RESUMEN
The antimicrobial peptide database (APD) has served the antimicrobial peptide field for 18 years. Because it is widely used in research and education, this article documents database milestones and key events that have transformed it into the current form. A comparison is made for the APD peptide statistics between 2010 and 2020, validating the major database findings to date. We also describe new additions ranging from peptide entries to search functions. Of note, the APD also contains antimicrobial peptides from host microbiota, which are important in shaping immune systems and could be linked to a variety of human diseases. Finally, the database has been re-programmed to the web branding and latest security compliance of the University of Nebraska Medical Center. The reprogrammed APD can be accessed at https://aps.unmc.edu.
Asunto(s)
Péptidos Antimicrobianos , Biología Computacional , Bases de Datos de Proteínas , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Biología Computacional/historia , Biología Computacional/tendencias , Bases de Datos de Proteínas/historia , Bases de Datos de Proteínas/tendencias , Historia del Siglo XXIRESUMEN
Clinical studies and preclinical investigations are essential in order to test new therapies and diagnostics with the aim of sustained improvement in the treatment of patients. Fortunately, the number of clinical studies is continuously increasing and pathology and tissue-based research are included more often. The German Society for Pathology (DGP) and the pathologists it represents want to and can support this process and our clinical partners as best as possible as an equal partner. With our technologies and our specific expertise we can make a substantial contribution to the quality and the success of preclinical investigations, clinical studies and implementation of the results into clinical pathological diagnostics. In order to support this process the DGP has formulated a statement on the participation and support of clinical studies and other scientific investigations.
Asunto(s)
Ensayos Clínicos como Asunto , Patología , Sociedades Médicas , Biomarcadores/análisis , Ensayos Clínicos Fase I como Asunto , Alemania , Humanos , Valor Predictivo de las Pruebas , Garantía de la Calidad de Atención de SaludAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Terapia Molecular Dirigida , Proteínas de Neoplasias/antagonistas & inhibidores , Trasplante de Células Madre de Sangre Periférica , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Adulto , Quinasa de Linfoma Anaplásico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Brentuximab Vedotina , Carmustina/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada , Ensayos de Uso Compasivo , Crizotinib , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Inmunoconjugados/uso terapéutico , Transfusión de Linfocitos , Linfoma Anaplásico de Células Grandes/complicaciones , Linfoma Anaplásico de Células Grandes/enzimología , Linfoma Anaplásico de Células Grandes/cirugía , Masculino , Melfalán/administración & dosificación , Proteínas de Neoplasias/análisis , Prednisona/administración & dosificación , Proteínas Tirosina Quinasas Receptoras/análisis , Inducción de Remisión , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Trasplante Homólogo , Vincristina/administración & dosificaciónRESUMEN
For the tribological characterization of artificial joints, various experimental methods are currently available. However, the in vitro test conditions applied are only comparable in a limited way and transferability to the in vivo situation is also restricted. This is due to the different wear simulation concepts used and partly insufficient simulation of clinical worst case situations. In the present paper current scientific methods and procedures for tribological testing of artificial joints are presented. In addition, the biological effects of wear products are described enabling clinicians to challenge tribological studies and to facilitate specific interpretation of scientific results taking the clinical situation into account.
Asunto(s)
Análisis de Falla de Equipo/métodos , Prótesis Articulares , Modelos Teóricos , Animales , Simulación por Computador , Fricción , HumanosRESUMEN
Primary stability of artificial acetabular cups, used for total hip arthroplasty, is required for the subsequent osteointegration and good long-term clinical results of the implant. Although closed-cell polymer foams represent an adequate bone substitute in experimental studies investigating primary stability, correct numerical modelling of this material depends on the parameter selection. Material parameters necessary for crushable foam plasticity behaviour were originated from numerical simulations matched with experimental tests of the polymethacrylimide raw material. Experimental primary stability tests of acetabular press-fit cups consisting of static shell assembly with consecutively pull-out and lever-out testing were subsequently simulated using finite element analysis. Identified and optimised parameters allowed the accurate numerical reproduction of the raw material tests. Correlation between experimental tests and the numerical simulation of primary implant stability depended on the value of interference fit. However, the validated material model provides the opportunity for subsequent parametric numerical studies.
