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INTRODUCTION: Depressive disorders affect nearly 350 million people worldwide and are the world's leading cause of incapacity. Patients who are depressed preferentially approach their general practitioner (GP), who is their first point of contact, in 50-60% of cases. The aim of our study is to assess whether the orientation of patients suffering from anxiety-depressive disorder towards a GP in a general emergency is a factor associated with hospitalization when compared to patients who present themselves spontaneously for the same disorders. Our secondary objective was to identify the different profiles of patients who were hospitalized for these disorders as an emergency. MATERIALS AND METHODS: We conducted a cross-sectional study for the year 2015, targeting patients who presented as general emergencies at the centre hospitalier de Troyes and who had received a psychiatric diagnosis in the context of an anxiety or depressive disorder. RESULTS: Five hundred and twenty four patients were included. A univariate analysis showed that referral by the attending physician was associated with hospitalization in 57.9% vs. 42.1% cases (P=0.007), at an odds ratio at 1.98 [1.22-3.21] by multivariate analysis. Analysis by ascending hierarchical classification made it possible to identify 3 profiles for hospitalized patients: 1) patients with a known psychiatric history, a history of past or current follow-ups directed by a psychiatrist, with at least one psychotropic treatment, the presence of psychotic symptoms and a low suicidal risk compared to the rest of the study population; 2) patients without a psychiatric history, or a history of past or ongoing psychiatric follow-up and the absence of ongoing psychotropic treatment. These patients were referred by a GP (67% vs 23%, P<0.001) and their suicidal risk was higher (59% vs 26%, P<0.001); 3) patients about whom the psychiatrist had little information at the time of the emergency consultation. CONCLUSIONS: The relevance of GPs in orientation towards emergencies pleads in favor of a partnership and an early exchange between treating physicians and the psychiatrists.
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Transtorno Depressivo/terapia , Serviços Médicos de Emergência/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Psiquiatria , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Emergências , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Encaminhamento e Consulta , Risco , Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.
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Autoanticorpos/sangue , Proteínas Cromossômicas não Histona/imunologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Adulto , Linhagem Celular , Etnicidade , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Prevalência , Estudos Retrospectivos , Ribonucleoproteínas Nucleolares Pequenas/imunologia , Análise de SobrevidaRESUMO
We demonstrate the first piezo-generator integrating a vertical array of GaN nanowires (NWs). We perform a systematic multi-scale analysis, going from single wire properties to macroscopic device fabrication and characterization, which allows us to establish for GaN NWs the relationship between the material properties and the piezo-generation, and to propose an efficient piezo-generator design. The piezo-conversion of individual MBE-grown p-doped GaN NWs in a dense array is assessed by atomic force microscopy (AFM) equipped with a Resiscope module yielding an average output voltage of 228 ± 120 mV and a maximum value of 350 mV generated per NW. In the case of p-doped GaN NWs, the piezo-generation is achieved when a positive piezo-potential is created inside the nanostructures, i.e. when the NWs are submitted to compressive deformation. The understanding of the piezo-generation mechanism in our GaN NWs, gained from AFM analyses, is applied to design a piezo-generator operated under compressive strain. The device consists of NW arrays of several square millimeters in size embedded into spin-on glass with a Schottky contact for rectification and collection of piezo-generated carriers. The generator delivers a maximum power density of â¼12.7 mW cm(-3). This value sets the new state of the art for piezo-generators based on GaN NWs and more generally on nitride NWs, and offers promising prospects for the use of GaN NWs as high-efficiency ultra-compact energy harvesters.
