RESUMO
BACKGROUND: New agents that are active in patients with metastatic colorectal cancer are needed. Patupilone (EPO906; epothilone B) is a novel microtubule-stabilising agent. METHODS: Patients with advanced colon cancer who progressed after prior treatment regimens received intravenous patupilone (6.5-10.0 mg m(-2)) once every 3 weeks by a 20-min infusion (20MI), 24-h continuous infusion (CI-1D) or 5-day intermittent 16-h infusion (16HI-5D). Adverse events (AEs), dose-limiting toxicities (DLTs), pharmacokinetics and anti-tumour activity were assessed. RESULTS: Sixty patients were enrolled. The maximum tolerated dose (MTD) was not reached in the 20MI arm (n=31), as no DLTs were observed. Three patients in the CI-1D arm (n=26) experienced 1 DLT each at 7.5, 8.0 and 9.0 mg m(-2), but MTD was not reached. However, the prolonged 16HI-5D arm was terminated at 6.5 mg m(-2) after two of the three patients developed a DLT. Diarrhoea was the most common AE and DLT, with increased severity at the higher doses (9.0 and 10.0 mg m(-2)). Grade 3 or 4 diarrhoea was observed in 11 (35%) of the patients in the 20MI arm, 4 (15%) of the patients in the CI-1D arm and 2 (67%) of the patients in the 16HI-5D arm. Patupilone activity was observed in the 20MI arm with a disease control rate of 58%, including four confirmed partial responses. The disease control rate in CI-1D arm was 39%. CONCLUSION: Patupilone given once every 3 weeks as a 20-min infusion had promising anti-tumour activity and manageable safety profile at doses that demonstrated therapeutic efficacy.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Epotilonas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Epotilonas/efeitos adversos , Epotilonas/farmacocinética , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do TratamentoRESUMO
BACKGROUND: This randomized phase II study was conducted to evaluate the efficacy of doxorubicin and docetaxel (DOC) administered either as a combination, an alternating or a sequential regimen in women with metastatic breast cancer. Secondary objectives included overall response, time to progression, survival and safety. PATIENTS AND METHODS: Patients with breast cancer (n=123) were randomized to receive doxorubicin and DOC either in combination (60 mg/m2 of each drug), or by alternated or sequential schedule (100 mg/m2 DOC and 75 mg/m2 doxorubicin) every 3 weeks for a maximum of eight cycles as first chemotherapy for stage IV disease. A second randomization allocated patients from each arm to receive prophylactic oral ciprofloxacin or no therapy to prevent febrile neutropenia. RESULTS: Patients received a median of eight cycles. In an intention-to-treat analysis, the overall response was 63%, 52% and 61% in the combination, alternating and sequential schedules, respectively. Corresponding rates of complete response were 15%, 14% and 11%. Grade 4 neutropenia was common in all arms (81%) and, together with febrile neutropenia, was significantly more frequent with the combination. Prophylaxis with ciprofloxacin did not reduce the incidence of febrile neutropenia or infection. Other frequent non-hematological adverse events included alopecia, nausea, vomiting, stomatitis and asthenia. Congestive heart failure only occurred in the combination arm (10%). CONCLUSION: All three schedules are feasible and endowed of good therapeutic activity. In view of the more pronounced toxicity and the risk of cardiac events because of the higher exposure to doxorubicin, the combination should be least favored when treating women with metastatic breast cancer. Prophylaxis with ciprofloxacin was ineffective and is not recommended.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/secundário , Progressão da Doença , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida , Taxoides/administração & dosagem , Fatores de TempoRESUMO
PURPOSE: To determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of docetaxel in combination with fixed doses of epirubicin. PATIENTS AND METHODS: Women with locally advanced or metastatic breast cancer were given docetaxel, 60 mg/m2 in escalated doses by steps of 10 mg/m2, in association with two fixed doses of epirubicin (90 mg/m2, and 75 mg/m2). Since neutropenia was foreseen to be the most likely DLT, a third group with prophylactic G-CSF support was planned to define the MTD of docetaxel with 90 mg/m2 of epirubicin. Selected patients underwent pharmacokinetic evaluation of docetaxel. RESULTS: Fifty-eight patients entered the study. At the first step (90 mg/m2 of epirubicin) the MTD was obtained at 60 mg/m2 of docetaxel. At the second step (75 mg/m2 of epirubicin) the MTD of docetaxel was 80 mg/m2. At the third step (epirubicin 90 mg/m2) G-CSF allowed a safe escalation of docetaxel up to 90 mg/m2. Neutropenia was the most common hematological adverse event. Without G-CSF, grade 4 neutropenia occurred in 69% of cycles, of which 11% was complicated by fever. In G-CSF group, grade 