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1.
Clin Nucl Med ; 49(7): 672-673, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38739529

RESUMEN

ABSTRACT: Prostate-specific membrane antigen (PSMA) PET/CT is widely used in the evaluation of suspected metastasis for initial definitive therapy and suspected recurrence of prostate cancer. We outline a case report of a 62-year-old man with history of prostate cancer treated with surgery, salvage radiation, and hormonal therapy presenting with rising PSA levels. There was incidental detection of a PSMA-avid subcutaneous abdominal wall mass on PSMA PET/CT study, which was consistent with desmoid fibromatosis on an ultrasound-guided biopsy.


Asunto(s)
Pared Abdominal , Antígenos de Superficie , Glutamato Carboxipeptidasa II , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Masculino , Persona de Mediana Edad , Glutamato Carboxipeptidasa II/metabolismo , Pared Abdominal/diagnóstico por imagen , Pared Abdominal/patología , Antígenos de Superficie/metabolismo , Fibromatosis Agresiva/diagnóstico por imagen , Neoplasias Abdominales/diagnóstico por imagen , Tomografía Computarizada por Rayos X
2.
Clin Nucl Med ; 49(6): 543-545, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38598733

RESUMEN

ABSTRACT: An 85-year-old man with prostate cancer and de novo bone metastases was treated with hormonal therapy with resolution of bone lesions, improved primary disease, and improved serum tumor markers. Although on hormonal therapy, biochemical recurrence prompted performance of 18 F-fluciclovine PET/CT. Fluciclovine PET/CT revealed primary prostate cancer progression with incidental note of avid foci in the colon for which colonoscopy was recommended. Colonoscopy with biopsy was performed with pathology revealing primary colon adenocarcinoma. Before reinitiation of prostate cancer therapy, segmental colon resection was performed with pathology positive for additional sites of colon cancer.


Asunto(s)
Adenocarcinoma , Ácidos Carboxílicos , Neoplasias del Colon , Ciclobutanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Masculino , Adenocarcinoma/diagnóstico por imagen , Neoplasias del Colon/diagnóstico por imagen , Anciano de 80 o más Años , Tomografía Computarizada por Rayos X , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología
3.
Clin Nucl Med ; 49(7): 683-684, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38537209

RESUMEN

ABSTRACT: A 54-year-old man with Gleason 9 prostate cancer with reported nodal and skeletal metastases was referred to us. Outside hospital reports described abnormal left proximal humerus activity on bone scan concerning for metastasis; however, concurrent PSMA PET/CT did not show activity in this lesion. Further review of the PET/CT images revealed characteristic features of enchondroma in the left humeral lesion.


Asunto(s)
Condroma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Tomografía Computarizada por Rayos X , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Condroma/diagnóstico por imagen , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Imagen Multimodal , Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Huesos/diagnóstico por imagen , Huesos/patología
4.
Clin Nucl Med ; 45(2): 125-126, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31789905

RESUMEN

A 59-year-old woman with history of metastatic melanoma, currently on nivolumab, presents for a restaging FDG PET/CT scan. New subcutaneous hypermetabolic foci are seen in bilateral lower extremities, suggestive of recurrent melanoma. She is referred for percutaneous image-guided biopsy for definitive diagnosis of progressive disease. Ultrasound shows the subcutaneous foci to be hyperechoic (fat density), and biopsy of the right thigh nodule shows fat necrosis with no evidence of tumor. Fat necrosis, an immune-related adverse event, can be FDG-avid and mimic malignancy on PET/CT scan.


Asunto(s)
Necrosis Grasa/inducido químicamente , Necrosis Grasa/inmunología , Fluorodesoxiglucosa F18/metabolismo , Nivolumab/efectos adversos , Grasa Subcutánea/patología , Necrosis Grasa/diagnóstico por imagen , Necrosis Grasa/patología , Femenino , Humanos , Biopsia Guiada por Imagen , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Cutáneas/tratamiento farmacológico , Grasa Subcutánea/efectos de los fármacos , Melanoma Cutáneo Maligno
5.
J Nucl Med Technol ; 47(4): 343-344, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31182662

