RESUMO
Membrane-limited inclusions were found in the cytoplasm of cells of the rectal mucosa, leukocytes, and cultured fibroblasts from two humans with cystinosis. Most of the inclusions contained amorphous material, presumably cystine. In cells of the rectal mucosa the material appeared frequently crystallized. This was rarely seen in leukocytes, and never in cultured fibroblasts. The fact that acid phosphatase could be demonstrated consistently in the organelles responsible for sequestration of cystine indicates that they are lysosomes.
RESUMO
Inoculation of 64-10 or Raji cultures with Epstein-Barr virus derived from the HRI-K clone of the P3J Burkitt's lymphoma line caused abortive infections in most of the lymphoblastoid cells with synthesis of "early antigens" but few, if any, capsids. Antibodies to early antigens were detected by indirect immunofluorescence in serums of many patients with infectious mononucleosis, Burkitt's lymphoma, or nasopharyngeal carcinoma. These antibodies were rarely present in other serums even though some of them showed high titers of antibodies to Epstein-Barr virus when assayed on EB3 Burkitt tumor cells; they also prevented synthesis of early antigens, provided the serums were mixed with the virus prior to inoculation. Antibodies to early antigens possibly reflect current or recent disease processes that are associated with the virus.
Assuntos
Reações Antígeno-Anticorpo , Antígenos , Herpesviridae/imunologia , Soros Imunes , Mononucleose Infecciosa/imunologia , Linfoma de Burkitt/imunologia , Linhagem Celular , Efeito Citopatogênico Viral , Imunofluorescência , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Imunidade Celular , Leucemia Mieloide , Neoplasias Nasofaríngeas/imunologiaRESUMO
Brequinar sodium (BQR), a substituted 4-quinoline carboxylic acid, was in clinical development in combination with cyclosporine (CsA) as a potentially effective therapy for the treatment and prophylaxis of rejection in organ transplant patients. This phase I study was performed in stable renal, hepatic, and cardiac transplant patients receiving CsA and prednisone maintenance therapy for immunosuppression. The pharmacokinetic objectives of this study were to characterize the pharmacokinetics of (a) single oral 0.5- to 4-mg/kg doses of BQR when given in combination with CsA and prednisone to stable renal, hepatic, and cardiac transplant patients and (b) steady-state oral doses of CsA, with and without single oral doses of BQR. In all three patient populations, the pharmacokinetics of BQR were characterized by a lower oral clearance (12-19 mL/min) than that seen in previous studies in patients with cancer (approximately 30 mL/min at similar doses) and a long terminal half life (13-18 hrs). This slower oral clearance for BQR could be due either to a drug interaction between BQR and CsA or to altered clearance or metabolic processes in patients with transplants. Steady-state CsA trough levels and the oral clearance of CsA were not affected by BQR coadministration. Among the three transplant populations, the cardiac transplant patients had lower oral clearance values of BQR and of CsA. The cause of this lower clearance is not known. Safety results indicate that BQR was well tolerated by this patient population.
Assuntos
Compostos de Bifenilo/farmacocinética , Transplante de Coração/fisiologia , Imunossupressores/farmacocinética , Transplante de Rim/fisiologia , Transplante de Fígado/fisiologia , Administração Oral , Adulto , Idoso , Compostos de Bifenilo/sangue , Ciclosporina/sangue , Ciclosporina/farmacocinética , Feminino , Humanos , Imunossupressores/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
The Merck, Sharp and Dohme hepatitis B vaccine formulated from HBsAg produced by a recombinant strain of Saccharomyces cerevisiae has proven to be highly immunogenic and safe. A 10 micrograms dose of the vaccine produced an anti-HBs response of greater than or equal to 10 IU/l in 91% or more of healthy adults who completed the three-dose regimen. Children responded well to all levels of vaccine antigen utilised but developed maximum anti-HBs titres with 5 micrograms doses. The age of the vaccine recipient affected responsiveness. Younger adults (20-29 years) responded more rapidly and with higher anti-HBs titres than did older adults (greater than or equal to 50 years). Children responded faster and with higher anti-HBs levels than younger adults. Clinical reactions reported after vaccination were mild and transient.