4 neutropenia and neutropenic fever occurred in 31% and 3%, respectively. Most frequent non-hematological adverse effects were asthenia (45%), nausea (39%) and mucositis (36%). No patient developed congestive heart failure. Two toxic deaths occurred. Overall response rate was 73% in 42 out of 58 patients, with no apparent epirubicin dose-related effect. No statistically significant effect of the two doses of epirubicin was observed in docetaxel pharmacokinetics. CONCLUSIONS: On the basis of the toxicity profile, the docetaxel pharmacokinetics and the response rate observed, epirubicin 75 mg/m2 combined with docetaxel 80 mg/m2 can be recommended for further studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Docetaxel , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversosRESUMO
BACKGROUND: Docetaxel is one of the most promising new drugs against squamous-cell carcinoma of the head and neck (SCCHN), while cisplatin is one of the most active single agents. A phase I study has shown the feasibility of the combination of the two drugs, and activity in SCCHN has been seen. PATIENTS AND METHODS: Patients with locally advanced, inoperable, or metastatic SCCHN, never pretreated with radiotherapy or chemotherapy, received three courses of docetaxel 75 mg/m2 and cisplatin 100 mg/m2, every three weeks. Thereafter, responsive metastatic patients received additional chemotherapy, while patients with locally advanced disease underwent radiation therapy. RESULTS: Forty-six patients (forty-five with locally advanced, one with metastatic disease) were entered into the study. Ten patients did not complete three courses of chemotherapy because of early death; one patient discontinued treatment after one course. Twenty-one objective responses were observed (46%, 95% confidence interval (CI): 31%-60%), including five complete responses (11%) and sixteen partial responses (35%). Following induction chemotherapy plus radiation therapy, 9 of 21 evaluable patients were rendered disease free, while 8 additional patients had a partial response. After a median follow-up of 18 months, the median duration of response was 12 months, (range 3-25+), and the median overall survival was 11 months. Six early deaths were considered possibly treatment-related (sepsis following grade 4 neutropenia in two cases, hypovolemic shock following severe diarrhea in four cases). Neutropenia was the most severe toxicity (grade 3-4 in 28 patients, median duration 4 days); diarrhea and vomiting were the most troublesome non-haematologic toxicities (grade 4 in 4 and 3 patients, respectively). CONCLUSIONS: The combination of docetaxel and cisplatin is active in SCCHN, but toxicity is substantial. This schedule does not appear to offer any advantage compared with conventional regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Taxoides , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivados , Prognóstico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The administration of granulocyte-monocyte colony stimulating factor (GM-CSF) should allow an increase in the doses of chemotherapy for patients with advanced cancers of the head and neck. PATIENTS AND METHODS: Eleven patients with histologically proven relapsed squamous cell carcinoma of the head and neck entered this Phase I study based on the combination of cisplatin (20 mg/m2/day for 5 days), escalating doses of 5-fluorouracil, both given by intravenous injection from day 1 to 5, and GM-CSF, 5 micrograms/kg from day 8 to day 19. RESULTS: The maximum tolerated 5-fluorouracil dosage was 300 mg/m2 i.v. bolus for 5 consecutive days q. 3 weeks. Thrombocytopenia was the limiting factor to further increase of 5-fluorouracil dosage. Moderate to severe stomatitis were quite rare despite the increased dose of the antimetabolite. GM-CSF was well tolerated: no significant local or systemic side effects attributable to this drug were recorded. CONCLUSIONS: Adding GM-CSF to the combination of cisplatin and 5-fluorouracil allowed to increase 5-fluorouracil dose up to 50% over the conventional dosage. Further increase of the dose was precluded by the development of severe thrombocytopenia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Idoso , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