RESUMEN

Waldenström macroglobulinemia is an indolent B-cell lymphoproliferative disorder. When there is involvement of the central nervous system, Waldenström macroglobulinemia is known as Bing-Neel syndrome. We present a case of Bing-Neel syndrome in a patient who presented with confusion and left orbital pain. 18F-FDG PET/CT was utilized in making the diagnosis.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Macroglobulinemia de Waldenström/diagnóstico por imagen , Anciano , Humanos , Masculino , Dolor/complicaciones , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/patología
6.
Pract Radiat Oncol ; 7(2): 120-125, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28274396

RESUMEN

PURPOSE: Evaluation of local tumor progression (LP) has typically been defined by contrast-enhanced computed tomography (CT) imaging after stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (PDAC). The purpose of this study is to determine the benefit of adding 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging to CT for LP assessment of PDAC after SBRT. METHODS AND MATERIALS: We retrospectively reviewed pretreatment, follow-up images, and outcomes of all patients treated with definitive SBRT for unresectable PDAC between December 2002 and December 2015 at our institution. For each patient, we independently analyzed LP both by CT and by FDG-PET criteria, using the Response Evaluation Criteria In Solid Tumors version 1.1 and the FDG-PET Response Evaluation Criteria In Solid Tumors version 1.0, respectively. RESULTS: Among 206 patients treated with definitive SBRT for unresectable PDAC, we identified 30 with LP on follow-up. Four did not undergo follow-up FDG-PET. Median time to LP after SBRT was 7.5 months (range, 2-25 months). Of the 26 patients with LP who had follow-up FDG-PET, 21 were diagnosed by FDG-PET (80.7%), 14 by CT (53.8%), and 9 by both FDG-PET and CT (34.6%). Use of CT alone revealed only 53.8% of cases of LP detected when FDG-PET and CT were combined. The cumulative incidence of LP, based on competing risk of death, at 1 and 2 years after SBRT was 9.6% and 16.7% by CT and 11% and 29.1% by FDG-PET, respectively. CONCLUSION: FDG-PET increases the chance of detecting LP of unresectable PDAC after SBRT and can have an important impact on reported outcomes. We recommend obtaining FDG-PET to assess treatment response when evaluating efficacy of SBRT and taking its use into account when comparing clinical data.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico por imagen , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiocirugia , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/radioterapia , Radiofármacos , Estudios Retrospectivos , Resultado del Tratamiento
7.
Clin Nucl Med ; 40(7): 592-5, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25899598

RESUMEN

The patient is a 44-year-old woman with Crohn's disease, who presented to the ED with abdominal pain. Initial imaging by CT and US showed mild biliary tree dilatation, mild gallbladder distension, and pericholecystic fluid. The cystic and common bile ducts were patent without bile leak on cholescintigraphy. The next day, MRCP revealed free fluid extending from the gallbladder fossa to the right lower quadrant. Subsequently, a repeat cholescintigraphy was performed which was positive for bile leak. This case highlights the use of multiple imaging modalities in assessing abdominal pain, pre-and post-biliary leak.


Asunto(s)
Enfermedades de las Vías Biliares/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Compuestos de Anilina , Femenino , Glicina , Humanos , Iminoácidos , Imagen Multimodal , Compuestos de Organotecnecio , Radiofármacos , Tomografía Computarizada por Rayos X
9.
J Clin Imaging Sci ; 4: 39, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25161808

RESUMEN

OBJECTIVES: To investigate the effects of ambient glucose on quantitative analysis of hepatic tumors on 2-deoxy-2-((18)F)-fluoro-D-glucose ((18)FDG) positron emission tomography (PET) and to establish a method for glucose correction. PATIENTS AND METHODS: Eighty-six patients with hepatic lesions identified on (18)FDG PET/computed tomography (CT) were analyzed. The serum glucose level (Glc) was recorded prior to imaging, and the maximum standardized uptake value (SUV) in the hepatic tumors and the average SUV in normal liver were determined. The inverse relationship of SUV to glucose can be defined as d (SUV)/d (Glc) = g*SUV/(Glc), where g is the glucose sensitivity. Simulations using glucose level from 70 to 250 mg/dl were performed to evaluate the effects of Glc on the maximum SUV of malignant hepatic lesions and normal liver. RESULTS: By logarithmic transformation and linear regression, g for metastasis was significantly higher than that for normal liver (-0.636 ± 0.144 vs. -0.0536 ± 0.0583; P = 0.00092). Simulation studies showed that the SUV in malignant lesions will decrease rapidly when Glc level is >120 mg/dl, while background liver remains relatively constant up to 250 mg/dl. CONCLUSION: The tumor FDG uptake is much more sensitive to ambient glucose level variation than the background liver. Therefore, correction by the glucose sensitivity factor will result in more accurate SUV measurements and make semi-quantitative analysis of (18)FDG PET scans more reliable.

