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Biomedical subjects

S E Wright

Publications and source records attributed to S E Wright.

At least 55 records · Page 3Linked to original sources

Prevalence of human T-lymphotropic virus in civilian applicants for the United States Armed Forces.

BACKGROUND: The wide range in human T-lymphotropic virus (HTLV) seroprevalences reported worldwide has made estimates of seroprevalence difficult in unique populations. In this study, the seropositivity of young adult civilian applicants for the US Armed Forces was determined. METHODS: Serum samples from nine geographic regions were screened by an Enzyme-Linked Immunosorbent Assay (ELISA), and repeatedly reactive samples were further tested by Western blot and radioimmunoprecipitation. Specimens were scored as positive when antibody to gag (p24) and env (gp46 or gp68) were detected. RESULTS: Of the 43,750 samples analyzed, 18 were positive for HTLV antibodies. Ten (55%) were from males and eight (45%) were from females. Nine (90%) of the males and seven (87.5%) of the females were Black. Twelve of the positive samples (66.6%) were from the New York City region, which represented only 18.8% of the sample population. CONCLUSIONS: The overall HTLV seroprevalence of civilian applicants for the US Armed forces was 0.41 per 1000. This was higher than the seroprevalence reported for volunteer blood donors.

Adolescent↗

Partitioning of teniposide into membranes and the role of lipid composition.

We have examined the partitioning behavior of the anticancer agent teniposide (VM-26) into multilamellar vesicles composed of various phospholipid species. Partitioning was found to be sensitive to the composition of the liposomal membrane since changes in the head group or acyl chain constituents could dramatically alter the affinity of the drug for the bilayer. [3H]VM-26 partitioned most readily into 1,2-monounsaturated species of phosphatidylcholine (PC) with a molar partition coefficient (Kp) of 4290 for dioleoyl-PC at 37 degrees C. Inclusion of additional phospholipids having a different head group reduced partitioning in the order cardiolipin greater than phosphatidylglycerol greater than phosphatidylserine greater than phosphatidylethanolamine. The Kp for dioleoyl-PC with 33 mol% cardiolipin was reduced to 1370. Partitioning into completely saturated species of PC was much less than that for unsaturated species and was inversely proportional to the hydrocarbon chain length at temperatures either above or below the chain melting temperature. The Kp for fluid phase dimyristoyl-PC was 2300. Partitioning into dimyristoyl-PC or dioleoyl-PC at 37 degrees C (fluid) or dipalmitoyl-PC at 25 degrees C (gel) was reduced by the addition of 5-30 mol% cholesterol in proportion to its bilayer concentration. Etoposide (VP-16) at concentrations up to 10 mol% did not compete with [3H]VM-26 for association with dioleoyl-PC. Addition of calf serum or serum albumin could significantly reduce the association of [3H]VM-26 with the liposomes.

Etoposide↗

Effects of the lipophilic anticancer drug teniposide (VM-26) on membrane transport.

The epipodophyllotoxin glucopyranosides have previously been shown to interact with membrane lipids and to alter the activity of several lipid-embedded membrane proteins. To determine if these agents are acting as general membrane perturbants, we have further examined their effects on membrane processes in Ehrlich ascites tumor cells. [3H]VM-26 and [3H]VP-16 were taken up rapidly and concentrated within the cells in proportion to their lipophilicity. Neither agent was found to have any significant effect on the influx of L-[3H]leucine or alpha-[3H]aminoisobutyric acid. Likewise, these drugs had no significant effects on the hexose transporter. The nucleoside transporter, which is structurally and functionally similar to the hexose transporter, was dramatically affected, however. VM-26 was a non-competitive inhibitor of equilibrium-exchange influx of cytosine arabinoside in Ehrlich cells with a Ki of 15 microM. Equilibrium-exchange influx increased with temperature in control cells (Q10 = 2) but not in VM-26-treated cells; thus, VM-26 was a more potent inhibitor at higher temperatures. VM-26 also significantly reduced zero-trans influx in Ehrlich, P388, L5178Y, and ML-1 cells, and these effects were immediate in onset. VM-26 inhibited high-affinity binding of the nucleoside transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR), but VM-26 enhanced non-specific NBMPR binding to Ehrlich cells. The apparent specificity of the epipodophyllotoxins for the nucleoside transporter is discussed.

