RESUMEN

Alveolar macrophages (AMs) are CD44 expressing cells that reside in the alveolar space where they maintain lung homeostasis by serving critical roles in immunosurveillance and lipid surfactant catabolism. AMs lacking CD44 are unable to bind the glycosaminoglycan, hyaluronan, which compromises their survival and leads to reduced numbers of AMs in the lung. Using RNA sequencing, lipidomics and multiparameter flow cytometry, we demonstrate that CD44-/- mice have impaired AM lipid homeostasis and increased surfactant lipids in the lung. CD44-/- AMs had increased expression of CD36, a lipid scavenger receptor, as well as increased intracellular lipid droplets, giving them a foamy appearance. RNA sequencing revealed the differential expression of genes associated with lipid efflux and metabolism in CD44-/- AMs. Lipidomic analysis showed increased lipids in both the supernatant and cell pellet extracted from the bronchoalveolar lavage of CD44-/- mice. Phosphatidylcholine species, cholesterol, oxidized phospholipids and levels of reactive oxygen species (ROS) were increased in CD44-/- AMs. Oxidized phospholipids were more cytotoxic to CD44-/- AMs and induced greater lung inflammation in CD44-/- mice. Reconstitution of CD44+/+ mice with CD44-/- bone marrow as well as adoptive transfer of CD44-/- AMs into CD44+/+ mice showed that lipid accumulation in CD44-/- AMs occurred irrespective of the lung environment, suggesting a cell intrinsic defect. Administration of colony stimulating factor 2 (CSF-2), a critical factor in AM development and maintenance, increased AM numbers in CD44-/- mice and decreased phosphatidylcholine levels in the bronchoalveolar lavage, but was unable to decrease intracellular lipid accumulation in CD44-/- AMs. Peroxisome proliferator-activated receptor gamma (PPARγ), downstream of CSF-2 signaling and a regulator of lipid metabolism, was reduced in the nucleus of CD44-/- AMs, and PPARγ inhibition in normal AMs increased their lipid droplets. Thus, CD44 deficiency causes defects in AMs that lead to abnormal lipid accumulation and oxidation, which exacerbates oxidized lipid-induced lung inflammation. Collectively, these findings implicate CD44 as a regulator of lung homeostasis and inflammation.

Asunto(s)

Colesterol/metabolismo , Homeostasis/genética , Receptores de Hialuranos/metabolismo , Macrófagos Alveolares/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolípidos/metabolismo , Neumonía/metabolismo , Animales , Antígenos CD36/metabolismo , Femenino , Receptores de Hialuranos/genética , Gotas Lipídicas/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oxidación-Reducción , PPAR gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética

RESUMEN

Hyaluronan is a hygroscopic glycosaminoglycan that contributes to both extracellular and pericellular matrices. While the production of hyaluronan is essential for mammalian development, less is known about its interaction and function with immune cells. Here we review what is known about hyaluronan in the lung and how it impacts immune cells, both at homeostasis and during lung inflammation and fibrosis. In the healthy lung, alveolar macrophages provide the first line of defense and play important roles in immunosurveillance and lipid surfactant homeostasis. Alveolar macrophages are surrounded by a coat of hyaluronan that is bound by CD44, a major hyaluronan receptor on immune cells, and this interaction contributes to their survival and the maintenance of normal alveolar macrophage numbers. Alveolar macrophages are conditioned by the alveolar environment to be immunosuppressive, and can phagocytose particulates without alerting an immune response. However, during acute lung infection or injury, an inflammatory immune response is triggered. Hyaluronan levels in the lung are rapidly increased and peak with maximum leukocyte infiltration, suggesting a role for hyaluronan in facilitating leukocyte access to the injury site. Hyaluronan can also be bound by hyaladherins (hyaluronan binding proteins), which create a provisional matrix to facilitate tissue repair. During the subsequent remodeling process hyaluronan concentrations decline and levels return to baseline as homeostasis is restored. In chronic lung diseases, the inflammatory and/or repair phases persist, leading to sustained high levels of hyaluronan, accumulation of associated immune cells and an inability to resolve the inflammatory response.

