RESUMO
BACKGROUND AND OBJECTIVE: Anti-epidermal growth factor receptor strategies are now established in cancer treatment We have recently described the presence of EGFRvIII (a variant EGFR) in prostatic tumours from UK white men and this is now a target for anti-prostate cancer treatments. However, there has been no report on the expression of this abnormal protein in black men. MATERIALS AND METHODS: We determined EGFRvIII expression in sections of normal, benign hyperplastic (BPH) and carcinomatous (CaP) prostatic archival tissues from Nigerian men and UK white men using streptavidin immunohistochemical techniques. The EGFRvIII immunoreactivity was scored visually using a semi-quantitative method and the results compared statistically. RESULTS: EGFRvIII expression increased with increasing malignancy in both study populations (CaP > BPH > Normal p, <0.0001). Furthermore, EGFRvIII expression was similar in both BPH and CaP tissues in black and white men (p, 0.86 and 0.31 respectively). CONCLUSION: These results demonstrate that EGFRvIII immunoreactivity in prostatic tumours in black men is similar to that in white men. Anti-cancer treatments directed at the EGFRvIII should be equally effective in men from both subpopulations.
Assuntos
População Negra , Receptores ErbB/fisiologia , Hiperplasia Prostática/fisiopatologia , Neoplasias da Próstata/fisiopatologia , População Branca , Estudos de Casos e Controles , Receptores ErbB/genética , Receptores ErbB/imunologia , Humanos , Imuno-Histoquímica , Masculino , Nigéria/epidemiologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/imunologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Estados Unidos/epidemiologiaRESUMO
The cellular pathways involved in the pathogenesis of hormone resistance remain unclear. Studies evaluating the role of changes in human androgen receptor (hAR) expression in the progression of prostatic tumors have been inconclusive. Androgenic influence over prostatic growth is mediated via the regulation of interactions between stromal and epithelial cells. We hypothesized that neoplastic transformation of the prostate would be associated with alterations in hAR expression in the adjacent stroma. Using immunohistochemical techniques, we determined hAR positivity in the epithelium and adjacent stroma of sections from 17 benign and 39 malignant prostatic glands. We found that whereas the expression of the receptor decreased in both cellular compartments as the tissues dedifferentiated, the depletion was more pronounced in the stromal nuclei (P<0.0001). However, in sections from both untreated and hormone-resistant prostate cancer tissues, although heterogeneity of hAR expression in malignant epithelia was increased, there appeared to be a unique field effect around the cancerous prostate glands that resulted in a decreased expression of the receptor in the adjacent benign glands and its total loss in the surrounding stroma. The loss of hAR in the stroma adjacent to malignant prostatic epithelium may play an important role in prostate cancer progression. Furthermore, the similarity of the lack of stromal hAR expression in newly diagnosed and hormone-resistant prostate cancer (P = 0.85) may be an indication that the mechanisms responsible for the acquisition of hormone independence are established early in the malignant transformation process.
Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Células Estromais/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Transformação Celular Neoplásica/patologia , Epitélio/patologia , Epitélio/fisiopatologia , Humanos , Imunoensaio , Masculino , Metástase Neoplásica , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/análise , Células Estromais/imunologia , Células Estromais/patologiaRESUMO
We present clinical manifestations of monozygotic male twins with different degrees of expression of the G syndrome. Monozygosity was confirmed using DNA mini-satellite "fingerprint" analysis. The findings in these twins suggest that expression of the G syndrome can be strongly influenced by the prenatal developmental environment.
Assuntos
Anormalidades Múltiplas/genética , Doenças em Gêmeos , Gêmeos Monozigóticos , Gêmeos , Humanos , Recém-Nascido , Masculino , Mapeamento de Nucleotídeos , SíndromeRESUMO
The possibility of recurrent colonic metaplasia occurring as a complication of pelvic ileal pouches after ileo-rectal anastomosis has been raised. Several reports have documented malignant bladder tumours developing in patients many years after an ileocystoplasty. The case of a 50 year old man, who developed a tubulovillous adenoma in the ileal patch 30 years after an ileocystoplasty had been performed to enlarge a tuberculous shrunken bladder, is reported. The adjacent small intestinal mucosa showed features suggestive of colonic metaplasia.
