RESUMO
Cooperative interactions among individuals are ubiquitous despite the possibility of exploitation by selfish free riders. One mechanism that may promote cooperation is 'negotiation': individuals altering their behaviour in response to the behaviour of others. Negotiating individuals decide their actions through a recursive process of reciprocal observation, thereby reducing the possibility of free riding. Evolutionary games with response rules have shown that infinitely many forms of the rule can be evolutionarily stable simultaneously, unless there is variation in individual quality. This potentially restricts the conditions under which negotiation could maintain cooperation. Organisms interact with one another in a noisy world in which cooperative effort and the assessment of effort may be subject to error. Here, we show that such noise can make the number of evolutionarily stable rules finite, even without quality variation, and so noise could help maintain cooperative behaviour. We show that the curvature of the benefit function is the key factor determining whether individuals invest more or less as their partner's investment increases, investing less when the benefit to investment has diminishing returns. If the benefits of low investment are very small then behavioural flexibility tends to promote cooperation, because negotiation enables cooperators to reach large benefits. Under some conditions, this leads to a repeating cycle in which cooperative behaviour rises and falls over time, which may explain between-population differences in cooperative behaviour. In other conditions, negotiation leads to extremely high levels of cooperative behaviour, suggesting that behavioural flexibility could facilitate the evolution of eusociality in the absence of high relatedness.
Assuntos
Evolução Biológica , Comportamento Cooperativo , Teoria dos Jogos , Animais , Comportamento SocialRESUMO
BACKGROUND: Some patients with multiple system atrophy (MSA) require surgical interventions such as tracheostomy and aspiration prevention. Few studies have investigated the postoperative clinical course of MSA patients. The aim of this study was to determine a management strategy for dysphagia and respiratory disorder in MSA. METHODS: From 2001 to 2014, 18 MSA patients (13 males and 5 females, 52-76 years) underwent tracheostomy (TR, n = 11) or laryngeal closure (LC, n = 12). Five patients underwent LC following TR. Vocal fold impairment, the degree of dysphagia and pre/post-operative oral ingestion, and postoperative survival time were evaluated retrospectively. Swallowing function was assessed using the penetration aspiration scale (PAS). RESULTS: TR was performed due to respiratory disorder in seven patients and due to dysphagia in four patients. PAS scores ranged 1-8 in TR patients and 7-8 in LC patients. Seven of 11 patients who underwent TR displayed worsened PAS scores, and no patients displayed improved PAS scores following TR. All patients who underwent LC regained complete or partial oral intake after surgery. There were no significant differences in postoperative survival time between the two groups. CONCLUSIONS: Considering the impacts of TR and LC on survival time, postoperative feeding and swallowing, LC is a good option for treating MSA patients with dysphagia.
Assuntos
Transtornos de Deglutição/cirurgia , Laringoplastia , Atrofia de Múltiplos Sistemas/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Traqueostomia , Idoso , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Laringoplastia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Traqueostomia/efeitos adversos , Resultado do TratamentoRESUMO
Virtual reality (VR)-based training has shown some benefits in medical education, supporting skill acquisition, and helping reduce anxiety in real-world settings. However, the use of VR simulators in veterinary education remains limited. This study aimed to introduce a VR simulator to support veterinarian training in canine anaesthesia induction and endotracheal intubation. This study involved a group that learned solely with instructional videos (video group), and one that learned concurrently with the video and VR simulator (VR group). Third- and fourth-year veterinary students were included and underwent a descriptive test on canine endotracheal intubation. Canine endotracheal intubation success rates were compared between the video (n = 364) and VR (n = 60) groups of fifth-year students. A survey on the VR usability was conducted (n=91). The median descriptive test scores improved in the VR (63.3/100) vs the video group (51.5/100). The canine intubation success rates were comparable in the VR and video groups at 84.3â¯% and 77.4â¯%, respectively. A total of 90.1â¯% of the surveyed students rated the ease of use of the simulator highly. Overall, VR simulators were well-received, suggesting benefits in new skill retention. Further studies are required to evaluate the extent of skill improvement through VR-based training, compared to conventional methods, and to assess its impact on student motivation. Evaluating the long-term effects of VR-based training on skill development and retention will also provide a deeper understanding of its educational benefits.