Asunto(s)
Acetábulo/química , Acetábulo/fisiología , Sustitutos de Huesos/química , Prótesis de Cadera , Modelos Biológicos , Modelos Químicos , Polimetil Metacrilato/química , Materiales Biocompatibles Revestidos/química , Simulación por Computador , Humanos , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
Staphylococcal colonization of implants is a serious complication of orthopaedic surgery. Anti-infectious modification of implant surfaces may serve to prevent bacterial colonization. The authors set out to develop an in vitro test system for the analysis of prevention of biofilm formation by Staphylococcus epidermidis and Staphylococcus aureus on implant materials. Biofilm growth was monitored over 10 days on titanium disks in order to develop appropriate test parameters. Bacterial cell counts following ultrasonic treatment of the colonized samples were compared with scanning electron microscope images of the specimens. Copper ion containing surfaces (ie copper [Cu] and inter-metallic Ti-Cu films) were used for growth inhibition assays: copper ion releasing specimens led to reduced bacterial numbers in biofilms and decreased bacterial persistence in the model used. The assay used represents an inexpensive and quick in vitro screen for the antibacterial effects of novel implant surface materials.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Cobre/farmacología , Prótesis e Implantes/microbiología , Infecciones Relacionadas con Prótesis/prevención & control , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Titanio/farmacología , Biopelículas/crecimiento & desarrollo , Materiales Biocompatibles Revestidos/farmacología , Medios de Cultivo , Pruebas de Sensibilidad Microbiana/métodos , Infecciones Relacionadas con Prótesis/microbiología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus epidermidis/crecimiento & desarrolloRESUMEN
BACKGROUND: An adequate primary stability and a subsequent stable osseous fixation (secondary stability) of artificial hip cups are required for long-term implant survival. The aim of this study was to analyse the design of cementless press-fit cups as an influencing factor of primary stability. MATERIAL AND METHODS: Different hemispherical and conical cup designs were analysed. The fixation stability of the cups was detected experimentally using a spongiosa and a cortical model based on artificial bone as well as a numerical simulation using a spongiosa model by pull-out and lever-out tests. In addition, the stress on the osseous cup cavity was determined in the finite-element analysis. RESULTS: All tested cup designs revealed higher fixation stability in the cortical bone model compared to the spongiosa model. The experimental tests did not show an increase of fixation stability with the conical cup profile in comparison to hemispherical cup profiles. CONCLUSION: Therefore, cementless press-fit cups with conical cup profile do not provide a higher primary stability in comparison to hemispherical cups. Moreover, the stress on the bone cavity was lower inserting the hemispherical cup profiles in contrast to the conical profiles.
Asunto(s)
Acetábulo/fisiopatología , Prótesis de Cadera/efectos adversos , Inestabilidad de la Articulación/prevención & control , Inestabilidad de la Articulación/fisiopatología , Modelos Biológicos , Simulación por Computador , Análisis de Falla de Equipo , Humanos , Diseño de PrótesisRESUMEN
AIMS: Although intraductal carcinoma has been demonstrated in intracapsular carcinoma ex pleomorphic adenoma (CEPA), the morphological and genetic stages of transformation of pleomorphic adenoma (PA) to CEPA are not fully understood. The aim of this study was to investigate the morphology of intracapsular CEPA. METHODS AND RESULTS: The largest series of intracapsular CEPA studied was subject to immunohistochemical double-staining to detect p53 protein and cellular proliferation in different types of cell combined with mutational analysis of the p53 gene in laser-microdissected material. Intraductal carcinoma with high-grade cellular atypia and frequent accumulation of p53 protein was found in 15/19 cases. Purely intraductal carcinoma was found in eight cases. Mutation of p53 was found in 7/19 cases, of which it was found in intraductal carcinoma in 5/15 cases. CONCLUSIONS: The frequent demonstration of intraductal carcinoma indicates that this preinvasive lesion is likely to be a constant feature in the malignant transformation of PA to CEPA. It appears to be a feature of CEPA developing from both primary and recurrent PA. The combined immunohistochemical and genetic data show that 14/19 cases of CEPA and 11/15 cases with intraductal carcinoma showed genetic or morphological evidence of dysfunctional p53, indicating that this is an early event in malignant transformation.
