Biomedical subjects

S L Anderson

Publications and source records attributed to S L Anderson.

At least 37 records · Page 2Linked to original sources

PubMed1996

Delivery of human interferon-gamma via gene transfer in vitro: prolonged expression and induction of macrophage antimicrobial activity.

Daily parenteral administration of exogenous interferon-gamma (IFN-gamma) induces or accelerates recovery in experimental and human infections. To develop an alternative delivery system, a replication-defective recombinant adenovirus expressing human IFN-gamma was constructed. The complete coding region of IFN-gamma was amplified by RT-PCR and inserted into an adenovirus cloning vector under the control of a human cytomegalovirus promoter. Recombinant adenovirus containing the IFN-gamma minigene (dAv-IFN-gamma) was isolated from 293 cells co-transfected with the linearized plasmid and an E1 region-deleted fragment of adenovirus genome. Following in vitro infection with dAv-IFN-gamma, dose-dependent and time-dependent expression of IFN-gamma, mRNA and production of soluble protein were demonstrated in human diploid fibroblat and HeLa cell cultures by Northern blot and ELISA, respectively. Extracellular protein secretion persisted for > = 4 weeks following initial transfection, and secreted IFN-gamma induced both antiviral activity (8000-25,000 U/ml) and macrophage activation with killing of intracellular Toxoplasma gondii and leishmania donovani. These results establish that dAv-IFN-gamma generates long-term secretion of biologically active IFN-gamma in vitro and suggest that this vector may be a useful delivery system for cytokine therapy.

Adenoviridae↗

PubMed1996

Comparison of Eating Disorder Inventory (EDI-2) scores of male bodybuilders to the male college student subgroup.

The intensity and effort of bodybuilding training suggest an overinvestment in body shape and physical appearance, which has been suggested to be a risk factor for developing eating disorders. The purpose of this study was to investigate the prevalence of eating disorder tendencies among a sample of collegiate male bodybuilders (BB, n = 68) and controls (C, n = 50) (nonbodybuilders), using the Eating Disorders Inventory 2 (EDI-2). T tests were used to test the hypothesis that bodybuilders' scores would be higher than those of controls. The mean scores on the EDI-2 did not indicate the presence of eating disorder tendencies for either group. Controls scored significantly higher than bodybuilders on the Body Dissatisfaction scale. Results indicate that when the EDI-2 is used, college-age male bodybuilders are not shown to be more likely to have eating disorders than a group of college-age male controls.

Adult↗

PubMed1996

Vaccination of black-footed ferret (Mustela nigripes) x Siberian polecat (M. eversmanni) hybrids and domestic ferrets (M. putorius furo)against canine distemper.

An inactivated canine distemper vaccine with adjuvant and a modified-live virus (MLV) vaccine were evaluated using black-footed ferret (Mustegla nigripes) x Siberian polecat (Mustela eversmanni) hybrids us surrogates for endangered black-footed ferrets. For comparative purposes, we also vaccinated domestic ferrets (Mustela putorius furo) with the MLV vaccine. Response to vaccination was measured by clinical observation, hematology, dynamics of serum virus neutralizing antibodies, and challenge with virulent canine distemper virus. No clinical signs attributable to the vaccines were observed. Transient leukopenia occurred in hybrid ferrets that received MLV vaccine and there was marked lymphopenia for approximately 52 days post-vaccination. Lymphopenia was present for approximately 21 days in domestic ferrets vaccinated with MLV vaccine. Neutralizing antibodies against canine distemper virus were detected 14 days post-vaccination in hybrids receiving MLV vaccine and most titers were > 1:1024 for the 791 days of the study. Antibody titers in hybrids vaccinated with the inactivated vaccine were significantly lower. All eight hybrid ferrets that received MLV vaccine survived challenge with virulent canine distemper virus without clinical disease. However, one of seven hybrids vaccinated with the inactivated vaccine developed canine distemper and was euthanized; two other hybrids became clinically ill but survived. The MLV vaccine may be useful in prevention of canine distemper in black-footed ferrets, but until additional studies of efficacy and safety are completed, use of the inactivated vaccine is appropriate.

