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Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN).Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled.There were 74 cases of IgAN with ATIN,and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶ 1).The two groups were well matched with age,gender,follow-up time,mesangial hypercellularity(M),endocapillaryhypercellularity (E),segmental glomerulosclerosis(S),tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C).The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed.A composite end point,defined as 30％ or 50％ estimated glomerular filtration rate (eGFR)decline and end stage renal disease (ESRD) was used.Renal function and proteinuria during follow-up were observed.Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models.Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled.Serum creatinine [(185.6±83.2) μmol/L vs (146.3 ±69.2) μmol/L,P=0.010] and incidence of acute kidney disease (AKD) (31.1％ vs 5.4％,P ＜ 0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group.Patients in ATIN group received more immunosuppressive treatment (86.5％vs 58.1％,P＜ 0.001).During 1 year after biopsy,mean eGFR increased significantly in IgAN with ATIN group [(39.7+ 14.6) ml· min-1· (1.73 m2)-1 vs (47.2+ 19.9) ml· min-1· (1.73 m2)-1,P=0.017],but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml· min-1· (1.73 m2)-1 vs (59.0±31.7) ml· min-1· (1.73 m2)-1,P=0.567].Median follow-up was 23.0 months in IgAN with ATIN group,and Median follow-up was 30.0 months in IgAN without ATIN group.Incidence of composite end point had no significant differences between two groups.IgAN with ATIN was not the independent risk factor for end point.IgAN patients with ATIN were divided into two groups (with AKD and without AKD),then renal survival rate was higher (Log-rank test,x2=5.293,P=0.021) and the risk for composite end point decreased by 79.2％ (HR=0.208,95％CI 0.046-0.939,P=0.041) in the group with AKD.Conclusions In IgAN,there is a subgroup of patients with the specific pathological phenotype combined with ATIN.Compared with those without AKD,the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2％ decrease.
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Objective To analyze the renal IgG subclasses in special patients whose renal HBsAg and HBcAg are positive, but plasma HBsAg, HBeAg, and HBcAg are negative.Methods Renal IgG subclasses were compared between 14 cases hepatitis-related nephropathy patients(diagnosed by renal biopsy pathology,whose blood hepatitis B antigens were negative) and 18 cases idiopathic membranous nephropathy patients.HBcAg and HBsAg were detected by indirect immunofluorescence assay, IgG, IgG1, 2, 3, 4 were stained by immunofluorescence.Results Renal IgG1-4 deposits were 100％ (14/14), 78.6％ (11/14), 78.6％ (11/14), 100％(14/14) separately in hepatitis B-related nephropathy group, and renal IgG1-4 deposits were 88.9％ (16/18), 5.6％ (1/18), 5.6％ (1/18), and 83.3％ (15/18) in idiopathic membranous nephropathy group.Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group (78.6％ vs 5.6％ ,78.6％ vs 5.6％;P =0.000) , but no significant difference in IgG1 and IgG4 deposit.Conclusion Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group, and may help some in diagnosis.
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<p><b>OBJECTIVE</b>To study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis.</p><p><b>METHODS</b>Five cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy.</p><p><b>RESULTS</b>The glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage.</p><p><b>CONCLUSIONS</b>Collagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.</p>
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Female , Humans , Basement Membrane , Metabolism , Biopsy , Collagen Type III , Genetics , Metabolism , Fluorescent Antibody Technique , Glomerular Mesangium , Metabolism , Immunohistochemistry , Kidney Diseases , Pathology , Kidney Glomerulus , Pathology , Microscopy, Electron , Prognosis , Proteinuria , DiagnosisABSTRACT
Objective To identify the prevalence of different amyloid types in renal biopsies.Methods The renal biopsies of 205 patients diagnosed as renal amyloidosis from January 1990 to December 2011 were reassessed.Immunohistochemistry was performed with a penal of antibodies directed against λ-light chain,κ-light chain,amyloid A,fibrinogen,transthyretin,apolipoprotein A1,and lysozyme.Immune electron microscopy and gene analysis were performed when the results of immunohistochemistry were indeterminate.Results Among 205 patients,190 cases (92.7％) were classified as immunoglobulin light chain amyloidosis (AL),1 (0.5％) case as amyloid A amyloidosis and 1 (0.5％) case as fibrinogen A α-chain amyloidosis.The amyloid types of remaining 13 (6.3％) cases were undetermined.In the AL patients,the distribution of λ and κ was 6.6∶1.Conclusion AL is the most common form of renal amyloidosis in China,with a predominant light chain type of λ.