Asunto(s)
Adenoma Pleomórfico/patología , Carcinoma Intraductal no Infiltrante/patología , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patología , Proteína p53 Supresora de Tumor/análisis , Adenoma Pleomórfico/genética , Adenoma Pleomórfico/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Queratina-14/análisis , Queratina-7/análisis , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Modelos Biológicos , Mutación , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Glándulas Salivales Menores/química , Glándulas Salivales Menores/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Plasmablastic leukemia (PL) as a complication of human herpes virus 8 (HHV8)-associated Castleman's disease is marked by a rapid and fatal outcome. In patients with AIDS, survival of 7 to 14 days after diagnosis has been reported. Prompt splenectomy and chemotherapy might lead to a significant survival benefit. Here we report a case of long-term survival in a patient with AIDS and multicentric Castleman's disease (MCD) complicated by PL.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Enfermedad de Castleman/etiología , Infecciones por Herpesviridae/etiología , Leucemia de Células Plasmáticas/etiología , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Castleman/tratamiento farmacológico , Enfermedad de Castleman/cirugía , Herpesvirus Humano 8 , Humanos , Leucemia de Células Plasmáticas/tratamiento farmacológico , Leucemia de Células Plasmáticas/cirugía , Masculino , EsplenectomíaRESUMEN
Previous studies indicated that the Tat protein of human immunodeficiency virus type-1 (HIV-1) is a progression factor for Kaposi's sarcoma (KS). Specifically, extracellular Tat cooperates with basic fibroblast growth factor (bFGF) in promoting KS and endothelial cell growth and locomotion and in inducing KS-like lesions in vivo. Here we show that Tat and bFGF combined increase matrix-metalloproteinase-2 (MMP-2) secretion and activation in endothelial cells in an additive/synergistic manner. These effects are due to the activation of the membrane-type-1-matrix-metalloproteinase and to the induction of the membrane-bound tissue inhibitor of metalloproteinase-2 (TIMP-2) by Tat and bFGF combined, but also to Tat-mediated inhibition of both basal or bFGF-induced TIMP-1 and -2 secretion. Consistent with this, Tat and bFGF promote vascular permeability and edema in vivo that are blocked by a synthetic MMP inhibitor. Finally, high MMP-2 expression is detected in acquired immunodeficiency virus syndrome (AIDS)-KS lesions, and increased levels of MMP-2 are found in plasma from patients with AIDS-KS compared with HIV-uninfected individuals with classic KS, indicating that these mechanisms are operative in AIDS-KS. This suggests a novel pathway by which Tat can increase KS aggressiveness or induce vasculopathy in the setting of HIV-1 infection.
Asunto(s)
Endotelio Vascular/enzimología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Productos del Gen tat/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloendopeptidasas/metabolismo , Síndrome de Inmunodeficiencia Adquirida/enzimología , Animales , Permeabilidad Capilar/fisiología , Células Cultivadas , Edema/metabolismo , Endotelio Vascular/citología , Activación Enzimática/fisiología , Cobayas , Humanos , Pulmón/citología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz Asociadas a la Membrana , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Sarcoma de Kaposi/enzimología , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
Inflammatory cytokines (IC) activate endothelial cell adhesiveness for monocytes and inhibit endothelial cell growth. Here we report the identification of the human guanylate binding protein-1 (GBP-1) as the key and specific mediator of the anti-proliferative effect of IC on endothelial cells. GBP-1 expression was induced by IC, downregulated by angiogenic growth factors, and inversely related to cell proliferation both in vitro in microvascular and macrovascular endothelial cells and in vivo in vessel endothelial cells of Kaposi's sarcoma. Experimental modulation of GBP-1 expression demonstrated that GBP-1 mediates selectively the anti-proliferative effect of IC, without affecting endothelial cell adhesiveness for monocytes. GBP-1 anti-proliferative activity did not affect ERK-1/2 activation, occurred in the absence of apoptosis, was found to be independent of the GTPase activity and isoprenylation of the molecule, but was specifically mediated by the C-terminal helical domain of the protein. These results define GBP-1 as an important tool for dissection of the complex activity of IC on endothelial cells, and detection and specific modulation of the IC-activated non-proliferating phenotype of endothelial cells in vascular diseases.
