Cellular competence plays a role in photoreceptor differentiation in the developing Xenopus retina.

Factors in the environment appear to be responsible for inducing many of the cell fates in the retina, including, for example, photoreceptors. Further, there is a conserved order of histogenesis in the vertebrate retina, suggesting that a temporal mechanism interacts in the control of cellular determination. The temporal mechanism involved could result from different inducing signals being released at different times. Alternatively, the inducing signals might be present at many stages, but an autonomous clock could regulate the competence of cells to respond to them. To differentiate between these mechanisms, cells from young embryonic retinas were dissociated and grown together with those from older embryos, and the timing of photoreceptor determination assayed. Young cells appeared uninfluenced by older cells, expressing photoreceptor markers on the same time schedule as when cultured alone. A similar result was obtained when the heterochronic mixing was done in vivo by grafting a small plug of optic vesicle from younger embryos into older hosts. Even the graft cells at the immediate margin of the transplant failed to express photoreceptor markers earlier than normal, despite their being in contact with older, strongly expressing host cells. We conclude that retinal progenitors intrinsically acquire the ability to respond to photoreceptor-inducing cues by a mechanism that runs on a cell autonomous schedule, and that the conserved order of histogenesis is based in part on this competence clock.

Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion.

Infant acute leukemia (IAL) frequently involves breakage and recombination of the MLL gene with one of several potential partner genes. These gene fusions arise in utero and are similar to those found in leukemias secondary to chemotherapy with inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in utero exposures to chemicals may cause IAL via an effect on topo-II. We report a pilot case-control study of IAL across different countries and ethnic groups. Cases (n = 136) were population-based in most centers. Controls (n = 266) were selected from inpatients and outpatients at hospitals serving the same populations. MLL rearrangement status was derived by Southern blot analysis, and maternal exposure data were obtained by interviews using a structured questionnaire. Apart from the use of cigarettes and alcohol, very few mothers reported exposure to known topo-II inhibitors. Significant case-control differences were apparent for ingestion of several groups of drugs, including herbal medicines and drugs classified as "DNA-damaging," and for exposure to pesticides with the last two being largely attributable, respectively, to one nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68 for mosquitocidals, P = 0.003). Although it is unclear at present whether these particular exposures operate via an effect on topo-II, the data suggest that specific chemical exposures of the fetus during pregnancy may cause MLL gene fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based insecticides in certain settings, confirmation of these apparent associations is urgently required.

Gender differences in musculoskeletal injury rates: a function of symptom reporting?

PURPOSE: This study determined gender differences in voluntary reporting of lower extremity musculoskeletal injuries among U.S, Marine Corps (USMC) recruits, and it examined the association between these differences and the higher injury rates typically found among women trainees. METHODS: Subjects were 176 male and 241 female enlisted USMC recruits who were followed prospectively through 11 wk (men) and 12 wk (women) of boot camp training. Reported injuries were measured by medical record reviews. Unreported injuries were determined by a questionnaire and a medical examination administered at the completion of training. RESULTS: Among female recruits the most commonly reported injuries were patellofemoral syndrome (10.0% of subjects), ankle sprain (9.1%), and iliotibial band syndrome (5.8%); the most common unreported injuries were patellofemoral syndrome (2.1%), metatarsalgia (1.7%), and unspecified knee pain (1.7%). Among male recruits iliotibial band syndrome (4.0% of subjects), ankle sprain (2.8%), and Achilles tendinitis/bursitis (2.8%) were the most frequently reported injuries; shin splints (4.6%), iliotibial band syndrome (4.0%), and ankle sprain (2.8%) were the most common unreported diagnoses. Female recruits were more likely to have a reported injury than male recruits (44.0% vs 25.6%, relative risk (RR) = 1.72, 95% confidence interval (CI) 1.29-2.30), but they were less likely to have an unreported injury (11.6% vs 23.9%, RR = 0.49, 95% CI 0.31-0.75). When both reported and unreported injuries were measured, total injury rates were high for both sexes (53.5% women, 45.5% men, RR = 1.18, 95% CI 0.96-1.44), but the difference between the rates was not statistically significant. CONCLUSIONS: Our results indicate that the higher injury rates often found in female military trainees may be explained by gender differences in symptom reporting.