Animals↗

PubMed1995

Prophylaxis of Plasmodium falciparum malaria with azithromycin administered to volunteers.

OBJECTIVE: To determine whether azithromycin, 250 mg/d, is effective prophylaxis for liver infection or for both liver and subsequent blood infection with Plasmodium falciparum. DESIGN: Controlled phase II trial with two cohorts entered sequentially. SETTING: Clinical trials center of Walter Reed Army Institute of Research, Washington, D.C. PATIENTS: Each of the two cohorts consisted of 12 normal adult volunteers who had not had malaria during the previous 2 years: 10 who received azithromycin prophylaxis and 2 controls who did not received treatment. INTERVENTION: For cohort 1, prophylactic efficacy against liver infection alone during the initial 7 days of the infection was determined by loading participants with azithromycin before challenge with P. falciparum-infected mosquitoes on day 0 and by then giving the drug for 7 days after the challenge. The regimen was 500 mg on day 14 before the challenge, followed by 250 mg/d from day 13 before the challenge through day 7 after the challenge. For cohort 2, prophylactic efficacy against both the liver infection and the subsequent blood infection was determined by continuing drug administration for 28 days after the challenge. MEASUREMENTS: Plasmodium falciparum infection was diagnosed through peripheral blood smears obtained up to 70 days after challenge. Malarial symptoms and adverse drug reactions were also monitored. RESULTS: In cohort 1, 4 of 10 volunteers who received azithromycin prophylaxis (40%) did not develop parasitemia. In cohort 2, none of the 10 volunteers receiving azithromycin prophylaxis (100%) developed parasitemia. For each cohort, both control volunteers became parasitemic on days 9 through 13 after the challenge. Adverse drug reactions were few and mild. CONCLUSIONS: In this model, prophylaxis with azithromycin (250 mg/d) was partially effective against liver parasites and completely successful against the combination of liver and blood parasites. These data suggest that azithromycin has the potential to be an effective, well-tolerated clinical prophylactic agent for P. falciparum malaria.

Adolescent↗

PubMed1995

Expression and function of a mislocalized form of peroxisomal malate dehydrogenase (MDH3) in yeast.

The malate dehydrogenase isozyme MDH3 of Saccharomyces cerevisiae was found to be localized to peroxisomes by cellular fractionation and density gradient centrifugation. However, unlike other yeast peroxisomal enzymes that function in the glyoxylate pathway, MDH3 was found to be refractory to catabolite inactivation, i.e. to rapid inactivation and degradation following glucose addition. To examine the structural requirements for organellar localization, the Ser-Lys-Leu carboxyl-terminal tripeptide, a common motif for localization of peroxisomal proteins, was removed by mutagenesis of the MDH3 gene. This resulted in cytosolic localization of MDH3 in yeast transformants. To examine structural requirements for catabolite inactivation, a 12-residue amino-terminal extension from the yeast cytosolic MDH2 isozyme was added to the amino termini of the peroxisomal and mislocalized "cytosolic" forms of MDH3. This extension was previously shown to be essential for catabolite inactivation of MDH2 but failed to confer this property to MDH3. The mislocalized cytosolic forms of MDH3 were found to be catalytically active and competent for metabolic functions normally provided by MDH2.

Amino Acid Sequence↗

PubMed1995

Functional dissection of circadian clock- and phytochrome-regulated transcription of the Arabidopsis CAB2 gene.