Asunto(s)
Proteínas de Unión al ADN/química , Endotelio Vascular/efectos de los fármacos , Proteínas de Unión al GTP/química , Mediadores de Inflamación/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , ADN sin Sentido/genética , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Endotelio Vascular/citología , Proteínas de Unión al GTP/biosíntesis , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/fisiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Infecciones por VIH/complicaciones , Humanos , Mediadores de Inflamación/farmacología , Interferón gamma/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Prenilación de Proteína , Procesamiento Proteico-Postraduccional , Estructura Terciaria de Proteína , ARN Mensajero/biosíntesis , Proteínas Recombinantes de Fusión/fisiología , Sarcoma de Kaposi/irrigación sanguínea , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Relación Estructura-Actividad , Células U937/metabolismo , Venas UmbilicalesRESUMEN
Fas and Fas-L regulate immune responses through the induction of cell death. Fas-L is commonly expressed in activated immune cells and in the endothelium. In the latter it contributes to the inhibition of transvascular cell migration by the induction of apoptosis in Fas-bearing lymphocytes. Here we investigated whether the Fas/Fas-L system may regulate lymphocyte invasion into angiosarcomas. Fas and Fas-L expression was quantitatively determined in different grade angiosarcomas (n = 40) and related to the number of extravasated tumor-infiltrating lymphocytes (TILs). Fas expression was detected in < 50% of the cases. In positive tumors both the number of Fas-positive cells and the staining intensity were highly variable and did not correlate with the number of TILs, the mean time of survival, and the histopathological tumor grade. By contrast, Fas-L expression was detected in >70% of the cases and the relative numbers of Fas-L-positive cells correlated inversely with the numbers of CD3- and CD8-positive TILs (P < or = 0.004). The survival times of patients with high Fas-L-expressing angiosarcomas were significantly reduced as compared to patients with low Fas-L-expressing tumors. Our results show that angiosarcomas with low Fas-L expression are characterized by numerous TILs, whereas sarcomas with high Fas-L expression show significantly reduced numbers of TILs. These results suggest that the Fas/Fas-L system may repress TIL invasion into angiosarcoma and by this may contribute to the evasion of the anti-tumor immune surveillance of angiosarcoma in the course of an apoptotic tumor counterattack mechanism.
Asunto(s)
Hemangiosarcoma/metabolismo , Hemangiosarcoma/patología , Linfocitos Infiltrantes de Tumor/patología , Glicoproteínas de Membrana/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Proteína Ligando Fas , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Receptor fas/metabolismoRESUMEN
Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/genética , Bases de Datos Factuales , Genes ras/genética , Mutación Puntual , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Codón/genética , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación Missense , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Valina/genéticaRESUMEN
Kaposi's sarcoma (KS) develops through discrete inflammatory-angiogenic stages of polyclonal nature (early-stage lesions) to monomorphic nodules of spindle-shaped cells that can be clonal (late-stage lesions) and resemble true sarcomas. Molecular and epidemiological studies indicate that development of KS is tightly associated with infection by the human herpesvirus-8 (HHV-8). However, only individuals with specific conditions of immunodysregulation develop KS. In these individuals the systemic and tissue increase of Th-1-type cytokines (IC) reactivate HHV-8 infection, leading to increased viral load, antibody titers, and an expanded cell tropism that precedes the clinical appearance of KS. Recruitment of the virus into tissues by infected monocytes and other cell types is facilitated by the endothelial cell activation due to IC. In clinical lesions, HHV-8 infection increases with lesion stage and in late-stage lesions most of the spindle cells are latently infected, whereas only few lyrically infected cells are present, suggesting that latent genes may have a role in the transformation of the early inflammatory-hyperplastic lesion into a real sarcoma. The development of tumors, however, is regulated through a multistep process based on the acquisition by cells of several different capabilities leading to malignant growth. Here we review the available data on the expression of HHV-8-encoded genes in primary KS lesions and, in view of their biological activity, analyze their potential function in different steps of tumorigenesis. By this pragmatic approach interesting insights into potential key functions of HHV-8-encoded genes are found and steps of potential cooperativity with other viral factors (HIV-1-Tat) in the pathogenesis of KS are identified.
