PubMed Health⌕ Search

Biomedical subjects

G Olson

Publications and source records attributed to G Olson.

At least 19 recordsLinked to original sources
PubMed2001

Androgen receptors in thymic epithelium modulate thymus size and thymocyte development.

Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistant testicular feminization (Tfm) mice also show significant thymus enlargement, which suggests that these changes are mediated by the androgen receptor (AR). The cellular targets of androgen action in the thymus are not known, but may include the lymphoid cells (thymocytes) as well as nonlymphoid epithelial cells, both of which have been believed to express AR. In the present study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiological significance of this epithelial cell AR expression was defined by further studies performed in vivo using chimeric mice, produced by bone marrow transplantation, in which AR expression was limited to either lymphoid or epithelial components of the thymus. Chimeric C57 mice engrafted with Tfm bone marrow cells (AR(+) epithelium and AR(-) thymocytes) had thymuses of normal size and showed the normal involutional response to androgens, whereas chimeric Tfm mice engrafted with C57 bone marrow cells (AR(-) epithelium and AR(+) thymocytes) showed thymus enlargement and androgen insensitivity. Furthermore, phenotypic analyses of lymphocytes in mice with AR(-) thymic epithelium showed abrogation of the normal responses to androgens. These data suggest that AR expressed by thymic epithelium are important modulators of thymocyte development.

Animals↗
PubMed2001

Pregnancy and primary pulmonary hypertension : successful outcome with epoprostenol therapy.

Primary pulmonary hypertension (PPH) associated with pregnancy carries a high maternal mortality rate. Short-term epoprostenol infusion has been demonstrated to improve the hemodynamic profile in patients with PPH. We report a successful maternal-fetal outcome with epoprostenol therapy during pregnancy, cesarean section, and postpartum in a patient with PPH. Epoprostenol therapy did not produce any physical or developmental abnormalities in the fetus. A favorable maternal-fetal outcome may occur with a multidisciplinary approach.

Adult↗
PubMed2001

Drug discovery.

Explore the source record for details and available documents.

Drug Design↗
PubMed2000

A role for poly(ADP-ribose) polymerase in the transcriptional regulation of the melanoma growth stimulatory activity (CXCL1) gene expression.

The melanoma growth stimulatory activity/growth-regulated protein, CXCL1, is constitutively expressed at high levels during inflammation and progression of melanocytes into malignant melanoma. It has been shown previously that CXCL1 overexpression in melanoma cells is due to increased transcription as well as stability of the CXCL1 message. The transcription of CXCL1 is regulated through several cis-acting elements including Sp1, NF-kappaB, HMGI(Y), and the immediate upstream region (IUR) element (nucleotides -94 to -78), which lies immediately upstream to the nuclear factor kappaB (NF-kappaB) element. Previously, it has been shown that the IUR is necessary for basal and cytokine-induced transcription of the CXCL1 gene. UV cross-linking and Southwestern blot analyses indicate that the IUR oligonucleotide probe selectively binds a 115-kDa protein. In this study, the IUR element has been further characterized. We show here that proximity of the IUR element to the adjacent NF-kappaB element is critical to its function as a positive regulatory element. Using binding site oligonucleotide affinity chromatography, we have selectively purified the 115-kDa IUR-F. Mass spectrometry/mass spectrometry/matrix-assisted laser desorption ionization/time of flight spectroscopy and amino acid analysis as well as microcapillary reverse phase chromatography electrospray ionization tandem mass spectrometry identified this protein as the 114-kDa poly(ADP-ribose) polymerase (PARP1). Furthermore, 3-aminobenzamide, an inhibitor of PARP-specific ADP-ribosylation, inhibits CXCL1 promoter activity and reduces levels of CXCL1 mRNA. The data point to the possibility that PARP may be a coactivator of CXCL1 transcription.

Adenosine Diphosphate Ribose↗
PubMed2000

Reinforced variability and operant learning.