RESUMO
The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.
Assuntos
Doenças Autoimunes/imunologia , Litostatina/imunologia , Síndrome de Sjogren/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/biossíntese , Autoanticorpos/fisiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/genética , Criança , Feminino , Humanos , Interleucina-6/biossíntese , Interleucina-6/genética , Interleucina-8/biossíntese , Interleucina-8/genética , Litostatina/biossíntese , Litostatina/genética , Masculino , Pessoa de Meia-Idade , Glândulas Salivares Menores/imunologia , Glândulas Salivares Menores/metabolismo , Síndrome de Sjogren/complicações , Síndrome de Sjogren/genética , Adulto JovemRESUMO
AIMS: Diffuse large B-cell lymphoma (DLBCL) usually proliferates effacing lymph follicles. In occasional cases, tumour cells show an interfollicular pattern of proliferation preserving lymph follicles. The aim was to analyse clinicopathological findings in DLBCL showing an interfollicular pattern of proliferation to determine whether this type of lymphoma is a distinct entity of DLBCL. METHODS AND RESULTS: Clinicopathological findings in 12 cases of DLBCL showing an interfollicular pattern of proliferation [interfollicular group (IF)] were examined and compared with those in 30 cases of DLBCL with ordinary morphology [control group (CG)]. IF showed a significantly lower lactate dehydrogenase level and International Prognostic Index scores than CG (P = 0.023 and P < 0.01, respectively). The frequency of localized disease, clinical stage 1 and 2, in IF was higher than that in CG (P = 0.016). A morphologically polymorphous pattern of proliferation was found in seven of 12 cases (58.3%) in IF, which was higher than that in CG, five (16.7%) of 30 cases (P < 0.01). Clonality analysis with the polymerase chain reaction method revealed that all 11 IF cases examined showed a monoclonal pattern. Immunohistochemically, the majority (11 of 12) of IF cases showed a non-germinal centre B-cell phenotype and the frequency was higher than that in CG (P = 0.021). CONCLUSION: Diffuse large B-cell lymphoma with an interfollicular pattern of proliferation shows distinct clinical and pathological findings from ordinary DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Proliferação de Células , Feminino , Centro Germinativo/citologia , Humanos , Imuno-Histoquímica , Japão , L-Lactato Desidrogenase/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenótipo , PrognósticoRESUMO
Betaine is one of the major compatible osmolytes accumulated by kidney derived Madin-Darby canine kidney cells cultured in hypertonic medium. Betaine is accumulated by Na(+)- and Cl(-)-dependent uptake from the medium. To gain insight into the mechanism by which hypertonicity evokes an increase in the Vmax of the betaine transporter in Madin-Darby canine kidney cells, we measured the relative abundance of mRNA for the transporter in cells shifted to a hypertonic medium and found parallel increases in mRNA abundance and cotransporter activity. The increase in mRNA levels preceded the increase in transporter activity slightly. Transcription of the gene for the transporter rose rapidly and to the same relative extent as mRNA abundance in cells shifted to hypertonic medium, indicating that transcription of the gene for the cotransporter plays a major role in regulating the accumulation of betaine in response to hypertonicity.
