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81.
Physiology of the prion protein 总被引:7,自引:0,他引:7
Linden R Martins VR Prado MA Cammarota M Izquierdo I Brentani RR 《Physiological reviews》2008,88(2):673-728
Prion diseases are transmissible spongiform encephalopathies (TSEs), attributed to conformational conversion of the cellular prion protein (PrP(C)) into an abnormal conformer that accumulates in the brain. Understanding the pathogenesis of TSEs requires the identification of functional properties of PrP(C). Here we examine the physiological functions of PrP(C) at the systemic, cellular, and molecular level. Current data show that both the expression and the engagement of PrP(C) with a variety of ligands modulate the following: 1) functions of the nervous and immune systems, including memory and inflammatory reactions; 2) cell proliferation, differentiation, and sensitivity to programmed cell death both in the nervous and immune systems, as well as in various cell lines; 3) the activity of numerous signal transduction pathways, including cAMP/protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt pathways, as well as soluble non-receptor tyrosine kinases; and 4) trafficking of PrP(C) both laterally among distinct plasma membrane domains, and along endocytic pathways, on top of continuous, rapid recycling. A unified view of these functional properties indicates that the prion protein is a dynamic cell surface platform for the assembly of signaling modules, based on which selective interactions with many ligands and transmembrane signaling pathways translate into wide-range consequences upon both physiology and behavior. 相似文献
82.
Daniel Fernández-Martínez Antonio Rodríguez-Infante Elsa Castelo-álvarez Iván Fernández-Vega Miguel Suárez-Hevia Nuria Truán-Alonso Ricardo F. Baldonedo-Cernuda José A. álvarez-Pérez Herminio Sánchez-Farpón 《International journal of surgery case reports》2014,5(9):584-588
INTRODUCTION
An infiltration of urological organs is found in 5–10% of patients with colorectal carcinoma. Total pelvic exenteration is the standard procedure for locally advanced rectal cancer. In selected patients with rectal cancer involving the prostate or seminal vesicles, the bladder can be preserved and en bloc radical prostatectomy with abdominoperineal rectal resection can be performed. We report two patients who treated with this combined approach.PRESENTATION OF CASE
Two patients with symptoms of rectal bleeding and pelvic pain were investigated. Colonoscopy demonstrated a tumor in the lower rectum. Biopsies revealed adenocarcinoma. Both pelvic MRI and endorectal ultrasound showed tumors that invaded the prostate and the seminal vesicles directly but without invasion of the bladder. After neoadjuvant chemoradiation, combined radical prostatectomy and abdominoperineal amputation was performed. None has developed local recurrence, but one of them was operated on for a single lung metastasis. After a follow-up of 28 and 20 months, respectively, the patients are alive without evidence of local recurrence or distant disease.DISCUSSION
This procedure obviates the need for urinary diversion without compromising the local tumor control. Intraoperative and postoperative diagnostic difficulties, and clinical aspects in relation to postoperative anastomotic leak and survival of patients are discussed.CONCLUSION
En bloc radical prostatectomy and proctosigmoidectomy is feasible in selected patients with rectal cancer and invasion limited to the prostate or seminal vesicles because it provides good local tumor control and significantly improves the patient''s quality of life in comparison to total pelvic exenteration. 相似文献83.