Asunto(s)

Ácido Hialurónico/inmunología , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Neumonía/inmunología , Animales , Humanos , Inflamación/inmunología , Inflamación/patología , Pulmón/patología , Macrófagos Alveolares/patología , Neumonía/patología

RESUMEN

CD44 is a widely expressed cell adhesion molecule that binds to the extracellular matrix component, hyaluronan. However, this interaction is not constitutive in most immune cells at steady state, as the ability of CD44 to engage hyaluronan is highly regulated. While activated T cells and macrophages gain the ability to bind hyaluronan by CD44, the status in other immune cells is less studied. Here we found a percentage of murine eosinophils, natural killer and natural killer T cells were capable of interacting with hyaluronan at steady state. To further investigate the consequences of hyaluronan binding by CD44 in the hematopoietic system, point mutations of CD44 that either cannot bind hyaluronan (LOF-CD44) or have an increased affinity for hyaluronan (GOF-CD44) were expressed in CD44-deficient bone marrow. Competitive bone marrow reconstitution of irradiated mice revealed an early preference for GOF-CD44 over WT-CD44 expressing cells, and for WT-CD44 over LOF-CD44 expressing cells, in the hematopoietic progenitor cell compartment. The advantage of the hyaluronan-binding cells was observed in the hematopoietic stem and progenitor populations, and was maintained throughout the immune system. Hematopoietic stem cells bound minimal hyaluronan at steady state, and this was increased when the cells were induced to proliferate whereas multipotent progenitors had an increased ability to bind hyaluronan at steady state. In vitro, the addition of hyaluronan promoted their proliferation. Thus, proliferating hematopoietic progenitors bind hyaluronan, and hyaluronan binding cells have a striking competitive advantage in bone marrow engraftment.

Asunto(s)

Células Madre Hematopoyéticas/citología , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Animales , Trasplante de Médula Ósea , Proliferación Celular , Eosinófilos/metabolismo , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/efectos de la radiación , Células Asesinas Naturales/metabolismo , Ratones , Mutación , Unión Proteica

RESUMEN

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can vary among different ethnic and racial groups. Objective The objective of this paper is to study the prevalence of various manifestations of SLE in a sample of the Egyptian population. Patients and methods Information in this study was derived from the medical records of SLE patients who sought medical advice at a private clinic in Cairo from January 1980 to June 2016. Results This study included 1109 SLE patients, of whom 114 (10.3%) were males and 995 were females (89.7%). Mean age of onset was 25.89 ± 10.81 years, while the median of disease duration from the onset of the disease till the last recorded visit was 26 months. The most common cumulative manifestations were arthritis (76.7%), malar rash (48.5%), leukopenia (45.7%), and photosensitivity (45.6%). A total of 33.1% of the patients had nephritis, and neuropsychiatric lupus was present in 6.4% of the patients. Secondary antiphospholipid syndrome was present in 11.5% of the patients. Antinuclear antibody and anti-double-stranded deoxyribonucleic acid were present in 1060/1094 (96.9%) and 842/1062 (79.3%) of the patients, respectively. Antiphospholipid antibodies were present in 266/636 (41.8%) of the patients, anti-Smith in 54/240 (22.5%), anti-SSA/Ro in 61/229 (20.4%), and anti-SSB/La in 32/277 (11.6%) of the patients. Male patients had a statistically higher prevalence of nephritis ( p = 0.01), whereas arthritis and alopecia were statistically higher in females ( p = 0.012 and p = 0.006, respectively). Patients with juvenile onset had a statistically higher prevalence of nephritis and seizures ( p < 0.001 and p = 0.012, respectively). Conclusions Arthritis and malar rash represented the most common clinical manifestations. Male and juvenile-onset patients had a predilection toward a more severe disease. These results are in agreement with many studies conducted in the Middle East and worldwide. On the other hand, major organ involvement was exceptionally low, which is contradictory to several reports from the Middle East and across the globe.

Asunto(s)

Lupus Eritematoso Sistémico/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Autoanticuerpos/sangre , Biomarcadores/sangre , Niño , Preescolar , Comorbilidad , Egipto/epidemiología , Femenino , Disparidades en el Estado de Salud , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de Tiempo , Adulto Joven

RESUMEN

Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site. However, CD44+/+ cells were out-competed by CD44-/- cells after the contraction phase in the lymphoid tissues, and the CD44-/- cells preferentially formed more memory cells. The hyaluronan-binding CD44+/+ CD8 effector T cells showed increased pAkt expression, higher glucose uptake, and were more susceptible to cell death during the contraction phase compared to non-binding CD44+/+ and CD44-/- OT-I CD8 T cells, suggesting that CD44 and its engagement with hyaluronan skews CD8 T cells toward a terminal effector differentiation state that reduces their ability to form memory cells.

