RESUMO
AIMS/HYPOTHESIS: We sought to establish if stem cells contained in cord blood cell allografts have the capacity to differentiate into insulin-expressing beta cells in humans. METHODS: We studied pancreases obtained at autopsy from individuals (n = 11) who had prior opposite-sex cord blood transplants to reconstitute haematopoiesis. Pancreatic tissue sections were stained first by XY-fluorescence in situ hybridisation and then insulin immunohistochemistry. Pancreases obtained at autopsy from participants without cord blood cell infusions served as controls (n = 11). RESULTS: In the men with prior transplant of female cord blood, there were 3.4 ± 0.3% XX-positive insulin-expressing islet cells compared with 0.32 ± 0.05% (p < 0.01) in male controls. In women with prior transplant of male cord blood cells we detected 1.03 ± 0.20% XY insulin-expressing islet cells compared with 0.03 ± 0.03 in female controls (p < 0. 001). CONCLUSIONS/INTERPRETATION: Cord blood stem cells have the capacity to differentiate into insulin-expressing cells in non-diabetic humans. It remains to be established whether these cells have the properties of beta cells.
Assuntos
Sangue Fetal/citologia , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Adolescente , Adulto , Idoso , Diferenciação Celular/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Transplante Homólogo , Adulto JovemRESUMO
A 6-year-old, neutered male Labrador Retriever was diagnosed with congestive heart failure, and an echocardiogram revealed a large mass inside the pericardial sac associated with the left ventricle. At necropsy, the dog had marked ascites, mild hydrothorax, marked hydropericardium, and an 11.0 x 7.0 x 6.0 cm, tan and red, firm, well-demarcated mass attached to the left ventricular free wall. The mass was diagnosed as a fibrosarcoma based on the morphologic appearance and supportive immunohistochemical staining. To our knowledge, this is the first case report of a primary fibrosarcoma involving the left ventricular free wall myocardium, epicardium, and pericardium with a pulmonary metastasis in a dog.
Assuntos
Doenças do Cão/patologia , Fibrossarcoma/veterinária , Neoplasias Cardíacas/veterinária , Neoplasias Pulmonares/veterinária , Animais , Cães , Fibrossarcoma/patologia , Neoplasias Cardíacas/patologia , Neoplasias Pulmonares/secundário , MasculinoRESUMO
AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disorder associated with T-cell mediated injury to multiple endocrine tissues. T-cell infiltration of the juxtaglomerular apparatus could be associated with changes in local renin angiotensin system activity and, thus, with changes in the renal microenvironment. We examined the frequency of juxtaglomerular apparatus T-cell infiltration early in Type 1 diabetes and tested whether this is associated with renal structure and function. METHODS: We classified 89 Type 1 diabetic patients by immunohistochemical analysis as either juxtaglomerular apparatus T-cell positive ( n=37) or T-cell negative ( n=38). Borderline cases ( n=14) were not considered further. RESULTS: T-cell positive patients had a shorter duration of diabetes (6.7+/-2.5 years) than T-cell negative patients (9.2+/-5.0 years, p=0.011) and lower albumin excretion rate, but they had a similar glomerular filtration rate and blood pressure. Renal biopsy morphometric analysis showed similar glomerular basement membrane width and mesangial fractional volume in these two groups. However, glomerular capillary surface density ( p=0.0012) and filtration surface per glomerulus ( p=0.0155) were greater in the T-cell positive patients. CONCLUSION/INTERPRETATION: Increased filtration surface per glomerulus could be associated with glomerular filtration rate preservation in diabetes. Thus, juxtaglomerular apparatus immunologic injury in Type 1 diabetes patients could delay the clinical consequences of diabetic nephropathy.
Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/patologia , Sistema Justaglomerular/patologia , Linfócitos T/imunologia , Adolescente , Adulto , Idade de Início , Pressão Sanguínea , Criança , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular , Humanos , Sistema Justaglomerular/imunologia , Linfócitos T/patologiaRESUMO
Patients often develop nausea, vomiting and bloating after bone marrow transplantation (BMT). These symptoms may interfere with nutrition and the ability to take oral medications. Gastroparesis is a recognized cause of these symptoms in non-transplant patients but less is known about patients who undergo BMT. Between January 1996 and March 1997, a total of 151 patients underwent BMT. Eighteen patients (12%) developed persistent symptoms suggestive of gastroparesis (persistent nausea, vomiting or bloating). Scintigraphic gastric emptying studies were performed to assess for gastroparesis. Prokinetic agents were administered at the time of study. The records on these patients were compared with those of all other patients undergoing BMT during the same time period without these symptoms. Nine patients who demonstrated delayed gastric emptying were further evaluated with esophagastroduodenoscopy and biopsy. Biopsy samples were reviewed for evidence of graft-versus-host disease (GVHD). Fourteen of 18 patients demonstrated delayed gastric emptying and most responded to prokinetic agents given at the time of study. Age, conditioning regimen, cytomegalovirus antigenemia and acute GVHD did not appear to be associated with the development of gastroparesis. Allogeneic BMT recipients were at higher risk than autologous BMT patients (26% vs 0%, P < 0.0001). of allogeneic bmt recipients, there was a nonsignificant trend of patients receiving tacrolimus to be less likely to experience gastroparesis than those receiving cyclosporine (27% vs 48%, P = 0.08). For the nine patients undergoing upper endoscopy, GVHD on gastric biopsy was an uncommon finding and was mild when present. Gastroparesis appears to be a common cause of nausea, vomiting and bloating following allogeneic BMT. This may occur less often with tacrolimus than cyclosporine because of the former agent's prokinetic properties. Patients usually respond to prokinetic drugs at the time of scintigraphy. GVHD and CMV infection do not appear to be major contributing factors.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Gastroparesia/etiologia , Adulto , Antieméticos/administração & dosagem , Antieméticos/farmacologia , Estudos de Casos e Controles , Eritromicina/administração & dosagem , Eritromicina/farmacologia , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/farmacologia , Gastroparesia/diagnóstico , Gastroparesia/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Masculino , Metoclopramida/administração & dosagem , Metoclopramida/farmacologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Doadores de Tecidos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversosRESUMO
Data presented in this report indicate short-term in vitro treatment of nonmetastatic MCF-7 breast carcinoma cells with the chemotherapeutic agents-, Adriamycin and/or 5-fluoro-2'-deoxyuridine (FUdR), induced changes in the expressed phenotype. Cells treated sequentially with Adriamycin and FUdR expressed a metastatic phenotype. The results also show short-term exposure of MCF-7 cells to either Adriamycin or FUdR rapidly increases, in a dose-dependent manner, the release of the angiogenic cytokine, interleukin-8(IL-8), which is released at consistently higher levels in metastatic cell lines. Cell populations surviving a single treatment with either one or both of these chemotherapeutic agents continue to stably release IL-8. Survivors of sequential treatment with Adriamycin and FUdR (MCF-7 A/F) release the most IL-8 and express the greatest phenotypic variance from the parental, MCF-7 cells. Parental MCF-7 cells and MCF-7 A/F cells both form primary tumors when used in an orthotopic tumor model; however, the MCF-7 A/F tumors have a more rapid initial growth phase in situ and give rise to spontaneous lung metastases within 10 weeks. A cell line that is established from lung metastases releases more IL-8, has a higher cloning efficiency, and forms looser colonies in monolayer than do their parental cells. These experiments indicate the in vitro exposure of tumor cells to chemotherapeutic agents either selects more aggressive cells or enhances the metastatic potential of the surviving cells.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Doxorrubicina/efeitos adversos , Floxuridina/efeitos adversos , Animais , Neoplasias da Mama/metabolismo , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Progressão da Doença , Feminino , Humanos , Interleucina-8/metabolismo , Camundongos , Camundongos Nus , Metástase Neoplásica , Fenótipo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologiaRESUMO
This study shows a strong correlation between the metastatic potentials of breast carcinoma cell lines and their ectopic expression of interleukin-8 (IL-8). Correlations exist for both constitutive and induced levels of IL-8 released. A correlation was also observed between cell morphology, metastatic potential, and IL-8 profile. Metastatic lines are fusiform in appearance, whereas, nonmetastatic lines are epithelioid. The metastatic potential of two breast carcinoma lines was examined using an orthotopic model of spontaneous metastasis. Metastatic cells formed rapidly growing, poorly differentiated primary tumors that metastasized. Nonmetastatic cells formed rapidly growing differentiated primary tumors that did not produce detectable metastases. Comparison of IL-8 expression by the parental cells and cell cultures developed from primary and metastatic tumors, demonstrates that IL-8 released by cultured cells from the primary tumor is higher than that of the parental cells, and IL-8 released by cultured cells derived from the metastatic lung tumors is greater than that released by cultured cells derived from the primary tumor. These data demonstrate a strong correlation between the metastatic phenotype of a cell and its IL-8 expression, suggesting a role for IL-8 in promoting the metastatic potential of breast tumor cells.