Nir Uriel Diego Medvedofsky Teruhiko Imamura Jiri Maly Eric Kruse Peter Ivák Poornima Sood Roberto M. Lang Francesco Maffessanti Dominik Berliner Johann Bauersachs Axel Haverich Michael Želízko Ivan Netuka Jan D. Schmitto 《Journal of cardiac failure》2019,25(1):36-43
Background
The Heartmate 3 (HM3) is a Conformiteé Européenne mark–approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape.Methods and Results
Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization. Three-dimensional echocardiographic (3DE) LV and RV datasets (Philips) were acquired, and volumetric (Tomtec) and shape (custom software) analyses were performed (LV: sphericity, conicity; RV: septal and free-wall curvatures). Data were recorded at up to 13 speed settings. Speed changes were in 100-rpm steps, starting at 4600 rpm and ramping up to 6200 rpm. 3DE was feasible in 50% of the patients. Mean original speed was 5306 ± 148 rpm. LV end-diastolic (ED) diameter (?0.15 ± 0.09 cm/100 rpm) and volumes (ED: 269 ± 109 mL to 175 ± 90 mL; end-systolic [ES]: 234 ± 111 mL to 146 ± 81 mL) progressively decreased as the shape became less spherical and more conical; RV volumes initially remained stable, but at higher speeds increased (ED: from 148 ± 64 mL to 181 ± 92 mL; ES: 113 ± 63 mL to 130 ± 69 mL). On average, the RV septum became less convex (bulging toward the LV) at the highest speeds.Conclusions
LV and RV shape changes were noted in HM3-supported patients. Although a LV volumetric decrease and shape improvement was consistently noted, RV volumes grew in response to increase in speed above a certain point. A next concern would be whether understanding of morphologic and function changes in LV and RV during LVAD speed change assessed with the use of 3DE helps to optimize LVAD speed settings and improve clinical outcomes. 相似文献84.
Mohammad Abumayyaleh Iván J. Núñez Gil Ibrahim El-Battrawy Vicente Estrada Víctor Manuel Becerra-Muñoz Alvaro Aparisi Inmaculada Fernández-Rozas Gisela Feltes Ramón Arroyo-Espliguero Daniela Trabattoni Javier López-País Martino Pepe Rodolfo Romero Diego Raúl Villavicencio García Carloalberto Biole Thamar Capel Astrua Charbel Maroun Eid Emilio Alfonso Ibrahim Akin 《Obesity research & clinical practice》2021,15(3):275-280
BackgroundObesity has been described as a protective factor in cardiovascular and other diseases being expressed as ‘obesity paradox’. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI).MethodsWe retrospectively collected data up to May 31st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m2; n = 1110, 25?30 kg/m2; n = 1464, and >30 kg/m2; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed.ResultsThe rate of respiratory insufficiency was more recorded in BMI 25?30 kg/m2 as compared to BMI < 25 kg/m2 (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m2 than BMI < 25 kg/m2, respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25?30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25?30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m2 and BMI > 30 kg/m2 did not impact the mortality rate (HR 1.15, 95% CI: 0.889?1.508; p = 0.27) (HR 1.15, 95% CI: 0.893?1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m2 is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538?1.004; p = 0.05).ConclusionsHOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality. 相似文献
85.
Marta Fernández‐Nogales María Santos‐Galindo Ivó H. Hernández Jorge R. Cabrera José J. Lucas 《Brain pathology (Zurich, Switzerland)》2016,26(6):772-778
Huntington's disease (HD) is caused by a CAG‐repeat encoding a polyglutamine (polyQ) tract in the huntingtin protein. There is plenty of evidence of polyQ‐driven toxicity. However, CAG repeat RNA‐driven alteration of splicing has recently been proposed in analogy to CUG‐repeat diseases. Here we review the reported alteration of the CAG‐repeat associated splicing factor SRSF6 in brains of HD patients and mouse models and how this correlates with altered splicing of, at least, two microtubule‐associated proteins in HD, namely MAPT (tau) and MAP2. Regarding tau, altered splicing of exon 10 has been reported, along with increased levels and 4R/3R‐tau ratio and detection of tau in a new nuclear rod‐shaped histopathological hallmark termed tau nuclear rod (TNR) or tau nuclear indentation (TNI). These findings, together with an attenuation of HD phenotype in R6/1 mice with tau deficiency and subsequent studies showing increased phosphorylation in mouse models and increased levels in CSF of patients, has led to proposing HD as a tauopathy. Regarding MAP2, an increase in its juvenile form and a decrease in total MAP2 together with redistribution from dendrites to soma is observed in HD patients, which may contribute to the dendritic atrophy in HD. Furthermore, MAP2 positive structures filling nuclear indentations have occasionally been found and co‐localized with tau. Therefore, altered MAP function with imbalance in tau/MAP2 content could contribute to HD striatal atrophy and dysfunction. Besides, TNIs might be indicative of such MAP abnormalities. TNIs are also found in early pathology Alzheimer's disease and in tauopathy mice over‐expressing mutant 4R‐tau. This indicates that tau alteration is sufficient for TNI detection, which becomes a marker of increased total tau and/or altered 4R/3R‐tau ratio and reporter of pathology‐associated nuclear indentations. Altogether, these recent studies suggest that correcting the SRSF6‐driven missplicing and/or microtubule‐associated imbalance might be of therapeutic value in HD. 相似文献
86.