10.
J Nucl Med Technol ; 42(3): 238-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24970898

RESUMEN

Stress injury is a common cause of exercise-induced anterior shin pain. It is important to distinguish between the various causes of stress injury in a timely manner in order to optimize favorable treatment outcomes. Here, we will discuss a case of medial tibial stress syndrome, or shin splints, as one of the causes of shin pain, as well as how to approach shin pain for a successful diagnosis.


Asunto(s)
Síndrome de Estrés Medial de la Tibia/complicaciones , Síndrome de Estrés Medial de la Tibia/diagnóstico por imagen , Dolor/etiología , Carrera , Adolescente , Diagnóstico Diferencial , Femenino , Humanos , Dolor/diagnóstico por imagen , Cintigrafía , Radiofármacos , Medronato de Tecnecio Tc 99m , Tibia/diagnóstico por imagen , Tibia/lesiones
11.
Am J Respir Cell Mol Biol ; 45(1): 111-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20870897

RESUMEN

Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) exert anti-inflammatory effects, we examined the effects of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dose-dependently reduced the IL-1ß-induced release of IL-6 and vascular endothelial growth factor, the TNF-α-induced release of eotaxin and regulated on activation, normal T expressed and secreted (RANTES), and the IL-4-induced release of eotaxin. Rosiglitazone also inhibited the TNF-α-stimulated release of RANTES. Although TZDs are known to activate peroxisome proliferator-activated receptor-γ (PPARγ), these anti-inflammatory effects were not affected by a specific PPARγ inhibitor (GW 9662) or by the knockdown of PPARγ using short hairpin RNA. Troglitazone and rosiglitazone each caused the activation of adenosine monophosphate-activated protein kinase (AMPK), as detected by Western blotting using a phospho-AMPK antibody. The anti-inflammatory effects of TZDs were largely mimicked by the AMPK activators, 5-amino-4-imidazolecarboxamide ribose (AICAR) and metformin. However, the AMPK inhibitors, Ara A and Compound C, were not effective in preventing the anti-inflammatory effects of troglitazone or rosiglitzone, suggesting that the effects of these TZDs are likely not mediated through the activation of AMPK. These data indicate that TZDs inhibit the release of a variety of inflammatory mediators from human ASM cells, suggesting that they may be useful in the treatment of asthma, and the data also indicate that the effects of TZDs are not mediated by PPARγ or AMPK.


Asunto(s)
Antiinflamatorios/farmacología , Cromanos/farmacología , Miocitos del Músculo Liso/metabolismo , Sistema Respiratorio/metabolismo , Tiazolidinedionas/farmacología , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Anilidas/farmacología , Antimetabolitos/farmacología , Asma/tratamiento farmacológico , Asma/genética , Asma/metabolismo , Asma/patología , Células Cultivadas , Citocinas/biosíntesis , Citocinas/genética , Activadores de Enzimas/farmacología , Inhibidores Enzimáticos/farmacología , Técnicas de Silenciamiento del Gen , Humanos , Hipoglucemiantes/farmacología , Mediadores de Inflamación/metabolismo , Metformina/farmacología , Miocitos del Músculo Liso/patología , PPAR gamma/antagonistas & inhibidores , PPAR gamma/genética , PPAR gamma/metabolismo , Pirazoles/farmacología , Pirimidinas/farmacología , Sistema Respiratorio/patología , Ribonucleótidos/farmacología , Rosiglitazona , Troglitazona , Vidarabina/farmacología
12.
Am J Respir Crit Care Med ; 176(7): 650-8, 2007 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-17641156