Assuntos
Neoplasias da Mama/metabolismo , Interleucina-8/metabolismo , Metástase Neoplásica/patologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/genética , Interleucina-8/fisiologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Lung injury is a frequent and severe complication of bone marrow transplantation (BMT). Over the past 5 years we have recognized a new noninfectious pulmonary complication of allogeneic BMT in 12 patients, presenting with fever, pulmonary nodules on chest computed tomography, and distinctive histopathologic appearance descriptively termed "pulmonary cytolytic thrombi" (PCT). All but one patient were children transplanted for malignant (9) and nonmalignant (3) conditions. Ten of the patients had active graft-versus-host disease (GVHD) of skin, bowel, or both at the time of diagnosis of the PCT. In all cases occlusive vascular lesions were present, most of them associated with hemorrhagic infarcts. The endothelial cell layer was discontinuous in all cases stained with antibody to CD31. The thrombi had entrapped recognizable leukocytes and CD45-positive cell fragments embedded in a tenacious basophilic material. The symptoms and radiologic findings resolved in weeks to months. PCT may represent a previously unrecognized form of pulmonary acute GVHD.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Embolia Pulmonar/etiologia , Embolia Pulmonar/patologia , Adolescente , Adulto , Transplante de Medula Óssea/imunologia , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lactente , Pulmão/microbiologia , Masculino , Embolia Pulmonar/microbiologia , Tomografia Computadorizada por Raios XRESUMO
Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p < .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.
Assuntos
Células Epidérmicas , Fator 2 de Crescimento de Fibroblastos/farmacologia , Pele/efeitos da radiação , Retalhos Cirúrgicos , Animais , Procedimentos Cirúrgicos Dermatológicos , Masculino , Oxigênio/análise , Doses de Radiação , Pele/metabolismo , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/patologia , SuínosRESUMO
Activated Ras has been shown to provide powerful antiapoptotic signals to cells through well defined transcriptional and post- translational pathways, whereas translational control as a mechanism of Ras survival signaling remains unexplored. Here we show a direct relationship between assembly of the cap-dependent translation initiation apparatus and suppression of apoptosis by oncogenic Ras in vitro and in vivo. Decreasing protein synthesis with rapamycin, which is known to inhibit cap-dependent translation, increases the susceptibility of Ras-transformed fibroblasts to cytostatic drug-induced apoptosis. In contrast, suppressing global protein synthesis with equipotent concentrations of cycloheximide actually prevents apoptosis. Enforced expression of the cap-dependent translational repressor, the eukaryotic translation initiation factor (eIF) 4E-binding protein (4E-BPI), sensitizes fibroblasts to apoptosis in a manner strictly dependent on its ability to sequester eIF4E from a translationally active complex with eIF4GI and the co-expression of oncogenic Ras. Ectopic expression of 4E-BP1 also promotes apoptosis of Ras-transformed cells injected into immunodeficient mice and markedly diminishes their tumorigenicity. These results establish that eIF4E-dependent protein synthesis is essential for survival of fibroblasts bearing oncogenic Ras and support the concept that activation of cap-dependent translation by extracellular ligands or intrinsic survival signaling molecules suppresses apoptosis, whereas synthesis of proteins mediating apoptosis can occur independently of the cap.
Assuntos
Apoptose/fisiologia , Proteínas de Transporte , Transformação Celular Neoplásica , Regulação da Expressão Gênica , Genes ras , Fatores de Iniciação de Peptídeos/metabolismo , Fosfoproteínas/metabolismo , Biossíntese de Proteínas , Proteínas ras/genética , Proteínas ras/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Ciclo Celular , Linhagem Celular Transformada , Clonagem Molecular , Cicloeximida/farmacologia , Fator de Iniciação 4E em Eucariotos , Fatores de Iniciação em Eucariotos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Nus , Biossíntese de Proteínas/efeitos dos fármacos , Ratos , Transdução de Sinais , Sirolimo/farmacologia , TransfecçãoRESUMO
A 2.5-year-old female Thoroughbred was examined because of lethargy, anorexia, and weight loss. Analysis of a CBC revealed erythrocytosis and an increase in PCV. Serum biochemical analysis revealed increases in activities of several hepatic enzymes. Ultrasonography revealed hepatomegaly and a heterogeneous appearance of the hepatic parenchyma. The horse did not improve despite supportive care, and it was euthanatized. Necropsy revealed numerous raised white to gray foci in the liver. Histologically, these foci consisted of neoplastic cells that resembled fetal hepatocytes, embryonal-type cells, and cells with features intermediate between those 2 cell types. Immunohistochemical staining revealed that hepatocytes stained strongly with anti-alpha-fetoprotein. On the basis of these results, hepatoblastoma was diagnosed. Diagnosis of hepatoblastoma is difficult, because it can appear histologically similar to other hepatic tumors, such as hepatocellular carcinomas. Definitive diagnosis requires histologic evaluation of tumor architecture and cell morphology. Immunohistochemical staining for alpha-fetoprotein in tumor cells may serve as a tumor marker but is not pathognomonic of hepatoblastoma. Paraneoplastic syndromes, such as erythrocytosis, can accompany hepatoblastoma. The prognosis for horses with hepatoblastoma is grave.