Reinforcement of variability may help to explain operant learning. Three groups of rats were reinforced, in different phases, whenever the following target sequences of left (L) and right (R) lever presses occurred: LR, RLL, LLR, RRLR, RLLRL, and in Experiment 2, LLRRL. One group (variability [VAR]) was concurrently reinforced once per minute for sequence variations, a second group also once per minute but independently of variations, that is, for any sequences (ANY), and a control group (CON) received no additional reinforcers. The 3 groups learned the easiest targets equally. For the most difficult targets, CON animals' responding extinguished whereas both VAR and ANY responded at high rates. Only the VAR animals learned, however. Thus, concurrent reinforcers--contingent on variability or not--helped to maintain responding when difficult sequences were reinforced, but learning those sequences depended on reinforcement of variations.

Animals↗
PubMed2000

Image-guided functional endoscopic sinus surgery.

INTRODUCTION: Computer-aided surgery (CAS) technology in functional endoscopic sinus surgery (FESS) has engendered considerable discussion. OBJECTIVE: The goals of this study were to describe CAS preoperative planning (software-based CT image analysis) and to develop intraoperative CAS strategies for endoscopic sinus surgery. STUDY DESIGN: Between October 1, 1997, and December 31, 1998, the StealthStation (Sofamor Danek, Memphis, TN) was used in 61 FESS cases, and a retrospective review of the findings was performed. The indication for surgery in all instances was chronic rhinosinusitis refractory to medical management. The StealthStation was used to review all CT scans before surgery. Anatomic fiducial registration supplemented by contour mapping was used. RESULTS: Localization accuracy was estimated to be within 2 mm or better. The StealthStation was used for both CT image review and intraoperative localization. CAS was useful in the frontal recess, sphenoethmoid region, posterior ethmoid system, and skull base area. CAS was deemed helpful in situations where the surgical anatomy was altered by previous surgery and extensive inflammatory disease (polyposis, fungal sinusitis, and pansinusitis). CONCLUSION: The paradigm of image-guided FESS surgery, which integrates CAS into FESS, will serve to increase surgical effectiveness and decrease surgical morbidity.

Adult↗
PubMed2000

The effect of fetal neck position on nuchal fold thickness.

OBJECTIVE: Our purpose was to determine whether ultrasonographic measurements of nuchal fold thickness are affected by the position of the fetal neck. STUDY DESIGN: Fetal nuchal fold thickness was prospectively measured in 258 women undergoing routine ultrasonography at 15 to 21 completed weeks of gestation. Patients with fetal structural or chromosomal anomalies were excluded. At the time of examination the position of the fetal head was noted as being extended or flexed on the basis of the angle between the spine and the base of the skull. Gestational age was based on menstrual dates or ultrasonographic biometric parameters. Data were tested for normality. Mann-Whitney U test and analysis of covariance were used (significance was considered to be P <.05). Data are presented as median and range. RESULTS: A total of 258 fetuses were examined with 167 (65%) in the flexed and 91 (35%) in the extended neck position. Gestational age was not significantly different between the flexed and extended groups (median, 19.1 weeks; range, 15.5-21.6 weeks; vs median, 19.1 weeks; range, 15.6-22 weeks; P =.23). Nuchal fold thickness was significantly lower in the flexed group than in the extended group (median, 3.5 mm; range, 1.3-6.2 mm; vs median, 3.9 mm; range, 2.2-4.9 mm; P =.0097). Nuchal fold thickness increased significantly with gestational age in both groups. The difference in nuchal fold thickness between the 2 groups persisted even after the increase in nuchal fold thickness was adjusted for with gestational age (P =.002, analysis of covariance). The difference between the 2 groups was higher at earlier gestations. CONCLUSION: Nuchal fold thickness is affected by gestational age and fetal neck position. Correction for these variables may improve the accuracy of nuchal fold thickness measurements in screening for fetal chromosomal anomalies.

Female↗
PubMed1998

Expression of the human antigen SPAG2 in the testis and localization to the outer dense fibers in spermatozoa.

