Characterization of folate receptor from normal and neoplastic murine tissue: influence of dietary folate on folate receptor expression

Membrane-associated folate receptors (FRs) have been detected in many mammalian species, and multiple isoforms have been identified. The pharmacological properties of FRs from murine kidney, liver, and six murine tumors were characterized. Murine kidney expressed primarily folate-binding protein 1, analogous to human FR-alpha, whereas murine liver expressed predominantly folate-binding protein 2, analogous to human FR-beta. Five of six murine tumors expressed high-affinity FRs with pharmacological properties consistent with folate-binding protein 1 isoform expression. Restriction of dietary folate resulted in significant changes in the FR expression in most murine tissues. Kidney and tumor FRs showed a decreased affinity for folic acid, suggesting a change in isoform expression in response to a low folate diet. Density of the FR in the kidney decreased, and, in contrast, density of the FR in all tumors increased. The response of the liver to a low folate diet was unique in that there were no detectable changes in affinity or density of liver FR. Changes in dietary folate that modulate FR isoform expression may have relevance for cancer patients treated with antifolates.     

Characterization of blood flow turbulence with pulsed-wave and power Doppler ultrasound imaging

Blood turbulence downstream of a concentric 86 percent area reduction stenosis was characterized using absolute and relative Doppler spectral broadening measurements, relative Doppler velocity fluctuation, and Doppler backscattered power. Bidimensional mappings of each Doppler index were obtained using a 10 MHz pulsed-wave Doppler system. Calf red cells suspended in a saline solution were used to scatter ultrasound and were circulated in an in vitro steady flow loop model. Results showed that the absolute spectral broadening was not a good index of turbulence because it was strongly affected by the deceleration of the jet and by the shear layer between the jet and the recirculation zones. Relative Doppler spectral broadening (absolute broadening divided by the frequency shift), velocity fluctuation, and Doppler power indices provided consistent mapping of the centerline axial variation of turbulence evaluated by hot-film anemometry. The best agreement between the hot-film and Doppler ultrasound methods was however obtained with the Doppler back-scattered power. The most consistent bidimensional mapping of the flow characteristics downstream of the stenosis was also observed with the Doppler power index. The relative broadening and the velocity fluctuation produced artifacts in the shear layer and in the recirculation zones. Power Doppler imaging is a new emerging technique that may provide reliable in vivo characterization of blood flow turbulence.     

Specificity of chromosome damage caused by the Rex element of Drosophila melanogaster

Alkylresorcinols, natural amphiphilic compounds commonly found in cereal grains, markedly decreased mutagenic activity of four standard mutagens examined in the Ames test. The effect was the strongest in the case of indirect-acting mutagens, benzo[a]pyrene and 2-aminofluorene. In the case of direct-acting mutagens, daunorubicin and methyl methanesulfonate, the diminution of the mutagenic activity by the alkylresorcinols was smaller but still noticeable. In the Sister Chromatid Exchanges test (SCEs) with cultured in vitro human blood-derived lymphocytes, a significant decrease of SCEs frequency induced by benzo[a]pyrene was observed in the presence of alkylresorcinols. These preliminary results seem to be important in the aspect of possible antimutagenic and anticarcinogenic potency of alkylresorcinols found in cereal grains.     

Emerging issues in sleep-disordered breathing

An amplified capture enzyme-linked immunosorbent assay (ELISA) has been developed by the use of the biotin-avidin detection system, for the measurement of canine plasma immunoglobulins (Ig) A, G and M. Test responses of dilutions of both the Ig standards and test plasma samples were consistently linear (r > 0.987) for the three Ig classes. The within-assay variation was 3.53 per cent for IgG, 5.84 per cent for IgM and 6.34 per cent for IgA. The analytical recoveries were 95 per cent for IgA, 97 per cent for IgG and 98 per cent for IgM. The lower detection limits of the assay were 38.4 ng ml-1 for IgG, 20.3 ng ml-1 for IgM and 41.2 ng ml-1 for IgA. The results indicate that this ELISA has a much higher sensitivity than the single radial immunodiffusion assay or the non-amplified ELISA for measurements of canine Igs, but has a comparable specificity and precision.     

