ATM, an unexpected new target in metabolic syndrome

ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
Schneider et al. (2006)
Cell Metabolism: 4 (5): 377–389     

Statistical design of toxicity assays: role of genetic structure of test animal population

This paper considers certain statistical aspects of the problem of among-strain differences in cancer susceptibilities and how these differences may affect the design of toxicity assays. First, in order to investigate the magnitude of within-study, between-strain differences in tumor induction, the data of Innes et al. (1969) were examined. It was found that although there was a very high overall association between mouse strains with respect to the induction of hepatomas, several compounds showed evidence of strain-to-strain variability. Next, a number of long-term carcinogenicity studies with DDT were considered, and among-strain differences in cancer susceptibility for this compound were noted. Finally, it was shown that if susceptible subgroups do exist and certain simplifying assumptions are made, then in many cases tumor increases can be detected more readily by using several inbred mouse strains for study rather than a single outbread stock.     

Work in progress: the application of temporal filtering techniques to hybrid subtraction in digital subtraction angiography

Temporal filtering methods were applied to iodine signal-to-noise ratio (SNR) restoration in intravenous hybrid subtraction digital subtraction angiography (DSA). For equal detected exposure rates hybrid subtraction had approximately 35% of the SNR of temporal subtraction. When matched filtering was applied to a DSA run, the filtered result had approximately two times higher SNR than the peak contrast image in the run. Thus, when matched filtering techniques were applied to the hybrid image sequence, the resultant SNR increased to about 70% of that of temporal subtraction. With an additional factor-of-two increase in exposure rate for the hybrid run, SNR parity with temporal subtraction could be achieved. This compared with a factor-of-nine increase in exposure that would be required if no filtering were performed. Experimental hybrid matched filter results, generated with intravenous canine DSA studies, supported the predictions in SNR performance.     

Toxicity and carcinogenicity of rotenone given in the feed to F344/N rats and B6C3F1 mice for up to two years

Toxicity and carcinogenicity studies of rotenone were conducted in F344/N rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were given rotenone in their diet for up to 103 weeks. The doses were 0, 38, and 75 ppm for rats and 0, 600, and 1,200 ppm for mice. Reduction in body weight gain occurred in male and female mice given rotenone. No effects on survival were observed for rats of either sex or female mice. Survival of male mice at 1,200 ppm was significantly greater than that of controls (47/50 vs. 29/50). There were no observed nonneoplastic effects due to rotenone, and for male and female mice no neoplasms were induced by rotenone. Parathyroid adenomas occurred at a higher incidence (4/44) in male rats at 75 ppm than in the controls (1/41). Because these tumors are rare (historical rate in NTP studies is 0.3%), the increase in the incidence of these benign tumors may have been related to rotenone administration. Hepatocellular neoplasms were reduced (p less than 0.01) in males receiving 1,200 ppm 1/50 relative to controls 12/47. Because this low rate of liver tumors is unusual in male B6C3F1 mice, this decrease was considered to be related to rotenone administration.     

The impact of toxicity on carcinogenicity studies: implications for risk assessment

This paper explores the inter-relationship between toxicity,genotoxicity, and carcinogenicity in laboratory rodents. Toour knowledge this is the first attempt to integrate these factorsand evaluate their implications for the process of risk assessment.The evaluation is based on information obtained from 2-yearlaboratory-animal studies involving 99 chemicals. The data suggestthat only seven of the 53 positive carcinogenicity studies exhibitedthe types of target organ toxicity that could have been thecause of all observed carcinogenic effects. Furthermore, noapparent difference in mutagenicity as measured by the AmesSalmonella assay was observed between ‘high dose only’carcinogens and the entire set of carcinogens. These findingssuggest that the number of chemical carcinogens that we canidentify solely through rodent studies as being potential tumorinducers through some indirect mechanism is small. Generallyspeaking, the identification of histopathological effects isnot sufficient in itself for justifying mechanistic assumptions,and supplemental biological information will be necessary toreach definitive conclusions.     

Chelate conjugates of monoclonal antibodies for imaging lymphoid structures in the mouse

Radiolabeling of a mouse monoclonal antibody (MoAb) specific for the mouse histocompatibility alloantigen IAk expressed by the B lymphocytes of BALB/k and C3H mice but not BALB/c mice was performed by mixing the chelate-labeled anti (alpha) IAk MoAb with purified, no-carrier-added 111In citrate. Labeling efficiency was 85-95%, and the labeled alpha IAk MoAb retained its antigen binding properties in vitro and in vivo. The organ, spleen, and lymph node distribution of intravenously and subcutaneously administered 111In alpha IAk MoAb was compared in mice, two IAk positive and one IAk negative strains, and to 125I alpha IAk MoAb in one IAk positive strain. The 111In alpha IAk MoAb was more stable in vivo compared to 125I alpha IAk MoAb, as shown by a much slower excretion and a higher absolute uptake in lymph nodes and spleen. Lymph node to blood ratio was increased twofold by intravenous anti-EDTA MoAb. Subcutaneous injection permitted clear images of the tiny lymph nodes in the mouse. Potential clinical applications of 111In alpha lymphocyte MoAb include localization of normal lymph nodes and T & B cell leukemias and lymphomas, as well as detecting lymphatic metastases of other cancers. Therapy may also be possible using MoAbs labeled with beta-emitting metal ions such as yttrium-90.     

Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: Report on 24 months of surveillance

Objective : To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization.
Methodology : Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described.
Results : Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days. Infection rates were significantly higher in lower birthweight groups. Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group. Antibiotic exposure averaged 12% of total admission days, less than previously published data.
Conclusions : The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.     

Accumulation of a bone imaging agent in liver metastases from prostate carcinoma

A patient with adenocarcinoma of the prostate presented with right upper quadrant abdominal pain and weight loss. Liver biopsy revealed hepatic metastases from prostate carcinoma. A bone scan demonstrated marked uptake of Tc-99m MDP within the hepatic metastases.     

消旋棉酚拆分的研究——Ⅳ.苏(-)或(+)-1-(对硝基苯基)-1,3-二羟基丙胺-2为拆分剂

本文介绍以光学活性苏-1-(对硝基苯基)-1,3-二羟基丙胺-2为拆分剂,与消旋棉酚缩合,用常压柱色谱或溶剂结晶法分离得到两个光学纯的非对映体,然后分别水解得(+)和(-)-棉酚。     

Proton spectroscopic imaging (Dixon method) of the liver: clinical utility

The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases.