Experimental spinal cord injury: effects of trauma or ischemia on TRH and muscarinic receptors

Traumatic spinal cord injury in rats and ischemic spinal cord injury in rabbits were associated with time-dependent, localized decreases in thyrotropin-releasing hormone (TRH) and muscarinic receptor binding. Changes were not evident in the first 24 to 48 hours, consistent with the hypothesis that secondary alterations in spinal cord may occur relatively late after injury. TRH receptor binding, but not muscarinic receptor binding, recovered by 3 weeks following trauma. Since TRH and acetylcholine may serve as excitatory neurotransmitters within the spinal cord, such changes could contribute to the functional neurologic impairment that follows injury.     

四环素类抗生素的RP-HPLC分析

报道了用反相高效波相色谱分析去甲基金霉素等四环素类抗生素和它们的差向异构体以及其脱水物的方法。采用Water 10C₁₈ 4.6mm ID×259mm的色谱柱,以14%乙腈-3%二甲基甲酰胺-83%0.02mol/L柠檬酸水溶液为流动相,流速1.0ml/min,UV 350 um检测,可将四环素、去甲基四环素、金霉素、去甲基金霉素和它们的差向异构体八种化合物完全分离;以15%乙腈-15%二甲基甲酰胺-70% 0.02mol/L柠檬酸水溶液为流动相,流速1.0ml/min,UV270nm检测,可将上述抗生素及其差向异构体以及它们的脱水物十六种化合物分离。它们的发酵液经简单处理亦可直接进样分析。同时还考查了pH、溶剂等因素对分析的影响。     

Contribution of videothoracoscopy to the management of the cancer patient

Background: Videothoracoscopy has rapidly become a popular procedure, but its technical feasibility has been emphasized without critically evaluating its role in the management of thoracic disease. To assess the value of videothoracoscopy in the diagnosis and staging of the cancer patient and to determine if it has added to our previous standard approach of thoracoscopy performed with a mediastinoscope without video, we established a prospective database when we initiated videothoracoscopy in January 1992. Methods: Patients were offered videothoracoscopy as an alternative to thoracotomy only if other standard approaches (e.g., needle biopsy, mediastinoscopy) were inadequate to diagnose or stage cancer or to restage patients after therapy. Parameters entered and analyzed in a prospective database were patient name; age; sex; past history; indications for videothoracoscopy; procedure type; surgical technique; whether conversion to thoracotomy was necessary, and if so, why; complications; and pathology. A complete case list of thoracoscopies performed in 1991 before videothoracoscopy was available provided historical comparison. Results: From January 1 to December 31, 1991, 82 patients underwent thoracoscopy using a mediastinoscope for diagnosis and therapy of pleural disease. From January 1 to July 31, 1992, 160 patients (male:female=81:79; mean age 56 years) had videothoracoscopy; 72 of 160 patients (44%) had procedures that previously would have required thoracotomy: 69 lung wedge resections, one pericardial window, one pleurectomy, one mediastinal node sampling. No major resectional procedures (e.g., lobectomy, esophagectomy) were performed by videothoracoscopy. Twenty-two percent of all patients (35 of 160), and 23% of wedge resection patients (16 of 69) required conversion to thoracotomy because videothoracoscopy was inadequate for diagnosis or staging. Reasons for conversion (multiple reasons in five patients) included further resection required in 23 patients; inability to evaluate lesion in 11; adhesions in five; and inability to tolerate one lung ventilation in two. The chest tube was in place postoperatively for a mean of 2.3 days. Thirty-day postoperative complications included ventilation for >48 h in one patient; prolonged air leak in one; pneumonia in one; arrhythmia in one; and death from progressive disease in two. Conclusions: Although the role of videothoracoscopy in the treatment of primary thoracic malignancies and pulmonary metastases is still undefined, this early experience indicates that videothoracoscopy often enhances the ability to diagnose and stage patients by obviating thoracotomy. Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

In vitro activation of the human Harvey-ras proto-oncogene by aflatoxin B1

Activation of ras proto-oncogenes occurs frequently in vivo in chemically induced rodent tumours, including rat hepatomas induced by aflatoxin B1. This study examines the in vitro activation of a human ras gene by this mycotoxin. A plasmid containing the human Ha-ras proto- oncogene, together with a neomycin resistance gene (pECneo), was incubated in vitro with a microsomal system generating aflatoxin B1 8,9- epoxide. Subsequent transfection of the plasmid into mouse NIH 3T3 fibroblasts, followed by G418 selection and s.c. injection of surviving cells into immunodeficient mice demonstrated that the proto-oncogene had acquired transforming capacity. Although a single tumour resulted from similar treatment of incubated unconjugated plasmid, no tumours were produced by a secondary round of transfections using DNA from this tumour. Selective PCR amplification of the human Ha-ras gene in extracted tumour DNA followed by sequencing demonstrated the presence of G-->T transversions either at the first or middle base of codon 12 in tumours resulting from transfection with the aflatoxin-B1-modified pECneo plasmid, but this was not detected in the single tumour resulting from transfection with the unmodified plasmid. Thus, although a mutation in the Ha-ras gene has not been reported for human primary hepatomas occurring in aflatoxin-exposed populations, metabolically activated aflatoxin B1 is capable of mutating this proto-oncogene to its oncogenic form in vitro. No mutations were observed in codon 61. It appears that, in contrast to the frequently reported G-->T transversions in codon 249 of the p53 gene in primary hepatomas in aflatoxin-exposed humans, the failure to detect Ha-ras mutations in these tumours is not due to an inability of aflatoxin B1 to activate this proto-oncogene. The G-->T transversions observed in this study contrast with the most frequent aflatoxin B1 in vivo induced mutations, G-->A transitions in the rat Ki-ras gene. Possible mechanisms for these differences are discussed.