Imprecise exposure assessment and the sample size requirements of case-control studies of residential magnetic field exposure and cancer in adults

A computer program simulating case-control studies is described. It is used to estimate the minimum sample size required and to assess how this is affected by imprecise exposure assessment. In particular, the consequences of neglecting measurements of nonresidential exposure in case-control studies of residentially exposed adults are investigated. According to this model, while the consequent loss of power is not as large as was predicted by algebraic methods, it would be unwise to neglect it when planning a study. © 1995 Wiley-Liss, Inc.     

Iron Regulation in the Developing Rat Brain: Effect of In Utero Ethanol Exposure

Abstract: Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brain-stem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron-dependent growth processes such as myelination.     

Simulation and dynamic optimisation of animal cell culture

In animal cell culture, there are some 25 substrates that both have a significant effect on the culture performance and which can be measured with relative ease. A detailed dynamic simulation for such a culture has been produced and an optimisation policy that use this model to identify ideal media conditions has been developed. This paper describes an extension of that work to include the dynamic optimisation of cultures under fed-batch operation. Two different types of feeding policy were considered – in the first, discrete shots of feed were supplied, while in the second, feed was added continuously. Both policies offered significant improvements in the predicted productivity of the culture - up to 30% that of an experimentally optimisedbatch culture.     

Urinary excretion of mercury, copper and zinc in subjects exposed to mercury vapour

The excretion of mercury, copper and zinc in urine, and mercury in whole blood andplasma, was determined in 40 chloralkali workers exposed to mercury vapour and 40age-matched referents. The Hg concentrations in whole blood, plasma and urine werehigher in the exposed group (35 nmol l, 30 nmol l,and 11.5 nmol mmol creatinine, respectively) in comparison with thereference group (15 nmol l, 6.3 nmol l, and 1.8nmol mmol creatinine, respectively). The urinary copper excretionwas similar in the two groups, while U-Zn excretion was significantly higher (P = 0.04)in the exposed group, median 0.83 mmol mmol creatinine versus 0.76mnmol mmol creatinine in the reference group. In a subgroup of exposedworkers with current U-Hg above 11.5 nmol lmmolcreatinine (20 mg g creatinine) the medianU-Zn was 1.1 mmol mmol creatinine. In both groups smokers had highU-Zn levels than non smokers. When both U-Hg and smoking were taken into account in alinear regression model, there was a significant association between U-Hg and U-Zn inthe combined group of exposed and referents (P = 0.002). This study indicates thatmercury exposure in humans, as in animals, causes increased urinary excretion of zinc.The mechanisms may be induced synthesis of metallothionein in the kidneys, displacementof Zn from preexisting metallothionein by Hg, or a decreased reabsorption of zinc in thekidneys owing to a slight tubular dysfunction.     

The Human Obesity Gene Map: The 1996 Update

An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.     

Brief overview of control of genetic expression by antisense oligonucleotides and in vivo applications

Over the past several years, the use of synthetic oligonucleotides and functional analogs thereof as a possibly general means of controlling genetic expression has received widespread attention. Following a brief overview of some of the basic principles and strategies for this approach, attention is focused here on summarizing some recent reports of in vitro and, in particular, in vivo investigations in various animal models using phosphorothioate analogs of 2′-deoxyoligo-nucleotides. In view of these findings, which include studies related to neurobiology, this field should find significant utility in applications of the antisense method for controlling genetic expression.     

Bioprocessing in space: Human cells attach to beads in microgravity

Attachment to a substrate and survival of human embryonic kidney (HEK) cells have been tested in an incubator installed in the flight-deck of the Space Shuttle ‘Challenger’ during its eighth mission.HEK cells are producing the enzyme urokinase and are presently investigated as candidates for electrophoretic separation in an apparatus developed and manufactured by McDonnell Douglas.Attachment of HEK cells to a substrate is mandatory for survival and production of urokinase after electrophoretic separation.Analysis of the samples shows that cells adhere, spread and survive in microgravity (< 10⁻³ ×g) conditions as well as the ground controls at 1 × g. This result represents an important step towards further bioprocessing in space.     

A circular waveguide irradiation system for nonhuman primates: design and dosimetry

A 275-MHz exposure system, consisting of a circular waveguide irradiator and a transparent plastic animal cage, has been developed to accommodate rhesus monkeys weighing up to 15 kg. The vertically oriented waveguide is composed primarily of stainless steel and is fitted with an inner cage fabricated from a tubular section of acrylic plastic. Circularly polarized electromagnetic energy at 275 MHz, either pulsed or continuous wave (CW), can be propagated from the removable top section of the waveguide. The cage is designed to function as the monkey's permanent home. It is fitted with a lever-actuated behavioral performance device on which the monkey responds according to a predetermined schedule to obtain a daily food ration. The system can be adapted to provide for the collection of metabolic and physiologic data as well. Dosimetric measurements were conducted with six rhesus monkeys weighing 3.0-7.2 kg and with a 4-kg model. The dosimetric results show that about one-third of the net incident energy is absorbed by a subject in this system at a normalized specific absorption rate (SAR) of 0.33 (W/kg)/(mW/cm2).     

Lack of repair of ultraviolet light damage in Mycoplasma gallisepticum

Molecules with single-stranded tails (rolling circles) were isolated as replicating intermediates in G4 progeny single-stranded DNA synthesis. Lysates from infected cells harvested late in infection during single-stranded DNA synthesis were not deproteinised but analysed directly in caesium chloride and propidium diiodide gradients. The gradient fractionated them on the basis of tail length. If the lysates were first deproteinised however, the tailed replicative intermediates banded as a peak at a density just greater than that of replicative form II DNA (RFII) and did not spread down the gradient. The origin of synthesis of the viral strand tail was mapped by electron microscopy as 55 to 60% away from the single EcoRI cleavage site. Termination molecules finishing a round of viral strand DNA synthesis have been identified as molecules consisting of a closed single-stranded DNA circle attached by a very small region to the parent double-stranded DNA circle.