Asunto(s)

Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Memoria Inmunológica/inmunología , Traslado Adoptivo , Animales , Linfocitos T CD8-positivos/trasplante , Diferenciación Celular/inmunología , Receptores de Hialuranos/genética , Listeria monocytogenes/inmunología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología

RESUMEN

BACKGROUND: A high seasonal incidence of Bacillus bacteremia was associated with the use of contaminated hospital linens. METHODS: An outbreak investigation was conducted to study the incidence and source of Bacillus bacteremia during the baseline, outbreak, and postoutbreak period from 1 January 2012 through 31 July 2016 at a university-affiliated teaching hospital in Hong Kong. Replicate organism detection and counting plates were used for microbial screening of linen samples. The Bacillus species isolated from patient and linen samples were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and were phylogenetically analyzed. RESULTS: During the study period, a total of 113 207 blood cultures were collected from 43 271 patients, of which 978 (0.86%) specimens from 744 (1.72%) patients were identified as Bacillus species. The incidence of Bacillus bacteremia per 10 000 patient admissions and per 10 000 patient-days was significantly higher during the summer outbreak as compared with baseline and 1 year postoutbreak after cessation of the linen supply from the designated laundry and change of laundry protocol (39.97 vs 18.21 vs 2.27; 13.36 vs 5.61 vs 0.73; P < .001). The mean total aerobic bacterial count per 100 cm2 was significantly higher among the 99 linen samples screened during the outbreak period compared to the 100 screened in the postoutbreak period (916.0 ± 641.6 vs 0.6 ± 1.6; P < .001). Blood culture isolates of Bacillus cereus group in 14 of 87 (16.1%) patients were phylogenetically associated with 9 linen sample isolates. CONCLUSIONS: Suboptimal conditions of hospital laundry contributed to the seasonal outbreak of Bacillus bacteremia.

Asunto(s)

Infecciones por Bacillaceae/epidemiología , Bacillus/aislamiento & purificación , Bacteriemia/epidemiología , Ropa de Cama y Ropa Blanca/microbiología , Brotes de Enfermedades , Estaciones del Año , Adulto , Bacillus/clasificación , Bacillus/genética , Bacteriemia/etiología , Bacteriemia/microbiología , Infección Hospitalaria/epidemiología , Femenino , Hong Kong/epidemiología , Hospitales de Enseñanza/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Servicio de Lavandería en Hospital , Masculino , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción

RESUMEN

BACKGROUND: Healthcare laundry-related infection is rare, and pulmonary zygomycosis due to contaminated hospital linens has never been reported. METHODS: We reported an outbreak investigation of zygomycosis in a university-affiliated teaching hospital. Air samplers, sponge swabs and Replicate Organism Detection and Counting (RODAC) contact plates were used for environmental sampling. The fungal isolates from clinical and environmental samples were identified by morphology, MALDI-TOF MS, and ITS1-5.8S-ITS2 rRNA gene cluster sequencing. RESULTS: From 2 June 2015 to 18 July 2015, 6 immunosuppressed patients developed pulmonary (n = 4) and/or cutaneous (n = 3) infection by a spore-forming mold, Rhizopus microsporus, through direct inhalation and skin contact of contaminated linen items supplied by a designated laundry. Seventy (27.8%) of 252 freshly laundered clothing and 15 (3.4%) of 443 nonclothing laundered linen items (pillow case, bed sheet, draw sheet) were contaminated by R. microsporus, which was significantly higher than those from other hospital laundries (0%, n = 451; P < .001) supplying linen to hospitals with no cases of zygomycosis reported during the same period. The fungal isolates from patients and linens were phylogenetically related. In sum, 61% of environmental samples and 100% of air samples at the designated laundry were also positive for zygomycetes, suggesting heavy environmental contamination. RODAC contact plates revealed mean total viable bacteria counts of freshly laundered items (1028 ± 611 CFU/100 cm(2)) far exceeded the "hygienically clean" standard of 20 CFU/100 cm(2) set by the US healthcare textile certification requirement. CONCLUSIONS: Suboptimal conditions of washing, drying, and storage contributed to the massive linen contamination and the outbreak of zygomycosis.

