Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

Predicting failure in polytetrafluoroethylene vascular access grafts for hemodialysis: a pilot study

In order to determine if serial, noninvasive evaluation of polytetrafluoroethylene (PTFE) vascular access grafts could identify a subgroup of patients at risk for thrombosis, the authors studied flow characteristics, using duplex ultrasonic scanning, in 18 hemodialysis patients with forearm loop grafts. On average, five examinations were performed per patient over the 10-month study period. Seven episodes of thrombosis occurred in six patients. The mean Doppler flow in grafts that subsequently thrombosed was significantly lower than in those that did not (544 +/- 218 ml/min versus 843 +/- 391 ml/min, p less than 0.001). The interval from last examination to thrombosis ranged from 13 to 58 days. At a defined cut-off flow of 450 ml/min, this test yielded a sensitivity of 83% and a specificity of 75% for episodes of thrombosis occurring within 2 to 6 weeks. The authors conclude that episodes of thrombosis in PTFE arm loop grafts are usually preceded by significantly lower Doppler-measured flow than grafts that do not thrombose and that it may be possible, by this means, to identify grafts at risk.     

Association of Hypoalbuminemia on the First Postoperative Day and Complications Following Esophagectomy

Objective Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications. Methods A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20–25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level. Results Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83–0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU. Conclusion Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Therapy-related acute myeloid leukemia secondary to inhibitors of topoisomerase II: from the bedside to the target genes.

In the past five years, several groups have reported acute myeloid leukemia (AML) often monoblastic, as a complication of chemotherapy regimens including the epipodophyllotoxins, etoposide and teniposide. This syndrome is distinct clinically, pathologically and cytogenetically from classical therapy-related myelodysplasia and AML. There is also evidence that other topoisomerase II inhibitors, such as the intercalating agents (including doxorubicin, mitoxantrone, and actinomycin D) may be leukemogenic. Furthermore, there may be further interactions from concomitant topoisomerase II inhibitors and alkylating agents. Topoisomerase II inhibitors induce DNA cleavage and other chromosomal aberrations, including sister chromatid exchanges. These clastogenic abnormalities are not fully understood, and may be specific for each cytotoxic agent. Work is in progress to clone breakpoints such as the t(9;11) and t(8;21) and the use of the resultant DNA probes will enhance our understanding of the leukemogenic process. Given the potential diversity in patients with secondary leukemia, cytogenetic studies should be mandatory for both enhancing our knowledge base and guiding treatment in individual patients. Clinicians must also be wary of the leukemogenic potential of 'dose-intense' regimens including agents such as etoposide and doxorubicin.     

Rates of Borrelia burgdorferi infection in Ixodes dammini (Acari: Ixodidae) in southwestern Wisconsin.

Ixodes dammini Spielman, Clifford, Piesman & Corwin collected from a study site in southwestern Wisconsin were examined for Borrelia burgdorferi infection. Adult spirochete infection rates varied seasonally (38.1%, spring 1990; 60.3%, fall 1990; 41.2%, spring 1991) and were similar to or higher than rates reported in various studies from the northeastern United States. Statistical comparison of seasonal infection rates indicated a significant difference between the fall 1990 adult population and the subsequent overwintered population of the same cohort (spring 1991). Additionally, a significant decrease in the intensity of spirochete infection was observed in the overwintered adult sample.     

Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is marked by circulating antibodies to a 64,000-M(r) islet cell antigen identified as glutamic acid decarboxylase (GAD). We describe a radioimmunoprecipitation assay with GAD isolated from pig brain. The sera tested were from 80 patients with IDDM including 26 with disease of recent onset and 54 with disease of longer duration (3-42 yr), 20 with non-insulin-dependent diabetes mellitus (NIDDM), and 55 nondiabetic subjects. Conventional assays for islet cell cytoplasmic antibodies were performed concurrently. The level of antibody in serum was expressed in units based on percentage reactivity of a standard reference serum. The frequency of antibody to GAD in IDDM was 69% in short-duration cases and 59% in long-duration cases. The latter was substantially higher than the frequency of islet cell cytoplasmic antibody. Antibodies to GAD were elevated (means +/- 3 SD) in 5% NIDDM cases and in none of the nondiabetic subjects. A simple laboratory test with a defined autoantigen has substantial implications for population screening and early diagnosis of IDDM and for better understanding of its pathogenesis.