Assuntos
Hepatoblastoma/veterinária , Doenças dos Cavalos/diagnóstico , Neoplasias Hepáticas/veterinária , Síndromes Paraneoplásicas/veterinária , Policitemia/veterinária , Animais , Diagnóstico Diferencial , Evolução Fatal , Feminino , Hepatoblastoma/diagnóstico , Cavalos , Neoplasias Hepáticas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Policitemia/etiologia , PrognósticoRESUMO
Colonic carcinomas with minimal or no glandular differentiation are a heterogeneous group of neoplasms which differ in their histologic appearance, clinical features, prognosis and molecular characteristics. Since 1990, we prospectively identified 11 patients with a predominantly solid (nonglandular) adenocarcinoma of the colon for which the term medullary adenocarcinoma of the colon (MAC) is proposed. The clinical, histological, histochemical, and immunohistochemical features of these neoplasms were studied. All patients with MAC were women with tumors in the cecum or proximal colon. Histological analysis showed nests or trabeculae of regular small to medium-sized cells with moderate amounts of eosinophilic cytoplasm; some cells contained mucin vacuoles. The nuclei had an open chromatin pattern and exhibited prominent nucleoli. Lymphatic permeation was present in most cases. Immunohistochemical reactions were positive for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen. Despite its histological resemblance with endocrine tumors, MAC is negative for endocrine markers. Of the eight patients for whom follow-up is available, four patients (two Dukes B and two Dukes C) are alive and well 1 to 4 years after surgery, one patient (Dukes C) died of tumor, one patient is alive with liver metastasis 4 years after surgery, and two patients died in the postoperative period. MAC appears to be a distinctive clinicopathologic entity. This tumor should be distinguished from other more aggressive, nonglandular tumors of the colon.
Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Estudos Prospectivos , Terminologia como AssuntoRESUMO
OBJECTIVE: To determine the vascular and collagen effects of supplemental basic fibroblast growth factor (bFGF) in irradiated porcine skin flaps. INTERVENTION: Animals were subjected to 2 fractions of 650 cGy orthovoltage radiation. Following this, the skin flaps were administered bFGF intracuticularly for 6 days before and after surgery. The animals were sacrificed 3 weeks after the start of bFGF administration. Tissues were analyzed for vascularity, collagen content, wound-breaking strength, and histopathological analysis. RESULTS: The bFGF-treated flaps showed a 62% increase in vascularity compared with controls (10.4%+/-2.4% vs 6.43%+/-2.27%; P<.05). The bFGF flaps had a significantly lower collagen concentration compared with control flaps when measured by hydroxyproline content (0.0619+/-0.0211 nm/microg vs 0.0784+/-0.0150 nm/microg). Wound-breaking strength was not significantly different, although the bFGF flaps had a trend toward lower breaking strength. Histologically, the bFGF-treated flaps showed increased cellularity, fibroblasts, and extracellular mucopolysaccharides compared with controls. CONCLUSIONS: This study provides evidence that supplemental bFGF can increase vascularity to skin flaps in previously irradiated porcine skin tissue. Histologically, radiation did not prevent the angiogenic effect of bFGF.
Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Pele/efeitos da radiação , Retalhos Cirúrgicos/patologia , Animais , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/patologia , Retalhos Cirúrgicos/irrigação sanguínea , SuínosRESUMO
Clusterin, a glycoprotein with potent cellular cohesive properties, is induced in many organs at times of tissue injury or remodeling. After renal infarction, for example, clusterin is localized to tubular epithelial cells in the peri-infarct zone. The purpose of this study was to examine the spatial and temporal expression of cardiac clusterin after myocardial infarction. Sprague-Dawley rats underwent permanent coronary ligation or sham operation. Hearts were harvested at 6 hours and at 2, 14, and 28 days after infarction. Cardiac clusterin expression was examined by immunohistochemistry and in situ hybridization. Left ventricular clusterin staining was evident at 6 hours and 2 days after myocardial infarction, although not at later time periods. Clusterin was localized to peri-infarct zone myocytes and endothelial cells of this region, and local synthesis of clusterin by myocytes was confirmed by in situ hybridization. Clusterin was not present in inflammatory cells or in left ventricular tissue distant from the infarct. The distribution of clusterin was different from the membrane attack complex of complement (C5b-9), with the latter being present diffusely throughout the infarct zone. Although the role of cardiac clusterin is not known, we speculate that clusterin's cohesive properties serve to promote myocyte interactions that are perturbed in the peri-infarct zone after myocardial infarction.
Assuntos
Glicoproteínas/metabolismo , Chaperonas Moleculares , Infarto do Miocárdio/metabolismo , Animais , Clusterina , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Técnicas Imunoenzimáticas , Hibridização In Situ , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in > or =5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type III: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist's diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of > or =1 tubule with tubulitis and > or =5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P < 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P > 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection.
Assuntos
Rejeição de Enxerto/diagnóstico , Transplante de Rim/patologia , Rim/patologia , Transplante Homólogo/patologia , Doença Aguda , Adolescente , Adulto , Idoso , Biópsia por Agulha , Feminino , Rejeição de Enxerto/classificação , Rejeição de Enxerto/patologia , Humanos , Inflamação , Córtex Renal/patologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Pleuropulmonary blastoma (PPB) is a unique dysontogenetic neoplasm of childhood that appears as a pulmonary and/or pleural-based mass and is characterized histologically by a primitive, variably mixed blastematous and sarcomatous appearance. METHODS: Histologic material from all cases was reviewed and the tumors subclassified as type I (purely cystic), type II (cystic and solid), or type III (purely solid). Data regarding presenting symptoms, family history, operative findings, pathologic subtypes, therapeutic interventions, and outcome were correlated with survival by standard statistical methods. RESULTS: The series was comprised of 24 males and 26 females. Respiratory difficulty with or without fever was the most common clinical symptom reported. Cyst formation in the affected lung was identified radiographically in 19 children (38%) at or before the definitive pathologic diagnosis. The ages at presentation of the 7 type I, 24 type II, and 19 type III PPBs were significantly different: 10, 34, and 44 months, respectively (P < 0.001). Local recurrence developed in 1 of 7 type I PPBs (14%) and in 18 of 43 type II and III PPBs (46%); distant metastasis occurred in 13 patients, chiefly to the brain/spinal cord or bone, and was observed only in those with type II or type III PPB. Patients with pleural or mediastinal involvement fared significantly worse than those without such involvement. Five-year survival was 83% for type I and 42% for types II and III. Survival differences on the basis of pathologic subtype did not reach statistical significance. CONCLUSIONS: PPB is an aggressive, intrathoracic neoplasm of early childhood with an unfavorable outcome. Although survival differences among patients with different histologic subtypes of disease did not reach statistical significance, the apparently better outcome for patients with purely cystic type I tumors may be borne out in a large series. These observations support the premise that type I and III PPB are bridged morphologically by type II PPB with its combined cystic and solid features. The PPB should be regarded as the pulmonary dysontogenetic analogue to Wilms' tumor in the kidney, neuroblastoma in the adrenal gland, and hepatoblastoma in the liver. Molecular genetic investigations, especially in constitutional PPB, should be revealing. In view of the poor outcomes for patients with types II and III, new and aggressive therapies must be developed.