Assuntos
Proteínas de Transporte/genética , Medula Renal/química , Medula Renal/citologia , Animais , Betaína/metabolismo , Proteínas de Transporte/fisiologia , Cães , Proteínas da Membrana Plasmática de Transporte de GABA , Soluções Hipertônicas/farmacologia , RNA Mensageiro/análise , Transcrição GênicaRESUMO
Madin-Darby canine kidney cells behave like the renal medulla and accumulate small organic solutes (osmolytes) in a hypertonic environment. The accumulation of osmolytes is primarily dependent on changes in gene expression of enzymes that synthesize osmolytes (sorbitol) or transporters that uptake them (myo-inositol, betaine, and taurine). The mechanism by which hypertonicity increases the transcription of these genes, however, remains unclear. Recently, it has been reported that yeast mitogen-activated protein (MAP) kinase and its activator, MAP kinase-kinase, are involved in osmosensing signal transduction and that mutants in these kinases fail to accumulate glycerol, a yeast osmolyte. No information is available in mammals regarding the role of MAP kinase in the cellular response to hypertonicity. We have examined whether MAP kinase and MAP kinase-kinase are regulated by extracellular osmolarity in Madin-Darby canine kidney cells. Both kinases were activated by hypertonic stress in a time- and osmolarity-dependent manner and reached their maximal activity within 10 min. Additionally, it was suggested that MAP kinase was activated in a protein kinase C-dependent manner. These results indicate that MAP kinase and MAP kinase-kinase(s) are regulated by extracellular osmolarity.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas Quinases/metabolismo , Animais , Células Cultivadas , Cães , Ativação Enzimática , Rim/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno , Concentração Osmolar , Proteína Quinase C/fisiologiaRESUMO
myo-inositol, a major compatible osmolyte in renal medulla, is accumulated in several kinds of cells under hypertonic conditions via Na+/myo-inositol cotransporter (SMIT). To investigate the physiological role of the SMIT, we sought to determine its localization by in situ hybridization and its acute regulation by NaCl and furosemide administration. Northern analysis demonstrated that SMIT is strongly expressed in the medulla and at low levels in the cortex of kidney. Intraperitoneal injection of NaCl rapidly induced SMIT mRNA in both the cortex and medulla, and furosemide completely abolished this induction. In situ hybridization revealed that SMIT it predominantly present in the medullary and cortical thick ascending limbs of Henle's loop (TALH) and macula densa cells. Less intense signals were seen in the inner medullary collecting ducts (IMCD). NaCl loading increased the signals throughout the TALH, and furosemide reduced the signals. SMIT in the IMCD is less sensitive to these kinds of acute regulation. Thus, the distribution pattern of SMIT does not correspond to the corticomedullary osmotic gradient, and SMIT in the TALH and macula densa cells is regulated very rapidly. These results suggest that SMIT expression in TALH may be regulated by intracellular and/or peritubular tonicity close to the basolateral membrane, which is supposed to be proportional to the magnitude of NaCl reabsorption.
Assuntos
Proteínas de Transporte/metabolismo , Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Rim/metabolismo , Proteínas de Membrana , Simportadores , Animais , Sequência de Bases , Northern Blotting , Proteínas de Transporte/análise , Proteínas de Transporte/biossíntese , Primers do DNA , Furosemida/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/análise , Proteínas de Choque Térmico/biossíntese , Hibridização In Situ , Rim/efeitos dos fármacos , Córtex Renal/metabolismo , Medula Renal/metabolismo , Cinética , Masculino , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Especificidade de Órgãos , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Fatores de TempoRESUMO