RESUMEN

RATIONALE: Epidemiologic data indicate an increased incidence of asthma in the obese. OBJECTIVES: To determine whether obese mice exhibit augmented pulmonary responses after allergen sensitization and challenge. METHODS: Lean, wild-type (C57BL/6), obese ob/ob, and obese db/db mice were sensitized to ovalbumin (OVA), and then challenged with aerosolized OVA or phosphate-buffered saline (PBS). Changes in total pulmonary resistance (Rl) induced by intravenous methacholine were measured by forced oscillation. Blood was collected, bronchoalveolar lavage (BAL) was performed, and lungs were harvested for measurement of cytokine expression by real-time reverse transcription-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: OVA challenge increased baseline Rl in ob/ob, but not wild-type, mice, and airway responsiveness was greater in ob/ob than wild-type mice, regardless of the challenge. Compared with PBS, OVA challenge caused an increase in the number of BAL fluid (BALF) cells, an increase in lung Th2 cytokine expression, and an increase in serum IgE. Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wild-type mice, whereas serum IgE levels were elevated significantly more in ob/ob versus wild-type mice. BALF and lung Th2 cytokine expression was not different in ob/ob versus wild-type mice. Airway responsiveness was greater in db/db versus wild-type mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wild-type mice, despite reduced BALF cells in OVA-challenged db/db versus wild-type mice. CONCLUSIONS: These results demonstrate that obesity enhances OVA-induced changes in pulmonary resistance and serum IgE and that these changes are not the result of increased Th2 type airway inflammation.


Asunto(s)
Obesidad/complicaciones , Hipersensibilidad Respiratoria/fisiopatología , Resistencia de las Vías Respiratorias , Animales , Pruebas de Provocación Bronquial , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Broncoconstrictores , Citocinas/metabolismo , Inmunización , Inmunoglobulina E/sangre , Pulmón/patología , Cloruro de Metacolina , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/fisiopatología , Ovalbúmina , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/patología , Células Th2/patología
13.
Am J Respir Cell Mol Biol ; 37(4): 477-84, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17575079

RESUMEN

Interleukin (IL)-1, a proinflammatory cytokine, is expressed in the lung after ozone (O(3)) exposure. IL-1 mediates its effects through the type I IL-1 receptor (IL-1RI), the only signaling receptor for both IL-1alpha and IL-1beta. The purpose of this study was to determine the role of IL-1RI in pulmonary responses to O(3.) To that end, wild-type, C57BL/6 (IL-1RI(+/+)) mice and IL-1RI-deficient (IL-1RI(-/-)) mice were exposed to O(3) either subacutely (0.3 ppm for 72 h) or acutely (2 ppm for 3 h). Subacute O(3) exposure increased bronchoalveolar lavage fluid (BALF) protein, interferon-gamma-inducible protein (IP)-10, soluble tumor necrosis factor receptor 1 (sTNFR1), and neutrophils in IL-1RI(+/+) and IL-1RI(-/-) mice. With the exception of IP-10, all outcome indicators were reduced in IL-1RI(-/-) mice. Furthermore, subacute O(3) exposure increased IL-6 mRNA expression in IL-1RI(+/+), but not IL-1RI(-/-) mice. Acute (2 ppm) O(3) exposure increased BALF protein, IL-6, eotaxin, KC, macrophage inflammatory protein (MIP)-2, IP-10, monocyte chemotactic protein-1, sTNFR1, neutrophils, and epithelial cells in IL-1RI(+/+) and IL-1RI(-/-) mice. For IL-6, eotaxin, MIP-2, and sTNFR1, there were small but significant reductions of these outcome indicators in IL-1RI(-/-) versus IL-1RI(+/+) mice at 6 hours after exposure, but not at other time points, whereas other outcome indicators were unaffected by IL-1RI deficiency. These results suggest that IL-1RI is required for O(3)-induced pulmonary inflammation during subacute O(3) exposure, but plays a more minor role during acute O(3) exposure. In addition, these results suggest that the induction of IL-6 via IL-1RI may be important in mediating the effects of O(3) during subacute exposure.