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Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 ％ (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074％.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.
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ObjectiveTo investigate the clinical and pathological features of patients with anti-glomerular basement membrane(GBM) disease lacking linear IgG deposition along GBM on renal biopsy.Method Ninety-three patients with anti-GBM disease were collected in our hospital from 1991 to 2008,with 40 patients presenting negative linear IgG deposition along GBM on renal biopsy by direct immunofluorescence(group A) and 53 patients presenting classical linear IgG deposition along GBM(group B).The clinical manifestation,pathological presentation and prognosis were compared between two groups.Results Between two groups,there were no significant differences in gender,age,hemoptysis,oliguria or anuria,gross hematuria,proteinuria,anemia,ANCA positivity,level of circulating anti-GBM antibodies,the percentage of crescent formation in glomeruli and patient outcomes(P＞0.05).Patients in group A were diagnosed significantly later than patients in group B(68 d vs 36 d,P=0.013) and serum creatinine was significantly lower at diagnosis(716.0 μmol/L vs 896.8 μmol/L,P=0.027).Direct immunofluorescence was performed on the paraffin-embedded renal sections from four patients in group A,and all of them revealed positive linear IgG deposition along GBM.Conclusions Patients with circulating anti-GBM antibodies but withont IgG deposition along GBM present slower progress of renal injury,but same clinical,pathological and prognostic features as those with classical anti-GBM disease.Serum anti-GBM antibodies should be prescribed earlier to the suspected patients,and the diagnosed patients should be treated with plasmapheresis and extensive immunosuppression to improve prognosis.
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Objective To elucidate the features of clinicopathology and mutation in Fabry disease complicated with thin basement membrane nephropathy (TBMN), and to investigate the kindred. Methods Data of clinicopathology and gene mutation of a female patient of Fabry disease complicated with TBMN admitted to the Department of Nephro]ogy in our hospital were analyzed. Members of her kindred were investigated simultaneously. Results Proband was a 41-year-old Chinese woman who presented syndrome of Fabry disease and TBMN including angiokeratomas, chronic pain, tinnitus, vertigo, left ventricular hypertrophy and nephropathy as proteinuria, microscopic hematuria and hypertension. A percutaneous renal biopsy was performed on the proband, which was consistent with FSGS and vaculization of podocytes by light microscopy.Electron microscopy showed concentric lamellated inclusions in some podocytes. Diffuse thinning of glomerular basement membrane (GBM) with a mean thickness of (216±31) nm was found. The diagnosis of TBMN with suspected Fabry disease was identified. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. One of her sisters only had microscopic hematuria. The activity of α-galacsidase A (α-Gal A )enzyme in the proband and her daughter was 33 units and 75 units respectively (the normal range is 100 to 500 units). They all carried the novel GLA mutation 1208 ins 21 bp and COL4A3 SNP c: 3627G＞A(p:M1209I). While her sister who only had microscopic hematuria just carried the variant of COL4A3 gene-c:3627G ＞A (p:M1209I), and had the normal activity of α-Gal A with no mutation of GLA.Conclusion TBMN should be considered in the patients of Fabry disease with the condition of benign familial hematuria.