Amino Acids↗

Nucleotide sequence and complementation studies of the gene 10 region of bacteriophage T3.

The nucleotide sequence of bacteriophage T3 gene 10 and surrounding regulatory elements has been determined and compared to the analogous region of bacteriophage T7. T3 genes 9, 10 and 11 have been shown to complement T7 mutants. The DNA sequences of T3 and T7 gene 10A are homologous, as are the amino acid sequences of the respective products. The translational shift to the -1 frame is predicted to occur at the same position in gene 10 of T3 and T7, though different nucleotide sequences are probably responsible. The resulting gp10B products have completely different C termini.

Base Sequence↗

Effects of the anticancer agent VM-26 on hexose uptake in Ehrlich cells.

The chemotherapeutic agent VM-26 is a membrane-interactive drug which we have previously demonstrated to be a potent inhibitor of nucleoside transport. Since the carriers mediating nucleoside and hexose transport are structurally and functionally similar, we have further characterized the membrane related properties of this agent by examining its effect on the transport and phosphorylation of hexoses in Ehrlich ascites cells. Under conditions in which only the transport component of hexose uptake was measured, VM-26 had no effect on the influx of 2-deoxyglucose, 3-0-methylglucose, or D-glucose. Glucose-sensitive cytochalasin B binding was only weakly inhibited by the drug. However, VM-26 was an apparent non-competitive inhibitor of the net uptake of 2-deoxyglucose (transport and phosphorylation). Measurement of hexokinase activity in cell extracts failed to demonstrate any significant effect of VM-26 on enzyme activity. In summary, although VM-26 is a potent inhibitor of the transport of nucleosides, it has no apparent effect on the transmembrane flux of hexoses indicating a differential effect on nucleoside and hexose transporters. The ability of the drug to decrease the net accumulation of hexoses in the absence of any detectable effect on hexokinase activity warrants further investigation.

3-O-Methylglucose↗

Immune exclusion of Haemonchus contortus larvae in sheep: dose dependency, steroid sensitivity and persistence of the response.

Naive and immune sheep, treated with anthelmintic, challenged directly into the abomasum and killed 48 hours later were used to examine the steroid sensitivity, persistence and dose dependency of immune mechanisms which result in the failure of incoming Haemonchus contortus larvae to establish (immune exclusion). Immune exclusion was almost totally abolished by corticosteroid treatment, the mean percentage of larvae establishing in the mucosa of immune sheep was 1.4 per cent of the challenge infection whereas in those treated with dexamethasone it was 24.4 per cent and in naive sheep 27.3 per cent. Immune animals challenged after seven and 42 days without antigenic experience excluded more than 90 per cent of the challenge larvae from their mucosae, whereas those challenged after 84 days without antigenic experience were as susceptible as naive animals. Immune exclusion was dose dependent, animals challenged with 10(6) and 10(5) larvae excluded 93 per cent and 82.5 per cent of the challenge dose whereas those challenged with 10(4) larvae failed to exclude larvae.

Adrenal Cortex Hormones↗

Transgenic chickens: insertion of retroviral genes into the chicken germ line.

We infected early chicken embryos by injection of wild-type and recombinant avian leukosis viruses into the yolk of unincubated, fertile eggs. The viremic males (designated generation 0 (G-0] were tested for transmission of proviral DNA to their G-1 progeny. Nine of 37 G-0 viremic males were mosiac and proviral DNA was transmitted to their progeny at frequencies varying from 1 to 11%. All of the G-1 progeny examined by restriction enzyme analysis for clonality of proviral junction fragments had one to three simple but different fragments. The proviral DNA was transmitted from G-1 to the G-2 progeny in a Mendelian fashion thus proving that retroviral genes have been inserted into the chicken germ line. One of the viruses is a candidate vector for insertion of foreign genes into the chicken germ line.

Animals↗

Immunization with envelope glycoprotein of an avian RNA tumor virus protects against sarcoma virus tumor induction: role of subgroup.

