RESUMEN
This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.
Asunto(s)
Monitoreo Epidemiológico , Síndromes de Inmunodeficiencia/epidemiología , Sistema de Registros/estadística & datos numéricos , Femenino , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/terapia , Masculino , Reino Unido/epidemiologíaRESUMEN
The aim of this study was to ascertain farmers' knowledge of the risk of spread of infection from animals to humans, and their transmission prevention practices. This was a survey of farmers who submitted material to Ireland's Regional Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers). Ninety per cent of farmers were not aware that infection can be acquired from apparently healthy animals. Over half were not aware that disease could be contracted from sick poultry or pets. Conversely, the knowledge of the risk to pregnant women of infection from birthing animals was high (88%). Four-fifths of farmers sourced drinking water from a private well, and of these, 62% tested their water less frequently than once a year. Of dairy farmers, 39% drank unpasteurised milk once a week or more frequently. Veterinarians were the most commonly cited information source for diseases on farms. The survey findings indicate that the level of farmers' knowledge and awareness of the spread of infection from animals to humans is a concern. Further education of the farming community is needed to increase awareness of both the potential biohazards present on farms and the practical measures that can be taken to mitigate the risk of zoonoses.
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Agricultores/psicología , Conocimientos, Actitudes y Práctica en Salud , Zoonosis/prevención & control , Zoonosis/transmisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Medición de Riesgo , Adulto Joven , Zoonosis/psicologíaRESUMEN
Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4(+) CD45RO(+) CXCR5(+) [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21(-) (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation.
Asunto(s)
Subgrupos de Linfocitos B/inmunología , Infecciones por VIH/inmunología , Memoria Inmunológica/inmunología , Receptores CXCR5/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Adolescente , Antirretrovirales/uso terapéutico , Subgrupos de Linfocitos B/virología , Niño , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Masculino , Receptores de Complemento 3d/inmunología , Linfocitos T Colaboradores-Inductores/virologíaRESUMEN
Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1(+) patients. DC from healthy controls, untreated HIV-1(+) and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1(+) patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1(+) patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.
Asunto(s)
Células Dendríticas/inmunología , Infecciones por VIH/inmunología , Células Mieloides/inmunología , Adulto , Antígenos CD/inmunología , Antígenos CD/metabolismo , Terapia Antirretroviral Altamente Activa/métodos , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Estudios de Cohortes , Células Dendríticas/metabolismo , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , VIH-1/inmunología , Humanos , Inmunofenotipificación , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Células Mieloides/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/metabolismo , Viremia/inmunología , Viremia/metabolismo , Adulto JovenRESUMEN
Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients. We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher's discriminant function analysis to establish the groups of classification mediators. There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients. These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution.
Asunto(s)
Biomarcadores/metabolismo , Neumología/métodos , Sarcoidosis/sangre , Esclerodermia Sistémica/sangre , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Fibrosis/sangre , Humanos , Sistema Inmunológico , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Singlet molecular oxygen ((1)Delta(g)) produced by the microwave discharge of ground state oxygen in a flow system was passed over a film of cis-polybutadiene. This treatment resulted in the formation, at the surface, of hydroperoxides which were detected by internal reflection infrared spectroscopy.
RESUMEN
Both virus-associated haemophagocytic syndrome (HPS) and human immunodeficiency virus-associated multi-centric Castleman's disease (HIV-MCD) induced by human herpesvirus-8 (HHV-8) are extremely rare. We therefore wished to investigate their occurrence together, and establish the degree of cytokine activation present. From a prospective cohort of individuals with HIV-MCD, we investigated the incidence and outcomes of HPS and measured 15 inflammatory cytokines and the plasma HHV-8 viral loads before and during follow-up. Of 44 patients with HIV-MCD with an incidence of 4.3/10,000 patient years, four individuals (9%) were diagnosed with HPS. All are in remission (range 6-28 months) following splenectomy, etoposide and rituximab-based therapy. Plasma HHV-8 levels were raised markedly at presentation (median 3,840,000 copies/ml). Histological samples from spleen, splenic hilar lymph nodes and bone marrow demonstrated increased phagocytosis by histiocytes and presence of HHV-8-infected plasmablasts outside the follicles. Surprisingly, many known inflammatory plasma cytokines were not elevated, although interleukin (IL)-8 and interferon-gamma were increased in all cases and IL-6 levels were raised in three of four patients. HPS in the setting of HIV-MCD is common and treatment can be successful provided the diagnosis is made appropriately. Systemic activation of cytokines was limited, suggesting that immunosuppressive therapy with steroids is not indicated in HHV-8-driven HPS.