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BACKGROUND: The optimal treatment for demyelinating neuropathy associated with MGUS and anti-MAG neuropathy is not known. METHODS: We retrospectively studied the efficacy of IVIg in 14 patients with DN-MGUS (seven IgM and seven IgG/A) and seven with anti-MAG neuropathies, treated in our reference center between 2002 and 2007. Patients were clinically evaluated before the first infusion, after the first infusion, and after the last IVIg treatment. RESULTS: Anti-MAG neuropathy: after a single infusion, one patient improved and six were stable. At last follow-up (mean: 15.6months [range: 3.5-31], mean number of IVIg courses: 8 [2-33]), one patient maintained her improvement from baseline. DN-MGUS: after a single infusion, nine patients improved (64%), four were stable and one deteriorated further. The factor predictive of short-term response to IVIg was relapsing neuropathy responding better in the walking score analysis (Fisher exact test: P=0.005). At last follow-up (mean: 22.6months [range 2-72], mean number of IVIg courses: seven [1-24]), neurological status improved in four patients, five patients remained stable, including three who are still under regular IVIg, and four had deteriorated. Improvement from baseline persisted for a prolonged period in two patients after IVIg were stopped. Patients who were responders on Norris after the first IVIg course were significantly better responders at long-term follow-up than the others (P=0.001). We report no serious adverse effect. CONCLUSION: IVIg are not very efficient in the management of anti-MAG neuropathies. Nevertheless, they have a frequent short-term beneficial effect in DN-MGUS, which was maintained at long-term follow-up in one-third of our patients. When a DN-MGUS patient is regularly treated by IVIg courses, frequent periodic clinical evaluations must be performed to determine when to stop treatment and switch to another one.
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Doenças Desmielinizantes/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Desmielinizantes/complicações , Feminino , Seguimentos , Hospitais , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/complicações , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Onconeuronal antibodies directed against intracellular antigens are strongly associated with paraneoplastic syndromes and their detection in the absence of cancer is unusual. We herein report a case of anti-Ma2 encephalitis associated with Sjogren's syndrome (SS). CASE REPORT: An 81-year-old woman followed for a cutaneous lupus with vasculitis associated with SS presented a flare of her disease with neurological worsening including walking difficulty, hypersialorrhea and dysphagia. A paraneoplastic origin of the symptoms was suspected and anti-Ma2 antibodies were positive in serum. The search for an underlying neoplasia was negative. The diagnosis of anti-Ma2 encephalitis secondary to a SS was made. In the literature, the association of anti-Ma2 encephalitis and SS has been previously reported twice. Cases of patients with other onconeuronal antibodies associated with SS have been also reported. Anti-Ma2 encephalitis is a rare condition with a wide spectrum of symptoms associated with a cancer in more than 90% of the cases. Anti-Ma2 encephalitis has also been described after the use of immune check points inhibitors underscoring the role of autoimmunity in its pathogenesis. CONCLUSION: Anti-Ma2 encephalitis is essentially associated with neoplasia but can occur in Sjogren's syndrome.
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Encefalite , Neoplasias , Síndromes Paraneoplásicas , Síndrome de Sjogren , Idoso de 80 Anos ou mais , Autoanticorpos , Encefalite/diagnóstico , Encefalite/etiologia , Feminino , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnósticoRESUMO
Lymphoproliferative syndromes (multiple myeloma, Waldenström's disease, chronic lymphocytic leukemia, lymphomas) may be associated with peripheral neuropathies. The mechanism can be dysimmune, associated or not with monoclonal gammopathies; paraneoplastic; infiltrative; or more commonly, iatrogenic or due to vitamin deficiency. The diagnosis can be complex, especially when the neuropathy is the presenting manifestation, requiring a close cooperation between internists and neurologists. The positive diagnosis of the neuropathy is based on a systematic electro-clinical investigation, which specifies the topography and the mechanism of the nerve damage, sometimes reinforced by imaging examinations, in particular, nerve and/or plexus MRI. The imputability of the neuropathy to a lymphoproliferative syndrome is based on a set of arguments including the clinical context (B signs, tumour syndrome), first-line laboratory tests (hemogram, protein electrophoresis, viral serologies, complement), auto-antibodies discussed according to the neuropathy (anti-MAG, anti-gangliosides) and sometimes more invasive examinations (bone marrow or neuro-muscular biopsies).