The results of a randomized, multicenter clinical trial of immunoprophylaxis of post-operative infections with intravenous Immunoglobulins (IVIG) (Sandoglobulin) in "septic-risk" patients undergoing surgery for gastrointestinal cancer are presented. "Septic-risk" patients were selected by an original multiparametric test based on delayed hypersensitivity skin testing and serum protein electrophoretic sub-fractions. This screening test had shown 76% positive predictivity in a previous validation assessment. In the present study, 159 "septic-risk" patients were selected prospectively from 369 patients undergoing colo-rectal (colon) and other kinds of gastrointestinal (non-colon) oncologic surgery: 80 "septic-risk" patients were included in the colon and 79 in the non-colon group. Immunoprophylaxis with IVIG (15 g on the day prior to operation, on the 1st and 5th postoperative days) was randomly associated with antibiotic prophylaxis (cefoxitin: 2 g one hour prior to, followed by 2 g at the end of operation plus 2 g every six hours for 24 hours) in colon surgery while the prophylactic schedule in non-colon surgery was only based on random administration of IVIG, at the same dosage as in the colon group. There was a clear-cut reduction of post-operative infections both in colon and non-colon "septic-risk" patients who had IVIG prophylaxis; in the colon group, 37 and 21 infections (P < 0.004) in antibiotic (A) versus IVIG plus antibiotic (IVIG + A) subset, respectively; in the non-colon group, 33 and 19 infections (P < 0.01) in control (C) versus (IVIG) subset, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções Bacterianas/prevenção & controle , Neoplasias Gastrointestinais/cirurgia , Imunoglobulinas Intravenosas/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Infecções Bacterianas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pré-Medicação , Fatores de Risco , Testes Cutâneos , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
BACKGROUND: The results of a randomized, multicenter clinical trial with perioperative short-term antibiotic plus intravenous immunoglobulins (IVIG + A) versus antibiotic alone (A) for prevention of postoperative infections in patients at risk for sepsis undergoing surgery for colorectal cancer are presented. METHODS: The patients at risk for sepsis were selected by an original multiparametric test based on delayed-hypersensitivity skin testing and serum protein electrophoretic subfractions. This screening had shown 76% positive predictability in a previous validation assessment. Eighty patients at risk for sepsis were selected prospectively from 210 patients undergoing surgery for colorectal cancer; 43 patients were randomly assigned to the IVIG + A group and 37 to the A group. IVIG was administered on the day before operation, on the first and fifth postoperative days. RESULTS: There was a clear-cut reduction of postoperative infections in the IVIG + A group: 21 infections in 20 patients versus 37 infections in 29 patients in the A group (p less than 0.004). With regard to serum immunoglobulin (Ig) G monitoring, basal IgG levels were significantly lower in patients given IVIG + A who had postsurgical infections (p less than 0.005) compared with patients with a regular outcome, whereas the same was not true in the A group of patients. CONCLUSIONS: A significant decrease (p less than 0.001) of postoperative IgG was evidenced in the A group of patients who had infections as opposed to a significant increase (p less than 0.001) of postoperative IgG in IVIG + A patients with a normal outcome.
Assuntos
Antibacterianos/uso terapêutico , Neoplasias do Colo/cirurgia , Imunização Passiva , Imunoglobulina G/sangue , Neoplasias Retais/cirurgia , Sepse/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Análise de Variância , Feminino , Humanos , Imunização Passiva/efeitos adversos , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Masculino , Fatores de Risco , Sepse/etiologia , Caracteres SexuaisRESUMO
Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study. The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score. A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls. The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.
Assuntos
Infecções Bacterianas/mortalidade , Imunoglobulina G/uso terapêutico , Procedimentos Cirúrgicos Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Causas de Morte , Cuidados Críticos , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/análise , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , Orosomucoide/análise , Placebos , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
We studied a group of healthy elderly subjects (satisfying the SENIEUR Protocol admission criteria), chosen as a model of age-associated immune deficiency on the basis of their reduced skin reactivity to recall antigens. Results show that aged subjects, taken as a whole, display impaired T-cell functions: reduced blastogenetic responses to mitogens, IL-2 production, responsiveness to exogenous IL-2, and percentage of Tac positive blasts. However, the age-associated immune defect shows a wide range of impairment, even in a relatively homogeneous group of anergic/hypoergic subjects. In fact, a considerable proportion of our elderly subjects displays responses comparable with those of adult controls. These observations suggest that (a) immune deficiency is not a characteristic of aging per se; (b) cutaneous delayed hypersensitivity is not a criterion sensitive enough to identify people with age-associated immune deficit; and (c) more than one test is required to evaluate T-cell impairment in aging.