ABSTRACT Antisperm antibodies (ASAs) have been implicated in some instances of infertility. To characterize sperm antigens relevant to immunologic and immunocontraceptive development, SPAG2 (sperm-associated antigen 2) was identified by screening a human testis cDNA library with human sera positive for ASAs. Subsequently, two isoforms, SPAG2-1 and SPAG2-2, were identified in testis and placenta libraries, respectively. In the current study, Southern analysis of human genomic DNA with a probe common to the two SPAG2 isoforms indicated a single SPAG2 gene; therefore, alternative splicing is a likely mechanism for production of variant mRNAs. In situ hybridization of human testis sections demonstrated the expression of SPAG2 in primary spermatocytes, with decreased or arrested expression in postmeiotic cells. Immunofluorescence of Triton X-100-extracted spermatozoa with an anti-SPAG2 peptide antiserum indicate that SPAG2 is an intracellular component of the sperm flagellum. Electron microscopy refined this localization to the outer dense fibers (ODFs), structural filaments associated with the mammalian sperm axoneme. The ODFs have been reported to be composed of keratin-like intermediate filament proteins. However, SPAG2 does not exhibit the molecular characteristics of such proteins, nor does SPAG2 demonstrate sequence homology with previously characterized ODF proteins. Therefore, SPAG2 represents a novel protein of human sperm ODFs. Characterization of SPAG2 will further our understanding of ODF function in normal sperm motility and of flagellar abnormalities that lead to male infertility.

Antigens, Surface↗
PubMed1998

Instrumentation for the diagnosis of term and preterm labour.

The problems associated with labor during pregnancy are among the most important health issues facing physicians. Understanding the role of the uterus and cervix in labor and developing methods to control their function is essential to solving problems relating to labor. At the moment, only crude, inaccurate and subjective methods are used to assess changes in the uterus and cervix that occur in preparation for or during labor. In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based respectively on recording of uterine electrical signals from the abdominal surface (uterine EMG) and measurement of light-induced cervical collagen fluorescence (LIF) with an optical device (Collascope). The methods are rapid and allow assessment of uterine contractility and cervical ripening. Studies in rats and humans indicate that uterine and cervical function can be successfully monitored during pregnancy using these approaches and that these techniques might be used in a variety of conditions associated with labor to better define management. The potential benefits of the proposed instrumentation and methods include a reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean section rate and improving research methods to understand uterine and cervical function.

Animals↗
PubMed1997

Prevention by retinoids of azoxymethane-induced tumors and aberrant crypt foci and their modulation of cell proliferation in the colon of rats.

Retinoids are proposed chemopreventive agents that inhibit cell proliferation and induce differentiation. Their ability to prevent azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors and to modulate cell proliferation was investigated in the colon of male F344 rats. Thirteen retinoids were evaluated for prevention of ACF and two of them, 9-cis-retinoic acid (RA) and 4-(hydroxyphenyl)retinamide (4-HPR), were also evaluated for prevention of colon cancer. The retinoids were administered continuously in the diet starting 1 week prior to the first of two weekly 15 mg/kg i.p. injections of AOM and for a total of either 5 or 36 weeks in order to evaluate their effect on colonic ACF and tumors. At a concentration of 1 mmol/kg diet, 2-(carboxyphenyl)retinamide caused the greatest reduction (57.7%) in the yield of ACF. 9-cis-RA was toxic at 1 mmol/kg so that it was evaluated at 0.1 mmol/kg, resulting in a 41.6% reduction in ACF. The ability of the retinoids to reduce the proliferating cell nuclear antigen (PCNA) labeling index in ACF and in non-involved crypts correlated with their ability to prevent ACF. Both 9-cis-RA (0.1 and 0.2 mmol/kg diet) and 4-HPR (1 and 2 mmol/kg diet) were highly effective in decreasing the yield of AOM-induced colon tumors. In summary, retinoids were demonstrated to reduce cell proliferation and to prevent ACF and tumors in the colon, suggesting promise as preventive agents for colon cancer.

Alitretinoin↗
PubMed1995

Mediation of inflammation by cyclooxygenase-2.

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

Animals↗
PubMed1991

Acute alterations in the regulation of lipid metabolism after intravascular reexposure to a single bolus of homologous virus during influenza B infection in ferrets: possible model of epiphenomena associated with influenza.