Asunto(s)
Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ozono/farmacología , Receptores Tipo I de Interleucina-1/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Tipo I de Interleucina-1/deficiencia , Respiración/efectos de los fármacos
14.
J Allergy Clin Immunol ; 118(2): 389-95, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16890763

RESUMEN

BACKGROUND: Epidemiologic data indicate an increased incidence of asthma in the obese. OBJECTIVE: Because serum levels of the insulin-sensitizing and anti-inflammatory adipokine adiponectin are reduced in obese individuals, we sought to determine whether exogenous adiponectin can attenuate allergic airway responses. METHODS: We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet micro-osmotic pumps were implanted in the mice to deliver continuous infusions of buffer or adiponectin (1.0 microg/g/d), which resulted in an approximate 60% increase in serum adiponectin levels. Two days later, mice were challenged with aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours after the last challenge. RESULTS: OVA challenge increased airway responsiveness to intravenous methacholine, bronchoalveolar lavage fluid cells, and T(H)2 cytokine levels. Importantly, each of these responses to OVA was reduced in adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in serum adiponectin levels and a corresponding decrease in adipose tissue adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA expression of each of 3 proposed adiponectin-binding proteins, adiponectin receptor 1, adiponectin receptor 2, and T-cadherin. CONCLUSION: Our results indicate that serum adiponectin is reduced during pulmonary allergic reactions and that adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice. CLINICAL IMPLICATIONS: The data suggest that adiponectin might play a role in the relationship between obesity and asthma.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Hiperreactividad Bronquial/prevención & control , Pulmón/efectos de los fármacos , Neumonía/prevención & control , Adiponectina/sangre , Adiponectina/genética , Adiponectina/farmacología , Tejido Adiposo/metabolismo , Alérgenos/farmacología , Animales , Hiperreactividad Bronquial/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Cadherinas/genética , Cadherinas/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inmunoglobulina E/sangre , Leucocitos/efectos de los fármacos , Pulmón/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/farmacología , Neumonía/inmunología , ARN Mensajero/biosíntesis , Receptores de Adiponectina , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Proteínas Recombinantes/farmacología
15.
Am J Physiol Lung Cell Mol Physiol ; 290(5): L856-65, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16373670

RESUMEN

Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O(3)), an asthma trigger, are increased in obese (ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-R(b)) is required for satiety; mice lacking this receptor (db/db mice) are also substantially obese. Here, wild-type (WT) and db/db mice were exposed to air or O(3) (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O(3)-induced increases in pulmonary resistance and airway responsiveness were also greater in db/db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O(3) exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O(3) was significantly greater in db/db than WT mice. Previously published results obtained in ob/ob mice were similar except for O(3)-induced neutrophils and MIP-2, which were not different from WT mice. O(3) also induced pulmonary IL-1beta and TNF-alpha mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-R(a)) was similar in db/db and WT mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O(3). Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-R(b) but not Ob-R(a), suggest leptin, acting through Ob-R(a), can modify some pulmonary responses to O(3).


Asunto(s)
Pulmón/fisiopatología , Obesidad/fisiopatología , Ozono/toxicidad , Animales , Secuencia de Bases , Líquido del Lavado Bronquioalveolar , Cartilla de ADN , Interleucina-6/fisiología , Leptina/deficiencia , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Ratones Mutantes , Neutrófilos/fisiología , Reacción en Cadena de la Polimerasa , ARN/genética , Fenómenos Fisiológicos Respiratorios/efectos de los fármacos
16.
Am J Respir Cell Mol Biol ; 34(2): 213-8, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16210693

RESUMEN

Th2 cytokines induce the release of vascular endothelial growth factor (VEGF) from cultured human airway smooth muscle cells. The objective of this study was to examine the mechanistic basis for IL-4- and IL-13-induced VEGF release and to determine whether genetic differences are responsible for donor-to-donor variability in VEGF release. We measured VEGF mRNA expression by real-time PCR, mRNA stability using actinomycin D, and promoter activity with a VEGF-promoter luciferase reporter construct. We measured IL-4- and IL-13-induced VEGF release in cells from 21 donors by ELISA, genotyped the cells for common single nucleotide polymorphisms in the IL-4R alpha (Ile50Val, Ser478Pro, and Gln551Arg) and VEGF (-460T/C, -160C/T, -152G/A, +405C/G and +936 C/T) genes, and stratified the data by IL-4R alpha and VEGF genotype. IL-4 and IL-13 increased VEGF release and VEGF mRNA expression. IL-4 also increased mRNA stability but did not affect VEGF promoter activity. There was marked donor-to-donor variability in VEGF release from smooth muscle cells. The presence of Val50, Pro478/Arg551, or the Val50/Pro478/Arg551 IL-4R alpha haplotype had little effect on VEGF release. VEGF genotype at +405 or +936 alone had no effect on VEGF release, whereas cells bearing at least one -460C/-152A/+405G VEGF allele had lower release of VEGF in response to IL-13 or IL-4 than cells with other genotypes. Our data suggest that IL-4 and IL-13 mediate their effects on VEGF expression post-transcriptionally and indicate that polymorphisms in the VEGF, but not the IL-4R alpha, gene affect VEGF release from smooth muscle cells.