Assuntos
Envelhecimento , Imunidade , Formação de Anticorpos , Feminino , Humanos , Hipersensibilidade Tardia/imunologia , Tolerância Imunológica , Imunidade Celular , Técnicas In Vitro , Interleucina-2/biossíntese , Interleucina-2/farmacologia , Ativação Linfocitária , Linfócitos/classificação , Masculino , Receptores Imunológicos/metabolismo , Receptores de Interleucina-2RESUMO
The effect of thymopentin treatment on the immune defects in drug addicts with persistent generalized lymphadenopathy and HTLV-III infection was investigated. Thymopentin was administered subcutaneously at two different dose schedules: 50 mg three times a week for 3 weeks (first cycle) and 50 mg/week for 3 months (second cycle). After the first cycle an increased number of OKT4+ lymphocytes and an improvement of PWM-induced blastogenesis and IgG synthesis in vitro was observed. The second cycle was unable to modify the same immune parameters in vitro. The treatment had no effect on the PHA responsiveness and on PHA-induced interleukin 2 production. The significance and the prognostic value of these findings are discussed in terms of the clinical evolution of the syndrome.
Assuntos
Complexo Relacionado com a AIDS/tratamento farmacológico , Dependência de Heroína/complicações , Fragmentos de Peptídeos/uso terapêutico , Timopoietinas/uso terapêutico , Hormônios do Timo/uso terapêutico , Complexo Relacionado com a AIDS/etiologia , Complexo Relacionado com a AIDS/imunologia , Adulto , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Ativação Linfocitária , Masculino , Fragmentos de Peptídeos/administração & dosagem , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologia , Linfócitos T/classificação , Timopentina , Timopoietinas/administração & dosagemRESUMO
The effect of thymopentin (TP-5) treatment on lymphocyte immune functions has been investigated in immunocompromised aged subjects. TP-5 was able to improve the cutaneous delayed hypersensitivity (CDH) to recall antigens and the proliferative response to phytohemagglutinin (PHA), concanavalin A, and Pokeweed (PWM) as well as the PHA-induced interleukin-2 (Il-2) production. On the other hand, no detectable changes were induced by TP-5 treatment either on PWM-induced immunoglobulin synthesis or on lymphocyte subsets identified by monoclonal antibodies. Our results suggest that the enhancement of Il-2 synthesis might be a crucial mechanism of the immunopharmacological action of TP-5 in aging humans.
Assuntos
Adjuvantes Imunológicos/farmacologia , Envelhecimento/imunologia , Síndromes de Imunodeficiência/imunologia , Interleucina-2/biossíntese , Fragmentos de Peptídeos/farmacologia , Timopoietinas/farmacologia , Hormônios do Timo/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/imunologia , Feminino , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/metabolismo , Lectinas/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/classificação , Linfócitos/efeitos dos fármacos , Masculino , Fragmentos de Peptídeos/uso terapêutico , Estimulação Química , Timopentina , Timopoietinas/uso terapêuticoRESUMO
A group of institutionalized elderly subjects, selected on the basis of their skin hypoergy and displaying different kinds of T and B lymphocyte impairments has been chosen as a model to verify the in vivo immunopotentiating activity of RU 41740 on human lymphocytes. Oral treatment with the drug was able to: restore or improve the cutaneous delayed hypersensitivity to recall antigens; significantly increase the blastigenetic response to mitogenic and submitogenic doses of PHA and PWM and improve the in vitro PWM-induced synthesis of IgG and IgM. The immunopharmacological activity of RU 41740 appeared to persist three months after the end of therapy, without any direct stimulating activity on the peripheral blood lymphocytes. The in vitro results seem to suggest that peripheral lymphocytes are not directly influenced by the drug.
