RESUMO
BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.
Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/cirurgia , Mamoplastia/métodos , Mastectomia Subcutânea/métodos , Terapia Neoadjuvante , Retalho Perfurante , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carboplatina/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Quimioterapia Adjuvante , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Docetaxel , Epirubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Taxoides/administração & dosagem , Trastuzumab , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. OBJECTIVE: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). METHODS: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. RESULTS: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months' supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). CONCLUSION: Three months' supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.
Assuntos
Ácido Araquidônico/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiologia , Ecocardiografia/métodos , Ecocardiografia Doppler em Cores/métodos , Métodos Epidemiológicos , Membrana Eritrocítica/diagnóstico por imagem , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/fisiologia , Feminino , Humanos , MasculinoRESUMO
The mechanisms by which pulmonary granuloma formation is caused by administration of mycobacterial glycolipids such as trehalose dimycolate (TDM), lipoarabinomannan (LAM) and phosphatidylinositol mannosides (PIM) were investigated. When peritoneal and alveolar macrophages were stimulated with TDM, LAM and PIM in vitro, TDM exhibited the strongest tumour necrosis factor (TNF)-inducing activity. Responsiveness of macrophages from mice defected Toll-like receptor 4 (TLR4) was much higher than that of the wild-type mice. Although PIM and LAM also had a significant activity, LAM rather than PIM stimulated higher TNF-alpha production by alveolar macrophage. When mycobacterial glycolipids were injected as water-in-oil-in-water emulsion into mice via the tail vein, development of pulmonary granuloma in response to glycolipids were related closely to their TNF-inducing activity and TDM exhibited the strongest activity. Granuloma formation was observed not only in mice lacking interleukin (IL)-12 signalling but also interferon (IFN)-gamma knock-out mice. Granuloma formation caused by glycolipids correlated with TNF-alpha levels in lungs. Administration of anti-TNF-alpha monoclonal antibody into TDM-injected IFN-gamma knock-out mice decreased in granuloma formation, suggesting that development of pulmonary granuloma by mycobacterial glycolipids such as TDM is due to IFN-gamma-independent and TNF-alpha-dependent pathway.
Assuntos
Antígenos de Bactérias/imunologia , Glicolipídeos/administração & dosagem , Granuloma/imunologia , Interferon gama/imunologia , Pneumopatias/imunologia , Mycobacterium tuberculosis/química , Adjuvantes Imunológicos/administração & dosagem , Animais , Fatores Corda/administração & dosagem , Feminino , Injeções , Lipopolissacarídeos/administração & dosagem , Macrófagos/imunologia , Macrófagos Alveolares/imunologia , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositóis/administração & dosagem , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.
Assuntos
Antibacterianos/uso terapêutico , Cefmenoxima/análogos & derivados , Cefmenoxima/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/metabolismo , Infecções Bacterianas/tratamento farmacológico , Temperatura Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Modelos Químicos , Placebos , Fatores de TempoRESUMO
BACKGROUND/PURPOSE: Rectourethral (RUF) or rectovaginal fistula (RVF) is a troublesome complication after anorectal surgery because of dense adhesions around the fistula. The authors applied a new technique for the redo surgery. METHODS: Case 1 is Hirschsprung's disease in a 1-year-old boy who underwent modified Duhamel's procedure and had RUF. Case 2 is rectovestibular fistula in an 11-year-old girl who had anterior sagittal anorectoplasty complicated by RVF. Case 3 is multiple urogenital anomalies including rectovesical fistula in a 4-year-old boy in whom transvesical repair was unsuccessful. The colon was mobilized as far as possible at laparotomy. The rectum was opened via a posterior sagittal approach leaving 1 cm of the anal canal. Extended endorectal mucosectomy was performed to the dentate line, and the fistula was closed from inside of the rectum. The remaining mucosal cuff was everted out of the anus and the intact colon was pulled through the rectum and anastomosed to the cuff extraanally. RESULTS: The postoperative contrast enema showed no recurrent fistula, and defecation was not impaired. CONCLUSIONS: Endorectal pull-through of the intact colon can spare troublesome mobilization of the fistula and can prevent the recurrence of fistula. Rectal incision via a posterior sagittal approach provides a direct view of the fistula.
