors controlling the secretion of MPL. The sensitivity of the assay was 1 ng MPL per ml. Human and monkey growth hormone, and human placental lactogen (HPL) showed minimal cross-reactions with MPL. Maternal MPL concentrations as measured in 40 rhesus monkeys increased progressively throughout pregnancy to a mean of 5000 ng/ml at term while umbilical vein MPL was less than 50 ng/ml. After term delivery maternal MPL concentrations decreased rapidly with a t(1/2) of 20 min.After fetectomy but with retention of the placenta, MPL concentrations decreased by 25% reaching a plateau over a 6 hr period. Experimental abruption of the secondary placenta within 1 hr produced a 50% decrease in MPL concentration. After ligation of the fetal vessels supplying the secondary placental disc, MPL increased transiently and then decreased to levels significantly below those of the control period. These studies suggest MPL secretion is not directly controlled by the fetus but is sensitive to changes in placental blood flow. The pregnant rhesus monkey serves as a useful model for investigating factors which may regulate HPL secretion because of the close similarity between MPL and HPL secretion.


Assuntos
Lactogênio Placentário/metabolismo , Animais , Reações Antígeno-Anticorpo , Cromatografia em Gel , Reações Cruzadas , Eletroforese Descontínua , Feminino , Feto/cirurgia , Idade Gestacional , Hormônio do Crescimento/análise , Cobaias , Haplorrinos , Humanos , Isótopos de Iodo , Métodos , Tamanho do Órgão , Placenta/anatomia & histologia , Placenta/metabolismo , Placenta/cirurgia , Extratos Placentários/análise , Lactogênio Placentário/análise , Lactogênio Placentário/biossíntese , Lactogênio Placentário/sangue , Gravidez , Radioimunoensaio
7.
Encephale ; 33(5): 738-43, 2007 Oct.
Artigo em Francês | MEDLINE | ID: mdl-18357843

RESUMO

This paper reviews the literature on the links between panic disorder with or without agoraphobia and vestibular dysfunction. To date, it has been established that these conditions are encountered in high proportions in psychiatric samples and in patients consulting for equilibrium problems. Three models have tried to hypothesize the mechanisms underlying this co-occurrence. Agoraphobic avoidance and high anxiety level seem to be characteristics of individuals affected by both conditions. Moreover, vestibular dysfunctions appear to be predicted by individuals feeling uncomfortable in situations characterized by spatial and/or motor particularities. Additional studies on that topic would be beneficial. Further studies should try to better understand people with both panic disorder and dysfunctions of the equilibrium system. These individuals who suffer from both conditions may avoid activities that particularly call upon the equilibrium system, such as walking on uneven surfaces or undertaking some forms of transportation. The cognitive substrates pertaining to the feared consequences of the physical symptoms may also differentiate this group from uncomplicated anxiety disorder patients. For example, these individuals with uncomplicated panic disorder may fear having a heart attack or suffocating as a result of a panic attack, whereas individuals suffering from both conditions may be more prone to apprehending falling or vomiting. The paper also proposes (1) the analysis of characteristics of individuals in remission from both conditions so that effective components of treatment are emphasized, and (2) targets for treatment for these comorbid patients.


Assuntos
Transtorno de Pânico/epidemiologia , Transtorno de Pânico/etiologia , Vertigem , Vestíbulo do Labirinto/fisiopatologia , Humanos , Prevalência , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/epidemiologia , Transtornos Psicofisiológicos/psicologia , Vertigem/epidemiologia , Vertigem/fisiopatologia , Vertigem/psicologia
8.
J Natl Cancer Inst ; 68(4): 537-9, 1982 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6951070

RESUMO

There was no overall relationship between a prior history of oral contraceptive (OC) use and the development of melanoma among 141 cases of nonfatal malignant melanoma and 2,820 age-matched controls drawn from respondents to a large postal survey of registered U.S. nurses; crude relative risk (RR) was 0.93 and 95% confidence limits (CL) were between 0.64 and 1.36. Adjustment for a number of additional variables did not alter this estimate materially. Duration of OC use and interval since first use were similarly unrelated to the occurrence of melanoma. For women diagnosed before age 40, there was a crude positive association of "ever" use of OC and melanoma (RR = 1.78; 95% CL, 1.11-2.86). However, adjustment for geography and other variables diminished this association and rendered it statistically not significant (RR = 1.43, 95% CL, 0.83-2.46). These data do not support the hypothesis that OC use is an independent risk factor for melanoma.


