Mycosis fungoides (MF) is the most common variant of primary cutaneous T‐cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia‐inducible factor ...1 alpha (HIF‐1α) may regulate FoxP3 expression; however, it is unknown whether HIF‐1α is expressed in the CD4+ T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF‐1α and FoxP3 in CD4+ T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4+ T cells with an aberrant phenotype among early stage MF patients. HIF‐1α was overexpressed in these CD4+ T cells. In addition, we found a decrease in the percentage of FoxP3+ cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF‐1α and FoxP3 expression. Skin HIF‐1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF‐1α degradation increases the percentage of FoxP3+ T cells in skin lesions. Our results suggest that overexpression of HIF‐1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.
What's new?
The most common variant of cutaneous T‐cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF‐1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF‐1 α compared with controls. They also observed that HIF‐1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF‐1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF‐1 α does reduce FoxP3 levels and perhaps promote disease progression.
Summary
Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system ...are recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll‐like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)‐1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM‐1 mRNA levels, measured by reverse transcription–polymerase chain reaction (RT–PCR), remained unchanged and TREM‐1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM‐1 expression by a post‐transcriptional mechanism. We also showed that TREM‐1/Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM‐1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM‐1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM‐1 during systemic inflammation.
Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal ...tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.
Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system are ...recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll-like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)-1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM-1 mRNA levels, measured by reverse transcription-polymerase chain reaction (RT-PCR), remained unchanged and TREM-1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM-1 expression by a post-transcriptional mechanism. We also showed that TREM-1-Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM-1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM-1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM-1 during systemic inflammation.
Hamartoma of the bile duct. Report of a case Ferat-Osorio, E; Barrera, R; Gómez-Jiménez, L M ...
Revista de gastroenterología de México,
2001 Oct-Dec, 20011001, Letnik:
66, Številka:
4
Journal Article
Recenzirano
Gallstones and neoplasms generally cause obstructions in the biliary duct. There are some infrequent problems that may lead to obstructions, such as hamartomas of the biliary duct.
A 34-year-old ...diabetic female patient begins with abdominal pain and jaundice. The diagnostic approach initiated with hepatobiliary ultrasound that reported cholelithiasis and enlargement of the biliary ducts. Cholangiopancreatography was subsequently performed and a biliary tree lesion was discovered; the patient underwent cholecystectomy with exploration of the biliary ducts. Clinical evolution was satisfactory. Pathologic findings indicated hamartoma of the biliary duct.
Antecedentes: La pandemia de COVID-19 ha ocasionado que los servicios de cirugía y de salud en todo el mundo tengan que reorganizarse y planear para poder brindar la mejor atención a los pacientes, ...con la protección necesaria para el personal de salud. Algunos de estos pacientes requerirán tratamiento quirúrgico, ya sea electivo o de urgencia. Objetivo: Reportar la experiencia inicial en el manejo de pacientes con COVID-19 que ameritaron tratamiento quirúrgico por los servicios de cirugía de un hospital de referencia. Método: Revisión de los protocolos quirúrgicos, equipo de protección personal usado por los equipos quirúrgicos y resultados del tratamiento de 42 pacientes sometidos a cirugía en un periodo de 4 meses. Resultados: Fueron intervenidos 42 pacientes con COVID-19. Treinta pacientes tenían diagnóstico de infección por SARSCoV-2 y en 12 casos el diagnóstico fue clínico y por imagen. Las cirugías más frecuentes fueron traqueostomía en 16 pacientes (38%) y laparotomías exploradoras en 8 pacientes (19%). La mediana de estancia posoperatoria fue de 17 días y la mortalidad durante los primeros 30 días fue del 26%. Conclusiones: Es necesaria la reorganización de los departamentos quirúrgicos y del hospital para poder atender adecuadamente a los pacientes con COVID-19 y proteger al personal de salud. Los pacientes pueden presentan patologías que requieran tratamiento quirúrgico. Relacionado con la infección y la mayor frecuencia de comorbilidad, la mortalidad de estos pacientes es elevada.
Los síntomas abdominales son frecuentes en el SIDA y el dolor abdominal es un reto diagnóstico que puede requerir cirugía electiva o urgente aunque la información acerca de esta última es pobre. En ...este estudio analizamos los hallazgos clínicos y evolución de pacientes con SIDA y dolor abdominal agudo. En un periodo de dos años, recolectamos variables demográficas y de laboratorio, síntomas clínicos, diagnóstico inicial, hallazgos quirúrgicos, diagnóstico postquirúrgico, hallazgos histopatológicos y complicaciones postoperatorias de pacientes con SIDA y dolor abdominal agudo. De 232 pacientes hospitalizados, 34 tuvieron dolor abdominal agudo: 32 hombres y 2 mujeres (mediana de edad = 32 años; intervalos 26 a 58). Veintidós pacientes requirieron manejo quirúrgico. Ocho pacientes presentaron complicaciones postquirúrgicas; cinco requirieron seis segundas intervenciones. Ocurrieron tres muertes en los 30 días luego de la cirugía inicial. La supervivencia para los pacientes tratados médicamente fue 4 meses (1 a 17), contra 6.5 meses (1 a 20) del grupo quirúrgico. El médico debe estar alerta acerca de las posibilidades diagnósticas del enfermo con SIDA y dolor abdominal agudo. Demorar la cirugía puede ser letal. La cirugía tiene un papel importante en el tratamiento integral del paciente con SIDA.
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