Assuntos
Complicações Pós-Operatórias/cirurgia , Fístula Retal/cirurgia , Doenças Uretrais/cirurgia , Fístula Urinária/cirurgia , Criança , Pré-Escolar , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Doença de Hirschsprung/cirurgia , Humanos , Lactente , Masculino , Fístula Retovaginal/cirurgia , Reto/cirurgiaRESUMO
BACKGROUND: The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). METHODS: In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. RESULTS: Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. CONCLUSIONS: CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.
Assuntos
Anemia Ferropriva/sangue , Ferritinas/sangue , Hemoglobinas/análise , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Transferrina/análise , Adulto , Anemia Ferropriva/etiologia , Anemia Ferropriva/terapia , Índices de Eritrócitos , Eritropoetina/uso terapêutico , Feminino , Humanos , Falência Renal Crônica/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Reticulócitos/químicaRESUMO
A rapid and highly sensitive LC-MS-MS method for simultaneous determination of 25-hydroxyvitamin D2 125(OH)D21 and 25-hydroxyvitamin D3 125(OH)D3] in human plasma has been developed using derivatization with a Cookson-type reagent, 4-12-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyll-1,2,4-triazoline-3,5-dione (DMEQTAD). The derivatization with DMEQTAD significantly improved the ionization efficiencies of 25(OH)D2 and 25(OH)D3 with detection limits of 20 and 12.5 fmol (8 and 5 pg) per injection, respectively. The method employed two steps of solvent extraction but did not require chromatographic purifications for sample pretreatment. The determination was carried out by mass chromatography of the protonated molecular ions formed by atmospheric pressure chemical ionization operating in the positive-ion mode after the derivatization, and 25-hydroxyvitamin D4 was used as an internal standard. The intra-assay coefficients of variation were below 4.02 and 3.24% for 25(OH)D2 and 25(OH)D3, respectively, and the analytical recoveries of both compounds were quantitative. Assay linearity was obtained in the range of 0.05-1 ng per tube and the determination limit was 3 ng/ml for a 20 microl plasma aliquot, for each compound. The developed method was applied to plasma samples obtained from volunteers, two of whom had received vitamin D2 supplementation, and gave satisfactory results.
Assuntos
Calcitriol/sangue , Adulto , Calibragem , Cromatografia Líquida , Feminino , Humanos , Indicadores e Reagentes , Masculino , Espectrometria de Massas , Reprodutibilidade dos TestesRESUMO
Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil [PEO; oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6], borage oil [oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1; P/S, 5.3], evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha-linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid.
Assuntos
Colesterol na Dieta/administração & dosagem , Colesterol/sangue , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Envelhecimento , Animais , Apolipoproteínas B/genética , Colesterol/análise , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Fezes/química , Ácido Linoleico/administração & dosagem , Lipídeos/análise , Lipoproteínas/sangue , Fígado/anatomia & histologia , Fígado/química , Masculino , Ácido Oleico/administração & dosagem , Tamanho do Órgão , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344 , Receptores de LDL/genética , Ácido alfa-Linolênico/administração & dosagem , Ácido gama-Linolênico/administração & dosagemRESUMO
Early-morning blood pressure is generally viewed as an important therapeutic target, for two reasons. First, for antihypertensive agents taken once daily in the morning, the timing of the trough plasma drug level, and thereby the lowest pharmacodynamic effect, often coincides with the early morning rise in blood pressure and heart rate. Evidence has been accumulated to suggest that blood pressure control throughout the 24 h period may be necessary to gain complete benefit from antihypertensive medication. In fact, in a longitudinal study, the regression of cardiac hypertrophy in patients with hypertension was more accurately predicted by treatment-induced changes in average 24 h ambulatory blood pressure than by clinic or home-monitored blood pressure readings. The other reason for the importance of morning blood pressure is that cardiovascular risk is heightened at this time of day. A morning surge in sympathetic activity alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. At the same time as this risk of plaque rupture is greatest, circadian variations in haemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal thrombi. We recently showed that, in older hypertensives, a greater morning blood pressure surge, mediated at least in part by an exaggerated alpha-sympathetic activity, is associated with more advanced silent cerebrovascular disease as well as a higher future incidence of stroke. The early morning surge in blood pressure could become a new therapeutic target for preventing target-organ damage and subsequent cardiovascular events in hypertension. Of greatest interest is the potential benefit of a chronotherapeutic approach, involving, for example, long-acting chronoformulations, which has not yet been extensively studied.
Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Hipertensão/complicações , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Cronoterapia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologiaRESUMO
2'-Deoxyguanosine residues of a 3',5'-end-modified hexadeoxyribonucleotide (R-95288) with anti-HIV-1 activity were substituted with N2-methyl-2'-deoxyguanosine (m2dG). These modified oligodeoxyribonucleotides (ODNs) showed a 2-fold higher activity than R-95288. Also, the CD spectra of these ODNs indicated that the m2dG modification stabilized the tertiary structure of the G-quadruplex.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Desoxiguanosina/química , HIV-1/efeitos dos fármacos , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/síntese química , Oligodesoxirribonucleotídeos/farmacologia , Linhagem Celular , Dicroísmo Circular , Avaliação Pré-Clínica de Medicamentos , Humanos , Metilação , Estrutura MolecularRESUMO
Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum alpha-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level >/=200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.
Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Embolização Terapêutica/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Óleo Iodado , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Necrose , Tomografia Computadorizada por Raios X , Resultado do Tratamento , alfa-Fetoproteínas/metabolismoRESUMO
Recently, there have been some reports indicating that calcium antagonists induce a reflex increase in sympathetic activity, triggering cardiac events, especially in coronary artery disease (CAD) patients. In this study, we assessed heart rate (HR) variability (HRV) using power spectral analysis of the 24-h RR interval in 25 hypertensive outpatients with CAD treated with nifedipine. We compared blood pressure (BP), HR, and HRV variation in the same patients substituting benidipine (long-acting) for nifedipine (intermediate-acting). There were no significant differences in 24-h, daytime, nighttime, and morning BP between the nifedipine phase and the benidipine phase. HRV parameters (LF: low frequency power, HF: high frequency power, LF/HF ratio) also showed no significant differences in 24-h, daytime, nighttime, and morning LF, HF, and LF/HF ratio between the nifedipine phase and the benidipine phase. Blood pressure, HR, and HRV parameters, except the LF component from 2 to 4 h after nifedipine administration (the most effective duration), showed no differences compared to before administration. The LF component after the nifedipine administration was lower than before administration. In conclusion, in hypertensive patients with CAD, whose BP levels were well-controlled by twice-daily use of intermediate-acting nifedipine, switching from nifedipine to a long-acting calcium antagonist, benidipine, maintained well-controlled BP levels to a similar degree, but it may not have additional benefit in sympatho-vagal balance.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ritmo Circadiano , Doença das Coronárias/tratamento farmacológico , Hipertensão/tratamento farmacológico , Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Doença das Coronárias/fisiopatologia , Preparações de Ação Retardada , Di-Hidropiridinas/uso terapêutico , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Resultado do TratamentoRESUMO
Tec, Btk, Itk, Bmx, and Txk constitute the Tec family of protein tyrosine kinases (PTKs), a family with the distinct feature of containing a pleckstrin homology (PH) domain. Tec acts in signaling pathways triggered by the B cell antigen receptor (BCR), cytokine receptors, integrins, and receptor-type PTKs. Although upstream regulators of Tec family kinases are relatively well characterized, little is known of the downstream effectors of these enzymes. The yeast two-hybrid system has identified several proteins that interact with the kinase domain of Tec, one of which is now revealed to be a previously unknown docking protein termed BRDG1 (BCR downstream signaling 1). BRDG1 contains a proline-rich motif, a PH domain, and multiple tyrosine residues that are potential target sites for Src homology 2 domains. In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/genética , Proteínas Tirosina Quinases/metabolismo , Sequência de Aminoácidos , Linfócitos B/metabolismo , Proteínas de Transporte/química , Linhagem Celular , Clonagem Molecular , DNA Complementar/metabolismo , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Humanos , Modelos Genéticos , Dados de Sequência Molecular , Fosforilação , Plasmídeos/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Transfecção , Técnicas do Sistema de Duplo-HíbridoAssuntos
Poluentes Ocupacionais do Ar/intoxicação , Brônquios/efeitos dos fármacos , Broncopatias/induzido quimicamente , Sulfeto de Hidrogênio/intoxicação , Doenças Profissionais/induzido quimicamente , Edema Pulmonar/induzido quimicamente , Adulto , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , PetróleoRESUMO
Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel.
