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排序方式: 共有751条查询结果,搜索用时 15 毫秒
31.
Subbaya Subramanian Venugopal Thayanithy Robert B West Cheng‐Han Lee Andrew H Beck Shirley Zhu Erinn Downs‐Kelly Kelli Montgomery John R Goldblum Pancras CW Hogendoorn Christopher L Corless Andre M Oliveira Sarah M Dry Torsten O Nielsen Brian P Rubin Jonathan A Fletcher Christopher DM Fletcher Matt van de Rijn 《The Journal of pathology》2010,220(1):58-70
Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive soft tissue tumours that occur either sporadically or in patients with neurofibromatosis type 1. The malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. We have determined the gene expression signature for benign and malignant PNSTs and found that the major trend in malignant transformation from neurofibroma to MPNST consists of the loss of expression of a large number of genes, rather than widespread increase in gene expression. Relatively few genes are expressed at higher levels in MPNSTs and these include genes involved in cell proliferation and genes implicated in tumour metastasis. In addition, a gene expression signature indicating p53 inactivation is seen in the majority of MPNSTs. Subsequent microRNA profiling of benign and malignant PNSTs indicated a relative down‐regulation of miR‐34a in most MPNSTs compared to neurofibromas. In vitro studies using the cell lines MPNST‐14 (NF1 mutant) and MPNST‐724 (from a non‐NF1 individual) show that exogenous expression of p53 or miR‐34a promotes apoptotic cell death. In addition, exogenous expression of p53 in MPNST cells induces miR‐34a and other miRNAs. Our data show that p53 inactivation and subsequent loss of expression of miR‐34a may significantly contribute to the MPNST development. Collectively, our findings suggest that deregulation of miRNAs has a potential role in the malignant transformation process in peripheral nerve sheath tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
32.
Acne is the most common disorder observed in ethnic skin. Clinical presentation is different than in white skin. Postinflammatory hyperpigmentation is a common sequelae of acne in darker skin. The management of acne in ethnic skin is based largely on the prevention and treatment of hyperpigmentation. 相似文献
33.
Kroese ED; Dortant PM; van Steeg H; van Oostrom CT; van der Houven van Oordt CW; van Kranen HJ; de Vries A; Wester PW; van Kreijl CF 《Carcinogenesis》1997,18(5):975-980
E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to
their low spontaneous tumour incidence and their increased sensitivity
towards the lymphomagen ethylnitrosourea these mice may present an
interesting model for short-term carcinogenicity testing. Here, we report
on the further exploration of this transgenic mouse model with two
additional carcinogens known to have, among others, the
lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and
12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week
(by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a
dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1
mice during the observation period of 40 weeks. B[a]P also induced tumours
of the forestomach within this observation period, though at a lower
incidence and apparently equally effective in wildtype and transgenic mice.
TPA, on the other hand, was unable to induce lymphomas (or tumours in any
other organ) in either transgenic or wildtype animals within the
observation period of 44 weeks, when applied dermally at the maximum
tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular
analysis showed that B[a]P-induced lymphomas in transgenic mice were of
T-cell origin, 80% of which had elevated levels of c-myc expression. None
of the lymphomas had increased N-myc expression and mutation analysis of
the ras-gene family revealed a K-ras mutation in only one out of eight
tumours investigated. Also, none of the lymphomas showed aberrant
expression of p53 as determined by immunohistochemistry. It is concluded
that the E mu-pim-1 mouse model will not be very suitable for short-term
carcinogenicity testing in general: only genotoxic chemicals that have the
lymphohaematopoietic system as target for carcinogenesis in wild- type
mice, appear to be efficiently identified.
相似文献
34.
Manon Auger Beverly Raney David Callender Patricia Eifel Nelson G. Ord ez 《Fetal and pediatric pathology》1994,14(5):763-770
A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli. 相似文献
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39.
McDougall NI McCluggage WG Coyle PV Sloan JM Callender ME 《The Ulster medical journal》2004,73(1):25-31
Chronic hepatitis C virus (HCV) infection has become a major health problem affecting an estimated 170 million people worldwide. The epidemiology of HCV and its response to treatment in Northern Ireland has not been described before. Our aims were to determine the epidemiology, histological stage, suitability for treatment and response to treatment in patients with hepatitis C presenting to one clinic in Northern Ireland. All patients were prospectively recruited with hepatitis C attending the Liver Clinic, Royal Victoria Hospital during the period December 1992 to June 1997. Sixty patients (33 male, mean age 44 years, range 19-84 years) who tested anti-HCV antibody positive were identified. The predominant genotypes were 1b (33%), 3a (28%) and 1a (26%). Most patients (78%) were asymptomatic at the time of detection and only four (7%) gave a history of jaundice. The most common modes of transmission were i.v. drug use in 30 (50%) and blood products in 20 (33%) patients. Forty-eight (86%) of the 56 patients tested were PCR positive for HCV RNA. Fifty-one patients (85%) underwent liver biopsy of whom 13 had cirrhosis (22% of original group). Twenty-nine patients were suitable for treatment, but three declined treatment and only 26 (43%) started interferon-alpha. During treatment 17 (65%) patients became PCR negative and eight (31%) remained PCR negative 12 months after completion of therapy. Liver histology was assessed before and after interferon treatment in 17 patients and showed no change in total necroinflammatory scores (p = 0.1) or staging of architectural change (p = 0.55). CONCLUSIONS: The epidemiology and response to therapy of HCV in Northern Ireland appear comparable to elsewhere in the UK. Only a minority of anti-HCV positive non-haemophiliac patients progress to have interferon therapy suggesting that the cost of treating chronic HCV may not be as great as initially thought. 相似文献
40.
Effect of standardized orders and provider education on head-of-bed positioning in mechanically ventilated patients 总被引:3,自引:0,他引:3
Helman DL Sherner JH Fitzpatrick TM Callender ME Shorr AF 《Critical care medicine》2003,31(9):2285-2290
OBJECTIVE: Semirecumbent head-of-bed positioning in mechanically ventilated patients decreases the risk of developing ventilator-associated pneumonia (VAP). The purpose of this study was to determine whether the addition of a standardized order followed by the initiation of a provider education program would increase the frequency with which our patients were maintained in the semirecumbent position. DESIGN: Prospective, pre-, and postintervention observational study. SETTING: A tertiary care, U.S. Army teaching hospital. PATIENTS: Mechanically ventilated medical and surgical intensive care unit patients. INTERVENTIONS: The first intervention involved the addition of an order for semirecumbent head-of-bed positioning to our intensive care unit order sets. This was followed 2 months later with a second intervention, which was a nurse and physician education program emphasizing semirecumbent positioning. MEASUREMENTS AND MAIN RESULTS: Data regarding head-of-bed positioning were collected on 100 patient observations at baseline and at 1 and 2 months after each of our interventions. The mean angle of head of bed increased from 24 +/- 9 degrees at baseline to 35 +/- 9 degrees (p <.05) 2 months after the addition of the standard order. The percentage of observations with head of bed >45 degrees increased from 3% to 16% 2 months after the standardized order (p <.05). Two months after our provider education program, the mean angle of the head of bed was 34 +/- 11 degrees and the percentage of patients with head of bed >45 degrees was 29% (p = NS compared with values after the first intervention). Data collected 6 months after completion of our education programs showed that these improvements were maintained. CONCLUSIONS: Standardizing the process of care via the addition of an order specifying head-of-bed position significantly increased the number of patients who were placed in the semirecumbent position. In an era of cost-conscious medicine, interventions that utilize protocols and education programs should be emphasized. 相似文献