Asunto(s)
Enfermedad de Castleman/virología , Citocinas/metabolismo , Infecciones por VIH/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Adulto , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos Fitogénicos/uso terapéutico , Terapia Antirretroviral Altamente Activa , Terapia Combinada , Quimioterapia Combinada , Etopósido/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Herpesvirus Humano 8 , Humanos , Factores Inmunológicos/uso terapéutico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/cirugía , Masculino , Persona de Mediana Edad , Rituximab , Esplenectomía , Adulto JovenRESUMEN
OBJECTIVE: We aim to find what is the relationship between B cell antibody responses and specific T cell help in the specific cases of allergy and tolerance to peanuts. BACKGROUND: B cell antibody responses to foreign proteins usually depend upon antigen-specific T cell help. However, specific antibody levels can sometimes be maintained lifelong after infections or vaccination. METHODS: We measured peanut-specific proliferation and antibody levels in peanut-allergic and non-allergic children using tritiated thymidine incorporation and UniCAP, respectively. We also investigated the corresponding tetanus toxoid specific responses in both groups. RESULTS: We found that tetanus-specific IgG did not correlate with lymphocyte proliferation (Spearman rank correlation coefficient r'=0.08, P=0.74) nor with tetanus-specific cytokine production (IFN-gamma: r'=0.198, P=0.285; TNF-alpha: r'=0.274, P=0.146; IL-4: r'=-0.007, P=0.96; P=0.221; IL-13: r'=0.363, P=0.056). Conversely, in peanut-allergic donors, peanut-specific IgE (average 21 kU/L, median 2.27 kU/L, range 0.34-100 kU/L) but not peanut-specific IgG was positively correlated with proliferation (r'=0.751, P=0.003). In these donors, specific IgE was positively correlated with peanut-specific Th2 cytokines production: r'=0.635, P=0.02 for IL-4 and r'=0.641, P=0.025 for IL-13 and negatively correlated with Th1 cytokines (r'=-0.71, P=0.007 for IFN-gamma and r'=-0.746, P=0.005 for TNF-alpha, respectively). However, peanut-specific IgE was not correlated with T cell proliferation or cytokine production in non-allergic individuals. In conclusion, in allergic individuals, B and T cell responses to peanut antigens are correlated whereas normal immune responses B and T cell responses are uncoupled. CONCLUSION: Our results support the view that B cell responses to allergens but not those to non-allergenic proteins are correlated with specific T cell responses and therefore specific immunotherapy targeting of such T cells would inhibit allergen-specific B cells.
Asunto(s)
Arachis/inmunología , Linfocitos B/inmunología , Citocinas/metabolismo , Inmunoglobulina E/sangre , Hipersensibilidad al Cacahuete/inmunología , Linfocitos T/inmunología , Toxoide Tetánico/inmunología , Linfocitos B/metabolismo , Proliferación Celular , Niño , Citocinas/inmunología , Humanos , Activación de Linfocitos , Linfocitos T/metabolismoRESUMEN
There are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count < 300 cells/microl). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-gamma secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98.2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-gamma spots to CD4 T cell count ratio was > 1.5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune-deficient HIV-1 patients. A combination of TB antigen-specific IFN-gamma responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Antígenos Bacterianos/inmunología , VIH-1 , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Adulto , Recuento de Linfocito CD4 , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Inmunidad Celular , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Tuberculosis/diagnósticoAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Adulto , Factores de Edad , Biomarcadores/análisis , Monitoreo de Drogas/métodos , Farmacorresistencia Viral , Infecciones por VIH/diagnóstico , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/clasificación , Enfermedades Hematológicas/diagnóstico , Humanos , Persona de Mediana Edad , Compartición de Agujas , Guías de Práctica Clínica como Asunto , Reino Unido , Carga Viral/métodosRESUMEN
Serum half-lives of unfractionated rat alpha-fetoprotein (AFP), concanavalin A (Con A)-nonreactive AFP, and Con A-reactive AFP in normal 45- to 55-day-old male and female F344 rats were determined to be 19 hours. No significant differences were seen between the half-lives of unfractionated AFP and either of the two Con A-affinity molecular variants of AFP studied. No evidence of interconversion of the Con A-affinity AFP variants during 24 hours in the circulation was found. These results supported the conclusion that the proportions of Con A-affinity molecular variants of AFP in the sera of fetal, newborn, and hematoma-bearing rats result from differences in the relative synthesis rates of the two variants.
