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991.
    
Myeloproliferative neoplasms represent a group of clonal hematopoietic disorders of which myelofibrosis (MF) is the most aggressive. In the context of myeloid neoplasms, there is a growing recognition of the dysregulation of immune response and T-cell function as significant contributors to disease progression and immune evasion. We investigated cytotoxic T-cell exhaustion in MF to restore immune response against malignant cells. Increased expression of inhibitory receptors like CTLA-4 was observed on cytotoxic T cells from MF patients together with a reduced secretion of IFNɣ and TNFɑ. CTLA-4 ligands CD80 and CD86 were increased on MF granulocytes and monocytes highlighting a possible role for myeloid cells in suppressing T-cell activation in MF patients. Unlike healthy donors, the activation of cytotoxic T cells from MF patients was attenuated in the presence of myeloid cells and restored when T cells were cultured alone or treated with anti-CTLA-4. Moreover, anti-CTLA-4 treatment promoted elimination of neoplastic monocytes and granulocytes in a co-culture system with cytotoxic T cells. To test CTLA-4 inhibition in vivo, patient-derived xenografts were generated by transplanting MF CD34+ cells and by infusing homologous T cells in NSGS mice. CTLA-4 blockade reduced human myeloid chimerism and led to T-cell expansion in spleen and bone marrow. Overall, these findings shed light on T-cell dysfunction in MF and suggest that CTLA-4 blockade can boost the cytotoxic T cell-mediated immune response against tumor cells.  相似文献   
992.
Background Neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) are growth factors implicated in the growth and differentiation of brain nerve cells. An involvement of these factors in the biology and progression of some specific tumours has been suggested. In accordance with the role of neurotrophic factors in tumour behaviour the aim of the present study was to investigate their expression in two childhood brain neoplasms, namely low-grade astrocytomas and ependymomas.Materials and methods We investigated the NGF, BDNF, GDNF and NGF receptors (TrkA and p75) expression in the tumour tissues, cerebrospinal fluid (CSF) and plasma of ten children affected by low-grade astrocytomas and ependymomas. Control tissue samples (together with CSF and plasma samples) were obtained from patients who underwent surgery for cerebral vascular or epileptogenic lesions.Results The expression of NGF decreases both in tumour samples and in the CSF of affected children compared with controls. BDNF instead increases in CSF, while the expression of GDNF remains unchanged both in tissues and in CSF. No differences were found in neurotrophic factor plasma levels in patients or in controls. Gene expression of NGF and its high-affinity receptor (TrkA) are reduced in tumour tissues, whereas the number of cells immunopositive to the low-affinity NGF receptor (p75) is increased.Conclusion Reduced expression of NGF and TrkA has been shown in low-grade astrocytomas and ependymomas. These findings may be related to the role of this neurotrophin in cell differentiation and apoptosis. The different expression of NGF, BDNF, and GDNF in low-grade astrocytomas and ependymomas suggests that a different degree of redundancy exists among members of the neurotrophic factor family and that their expression may be correlated with the biology and the behaviour of these tumours.  相似文献   
993.
I M Paul  J Sanders  F Ruggiero  T Andrews  D Ungar  M E Eyster 《Blood》1999,93(11):3672-3677
The natural history of chronic hepatitis C (HCV) infections in long-term leukemia survivors has not been well characterized. We studied the prevalence of HCV infections, measured HCV RNA levels, and evaluated the severity of liver disease in patients with leukemia who achieved long-term remissions after intensive chemotherapy or bone marrow transplantation (BMT). HCV antibody tests were performed by the enzyme-linked immunosorbent assay (ELISA) and positive tests confirmed by the recombinant immunoblot assay (RIBA). HCV RNA levels were measured by the branched DNA (bDNA) assay. Seventy-five leukemia survivors with 25 or more blood donor exposures were identified. Nine (12%) were anti-HCV positive. All were infected before 1992 when second generation HCV screening tests were implemented. Mean HCV RNA levels were 10.3 x10(6) eq/mL versus 3.2 x 10(6) eq/mL (P =.056) in a control group of 20 anti-HCV positive immunocompetent individuals of comparable age who were infected twice as long (17.8 +/- 6.5 years v 9.0 +/- 4.4 years in leukemia survivors, P =.001). Liver biopsies were performed on six of the nine anti-HCV positive leukemia survivors. All showed at least moderate portal inflammation and half had evidence of bridging fibrosis. We conclude that viral loads in anti-HCV positive leukemia survivors are markedly higher than in immunocompetent controls. Our results suggest that long-term leukemia survivors with chronic HCV may have more rapidly progressive liver disease than has been previously recognized.  相似文献   
994.
