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Rita A. Busuttil Giada V. Zapparoli Sue Haupt Christina Fennell Stephen Q. Wong Jia-Min B. Pang Elena A. Takeno Catherine Mitchell Natasha Di Costanzo Stephen Fox Ygal Haupt Alexander Dobrovic Alex Boussioutas 《Oncotarget》2014,5(23):12016-12026
Intestinal metaplasia (IM) is a premalignant lesion associated with gastric cancer (GC) but is poorly described in terms of molecular changes. Here, we explored the role of TP53, a commonly mutated gene in GC, to determine if p53 protein expression and/or the presence of somatic mutations in TP53 can be used as a predictive marker for patients at risk of progressing to GC from IM. Immunohistochemistry and high resolution melting were used to determine p53 protein expression and TP53 mutation status respectively in normal gastric mucosa, IM without concurrent GC (IM-GC), IM with concurrent GC (IM+GC) and GC. This comparative study revealed an incremental increase in p53 expression levels with progression of disease from normal mucosa, via an IM intermediate to GC. TP53 mutations however, were not detected in IM but occurred frequently in GC. Further, we identified increased protein expression of Mdm2/x, both powerful regulators of p53, in 100% of the IM+GC cohort with these samples also exhibiting high levels of wild-type p53 protein. Our data suggests that TP53 mutations occur late in gastric carcinogenesis contributing to the final transition to cancer. We also demonstrated involvement of Mdmx in GC. 相似文献
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Ricardo A. Maselli William Ellis Raul N. Mandler Firdos Sheikh Grace Venton Stephen Knox Hamid Salari-Namin Mark Agius Robert L. Wollmann David P. Richman 《Muscle & nerve》1997,20(10):1284-1295
Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness. Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases. Muscle biopsies showed variable signs of neurogenic atrophy. In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder. Mechanical ventilation was required in 5 patients. Half of the patients were treated with polyvalent antitoxiin. Prognosis was favorable, though recovery was slow. In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism. High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1284–1295, 1997 相似文献
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Rehna Rasheed Gopal S Pillai Harish Kumar Adish Thayyil Shajan Natasha Radhakrishnan Greeshma C Ravindran 《Indian journal of ophthalmology》2021,69(11):3370
Purpose:To determine the relationship between diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and their associated risk factors.Methods:We conducted a cross-sectional analysis on 500 patients who attended the Endocrinology department at a quaternary health care center in Kerala between November 2017 and April 2018. Patients above the age of 30 years with type 2 diabetes mellitus (DM) were included. They underwent a detailed medical history, dilated fundus examination for DR, assessment and grading of DPN, and blood investigations. Among these, 49 randomly selected patients without DR had peripapillary retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) assessed by optical coherence tomogram. RNFL and GCIPL changes in different grades of neuropathy were evaluated.Results:Out of 500 patients, 303 (60.6%) were males and 197 (39.4%) were females. Prevalence of DR was 48% and DPN 71.8%. Risk factors for the development of DR included duration of DM >15 years, HbA1c (glycated hemoglobin) greater than 6.5%, serum creatinine more than 1.5 mg/dl, and the presence of DPN. There was a statistically significant association between DR and DPN. There was significant thinning of GCIPL in patients with moderate to severe neuropathy without DR.Conclusion:There is a significant association between DR and DPN and their severities. There are early changes in inner retinal layers of diabetic patients without microvascular changes of DR. These neurodegenerative changes parallel DPN in the course of DM. Our study stresses the importance of multidisciplinary approach in the management of diabetes and its complications. 相似文献
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Sheikh Shawkat Kamal 《世界耳鼻咽喉头颈外科杂志(英文)》2021,7(4):265-269
ObjectiveTo evaluate the necessity and effectiveness of a preplanned technique for drilling during transcanal endoscopic ear surgery.MethodsStudy design: Retrospective case series study from June 2011 to June 2015. Setting: Private tertiary care hospital. Patients: Eighty-five ears of 78 patients, age ranging from 9 to 57 years underwent transcanal endoscopic drilling for various types of pathology in their middle and external ear. Interventions: Application of a preplanned technique for transcanal drilling in endoscopic ear surgery that involved short timed drilling with use of intermittent irrigation and suction. Every events of the procedure were done one after another with the single hand of the surgeon. An attachment providing protecting sheath around rotating burr was used during each time of drilling. Main outcomes measure: Efficacy of such drilling technique in single handed endoscopic ear surgery. Presence of any postoperative thermal injury of facial nerve and any lacerated injury of skin of external ear.ResultsThis preplanned technique was found suitable for transcanal endoscopic drilling with the single hand of the surgeon. Postoperative facial nerve palsy or laceration of skin of external ear was not noted in any patient.ConclusionAfter using the present technique, transcanal endoscopic drilling could be done easily and safely with single hand of the surgeon. 相似文献
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Baylee Roy Sara Knapke Natasha Pillay-Smiley Xue Zhang Kate Queen Rebecca Sisson 《Pediatric blood & cancer》2024,71(1):e30725
An estimated 8.6% of all pediatric patients with central nervous system tumors (CNSTs) have underlying hereditary cancer predisposition (HCP). Identifying HCP affects risk assessment and medical management options for the patients and their family members. However, there is a lack of consensus on the optimal germline genetic testing (GT) approach for pediatric patients with CNSTs. As a first step in addressing the need for consensus, we surveyed oncology and genetics providers from 47 institutions in professional organizations across the United States. We investigated their current practice (e.g., GT decisions and ordering practices) when assessing pediatric patients with CNSTs for HCP. We received 60 responses from 21 pediatric oncologists, 10 neuro-oncologists, 28 genetics providers, and one neuro-oncologist/geneticist. Results demonstrate genetic counselors, followed by oncologists, most often facilitated consent, ordered testing, and selected which test to order. The most ordered test was a multi-gene panel (60%). Of 18 CNST diagnoses, choroid plexus carcinoma (CPC) was the diagnosis for which most providers (78%) reported they would offer GT. For medulloblastoma, 56% overall reported they would offer GT (64% of genetics providers, 62% of neuro-oncologists, 20% of pediatric oncologists; p = .050). Findings suggest that even for the CNSTs most commonly known to be associated with HCP regardless of family history, there was variability in providers’ decisions to offer GT. The lack of consensus in GT decisions in our study indicates inconsistencies in the genetics care of pediatric patients with CNSTs, demonstrating a need for consensus guidelines to promote consistent genetics care. 相似文献