Overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in head and neck squamous cell carcinomas

Squamous cell carcinoma of the head and neck region (HNSCC) is the sixth most frequent cancer worldwide. In the USA, 30,000 new cases and 8,000 deaths are reported each year. Differences between normal epithelium and cancer cells from the upper aerodigestive tract arise from alterations in expression of specific genes controlling proliferation and immortalization. The protein products of these genes include growth factor receptors, cell cycle regulators, and tumor suppressors which affect a variety of intracellular signaling pathways. To determine how altered expression of these gene products contribute to HNSCC progression, we examined expression of epidermal growth factor receptor (EGFR), cyclins, p16INK4A, c-myc, proliferating cell nuclear antigen (PCNA), and telomerase in archival pathology specimens by immunohistochemistry. A substantial majority of HNSCC tumors showed loss of p16INK4A expression and dramatic overexpression of EGFR. Overexpression of this receptor correlated with increased cyclin A levels and high mitotic index. EGFR, cyclins A, -B1, -E, and c-myc overexpression was significantly increased in stage III and IV tumors compared to early stage cancers. hTERT was expressed in all tumors and primarily in the basal layer cells of dysplastic epithelial lesions. Suprabasal expression of hTERT was found in a significantly higher number of HNSCC cases than in dysplastic lesions. These results indicate that overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in HNSCC.     

Ethics Seminars HIV Testing, Consent, and Physician Responsibilities

Emergency physicians constantly have multiple ethical obligations in the emergency department. They must understand these sometimes conflicting obligations and learn to prioritize. A case discussion is presented that exemplifies the conflict between patient privacy and society's right to know. Specific aspects of HIV testing and obtaining patient consent are presented. Teaching physicians are encouraged to use such common cases for "ethics case discussion."     

Gene interventions in the beta-adrenergic system for treating heart failure

Cardiovascular disease accounts for nearly 40% of all deaths annually in this country. Prevention management and advances in medical treatments have dramatically reduced the overall mortality rate due to heart disease. However, death due to chronic heart failure (HF) continues to rise, and effective therapy, particularly for end-stage HF, has been elusive. The myocardial beta-adrenergic receptor (betaAR) system is critical not only in chronic HF but also in acute settings where cardiac function is compromised. Adding to its importance is the fact that drugs that act by altering betaAR signal transduction are at the forefront of conventional HF therapeutic strategies. Accordingly, the ability to genetically manipulate betaAR signaling in the heart is of great interest since it may provide unique inotropic support and improve existing therapeutic strategies for HF.     

Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity

PURPOSE: To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause. DESIGN: Observational case series and genetic study. PARTICIPANTS: Two unrelated probands presenting with absent central retinal vessels and 11 available family members. TESTING: Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed. MAIN OUTCOME MEASURES: Better defined characteristics of the papillorenal syndrome. RESULTS: Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected. CONCLUSIONS: In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.     

Evaluation of the Sheffield system for identifying children at risk from unexpected death in infancy. Results from Birmingham and Newcastle upon Tyne

The "at birth" system which is used in Sheffield to identify children likely to die unexpectedly in infancy, was tested retrospectively in Birmingham (83 cases) and in Newcastle upon Tyne (56 cases). The discrimination between cases and age-matched controls was poor in both cities. Analysis of the 8 factors used in the system showed that only 2 maintained significant case/control differences in Birmingham and Newcastle. Further investigation showed that other factors from maternity records showed significant case/control differences in these cities. Although the system used in Sheffield would not be of use in a prospective prevention programme in either Newcastle or Birmingham, the possibility of evolving an "at risk" system which might apply more widely is discussed.     

高三尖杉酯碱酰胺的结构测定

三尖杉树皮粗提取物中的一个新生物碱—高三尖杉酯碱酰胺(homoharringtonamide)的结构,经质谱—质谱分析,初步建议为16。类似的酰胺类生物碱,例如三尖杉碱酰胺(cephalotaxamide,6)、11-羟基三尖杉碱酰胺(11-hydroxycephalotaxamide,9)、三尖杉酯碱酰胺(harfingtonamide,14)或异三尖杉酯碱酰胺(isoharringtonamide,15)也可能存在,后三者(9,14,15)尚未见报道。