Both the circadian clock and phytochrome regulate expression of the Arabidopsis genes encoding the light-harvesting chlorophyll a/b-binding proteins (CAB genes). Phytochrome activates CAB transcription, and it has been proposed that the circadian clock negatively regulates CAB transcription. The tobacco nuclear proteins CUF-1 (CAB upstream factor 1) and CGF-1 (CAB GATA factor 1) bind the Arabidopsis CAB2 promoter, and the CGF-1 binding site is contained within a minimal clock- and phytochrome-regulated region of the promoter. We have used in vivo cab2::luciferase gene bioluminescence markers containing site-directed mutations in the CUF-1 and CGF-1 binding sites to define the role of these proteins in CAB2 regulation and to further delineate the terminal genomic targets of the phytochrome and circadian clock signal transduction pathways. Results from these studies confirm that CUF-1 is not required to generate the circadian clock- or phytochrome-responsive CAB2 expression pattern but rather functions as a positive factor to increase CAB2 expression levels. CGF-1 interaction with the CAB2 promoter mediates the acute increase in CAB2 expression in response to phytochrome activation and contributes to the light-induced high-amplitude circadian oscillation in CAB2 expression.

Arabidopsis↗

PubMed1994

The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells.

A cDNA clone complementary to an interferon (IFN)-induced mRNA approximately 3 kb in length was identified and sequenced revealing homology with the endoplasmic reticular heat shock protein/ATPase gp96. Both IFN-alpha and -gamma transcriptionally upregulate expression of this gene. gp96 transcripts, protein, and ATPase activity are shown to be enhanced as a result of IFN treatment in two human cell lines and this effect requires de novo protein synthesis. gp96 molecules have recently been implicated in the presentation of endogenous antigens. A number of the key elements in this pathway, the transporter proteins, the major histocompatibility complex (MHC)-linked units of the proteasomes and the MHC class I molecules are known to be IFN inducible. Our results show that yet another molecule suggested to play an accessory role in the endogenous presentation pathway is IFN inducible. Further, our studies represent the first demonstration of modulation of expression of a heat shock protein by a cytokine and identify a new enzymatic activity upregulated in IFN-treated cells.

Adenosine Triphosphatases↗

PubMed1994

Isolation, characterization, and disruption of the yeast gene encoding cytosolic NADP-specific isocitrate dehydrogenase.

The cytosolic isozyme of NADP-specific isocitrate dehydrogenase (IDP2) was purified from a Saccharomyces cerevisiae mutant containing a chromosomal disruption in the gene encoding the mitochondrial isozyme (IDP1). IDP2 was shown to be a homodimer with a subunit molecular weight of approximately 45,000 and an isoelectric point of 5.5. Amino acid sequences were obtained for tryptic peptides of IDP2 and used to plan polymerase chain reactions. A resulting 400 bp DNA fragment was used as a hybridization probe to isolate the IDP2 gene from a yeast genomic DNA library. The complete nucleotide sequence of the IDP2 coding region was determined and translated into a 412-residue amino acid sequence. IDP2 and IDP1 were found to be identical in 71% of the aligned residue positions. The identity of the IDP2 gene was confirmed by genomic replacement with a disrupted IDP2 coding region. Haploid yeast strains lacking either or both IDP2 and IDP1 were constructed by genetic crosses of mutant strains containing disruptions in chromosomal IDP2 and IDP1 loci. No dramatic differences in growth rates with common carbon sources could be attributed to these disruptions.

Amino Acid Sequence↗

PubMed1994

Circadian clock- and phytochrome-regulated transcription is conferred by a 78 bp cis-acting domain of the Arabidopsis CAB2 promoter.

The Arabidopsis CAB2 promoter was used to define the terminal genomic targets that are subject to regulation by the circadian clock. An in vivo cab::luciferase bioluminescent marker was used to enable the assaying of the expression of chimeric constructs with unprecedented sensitivity and time resolution in living seedlings. Dissection of -322 to +1 of the CAB2 promoter has revealed several interesting features: it was demonstrated that the 323 bp fragment contains at least one strong general positive element. The positive element contains an ACGT core sequence specifically bound by a protein activity, termed CUF-1, and contributes to high level expression but is not required for phytochrome- or circadian-regulation. Moreover, a 78 bp domain was defined that confers both circadian- and phytochrome-regulation upon heterologous promoters. Conserved GATA sequences within the 78 bp regulatory domain are specifically bound by a protein factor designated CGF-1. The binding specificity of CGF-1 appears to be related to the GT-family of trihelix DNA-binding proteins. The role of these DNA-protein interactions is discussed in terms of clock- and phytochrome regulation, and their relevance as targets for pathways defined by photomorphogenic mutants.