Asunto(s)
Interleucina-13/farmacología , Interleucina-4/farmacología , Miocitos del Músculo Liso/metabolismo , Tráquea/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Cultivadas , Dactinomicina/farmacología , Relación Dosis-Respuesta a Droga , Variación Genética , Haplotipos/genética , Humanos , Miocitos del Músculo Liso/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-4/genética , Tráquea/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos
17.
J Allergy Clin Immunol ; 115(3): 514-20, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15753898

RESUMEN

BACKGROUND: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. OBJECTIVE: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. METHODS: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4R alpha, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. RESULTS: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4R alpha mRNA and protein levels. CONCLUSIONS: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4R alpha expression.


Asunto(s)
Quimiocinas CC/metabolismo , Inhibidores de Crecimiento/farmacología , Pulmón/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Péptidos/farmacología , Western Blotting , Quimiocina CCL11 , Quimiocinas CC/inmunología , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/inmunología , Proteínas de Unión al ADN/metabolismo , Sinergismo Farmacológico , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Interleucina-13/inmunología , Interleucina-13/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/inmunología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Liso/inmunología , Músculo Liso/metabolismo , Oncostatina M , Fosforilación , ARN Mensajero/análisis , Receptores de Interleucina-4/efectos de los fármacos , Receptores de Interleucina-4/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3 , Transactivadores/efectos de los fármacos , Transactivadores/inmunología , Transactivadores/metabolismo
18.
J Allergy Clin Immunol ; 115(1): 103-9, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15637554

RESUMEN

BACKGROUND: Epidemiologic data indicate that the incidence of asthma is increased in obese patients. OBJECTIVE: Because the serum levels of the satiety hormone and proinflammatory cytokine leptin are increased in obese individuals, we sought to determine whether leptin can augment allergic airway responses. METHODS: We sensitized and challenged BALB/cJ mice with ovalbumin. Alzet micro-osmotic pumps were implanted in the mice to deliver a continuous infusion of either saline or leptin (1.75 mug/g/d). Two days later, the mice were challenged with either aerosolized saline or ovalbumin once per day for 3 days. We measured airway responsiveness, performed bronchoalveolar lavage, and obtained blood to measure serum leptin and IgE 24 or 48 hours after the last challenge. RESULTS: Leptin infusion increased serum leptin concentrations, which were increased further after ovalbumin sensitization and challenge. Ovalbumin challenge increased bronchoalveolar lavage fluid cells and cytokines, serum IgE, lung cytokine mRNA expression, and responses to inhaled, aerosolized methacholine. It is important to note that the changes in methacholine responsiveness and IgE were augmented in leptin- versus saline-infused mice. CONCLUSIONS: These results indicate that serum leptin is increased during allergic reactions in the airways and may play a role in the relationship between obesity and asthma.


Asunto(s)
Leptina/inmunología , Hipersensibilidad Respiratoria/inmunología , Administración Cutánea , Alérgenos , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/análisis , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina E/sangre , Bombas de Infusión Implantables , Leptina/sangre , Leptina/farmacología , Pulmón/inmunología , Masculino , Cloruro de Metacolina , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , ARN Mensajero/análisis , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/etiología
19.
Am J Physiol Lung Cell Mol Physiol ; 288(6): L1040-8, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15665043