Assuntos
Adenoma/patologia , Complicações Pós-Operatórias/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Storage of unstained paraffin slides may lead to the deterioration of specimens and failure to detect cellular proteins immunohistochemically. Although the implication of age-induced alterations on multicenter immunohistochemical studies would be considerable, they have not been investigated previously. The current study was undertaken to examine the effect of this factor further and to explore new ways of overcoming the resultant shortcomings. The authors now report on the immunodetection of a host of antigens in similarly preserved unstained serial paraffin slides obtained from three centers using a panel of eight antibodies. Staining of recently prepared sections from the authors' centers resulted in similar strong patterns in seven of eight antibodies, with one antibody demonstrating variable immunoreactivity. However, storage of unstained paraffin sections at room temperature resulted in a variable but progressive decrease in expression of several tissue antigens. Although the loss in antigenicity was proportional to the length of storage, the effect was reversible if super antibody concentrations were used. The authors conclude that recently prepared paraffin sections from centers with similar fixation protocols have similar immunoreactivity and are suitable for use in comparative multicenter studies. However, in view of the delays that may attend tissue transportation during these projects, the authors suggest that test systems should be checked for age-induced antigen degradation by incubating sections with higher antibody concentrations.
Assuntos
Inclusão em Parafina , Manejo de Espécimes , Anticorpos/imunologia , Humanos , Imuno-Histoquímica , Estudos Multicêntricos como AssuntoRESUMO
A case of chronic lymphocytic leukemia complicated by the nephrotic syndrome (due to membranoproliferative glomerulonephritis) is reported. There was complete remission of the proteinuria on two occasions in response to treatment of the leukemia. Possible etiological mechanisms are discussed and review of the literature is presented.
Assuntos
Glomerulonefrite/complicações , Leucemia Linfoide/complicações , Proteinúria/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/etiologia , RecidivaRESUMO
Classic malakoplakia was found in the colon of a patient with a 30-year history of proven ulcerative colitis. She had undergone total proctocolectomy after failure of medical treatment to control her illness. Immunoperoxidase studies showed immunoglobulins and muramidase within the malakoplakic histiocytes, and electron microscopy showed bacteria resembling Escherichia coli in the same cells. Immunologic studies on the patient showed an unusually high E coli antibody titer (1:512) in her serum and reduced numbers of circulating T-lymphocytes with reduced cytotoxic activity. This case shows the paradoxical rarity of malakoplakia in ulcerative colitis and reaffirms the presence of an immunologic defect that may be pathogenetically significant.
Assuntos
Colite Ulcerativa/patologia , Malacoplasia/patologia , Anticorpos Antibacterianos/análise , Colite Ulcerativa/complicações , Colite Ulcerativa/imunologia , Colo/patologia , Escherichia coli/imunologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Malacoplasia/etiologia , Malacoplasia/imunologia , Pessoa de Meia-IdadeRESUMO
Prostatic carcinogenesis has been associated with alterations in the expression of the androgen receptor (AR) and the epidermal growth factor receptor (WT-EGFR), and over-expression of the constitutively active variant epidermal growth factor receptor (EGFRvIII). Changes in the expression of AR, WT-EGFR and EGFRvIII were evaluated in serial sections from 26 normal and 26 benign hyperplastic and 50 prostate cancer tissues using specific immunostaining techniques. The loss of AR expression in peri-epithelial stroma as prostatic tissues de-differentiated correlated strongly with the depletion of WT-EGFR and with increasing expression of the EGFRvIII in the adjacent epithelium. In contrast, changes in epithelial AR immunopositivity in these tissues correlated weakly with the changes in normal and variant EGFR levels. This is the first report correlating the changes in the expression of these three proteins in archival material from the different human prostatic tissue histotypes. The loss of expression of proteins that contribute to the regulation of prostatic homeostasis (AR and WT-EGFR) correlates strongly with the expression of a constitutively active variant EGF receptor (EGFRvIII) in human prostate cancer. These changes occur at an early stage of neoplastic transformation and may contribute to the progression of the disease to hormone independence.
Assuntos
Receptores ErbB/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Endotélio Vascular/metabolismo , Humanos , Imunoquímica , MasculinoRESUMO
Transvenous right ventricular endomyocardial biopsy in an 11-yr-old boy with a proximal skeletal myopathy and a cardiomyopathy, has shown a major increase in mitochondrial size and numbers on electron-microscopic morphometry, with formation of unique ring-shaped mitochondria in cardiac muscle cells. The significance of this finding and the use of cardiac biopsy in children are discussed.