We investigated the effects of change in basolateral osmolality on Na(+)-dependent myo-inositol uptake in Madin-Darby canine kidney cells to test our hypothesis that the Na+/myo-inositol transporter (SMIT), an osmolyte transporter, is mainly regulated by osmolality on the basolateral surface. A significant osmotic gradient between both sides of the epithelium persisted at least 10 h after basolateral osmolality was increased. [3H]myo-inositol uptake increased in a basolateral osmolality-dependent manner. The magnitude of the increase is comparable to that for making both sides hypertonic. Apical hypertonicity also increased the uptake on the basal side, but the magnitude of the increase was significantly smaller than the basolateral or both sides hypertonicity. Betaine-gamma-amino-n-butyric acid transporter activity, measured by [3H]gamma-amino-n-butyric uptake, showed a pattern similar to SMIT activity in response to basolateral hypertonicity. The most plausible explanation for the polarized effect of hypertonicity is that the basal membrane is much more water permeable than the apical membrane. These results seem to be consistent with the localization and regulation of the SMIT in vivo.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Choque Térmico/metabolismo , Inositol/metabolismo , Rim/metabolismo , Proteínas de Membrana , Simportadores , Animais , Betaína/metabolismo , Transporte Biológico , Linhagem Celular , Polaridade Celular , Cães , Proteínas da Membrana Plasmática de Transporte de GABA , Soluções Hipertônicas , Rim/citologia , Concentração Osmolar , Sódio/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
BACKGROUND/AIMS: In patients with primary renal diseases the current knowledge of hyperglycemia associated with corticosteroid therapy is limited. We therefore examined the prevalence and risk factors of glucocorticoid-induced diabetes mellitus (DM) in primary renal diseases. METHODS: Patients were recruited with primary renal diseases who were started on corticosteroids between April 2002 and June 2005. In patients with DM, an impaired fasting glucose level and/or positive urinary glucose analyses before corticosteroids therapy were excluded. RESULTS: During corticosteroid therapy (initial dose: prednisolone 0.75 +/- 0.10 mg/kg/day), DM was newly diagnosed in 17 (40.5%) of 42 patients. All of the 17 patients were diagnosed as having DM by postprandial hyperglycemia at 2 h after lunch, although they had normal fasting blood glucose levels. Age (OR 1.40, 95% CI 1.06-1.84) and body mass index (OR 1.87, 95% CI 1.03-3.38) were determined as independent risk factors for glucocorticoid-induced DM. CONCLUSION: Over 40% of patients with primary renal disease developed DM during treatment with corticosteroids. A high age and high body mass index are the independent risk factors for glucocorticoid-induced DM. 24-hour urinary glucose analyses and postprandial plasma glucose are useful for detecting glucocorticoid-induced DM.
Assuntos
Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Glucocorticoides/efeitos adversos , Nefropatias/tratamento farmacológico , Adulto , Fatores Etários , Glicemia/análise , Índice de Massa Corporal , Ritmo Circadiano , Diabetes Mellitus/diagnóstico , Feminino , Glucocorticoides/uso terapêutico , Glicosúria/fisiopatologia , Humanos , Hiperglicemia/induzido quimicamente , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Período Pós-Prandial , Prednisolona/efeitos adversos , Prevalência , Fatores de RiscoRESUMO
A 70-year-old male, who had complained sudden chest pain and sweating, was admitted to our hospital and diagnosed as a type B intramural hematoma rupture. Emergency repair was performed with arch replacement and open-stent method. Post-operative recovery was satisfactory and the patient was discharged. A type B intramural hematoma rupture is relatively rare. Trans-esophagial echocardiography is quite useful to detect the aortic lesion and to determine the ideal depth of the stent-graft.