Asunto(s)

Ropa de Cama y Ropa Blanca/microbiología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Servicio de Lavandería en Hospital/normas , Pulmón/microbiología , Rhizopus/aislamiento & purificación , Cigomicosis/microbiología , Adulto , Anciano , China/epidemiología , Infección Hospitalaria/microbiología , Femenino , Hospitales de Enseñanza/estadística & datos numéricos , Hospitales Universitarios , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Filogenia , Rhizopus/genética , Análisis de Secuencia de ADN , Cigomicosis/epidemiología

RESUMEN

Hyaluronan is made and extruded from cells to form a pericellular or extracellular matrix (ECM) and is present in virtually all tissues in the body. The size and form of hyaluronan present in tissues are indicative of a healthy or inflamed tissue, and the interactions of hyaluronan with immune cells can influence their response. Thus, in order to understand how inflammation is regulated, it is necessary to understand these interactions and their consequences. Although there is a large turnover of hyaluronan in our bodies, the large molecular mass form of hyaluronan predominates in healthy tissues. Upon tissue damage and/or infection, the ECM and hyaluronan are broken down and an inflammatory response ensues. As inflammation is resolved, the ECM is restored, and high molecular mass hyaluronan predominates again. Immune cells encounter hyaluronan in the tissues and lymphoid organs and respond differently to high and low molecular mass forms. Immune cells differ in their ability to bind hyaluronan and this can vary with the cell type and their activation state. For example, peritoneal macrophages do not bind soluble hyaluronan but can be induced to bind after exposure to inflammatory stimuli. Likewise, naïve T cells, which typically express low levels of the hyaluronan receptor, CD44, do not bind hyaluronan until they undergo antigen-stimulated T cell proliferation and upregulate CD44. Despite substantial knowledge of where and when immune cells bind hyaluronan, why immune cells bind hyaluronan remains a major outstanding question. Here, we review what is currently known about the interactions of hyaluronan with immune cells in both healthy and inflamed tissues and discuss how hyaluronan binding by immune cells influences the inflammatory response.

RESUMEN

We report a fatal case of Schizophyllum commune empyema thoracis with cross-reactive cryptococcal antigenemia. In vitro testing confirmed the ability of the fungus to cause a positive cryptococcal antigen latex agglutination system (CALAS) test result. Such a result may lead to delay in diagnosis and treatment, as most strains of S. commune are resistant to fluconazole.

Asunto(s)

Antígenos Fúngicos/sangre , Reacciones Cruzadas , Cryptococcus/inmunología , Empiema Pleural/diagnóstico , Pruebas de Fijación de Látex/métodos , Micosis/diagnóstico , Schizophyllum/aislamiento & purificación , Anciano , ADN de Hongos/química , ADN de Hongos/genética , Empiema Pleural/microbiología , Reacciones Falso Positivas , Resultado Fatal , Humanos , Masculino , Datos de Secuencia Molecular , Micosis/microbiología , Análisis de Secuencia de ADN

RESUMEN

We report the first case of spontaneous intrapartum Atopobium vaginae bacteremia identified by 16S rRNA gene sequencing. The bacterium was misidentified by RapID ANA II, API Rapid ID 32A, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The likely source of bacteremia was the female genital tract. In invasive infections caused by A. vaginae, ß-lactams and clindamycin are the antibiotics of choice, as most strains are resistant to metronidazole.

Asunto(s)

Actinobacteria/aislamiento & purificación , Bacteriemia/diagnóstico , Infecciones por Bacterias Grampositivas/diagnóstico , Complicaciones Infecciosas del Embarazo/diagnóstico , Actinobacteria/clasificación , Actinobacteria/genética , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Bacteriemia/patología , Clindamicina/uso terapéutico , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Farmacorresistencia Bacteriana , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/patología , Humanos , Datos de Secuencia Molecular , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/patología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , beta-Lactamas/uso terapéutico