Changes in limbic and prefrontal functional interactions in a working memory task for faces

Regional cerebral blood flow, measured with positron emission tomography, was used to identify brain regions that play a special role(s) in a working memory task for faces. Perceptual matching (no retention interval), short-delay (average = 3.5 s retention interval), intermediate-delay (average = 12.5 s), and long-delay (21 s) tasks were considered. From the idea that brain function is the result of neural interactions, the data were analysed using anatomically based, covariance structural equation modeling. In perceptual matching, the dominant functional interactions were observed among the ventral cortical areas, from extrastriate regions, to the anterior temporal, and into the inferior prefrontal cortex. These interactions decreased with longer delay intervals. In the short-delay functional model, interactions along this ventral stream in the right hemisphere appeared to be rerouted through limbic areas with strong interactions among the hippocampal region, the anterior and posterior cingulate, and the inferior prefrontal cortices. For the intermediate-delay model, the hippocampocingulate interactions continued, but showed a shift to more left hemisphere involvement. In the long-delay network, interactions within the right limbic circuit were reduced in favor of strong bilateral inferior prefrontal and frontocingulate interactions. Effects from the prefrontal cortex, especially from the left hemisphere, to temporal and occipito-temporal cortices were particularly strong in the long-delay model, suggesting recruitment of some of the same circuits primarily involved in face perception. The strong corticolimbic interactions at short and intermediate delays may represent maintenance of an iconic representation of the face during the retention interval. However, at longer delays, where image was more difficult to maintain, a frontocingulate-occipital network was used that could represent an expanded encoding strategy resulting in a more resilient memory.     

The characteristics of gastroduodenal pathology in the workers of a plant for plastic construction materials

Out of 162 workers exposed to chemicals in the manufacture of construction plastics an outpatient and inpatient examination revealed gastrointestinal problems in 84.3%, vegetative nervous disorders in 62.6% of the examinees. In a random sample of 47 workers high acid production occurred in 63.3% and erosions, ulcers, cicatrices in the stomach and duodenum in 45.2% of them. No HLA genetic predisposition to duodenal ulcer was reported. Histological findings on gastroduodenal mucosa biopsies were indicative of the dystrophy in the chief and lining cells of the gastric glands, epithelium and stroma with formation of the dark cells. The authors insist on consideration of the above facts in examination and treatment of workers exposed to chemicals at construction plastics plants.     

Activations of mitogen-activated protein kinases and phospholipase D in A7r5 vascular smooth muscle cells

Activation of mitogen-activated protein kinases (MAPKs) was examined in the A7r5 rat vascular smooth muscle cell line. Treatment of A7r5 cells with vasopressin, phorbol ester (PMA), or serum resulted in activation of two MAPKs, Erk-1 and Erk-2. Phosphatidylinositol-specific phospholipase C was activated in response to vasopressin but not to PMA. Vasopressin and PMA both caused maximal activation of PLD within 5 minutes. Application of bacterial phospholipase D (PLD) to A7r5 cells increased phosphatidic acid to levels similar to those seen with vasopressin or PMA. Acute exposure of the cells to vasopressin, PMA, or PLD increased phosphorylation of many of the same cytosolic and membrane proteins. However, bacterial PLD did not promote significant activation of Erk-1 and Erk-2. Phosphatidic acid and lysophosphatidic acid (LPA) likewise did not stimulate MAPK activity in A7r5 cells. Serum and vasopressin stimulated DNA synthesis when present for more than 30 min, while PLD, PMA, phosphatidic acid, and LPA were not mitogenic. These data suggest that activations of MAPKs and PLD are concurrent but independent responses to vasopressin in A7r5 cells. Acute activation of these enzymes is not sufficient to simulate DNA synthesis.     

Star scientists and institutional transformation: patterns of invention and innovation in the formation of the biotechnology industry

The most productive ("star") bioscientists had intellectual human capital of extraordinary scientific and pecuniary value for some 10-15 years after Cohen and Boyer's 1973 founding discovery for biotechnology [Cohen, S., Chang, A., Boyer, H. & Helling, R. (1973) Proc. Natl. Acad. Sci. USA 70, 3240-3244]. This extraordinary value was due to the union of still scarce knowledge of the new research techniques and genius and vision to apply them in novel, valuable ways. As in other sciences, star bioscientists were very protective of their techniques, ideas, and discoveries in the early years of the revolution, tending to collaborate more within their own institution, which slowed diffusion to other scientists. Close, bench-level working ties between stars and firm scientists were needed to accomplish commercialization of the breakthroughs. Where and when star scientists were actively producing publications is a key predictor of where and when commercial firms began to use biotechnology. The extent of collaboration by a firm's scientists with stars is a powerful predictor of its success: for an average firm, 5 articles coauthored by an academic star and the firm's scientists result in about 5 more products in development, 3.5 more products on the market, and 860 more employees. Articles by stars collaborating with or employed by firms have significantly higher rates of citation than other articles by the same or other stars. The U.S. scientific and economic infrastructure has been particularly effective in fostering and commercializing the bioscientific revolution. These results let us see the process by which scientific breakthroughs become economic growth and consider implications for policy.