Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.

BACKGROUND: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. PURPOSE: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. RESULTS: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. CONCLUSIONS: Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.     

Fetal erythropoiesis in steel mutant mice. III. Defect in differentiation from BFU-E to CFU-E during early development

Erythroid progenitor cells in +/+ and Sl/Sld fetal livers manifested as burst-forming units-erythroid (BFU-E) and colony-forming units- erythroid (CFU-E) were assayed in vitro during early development. The proportion of BFU-E was higher as mutant than in normal fetal livers. On the other hand, the proportion of CFU-E was less in the mutant than in the normal. These results suggest that the defect in Sl/Sld fetal hepatic erythropoiesis is expressed at the steps of differentiation that effect the transition from BFU-E to CFU-E.     

Intense pulsed light vs. pulsed‐dye laser in the treatment of facial acne: a randomized split‐face trial

Background Various laser and light therapy have been increasingly used for the treatment of acne vulgaris. Patients and methods Twenty patients with facial acne were treated using intense pulsed light (IPL) on one side of the face and pulsed dye laser (PDL) on the other to compare the efficacy and safety of IPL and PDL. Treatment was performed 4 times at 2‐week intervals. Treatment effectiveness was determined using lesion counts, acne severity, patient subjective self‐assessments of improvement, and histopathological examinations, which included immunohistochemical staining for transforming growth factor‐β (TGF‐β). Results Numbers of total acne lesions decreased following both treatments. For inflammatory lesions such as papules, pustules and nodules, IPL‐treated sides showed an earlier and more profound improvement than PDL‐treated sides. However, at 8 weeks after the 4th treatment, a rebound aggravation of acne was observed on IPL‐treated sides. On the contrary, PDL produced gradual improvements during the treatment sessions and these improvements lasted 8 weeks after the 4th treatment. Non‐inflammatory lesions as open and closed comedones also showed improvement following both treatments and PDL‐treated sides showed better improvement as the study proceeded. Histopathological examinations showed amelioration in inflammatory reactions and an increase in TGF‐β expression after both treatments, which were more prominent for PDL‐treated sides. Conclusion Both PDL and IPL were found to treat acne effectively, but PDL showed a more sustained effect. TGF‐β might play a key role in the resolution of inflammatory acne lesions.     

Non‐ablative 1550‐nm erbium‐glass and ablative 10 600‐nm carbon dioxide fractional lasers for acne scars: a randomized split‐face study with blinded response evaluation

Background Non‐ablative 1550‐nm erbium‐doped fractional photothermolysis systems (FPS) and 10 600‐nm carbon dioxide fractional laser systems (CO₂ FS) have been effectively used to treat scars. Objective We compared the efficacy and safety of single‐session treatments of FPS and CO₂ FS for acne scars through a randomized, split‐face, evaluator‐blinded study. Methods Eight patients with acne scars were enrolled in this study. Half of each subject’s face was treated with FPS and the other half was treated with CO₂ FS. We used a quartile grading scale for evaluations. Results At 3 months after the treatment, the mean grade of improvement based on clinical assessment was 2.0 ± 0.5 for FPS and 2.5 ± 0.8 for CO₂ FS. On each side treated by FPS and CO₂ FS, the mean duration of post‐therapy crusting and scaling was 2.3 and 7.4 days respectively and that of post‐therapy erythema was 7.5 and 11.5 days respectively. The mean VAS pain score was 3.9 ± 2.0 with the FPS and 7.0 ± 2.0 with the CO₂ FS. Conclusion We demonstrated the efficacy and safety of single‐session acne scar treatment using FPS and CO₂ FS in East Asian patients. We believe that our study could be used as an essential reference when choosing laser modalities for scar treatment.     