Assuntos
Neoplasias Pulmonares/epidemiologia , Blastoma Pulmonar/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Blastoma Pulmonar/patologia , Blastoma Pulmonar/terapia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Clusterin is a ubiquitous glycoprotein induced in many organs, including the kidney, at times of tissue injury and/or remodeling. It is speculated in this study that clusterin preserves cell interactions that are otherwise perturbed by renal insults. The purpose of this study was to examine clusterin expression after cisplatin nephrotoxicity, a model characterized by a delayed time course of injury and a well-defined site of that injury (proximal tubule). Sprague-Dawley rats were treated with intravenous cisplatin (6 mg/kg) or vehicle. Serum creatinine concentrations were measured and kidneys harvested at 1, 2, and 5 days. Marked induction of clusterin mRNA was seen only at 5 days, a time when serum creatinine concentration was the highest. Histology of kidney tissue 5 days after cisplatin administration revealed marked tubular necrosis localized to the outer stripe of the outer medulla, a region rich in proximal tubules. Immunohistochemistry and in situ hybridization at 5 days demonstrated clusterin primarily in the inner stripe of the outer medulla. In conclusion, expression of clusterin follows renal injury with cisplatin at a time corresponding to the morphologic evidence of tubular necrosis and cell detachment; quite surprisingly, such expression occurs at a site distant from the primary injury.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Glicoproteínas/biossíntese , Rim/efeitos dos fármacos , Rim/metabolismo , Chaperonas Moleculares , Animais , Clusterina , Modelos Animais de Doenças , Glicoproteínas/genética , Rim/lesões , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
PURPOSE: We gained knowledge of the etiology, treatment and prevention of cyclophosphamide associated urothelial cancer. MATERIALS AND METHODS: The medical records of 6 men and 6 women (mean age 55 years) with cyclophosphamide associated bladder cancer were reviewed. RESULTS: All tumors were grade 3 or 4 transitional cell carcinoma. Of the 5 patients initially treated with endoscopic resection alone only 1 is alive without disease. Of the 6 patients who underwent early cystectomy 4 were alive at 24 to 111 months. The remaining patient with extensive cancer underwent partial cystectomy for palliation and died 3 months later. CONCLUSIONS: Cyclophosphamide associated bladder tumor is an aggressive disease. However, long-term survival is possible when radical cystectomy is performed for bladder tumors with any sign of invasion and for recurrent high grade disease, even when noninvasive.
Assuntos
Carcinoma de Células de Transição/induzido quimicamente , Ciclofosfamida/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Adulto , Idoso , Carcinoma de Células de Transição/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Bile duct cells (BDCs), especially intrahepatic cholangiocytes, are primary targets of immune-related injury in such pathologic processes as liver graft rejection, liver graft-versus-host disease, and primary sclerosing cholangitis. Cholestasis and progressive loss of intrahepatic BDCs indicate chronicity in these diseases. The present investigation characterizes the acquisition of immune markers of intrahepatic BDCs isolated from mice after bile duct ligation. Purified BDCs from cholestatic C57BL/6 (H-2b) mice express not only the major histocompatibility complex (MHC) class I and class II antigens but also the costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The expression of the MHC class II molecules on BDCs before and after interferon (IFN)-gamma exposure is also demonstrated by immunohistochemistry on the cultured cells. Cytotoxicity assays indicate the vulnerability of these cells as targets for immunologic injuries. Effector cells generated from B10.BR splenocytes (H-2k) against C57BL/6 splenocytes (H-2b) show comparable killing of BDCs and EL4 cells, the latter being a lymphoma line that was established from the C57BL/6N (H-2b) mouse. An immortalized mouse BDC line (IBDC) is included in this study to validate some of the findings from BDCs isolated from bile duct-ligated mice. We suggest that cholestatic BDCs express surface antigens different from those of normal epithelial cells that result in increased susceptibility to damage by immune mechanisms.
Assuntos
Ductos Biliares Intra-Hepáticos/citologia , Moléculas de Adesão Celular/biossíntese , Animais , Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/imunologia , Biomarcadores , Técnicas de Cultura de Células , Linhagem Celular Transformada/citologia , Linhagem Celular Transformada/metabolismo , Cromo/metabolismo , Citotoxicidade Imunológica/fisiologia , Feminino , Citometria de Fluxo/métodos , Imuno-Histoquímica/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
Oral leiomyomas are rare because of the paucity of smooth muscle in the mouth. The solid and vascular types are the most frequent variants. The purpose of this article is to present the pathologic features and differential diagnosis of an example of epithelioid leiomyoma. A 50-year-old woman presented with a small raised nonpainful polypoid lesion of unknown duration on the right buccal mucosa. The tumor was well demarcated and consisted of large epithelioid cells with distinct cytoplasmic borders, round to oval nuclei, and prominent nucleoli. A few mitoses (4 in 20 high power fields) were present. Scattered spindle cells were also seen. The cytoplasm was eosinophilic to amphophilic and showed frequent clearing and retraction. Small capillaries were identified and surrounded by neoplastic cells that gave the lesion an angiomyomatous appearance. Masson trichrome stain highlighted focally smooth muscle cells. Immunohistochemical evaluation revealed staining for vimentin, desmin, and muscle-specific actim.