Assuntos
Anticoncepcionais Orais/efeitos adversos , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Adulto , Fatores Etários , Feminino , Humanos , Melanoma/epidemiologia , Enfermeiras e Enfermeiros , Risco , Neoplasias Cutâneas/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Estados Unidos
9.
J Natl Cancer Inst ; 72(1): 39-42, 1984 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6363789

RESUMO

Among 989 cases of breast cancer and 9,890 controls selected from a cohort of married, female registered nurses aged 30-55 years, the relative risk (RR) of breast cancer for women who had ever used oral contraceptives (OC) compared with those who had never used them was 1.0, with 95% confidence limits 0.9-1.2. Among OC users, there was no consistent pattern of excess risk with increasing duration; in fact, the few women who had used OC longest (greater than 10 yr) had a slightly lower risk than never-users. Moreover, there was no association between OC use and breast cancer among women with a positive history of breast cancer in the mother or sister or with OC use before their first pregnancy. The only subgroup of women among whom any adverse effect was apparent was current OC users aged 50-55 years (two onsets expected vs. seven observed). This finding is consistent with earlier reports of an increased risk of breast cancer among older OC users; however, it is also likely to reflect, at least to some extent, the play of chance, since at ages 45-49 and in each younger age group fewer cases than expected were observed among current OC users.


Assuntos
Neoplasias da Mama/induzido quimicamente , Anticoncepcionais Orais/efeitos adversos , Adulto , Ensaios Clínicos como Assunto , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco
10.
J Clin Oncol ; 19(3): 742-9, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11157026

RESUMO

PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Oculares/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Neoplasias Oculares/tratamento farmacológico , Estudos de Viabilidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Imunoblástico de Células Grandes/tratamento farmacológico , Linfoma Imunoblástico de Células Grandes/terapia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/terapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Doenças do Sistema Nervoso/induzido quimicamente , Terapia de Salvação , Tiotepa/administração & dosagem
11.
Leukemia ; 14(4): 573-5, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10764141

RESUMO

Splenic lymphoma with villous lymphocytes (SLVL) is a B cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second-line treatment remains questionable. In a retrospective study, we evaluated the efficacy and toxicity of fludarabine (FDR) in 10 SLVL patients. The median duration between diagnosis and treatment was 17 months (range, 1-30). Two patients were previously untreated. The patients received FDR 25 mg/m2/day by venous infusion for 5 days with a median of four cycles of chemotherapy (range, 2-6). All patients were assessable: five patients achieved a good and persistent response after a median follow-up of 14 months (5-31), two achieved a good response but relapsed after a follow-up of 15 and 36 months. One out of the three partial responders have a persistent response. The treatment was well tolerated. FDR appears to be an efficient therapy with a favorable toxicity profile for patients in relapse after splenectomy or resistant to CLB. Furthermore it could constitute an alternative to splenectomy in older patients. A longer follow-up and the study of a larger group of patients are warranted to confirm our findings.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Neoplasias Esplênicas/tratamento farmacológico , Vidarabina/análogos & derivados , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Clorambucila/uso terapêutico , Terapia Combinada , Avaliação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma de Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Indução de Remissão , Estudos Retrospectivos , Esplenectomia , Neoplasias Esplênicas/cirurgia , Vidarabina/uso terapêutico
12.
Leukemia ; 16(4): 587-93, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11960337

RESUMO

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Célula do Manto/terapia , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imunofenotipagem , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Biol Psychiatry ; 40(5): 353-60, 1996 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8874835

RESUMO

Both clinical symptomatology and stress research suggest that panic attacks might be partially attributable to exaggerated psychophysiological responses to environmental stressors. In the present study, we aimed to explicitly test this idea by measuring the physiological responses to a mild psychological stressor in both healthy controls (n = 8) and fully remitted, medication-free panic disorder patients (n = 8). One hour before the stressor, former patients, compared to healthy controls, exhibited higher diastolic blood pressure. From a blood sample taken 30 min before the stressor, patients, compared to controls, had lower paroxetine platelet binding site densities. During the stressor, patients, compared to controls, had greater increases in plasma levels of cortisol. These preliminary findings suggest that remitted panic disorder patients might have disturbed physiological responses to mild psychological stressors. These disturbances might be related to the development of future episodes.