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ObjectiveTo investigate the clinicopathological characteristics of non-diabetic renal diseases (NDRD) in the patients with diabetes mellitus.MethodsClinicopatholigical data of 202 patients with diabetes mellitus and NDRD identified by renal biopsy from January 1st,2003 to December 31st,2010 were analyzed retrospectively.All the patients were divided into three groups:the young (≤35 years old),the middle-aged (36-59 years old) and the elder (≥60 years old).Clinicopathological characteristics were compared among 3 groups.ResultsIn the young group (n=33),42.4％ of patients presented as chronic glomerulonephritic syndrome,while 36.4％ as IgA nephropathy for pathology.In the middle-aged group(n=136),35.3％ of patients presented as chronic glomerulonephritic syndrome,27.2％ as nephritic syndrome,17.6％ as chronic renal failure,14.7％ as latent glomerulonephritis,and 5.1％ as acute renal failure,while42.6％ as IgA nephropathy for pathology.In the elder group(n=33),30.3％ of patients presented as nephritic syndrome,30.3％ as chronic renal failure,while 27.3％ as membranous nephropathy for pathology.ConclusionsIn clinical manifestation,young patients are mainly chronic glomerulonephritic syndrome,middle-aged patients are diversified,and elder patients are mainly nephritic syndrome andchronicrenalfailure. Inpathology, youngandmiddle-agedpatientsaremainlyIgA nephropathy,and elder patients are mainly membranous nephropathy.
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ObjectiveTo investigate the clinical significance and histological origin of glomerular epithelial proliferative lesion in patients with focal segmental glomerulosclerosis (FSGS). MethodsSeventy-four patients with idiopathic FSGS hospitalized in Peking University First Hospital from Jan. 2000 to Dec.2005 were enrolled in this study. Patients were classified into two groups according to with or without glomerular epithelial proliferative lesion. Estimation of active and chronic pathological scores was carried out using a semi-quantitative grade system by two pathologists. Clinical and pathological characteristics were compared between two groups. Immunohistochemical studies were performed to analyze the histological origin of glomerular epithelial proliferative lesion. ResultsThirty-one patients with glomerular epithelial proliferative lesion showed shorter interval from presentation to biopsy (P<0.05), higher percentage of nephrotic syndrome (NS) (P<0.05), higher frequency of segmental glomerulosclerosis(P<0.05), higher pathological active scores (P<0.05) and lower pathological chronic scores (P<0.05)as compared to 43 patients without glomerular epithelial proliferative lesion. Twenty-nine patients were followed up and renal survival rate in patients with glomerular epithelial proliferative lesion (39.7%) was significantly lower than that in patients without glomerular epithelial proliferative lesion (83.3%) (P=0.049). The frequency of glomerular epithelial proliferative lesion and the serum creatinine (Scr) level at biopsy were independent predictors of ESRD (OR value was 1.204, 1.008 respectively ). Glomerular epithelial proliferative lesion did not express mature podocyte markers including WT-1 and pedocalyxin, but stained positive for PCNA, PAX-2 and CK-8. ConclusionsGlomerular epithelial proliferative lesion represents the pathological change of acute stage and active lesion of FSGS, and also may be the pathological marker of severe clinical presentation and worse renal survival. Glomerular epithelial proliferative lesion may be derived from proliferation of parietal epithelial proliferation or de-differentiated podocytes.
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Objective To compare the clinicopathological features between two kinds of obesity-related glomerulopathy (ORG). Methods Twenty-three patients with obesity-associated glomerulomegaly (OB-GM) and 22 patients with obesity-associated focal and segmental glomerulosclerosis (OB-FSGS) diagnosed by renal biopsy during 1998 to 2008 in our center were enrolled in this study. A retrospective analysis of clinical and pathological data was carried out. Results (1) All the patients in these two groups were with abdominal obesity. Most of them were middle-aged male. There were no significant differences in gender, age, body mass index and waist circumference between these two groups (P>0.05). The mean course of disease in OB-FSGS group was significantly longer than that in OB-GM group[(21.7±29.7) vs (6.8±9.3) months,P<0.05]. (2) Metabolic syndrome was found in the most patients of these two groups, but there were no significant differences in the levels of serum glucose, triglycerides, HDL-cholesterul, uric acid and blood pressure between them(P>0.05). (3) The 24-hour urinary protein and Ser level in OB-FSGSgroup were significantly higher than those in OB-GM group[(2.49±1.58) vs (0.83±0.87) g/d, P<0.05; (102.09±25.07) vs (87.84±20.63) μmol/L, P<0.05]. The serum albumin level, creatinine clearance and urinary osmotic pressure in the former were significantly lower than those in the latter [(38.67±7.00) vs (44.05±3.55) g/L, P<0.01; (95.78±37.83) vs (128.72±31.20) ml/min, P<0.01; (678.72±91.76) vs (840.69±133.88) mmol/L, P<0.01]. (4) The mean glomerular diameters of both OB-FSGS group and OB-GM group were increased, whose difference was not significant [(204.3±23.1) vs (205.3±14.3) μm, P>0.05]. Conclusion There are significant differences in the mean course of disease, 24-h urinary protein excretion, serum albumin level and renal function between these two different kinds of ORG.