Asunto(s)
Herpesvirus Humano 8/metabolismo , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/epidemiología , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/virología , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/genética , Translocación GenéticaRESUMEN
Solid pseudopapillary tumor of the pancreas was studied in a 20-year-old woman and a 54-year-old woman. In the younger patient, the tumor had metastasized to the liver 8 years after distal pancreatectomy. In both neoplasms, the distinct histologic pattern of solid, pseudopapillary, and degenerative cystic areas was present. Analysis by means of immunohistochemistry revealed a diffuse expression for vimentin, neuron-specific enolase, and a focal positivity for al-antitrypsin, whereas epithelial markers were negative in the tumor of the older patient and only focally expressed in the tumor of the younger patient. Immunohistochemical analysis of cell cycle-associated proteins provided an overexpression of cyclin D1 and cyclin D3 in both tumors, although to varying degrees. In addition, the cyclin-dependent kinase inhibitors p21, and to a lesser extent p27, were up-regulated just as mdm2. There was no accumulation of p53 protein, and Ki67-positive cells were extremely scarce. Analysis of the liver metastases showed an immunoreactive profile similar to that of the primary tumor. The results show a deregulation of the cell cycle with overexpression of cell cycle-activating proteins D1 and D3 and a probably counterbalancing upregulation of the cyclin-dependent kinase inhibitors p21 and p27. The findings may explain the low pool of Ki67-reactive tumor cells and the generally good clinical outcome of these tumors. Whether a more profound dysbalance of the cell cycle regulation is responsible for the development of metastatic disease remains to be clarified.
Asunto(s)
Carcinoma Papilar/metabolismo , Ciclina D1/metabolismo , Ciclinas/metabolismo , Proteínas Musculares , Neoplasias Pancreáticas/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Niño , Ciclina D3 , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Inhibidores Enzimáticos/metabolismo , Femenino , Humanos , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Regulación hacia ArribaRESUMEN
We present a 28-year-old women with a 3 yr history of duodenal ulcers. Following four treatment attempts to eradicate helicobacter pylori she was admitted because of gastric outlet obstruction and a weight loss of 20 kg within the last two years. Endoscopy and x-ray showed a circular inflammatory stenosis of the proximal duodenum extending over 8 cm. Additionally, chest x-ray showed a circumscript infiltrate in the third segment of the right lung. Mycobacterial infection could be excluded. Ileocolonoscopy and small intestinal follow-through beyond the duodenum were unremarkable, and Zollinger-Ellison-syndrome was ruled out. Bronchopulmonary histology showed intramucosal epithelioid-cell granulomas and bronchiolitis obliterans. Because the patient did not improve under conservative therapy a Billroth-II-resection was carried out. Histologically the resected specimen showed Crohn-like lesions. Postoperatively, severe peripheral arthritis was treated by steroids over 6 weeks. At follow-up the patient regained 20 kg and was free of symptoms without any medication. The pulmonary infiltrate had subsided almost completely. In summary, this extremely rare coincidence of isolated stenosing duodenal Crohn's disease and pulmonary involvement was successfully treated by Billroth-II-resection. This course of disease is compatible with the hypothesis that Crohn's disease may be maintained by antigens derived from ingested food.
Asunto(s)
Enfermedad de Crohn/cirugía , Gastrectomía , Obstrucción de la Salida Gástrica/cirugía , Enfermedades Pulmonares/cirugía , Adulto , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Diagnóstico Diferencial , Duodeno/patología , Femenino , Obstrucción de la Salida Gástrica/diagnóstico , Obstrucción de la Salida Gástrica/patología , Humanos , Pulmón/patología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/patología , Estómago/patologíaRESUMEN
Aspergillus fumigatus is increasingly recognized as an important nosocomial pathogen in severely immunocompromised patients. Infection is difficult to diagnose antemortem and typically has a fatal outcome. Here we report the case of a cardiac transplant recipient with disseminated A. fumigatus infection which clinically presented as thyrotoxicosis due to massive involvement of the thyroid gland.