Assuntos
Monoaminas Biogênicas/metabolismo , Hemodinâmica/fisiologia , Sistemas Neurossecretores/fisiologia , Transtorno de Pânico/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto , Plaquetas/metabolismo , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Transtorno de Pânico/metabolismo , Transtorno de Pânico/psicologia , Paroxetina/sangue , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Radioimunoensaio , Receptores de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/sangue , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
14.
Gene ; 97(2): 283-8, 1991 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-1999293

RESUMO

The structural organization of the entire nuclear gene (NMDMC) encoding the mitochondrial (mt) NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase enzyme (NMDMC) was determined by analysis of clones obtained from a lambda EMBL3 murine genomic DNA library. The gene is approx. 13 kb in length and contains eight exons and seven introns. All exon/intron splice junctions follow the GT/AG rule. The amino acid presequence, which is essential for transport of the NMDMC enzyme precursor into mt, is encoded almost entirely in the first exon. Two major transcriptional start points (tsp), located 33 and 75 nucleotides upstream from the AUG start codon, were revealed by S1 nuclease mapping and RNase protection analyses. The immediate 5'-flanking region of the first exon contains one CAAT box, a TATA-like box and three sites homologous to the consensus sequence for the binding of transcription factor Sp1.


Assuntos
Aminoidrolases/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Animais , Sequência de Bases , Clonagem Molecular , Sequência Consenso , Éxons , Genes , Íntrons , Camundongos , Dados de Sequência Molecular , NAD/metabolismo , Mapeamento por Restrição , Transcrição Gênica
15.
FEBS Lett ; 499(1-2): 59-64, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11418112

RESUMO

Palmitoylation is a post-translational modification that occurs on selected cysteines of many proteins. Since a high proportion of basic and hydrophobic residues is often found near the palmitoylated cysteine, the role of these residues in the selection of specific palmitoylation sites was assessed. Short peptides derived from the beta(2)-adrenergic receptor sequence, modified to present different proportions of basic, acidic and hydrophobic residues, were tested in an in vitro S-acylation assay. Basic residues proved to be essential, whereas hydrophobic residues greatly enhanced S-acylation and acidic residues inhibited it. Taken together, these results show that short peptides contain the required molecular determinants leading to selective S-acylation. Whether or not these sequence characteristics also contribute to the selectivity of palmitoylation in vivo will need to be further investigated.


Assuntos
Ácido Palmítico/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/metabolismo , Acilação , Sequência de Aminoácidos , Aminoácidos/análise , Aminoácidos/metabolismo , Cisteína/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Fragmentos de Peptídeos/síntese química
16.
Transplantation ; 74(12): 1797-800, 2002 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-12499902

RESUMO

The authors report two cases of hypereosinophilia as the major presenting sign of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Tissue biopsies of the skin, salivary gland, gut, and liver showed evidence of acute GVHD (aGVHD). In one case, further investigations have been performed. Elevated levels of interleukin (IL)-5 and soluble IL-2 receptor were found in the blood, and skin biopsy specimens demonstrated high levels of IL-5 messenger ribonucleic acid (mRNA). In contrast, skin biopsy specimens from other patients with aGVHD but without eosinophilia were negative for IL-5 mRNA. The authors also demonstrated the presence of IL-4 and interferon(IFN)-gamma mRNA within the same skin biopsy specimen, suggesting that this case of aGVHD was mediated by both Th1 and Th2 cell type. These two patients were treated by glucocorticoids with resolution of the hypereosinophilia and the symptoms of GVHD. The authors briefly discuss the possible mechanisms of this hypereosinophilia with respect to aGVHD.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/patologia , Síndrome Hipereosinofílica/etiologia , Síndrome Hipereosinofílica/patologia , Doença Aguda , Adulto , Biópsia , Humanos , Interleucina-5/sangue , Interleucina-5/genética , Masculino , RNA Mensageiro/análise , Pele/patologia , Transplante Homólogo
17.
Leuk Res ; 15(2-3): 121-8, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1826751