Avian RNA tumor virus envelope glycoprotein protects against sarcoma development by an avian sarcoma virus of the same subgroup. Avian RNA tumor viruses, members of the retrovirus family, induce various malignancies in fowl (Weiss et al. (eds.), 1982, RNA Tumor Viruses, Cold Spring Harbor, N.Y.). These viruses consist of a genomic RNA core surrounded by an envelope with embedded glycoproteins, of 85 and 37 kDa. The 85 kDa glycoprotein is antigenically specific for each subgroup as determined by neutralization. The envelope glycoprotein can be removed from the virion with retention of its antigenicity (Duesberg et al., 1970, Virology 41, 631-646). Two fractions of 4-6S and 8S, separated by sedimentation, were shown to retain antigenicity by interference of neutralization of virus by antibody. Thus, the 4-6S and 8S preparations could possibly serve as immunogens. The objective of this study was to determine if such envelope glycoprotein preparations could function as potential vaccines, and if so, whether the protection afforded would be subgroup specific.

Animals↗

Membrane ordering effects of the anticancer agent VM-26.

The effect of the anticancer agent VM-26 on acyl chain order of cellular and model membranes was examined by electron spin resonance techniques. The order parameter for the paramagnetic probe 5-doxyl stearate was increased when VM-26 was incorporated into the bilayer of fluid-phase dimyristoylphosphatidylcholine (DMPC) or gel-phase dipalmitoylphosphatidylcholine (DPPC) liposomes at concentrations up to 4.8 mol%. The ordering effect of VM-26 in DMPC was greater than that of cholesterol on an equimolar basis. The less cytotoxic congener of VM-26, VP-16, was only one-third as active as VM-26 in its ordering effects on DMPC. Higher order parameters for 5-doxyl stearate were also noted in asolectin liposomes, Ehrlich ascites tumor cells, and CCRF-CEM cells treated with VM-26. We conclude that VM-26 has significant membrane associated activity in addition to its previously recognized nuclear effects.

1,2-Dipalmitoylphosphatidylcholine↗

Teniposide-induced changes in the physical properties of phosphatidylcholine liposomes. A calorimetric study.

The anticancer agent teniposide has significant effects on plasma membrane components, in addition to its well known nuclear effects. Alterations in the properties and function of cellular membranes by various amphipathic compounds have been attributed previously to their relatively non-specific interactions with membrane components. We have examined the interaction of teniposide with defined model membranes by monitoring drug-induced changes in the melting profile of phospholipids by differential scanning calorimetry. The main phase transition temperature of dimyristoyl- or dipalmitoylphosphatidylcholine was lowered and broadened by the presence of teniposide in the liposomes. These effects were essentially linear over the concentration range of 1-5 mole %. The calorimetric enthalpy of the gel to liquid-crystalline transition of the phospholipids was not changed by the addition of the drug. The characteristic pretransition of these saturated phospholipids was decreased by teniposide concentrations as low as 0.1 mole % and was abolished at teniposide concentrations greater than 1 mole %. The data confirm the lipophilic nature of teniposide and indicate that the non-specific interactions with membrane lipids should be considered when evaluating the membrane-related effects of this agent.

Antineoplastic Agents↗

Region coding for subgroup specificity of envelope of avian retroviruses does not determine lymphomagenicity.

The purpose of this study was to test whether the region coding for subgroup envelope specificity was a determinant of oncogenic potential. An avian retrovirus recombinant was constructed to contain the envelope gene (env) determinant for subgroup A of an avian RNA tumor virus in one of the non-oncogenic, endogenous avian retroviruses, RAV-0. The results show that such a recombinant virus does not induce lymphoma when injected into susceptible, newborn chicks. Thus, it is concluded that the envelope determinant for subgroup of avian RNA tumor viruses does not determine malignant potential.

Animals↗

Gene insertion into the chicken germ line by retroviruses.

