Genetic and Environmental Contributions to Perceived Intensity and Pleasantness of Androstenone Odor: An International Twin Study

We estimated the genetic and environmental components of variation in perceived intensity and pleasantness of androstenone, an odorous compound showing specific anosmia, by modeling twin data from Finland, Denmark, the UK, and Australia. The pooled data comprised 917 twin individuals (338 are male and 579 are female; aged from 10 to 83years) including 126 complete monozygous and 264 dizygous twin pairs as well as 137 twin individuals without their co-twin. They rated intensity and pleasantness of androstenone and citronellal (control) odors using nine categories. Additive genetic effects (heritability) contributed 28 and 21% to the variation in the perceived intensity and pleasantness of androstenone, respectively, but negligibly to variations in citronellal perception. A strong genetic correlation existed between the intensity and pleasantness of androstenone, whereas the environmental correlation was negligible. These results suggest that both intensity and pleasantness of androstenone are moderately influenced by genetic factors and that the traits are modified by an overlapping set of genes.     

Dithiothreitol enhances arsenic trioxide-induced apoptosis in NB4 cells.

Recently, arsenic trioxide (As2O3) was reported to induce clinical remission in patients with acute promyelocytic leukemia. Modulation of protein phosphorylation by binding to the vicinal thiols has been suggested as a possible mechanism. We found that phenylarsine oxide, a strong vicinal thiol-binding agent, neither induced nuclear fragmentation or DNA laddering nor increased caspase activity in NB4 cells; however, As2O3 and a weak thiol-binding agent, dimethylarsinic acid, did increase activity. Dithiothreitol (DTT) effectively suppressed the phenylarsine oxide-inhibited cellular reductive capacity, but unexpectedly, enhanced As2O3-induced apoptosis in NB4 cells. As2O3-induced and As2O3-plus-DTT-induced apoptosis in NB4 cells was modulated by oxidant modifiers, but not by nitric oxide synthase inhibitors. These results demonstrate that DTT, a dithiol agent and known antidote for trivalent inorganic arsenic, enhances the toxicity of As2O3, thereby opening a new research direction for the mechanisms of arsenic toxicity and perhaps also helping in the development of new therapeutic strategies for treating leukemias.     

The Translational Research Working Group developmental pathway for interventive devices

The interventive device pathway refers to one of six pathways developed by the Translational Research Working Group (TRWG) that, together, describe the core domains of early translational cancer research. This pathway focuses on the development of devices (as classified by the Food and Drug Administration), designed for local ablation of cancer or precancerous lesions (e.g., radiation therapy, microwave, radiofrequency ablation, and high-intensity focused ultrasound systems). This article describes the distinctive features of the pathway and issues that are encountered in the real-world development of interventive devices for the treatment of cancer. The interventive device pathway is envisioned to be a general guideline of the steps required for effective development, optimization, testing, and validation of developing devices, to be dynamic and adaptable, and to form a framework for discussions focused on improving the efficiency and effectiveness of new device development.     

A randomized clinical trial of bifocal glasses for myopic children with esophoria: results after 54 months.

BACKGROUND: We previously reported results of a randomized clinical trial of bifocals as a type of myopia correction for children with near-point esophoria. After 30 months, the rate of myopia progression in 36 children wearing bifocals averaged 0.40 D/yr compared to 0.50 D/yr in 39 children wearing single-vision glasses (p= 0.046, age-adjusted). Here we report on the 46 children in that study who completed 54 months of followup. METHODS: For each treatment group, we examined the pattern of change in myopia over the first and second halves of the 54-month period to see if the beneficial effect of wearing bifocals was present initially for those 46 children, as it was in the entire group, and to see if the myopia-slowing effect continued to accumulate during the second part of the study. During the last 12 months of the 54-month period, subjects were free to select any mode of myopic treatment, but this intent-to-treat analysis classified all children according to their original treatment assignment. RESULTS: During the first 24 months, the pattern of change in myopia differed between the two groups (p = 0.041), with those in bifocals showing slower progression. A similar trend was observed for vitreous chamber growth (p= 0.059). During the last 30 months, myopia progressed at a similar rate for both groups, including during the last year, when many subjects changed their mode of myopia correction. CONCLUSION: Wearing bifocals instead of single-vision glasses caused a slowing of myopia progression evident during the first two years. During the subsequent two-and-a-half years of followup, the difference in the degree of myopia was maintained, but did not increase.     

Biological response modifiers in the management of patients with breast cancer

Summary Despite impressive progress in understanding the biology of breast cancer, mechanisms of host defense, and the pathophysiology of the metastatic process, this burgeoning fact bank has made little impact on the management of patients with breast cancer. There are many interesting ideas for improved diagnosis and therapy in various stages of development, but few have actually translated into improved survival of patients with breast cancer. Potentially useful biological agents include cytokines, monoclonal antibodies, immunotoxins, vaccines, and adoptive cellular therapies. Therapies targetting growth factor receptors and the cellular machinery required for metastasis may become useful, especially when used in combination with other cytotoxic agents. Colony-stimulating factors may allow a test of the hypothesis that augmented dose-intensity of cytotoxic chemotherapy will cure more patients. Though we are not yet sure precisely how to use all of these new tools, there can be little doubt that their application will make a significant impact on the management of patients with breast cancer and other malignancies in the next decade.     

Henoch Sch?nlein nephritis

Glomerulonephritis is the main determinant of mortality in the Henoch Sch?nlein syndrome. We report a prospective study on 17 patients with the Henoch Sch?nlein nephritis who underwent a renal biopsy during a 12-year period. Three patients have developed end-stage renal failure, 13 are alive with normal renal function and one was lost to follow-up. We recommend that patients with Henoch Sch?nlein nephritis be followed up, with urinalysis and assessment of renal function, for at least five years.     

Glycolytic inhibition by 2-deoxyglucose reduces hyperglycemia-associated mortality and morbidity in the ischemic rat

Numerous laboratories have shown that hyperglycemia increases cerebral ischemic damage. This presumably results from increased lactate production and accumulation during ischemia. Although increased tissue lactic acidosis is associated with increased ischemic brain damage, this damage has not been directly linked to glycolytic flux. Because 2-deoxyglucose (2-DG) is a competitive inhibitor of glycolysis we tested its ability to reduce hyperglycemia-exacerbated ischemic brain damage. Severe forebrain ischemia was produced by the four-vessel occlusion model in rats. Four rats received 3 g/kg glucose and saline while a second group (n = 5) was injected with 3 g/kg glucose plus 1.6 g/kg 2-DG. A third group (n = 5) was treated with 1 g/kg glucose plus saline and a fourth group (n = 5) received 1 g/kg glucose and 1.6 g/kg 2-DG. All rats were injected i.p. 10 minutes prior to the ischemic insult with the same volume/kg body weight. All rats receiving the high dose of glucose alone (3 g/kg) were dead within 24 hours postischemia. Rats who received 2-DG in addition to 3 g/kg glucose showed only 40% mortality (p = 0.119 Fisher's Exact). 2-DG completely eliminated convulsions during the initial two hours of recovery which was significant (p = 0.008), however, all rats in both groups showed some convulsions by 24 hours postischemia. Among rats receiving the low glucose dose (1 g/kg), none of the rats receiving 2-DG died or convulsed by 24 hours postischemia.(ABSTRACT TRUNCATED AT 250 WORDS)