Assuntos
Antagonistas Adrenérgicos alfa/uso terapêutico , Transplante de Pulmão/efeitos adversos , Prazosina/uso terapêutico , Edema Pulmonar/prevenção & controle , Ioimbina/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos , Insuficiência Cardíaca/etiologia , Hemodinâmica , Isquemia/etiologia , Ligadura , Pulmão/irrigação sanguínea , Masculino , Artéria Pulmonar , Circulação Pulmonar , Edema Pulmonar/etiologia , Ratos , Ratos Endogâmicos BUF , Simpatectomia Química , Resistência VascularRESUMO
BACKGROUND: Tec is a member of the recently emerging subfamily among nonreceptor protein-tyrosine kinases (PTKs). Although many members of this family have been shown to be involved in a wide range of cytokine-mediated signalling systems, the molecular mechanism by which they exert in vivo effects remains obscure. To gain insights into the downstream pathways of Tec, we here looked for Tec-interacting proteins (TIPs) by using the yeast two-hybrid screening. RESULTS: One of TIPs turned out to be Grb10/GrbIR, which carries one pleckstrin homology domain and one Src homology 2 domain. Grb10/GrbIR was known to bind receptor PTKs in a ligand-dependent fashion, but not to be phosphorylated on tyrosine residues. In a transient expression system in human kidney 293 cells, however, Grb10/GrbIR becomes profoundly tyrosine-phosphorylated by Tec, but not by Syk, Jak2 or insulin receptor. We also reveal that expression of Grb10/GrbIR suppresses the cytokine-driven and Tec-driven activation of the c-fos promoter. CONCLUSION: Our results indicate a novel role of Grb10/GrbIR as an effector molecule to a subset of nonreceptor PTKs.
Assuntos
Proteínas Tirosina Quinases/metabolismo , Proteínas/genética , Proteínas/metabolismo , Transdução de Sinais/fisiologia , Sequência de Aminoácidos , Linhagem Celular , Cromossomos Humanos Par 7/genética , Clonagem Molecular , DNA Complementar , Proteína Adaptadora GRB10 , Regulação da Expressão Gênica/genética , Genes fos/genética , Humanos , Dados de Sequência Molecular , Fosforilação , Mapeamento Físico do Cromossomo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas Tirosina Quinases/genética , RNA Mensageiro , Análise de Sequência de DNA , Especificidade por Substrato , Tirosina/metabolismoRESUMO
A 74-year-old man developed Cushing's syndrome and hypokalemia due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of mineralocorticoid hormones. Plasma concentrations of weak mineralocorticoids were high. The increase in plasma cortisol did not have a diurnal rhythm, and was not suppressed by a high dose of dexamethasone. Plasma ACTH was undetectable, but plasma cortisol was increased by ACTH administration. The concentrations of mineralocorticoids, especially deoxycorticosterone and corticosterone were increased, and augmented the response to ACTH administration. Plasma renin activity and aldosterone concentrations were rather suppressed. Both adrenal glands, with a total weight of 110 g, were enlarged and contained several macronodules. These nodules were composed of hyperplasia of small cortical cells and usual clear cells. This is a rare case of ACTH-independent bilateral macronodular adrenocortical hyperplasia because there were excessive secretion of mineralocorticoid and hypokalemia.