995.
many studies sustained that the clock drawing test (CDT) was not able to accurately detect people with CDR = 0.5. Other researchers have promoted the use of scoring approaches with multiple scales that rate quantitative and qualitative features of the production. Nevertheless, these scoring systems are complex and time-consuming. We propose a new brief CDT’ scoring system in order to find a good measure for mild cognitive decline which is at the same time easy to administer. we enrolled 719 subjects: n. 181 with mild Alzheimer’s disease (AD); n. 200 with amnesic mild cognitive impairment (MCI) and n. 338 healthy elderly subjects (C). our CDT-three-cluster scoring system demonstrated a good sensitivity and an excellent specificity to discriminate MCI subjects from normal elderly (76 and 84 %, respectively) and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer disease (CDR: 1) from normal elderly (91 and 90 %, respectively). We found that CDT’ score = 1.30 discriminate people with MCI, whereas a score = 4.38 discriminate AD patients. The three-cluster-scoring-system demonstrated a good diagnostic accuracy, taking into account those error-items more predictive of cognitive decline: omission of numbers or hands, writing numbers or hands in a wrong position and writing numbers or hands in a different code. Our CDT’ scoring system is very short and easy method which can be used also by non-specialist.  相似文献   
996.
Background  We have modified our technique of fascial suspension mastopexy to be used in combination with augmentation mammaplasty. This study aimed to assess the results of the combined procedure in our first consecutive 10 patients. The surgery aims to maximize long-term upper-pole fullness as well as optimal projection and shape in volume-depleted ptotic breasts. Methods  A retrospective case notes review was carried out, with details of patient demographics, indications, operative detail, and postoperative assessment recorded. In addition, patients were directly questioned to gain their opinion of the procedure. Results  Nineteen breasts were operated on in ten patients. On preoperative assessment two women (20%) had grade 3 ptosis and the rest had grade 2 (83%). The majority of women had had children and had breast-fed (70%). The mean follow-up period was 33 months (range = 4–55) and overall patient satisfaction was high despite six of the 10 patients undergoing minor scar revisions for dog-ears under local anesthetic and two undergoing implant exchange to correct minor asymmetries. There were no major postoperative complications in this series. All patients demonstrated good projection and upper-pole fullness at postoperative review. Conclusion  The combined technique of fascial suspension mastopexy and breast augmentation with implants is a safe and reliable method to correct ptosis in volume-depleted breasts. Patients should be counseled on the possible need for minor revisional procedures. Importantly, the technique achieves excellent upper-pole fullness and the projected and rejuvenated breast has an overall pleasing result.  相似文献   
997.
Severe hyperleukocytosis caused by acute lymphoblastic leukaemia (ALL) is associated with an increased risk of early death due to the intracranial haemorrhage. We report on a boy who presented with ALL with an extremely high leukocyte count, who developed neurological deterioration due to multiple intracerebral haemorrhages. Adequate measures for managing this medical emergency include appropriate supportive measures and initiation of therapy to prevent symptoms of leukostasis. Aggressive measures as a decompressive craniectomy should be considered to improve the poor outcome observed in this subset of patients.  相似文献   
998.
999.
Background/purpose: Polymorphous light eruption (PLE) heterogeneity has been postulated, but the existence of benign summer light eruption (BSLE) is controversial. We studied the prevalence of the clinical patterns, criteria distinguishing BSLE from PLE, and diagnostic usefulness of phototest. Methods: Five Italian Photodermatology Centres recruited retrospectively 346 patients with typical clinical history and/or presentation of PLE. Age, gender, skin type, family history and presence of atopy were considered. UVA and UVB MEDs and provocative phototests with UVA and UVB were obtained with a standardized procedure. Photopatch tests were applied according to the IRCDG rules. ANA were assessed by indirect immunofluorescence. Results: Four criteria (predominance of women, shorter latency, uninvolvement of the face and absence of relapse during summer) identified BSLE in only 6.1% of cases. All had positive phototests, mostly with UVA. Uninvolvement of face, short latency and no seasonal relapses identified 11.7% patients, mostly with positive phototests to UVA. Short latency and no seasonal relapses in women identified 11.2% patients. Uninvolvement of face and no seasonal relapses in women identified 8.1% of patients. Uninvolvement of face and short latency in women identified 17.6% of patients. Conclusion: Criteria diagnosed BSLE in only a minority of patients, who were positive at phototesting, mostly with UVA.  相似文献   
1000.
Aortic valve endocarditis with an aortic root abscess cavity was treated by a modification of the standard technique of aortic homograft implantation in 3 patients. At a mean follow-up of 35 months, all 3 patients were well without reoperation or signs of aortic incompetence. This technique may, in some cases, be an alternative to the more complex procedure of homograft aortic root replacement with coronary reimplantation.  相似文献   
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