Arabidopsis↗

PubMed1994

Suppression of mitochondrial mRNA levels and mitochondrial function in cells responding to the anticellular action of interferon.

A lambda cDNA library prepared from polyadenylated RNA isolated from Daudi cells was differentially screened to isolate cDNAs that recognize mRNA whose levels are reduced following interferon (IFN) treatment. Southern blot and DNA sequence analysis of 20 cDNA clones that were isolated revealed that they represented mitochondrially encoded mRNAs for the following proteins: cytochrome c oxidase subunits II and III, ATPase 6, cytochrome b, and subunit 1 of the NADH dehydrogenase. Northern blot analysis employing these cDNAs and oligonucleotides generated to the remaining mitochondrially encoded mRNAs demonstrated that IFN-alpha treatment of Daudi cells mediates a time-dependent suppression of the level of all of the mitochondrially encoded mRNAs. Study of this IFN-mediated effect reveals that: (i) the suppression of the level of these mRNAs is dependent on protein synthesis, (ii) it can be observed to occur prior to any detectable effect on thymidine incorporation, (iii) the degree of suppression correlates with the sensitivity of the cells to the anticellular action of IFN, and (iv) the suppression of the level of these RNAs appears to result from an effect on the level of transcription rather than on the stability of these mRNAs. A study of the level of cellular respiration in IFN-treated Daudi cells reveals a clear suppression 3 h following IFN treatment.

Base Sequence↗

PubMed1994

Linking genotoxic responses and reproductive success in ecotoxicology.

The potential of genotoxicity biomarkers as predictors of detrimental environmental effects, such as altered reproductive success of wild organisms, must be rigorously determined. Recent research to evaluate relationships between genotoxic responses and indicators of reproductive success in model animals is described from an ecotoxicological perspective. Genotoxicity can be correlated with reproductive effects such as gamete loss due to cell death; embryonic mortality; and heritable mutations in a range of model animals including polychaete worms, nematodes, sea urchins, amphibians, and fish. In preliminary studies, the polychaete worm, Neanthes arenaceodentata, and the nematode, Caenorhabditis elegans, have also shown the potential for cumulative DNA damage in gametes. If DNA repair capacity is limited in gametes, then selected life history traits such as long and synchronous periods of gametogenesis may confer vulnerability to genotoxic substances in chronic exposures. Recommendations for future research include strategic development of animal models that can be used to elucidate multiple mechanisms of effect (multiend point) at varying levels of biological organization (multilevel).

Animals↗

PubMed1994

Effects of chronic irradiation on the reproductive success of the polychaete worm, Neanthes arenaceodentata.

Effects of lifetime exposure to chronic irradiation on reproductive success were assessed for laboratory populations of Neanthes arenaceodentata. Exposure was initiated upon the spawning of the parental (P1) female and was terminated upon spawning of the first filial (F1) generation female; broods from the F1 pairs were sacrificed before hatching occurred. Groups of worms in the experiments received either no radiation (controls) or 0.19, 2.1 or 17 mGy h-1. The total dose received was either background or approximately 0.55, 6.5 or 54 Gy, respectively. The mean number of embryos in the broods from the F1 females exposed to 17 mGy h-1 was statistically significantly different from the mean number of embryos from control females; however, the mean number of embryos in the broods from the F1 females exposed to 0.19 and 2.1 mGy h-1 was not significantly different from the mean number from control females. For all the radiation-exposed groups, there was a statistically significant reduction in the number and percentage of live embryos in the broods from the F1 pairs as well as a statistically significant increase in the numbers and percentages of abnormal embryos. Results on embryo abnormalities and mortalities indicate that dominant- and recessive-lethal mutations were most likely induced in the germ cells and that these mutations had an adverse effect on reproductive success by affecting the survival of early-life stages. Except for pairs exposed to 17 mGy h-1, there was no evidence of gamete killing or reduced fertilization success, because the number of developing embryos in the broods did not decrease with increased dose. Data for the estimated hatch number and actual hatch number indicated that doses as low as 0.19 mGy h-1 can reduce significantly the number of larvae that hatch when lifetime doses are given.