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Objective To investigate the elinicopathoiogical features of Castleman disease with kidney injury. Methods Clinicopathological data of 10 Castleman disease patients with kidney injury from Peking University First Hospital and China-Japan Friendship Hospital were analyzed retrospectively. All the cases received biopsies of lymph node and kidney. Their renal tissues were examined by light microscopy, immunofluorescence and electron microscopy. Results Ten patients were all male with mean age (493:14) years. They presented edema and proteinuria, with mean urinary protein at (2.79±3.56) g/24 h, including one nephrotie syndrome (NS). Hematuria occurred in 8 cases, acute renal insufficiency in 6 cases, hypertension in 4 cases. Most of the patients had fever, fatigue, anorexia, weight loss, increased ESR and CRP, hypergammaglobulinaemia and decreased complements. Other abnormalities included anemia, thrombocytopenia, pleural effusion, hepatomegaly, splenomegaly, hypothyroidism, etc. Two cases demonstrated POEMS syndrome, one presented Sjogren syndrome. The enlargement of multiple cervical, axillary and inguinal lymph nodes were identified in all the patients. The pathological patterns of lymph node were plasma cell type in 4 cases, hyaline-vascular type in 3 cases, and mixed type in 3 cases. Pathological examination of renal biopsy showed thrombotic microangiopathy in 5 cases, crescentic glomerulonephritis in 2 cases, renal amyloidosis, minimal change disease and chronic tubular interstitial nephropathy in 1 case respectively. After immunosupressive reagents or COP therapy, lymph nodes became smaller, systemic symptoms were alleviated, proteinuira was decreased or disappeared, and renal function was recovered in most of patients. Conclusions Castleman disease with kidney injury manifests various symptoms with high prevalence of renal insufficiency and multiple systemic damage. Renal lesions present many patterns of pathological change with a higher frequency of thrombotic microangiopathy. It is necessary to examine the lymph nodes by ultrasound, radiology or biopsy for the patients of renal diseases with multiple systemic symptoms.
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Objective To introduce a case of varicella.zoster virus(VZV)-related glomerulonephritis and encephalitis. Methods The clinical data and renal pathology were analyzed.Associated literatures were reviewed. Results A 15 years old male patient presented nephritic syndrome,nephrotic syndrome and renal dysfunction with reduced serum complement C3 level from the 5th day after he suffered from varicella.The pathological diagnosis of his kidney tissue was endocapillary proliferative glomerulonephritis with podocyte proliferation and severe renal tubular injury by light microscopy.Immunofluorescent and electron microscopic examinations showed "full-house"staining and granular electron-dense deposits in multiple sites.respectively. Furthermore.virus-like particles or/and inclusions could also be seen by electron microscopy and Mann staining light microscopy.Positive varicella-zoster virus (VZV) specific lgM antibody was detected by serum virological test.VZV antigen and RNA transcript were found in glomerular and tubular cells by immunohistochemical staining and in situ hybridization of renal tissues,respectively. The patient had epileptic episodes for many times in his disease course and his brain MRI and electroencephalogram findings accorded with viml encephalitis with secondary epilepsy.So,the diagnosis of VZV-related glomerulonephritis and encephalitis was established. Conclusion This is the first report of VZV-related glomerulonephritis and encephalitis confirmed by serum virology and tissue virology.