Clinical data of 70 patients, treated and observed with myelodysplastic syndrome between 1977 and 1989 were analysed. Two-thirds of the patients belonged to the elder age-group and a mild female predominance was registered. With the application of complex cytochemical-histological and cytogenetical methods, correct diagnosis could be established. The clinical material included patients from different morphologic subtypes: 19 with refractory anaemia (with a longer course of the illness). 20 with sideroblastic anaemia, 26 with chronic myelomonocytic leukaemia and the remaining 5 with refractory anaemia with excess of blasts (a more progressive type of the myelodysplastic syndrome, with a short duration). The mean survival of all patients were 42 months. 45 (69%) died during this period and 12 (18.5%) among them in acute myelogenous leukaemia (mean survival: 16 month). Megakaryoblastic leukaemic transformation was observed in three patients with sideroblastic refractory anaemia. Haemorrhage and infection-sepsis, due to thrombocytopenia and/or granulocytopenia, was fatal in 30 cases. In the treatment of the myelodysplastic syndrome an appropriate supportive therapy (blood transfusion, antibiotics) has a decisive importance. A more aggressive treatment with cytostatic drugs is suggested in the progressive form of the disease of younger patients and in patients with overt acute leukaemia. 相似文献
87.
Authors review a case of urinary schistosomiasis, where the process caused left sided urinary obstruction. Because of the suspicion of a tumor transurethral resections was performed, where after the ureter passage became unhindered. Diagnosis became clear upon the histological examination of the resected tissue. Based on the cited literature, reference is made to the mortality rate of the disease in the expanded endemic areas, as well as to the high number of patients at risk. A brief summery is given of the pathology, symptoms, diagnostics of the disease, with mention of differentiation and therapeutic possibilities as well. With regard to importation of the disease, attention is called to the importance of careful anamnesis. 相似文献
88.
Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison's disease 总被引:1,自引:0,他引:1
The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism and in 6 with Addison's disease. Plasma AVP was measured by radioimmunoassay. Patients with primary hypothyroidism were classified into subgroups with elevated (6.81 +/- 1.12 pmol/l) or normal (3.92 +/- 0.96 pmol/l) basal levels of plasma AVP. Following the infusion of 2.5% saline, a positive correlation was established between plasma AVP and plasma osmolality. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels (pAVP = 0.37 (pOs-265), r = 0.71, P less than 0.01) as compared with that in hypothyroid patients with a normal AVP level (pAVP = 0.42 (pOs-280), r = 0.93, P less than 0.001). A relationship was demonstrated between the alteration in the AVP osmoregulation and the severity of the thyroid insufficiency. Patients with Addison's disease exhibited an increased basal level of plasma AVP (9.59 +/- 1.25 pmol/l) and a decreased osmotic threshold (pAVP = 0.42 (pOs-261), r = 0.63, P less than 0.01) contrasted to that of healthy volunteers (pAVP = 0.41 (pOs-280), r = 0.83, P less than 0.001). The osmoregulation disturbance of the AVP secretion may play a major role in the impaired water metabolism in primary hypothyroidism and in Addison's disease. 相似文献
89.
On a general medical department with 54 beds, 801 patients (8.6%) expired between 1980 and 1984 in 780 of them (97.3%) autopsy has revealed. 58.4% of expired patients were over seventy years. In this age group autopsy data diverged from the underlying disease in 9.58%, however this ratio of patients under seventy was 8.56%, as well. Mistake of clinical diagnosis in the direct cause of death was 18.9% in the group of under seventy and 21.3% of over seventy. The highest ratio of mistakes in the underlying disease has occurred in diseases of malignancies (progressing with age). Referring to the direct cause of death, undiagnosed pulmonary embolism had in each age group an equal high ratio. Because of the augmented multimorbidity with age the autopsy in the elderly can serve for an improvement of diagnosis. 相似文献
90.