Animals↗

PubMed1994

Effects of acute irradiation on reproductive success of the polychaete worm, Neanthes arenaceodentata.

Effects of acute irradiation on the reproductive success of a relatively low-fecundity species were investigated by exposing pairs of female and male polychaete worms (Neanthes arenaceodentata) to either no radiation (controls) or 0.5, 1.0, 2.0, 5.0, 10 or 50 Gy of acute irradiation (5 Gy min-1) at the time when oocytes were visible in the female. The broods from the pairs were sacrificed before hatching occurred, and information was obtained on the number in the brood, the number of normal and abnormal embryos, and the number of embryos that were living, dying and dead. Developing gametes of N. arenaceodentata appeared to be sensitive to acute irradiation. There was a significant reduction in the percentage of live embryos in the broods from pairs receiving doses as low as 0.5 Gy, which is lower than the lowest dose at which effects in invertebrates have been reported previously. This was most likely due to the induction of lethal mutations in the developing gametes, which affected the survival of embryos in early stages of life. Except for those pairs receiving 10 or 50 Gy, there was no evidence of decreased fertility or fecundity or of reduced fertilization success; the number of embryos in the broods from only these irradiated groups was significantly different from the controls.

Animals↗

PubMed1993

Dietitians' practices and attitudes regarding the Code of Ethics for the Profession of Dietetics.

Three hundred forty-one dietetics practitioners responded (a 34% response rate) to a 103-item questionnaire that included four subscales. This article focuses on one subscale: assessment of the extent to which dietitians reportedly adhere to the profession's code of ethics as it applies to their own practices. The validity of the survey instrument was confirmed by a panel of experts, and the overall internal consistency reliability for the instrument was .82 using Cronbachs' alpha. The internal consistency reliability for the code of ethics subscale was .84 (items 1 through 16) and .88 (items 17 through 20). Respondents to the questionnaire were typically college-educated, married, white women over 40 years of age who practiced as consultant or clinical dietitians. Almost one fourth of the respondents fell into the 60 years and older age group. More than 75% of the respondents reported that they either "always" practiced specific components from the code of ethics or "strongly agreed" with code statements. No statistically significant differences were found among selected personal and professional characteristics and responses to the subscale items. These findings indicate that the dietitians in the sample reportedly adhere to and agree with the Code of Ethics for the Profession of Dietetics.

Adult↗

PubMed1993

Brucellosis in free-ranging bison (Bison bison) from Teton County, Wyoming.

Brucellosis was studied opportunistically in bison (Bison bison) in the free-ranging Jackson herd of approximately 120 in Teton County, Wyoming (USA) in March 1989. Recent abortion was diagnosed in a 2-yr-old cow and Brucella abortus biovar 1 was isolated from vaginal discharge, uterine contents, uterus, and supramammary lymph nodes. Endometritis was characterized by lymphoplasmacytic infiltrates in the lamina propria and neutrophils in uterine glands and within necrotic debris and exudate in the uterine lumen. A 5-yr-old bull had diffuse lymphoplasmacytic infiltrates in epididymis and accessory sex glands; B. abortus was isolated from seminal vesicle and ampulla. Twenty-seven (77%) of 35 bison tested from 1989 to 1990 were serologically positive or suspect on tests for Brucella antibodies. We report the occurrence of abortion due to brucellosis in free-ranging bison in the Jackson herd, suggest that bison in this herd are capable of transmitting brucellosis to other susceptible hosts, and report the first confirmation of brucellosis in this herd.