Asunto(s)
Concanavalina A/sangre , alfa-Fetoproteínas/metabolismo , Factores de Edad , Animales , Femenino , Semivida , Neoplasias Hepáticas Experimentales/sangre , Masculino , Ratas , Ratas Endogámicas F344 , Especificidad de la Especie , alfa-Fetoproteínas/biosíntesisRESUMEN
Line 10 hepatocarcinoma cells derived from ascites in a strain 2 guinea pig were tumorigenic when transferred intradermally. After they had been cultured in vitro for 20 days or more in medium enriched with 10% fetal bovine serum (FBS), they became immunogenic. Injections of immunogenic cells did not cause lethal tumors, and recipients were resistant to subsequent challenges with tumorigenic line 10 cells. Resistance was specific since growth of line 1 cells, a syngeneic but antigenically distinct tumor, was not affected. Cells cultured in medium enriched with 10% calf bovine serum or 10% normal guinea pig serum or in reduced concentrations of FBS were less effective in inducing resistance. When cultured line 10 cells were injected ip into normal guinea pigs, ascites tumors developed that were tumorigenic. The growth rate of line 10 cells in culture was considerably decreased as determined by reduced [3H]thymidine incorporation and mitotic indices. The mechanism(s) responsible for enhancement of immunogenicity in cultured line 10 cells is discussed but was not determined.
Asunto(s)
Neoplasias Hepáticas Experimentales/inmunología , Animales , Línea Celular , Células Cultivadas , Dietilnitrosamina/farmacología , Femenino , Cobayas , Inmunidad Celular , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Mitosis , Trasplante de Neoplasias , Factores de Tiempo , Inmunología del TrasplanteRESUMEN
Fourteen patients with chronic myelogenous leukemia were treated with partially pure leukocyte interferon (HuIFN alpha). The binding of recombinant leukocyte clone A IFN and the induction of 2',5'-oligoadenylate synthetase (2,5A) in peripheral blood cells were studied to determine whether they correlate with clinical response to IFN therapy. The mean pretherapy binding of radiolabeled recombinant leukocyte clone A IFN to peripheral blood cells was 0.053 +/- 0.02 (SE) fmol (53 +/- 20 amol)/10(6) cells and 0.049 +/- 0.015 fmol/10(6) cells in sensitive and resistant patients, respectively. Twenty-four h after the first HuIFN alpha dose, the binding of recombinant leukocyte clone A IFN decreased 3- to 8-fold in both sensitive and resistant patients. The activity of 2,5A synthetase was induced approximately 100-fold in sensitive patients from a pretherapy mean of 3 +/- 2 nmol/mg to a maximum of 317 +/- 184 nmol/mg during therapy. In contrast, 2,5A synthetase was induced from a pretherapy mean of 0.9 +/- 0.9 nmol/mg to only 6.7 +/- 4.9 nmol/mg in resistant patients. In two patients originally sensitive to HuIFN alpha who developed resistance to therapy, receptors were present in both sensitive and resistant disease stages and appeared to down regulate with therapy regardless of response. In these two patients, 2,5A synthetase was significantly induced with therapy in the sensitive stage but not in the resistant stage. This study shows that lack of clinical response to interferon therapy may coincide with failure to induce 2,5A synthetase activity. This suggests that resistance to alpha-interferon therapy may be mediated by events beyond receptor binding resulting in a failure to induce enzymes responsible for mediation of interferon antiproliferative effects.
Asunto(s)
2',5'-Oligoadenilato Sintetasa/sangre , Interferón Tipo I/uso terapéutico , Leucemia Mieloide/terapia , Receptores Inmunológicos/metabolismo , Proteínas Recombinantes/uso terapéutico , Resistencia a Medicamentos , Humanos , Interferón Tipo I/metabolismo , Leucemia Mieloide/enzimología , Leucocitos/enzimología , Leucocitos/metabolismo , Cromosoma Filadelfia , Receptores de Interferón , Proteínas Recombinantes/metabolismoRESUMEN
Alpha1-Fetoprotein present in fetal/newborn rat serum and in hepatoma-bearing human serum has been resolved into two molecular variants by concanavalin A-agarose affinity chromatography. The concanavalin A-reactive variant has been purified by gel filtration column chromatography, preparative block electrophoresis and immunoadsorption affinity chromatography.