RESUMO

We investigated the correlations between the biological effects of interferon-alpha (IFN-alpha) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40-50% of cases respond to IFN-alpha therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 x 10(6) U of IFN-alpha 2a. Binding experiments with [125I]IFN-alpha 2a showed the presence of IFN-alpha receptors on tumor B-cells isolated from lymph nodes before therapy in 9 out of 10 patients. Receptor levels were not related to the subsequent clinical responses. However, no specific binding was detected in one patient who turned out to be unresponsive to IFN-alpha treatment. Single injections of IFN-alpha 2a before beginning the therapeutic protocol resulted in down-regulation of IFN-alpha receptors without change in their affinity in peripheral blood leukocytes from only patients who subsequently responded to therapy (4/10). In 4/5 non-responders and one patient displaying a minor response, receptor numbers did not decrease but Kd values rose markedly in all six cases. These results indicate that lack of in vivo IFN-alpha receptor down-regulation and reduced receptor affinity, as detected before therapy, may be correlated with failure of IFN-alpha therapy in nodular NHL.


Assuntos
Regulação para Baixo , Interferon Tipo I/uso terapêutico , Linfoma Folicular/terapia , Linfoma não Hodgkin/terapia , Receptores Imunológicos/metabolismo , 2',5'-Oligoadenilato Sintetase/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Divisão Celular , Avaliação de Medicamentos , Humanos , Interferon Tipo I/metabolismo , Interleucina-4/farmacologia , Leucócitos Mononucleares/metabolismo , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Receptores de Interferon , Indução de Remissão , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologia
18.
Bone Marrow Transplant ; 11(4): 293-7, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8485477

RESUMO

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.


Assuntos
Anticorpos Monoclonais/imunologia , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Terapia de Imunossupressão/métodos , Receptores de Interleucina-2/imunologia , Análise Atuarial , Doença Aguda , Adolescente , Adulto , Animais , Anticorpos Monoclonais/uso terapêutico , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/uso terapêutico , Incidência , Lactente , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Ratos , Taxa de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
19.
Bone Marrow Transplant ; 10(5): 409-13, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1464001

RESUMO

Peripheral blood stem cells (PBSC) were collected from 29 patients with high risk Hodgkin's disease (n = 3) or non-Hodgkin's lymphoma (n = 26) in partial remission or first sensitive relapse. Patients had either bone marrow involvement or hypoplastic bone marrow. The conditioning regimen prior PBSC collection included amsacrine and cytosine arabinoside (Ara-C) or Ara-C alone. PBSC collection was performed after leukocyte counts reached 1 x 10(9)/1. A good yield was obtained in 23 patients, whereas sufficient numbers of CFU-GM were not obtained in six cases. Twenty-one patients have been transplanted. All patients except one achieved bone marrow engraftment. Eight patients are in complete remission (mean duration 15 months). The estimated 2 years survival rate is 46.4% (CI 25-68%). This procedure would seems a good alternative in poor prognosis lymphomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Sangue Autóloga , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco , Adulto , Amsacrina/administração & dosagem , Remoção de Componentes Sanguíneos , Citarabina/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Complicações Pós-Operatórias , Taxa de Sobrevida
20.
Leuk Lymphoma ; 35(5-6): 501-5, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10609787

RESUMO

Mobilization techniques for peripheral blood stem cell (PBSC) collection include the administration of chemotherapy followed by hematopoietic growth factors or growth factors alone. Two forms of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available for PBSC mobilization: lenograstim and filgrastim which are the glycosylated and non-glycosylated forms respectively. In order to determine the influence of the two forms of G-CSF following chemotherapy on PBSC collection, we conducted a retrospective study in 126 patients with various hematological malignancies: 65 and 61 for the lenograstim and filgrastim groups respectively. No significant differences between the two groups were observed in terms of sex, age and diagnosis. Prior therapies and PBSC mobilization regimen were also equivalent. No significant difference was observed between the groups for the median CD34+ cells harvested. The number of leukapheresis necessary to obtain a minimal number of 3 x 10(6) CD34+ cells/kg was equivalent for the two groups. The proportion of patients affected by a failure in PBSC collection was similar in the two groups. Our data suggest that lenograstim and filgrastim are equivalent for PBSC mobilization after chemotherapy.


Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Neoplasias Hematológicas/sangue , Mobilização de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Avaliação de Medicamentos , Feminino , Filgrastim , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Humanos , Lenograstim , Leucaférese , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Estudos Retrospectivos
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