Assuntos
Mitocôndrias Musculares/ultraestrutura , Doenças Musculares/patologia , Miocárdio/ultraestrutura , Cardiomiopatias/patologia , Criança , Glicogênio/metabolismo , Humanos , Masculino , Microtúbulos , Miocárdio/metabolismo , MiofibrilasRESUMO
Endomyocardial biopsy was attempted in 18 children aged 5 months to 15 years with 82% success. Biopsies obtained from 15 children were examined by light and electron microscope making positive morphological diagnoses in 3 cases. The biopsy findings were actively helpful in 7 other cases, which contrasts with experience in adult biopsy series. This is a low risk procedure which does not add to the hazards of cardiac catheterization in children.
Assuntos
Biópsia/métodos , Cardiopatias/diagnóstico , Adolescente , Criança , Pré-Escolar , Endocárdio/ultraestrutura , Feminino , Cardiopatias/patologia , Humanos , Lactente , Masculino , Microscopia Eletrônica , Miocárdio/ultraestruturaRESUMO
Circumferential strips of pulmonary vessel wall were obtained at necropsy from the major arterial and venous branches at the lung hilum in patients aged 7-87 years. The extensibility of these strips was measured using the tension balance method of Harris et al. (British Heart Journal, 1965, 27, 651-659). The vessels were then bisected, and half of each strip was submitted for structural analysis using morphometric methods on paraffin sections stained to show the collagen, elastin, and muscle content. The other halves of the formalin-fixed vessel strips were examined chemically to determine their collagen content by estimation of the total hydroxyproline content. The thickness of the vessel media was measured microscopically on all of the sections examined. Quantitative measurements were made on 42 arteries and 37 veins. Contrary to expectation, there was a steady fall in medial collagen content with increasing age in arteries and veins. The decrease in collagen content was similar in the morphometric and chemical studies and was statistically significant. The thickness of the vessel media did not change significantly with age. The pulmonary artery and vein strips were less extensible in the older age groups, the main change occurring in the elastic phase of the vascular stress/strain curves. It is suggested that changes in the elastic tissue at a molecular and lamellar level are responsible for the increasing stiffness of pulmonary vessels rather than changes in the medial collagen content.
Assuntos
Envelhecimento , Artéria Pulmonar/fisiologia , Veias Pulmonares/fisiologia , Adolescente , Adulto , Idoso , Criança , Colágeno/análise , Complacência (Medida de Distensibilidade) , Elastina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/análise , Artéria Pulmonar/análise , Artéria Pulmonar/anatomia & histologia , Veias Pulmonares/análise , Veias Pulmonares/anatomia & histologiaRESUMO
Right or left ventricular endomyocardial biopsy with the Konno or the Olympus bioptome was attempted in 73 patients aged 5 months to 61 years, with 82 per cent success. Light and electron microscopy showed non-specific features in over half the biopsies with new or diagnostically useful information in only 10 per cent of cases, usually as a result of electron microscopy. The method is safe but is of strictly limited diagnostic value and is likely to be of most help as a research tool in the biochemical study of cardiomyopathies.
Assuntos
Biópsia/métodos , Cardiopatias/diagnóstico , Miocárdio/patologia , Adolescente , Adulto , Biópsia/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
1. We have studied the extensibility of circumferential strips of main pulmonary artery and large pulmonary veins obtained at post mortem from patients of all ages, dying from conditions other than heart and lung disease. 2. The vessel strips were submitted to increasing loads in a tension balance. The pulmonary arteries were found to be readily extensible. This extensibility became less with increasing age. The pulmonary veins were virtually inextensible at all ages. 3. It is postulated that the large extraparenchymal pulmonary veins have a capacitative role in supplying blood from the lungs to the left atrium. This may be accomplished by their collapsible nature, as they have little capability of distension.
Assuntos
Artéria Pulmonar/fisiologia , Veias Pulmonares/fisiologia , Adolescente , Adulto , Idoso , Envelhecimento , Criança , Elasticidade , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Estresse Mecânico , Resistência à TraçãoRESUMO
A 60-year-old man with rheumatoid arthritis, who developed acute reversible renal failure with nephrotic syndrome and tubulointerstitial nephritis in association with multiple-drug therapy, is described. The episode was ascribed to the nonsteroidal anti-inflammatory agent fenbufen, and the patient was reexposed to D-penicillamine within 6 months, reproducing the same renal lesion. There was no evidence of the glomerular lesions characteristically associated with D-penicillamine nephrotoxicity. D-penicillamine was the only drug therapy common to both episodes and it is concluded that it may cause tubulointerstitial nephritis with nephrotic syndrome.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Nefrite Intersticial/induzido quimicamente , Penicilamina/efeitos adversos , Injúria Renal Aguda/complicações , Artrite Reumatoide/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/complicaçõesRESUMO
BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population. AIMS: To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening. PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded. RESULTS: Three subjects had a total of four flat lesions--that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer.