Asunto(s)
Técnicas de Química Analítica/métodos , Cromatografía de Afinidad/métodos , Concanavalina A/química , Sefarosa/química , alfa-Fetoproteínas/aislamiento & purificación , Adsorción , Animales , Animales Recién Nacidos , Cromatografía en Agarosa/métodos , Cromatografía en Gel/métodos , Electroforesis , Regulación del Desarrollo de la Expresión Génica , Humanos , Ratas , Reproducibilidad de los Resultados , alfa-Fetoproteínas/químicaRESUMEN
The synthesis and the turnover of phosphatidylinositol in frog retinal rod outer segments and microsomes were studied by following the time course of incorporation into lipids of the following radioactive precursors: [3H]glycerol, 33PO4, and [3H]inositol. 1. Although all precursors were incorporated into lipid, glycerol was the only true pulse of radioactive substrate because the precursor pools of phosphate and inositol in the retina have a slow rate of turnover. 2. A precursor-product relationship exists between retinal microsomes and rod outer segments for phosphatidylinositol synthesized from glycerol. 3. The specific activity in the rod outer segment phosphatidylinositol derived from labeled glycerol was ten times that of the other glycerolipids. Since the labeled precursor for each phospholipid class is derived from a common pool of glycerol 3-phosphate, the synthesis rate of phosphatidylinositol in the retina is much greater than that of the other phospholipids. 4. Two pools of phosphatidylinositol were identified in the rod outer segments; one turned over with a t1/2 of about 3.5 days, while the other turned over at the same rate as the other phospholipids labeled with glycerol. 5. Turnover of phosphatidylinositol in the rod outer segments after glycerol injection was followed by an increase in specific radioactivity in 1,2-diacylglycerols, consistent with the latter being a lipolytic product of phosphatidylinositol in these membranes. 6. The present studies demonstrate a unique metabolism of phosphatidylinositol in the rod outer segments compared to the other phospholipids, and it is suggested that the rapid turnover of this phospholipid may be related to membrane fusion events associated with the assembly and/or turnover of rod outer segment membranes.
Asunto(s)
Microsomas/metabolismo , Fosfatidilinositoles/metabolismo , Células Fotorreceptoras/metabolismo , Animales , Glicerol/metabolismo , Inositol/metabolismo , Cinética , Fosfatos/metabolismo , Fosfolípidos/metabolismo , Radioisótopos de Fósforo , Técnica de Dilución de Radioisótopos , Rana pipiens , TritioRESUMEN
The synthesis and the turnover of phosphatidylethanolamine in frog retinal rod outer segments and microsomes were studied by monitoring the incorporation of five radioactive precursors: 32PO4, 33PO4 [3H]glycerol, [3H]serine, and [3H]ethanolamine. 1. Labeled serine was actively incorporated into phosphatidylethanolamine. The kinetics of the labeling patterns in both microsomes and rod outer segments was consistent with formation via decarboxylation of phosphatidylserine. 2. Ethanolamine was found to be an ineffective precursor of phosphatidylethanolamine, suggesting that the major pathway for phosphatidylethanolamine synthesis in the retina is via the decarboxylation reaction. 3. An active methylation of phosphatidylethanolamine to phosphatidylcholine was observed in both retinal microsomes and rod outer segments. 4. The kinetics of labeling of phosphatidylethanolamine in the rod outer segments was different for the various isotopic precursors, and was found to depend on the relative turnover times of the precursor pools. Glycerol was the only precursor that gave a true pulse of radioactivity. 5. The specific activity of phosphatidylethanolamine derived from labeled glycerol declined exponentially, demonstrating that the labeled lipid was diffusely distributed throughout the rod outer segments. The half-life of phosphatidylethanolamine in the rod outer segments was determined to be 18 days. Comparison of this value to the turnover time of rod outer segment integral proteins revealed that rod outer segment lipid is renewed at a faster rate than protein.
Asunto(s)
Microsomas/metabolismo , Fosfatidiletanolaminas/metabolismo , Células Fotorreceptoras/metabolismo , Animales , Etanolaminas/metabolismo , Glicerol/metabolismo , Cinética , Fosfatos/metabolismo , Fosfolípidos/metabolismo , Radioisótopos de Fósforo , Técnica de Dilución de Radioisótopos , Rana pipiens , Serina/metabolismo , TritioRESUMEN
The biosynthesis and the turnover of phosphatidylcholine were studied in the frog retina following either (a) injection into the animal of 32PO4, 33PO4, [1,3-3H]glycerol, [2-3H]glycerol, or [methyl-3H]choline, or (b) incubation of isolated retinas in solutions containing [methyl-3H]choline. 1. Examination of the pools of lipid precursors in the retina demonstrated that the choline and phosphate pools are long-lived compared to the glycerol pool, which is metabolically very active and turns over rapidly. 2. The peak in specific activity of phosphatidylcholine synthesized from labeled glycerol occurred earlier, and was higher in the microsomal fraction than in the rod outer segments, which is consistent with synthesis of phosphatidylcholine on the microsomes of the inner segment and subsequent incorporation into the rod outer segments. 3. Autoradiography of retinas incubated in vitro with tritiated choline revealed a diffuse labeling pattern in the rod outer segments. Biochemical studies following injection of labeled glycerol showed an exponential decline in specific radioactivity of phosphatidylcholine in the rod outer segments, which is consistent with a diffuse labeling of these membranes. 4. The half-life of phosphatidylcholine in the rod outer segments synthesized from labeled glycerol was found to be 18-19 days. Based on these values, calculations were made which indicated that phosphatidylcholine in the outer segments is turning over faster than integral disc membrane proteins.
