RESUMO
PURPOSE: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. EXPERIMENTAL DESIGN: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. RESULTS: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P<0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. CONCLUSIONS: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Radioisótopos de Índio , Radioimunodetecção , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Biespecíficos , Antígeno Carcinoembrionário/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Haptenos , Humanos , Linfonodos , Metástase Linfática/diagnóstico por imagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligopeptídeos/química , PrognósticoRESUMO
HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.
Assuntos
Terapia Antirretroviral de Alta Atividade , Linfoma Relacionado a AIDS/prevenção & controle , Contagem de Linfócito CD4 , Estudos de Coortes , Bases de Dados como Assunto , Feminino , França/epidemiologia , HIV/isolamento & purificação , Humanos , Incidência , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/mortalidade , Masculino , Estudos Retrospectivos , Fatores de Risco , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa , Taxa de Sobrevida , Fatores de Tempo , Carga ViralRESUMO
BACKGROUND: Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known. PATIENTS AND METHODS: Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry. RESULTS: Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. CONCLUSION: These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Diarreia/complicações , Mucosa Intestinal/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/efeitos adversos , Colite/induzido quimicamente , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-IdadeRESUMO
UNLABELLED: Morphologically, polymorphic prostatic lipochrome pigment has been classified and subclassified in the last few years. Type 2B lipochrome pigment granules (LPGs) are frequently found in prostatic epithelium in patients who had died of AIDS. Intensive apoptosis is observed in the same epithelium which lends support to the hypothesis of heterophagocytic (apoptotic) origin of type 2B pigment granules. Detection of nuclear chromatin material is necessary for the differentiation of an autophagosomal from a heterophagosomal structure in the cellular cytoplasm. OBJECT OF THE STUDY: Application of in situ hybridization (ISH) for elucidating the origin of subtype 2B LPGs in the prostate epithelial cells of patients who had died of AIDS. METHODS: ISH was used on routine necropsic prostate epithelial samples from three patients who had died of AIDS. A DNA probe raised against total human DNA was employed. RESULTS: Multiple hybridization signals were detected in type 2B LPGs which shows the presence of nuclear material in those structures. The chromatin material localized to the periphery of pigment granules. CONCLUSION: Type 2B LPGs have a heterophagocytic origin and represent phagocytosed apoptotic bodies in the phase of phagolysosomal degradation. They can be used as a morphologic tissue marker of intensive epithelial apoptosis.
Assuntos
Síndrome da Imunodeficiência Adquirida/fisiopatologia , Grânulos Citoplasmáticos/metabolismo , Lipofuscina/metabolismo , Fagocitose/fisiologia , Próstata/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Histocitoquímica , Humanos , Hibridização In Situ , Masculino , Próstata/patologia , Próstata/ultraestruturaRESUMO
Enolase is a dimeric glycolytic enzyme exhibiting tissue specific isoforms. During ontogenesis, a transition occurs from the embryonic alphaalpha towards the specific alphabeta, and betabeta isoforms in striated muscle. Immunocytochemical analyses on transverse sections of adult mouse gastrocnemius muscle, allowed us to compare the expression of alpha and beta subunits to that of myosin heavy chain (MHC) isoforms. Levels of beta immunoreactivity followed the order IIB > IIX > IIA > I. This gradient parallels the ATPase activity associated to MHC isoforms, indicating that the expression of beta enolase in myofibres is finely regulated as a function of energetic requirements. By contrast, variations in alpha immunolabelling intensity appeared independent of fibre types. Longitudinal muscle sections exhibited a striated pattern of alpha immunoreactivity. Confocal microscopy analyses demonstrated that alpha was localised at the M band. Most beta immunoreactivity was diffuse all over the sarcoplasm. However, some beta immunoreactivity was striated and localized at both Z and M bands. Thus, betabeta enolase could participate to multi-enzyme complexes present at the I band, and involved with local ATP production. Our results support the notion that isozymes differ in their ability to interact with other macromolecules, thus segregating to different subcellular sites where they would respond to specific functional demands.