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Paraproteinemias , Doenças do Sistema Nervoso Periférico , Autoanticorpos , Humanos , Glicoproteína Associada a Mielina , SíndromeRESUMO
BACKGROUND: Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. AIM: To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. METHODS: 186 treatment-naïve chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score. RESULTS: NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. CONCLUSION: NOSAs were associated with the most severe forms of chronic HCV infections.
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Autoanticorpos/imunologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Feminino , Humanos , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , gama-Globulinas/análise , gama-Glutamiltransferase/sangueRESUMO
Heat shock induces in cells the synthesis of specific proteins called heat shock proteins (HSPs) and a transient state of thermotolerance. The putative role of one of the HSPs, HSP27, as a protective molecule during thermal stress has been directly assessed by measuring the resistance to hyperthermia of Chinese hamster and mouse cells transfected with the human HSP27 gene contained in plasmid pHS2711. One- and two-dimensional gel electrophoresis of [3H]leucine- and [32P]orthophosphate-labeled proteins, coupled with immunological analysis using Ha27Ab and Hu27Ab, two rabbit antisera that specifically recognize the hamster and the human HSP27 protein respectively, were used to monitor expression and inducibility of the transfected and endogenous proteins. The human HSP27 gene cloned in pHS2711 is constitutively expressed in rodent cells, resulting in accumulation of the human HSP27 and all phosphorylated derivatives. No modification of the basal or heat-induced expression of endogenous HSPs is detected. The presence of additional HSP27 protein provides immediate protection against heat shock administered 48 h after transfection and confers a permanent thermoresistant phenotype to stable transfectant Chinese hamster and mouse cell lines. Mild heat treatment of the transfected cells results in an induction of the full complement of the endogenous heat shock proteins and a small increase in thermoresistance, but the level attained did not surpass that of heat-induced thermotolerant control cells. These results indicate that elevated levels of HSP27 is sufficient to give protection from thermal killing. It is concluded that HSP27 plays a major role in the increased thermal resistance acquired by cells after exposure to HSP inducers.
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Proteínas de Choque Térmico/fisiologia , Animais , Western Blotting , Sobrevivência Celular , Células Cultivadas , Cricetinae , Eletroforese em Gel Bidimensional , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Temperatura Alta , Humanos , Camundongos , Peso Molecular , Fosfoproteínas/fisiologia , TransfecçãoRESUMO
Serums from tumor-bearing patients, cured patients, and normal subjects were examined for antibodies to the separated complement-fixing reactive components of nonvirion antigens of herpesvirus type 1 and type 2. The occurrence of antibodies to the antigens was similar in serums from tumor-bearing patients and cured patients. Antibodies to the antigens were observed among 21 of 24 (87 percent) cervical cancer cases, 44 of 49 (90 percent) laryngeal cancer cases, 15 of 24 (62 percent) cases of squamous cell carcinomas of the head and neck excluding the larynx, 2 of 24 (8 percent) nonsquamous cell cancer cases, and 3 of 51 (6 percent) normal subjects. By contrast, no differences were found in the titers of neutralizing antibodies to the virus in serums from laryngeal cancer patients and controls. The observations support an etiologic role of herpesviruses in cervical cancer and in laryngeal cancer, and possibly other squamous cell cancers of the head and neck.