Collapsin-1/semaphorin-III/D is regulated developmentally in Purkinje cells and collapses pontocerebellar mossy fiber neuronal growth cones

Most axons in the CNS innervate specific subregions or layers of their target regions and form contacts with specific types of target neurons, but the molecular basis of this process is not well understood. To determine whether collapsin-1/semaphorin-III/D, a molecule known to repel specific axons, might guide afferent axons within their cerebellar targets, we characterized its expression by in situ hybridization and observed its effects on mossy and climbing fiber extension and growth cone size in vitro. In newborn mice sema-D is expressed by cerebellar Purkinje cells in parasagittal bands located medially and in some cells of the cerebellar nuclei. Later, sema-D expression in Purkinje cells broadens such that banded expression is no longer prominent, and expression is detected in progressively more lateral regions. By postnatal day 16, expression is observed throughout the cerebellar mediolateral axis. Collapsin-1 protein, the chick ortholog of sema-D, did not inhibit the extension of neurites from explants of inferior olivary nuclei, the source of climbing fibers that innervate Purkinje cells. In contrast, when it was applied to axons extending from basilar pontine explants, a source of mossy fiber afferents of granule cells, collapsin-1 caused most pontine growth cones to collapse, as evidenced by a reduction in growth cone size of up to 59%. Moreover, 63% of pontine growth cones arrested their extension or retracted. Its effects on mossy fiber extension and its distribution suggest that sema-D prevents mossy fibers from innervating inappropriate cerebellar target regions and cell types.     

Breast cancer detection: one versus two views

Mammographic examinations of 169 patients with 172 biopsy-proved carcinomas, and of 194 healthy subjects, were interpreted independently and retrospectively by three experienced mammographers, initially as single-view oblique examinations and 6 months later as two-view oblique-cephalocaudal examinations. For the single-view examinations of the cancer patients, 67% of the cancers were correctly recommended for biopsy, additional views were requested for 23%, and a "negative" interpretation was made for 10%. For the single-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were recommended for 32%. For the two-view examinations of women with cancer, 80% of the cancers were correctly recommended for biopsy, additional views were requested for 4%, and a "negative" interpretation was made for 16%. For two-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were requested for only 5%. The authors conclude that single-view screening should not be performed, because it would lead to an excessive number of "call-back" examinations of healthy patients, producing additional cost and anxiety that would outweigh any theoretical benefit.     

The efficacy of subcutaneous recombinant human erythropoietin in the correction of phlebotomy-induced anemia in autologous blood donors

The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3- week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 +/− 1.0 g/dL [140 +/− 10 g/L]) was completely recovered before surgery (14.0 +/− 1.6 g/dL [140 +/− 16 g/L]) in the EPO group, while a decrease from 13.8 +/− 1.1 to 12.2 +/− 1.3 g per dL (138 +/− 11 to 122 +/− 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 +/− 29 micrograms per L in the EPO group and to 54 +/− 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

多普勒超声诊断移植肾排斥反应与病理检查及肾功能指标的对比分析

目的：以病理活检结果为金标准，评估多普勒超声检查对移植肾排斥反应的诊断价值。方法：选择2003—01/2006—12在中国医科大学附属第一医院器官移植科行肾移植并在术后行超声检查的患者176例，均知情同意。①实验分组：根据术后移植肾功能分为2组，移植肾功能不良组78例，其中30例次行病理活检；移植肾功能正常组98例。②实验方法及评估：对患者移植肾行多普勒超声检查，参数选择峰收缩期流速、平均舒张期流速、阻力指数及血管显示率。血管显示率的评估标准（0～5级）：0级为肾动脉及其远侧血管未显示；5级为肾各级血管均显示良好。以病理活检结果为金标准，分别选取阻力指数=0．7，0．75，0．8，0．85为诊断界值进行诊断试验。结果：169例患者进入结果分析，脱落7例。①峰收缩期流速、平均舒张期流速不呈正态分布，无法作为肾功能评价指标。30例次病理活检中共有28例次被确诊为排斥反应，急性排斥反应15例次，慢性排斥反应13例次。②肾功能正常组患者中血管显示率5级者占63．30％，4级者占36．73％。肾功能不良组患者中血管显示率4级者占41．03％，3级者占46．15％，2级者占10．30％，1级者占2．60％。③移植肾功能不良组患者阻力指数显著高于移植肾功能正常组（P〈0．01）。移植肾功能不良组患者移植肾功能恢复后阻力指数显著低于移植肾尚未恢复时（P〈0．01），其中99％以上的患者△（阻力指数）≥0.20。④界值阻力指数=0．75的诊断试验的敏感性、特异性和准确性最高，均达到100％。结论：当移植肾血管阻力指数升高至0．75以上，特别是同一患者自身对照升高超过0.2以上和或血管显示率低于4级，结合临床表现和生化结果，提示可能出现移植肾排斥反应。