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Introduction: IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD). Methods: We conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD. Results: The mean age at biopsy (n = 120) or nephrectomy (n = 5) was 63 years; 80% were male. One hundred eighteen patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). Fifty-two percent patients (41/79) had abnormal radiographic findings, including masses in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extrarenal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dl (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. Ninety-two percent of patients showed increased IgG4+ plasma cells. Seven percent showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response. Conclusion: This largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD.
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INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.
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Apoptosis , Proliferación Celular , Proteínas Cromosómicas no Histona , Regulación Neoplásica de la Expresión Génica , Ribonucleósido Difosfato Reductasa , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Proliferación Celular/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Ribonucleósido Difosfato Reductasa/genética , Ribonucleósido Difosfato Reductasa/metabolismo , Línea Celular Tumoral , Apoptosis/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Progresión de la Enfermedad , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms.
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Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/uso terapéutico , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/uso terapéutico , Neoplasias/radioterapia , Neoplasias/tratamiento farmacológico , Enzimas Desubicuitinizantes/metabolismo , Tolerancia a RadiaciónRESUMEN
BACKGROUND: Lithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare. CASE PRESENTATION: We herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started. CONCLUSION: Based on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Nefritis Intersticial , Nefrosis Lipoidea , Anciano , Humanos , Litio , Compuestos de Litio , Masculino , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/diagnósticoRESUMEN
BACKGROUND: In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis. METHODS: We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared. RESULTS: Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003). CONCLUSIONS: The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.
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Glomerulonefritis Membranosa/metabolismo , Nefritis Lúpica/metabolismo , N-Acetilglucosaminiltransferasas/metabolismo , Adulto , Biomarcadores/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Fenotipo , Estudios RetrospectivosRESUMEN
Death with a functioning graft and death-censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5-year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m2 ) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5-year biopsies, moderate-to-severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1-year post-transplant. Moderate-to-severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death-censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow-up post-transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.
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Diabetes Mellitus Tipo 2 , Trasplante de Riñón , Diabetes Mellitus Tipo 2/etiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo , Resultado del TratamientoAsunto(s)
Lesión Renal Aguda , Biopsia/métodos , COVID-19 , Riñón/patología , Proteinuria , Insuficiencia Renal Crónica , SARS-CoV-2/aislamiento & purificación , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Lesión Renal Aguda/virología , Población Negra/estadística & datos numéricos , COVID-19/etnología , COVID-19/patología , COVID-19/fisiopatología , Femenino , Humanos , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Proteinuria/diagnóstico , Proteinuria/etiología , Proteinuria/virología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/patología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estados UnidosRESUMEN
The association of fibrillary glomerulonephritis (FGN) with monoclonal gammopathy has been controversial, although monotypic FGN is currently classified as a monoclonal gammopathy of renal significance (MGRS) lesion. To define this lesion, we correlated findings by immunofluorescence on frozen and paraffin tissue, IgG subtype staining and serum protein electrophoresis with immunofixation in patients with monotypic FGN. Immunofluorescence was performed on paraffin sections from 35 cases of DNAJB9-associated FGN that showed apparent light chain restriction of glomerular IgG deposits by standard immunofluorescence on frozen tissue. On paraffin immunofluorescence, 15 cases (14 lambda and one kappa restricted cases on frozen tissue immunofluorescence) showed no light chain restriction, 19 showed similar light chain restriction, and one was negative for both light chains. Seven of the 15 cases with masked polyclonal deposits also had IgG subclass restriction and these cases would have been diagnosed as a form of monoclonal protein-associated glomerulonephritis if paraffin immunofluorescence was not performed. Monotypic FGN (confirmed by paraffin immunofluorescence and IgG subclass restriction) accounted for only one of 151 (0.7%) patients with FGN encountered during the last two years. Only one of 11 of cases had a detectable circulating monoclonal protein on serum protein electrophoresis with immunofixation. We propose that paraffin immunofluorescence is required to make the diagnosis of lambda-restricted monotypic FGN as it unmasked polytypic deposits in over half of patients. When confirmed by paraffin immunofluorescence and IgG subclass staining, DNAJB9-positive monotypic FGN is very rare and is not associated with monoclonal gammopathy in the vast majority of patients. Thus, there is a question whether this lesion should be included in MGRS-related diseases.
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Glomerulonefritis , Gammopatía Monoclonal de Relevancia Indeterminada , Paraproteinemias , Glomerulonefritis/diagnóstico , Proteínas del Choque Térmico HSP40 , Humanos , Inmunoglobulina G , Glomérulos Renales , Proteínas de la Membrana , Chaperonas Moleculares , Paraproteinemias/complicaciones , Paraproteinemias/diagnósticoRESUMEN
Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.