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Anticorpos Antivirais/análise , Carcinoma de Células Escamosas/imunologia , Herpesviridae/imunologia , Neoplasias Laríngeas/imunologia , Neoplasias do Colo do Útero/imunologia , Fatores Etários , Antígenos Virais , Testes de Fixação de Complemento , Feminino , Cabeça , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes de NeutralizaçãoRESUMO
In rats, naturally occurring variations in maternal care contribute to the development of individual differences in the behavioral and neuroendocrine responses to stress during adulthood. The dopamine (DA) projection to the medial prefrontal cortex (mPFC) plays an important role in mediating stress responsivity and is thought to be involved also in regulating sensorimotor gating. In the present study, we compared prepulse inhibition (PPI) of acoustic startle as well as the left and right mPFC DA stress responses in the adult offspring of high- and low-licking/grooming (LG) dams. Our data indicate that the offspring of low-LG animals are impaired on measures of PPI compared with high-LG animals. We also observed in low-LG animals a significant blunting of the mPFC DA stress responses that was lateralized to the right hemisphere, whereas in high-LG animals, the left and right mPFC DA stress responses were equally attenuated. Although mPFC levels of DA transporter did not differ between the two groups of animals, mPFC levels of catechol-O-methyl transferase immunoreactivity of low-LG animals were significantly lower than those of high-LG animals. These data provide evidence that variations in maternal care can lead to lasting changes in mPFC DA responsivity to stress and suggest the possibility that such changes in mesocorticolimbic DA function can also lead to deficits in sensorimotor gating.
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Estimulação Acústica , Percepção Auditiva/fisiologia , Dopamina/fisiologia , Habituação Psicofisiológica/fisiologia , Comportamento Materno , Córtex Pré-Frontal/fisiopatologia , Reflexo de Sobressalto/fisiologia , Estresse Fisiológico/fisiopatologia , Animais , Catecol O-Metiltransferase/análise , Suscetibilidade a Doenças , Dopamina/análise , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Asseio Animal , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Long-EvansRESUMO
The HL-A antigens were determined retrospectively in a group of 14 surgically cured bronchogenic carcinoma patients and prospectively in another group of 100 untreated patients. In the retrospective group, the frequencies of antigens W-19 and HL-A5 were significantly increased when compared with the noncancer control and the prospective lung cancer populations. In the latter group, 60% of the patients with W-19 and 58% with HL-A5 survived without evidence of tumor for at least 1 year after treatment compared with 15% of patients with neither of these antigens, P less than 0.01 and 0.005, respectively. These comparisons were for adenocarcinoma and squamous carcinoma. The patient groups for oat cell and undifferentiated carcinoma were too small for valid statistical comparisons. This preliminary study suggests that the presence of HL-A antigens W-19 and HL-A5 confers resistance to dissemination of bronchogenic carcinoma.
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Adenocarcinoma/imunologia , Carcinoma Broncogênico/imunologia , Carcinoma de Células Escamosas/imunologia , Antígenos HLA/análise , Antígenos de Histocompatibilidade/análise , Adenocarcinoma/cirurgia , Carcinoma Broncogênico/cirurgia , Carcinoma de Células Escamosas/cirurgia , Humanos , Pneumonectomia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Hyperthermia-induced cell inactivation, thermotolerance development, and heat shock protein synthesis were characterized in a Chinese hamster cell line and its two derivatives, respectively, deficient in glycolysis and respiration. No difference was found in the intrinsic thermosensitivity of the cells or in their ability to respond to heat by developing thermotolerance and synthesizing the heat shock proteins. The results indicate that the direct thermal inactivation of either respiration or glycolysis is not an obligatory rate-limiting event in hyperthermic cell killing and that thermotolerance and heat shock proteins are not triggered exclusively as a consequence of damages induced directly by heat in energy metabolism nor do they result specifically in an increased thermostability of respiration or glycolysis. It is concluded that if energy metabolism is involved somehow in the induction by heat of cell death, thermotolerance, and heat shock protein synthesis, it is due to a heat-induced alteration that indirectly causes changes in the cellular energy status rather than to a direct interaction of heat with energy production.
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Glicólise , Proteínas de Choque Térmico/biossíntese , Temperatura Alta , Consumo de Oxigênio , Animais , Linhagem Celular , Sobrevivência Celular , Cricetinae , Cricetulus , Feminino , MutaçãoRESUMO
Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients with central nervous system tumors show similar changes, levels of acute-phase proteins (alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, C-reactive protein) and immunoglobulins (immunoglobulins G, M, and A) were assayed in patients with gliomas prior to treatment. Compared to normals, significant increases (p less than 0.001) in the acute-phase proteins were found, and the levels were similar to those in patients with nonneural solid neoplasms. Serum immunoglobulins were not significantly increased in patients with gliomas.