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Objective To report the clinicopathological features of 2 cases of nephronophthisis-medullary cystic kidney disease (NPH-MCKD). Methods The clinical data and pathological changes of renal biopsy in two patients of NPH-MCKD from our hospital were analyzed, and associated literatures were reviewed simultanously. The clinicopathological featuresand diagnosis of NPH-MCKD were discussed. Results Two adolescent patients were admitted to our hospital for indolent renal insufficiency, polyuria accompanied by polydipsia as first signs.Urine analysis showed low specific density urine, mild proteinuria, and few formed elements in urinary sediments. The ability of urine concentration and acidification was decreased. Familial history of renal disease and extra-renal lesions were not found. Renal ultrasound presented an increased echogenicity with diminished cortico-meduUary differentiation, and multiple small cysts in renal corticomedullary border were identified in one case by computed tomography. Pathological examination of renal biopsy revealed diffuse tubular interstitial lesion which was characterized by the triad of tubular basement disintegration, tubular atrophy with cyst development, and interstitial fibrosis. Some of glomerular sclerosis occurred. Cyst development at the corticomedullary border of the kidneys was the specific feature of NPH-MCKD. Conclusions Young patients with impaired tubular function should be suspected of NPH-MCKD. Renal ultrasound or computed tomography can provide an important clue. Multiple renal cysts at the corticomedullary border identified by renal biopsy can be a diagnostic indication for NPH-MCKD.
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Objective: To investigate the morphological characteristics and expression of cell cycle regulatory proteins in cellular variants of idiopathic focal segmental glomerulosclerosis (FSGS). Methods: Seventeen cases of cellular variants of FSGS were studied by light microscopy, immunofluorescence (IF), and electron microscopy (EM). The immunohistochemistry and immunoelectron microscopy for the detection of cyclins (cyclin D1, cyclin E, cyclin A, cyclin B1) and cyclin dependent kinase inhibitors (CKIs, including p21, p27, p57) were performed in these cases. Results: The hypertrophy and hyperplasia of epithelial cells overlying sclerotic or collapsed glomerular tufts were the prominent characteristics of cellular variants of FSGS; IF showed segmental deposits of IgM; hyperplastic epithelial cells possessed the features of both podocyte and parietal epithelial cells ultrastructurally. Hyperplastic epithelial cells of cellular lesions showed positive staining for cyclin E, cyclin A, cyclin B1 and p21, and negative staining for cyclin D1, p27 and p57. Conclusion: The hyperplastic epithelial cells in cellular variants of FSGS may be derived from damaged podocytes, which mimic the immature podocytes, re engage the cell cycle to proliferate and form the cellular lesions. The up regulation of cyclins (cyclin E, cyclin A, cyclin B1) concurrent with the loss of CKIs (p27, p57) contributes to the cell cycle regulation of cellular lesions of FSGS.
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Objective:To investigate the relative frequency of idiopathic focal segmental glomerulosclerosis (FSGS) in renal biopsy proven diseases, and its criteria and significance of clinicopathological diagnosis. Methods: We reviewed all the inpatients that were diagnosed by renal biopsies from 1990 to 2001, of whom 65 were identified as idiopathic FSGS. Their histological characteristics were analyzed together with their clinical findings. Results: (1) The incidence of idiopathic FSGS accounted for 2.2% of all the renal biopsies, 3.2% of primary glomerular diseases, and 5.8% of patients with massive proteinuria. (2) The subtypes of idiopathic FSGS were hilar lesion (12.3%), peripheral lesion (23.1%), mixture lesion (60.0%), collapsing lesion (3.1%), and tip lesion (1.5%), which were frequently accompanied by other morphologic variants, such as synechia of Bowman's capsule, podocyte hyperplasia and hypertrophy, segmental endothelial and mesangial proliferation, and interstitial fibrosis, etc. As the sclerotic lesions distributed segmentally and overlapped by other variants, it was difficult to get the correct diagnosis. (3) Most of the patients with segmental endothelial and mesangial proliferation had massive proteinuria. Conclusion: Idiopathic FSGS was not a common glomerular disease in our study. Podocyte lesion, segmental endothelial and mesangial proliferation may play an important role in the formation of segmental sclerosis in idiopathic FSGS.
