Kinetics of DNA methylation by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in F344 rats

The carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was injected intravenously (0.41 mmol/kg) into F344 rats. DNA from target organs (lung, liver) and a non-target organ (kidney) was extracted hydrolysed and analysed for methylated guanines by cation-exchange high-performance liquid chromotography-fluorimetry. Levels of O6-methylguanine, a promutagenic lesion, and 7-methylguanine were three to eight times higher in the liver than in the lung. Neither base could be detected in the kidneys. The extent of methylation of hepatic DNA by NNK was 35 times lower than observed with an equimolar dose of NDMA by Swann et al. (1983). The levels of the two methylated guanines in liver and lung DNA increased between 4 and 24 h following NNK injection. NNK is metabolized rapidly in F344 rats to 4-(methylnitrosamino)-1(3-pyridyl)-butan-1-ol (NNA1). The relatively slow methylation of hepatic DNA after injection of NNK could be due to a slow release of methylating species from the major circulating metabolite NNA1. This low but sustained level of O6-methylguanine induced by NNK could, in part, explain its carcinogenic potency.     

Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver

Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.     

Surgical Treatment of the Denervated or Sagging Lower Lid

Paralytic ectropion of the lower eyelid and increased curvature of the lower eyelid associated with anophthalmos both can be optimally treated by use of an autogenous fascia lata sling. Some patients also have problems with prosthesis retention due to lower eyelid deformity with a shortened inferior fornix. In some instances, it is also necessary to perform a horizontal shortening operation on the lower eyelid. In anophthalmic patients, the relationship between prosthesis size and weight and a sagging lower lid is discussed. In some patients when the lower eyelid is elevated, the patient then has an upper lid ptosis for which it is necessary to perform an appropriate levator shortening operation. Surgical technique and illustrative pre- and post-operative photographs are shown.     

Metabolites of a tobacco-specific lung carcinogen in nonsmoking casino patrons.

Epidemiologic data have shown increased risks of lung cancer in nonsmokers exposed to environmental tobacco smoke (ETS). We measured biomarkers in urine samples from nonsmokers before and after a 4-h visit to a casino where smoking is allowed. The tobacco-specific lung carcinogen, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is a constituent of ETS. Urinary metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Gluc), are excellent biomarkers of human uptake of NNK and NNAL. NNAL, as with NNK, is a potent pulmonary carcinogen. Subjects collected a spot urine sample before the casino visit and all urine samples for the 24-h period starting after the visit. We analyzed samples for creatinine, total cotinine (cotinine and cotinine-glucuronide), and total NNAL (NNAL plus NNAL-Gluc). Paired samples showed statistically significant mean increases in total cotinine (0.044 nmol/mg creatinine, P < 0.0001) and total NNAL (0.018 pmol/mg creatinine, P < 0.001). These findings demonstrate that exposure of nonsmokers to ETS in a commercial setting results in uptake of a tobacco-specific lung carcinogen.     

Hematopoietic growth factors in bone marrow transplantation.

Preliminary clinical results demonstrate the activity of recombinant human granulocyte (rHuG) and granulocyte/macrophage (rHuGM) colony stimulating factors (CSFs) in enhancing bone marrow engraftment after autologous and allogeneic bone marrow transplantation (BMT). In several analyses of prospective, controlled clinical trials of rHuG- and rHuGM-CSF, reduced morbidity and cost, as well as improved survival have been observed. There is reason to hope that more profound understanding of the in vivo biology of these and other cytokines will lead to further reduction in morbidity and mortality associated with both autologous as well as allogeneic BMT. These advances could significantly broaden the spectrum of diseases amenable to treatment by BMT.     

The frequency of social dysfunction in a general population sample and in patients with mental disorders

Summary The frequency of social dysfunctions in a general population sample and in different diagnostic groups was investigated by using the Social Interview Schedule (SIS). Based on the results of the general population sample, several of the a priori derived cut-off scores of the SIS were modified. The analysis of the general population sample revealed sex-specific relationships between age and different aspects of social functioning. Especially for younger women significantly more objective social restrictions, were found due to the burden of multiple role responsibilities. With regard to different diagnostic subgroups including patients and mostly untreated cases from the community sample with Affective Disorders and Anxiety Disorders, results indicate that the degree of social impairment and dysfunctions and the degree of satisfaction with different role areas are strongly dependent on type of disorder and on former treatment status. Specific findings are: (1) The highest number of social impairments and dysfunctions were found in cases and patients with affective syndromes and in schizophrenic patients, but not in schizoaffective patients. (2) Management difficulties and dissatisfaction in intimate relationships were primarily found in depressed women. (3) Unlike anxiety patients, anxiety cases, although mostly chronically ill, had significantly less objective impairments and a lower rate of dissatisfaction than depressed cases. The results are discussed with special reference to the possible key role of depression for the development of social dysfunctions, as measured by the SIS. (4) Problems were, however, acknowledged concerning the use of the SIS with severely disturbed chronic schizophrenic patients.This study is part of the Munich Follow-up Study (MFS), funded by the Robert Bosch Foundation.     

人参皂甙Rg1对老年大鼠免疫调节作用的机制分析

采用流式细胞检测和Western印迹分析法证明,人参皂甙Rg₁可明显促进IL-2受体α链的表达和抑制可溶性IL-2受体的释放。Fura-2荧光检测发现,Rg₁对大鼠脾淋巴细胞的静息钙离子浓度和ConA诱导的升钙效应均无明显影响,但却使cAMP和cGMP水平升高。鉴于环核苷酸在机体免疫调节中所起的重要作用,故可推测Rg₁调节老年大鼠免疫功能的分子机制与其选择性提高脾淋巴细胞内环核苷酸水平有关。