Abortion, Veterinary↗

PubMed1992

A canine model for hepatic venoocclusive disease.

Hepatic venoocclusive disease is a frequent lethal complication of bone marrow transplantation. It has also been associated with hepatic irradiation and administration of chemotherapeutic agents without BMT. The pathogenesis and therapy of VOD are unclear. The present studies were directed at developing a canine model for VOD. Three groups of dogs were studied. Group one consisted of 8 dogs in which monocrotaline (MC) was administered at 125 mg/kg orally on an intermittent schedule. In 7 of the 8 dogs 6 to 9 doses of drug were administered between 42 and 110 days. Group 2 consisted of 6 dogs receiving busulfan 2 mg/kg/day for 17-25 days, when platelet counts decreased to less than 5 x 10(4)/mm3 or clinical bleeding occurred. Group 3 consisted of 2 dogs receiving 24 Gy and 4 dogs receiving 36 Gy of whole-liver irradiation. Seven of 8 dogs in group 1 developed significant liver function abnormalities and evidence of portal hypertension. Histologic findings of VOD were present at autopsy. Group 2 dogs failed to develop clinical or laboratory liver abnormalities, but 3 of 6 animals had minimal histologic evidence of VOD. Three of 6 dogs in group 3 receiving 36 Gy developed hepatic dysfunction and had findings of fibrosis at autopsy. It was concluded that MC administration produced consistent clinical and histologic features of VOD in dogs. Changes occurring after busulfan or total-liver irradiation administration were less reproducible. Dogs are a suitable large-animal model for studies of VOD.

Animals↗

PubMed1992

Comparative vaginal cytology of the estrous cycle of black-footed ferrets (Mustela nigripes), Siberian polecats (M. eversmanni), and domestic ferrets (M. putorius furo).

Vaginal cytology and vulva size were used to characterize the reproductive cycle of female black-footed ferrets (Mustela nigripes), Siberian polecats (M. eversmanni), and domestic ferrets (M. putorius furo). Emphasis was on black-footed ferrets because of the need to breed these critically endangered animals and on Siberian polecats because of the close taxonomic relationship to black-footed ferrets. Vaginal cytology of the 3 species of ferret is similar. Proestrus was characterized by an increasing percentage of superficial epithelial cells and enlargement of the vulva. During estrus, superficial cells were usually greater than or equal to 90% of epithelial cells in the vaginal lavage and after several days were fully keratinized. Neutrophils were more common during all stages of the estrous cycle in domestic ferrets than they were in the other species. Following copulation, percentage of superficial calls in the vagina declined and vulva swelling subsided. Large cells, probably of uterine symplasma origin, were observed in vaginal lavages following whelping or pseudopregnancy. Vaginal cytology is extremely useful in the reproductive management of black-footed ferrets and Siberian polecats. Knowledge of normal vaginal cytology could be applied to the diagnosis of female reproductive abnormalities in all 3 species.

Animals↗

PubMed1991

Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts.

A cDNA clone complementary to an interferon (IFN)-induced mRNA was isolated and used to characterize the regulation of expression of its RNA by the IFNs and to identify the protein its RNA encodes. This cDNA hybridizes to IFN-induced 3.1- and 2.3-kilobase mRNAs that are synthesized in response to both IFN-alpha and IFN-gamma. IFN-gamma induces the sustained accumulation of these mRNAs while IFN-alpha induces their transient accumulation. Cycloheximide (50 micrograms/ml) failed to inhibit the induction of these mRNAs by either IFN-alpha or IFN-gamma, suggesting that their induction does not require de novo protein synthesis. DNA sequence analysis of this cDNA reveals that it encodes a protein of Mr 53,168 that has sequence homology with and the biological activity of a tryptophanyl-tRNA synthetase, an enzymatic activity that has been demonstrated to play a role in and be modulated by the growth of cells. Elevated levels of this enzyme may be involved in the cell growth inhibitory activity of the IFNs.

Amino Acid Sequence↗