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Objective: To study the role of hTERT and c myc, P53, ER, PR in endometrial carcinoma carcinogenesis. Methods: The expression of hTERT, c myc mRNA, P53 protein, ER and PR examined by in situ hybridization and immunohistochemistry in 14 cases of endometrial simple hyperplasia, 10 of complex hyperplasia, 8 of atypical hyperplasia and 52 with endometrial carcinoma. Results: (1) The positve rate of hTERT in simple, complex, atypical hyperlasia and carcinoma were 14.3% (2/14), 50.0% (4/8), 80.0% (8/10) and 92.3% (48/52), respectively. The prevalence and intensity of hTERT signal were greater in the carcinomas and atypical hyperplasia than those in simple or complex hyperplasia (P
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Objective: Cellular proliferate inhibition, senescence or apoptosis are induced by telomere shortening through the activation of P53 pathway, but so far, little is known of the mechanism. This study aimed to clarify the molecular regulation of P53 through telomere pathway by the investigation of molecular interaction between P53 and the main telomere associated protein telomeric repeat binding protein 1(TRBP1) in vitro. Methods: Glutathione S-transferase (GST) alone and 4 different human P53-GST fusion proteins were expressed in E. coli. and purified through glutathione Sepharose TM 4B by affinity chromatography, P53s were wild type P53 (1-393), N terminal truncated form P53 2C (95-393), C terminal truncated form P53 N5 (2-293) and single amino acid mutant P53 R175H (175 arginine to histidine). Glutathione Sepharose TM 4B, purified GST alone and P53 fusions were mixed with human breast cancer cell line MCF-7 cellular protein extracts through in vitro binding assay-pull down, the molecular interaction between P53 and TRBP1 were detected by Western blot. Results: SDS-PAGE and Coomassie brilliant blue staining showed that the molecular weights of all the purified proteins were as expected and purities were over 90%. Western blot of TRBP1 showed that both wild type P53 and P53 R175H could bind to TRBP1 of MCF-7 cells, and their binding capacities are similar, whereas GST alone and Glutathione Sepharose TM 4B beads couldn’t. Compared with both of them, the interaction between P53 2C and TRBP1 enhanced dramatically, but between P53 N5 and TRBP1 reduced significantly.Conclusion: P53 can interact with TRBP1 directly and in vitro, C terminus of P53 (293-393) is the structural domain of their interaction. This C terminus domain dependent interaction between P53 and TRBP1 may be related to the cellular activities induced by telomere dynamic changing.
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Objective: To study the relationship between monocyte/macrophage(MC/MP) accumulation and tubulointerstitial fibrosis.Methods: The renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were fed for 25 days. The kidneys were obtained every 5 days by killing the rats. The morphological changes of tubulointerstitial fibrosis were observed by light microscopy with HE,PAS, PASM and Masson staining. Immunohistochemistry and double immunohistochemistry were used to observe MC/MP accumulation and proliferation. In situ hybridization and immunochemistry were used to observe MCP 1 and M CSF expression in experimental renal tissue. The MCP 1 protein expression was inspected by Western blot. All the data were analyzed statistically.Results: The pathological changes of tubulointerstitial fibrosis were typical. There were many MC/MPs accumul sated in the interstitial space at the early stage and some of them were PCNA positive. At the late stage both accumulation and proliferation of MC/MPs were decreased. The portion of monocyte proliferation was high correlated with the MC/MP accumulation. In situ hybridization showed the positive signals of MCP 1 and M CSF were mainly located in the cytoplasm of degenerated tubular epithelium and they were strong at the early stage, weak at the late stage. MCP 1 by immunochemistry and Western blot were consistent with in situ hybridization. The MC/MP accumulation was high correlated with the expression of MCP 1 and tubular epithelium degeneration. The portion of monocyte proliferation was high correlated with the expression of M CSF.Conclusion:There was obvious accumulation of MC/MP at the early stage of tubulointerstitial fibrosis. The accumulation came from infiltration and proliferation which were regulated by degenerated tubular epithelial cells producing MCP 1 and M CSF. MC/MP accumulation was highly correlated with tubular degeneration. MC/MP promoted tubulointerstitial fibrosis and damaged tubular epithelium by secreting a variety of cytokines.