Assuntos
Pólipos Adenomatosos/patologia , Neoplasias Colorretais/patologia , Programas de Rastreamento/métodos , Biópsia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sigmoidoscopia/métodosRESUMO
After the death of a 12-year old girl with newly discovered insulin-dependent diabetes mellitus, we used monoclonal antibodies in an effort to identify the cells invading the pancreas. The majority of infiltrating lymphocytes were of the T cytotoxic/suppressor phenotype, but other T-cell subpopulations were present. Some of the T cells were "activated" (positive for HLA-DR antigen, and the interleukin-2 receptor). Immunocytes bearing IgG were scattered in the gland, and complement-fixing IgG antibodies were deposited in some islets. Increased expression of Class I (HLA-A, B, and C) molecules was observed in the affected islet cells, and in damaged islets showing scant lymphocytic infiltration, some beta cells (still producing insulin), but not glucagon or somatostatin cells, were HLA-DR positive. The capillary endothelium was markedly dilated and strongly HLA-DR positive. These findings may contribute to an understanding of the sequence of events leading to the destruction of beta cells in classic Type I diabetes mellitus.
Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA/análise , Ilhotas Pancreáticas/imunologia , Anticorpos Monoclonais , Anticorpos Antivirais/análise , Linfócitos B/patologia , Capilares/imunologia , Capilares/patologia , Criança , Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 1/patologia , Endotélio/imunologia , Endotélio/patologia , Feminino , Antígenos HLA/imunologia , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-C , Antígenos HLA-DR , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Imunoglobulina G/análise , Inflamação , Ilhotas Pancreáticas/microbiologia , Ilhotas Pancreáticas/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
South Asians in Britain have a high incidence of ulcerative colitis and a low incidence of colorectal cancer. The pattern of mucus production in 12 South Asian and 16 European colitics and a control group of 19 South Asians was studied. Three types of mucin were identified after organ culture of colonic biopsy specimens with a dual label of [3H]-glucosamine and sodium [35S]-sulphate: type A had a high [35S]:[3H] ratio and high incorporation ([3H] dpm/micrograms DNA > 500); type B had a low ratio and high incorporation; and type C had low incorporation but with either high (C1) or low (C2) ratios. European colitic mucins show a significant reduction in the level of sulphation detected by mucin histochemistry with high iron diamine/Alcian blue staining, together with predominantly type B or C2 mucins (low sulphation). South Asian colitics showed histochemically normal patterns of high sulphation and largely type A and C1 mucins (high sulphation). There was no correlation of mucin type with disease activity index in either ethnic group. The appearance of apparently normal mucin in patients with ulcerative colitis may be a useful marker for the identification of a subgroup at low risk of colorectal cancer.
Assuntos
Colite Ulcerativa/metabolismo , Colo/metabolismo , Mucinas/metabolismo , Muco/metabolismo , Sudeste Asiático/etnologia , Colite Ulcerativa/etnologia , Colite Ulcerativa/patologia , Colo/patologia , Suscetibilidade a Doenças , Europa (Continente)/etnologia , Humanos , Técnicas de Cultura de ÓrgãosRESUMO
Earlier studies have demonstrated an unexplained depletion of the epidermal growth factor receptor (EGFR) protein expression in prostatic cancer. We now attribute this phenomenon to the presence of a variant EGFR (EGFRvIII) that is highly expressed in malignant prostatic neoplasms. In a retrospective study, normal, benign hyperplastic and malignant prostatic tissues were examined at the mRNA and protein levels for the presence of this mutant receptor. The results demonstrated that whilst EGFRvIII was not present in normal prostatic glands, the level of expression of this variant protein increased progressively with the gradual transformation of the tissues to the malignant phenotype. The selective association of high EGFRvIII levels with the cancer phenotype underlines the role that this mutant receptor may maintain in the initiation and progression of malignant prostatic growth, and opens the way for new approaches in the management of this disease including gene therapy.