Assuntos
Córtex Suprarrenal/patologia , Hormônio Adrenocorticotrópico , Síndrome de Cushing/patologia , Mineralocorticoides/metabolismo , Córtex Suprarrenal/metabolismo , Idoso , Aldosterona/sangue , Síndrome de Cushing/diagnóstico , Dexametasona , Glucocorticoides , Humanos , Hidrocortisona/sangue , Hiperplasia/sangue , Hiperplasia/tratamento farmacológico , Masculino , Metirapona , Radioimunoensaio , Renina/sangueRESUMO
This paper presents survey results of connectivity to the Internet from preventive and environmental medicine-related departments in medical schools and other institutions in Japan and propose means to establish connectivity among them. Of 191 facilities surveyed, 134 (70%) responded by March 31, 1996. The data presented here are from 132 facilities. One hundred seventeen facilities (89%) answered that they were connected to the Internet. More than 80% of them got access to the Internet in the past two years. One hundred three facilities (78%) answered that e-mail was available. Despite the large percentage being connected, only 11 facilities (8%) had their own homepages. However, just 6 months later more than 25 facilities could be found by their own homepages. The Global Health Network (GHNet) has been developed in the USA based upon the concept that the best means to produce improved health is a better surveillance and information system applying the latest telecommunication technology to public health. The GHNet will offer an initial homepage for Preventive and Environmental Medicine related facilities in Japan to promote and establish sustainable connectivity among them.
RESUMO
The effects of water deprivation on the secretion of vasotocin (AVT) and expression of the AVT gene were studied in White Leghorn cockerels. Animals deprived of water for 4 days were compared with normally hydrated controls. Blood samples were obtained for measurements of plasma osmolality and AVT levels, and the hypothalamus was collected for extraction of total cellular RNA. A 519-bp AVT cDNA was prepared by reverse transcriptase-polymerase chain reaction and a 209-bp PstI/EcoRI restriction fragment from the 3' region of the fowl AVT cDNA was used as a probe for Northern blot analysis. Plasma osmolality and AVT levels in dehydrated birds were about 30 and 350% greater, respectively, than those in normally hydrated controls. The quantity of hypothalamic AVT mRNA was 2. 3-fold greater in water-deprived birds compared to controls. The size of the hypothalamic AVT transcript was about 100-bp longer in the water-deprived birds. As determined by RNase H treatment in the presence and absence of oligo(dT)12-18, the increase in mean size of the AVT mRNA in dehydrated animals was due to a longer poly(A) tract. Our results indicate that osmotic stress up-regulates expression of the AVT gene and increases the accumulation of AVT mRNA in the hypothalamus. This accumulation may, in part, be due to lengthening of the AVT mRNA poly(A) tail which is a general mechanism associated with stabilization of vertebrate mRNAs.
Assuntos
Galinhas/fisiologia , Hipotálamo/metabolismo , RNA Mensageiro/genética , Vasotocina/genética , Privação de Água/fisiologia , Animais , Autorradiografia , Sequência de Bases , Northern Blotting , Galinhas/sangue , Primers do DNA/química , Sondas de DNA , DNA Complementar/genética , Expressão Gênica , Hipotálamo/química , Masculino , Concentração Osmolar , Reação em Cadeia da Polimerase , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Distribuição Aleatória , Kit de Reagentes para Diagnóstico , Ribonuclease H/metabolismo , Vasotocina/sangue , Vasotocina/imunologiaRESUMO
We used expressed sequence tags (ESTs) to identify genes expressed in mouse embryonal carcinoma F9 cells and prepared 2132 ESTs from undifferentiated F9 cDNA libraries: 1026 were prepared after randomly selecting clones from one of the libraries and the remaining 1106 ESTs were prepared after classifying 2896 clones of the libraries into four classes, according to the levels and patterns of expression. Among the former 1026 ESTs, 797 (78%) matched known genes, 61 (6%) matched database sequences of uncharacterized cDNAs, and 168 (16%) represented novel genes. The ESTs matching known genes were catalogued according to putative structural and cellular functions. As many as 53% were related to transcription and translation, and 19% were related to energy metabolism, including transcripts of mitochondrial DNA. These percentages were significantly higher in F9 cells than in the human heart and brain, and a human liver cell line, HepG2. We found that approximately 7% of the ESTs corresponding to low-abundance mRNAs are either related to retinoic acid-regulated genes or mammalian development- and/or differentiation-related genes. Cataloguing of the genes expressed in the F9 cells paves the way for isolating genes involved in early mammalian development.