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Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Riñón/patología , Síndrome Nefrótico/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Captura por Microdisección con Láser/estadística & datos numéricos , Masculino , Espectrometría de Masas/estadística & datos numéricos , Persona de Mediana Edad , Síndrome Nefrótico/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Estados UnidosRESUMEN
INTRODUCTION: Previous investigations have studied the importance of imprint cytology (IC) testing of core needle biopsy (CNB) from various organs. We have presented the largest series, to the best of our knowledge, of IC testing of CNB for patients with kidney tumors. MATERIALS AND METHODS: The present retrospective study (January 1, 2015, through January 30, 2016) identified laboratory information through a computer search of the cytology archived reports for 200 consecutive IC testing with CNB for renal tumors cases. A board-certified cytopathologist and cytology-trained fellow reviewed the IC testing and CNB slides and rendered them as nondiagnostic, positive for malignancy, negative for malignancy, positive for neoplasm, or atypical. The tumors were graded using the International Society of Urological Pathology grading system. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: The IC testing cases classified as atypical (n = 53) or positive for neoplasm (n = 28) were evaluated separately because of the ambiguous morphologic characteristics. Of the other 119 cases, IC testing classified 95 (80%) as positive for malignancy, 5 (4%) as negative for malignancy, and 19 (16%) as nondiagnostic. The corresponding CNB histologic diagnoses showed that 85 of 95 cases (89%) were true positive for malignancy. Of these 85 cases, 45 (53%) were low grade, 21 (25%) were high grade, and 19 (22%) were ungraded. The corresponding sensitivity, specificity, and accuracy were 85%, 11%, and 58%, respectively. The 53 IC-identified atypical cases were more likely to be malignant (n = 40; 75%). Of the remaining IC testing atypical cases, 12 (23%) were negative for malignancy and 1 (2%) was nondiagnostic. Of the 28 cases positive for neoplasm using IC, 13 (46%) were positive and 15 (54%) were negative for malignancy. CONCLUSIONS: The relatively low diagnostic value of IC testing for renal tumors showed it to be less powerful for screening than its use in other organs.
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Carcinoma/patología , Neoplasias Renales/patología , Anciano , Biopsia con Aguja Gruesa/normas , Carcinoma/clasificación , Errores Diagnósticos , Femenino , Humanos , Neoplasias Renales/clasificación , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) has been recognized as a distinct entity in recent years. To the best of our knowledge, all patients with PGNMID reported thus far were older than 20 years of age. We now report five cases of PGNMID in patients under 20 years of age. METHODS: The clinical database was searched for patients with native kidney biopsies from 9/2011 to 8/2017, and cases with a diagnosis of PGNMID were retrieved. Light microscopy specimens and immunofluorescence and electron microscopy images were revisited. Clinical data and kidney biopsy findings for patients under the age of 20 were recorded. RESULTS: Five (0.78%) of a total of 637 patients younger than 20 with native renal biopsies had a diagnosis of PGNMID, including three males and two females with an average age of 14 years old (range 10-19). All five patients presented with microscopic hematuria and proteinuria. Three patients were nephrotic and their C3 levels were low. All five cases showed a membranoproliferative pattern with abundant mesangial and subendothelial monoclonal IgG3 deposits (3 κ and 2 λ light chain, respectively). The patients were followed up to 56 months. Two patients had re-biopsies 28 and 18 months after initial diagnosis and both showed similar morphologic changes. Various treatments were attempted including prednisone, mycophenolate mofetil, tacrolimus, rituximab, and eculizmab, with mixed responses. CONCLUSIONS: PGNMID does occur in children and young adults. Membranoproliferative glomerulonephritis pattern with monoclonal IgG3 deposits is a common feature. Despite various immunosuppressive treatments, the disease appears slowly progressive.
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Anticuerpos Monoclonales/inmunología , Glomerulonefritis Membranoproliferativa/inmunología , Inmunoglobulina G/inmunología , Inmunosupresores/uso terapéutico , Adolescente , Adulto , Edad de Inicio , Anticuerpos Monoclonales/análisis , Biopsia , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/patología , Humanos , Inmunoglobulina G/análisis , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether supplementation with lutein improved visual function in patients with nonproliferative diabetic retinopathy (NPDR). METHODS AND STUDY DESIGN: In this randomized, double-blind, placebo-controlled trial, 31 patients with NPDR were assigned randomly to 10 mg/d of lutein or identical placebo for 36 weeks. Visual performance indices, including visual acuity (VA), contrast sensitivity (CS) and glare sensitivity (GS) at four different spatial frequencies, were measured at baseline, week 18 and 36. RESULTS: At 36 weeks, a slight improvement in VA was found in the lutein group. A significant association was observed between the changes in VA and the corresponding baseline values in treatment group (r=-0.53; p=0.04). At 36 weeks, the lutein treatment group increased CS at four spatial frequencies, and the improvement achieved statistical significance at 3 cycles/degree (p=0.02). The changes in CS at 3 cycles/degree for the lutein group was marginally significantly greater than those for the placebo group (p=0.09). There was also a slight increase in GS in the lutein group up to week 36, however, no significant changes were found over time in any cycles/degree. CONCLUSIONS: In patients with NPDR, supplementation with lutein resulted in potential improvements in CS at low spatial frequency. Further studies are required to determine the possibility that such intervention could be used as an adjunct therapy to prevent vision loss in diabetic patients.