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<p><b>OBJECTIVE</b>To investigate the morphological features, immunohistochemical speciality of the gastrointestinal stromal tumors (GISTs), and its histogenesis as well.</p><p><b>METHODS</b>The morphologic characteristics of GISTs were studied in 65 cases using light microscopy and 17 cases by electron microscopy. The expression of c-kit (CD117), CD34, vimentin, SMA, actin, desmin, S-100 and MBP were detected in all the cases with EnVision trade mark staining.</p><p><b>RESULTS</b>Among 65 cases of GISTs, 46 were spindle cell type, 6 epithelioid cell type and 13 mixture type, equivalent to 85.5% (65 of 76) of all of the mesenchymal tumors of gastrointestinal tract admitted in the same period. The epithelioid cell type tumors composed of mainly the epithelioid cells, predominantly short spindle, oval or round in pattern, with an overall eosinophilic cytoplasm by hematoxylin-eosin stain. Focal cytoplasmic vacuolization was often seen. Sometimes signet-ring like cells and cells with a clear cytoplasm were seen in the epithelioid stromal tumor. The tumor cells arranged in interlacing fascicles forming whorls or sometimes cell clusters. Electronic microscopy showed the presence of interdigitating cell processes, in some areas, synapse-like structure and numerous desmosome-like junctions as well as a few gap junctions and small round neurosecretory granules. There were also abundant intermediate filaments and thin filaments of actin-type with longitudinal condensations (dense bodies). All of the 65 stromal tumors were strongly positive for vimentin (100%), 61 out of 65 tumors positive for CD117 (c-kit) (93.8%) and 51 out of 65 positive for CD34 (78.5%). Some cases also expressed SMA, actin, S-100 and MBP.</p><p><b>CONCLUSIONS</b>GISTs were the most frequent mesenchymal tumor seen in the gastrointestinal tract. Under light microscope, the morphology of stromal tumors looks sometimes like a leiomyoma and Schwannoma. The application of immunohistochemical markers (particularly CD117 and CD34) and ultrastructural study are considered necessary for the differential diagnosis. GISTs may originate from the pluripotential precursor cells like the interstitial cells of Cajal.</p>
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Humans , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Immunohistochemistry , Leiomyoma , Microscopy, Electron , Proto-Oncogene Proteins c-kit , MetabolismABSTRACT
<p><b>OBJECTIVE</b>The clinicopathologic and immunohistochemical features of 11 pseudomyxoma peritonei (PMP) cases were studied to determine pathologic diagnosis, site of origin and prognosis.</p><p><b>METHODS</b>Clinical files of 11 cases of PMP were reviewed with follow up. The changes in mucinous tumors of peritoneum and primary tumors under microscope and immunostaining were reviewed.</p><p><b>RESULTS</b>Eleven cases (8 women, 3 men) are reported. The patients age ranged from 36 to 76 (average 56). One died 2 years after operation, and one case was lost. The remaining 8 cases were alive 1 to 60 months postoperatively. Of the 11 cases, 8 cases had appendiceal mucinous neoplasm of the 11 cases, and 5 women had synchronous ovarian mucinous tumors; colon mucinous adenocarcinoma was present in one case with synchronous ovarian mucinous tumor; simple ovarian mucinous tumors were present in two cases. Immunostainings were consistent on mucinous tumors of appendix, ovary and peritoneum in the same case.</p><p><b>CONCLUSIONS</b>To diagnose the PMP, the type of tumor should be considered whether it is benign, low malignant or malignant. The appendix neoplasm is closely related to PMP. The prognosis depends greatly on the growth speed of the mucinous neoplasm.</p>