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alfa-Globulinas/análise , Astrocitoma/imunologia , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Imunoglobulinas/análise , Astrocitoma/sangue , Neoplasias Encefálicas/sangue , Feminino , Glioblastoma/sangue , Humanos , Imunidade Celular , Masculino , Proteínas de Neoplasias/análiseRESUMO
Normal and transformed chick embryo cells and their respective ethidium bromide-treated derivatives that are devoid of a functional respiratory chain were comparatively evaluated for their responses to hyperthermia treatment. No significant difference was found between the control and the respiration-deficient cells. The cells have a similar intrinsic thermosensitivity as judged by their capacity to form colonies after treatment at supraoptimal temperatures, and heat triggers in both cases an equal production of heat shock proteins and a strong induction of thermotolerance. In addition, sodium arsenite, carbonyl cyanide m-chlorophenylhydrazone, oligomycin, and antimycin A induce a similar heat shock protein response in the control and the treated cells. Based on these results, it is concluded that the inhibition by heat of the mitochondrial energy production does not constitute an obligatory rate-limiting event in hyperthermic cell killing and that the intracellular signal triggering development of thermotolerance or heat shock protein production does not obligatorily originate from damages to the respiratory chain. Moreover, the results indicate that the modifications responsible for the increased heat resistance of thermotolerant cells may not, or do not necessarily, involve a stabilization of the mitochondrial energy production.
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Proteínas de Choque Térmico/biossíntese , Temperatura Alta , Consumo de Oxigênio , Animais , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Sobrevivência Celular , Embrião de Galinha , Fibroblastos/metabolismo , Glicólise , Oligomicinas/farmacologiaRESUMO
A family of 10 thermoresistant cell lines cloned from Chinese hamster cells transfected with a plasmid containing the structural gene for the small human Mr 27,000 heat shock protein (HSP27) was used to assess the putative role of this heat shock protein in chemoresistance. These cells express varying amounts of human HSP27 in addition to the normal level of endogenous hamster HSP27. As previously observed in the case of thermoresistance, a significant positive linear correlation (P less than 0.05) was found between cell survival in response to doxorubicin and the total amount of HSP27 expressed. Some clones were also examined for resistance to other drugs and chemicals. A statistically significant increased survival relative to the parental cells was observed following treatment with daunorubicin (three clones studied), colchicine, vincristine, actinomycin D, hydrogen peroxide, and sodium arsenite (one clone studied). However, the clone which expressed the highest level of HSP27 was as sensitive as control cells to the cytotoxic action of bis-chloronitrosourea and 5-fluorouracil. The relationship between HSP27 overexpression and increased resistance to cytotoxic agents was also evaluated in three independent pooled cell populations stably transformed with both the human HSP27 and the xanthine-guanine phosphoribosyltransferase gene and selected on the basis of resistance to mycophenolic acid and aminopterin. The results indicated that these cells survived significantly better than the control cells transfected with the marker gene only when exposed to doxorubicin. HSP27-mediated cellular protection was not associated either with decreased drug accumulation or with overexpression of P-glycoprotein. It is suggested that HSP27 might be involved in some form of chemoresistance and could participate in the development of clinical resistance to antineoplastic drugs.