RESUMEN

CD44 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan and is involved in processes ranging from leukocyte recruitment to wound healing. In the immune system, the binding of hyaluronan to CD44 is tightly regulated, and exposure of human peripheral blood monocytes to inflammatory stimuli increases CD44 expression and induces hyaluronan binding. Here we sought to understand how mouse macrophages regulate hyaluronan binding upon inflammatory and anti-inflammatory stimuli. Mouse bone marrow-derived macrophages stimulated with tumor necrosis factor α or lipopolysaccharide and interferon-γ (LPS/IFNγ) induced hyaluronan binding by up-regulating CD44 and down-regulating chondroitin sulfation on CD44. Hyaluronan binding was induced to a lesser extent in interleukin-4 (IL-4)-activated macrophages despite increased CD44 expression, and this was attributable to increased chondroitin sulfation on CD44, as treatment with ß-d-xyloside to prevent chondroitin sulfate addition significantly enhanced hyaluronan binding. These changes in the chondroitin sulfation of CD44 were associated with changes in mRNA expression of two chondroitin sulfotransferases, CHST3 and CHST7, which were decreased in LPS/IFNγ-stimulated macrophages and increased in IL-4-stimulated macrophages. Thus, inflammatory and anti-inflammatory stimuli differentially regulate the chondroitin sulfation of CD44, which is a dynamic physiological regulator of hyaluronan binding by CD44 in mouse macrophages.

Asunto(s)

Sulfatos de Condroitina/metabolismo , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Interleucina-4/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , Animales , Línea Celular Tumoral , Sulfatos de Condroitina/inmunología , Regulación de la Expresión Génica , Humanos , Receptores de Hialuranos/inmunología , Ácido Hialurónico/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interferón gamma/farmacología , Interleucina-4/inmunología , Interleucina-4/farmacología , Lipopolisacáridos/farmacología , Macrófagos/inmunología , Ratones , Ratones Noqueados , Sulfotransferasas/inmunología , Sulfotransferasas/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Carbohidrato Sulfotransferasas

RESUMEN

We report a rare case of multiple myeloma presenting with native aortic valve endocarditis with secondary embolic mycotic abdominal aortic aneurysm, contiguous paraspinal and iliopsoas abscesses, and pneumonia due to Streptococcus pneumoniae in a Chinese man. He was treated with aortic valve replacement, endovascular stenting of aneurysm, image-guided drainage of abscesses, and a 6-week course of endocarditic antibiotic therapy followed by chronic suppressive antibiotic therapy. Cases of multiple myeloma presenting with invasive pneumococcal infection were reviewed.

Asunto(s)

Aneurisma de la Aorta Abdominal/diagnóstico , Endocarditis Bacteriana/diagnóstico , Hongos/aislamiento & purificación , Mieloma Múltiple/diagnóstico , Infecciones Neumocócicas/diagnóstico , Absceso del Psoas/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Antibacterianos/administración & dosificación , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/terapia , Válvula Aórtica/patología , Pueblo Asiatico , Drenaje , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/terapia , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Infecciones Neumocócicas/complicaciones , Infecciones Neumocócicas/patología , Infecciones Neumocócicas/terapia , Neumonía Neumocócica/complicaciones , Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/patología , Neumonía Neumocócica/terapia , Absceso del Psoas/complicaciones , Absceso del Psoas/patología , Absceso del Psoas/terapia , Stents

RESUMEN

CD44 is expressed on T cells where its ability to bind hyaluronan is tightly regulated. Here, we investigated when T cells bind hyaluronan during an immune response. We found that naïve, murine T cells do not bind fluoresceinated hyaluronan but are induced to bind upon antigen-induced T-cell activation in vitro and in vivo. Hyaluronan binding occurred on proliferating T cells and the percentage of hyaluronan-binding cells correlated with the strength of the activation stimulus. A small percentage of hyaluronan-binding cells persisted after in vitro activation and had a memory phenotype (CD122(+) CD44(hi)). This hyaluronan-binding population increased after culture with IL-7 or IL-15 and proliferated more rapidly than nonbinding cells. In vivo, approximately 20-30% of antigen-specific OT-I CD8(+) memory T cells in the spleen and BM bound hyaluronan. Hyaluronan binding identified memory cells that proliferated faster in IL-7 and IL-15, and enriched for CD62L(+) central memory cells. In vivo homeostatic proliferation induced hyaluronan binding on a small percentage of the most rapidly dividing cells after several cell divisions. This study demonstrates that hyaluronan binding is induced upon antigen-induced T-cell activation and occurs on a percentage of the most proliferative activated and memory T cells.