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Retinopatía Diabética/tratamiento farmacológico , Luteína/administración & dosificación , Agudeza Visual/efectos de los fármacos , Anciano , Sensibilidad de Contraste , Retinopatía Diabética/fisiopatología , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , PlacebosRESUMEN
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood.
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Inmunoglobulina G/inmunología , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/inmunología , Diagnóstico Diferencial , Humanos , Inmunoglobulina G/sangre , Imagen por Resonancia Magnética , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/patología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: Spindle cell lipomas (SCLs) are benign lipomatous neoplasms that classically arise in the posterior neck, upper back, and shoulders of older male patients. We sought to characterize the occurrence of this entity at nonclassic sites. METHODS: All cases of SCL arising at atypical sites were retrieved from our archives. RESULTS: Of 439 total cases of SCL, 57 arose at atypical locations in 32 men and 25 women (age range, 27-79 years). The tumor sites included leg (n = 23), buttock/perineum/inguinal (n = 10), forearm (n = 9), finger (n = 9), foot (n = 2), toe (n = 2), hand (n = 1), and flank (n = 1). CD34 was positive staining in all cases tested (52/52), while desmin was negative in most tumors (48/50). Thirty-eight of 38 cases tested exhibited loss of Rb expression. No cases showed CPM/MDM2 amplification (0/48). No local recurrences have been reported (n = 39). CONCLUSIONS: SCLs may arise in the trunk, lower extremities, and distal upper extremities. While most SCLs arising in classic sites occur in male patients, there is a relatively equal sex distribution in tumors at atypical sites. Pathologists should be aware that SCLs arise at atypical locations to avoid misclassification as other lipomatous neoplasms, including atypical lipomatous tumor.
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Nalgas/patología , Pie/patología , Antebrazo/patología , Pierna/patología , Lipoma/patología , Neoplasias de los Tejidos Blandos/patología , Torso/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica , Lipoma/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
BACKGROUND: Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. METHODS AND RESULTS: Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery. After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion results. Arteriole density and wall motion abnormalities improved in the cells+matrix group. There was also a strong trend toward an improvement in ejection fraction (P=0.07). CONCLUSIONS: In this preclinical swine model of ischemic and hibernating myocardium, the combined delivery of circulating angiogenic cells and a collagen-based matrix restored perfusion, reduced hibernation, and improved myocardial wall motion.
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Biopolímeros , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Micropartículas Derivadas de Células , Circulación Coronaria/fisiología , Aturdimiento Miocárdico/terapia , Función Ventricular Izquierda , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Aturdimiento Miocárdico/diagnóstico , Aturdimiento Miocárdico/fisiopatología , Porcinos , Porcinos Enanos , Resultado del TratamientoRESUMEN
Arsenic (As) is a toxic metalloid existing widely in the environment, and chronic exposure to it through contaminated drinking water has become a global problem of public health. The present study focused on the protective effects of selenium on oxidative damage of chronic arsenic poisoning in rat liver. Rats were divided into four groups at random and given designed treatments for 20 weeks. The oxidative damage of liver tissue was evaluated by lipid peroxidation and antioxidant enzymes. Oxidative stress related genes were detected to reflect the liver stress state at the molecular level. Compared to the control and Na2SeO3 groups, the MDA content in liver tissue was decreased and the activities of antioxidant enzymes were increased in the Na2SeO3 intervention group. The mRNA levels of SOD1, CAT, GPx and Txnrd1 were increased significantly (P<0.05) in the combined Na2SeO3+NaAsO2 treatment group. The expressions of HSP70 and HO-1 were significantly (P<0.05) increased in the NaAsO2 group and reduced in the combined treatment group. The results indicate that long-term intake of NaAsO2 causes oxidative damage in the rat liver, and Na2SeO3 protects liver cells by adjusting the expression of oxidative stress related genes to improve the activities of antioxidant enzymes.