RESUMEN

Vascular endothelial growth factor (VEGF), a potent angiogenesis factor, likely contributes to airway remodeling in asthma. We sought to examine the effects and mechanism of action of IL-6 family cytokines on VEGF release from human airway smooth muscle (HASM) cells. Oncostatin M (OSM), but not other IL-6 family cytokines, increased VEGF release, and IL-1beta enhanced OSM-induced VEGF release. OSM increased VEGF mRNA expression and VEGF promoter activity, whereas IL-1beta had no effect. IL-1beta did not augment the effects of OSM on VEGF promoter activity but did augment OSM-induced VEGF mRNA expression and mRNA stability. The STAT3 inhibitor piceatannol decreased both OSM-induced VEGF release and synergy between OSM and IL-1beta, without affecting responses to IL-1beta alone. Piceatannol also inhibited OSM-induced VEGF mRNA expression. In contrast, inhibitors of MAPK pathway had no effect on OSM or OSM plus IL-1beta-induced VEGF release. OSM increased type 1 IL-1 receptor (IL-1R1) mRNA expression, as measured by real-time PCR, and piceatannol attenuated this response. Consistent with the increase in IL-1R1 expression, OSM markedly augmented IL-1beta-induced VEGF, MCP-1, and IL-6 release. In summary, our data indicate OSM causes VEGF expression in HASM cells by a transcriptional mechanism involving STAT3. IL-1beta also synergizes with OSM to increase VEGF release, likely as a result of effects of IL-1beta on VEGF mRNA stability as well as effects of OSM on IL-1R1 expression. This is the first description of a role for OSM on IL-1R1 expression in any cell type. OSM may contribute to airway remodeling observed in chronic airway disease.


Asunto(s)
Inhibidores de Crecimiento/farmacología , Interleucina-1/farmacología , Pulmón/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Péptidos/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Proteínas de Unión al ADN/antagonistas & inhibidores , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Humanos , Mediadores de Inflamación/farmacología , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmón/citología , Pulmón/metabolismo , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Liso/citología , Músculo Liso/metabolismo , Oncostatina M , Fosforilación/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1 , Factor de Transcripción STAT3 , Transducción de Señal , Estilbenos/farmacología , Transactivadores/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética
20.
Am J Physiol Lung Cell Mol Physiol ; 288(2): L390-7, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15516495

RESUMEN

This study sought to examine the role of interleukin-6 (IL-6) in ozone (O(3))-induced airway injury, inflammation, and hyperresponsiveness (AHR). Subacute (72 h) exposure to 0.3 ppm O(3) significantly elevated bronchoalveolar lavage fluid (BALF) protein, neutrophils, and soluble TNF receptors (sTNFR1 and sTNFR2) in wild-type C57BL/6 (IL-6(+/+)) mice; however, all four outcome indicators were significantly reduced in IL-6-deficient (IL-6(-/-)) compared with IL-6(+/+) mice. Acute O(3) exposure (2 ppm for 3 h) increased BALF protein, KC, macrophage inflammatory protein(MIP)-2, eotaxin, sTNFR1, and sTNFR2 in IL-6(+/+) mice. However, MIP-2 and sTNFR2 were not significantly increased following O(3) exposure in IL-6(-/-) mice. Increases in BALF neutrophils induced by O(3) (2 ppm for 3 h) were also significantly reduced in IL-6(-/-) vs. IL-6(+/+) mice. Airway responsiveness to methacholine was measured by whole body plethysmography before and following acute (3 h) or subacute (72 h) exposure to 0.3 ppm O(3). Acute O(3) exposure caused AHR in both groups of mice, but there was no genotype-related difference in the magnitude of O(3)-induced AHR. AHR was absent in mice of either genotype exposed for 72 h. Our results indicate that IL-6 deficiency reduces airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following acute high dose and/or subacute low-dose O(3) exposure, but has no effect on O(3)-induced AHR.


Asunto(s)
Bronquios/efectos de los fármacos , Bronquios/metabolismo , Hiperreactividad Bronquial/inducido químicamente , Interleucina-6/fisiología , Ozono/farmacología , Animales , Hiperreactividad Bronquial/patología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar/química , Esquema de Medicación , Femenino , Interleucina-6/deficiencia , Interleucina-6/genética , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/patología , Ozono/administración & dosificación , ARN Mensajero/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/química , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/química , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Solubilidad
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