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Antineoplásicos , Arsenitos , Resistência a Medicamentos/fisiologia , Proteínas de Choque Térmico/fisiologia , Compostos de Sódio , Animais , Arsênio/farmacologia , Western Blotting , Carmustina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Colchicina/farmacologia , Cricetinae/genética , Dactinomicina , Daunorrubicina/farmacocinética , Relação Dose-Resposta a Droga , Doxorrubicina , Etoposídeo/farmacologia , Fluoruracila/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Pentosiltransferases/fisiologia , Teniposídeo/farmacologia , Vincristina/farmacologiaRESUMO
Morris hepatoma 7777 cells, heat conditioned at 43 degrees for 0.5 hr, become gradually thermoresistant during an incubation at 37 degrees as judged by their ability to form colonies following a second heat challenge. Pulse incorporation of [35S]methionine into proteins at various times after the conditioning treatment and subsequent fractionation of the proteins by polyacrylamide gel electrophoresis indicate that the gradual putative modifications occurring at the cellular level and leading to the thermotolerance state are accompanied by an elevated synthesis above the normal level of a small set of polypeptides with apparent molecular weights of 27,000, 65,000, 68,000, 70,000, 89,000, and 107,000. Both thermotolerance development and protein induction are completed after a 6- to 8-hr period. At the end of this period, thermotolerance is at its maximum level and heat shock protein synthesis is returned to normal. This acquired thermal resistance eventually disappears between 60 and 80 hr following conditioning treatment. In a parallel manner, the heat shock-induced proteins synthesized during the first 4 hr following the conditioning treatment are maintained in the cells at a high level for several hr but become undetectable by 82 hr. The results provide strong circumstantial evidence that heat shock proteins are involved in the acquisition, maintenance, and decay of thermotolerance.
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Neoplasias Hepáticas Experimentais/metabolismo , Proteínas/metabolismo , Animais , Eletroforese em Gel de Poliacrilamida , Proteínas de Choque Térmico , Temperatura Alta , Cinética , Biossíntese de Proteínas , RatosRESUMO
In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected in pleural effusions, contrasting with low levels of IL-1 beta and tumor necrosis factor alpha. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human gamma-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and soluble CD8 concentrations. In vitro gamma-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, cachexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local gamma-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.
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Interferon gama/administração & dosagem , Interleucina-6/biossíntese , Mesotelioma/metabolismo , Derrame Pleural/metabolismo , Neoplasias Pleurais/metabolismo , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Antígenos CD8/metabolismo , Humanos , Interleucina-1/metabolismo , Mesotelioma/terapia , Neopterina , Derrame Pleural/terapia , Neoplasias Pleurais/terapia , Proteínas Recombinantes , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cross-reacting tumor-associated antigens have been demonstrated to be present in the cytoplasm of melanocytes in malignant melanoma. We have utilized both the leukocyte migration inhibition and the lymphocyte stimulation assays to determine the intracellular location(s) of these antigens in both human malignant melanoma and B-16 murine melanoma. The results of both assays indicate that this antigen(s) is associated with the membranous organelles, particularly the melanin granules, and is not found in the soluble components of the cytoplasm, as suggested by other studies.
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Antígenos de Neoplasias/análise , Melanoma/imunologia , Animais , Inibição de Migração Celular , Humanos , Ativação Linfocitária , Camundongos , Neoplasias Experimentais/imunologia , Organoides/imunologiaRESUMO
An additional 244 unfiltered sera have now been studied in a series of controlled, coded tests to determine the relationship of squamous carcinomas of the head and neck and cervix to the presence of complement-fixing antibodies to herpesvirus-tumor-associated antigens (HSV-TAA) in both tumor-bearing and cured patients. Ninety % of sera from patients with squamous carcinomas had antibodies to HSV-TAA, in contrast to 11% of sera from patients with nonsquamous cancers and 4% of sera from noraml individuals. The temporal relationship of Stage 1 laryngeal carcinomas suggests that HSV-TAA appearance precedes the immune defects. An in vitro correlate of the previously demonstrated specific delayed hypersensitivity reactions in controlled skin tests of squamous carcinoma patients with HSV-TAA is reported. In leukocyte migration inhibition tests, the migration indices after incubation with HSV-TAA of peripheral blood leukocytes from patients with squamous carcinoma (x = 0.847) were in definite contrast to migration indices seen for normal leukocytes (x = 1.037) and patients with nonsquamous solid cancers (x = 1.03). Thus, these polypeptides elicit both humoral antibody response and cell-mediated reactivity.