Assuntos
Isoenzimas/metabolismo , Fibras Musculares Esqueléticas/enzimologia , Músculo Esquelético/enzimologia , Miocárdio/enzimologia , Cadeias Pesadas de Miosina/metabolismo , Fosfopiruvato Hidratase/metabolismo , Animais , Imuno-Histoquímica , Camundongos , Microscopia Confocal , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/metabolismo , Músculo Esquelético/ultraestrutura , Miocárdio/citologia , Miocárdio/metabolismoRESUMO
Spatial gene expression in the intestine is mediated by specific regulatory sequences. The three genes of the apoA-I/C-III/A-IV cluster are expressed in the intestine following cephalocaudal and crypt-to-villus axes. Previous studies have shown that the -780/-520 enhancer region of the apoC-III gene directs the expression of the apoA-I gene in both small intestinal villi and crypts, implying that other unidentified elements are necessary for a normal intestinal pattern of apoA-I gene expression. In this study, we have characterized transgenic mice expressing the chloramphenicol acetyltransferase gene under the control of different regions of the apoC-III and apoA-IV promoters. We found that the -890/+24 apoC-III promoter directed the expression of the reporter gene in crypts and villi and did not follow a cephalocaudal gradient of expression. In contrast, the -700/+10 apoA-IV promoter linked to the -500/-890 apoC-III enhancer directed the expression of the reporter gene in enterocytes with a pattern of expression similar to that of the endogenous apoA-IV gene. Furthermore, linkage of the -700/-310 apoA-IV distal promoter region to the -890/+24 apoC-III promoter was sufficient to restore the appropriate pattern of intestinal expression of the reporter gene. These findings demonstrate that the -700/-310 distal region of the apoA-IV promoter contains regulatory elements that, in combination with proximal promoter elements and the -500/-890 enhancer, are necessary and sufficient to restrict apoC-III and apoA-IV gene expression to villus enterocytes of the small intestine along the cephalocaudal axis.
Assuntos
Apolipoproteínas A/genética , Apolipoproteínas C/genética , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Animais , Apolipoproteína C-III , Cloranfenicol O-Acetiltransferase/genética , Intestino Delgado/metabolismo , Camundongos , Camundongos Transgênicos , RNA Mensageiro/genética , Sequências Reguladoras de Ácido NucleicoRESUMO
We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRgamma gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.
Assuntos
Doença Celíaca/classificação , Linfoma de Células T/classificação , Adulto , Atrofia , Medula Óssea/patologia , Doença Celíaca/complicações , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Células Clonais/patologia , DNA de Neoplasias/genética , Progressão da Doença , Suscetibilidade a Doenças , Duodeno/patologia , Dispepsia/patologia , Enterite/patologia , Evolução Fatal , Glutens/efeitos adversos , Humanos , Mucosa Intestinal/patologia , Jejuno/patologia , Fígado/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Células T/patologia , Microvilosidades/patologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Falha de Tratamento , Úlcera/patologiaRESUMO
We describe a combination of epithelial cell apoptosis and intracytoplasmic inclusions in prostatic epithelium in 6 patients who died from the acquired immunodeficiency syndrome. Two different types of apoptosis were detected: simple cell shrinkage and exploding glandular cells. No intracellular or extracellular viral particles were detected, either ultrastructurally or immunohistochemically. Intracytoplasmic inclusions are apoptotic bodies in a state of degradation and in close association with lipofuscin. The cell degeneration we observed confirms the theory that increased apoptotic cell depletion is responsible for weight loss in the acquired immunodeficiency syndrome. In the prostate itself, the combination of excessive apoptosis and active phagosomal digestion of apoptotic bodies presents a "human model" of postcastration rat ventral prostate, under the conditions of severe immune deficiency.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Apoptose/fisiologia , Células Epiteliais/patologia , Corpos de Inclusão/patologia , Próstata/patologia , Adulto , Autopsia , Estudos de Casos e Controles , Histocitoquímica , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Pessoa de Meia-IdadeRESUMO
The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.