Assuntos
Doenças da Aorta/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Hematoma/cirurgia , Idoso , Aorta/cirurgia , Doenças da Aorta/diagnóstico , Ruptura Aórtica/diagnóstico , Ecocardiografia Transesofagiana , Emergências , Humanos , Masculino , Stents , Resultado do TratamentoRESUMO
We have shown that cell cycle progression of human T-cell leukemia virus type I (HTLV-I)-transformed T-cell lines was inhibited by 13-cis-retinoic acid (13cRA). In the present study, we report that 13cRA inhibited proliferation and induced cell death of peripheral blood mononuclear cells obtained from four patients with acute adult T-cell leukemia but not of mitogen- or interleukin 2-activated peripheral blood mononuclear cells from HTLV-I-negative healthy donors. Because HTLV-I-infected lymphocytes are susceptible to oxidative stress, we examined the role of the intracellular redox state in 13cRA-induced cell death using a HTLV-I-positive T-cell line, ATL2, as a model. 13cRA induced apoptosis in ATL2 cells within 48 h in a dose-dependent manner. The ability of 13cRA to induce apoptosis was more potent than that of all-trans-retinoic acid. Apoptosis induction by 13cRA was significantly enhanced by buthionine sulfoximine (BSO), which decreased the levels of intracellular reduced glutathione, although 13cRA by itself did not alter them, suggesting that intracellular reduced glutathione may modulate 13cRA-induced apoptosis. In addition, flow cytometric analysis revealed that 13cRA increased intracellular peroxides in 24 h and that the addition of BSO further enhanced them. Although N-acetylcysteine had only a marginal effect, pretreatment with catalase markedly inhibited 13cRA-induced apoptosis. These results suggest that peroxide generation, ie., oxidative stress, may play a crucial role in the induction of apoptosis by 13cRA and further demonstrate that combined treatment with 13cRA and BSO induces apoptosis of HTLV-I-positive lymphocytes even more potently.
Assuntos
Apoptose/efeitos dos fármacos , Isotretinoína/farmacologia , Ceratolíticos/farmacologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Estresse Oxidativo/fisiologia , Adulto , Butionina Sulfoximina/farmacologia , Catalase/farmacologia , Divisão Celular/efeitos dos fármacos , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Oxirredução , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2RESUMO
Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.
Assuntos
Linfócitos/efeitos dos fármacos , Neoplasias/genética , Troca de Cromátide Irmã/efeitos dos fármacos , 4-Nitroquinolina-1-Óxido/farmacologia , Idoso , Carbolinas/farmacologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Metanossulfonato de Metila/farmacologia , Pessoa de Meia-Idade , Neoplasias/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
The transports of tritiated ATP, ADP and AMP from the aqueous to scintillator phase with and without octadecylamine (or dodecyl guanidine) have been studied by the layered scintillation method and a theory suitable for an explanation of the results has been presented. (1) Transport processes were all expressed by the first order kinetics. (2) For the simple partitioning of ATP, the reciprocal of the rate constant of the backward permeation was linear with respect to the square of the partition coefficient. (3) For the transport of nucleotide with chemical reaction, the reciprocal of the rate constant of the backward permeation was linear against the overall partition coefficient of nucleotide. (4) A theory was presented on the basis of a general diffusion equation by assuming the two-film model with potential energy near the interface. (5) The theory could explain the dependences of the permeation rates on the partition coefficients. (6) From the finding that the ratio of the apparent diffusion coefficient in aqueous to scintillator phase was much smaller than unity, the occurrence of an energy barrier at interface was suggested. For the simple partitioning of ATP, the energy barrier was not significant.
Assuntos
Nucleotídeos de Adenina , Aminas , Guanidinas , Membranas Artificiais , Difosfato de Adenosina , Monofosfato de Adenosina , Trifosfato de Adenosina , Difusão , Cinética , Modelos Químicos , Óleos , Permeabilidade , Propriedades de Superfície , Termodinâmica , ÁguaRESUMO
Human immunoglobulin G (IgG) anti human pancreatic elastase 1 autoantibodies were detected in sera of patients with pancreatic disorders. The characteristics of these anti elastase 1 autoantibodies and their influence on radioimmunoassay (RIA) for elastase 1 were investigated. They were placed in the IgG class by the double antibody method, and most were assumed to be of a monoclonal type from their elution profiles in gel filtration analysis. The presence of autoantibodies in serum caused an increase in apparent elastase 1 values and a decrease in the recovery of elastase 1 exogenously added to the serum. These results suggest that elastase 1 immunoassay data for autoantibody positive sera can cause misjudgement of clinical stages of patients.