Asunto(s)

Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Proliferación Celular , Ácido Hialurónico/inmunología , Memoria Inmunológica , Activación de Linfocitos , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Homeostasis , Ratones , Ratones Endogámicos C57BL

RESUMEN

Iliopsoas abscess is usually secondary to the spread of infection from a contiguous focus. Primary disease is uncommon, except in children where Staphylococcus aureus is the main pathogen. We report a 60-year-old woman who developed a primary iliopsoas abscess as a result of haematogenous spread of Capnocytophaga sputigena from a palatal fistula and chronic sinusitis due to previous treatment for nasopharyngeal carcinoma. Pyomyositis due to unusual and fastidious Gram-negative bacilli should be considered in patients with head and neck tumours who have previously received radiotherapy.

Asunto(s)

Capnocytophaga/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/diagnóstico , Sinusitis Maxilar/complicaciones , Neoplasias Nasofaríngeas/complicaciones , Absceso del Psoas/microbiología , Femenino , Fístula/complicaciones , Fístula/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Sinusitis Maxilar/microbiología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/terapia , Pelvis/diagnóstico por imagen , Radiografía Abdominal , Tomografía Computarizada por Rayos X

RESUMEN

In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.

Asunto(s)

Ciclosporinas/uso terapéutico , Enfermedades Renales/parasitología , Prednisolona/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Adulto , Antígenos Helmínticos/análisis , Quimioterapia Combinada , Femenino , Humanos , Enfermedades Renales/tratamiento farmacológico , Masculino , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

Twenty-one patients with schistosomal-specific nephropathy (18 nephrotics and three with non-nephrotic proteinuria) were given anti-schistosomal treatment (oxamniquine and praziquantel). The schistosomal specificity of the kidney lesions was assessed by the detection of schistosomal-specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. After anti-schistosomal treatment, the patients were followed for clinical and laboratory changes occurring within 12 months. In addition, 15 patients had a second kidney biopsy and the histopathological and the immunopathological findings were compared with those observed in the first biopsy. Based on clinical, laboratory and histopathological evaluations, none of the patients subjected to the study showed regression of the kidney lesion following antischistosomal treatment; in fact three patients showed progression in their lesions, one of them reaching end-stage renal failure. The histopathology of these three cases was focal segmental glomerulosclerosis. Our data suggest that anti-schistosomal treatment in an established disease state, will not produce remission.

Asunto(s)

Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Nitroquinolinas/uso terapéutico , Oxamniquina/uso terapéutico , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Adulto , Anticuerpos Antihelmínticos/análisis , Antígenos Helmínticos/análisis , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/patología , Glomeruloesclerosis Focal y Segmentaria/etiología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Masculino , Esquistosomiasis mansoni/patología

RESUMEN

In this work 42 patients with active Schistosoma mansoni infection and renal involvement were examined. Of these, 16 had asymptomatic proteinuria (group I) and 26 had the nephrotic syndrome (group II). Fifteen nonschistosomal patients with idiopathic nephrotic syndrome were included as control cases (group III). Renal biopsy specimens were obtained from all patients and controls. These were examined by light microscopy (LM), by direct immunofluorescence microscopy using antisera against human IgG, IgM, IgA, C3, C4, C1q, and fibrinogen, and by indirect immunofluorescence microscopy using monoclonal antibodies directed against the circulating schistosome antigens, circulating anodic antigen (CCA) and circulating cathodic antigen (CCA). Schistosomal-specific deposits were seen in the renal glomeruli in 24 of the 42 schistosomal patients but in none of the 15 control patients. Although schistosomal-specific deposits were seen in seven of the 16 patients presenting with asymptomatic proteinuria, no morphological changes could be seen by LM. On the other hand, schistosomal-specific deposits could be seen in the kidneys of 17 of the 26 patients presenting with the nephrotic syndrome. All but one specimen showed morphological changes when examined by LM. These were consistent with mesangioproliferative glomerulonephritis in seven, focal segmental glomerulosclerosis in five, mesangiocapillary glomerulonephritis in two, membranous glomerulonephritis in one, and focal segmental hyalinosis in one patient. The present study clearly suggests that (a) schistosomal-specific nephropathy does exist in human settings, (b) it is an immune complex disease, and (c) CAA and CCA are major responsible antigens.

Asunto(s)

Enfermedades Renales/patología , Riñón/patología , Esquistosomiasis/patología , Adolescente , Adulto , Antígenos Helmínticos/análisis , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Enfermedades Renales/inmunología , Glomérulos Renales/parasitología , Masculino , Síndrome Nefrótico/patología , Proteinuria/patología , Esquistosomiasis/inmunología