Assuntos
Adjuvantes Imunológicos , Proteínas de Bactérias , Glicoproteínas/farmacologia , Linfócitos/efeitos dos fármacos , Administração Oral , Idoso , Feminino , Glicoproteínas/administração & dosagem , Humanos , Hipersensibilidade Tardia , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Técnicas In Vitro , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Mitógenos/farmacologiaRESUMO
Peripheral blood mononuclear cells (PBMC) from patients with Essential Mixed Cryoglobulinemia (EMC) were studied for their ability to synthesize polyclonal IgM and rheumatoid factor (RF) IgM in vitro. Our results indicate: that EMC-PBMC produce smaller amounts of polyclonal IgM but higher quantities of IgM-RF than normal PBMC after pokeweed mitogen (PWM) or Staphylococcus aureus activation, so that the IgM-RF to total IgM ratio is significantly greater in EMC than in normal cultures; that enriched EMC-B lymphocytes display a significantly higher spontaneous synthesis of IgM-RF than normal B lymphocytes and that the IgM-RF B cell clones are receptive to T cell regulation. Taken together these findings suggest an expansion of B cell clones committed to IgM RF production and the presence in peripheral blood of differentiated B lymphocytes capable of secreting IgM-RF in EMC.
Assuntos
Crioglobulinemia/imunologia , Imunoglobulina M/biossíntese , Linfócitos/imunologia , Fator Reumatoide/biossíntese , Adulto , Idoso , Linfócitos B/imunologia , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mitógenos/farmacologia , Linfócitos T/imunologiaRESUMO
The persistent generalized lymphadenopathy (PGL) in drug addicts displays the same immunological abnormalities previously found in homosexual and haemophiliac men with PGL: impaired in vivo and in vitro T cell functions, inverted T4/T8 ratio in blood and B cell abnormalities. The peripheral blood B-lymphocytes, in fact, show a reduced in vitro immunoglobulin synthesis after pokeweed mitogen and Staphylococcus aureus activation, with an increased spontaneous IgG secretion. In the lymph node biopsies, the immuno-histological studies reveal an infiltration of OKT8 positive cells in the germinal centers, a depletion of OKT4 positive lymphocytes slighter than in the blood and an explosive follicular hyperplasia with a striking destruction of the dendritic reticulum cell framework. This latter finding, together with the high levels of serum IgG and the presence of preactivated B cells in the blood, seems to be consistent with the presence of an in vivo polyclonal B cell activation. A high incidence of anti-HTLV III antibodies was also found in the PGL drug addicts. The significance of these findings is discussed in this report.
Assuntos
Doenças Linfáticas/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Anticorpos Monoclonais , Feminino , Histocitoquímica , Humanos , Hipersensibilidade Tardia , Técnicas Imunoenzimáticas , Linfonodos/patologia , Doenças Linfáticas/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Masculino , Transtornos Relacionados ao Uso de Substâncias/imunologiaRESUMO
The T-cell requirement for the B-lymphocyte immunoglobulin synthesis induced by Pokeweed mitogen (PWM) and by Staphylococcus aureus Cowan I (SAC) was investigated. We found that the PWM induced B-cell activation was controlled by an absolute Mitomycin-C resistant T-cell helper activity and by a Mitomycin-C sensible T-cell suppressor activity. On the other hand the SAC induced B-cell activation was less thymus dependent and was not influenced by Mitomycin-C treated or irradiated T cells. The different T-cell requirement could be an expression of different responding B-cell subpopulations.
Assuntos
Formação de Anticorpos , Linfócitos B/imunologia , Linfócitos T/imunologia , Adulto , Células Cultivadas , Humanos , Ativação Linfocitária , Cooperação Linfocítica , Mitógenos de Phytolacca americana , Staphylococcus aureus/imunologiaRESUMO
Sera from 84 patients with progressive systemic sclerosis (PSS) were tested for the presence of antinuclear antibodies by immunofluorescence on HEp2 cells and gel immunodiffusion. Fluorescent antinuclear antibodies were detected in 80 subjects with PSS (95%). Ninety-three percent of patients with CREST syndrome and 3% of those with diffuse scleroderma had a centromere staining. Precipitating antibodies were found in 57% of PSS sera and identified as anti-Scl 70 in 42 cases (50%). This specificity was found in 42 of 70 subjects with diffuse scleroderma (60%); another patient was positive for anti-nRNP antibodies, and 5 more sera from PSS patients showed precipitin lines of unknown specificity. No serum from 14 patients with CREST syndrome was positive for anti-Scl 70 antibodies. Significant relationships have been found between centromere staining and CREST syndrome (p less than 0.0005) and between the presence of anti-Scl 70 antibodies and the diffuse form of scleroderma (p less than 0.0005). The latter specificity is strongly associated with grainy speckled pattern on HEp2 fluorescence (p less than 0.0005). These data suggest that anti-Scl 70 antibodies and anti-centromere antibodies are useful markers for different subgroups of patients with PSS.