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Fosfatidilcolinas/metabolismo , Retina/metabolismo , Animales , Cinética , Microscopía Electrónica , Microsomas/metabolismo , Radioisótopos de Fósforo , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/ultraestructura , Técnica de Dilución de Radioisótopos , Rana pipiens , Retina/ultraestructura , TritioRESUMEN
Photoreceptor membrane preparations were made from retinas of the squid Loligo (Doryteuthis) plei for protein and lipid analysis. Lipid analysis was also completed on a single membrane preparation from Loligo pealei. (1) The membranes contain 75 wt. % protein and 25 wt. % lipid. Neutral lipids make up 26 mol % of the total lipid, the remaining 74% being phospholipid. No glycolipids were observed. (2) Free fatty acids and cholesterol comprise 8.6 and 17 mol %, respectively of the total lipid. No other neutral lipids were found. (3) Phosphatidylethanolamine and phosphatidylcholine are the major phospholipids. Lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, and phosphatidylserine are present in small quantities. Phosphatidylinositol was not detected in the membranes. (4) The levels of polyunsaturated fatty acids, principally 20:4 omega 6, 20:5 omega 3, and 22:6 omega 3 are higher in the squid membranes than in any othr vertebrate or invertebrate retina that has been examined thus far. These acids account for 58 mol % of the fatty acids in phosphatidylcholine and phosphatidylserine, 75 mol % of the free fatty acids, and nearly 90% of the fatty acids of lyso- and phosphatidylethanolamine. The results from L. plei and L. pealei were indistinguishable. (5) Rhodopsin is the major protein of the membrane preparations and has a molecular weight of 50 500 +/- 850 determined by sodium dodecyl sulfate polyacrylamide gel disc electrophoresis.
Asunto(s)
Decapodiformes/análisis , Células Fotorreceptoras/análisis , Retina/análisis , Animales , Colesterol/análisis , Ácidos Grasos no Esterificados/análisis , Ácidos Grasos Insaturados/análisis , Lípidos de la Membrana/análisis , Proteínas de la Membrana/análisis , Fosfolípidos/análisis , Rodopsina/análisisRESUMEN
Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.
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Síndrome de Fatiga Crónica/terapia , Inmunoglobulinas Intravenosas/uso terapéutico , Infecciones por Parvoviridae/terapia , Parvovirus B19 Humano/inmunología , Adulto , Síndrome de Fatiga Crónica/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Rauscher leukaemia virus (RLV) infection in mice causes production of lymph node and skin dendritic cells (DC) that fail to stimulate a primary mixed leukocyte reaction (MLR). Treatment of mice with IL-12 around the time of infection results in DC with normal stimulatory function (N.J. Williams, J.J. Harvey, I. Duncan, R.F.G. Booth, S.C. Knight, Cell Immunol. 183 (1988) 121-130). Here we derived DC from mouse bone marrow by culture with granulocyte macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha) for 10-12 days; DC were generated from bone marrow cells taken from normal mice, from mice injected 15 days earlier with RLV or from those receiving RLV plus five daily doses of 100 ng of IL-12 starting 2 days before infection. Infection of the DC with RLV was assessed from nested PCR with doubling dilutions of DNA and the capacity of DC to stimulate a MLR was tested. DC derived from bone marrow of IL-12 treated animals showed at least twice the level of infection with RLV as those from non-treated animals although infection never exceeded 20% of the cells. DC derived from bone marrow of mice given RLV caused negligible stimulation of the MLR but those from mice additionally treated with IL-12 functioned normally. Thus, treatment of mice with IL-12 promoted the potential of stem cells taken 12 days after the last IL-12 injection to develop into functional DC despite increased infection with virus. Treatment of mice with IL-12 may have a long term effect on the potential growth of DC from stem cells which may contribute to the potency of this cytokine in promoting cell mediated immune responses.