We injected chick syncytial strain of reticuloendotheliosis virus (CS-REV) and wild type and recombinant avian leukosis virus (ALV) near the blastoderm of unincubated fertilized embryos and CS-REV intra-abdominally at day of hatch, and we progeny tested the surviving ALV viremic males and REV viremic males and females for transmitted viral genetic material. A number of positive progeny were identified and their deoxyribonucleic acid (DNA) analyzed for restriction enzyme fragments that hybridized with viral genetic material. Most of the progeny had simple restriction enzyme patterns unlike the viremic parents or congenitally infected progeny. This is suggestive evidence that retroviral genetic information has been inserted into the germ line of chickens.

Animals↗

Both acidic-type and neutral-type asparaginyl-oligosaccharides of host-cell glycoproteins are altered in Rous-sarcoma-virus-transformed chick-embryo fibroblasts.

In comparisons of [3H]mannose-labelled glycopeptides from chick-embryo fibroblasts infected and transformed with non-defective Prague C Rous-sarcoma virus and from untransformed fibroblasts infected with a transformation-defective derivative of Prague C Rous-sarcoma virus, we have detected transformation-dependent alterations in both the acidic-type and the neutral-type asparagine-linked oligosaccharides of cellular glycoproteins. Pronase-digested glycopeptides were analysed by the combined techniques of gel filtration, exo- and endo-glycosidase digestion and concanavalin A-agarose affinity chromatography. The transformed cell glycoproteins contained more sialic acid and were enriched for more highly branched (versus biantennary) acidic-type structures compared with the untransformed cell glycoproteins, similarly to previously reported transformation-dependent alterations. In addition, the glycopeptides from the virus-transformed cells contained several neutral-type structures that were apparently absent from the untransformed cells: small neutral-type oligosaccharides (Man3GlcNAc2) that were sensitive to endo-beta-N-acetylglucosaminidase D but resistant to endo-beta-N-acetylglucosaminidase H, and oligosaccharides with the property of 'truncated' precursor oligosaccharides (endoglycosidase-resistant, alpha-mannosidase-sensitive). Endoglycosidase-released oligosaccharides with the properties of hybrid-type structures were derived from the glycoproteins of both transformed and untransformed cells.

Acetylglucosaminidase↗

Growth of the visual system in the African cichlid fish, Haplochromis burtoni. Optics.

We have measured the chromatic aberration and optical resolution of the lens of the African cichlid fish, Haplochromis burtoni as a function of growth. We found that in H. burtoni, lenses of all sizes have a longitudinal chromatic aberration of ca 1.9% of the focal length. The resolution of the lens increases as the lens grows larger, presumably because diffraction effects decrease and any imperfections in the lens become relatively less significant. We found the lens in H. burtoni is very nearly diffraction limited so that a small lens (0.59 mm) has a resolution of 289 sec of arc and a large lens (2.90 mm) has a resolution of 66 sec of arc in red light (604 nm). This resolution is nearly ten times greater than can be resolved by the cone matrix.

Animals↗

Growth of the visual system in the African cichlid fish, Haplochromis burtoni. Accommodation.

We have both measured directly and computed the amplitude of accommodation as a function of fish size to discover how the accommodative process changes during growth in the African cichlid fish, Haplochromis burtoni. We found that accommodation is achieved by lens movement in the pupillary plane along the naso-temporal axis. Accommodative lens movement is thereby directed toward a region of retinal specialization characterized by higher density of all cell types (except rods) in H. burtoni. When relaxed, the temporal retina is focused for near vision and active accommodation through lens movement adjusts the focus in the temporal retina for far vision. As the animal grows, the near and far focus points change appropriately for the fish size.

Accommodation, Ocular↗

Spatial contrast sensitivity: effects of peripheral field stimulation during monocular and dichoptic viewing.

This report examines whether a radial grating with a blank 2 deg central aperture viewed with one eye can affect contrast sensitivity for foveally-viewed, counterphasing or stationary, sine-wave gratings seen with the other eye. We find that the moving radial grating preferentially raises the threshold for the low spatial frequencies of the counterphasing but not the stationary foveal stimulus. These results closely parallel recent primate electrophysiological work which suggests that visual stimulation of the peripheral field with a moving radial grating can activate inhibitory corticofugal influences on lateral geniculate neurons. The current data are evaluated in terms of a model which suggests that the peripheral stimulus activates corticofugal mechanisms.

Form Perception↗