Splitting of the squashing collective mode of superfluid 3He-B by a magnetic field.
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Biomedical subjects
Publications and source records attributed to N Kim.
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The effect of 4-cis-hydroxy-L-proline (CHP), a proline analogue, on the anchorage-dependent and -independent growth of several transformed rodent cell lines was studied. Mouse NIH-3T3 fibroblasts transformed by a variety of different oncogenes (Ki-ras, mos, src, fms, fes, met, and trk) by a DNA tumor virus (SV40) or by a chemical carcinogen (N-methylnitrosourea) were all found to be more sensitive (50% inhibitory dose, 20 to 55 micrograms/ml) to the dose-dependent inhibitory effects of CHP on growth in monolayer culture than were NIH-3T3 cells (50% inhibitory dose, 120 micrograms/ml). CHP was generally found to be even more effective in inhibiting the growth of these transformed cells as colonies in soft agar than in monolayer cultures. In addition, rat embryo fibroblasts (CREF) and normal rat kidney fibroblasts (NRK) after transformation with a Ki-ras oncogene exhibit a similar increase in their sensitivity to CHP-induced growth inhibition. Treatment of NRK cells with transforming growth factor alpha (TGF-alpha) and beta (TGF-beta), which reversibly induces phenotypic transformation of these cells, increases their sensitivity to CHP to a level comparable with that observed in Ki-ras-transformed NRK cells (K-NRK). The growth inhibitory effects of CHP are reversible, since removal of CHP results in a normal resumption of cell growth. CHP uptake occurs primarily through the Na+- and energy-dependent neutral amino acid transport A system, which is 6- to 7-fold more elevated in K-NRK cells compared with NRK cells. Treatment of NRK cells with TGF-alpha and/or -beta increases the uptake of [3H]methylaminoisobutyric acid on the A system to a level that is similar to that found in K-NRK cells. The functions of the Na+/K+ and Na+/H+ exchange systems are apparently necessary for the enhanced A system activity, since ouabain and amiloride can inhibit the uptake of [3H]methylaminoisobutyric acid in K-NRK cells and in NRK cells treated with TGF-alpha and/or -beta. The activity of the A system is specifically increased in K-NRK and in TGF-alpha- and/or -beta-treated NRK cells, since the other two major neutral amino acid uptake systems, the ASC and the L systems, and the Ly+ system for basic amino acid uptake show no apparent changes in their activity in NRK cells after treatment with TGF-alpha and/or -beta or in these cells after transformation with the Ki-ras oncogene. These results suggest that the differential growth sensitivity to CHP of transformed rodent cells and of normal fibroblasts treated with TGF-alpha and/or -beta is due in part to an elevated uptake of this amino acid analogue on the neutral amino acid transport A system.
NOG-8 ras cells are a normal mouse mammary epithelial cell line transfected with a plasmid containing a glucocorticoid-inducible mouse mammary tumor virus long terminal repeat linked to the activated c-Ha-ras protooncogene. After addition of dexamethasone, there is a rapid induction (within 1-3 h) of p21ras protein that is concomitant with a parallel induction of the c-Ha-ras specific mRNA. After 4-6 days of dexamethasone treatment, NOG-8 ras cells are able to grow as colonies in semisolid medium. Between 9 and 12 days of dexamethasone treatment, there is a 5- to 6-fold increase of transforming growth factor alpha (TGF alpha) activity in the conditioned medium from NOG-8 ras cells. A 60-65% reduction in epidermal growth factor cell surface receptors on NOG-8 ras cells also occurs during this time interval. A 3- to 4-fold increase of the expression of a specific TGF alpha mRNA can be detected within 2 days of dexamethasone treatment, preceding the increase in TGF alpha protein found in the conditioned medium. Exogenous TGF alpha is able to stimulate in a dose-dependent fashion the anchorage-dependent and anchorage-independent growth of NOG-8 ras cells to a level comparable to that observed in dexamethasone treated ras-transformed NOG-8 ras cells. These results suggest that the enhanced expression of TGF alpha after induction of an activated ras protooncogene may be necessary for the anchorage-independent growth and subsequent morphological changes and the enhanced growth rate observed in ras-transformed mammary epithelial cells.
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Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the "2,3,7,8-TCDD equivalent" concentration of a mixture in order to "predict" its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.
The sensory ending of the frog muscle spindle consists of bulbous swellings interconnected by thin, tube-like axonal branches. This study was made to determine if the bulb or thin tube regions are deformed to the same degree during dynamic stretch, by comparing spindles prepared in the relaxed and stretched states. Isolated muscle spindles were rapidly frozen, either in a completely relaxed state or at the end of dynamic stretch to 130% of the in situ length. Longitudinal sections for ultra-high-voltage electron microscopy revealed that dynamic stretch caused a decrease of 61.7% in bulb diameter, an increase of 88% in bulb length and an increase of 34.6% in bulb volume. The cross-sectional areas of the nonmyelinated terminals in the reticular and compact zones measured in electron micrographs decreased by 79.2% in the bulb region and 66.7% in the tube region during dynamic stretch.
Spindle potential recorded from the sensory nerve terminal of isolated frog muscle spindles disappeared within 20-30 min after the spindle receptor was perfused with Na+-free (Li, Tris or choline) Ringer's solution, whereas the amplitude of spindle potential was not attenuated for periods up to 60 min when the spindles were perfused in a Na+-free Ringer's solution containing both 10 mM TEA and 0.1 mM 4-aminopyridine after being washed with a normal Ringer's solution containing both the K+-channel blockers. It is concluded that the time-dependent decrease in the amplitude of spindle potential during the application of Na+-free solution is not ascribable to a decrease in the inward current carried by Na+, but is due to an increase in an outward current carried by K+.
In the general hematology laboratory, quantitation of hemoglobin A2 by the microchromatographic method is superior to the method of elution from cellulose acetate membranes. A permanent record of microchromatographic patterns for the detection of hemoglobins S and C at birth can be easily obtained by using a photocopying machine and a flat mirror. These copies can be stored for comparison with definitive results when the children are retested at 6 months of age or later.
The 25,000 dalton protein of Mason-Pfizer monkey virus (MPMV) was isolated by gel filtration chromatography. In agreement with results from other laboratories, antisera to type-C and the non-type-C bovine leukemia and equine infectious anemia viruses did not precipitate 125I-labelled MPMV p25. In addition, these viruses did not cross-react in a competition radioimmunoassay for MPMV p25. Twenty-one human tissues (15 breast carcinomas, 2 normal breasts, 3 acute myelogenous leukemias and 1 sarcoma) were fractionated by detergent solubilization, ammonium sulfate precipitation, and DE-52 anion exchange chromatography. These methods were shown to be highly effective for purification of MPMV p25. Under assay conditions which minimized incubation damage to the 125I-MPMV p25, all tissues failed to react in the competition radioimmunoassay (RIAT). Two hundred and two human sera or plasma specimens, including those from patients with breast cancer and 33 age-matched controls, from 50 patients with hematologic malignancies, from 12 patients with amyotrophic lateral sclerosis, and from 14 patients with systemic lupus erythematosis, were examined for antibodies to MPMV p25. With the exception of two multiple myeloma plasma which produced artifactual false positive reactions based on hypergammaglobulinemia, a known complication of salt precipitation radioimmunoassays, the remainder of the specimens were negative for evidence of MPMV p25 antibodies.
Natural and experimental cat sera were tested in radioimmune precipitation assays vs purified p30s from FeLV, RD114 and MuLV. Antibodies with specificity for FeLV p30 comparable to hyperimmune sera from heterologous species but of low titer were found in a high percentage of normal cats from households with a high incidence of FeLV and neoplasia. Sera from cats with neoplasms were generally negative. Cats immunized with FeLV gave low-level immune response, also of the same general specificity as heterologous hyperimmune sera. Cat sera do not normally show antibody to RD114 p30 although two immunized weanling cats produced low titered but highly specific p30 antibody. Thus, for both classes of feline type-C virus p30s, there is an evident capability of the cat to mount an immune response to natural or experimental exposure to the respective proteins. The magnitude of the response is between 100 and 1,000 fold below that seen in heterologous species. In contrast, cats immunized with MuLV p30 gave immune responses comparable to those seen in guinea-pigs, rabbits and goats. Several very old cats with carcinoma had antibody which preferentially precipitated MuVL p30. A competition assay using one such serum and labelled MuVL p30 was inhibited by FeVL, RD114, and MuLV p30s. This indicates that the assay is "interspecies" in nature. Among the possible explanations of this reaction category is that it represents antibody to the p30 of an as yet undefined class of feline type-C virus.