Asunto(s)
Aspergilosis/complicaciones , Aspergillus fumigatus , Huésped Inmunocomprometido , Tirotoxicosis/microbiología , Anciano , Aspergilosis/microbiología , Aspergilosis/patología , Resultado Fatal , Trasplante de Corazón , Humanos , Masculino , Glándula Tiroides/microbiología , Glándula Tiroides/patología , Tirotoxicosis/patologíaRESUMEN
A 67-year-old patient with upper gastrointestinal bleeding. HISTORY AND CLINICAL FINDINGS: A 67-year old patient with melaena and anaemia (haemoglobin 4.8 g/dl) for 14 days had been admitted to hospital under suspicion of upper gastrointestinal bleeding. The patient had a history of 2/3 resection of the stomach for recurrent duodenal ulcer and of a right nephrectomie for hypernephroma 18 years ago. There was no abdominal pain on pressure, nor muscular guarding. INVESTIGATIONS: Endoscopy (oesophago-duodenoscopie, coloscopie), radiography (angiography, gastrografin passage) and ultrasound failed to locate the source of bleeding. TREATMENT AND COURSE: After repeated endoscopic attempts to localize the source of bleeding and growing need of transfusions (12 blood-concentrates in 5 days) an exploratory laparotomie was done. Surprisingly a bleeding fistula between the stump of the right renal arteria and duodenum was found. The defects were excised and directly closed. CONCLUSIONS: Secondary aortoduodenal fistula after nephrectomy is rare. If the source of bleeding can't be found, and there is in any doubt an exploratory laparotomy should be done.
RESUMEN
Several salivary gland diseases present with the histomorphological features of a lymphoepithelial lesion with or without cyst formation. Some of the most important differential diagnoses (Sjögren's syndrome, marginal zone B-cell lymphoma, HIV-associated cystic lymphoepithelial lesion) are systemic diseases and require further investigation and therapy. However, in small biopsy specimens and in cases without relevant clinical information an exact diagnosis may be difficult to obtain. We have recently determined that the characteristic lymphoepithelial duct lesions develop by proliferation of basal cells of striated ducts, while we could not confirm the previously postulated participation of myoepithelial cells ("epimyoepithelial lesion/sialadenitis"). Although these duct lesions are typical of Sjögren's syndrome, they manifest in several diseases of salivary glands, exhibiting characteristic patterns concerning frequency and localization. This review discusses the most important lymphoepithelial diseases of salivary glands with respect to clinical presentation and histomorphology. Particular emphasis is placed on the lymphoepithelial duct lesions.
Asunto(s)
Enfermedades de las Glándulas Salivales/patología , Glándulas Salivales/patología , Sialadenitis/patología , Diagnóstico Diferencial , Células Epiteliales/patología , Humanos , Mucosa Bucal/patologíaRESUMEN
BACKGROUND: Human herpesvirus 8 (HHV8) infection is associated with all forms of Kaposi's sarcoma (KS). The HHV8 genome locus ORFK13-72-73 (ORF = open reading frame) encodes proteins that may be important in HHV8-mediated pathogenesis, i.e., the latency-associated nuclear antigen (encoded by ORF73), viral-cyc-D (v-cyc-D), a viral homologue of cellular cyclin D (encoded by ORF72), and viral-FLIP (v-FLIP), a homologue of the cellular FLICE (Fas-associated death domain-like interleukin 1 beta-converting enzyme) inhibitory protein (encoded by ORFK13; is an inhibitor of apoptosis [programmed cell death]). Through differential splicing events, this locus expresses individual RNA transcripts that encode all three proteins (tricistronic transcripts) or just two of them (v-FLIP and v-cyc-D; bicistronic transcripts). We examined expression of these transcripts in KS tissues. METHODS: We collected tissues from patients with KS of different stages. By use of an optimized in situ hybridization procedure, we examined different ORFK13-72-73 locus transcripts in HHV8-infected cells in skin lesions and in one adjacent lymph node. Apoptosis in KS lesions was determined by use of an in situ assay. RESULTS AND CONCLUSIONS: Our results indicate the following: 1) Transcripts from the ORFK13-72-73 locus appear to be spliced differentially in latently infected KS cells in skin lesions and in HHV8-infected cells in lymph nodes; specifically, ORFK13-ORF72 bicistronic transcripts were expressed abundantly in KS cells, whereas ORFK13-ORF72-ORF73 tricistronic transcripts were detected only in lymph node cells. 2) Sequences encoding the antiapoptotic protein v-FLIP are expressed at very low levels in early KS lesions, but expression increases dramatically in late-stage lesions. 3) The increase in expression of v-FLIP-encoding transcripts is associated with a reduction in apoptosis in KS lesions. IMPLICATIONS: These data suggest that functional v-FLIP is produced in vivo and that antiapoptotic mechanisms may be involved in the rapid growth of KS lesions, where only a few cells undergoing mitosis are generally observed.