Assuntos
Colite/diagnóstico , Colo/patologia , Infecções por Citomegalovirus/diagnóstico , Diarreia/diagnóstico , Infecções por HIV/complicações , Adulto , Biópsia , Linhagem Celular , Colite/patologia , Colo/virologia , Colonoscopia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/patologia , Diarreia/patologia , Fezes/microbiologia , Fezes/parasitologia , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções por Citomegalovirus/complicações , Rim/irrigação sanguínea , Trombose/etiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Antifúngicos/efeitos adversos , Brônquios/patologia , Estudos de Casos e Controles , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Feminino , Fluconazol/efeitos adversos , Humanos , Rim/patologia , Rim/fisiopatologia , Pulmão/patologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Insuficiência Renal/complicações , Insuficiência Renal/patologia , Estudos Retrospectivos , Fatores de Risco , Trombose/patologia , Trombose/terapiaAssuntos
Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Acanthamoeba , Amebíase/complicações , Dermatopatias/parasitologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Amebíase/patologia , Animais , Humanos , Masculino , Dermatopatias/complicações , Dermatopatias/patologiaRESUMO
Expression in mice of transgenes directed by regulatory regions of the rat aldolase B gene requires the presence of a B element located in the first intron, while constructs devoid of this intronic enhancer are silent. Histo- and immunochemical staining of transgenic tissue sections showed that the longer transgene was expressed in the proximal tubular cells of the kidney, enterocytes located in small intestine villi and liver parenchymal cells. In the liver, a maximal expression was observed in perivenous hepatocytes, while the transgene was weakly active in periportal hepatocytes, which reproduced the pattern of functional zonation already reported for other glycolytic and gluconeogenic genes in the liver. We also established that the transgene retained the necessary elements for a correct chronological expression during development but was lacking elements necessary for activation by high carbohydrate diet. Instead, transgene expression was paradoxically stimulated in fasted animals, suggesting that the endogenous gene, which must be active under both glycolytic and gluconeogenic conditions, could possess distinct elements activating it in fasted as well as in carbohydrate-fed animals; the former element might be conserved in the transgene and the latter one might be lost.
Assuntos
Elementos Facilitadores Genéticos , Frutose-Bifosfato Aldolase/biossíntese , Regulação Enzimológica da Expressão Gênica , Íntrons , Envelhecimento/metabolismo , Animais , Animais Recém-Nascidos , Northern Blotting , Encéfalo/enzimologia , Cloranfenicol O-Acetiltransferase/biossíntese , Desenvolvimento Embrionário e Fetal , Feminino , Frutose-Bifosfato Aldolase/genética , Idade Gestacional , Gluconeogênese , Glicólise , Imuno-Histoquímica , Intestinos/enzimologia , Túbulos Renais Proximais/enzimologia , Fígado/citologia , Fígado/embriologia , Fígado/enzimologia , Camundongos , Camundongos Transgênicos , Especificidade de Órgãos , Gravidez , Ratos , Proteínas Recombinantes/biossíntese , Baço/enzimologiaRESUMO
Three cases are presented of lymphocytic colitis with chronic diarrhoea concurrent with longterm use of Cyclo 3 Fort, a phlebotonic drug used in France. The histological and immunopathological features of lymphocytic colitis are described. We show that lymphocytic colitis is drug induced, particularly in one patient where the immunopathological features of mucosal immune cell activation were induced by drug rechallenge. It is concluded that lymphocytic colitis may be drug induced, secondary to a chronic activation of the mucosal immune system by one or several components of the drug.
Assuntos
Colite/induzido quimicamente , Extratos Vegetais/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colite/imunologia , Colite/patologia , Colo/patologia , Diarreia/induzido quimicamente , Feminino , Antígenos HLA-DR/análise , Humanos , Contagem de Leucócitos , Receptores de Interleucina-2/análise , Doenças Vasculares/tratamento farmacológicoRESUMO
In patients with the acquired immunodeficiency syndrome (AIDS), manifestations of generalized Mycobacterium avium intracellulare infection are non-specific and pneumopathy is rarely encountered. We report a case of a patient with AIDS who had clinical and radiological manifestations of multifocal alveolar pneumopathy which was found on autopsy to be due to disseminated Mycobacterium avium intracellulare.