Radioimmunoprecipitation was used to test cat sera for ability to bind to the purified major internal protein p30 of feline leukemia viurs (FeLV), to the endogenous cat virus (RD-114), and to murine leukemia virus (MuLV). The data were compared with results of tests for antibody to the feline oncornavirus-associated cell membrane antigen FOCMA and for the presence of viremia. In contrast to the general lack of free antibody to FeLV p30 in a random sample of healthy cats, high levels of antibody to FeLV p30 and FOCMA were found in normal animals from high-leukemia-cluster households. Titers of greater than or equal to 200 for p30 and greater than or equal to 32 for FOCMA were found in nonviremic animals; a percentage of animals with high FOCMA titers and lower or no p30 binding activity were viremic. Animals with neoplasms were low or negative for FOCMA antibody and did not have high titers of free p30 antibody. The p30 binding activity could be divided into three main categories: high binding with FeLV p30 and much lower activity with RD-114 and MuLV p30's, as seen with hyperimmune sera; high binding with FeLV and RD-114 p30's and low activity with MuLV p30, possibly indicative of specific antibody to both of the aforementioned proteins; and low level binding to all three p30's.
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Using sensitive radiommunoprecipitation assays for highly purified type-C RNA tumor virus proteins, we found that 5 of 16 clinically normal gibbons (including 4 of 5 normal animals from a colony with 2 cases of lymphoma) and 4 of 4 experimentally inoculated gibbons formed antibodies to the major structural protein (p30) of gibbon ape leukemia virus (GaLV). An additional woolly monkey immunized with the closely related simian sarcoma virus also formed antibodies detectable with GaLV p30. Of 20 patients immunized with formalin-inactivated Rauscher murine leukemia virus (R-MuLV), 10 were previously reported to have antibodies to MuLV as determined by an internally labeled banded virus radioimmunoprecipitation assay. In comparison studies with purified R-MuLV proteins, 7 of 20 patients formed antibodies: 3/20 to R-MuLV p30 only, 1/20 to R-MuLV glycoprotein (gp) 70 only, and 3/20 to both p30 and gp70. Most responders were melanoma patients receiving immunotherapy with BCG. Additionally, rhesus monkeys produced antibodies to the endogenous cat virus RD114 and closely related endogenous baboon leukemia virus p30's. Thus these studies demonstrated the ability of primates (including humans) to form antibodies to well-characterized proteins from endogenous and exogenous type-C viruses and the potential utility of these assays for seroepidemiologic studies.
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A radioimmunoassay for the major, group-specific antigen (p30) of hamster type C viruses was developed. The test detected approximately 5 ng of viral protein per ml and was highly specific for hamster viruses when used with homologous antibody. Comparison of three hamster viruses, two being mouse-hamster pseudotypes, in homologous and heterologous intraspecies assays, showed no evidence of type specificity for these proteins. The pseudotype viruses showed no evidence of mouse virus p30 antigenic determinants. An interspecies antigen assay employing (125)I-labeled hamster p30 and anti-feline p30 was completely inhibited by cat (feline leukemia virus), hamster, and rat viruses, to a slightly lesser degree by mouse viruses, and only poorly by RD 114 and Gibbon ape viruses. The Mason-Pfizer virus did not inhibit this assay. Hamster p30 was detected by radioimmunoassay in individual embryos from two LSH hamsters and in several adult tissues, excluding muscle at levels below that required for detection in complement-fixation tests.
We report a case of scrub typhus pneumonitis in a laboratory worker who apparently acquired it through the respiratory tract. The patient was suffering from fever, cough and dyspnea. He had both cervical and axillary lymphadenopathy, and hepatomegaly. A chest X-ray showed interstitial infiltrates. A diagnosis of scrub typhus was established upon isolation of Orientia tsutsugamushi. 12 days before the patient showed symptoms, he had purified O. tsutsugamushi proteins from infected cells using an ultrasonication method which could generate aerosols containing O. tsutsugamushi.
Acetylcholine is found within key sectors of the olfactory pathway, and is the neurotransmitter for many bulbopetal axons terminating in the glomerular and internal plexiform layers of the olfactory bulb. The present study determined whether systemically administered physostigmine, a cholinesterase inhibitor, alters the rat's ability to discern among odorant mixtures. Following appropriate training, the performance of eight rats was measured every third day on an odor mixture discrimination test with six levels of difficulty. On each test day (separated from one another by 3 days), a different drug treatment was administered [i.e., 0.00 (saline), 0.05, 0.10, or 0.20 mg/kg physostigmine]. The presentation order of the treatments was counterbalanced across subjects using 4 x 4 Latin squares. The mixture discrimination test consisted of discerning the odor of an airstream coming from the saturated head space of a 1% concentration of ethyl acetate from an airstream saturated with a 1% concentration of ethyl acetate and various concentrations of butanol (i.e., 1, 0.5, 0.1, 0.05, 0.01, or 0.005%). Physostigmine was found to enhance odor discrimination performance on the more difficult discrimination tasks in a dose-related manner, suggesting that cholinergic activation may sharpen the ability of rats to discern subtle differences among complex odor stimuli.