Assuntos
Anticorpos Anti-Hepatite B/biossíntese , Vacinas contra Hepatite Viral/imunologia , Adulto , Fatores Etários , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , DNA Recombinante , Antígenos de Superfície da Hepatite B/genética , Vacinas contra Hepatite B , Humanos , Imunoglobulina G/análise , Lactente , Pessoa de Meia-Idade , Proteínas Recombinantes , Saccharomyces cerevisiae/genética , Vacinas contra Hepatite Viral/efeitos adversosAssuntos
Técnicas de Cultura , Interferons/biossíntese , Artrite Reumatoide , Linfoma de Burkitt , Linhagem Celular , Cromatografia em Gel , Células Clonais , Meios de Cultura , Humanos , Interferons/análise , Rim , Leucemia Linfoide , Leucemia Mieloide , Leucemia Mieloide Aguda , Leucócitos , Vírus da Doença de Newcastle/metabolismo , Puromicina/farmacologia , Reoviridae/metabolismo , Fatores de Tempo , Vírus da Estomatite Vesicular Indiana/metabolismoRESUMO
Accumulation of the nucleoprotein of vesicular stomatitis virus (VSV) in the cytoplasm of BHK-21 cells and in two of four human cell lines was demonstrated. Appearance and progression of the nucleoprotein inclusions paralleled development of virus-specific immunofluorescence and production of virus progeny. The inclusions appeared early as discrete foci of filamentous material which eventually increased in size to form large masses which replaced normal cytoplasmic constituents. The filamentous strands were found in close proximity to budding virions. The inclusion material was extracted from infected cells and purified in cesium chloride gradients. The isolated filaments resembled the ribonucleoprotein isolated from purified virions. They incorporated (3)H-uridine, exhibited virus-specific complement-fixing activity, had a buoyant density of 1.32 g/cm(3), and appeared as single wavy strands the width of which varied from 2.5 to 8.5 nm, depending on the angle of viewing.
Assuntos
Técnicas de Cultura , Nucleoproteínas/metabolismo , Vírus da Estomatite Vesicular Indiana/crescimento & desenvolvimento , Proteínas Virais/metabolismo , Âmnio , Animais , Linhagem Celular , Membrana Celular/microbiologia , Centrifugação com Gradiente de Concentração , Césio , Cloretos , Testes de Fixação de Complemento , Cricetinae , Citoplasma/microbiologia , Fibroblastos , Imunofluorescência , Humanos , Soros Imunes , Corpos de Inclusão Viral , Rim , Linfócitos , Masculino , Microscopia Eletrônica , Nucleoproteínas/análise , Pênis , Coelhos , Espectrofotometria , Coloração e Rotulagem , Trítio , Uridina/metabolismo , Vírus da Estomatite Vesicular Indiana/imunologia , Vírus da Estomatite Vesicular Indiana/metabolismo , Vírus da Estomatite Vesicular Indiana/patogenicidade , Proteínas Virais/análise , Replicação ViralRESUMO
These data describe the use of a passive hemagglutination test (PHAT) for the detection of antibodies to the Epstein-Barr virus (EBV) associated antigen, early antigen-D (EA-D). EA-D was obtained from EBV-superinfected RPMI 64-10 cell preparations which showed by immunofluorescent staining (IF) that 25-35% of the cells contained EA-D. Solubilization of EA-D was achieved by sonic oscillation, treatment of the pellet-associated material with triton X 100, ammonium sulfate precipitation, and chromatography on diethylaminoethyl celluiose. Successful use of the PHAT for detection of antibodies to EA-D was dependent on the degree of purity of the partially purified antigen. Throughout these studies preparations from uninfected 64-10 cells were used as control reagents. More than 100 human antisera from patients with EBV-associated diseases, which had been previously tested by standard IF procedures were assayed by PHAT. A good correlation was found between IF and PHAT titers for EA-D and, in addition, the PHAT was 50-100 times more sensitive. Most human sera gave no agglutination of red cells coated with control preparations. An inhibition (blocking) of PHAT was developed which was useful in the purification and characterization of EA-D. These data indicate that the PHAT may provide a rapid, reliable, objective and sensitive method for studying EA-D and possibly other virus-associated antigens.
Assuntos
Anticorpos Antivirais/análise , Antígenos Virais/análise , Herpesvirus Humano 4/imunologia , Antígenos Virais/isolamento & purificação , Linhagem Celular , Imunofluorescência , Testes de Inibição da Hemaglutinação , Testes de Hemaglutinação , Humanos , Mononucleose Infecciosa/imunologia , Neoplasias Nasofaríngeas/imunologiaRESUMO
We studied the growth of surgically resected human bladder cancer in three dimensional tissue culture, Observations were made in the living cultures and after the sponge matrix cultures were fixed and prepared as histologic sections. We compared the histologic appearance of each tumor immediately after removal and after a week in culture. In a few instances the donor tumor was kept in medium at room temperature for one day before being inoculated into the matrix. This delay had only slight deleterious effect on the growth in culture. Over 85 consecutive cases have been placed in culture and the first 47 have been evaluated in histologic preparations. Tumors grew into the matrix with distinctly different patterns even when the zero time specimens were of similar histopathology. We also studied several antibiotics to idenify conditions that would suppress the usual urinary bacterial contaminants without producing cytotoxicity to tumor cells by microscopic evaluation. A combination of gentamicin and kanamycin, each at a concentration of 50 microgram/ml was effective.
