Does preoperative needle localization lead to an increase in local breast cancer recurrence?

Between 1978 and 1981, 74 women with nonpalpable breast cancer underwent surgery after localization guides were placed. In 72 patients, guides were introduced parallel to the chest wall; in two the needle was positioned anteroposteriorly under computed tomographic guidance. Fifty-six cases (76%) were infiltrating cancer; 13 (17%), intraductal cancers; two (3%), inflammatory; and three (4%), lobular carcinoma in situ. Surgery was not used to treat the latter five patients. In the remaining 69 women, 42 (61%) were treated by means of modified radical mastectomy; six (9%), total mastectomy; 12 (17%), local excision and radiation therapy; and seven (10%), local excision alone; exact therapy for two women (3%) was unknown. At a minimum follow-up of 5 years, none of the 67 women in whom the parallel approach was used had a local recurrence. The authors conclude that preoperative placement of guides parallel to the chest wall does not appear to increase the risk of local breast cancer recurrence.     

Mutant constructs of the beta-adrenergic receptor that are uncoupled from adenylyl cyclase retain functional activation of Na-H exchange.

beta-Adrenergic receptor (beta AR) agonists modulate a number of intracellular effectors; for example, they stimulate adenylyl cyclase and Ca2+ channels, inhibit Na+ channels and Mg2+ efflux, and activate Na-H exchange. Regulation of adenylyl cyclase, Ca2+, Na+, and Mg2+ by the beta AR is mediated through receptor coupling to the GTP-binding protein Gs. We have previously determined, however, that beta AR stimulation of Na-H exchange occurs independently of receptor coupling to Gs. In the present study, we analyzed mutant beta ARs containing deletions of amino acid residues within the third cytoplasmic domain, to determine whether there is a structural basis for the ability of the beta AR to couple divergently to the Gs-dependent stimulation of adenylyl cyclase and the Gs-independent activation of Na-H exchange. Receptor constructs with deletions of residues 222-229 and 258-270, which were previously shown to be defective in coupling to Gs and adenylyl cyclase, retained an isoproterenol-induced activation of Na-H exchange that was similar in time course and magnitude to that observed with the wild-type beta AR. These results confirm our previous findings that the beta AR activates Na-H exchange independently of Gs, and they further suggest that distinct molecular determinants of the receptor divergently stimulate adenylyl cyclase and Na-H exchange.     

Application of image-guided surface coil P-31 MR spectroscopy to human liver, heart, and kidney

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.     

环孢菌素A阻断人HL-60抗药性细胞于G1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的HL-60细胞(HR20)抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明,环孢菌素A(CsA)20,10μg·ml^-1诱导HL-60细胞发生凋亡,而阻断HR20细胞于G₁期,就不能诱导细胞发生凋亡。低浓度的CsA明显增加柔红霉素在HR20细胞内的积聚,其逆转抗药性作用与阻断细胞周期运行无关。CsA10μg·ml^-1处理HR20细胞,可引起50kDa的蛋白质高度磷酸化。结果提示:环孢菌素A阻断抗三尖杉酯碱的HL-60细胞于G₁期,而诱导敏感的HL-60细胞发生凋亡,其阻断作用与抗药性无关。     

Evaluation of reproductive parameters in adult male Wistar rats after subchronic exposure (gavage) to benomyl

Proven-breeder 102-d-old male Wistar rats were gavaged daily with 0, 1, 5, 15, or 45 mg/kg.d benomyl. The animals were bred to untreated females after 62 d and killed after 76-79 d for evaluation of selected male reproductive end points. Minimal to moderate changes were observed in rats dosed with 45 mg/kg.d; these included decreased testis and epididymis weight, reduced cauda sperm reserves, decreased sperm production, increased numbers of decapitated spermatozoa, and increased numbers of seminiferous tubules containing multinucleated giant cells. Reproductive performance, seminal vesicle and prostate weight, sperm motility, serum luteinizing hormone, follicle-stimulating hormone, prolactin, and androgen binding protein were not affected by any of the dosages tested. Based on these end points, the no-effect level was 15 mg/kg.d.     

Complications of spinal cord arteriography: prospective assessment of risk for diagnostic procedures

A prospective study was done of complications associated with 134 consecutive diagnostic spinal cord arteriograms in 96 patients (63 men and 33 women aged 17-78 years). Patients were examined for either arteriovenous malformation (n = 88) or tumor (n = 8), as indicated by myelography. Among the complications, 11 (8.2%) were local, five (3.7%) were systemic nonneurologic, and three (2.2%) were neurologic (two were associated with full recovery in less than 24 hours, and one was associated with full recovery in less than 1 week). No specific clinical or technical factors were significantly associated with the development of neurologic complications. Details of the clinical profile, angiographic technique, and pathologic findings for each patient were recorded and analyzed with respect to the potential risk for arteriographic complications. Diagnostic spinal cord arteriography had an acceptable risk within the range of other neuroangiographic diagnostic procedures.     

Acute effects and long-term sequelae of 1,3-dinitrobenzene on male reproduction in the rat. I. Sperm quality, quantity, and fertilizing ability

Groups of eight adult male rats were given a single oral dose of 0 or 48 mg/kg of 1,3-dinitrobenzene and sacrificed at 1, 2, 4, 8, 16, 24, 32, 72, and 175 days posttreatment. The groups killed at 175 days were bred to untreated females during weeks 3, 4, 6, 9, 13, and 24. Decreased testis weight and testicular sperm numbers were observed by day 4; decreased cauda sperm reserves and epididymis weight occurred by day 8 and day 16, respectively. Reduced numbers of motile spermatozoa and abnormal sperm morphology were seen in spermatozoa from the cauda epididymidis by day 16. Fertilizing ability, as indicated by the presence of two pronuclei and a sperm tail in eggs flushed from the oviducts of inseminated females, was slightly reduced by week 4 and declined to zero by week 6. Group means for reproductive organ weights, sperm production, and sperm reserves failed to return to control levels although some individual animals approached full recovery. Normal fertilizing ability was restored in most animals by week 13, but two of seven remained infertile. Occlusion of some efferent ductules was observed in three of seven animals at 175 days. This study indicates that 1,3-dinitrobenzene is a potent testicular toxicant in the rat, capable of producing marked testicular damage, infertility, and possibly sterility from a single exposure.