Assuntos
Autoanticorpos/análise , Imunoglobulina G/análise , Pancreatopatias/enzimologia , Elastase Pancreática/imunologia , Autoanticorpos/química , Cromatografia Líquida de Alta Pressão , Reações Falso-Negativas , Humanos , Imunoglobulina G/química , Radioisótopos do Iodo , Pancreatopatias/patologia , Elastase Pancreática/análise , RadioimunoensaioRESUMO
Estrogen receptor (ER) and p53 are important transcription factors in the growth regulation of tumor cells in breast cancer. We reported previously that thioredoxin (TRX) regulates the DNA binding activities of ER and p53 in vitro. The expression of pS-2, a trefoil factor, is also correlated with that of ER. To clarify the regulation mechanism of tumor growth in breast cancer, here we investigated the expression of TRX, ER, pS-2, and p53 and the mitotic index (MI) in 147 breast cancer tissues using immunohistochemical analysis. Of 123 TRX+ cases, ER+ cases (n = 62) showed a higher pS-2 score and lower MI than did ER- cases (n = 61). Furthermore, p53- cases (no mutation in p53; n = 76) also showed a lower MI than did p53+ cases (n = 47). There was no significant correlation between pS-2 and ER, MI and ER, or p53 and MI in the TRX- group. Among the ER+ and p53- cases (ER+/p53- group; n = 61), MI was lower in the TRX+ group (n = 46) than in the TRX- group (n = 15). However, in all other groups (n = 86) with abnormalities in the immunohistochemical expression of either p53 or ER, there was no significant correlation between MI and TRX expression. In the TRX+ and ER +/p53- group (n = 46), histological grading was lower than that in all other groups (n = 101). These findings suggest that TRX expression is linked to the ER- and p53-dependent regulation of tumor growth in breast cancer. In addition, TRX expression in ER+ and p53 intact (wild-type p53+) groups may mean better prognosis than in other conditions.
Assuntos
Neoplasias da Mama/patologia , Receptores de Estrogênio/fisiologia , Tiorredoxinas/biossíntese , Proteína Supressora de Tumor p53/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Divisão Celular , Análise Mutacional de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Eletroforese/métodos , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Índice Mitótico , Mutação , Proteínas/análise , Estatística como Assunto , Fator Trefoil-1 , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de TumorRESUMO
BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.
Assuntos
Proteína BRCA1/biossíntese , Neoplasias da Mama/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos , Proteína BRCA1/imunologia , Proteína BRCA1/metabolismo , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Immunoblotting , Imuno-Histoquímica , Japão , Neoplasias Mamárias Experimentais/metabolismo , Testes de Precipitina , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Nus , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Fixação de Tecidos , Proteína Supressora de Tumor p53/metabolismoRESUMO
ADF (adult T-cell leukemia-derived factor), an inducer of IL-2R with growth promoting activity, is a homologue of thioredoxin which is involved in many thiol-dependent reducing reactions. ADF is constitutively produced and released by human lymphoid cell lines transformed by lymphocyte-tropic viruses, such as human T-lymphotropic virus type I (HTLV-I) and Epstein-Barr virus (EBV). We found that the viability and growth of these ADF high-producer cell lines (ATL-2, HUT102, MT-2, 3B6 and RPM18866) were highly dependent on L-cystine in the culture. In contrast to the relative cystine independency of ADF low-producer cells (Jurkat, Jijoye, U937 and K562), the growth of ADF high-producer cells was almost completely suppressed in L-cystine-free condition. Their viability and growth in L-cystine-free medium were markedly improved by 5 x 10(-5) M L-cysteine, 5 x 10(-5) M 2-ME or 10(-3) M GSH and partially by 10(-3) M DTT. The results demonstrate the requirement of reducing condition involving thiol compounds for the optimal growth of the virally transformed lymphoid cells. Furthermore, recombinant ADF (rADF) and suboptimal dose of 2-ME additively enhanced the growth of ATL-2 cells in L-cystine-free medium, implying the possible involvement of endogenous reducing agents such as ADF/thioredoxin homologue in the process of lymphocyte transformation/activation.