Assuntos
Neoplasias da Bexiga Urinária/patologia , Meios de Cultura , Técnicas de Cultura , Gentamicinas/administração & dosagem , Humanos , Canamicina/administração & dosagem , Métodos , Neoplasias Experimentais/patologia , Fatores de Tempo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/microbiologiaRESUMO
We studied the interaction of human polymorphonuclear leukocytes (PMNs) with umbilical vein endothelial cells infected with herpes simplex virus (HSV) type 1. PMNs labeled with 51Cr were added to endothelial monolayers at varying times after infection and their adherence assessed 1 h later. Granulocyte adherence (GA) to uninfected cells averaged 26.5 +/- 1.9%. Increased adherence began 6 h postinfection and rose to a maximum at 20 to 24 h. HSV-1 glycoproteins seemed to mediate the increase in GA: tunicamycin treatment of infected monolayers for 18 h abolished the increased GA as did incubation of infected cells with F(ab')2 fragments prepared from human antiserum containing HSV-1 antibody.
Assuntos
Adesão Celular , Endotélio Vascular/citologia , Neutrófilos/citologia , Simplexvirus , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/microbiologia , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Técnicas Imunológicas , Técnicas In Vitro , Glicoproteínas de Membrana/metabolismo , Tunicamicina/farmacologia , Proteínas Virais/metabolismoRESUMO
Oka strain varicella vaccine generally has been well tolerated by children with acute lymphocytic leukaemia (ALL) in remission and has induced protection against disease caused by wild-type varicella virus. At the end of 1985, four extensive vaccine-associated rashes were reported among children on maintenance chemotherapy. Steroid therapy in the week before vaccination or in the week following vaccination was significantly associated with rash in a retrospective analysis (odds ratio = 3.84, p = 0.0006). These findings were confirmed prospectively (OR = 2.38, p less than 0.05, one-sided) in a second smaller group of children with ALL on maintenance therapy who received varicella vaccination after the end of the data collection for the initial study but before the relationship between rash and steroids was discovered. As a result of these studies, investigators have been asked to withhold steroids for 1 week before vaccination and to delay resumption of steroid therapy for at least 2 weeks after vaccination. These results should serve as a caution that vaccination of these children should be undertaken only with full knowledge of their therapeutic regimen and a thorough clinical understanding of the competing risks of varicella, vaccination and modification of the child's chemotherapy.
Assuntos
Herpesvirus Humano 3/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Dermatopatias/etiologia , Esteroides/efeitos adversos , Vacinas Virais/efeitos adversos , Adolescente , Varicela/prevenção & controle , Vacina contra Varicela , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Contagem de Leucócitos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Dermatopatias/prevenção & controle , Vacinação/efeitos adversosRESUMO
Imipenem-cilastatin was given in doses of 1 g intravenously every 6 h to 31 patients. Twenty-five patients, with 27 infections, were clinically evaluable and received 20 to 210 g of imipenem for a duration of 5 to 56 days (average 16.3 days). Infections included seven cases of osteomyelitis, seven of bacteremia, five of cellulitis, two of pneumonia, three of pelvic cellulitis, two of intraabdominal abscess, and one each of empyema, mediastinitis, and endometritis. Fifty-five percent of the infections were caused by gram-negative bacilli, 33% were due to gram-positive organisms, and 10% were caused by anaerobes. Twenty-two patients (81%) were cured, three improved, one relapsed, and one became superinfected with a resistant organism. In 5 of 11 cases with Pseudomonas aeruginosa, the imipenem MIC for organisms isolated by the end of treatment was higher than it was initially, raising concern that imipenem should not be used alone to treat Pseudomonas aeruginosa infections. Twenty-one patients had no adverse reaction; of the remaining 10 patients, 4 had nausea, 1 had urticaria, and 6 had mild abnormalities in hepatic function; three episodes of diarrhea included two with Clostridium difficile toxin in stool and one with pseudomembranous colitis, as determined by sigmoidoscopy. Levels of creatinine, hemoglobin, leukocytes, platelets, prothrombin, and urine components were unchanged. Imipenem-cilastatin is a clinically effective antibiotic with freedom from nephrotoxicity and hematological abnormalities in the large doses used in this study.
Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Ciclopropanos/administração & dosagem , Dipeptidases/antagonistas & inibidores , Tienamicinas/administração & dosagem , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Cilastatina , Ciclopropanos/efeitos adversos , Ciclopropanos/farmacologia , Combinação de Medicamentos , Feminino , Humanos , Imipenem , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tienamicinas/efeitos adversos , Tienamicinas/farmacologiaRESUMO
Three hundred and twenty-two (322) persons with severe mental handicaps were given plasma-derived hepatitis B vaccine (20 micrograms dose at 0, 1 and 6 months). Following the third injection, 95% of the vaccinees were positive for anti-HBs, while 92% achieved a protective level of antibody (greater than or equal to 10 mIU ml-1) with a geometric mean titre of 2568 mIU ml-1. Females responded better than males. Antibody responses declined with increasing age in both sexes, but they were not significantly influenced by body weight. Persistence of antibody in responders was followed over 4 years. The proportion of responders maintaining greater than or equal to 10 mIU ml-1 was a function of initial antibody titre but was not significantly affected by sex, age or body weight. Overall, 76% of the responders are estimated to have greater than or equal to 10 mIU ml-1 of anti-HBs 4 years after the first injection of vaccine.