Metabolic responses occurring 24 h following the secondary haematogenous dissemination of influenza B virus during convalescence from infection were examined in the ferret as a possible model for epiphenomena which can occur following infection with influenza. Among the major changes found were a further rise in the mean fasting serum free fatty acid (FFA) level to three times the control mean value and a 50% drop in the mean serum triglyceride (TG) concentration after the intravascular administration of a single bolus of virus compared to levels found in uninfected or convalescent animals. In adipose tissue, hormone-sensitive and lipoprotein lipase activities were increased six and three-fold, respectively, over mean control values, probably accounting for the changes that were observed in serum lipid concentrations. In the liver, total carnitine palmitoyltransferase (CPT) activity was affected only slightly and the total lipid content of the liver remained unchanged. These findings indicate that 24 h after the intravascular dissemination of homologous virus in a single bolus during convalescence from influenza B infection, major distortions in the regulation of lipid metabolism occur in the ferret. Loss of the synchronous regulation of the two adipose tissue lipases is a significant consequence leading to the mobilization of a large amount of FFA during fasting from both adipose tissue and the circulating plasma TG stores.

Adipose Tissue↗
PubMed1990

Growth, feed efficiency and carcass composition of finishing Friesian steers fed the beta-adrenergic agonist L-644,969.

The beta-adrenergic agonist L-644,969 was evaluated to determine its effects on growth performance and carcass composition of Friesian steers. L-644,969 is the R,R isomer of 6-amino [[(1-methyl-3-phenylpropyl) amino] methyl]-3-pyridine methanol dihydrochloride. Four groups of 18 steers, averaging 380 kg body weight, were individually given ad libitum access to a pelleted concentrate diet that contained either 0, .25, 1.0 or 4.0 ppm L-644,969 for the final 12 wk of the finishing period. Live weight gain was not affected by L-644,969, but feed consumption was linearly reduced (5.5, 6.3 and 15.7%; P less than .01) and feed conversion efficiency was linearly increased (16, 25 and 31%; P less than .01) relative to unmedicated controls, respectively. In addition, L-644,969 quadratically increased carcass weight (3.7, 9.3 and 8.5%; P less than .01) and dressing percentage (2.7, 7.9 and 7.9%; P less than .001). The proportion of trimmed fat in the carcass was quadratically reduced (14.5, 29 and 36%; P less than .001) and yield of lean meat quadratically increased (6.7, 13 and 15.6%; P less than .001). beta-adrenergic agonist treatment altered the distribution of lean meat such that a greater (P less than .001) proportion of the total lean was in the hind portion of carcasses from treated animals. Based on these findings, we suggest that L-644,969 may have utility as an agent to improve efficiency of production of lean beef.

Adrenergic beta-Agonists↗
PubMed1990

Hepatic steatosis during convalescence from influenza B infection in ferrets with postprandial hyperinsulinemia.

The possibility that postprandial hyperinsulinemia could play a role in the development of hepatic lipid disturbances during convalescence from influenza B infection was explored in the ferret as a possible model of the steatosis of Reye's syndrome. Postprandial hyperinsulinemia was produced by feeding young ferrets glucose/water and a regular diet (glucose-treated group), as reflected by the mean serum insulin levels attained, which were 57 and 135 microU/ml during control and postinfluenza periods, respectively. By comparison, ferrets fed water and a regular diet (untreated group) had mean insulin levels of 19 and 22 microU/ml, while postprandial glucose levels were comparable in the two groups of animals for each period. In contrast to untreated animals, grossly visible fatty livers were found in glucose-treated ferrets during convalescence. The total lipid content of these livers had doubled compared with preinfection samples and compared with livers of untreated ferrets. By electron microscopy hepatic mitochondria showed striking changes with diminution of matrix density and reduction in cristae surface area only in convalescent samples from glucose-treated animals. Serum free fatty acid (FFA) levels were considerably higher in the glucose-treated animals during fasting before influenza and also after feeding during convalescence. Serum triglyceride (TG) levels were also high during convalescence in the glucose-treated group. Adipose tissue lipoprotein lipase activities were similar between groups, but hormone-sensitive lipase activity was twelvefold higher in glucose-treated ferrets before and after influenza B. These findings indicate that for a given stimulus, glucose-treated ferrets would mobilize more FFA than untreated ferrets. The total capacity for beta-oxidation of FA by the mitochondrial pathway was identical in all groups of animals. Total carnitine palmitoyl transferase (CPT) activity was the same in both control groups, but was significantly diminished in glucose-treated animals during convalescence. As CPT regulates the entry of FA into the mitochondrial matrix, its reduction in response to higher insulin concentrations would limit the oxidation of FA and stimulate TG accumulation. Therefore, the accumulation of lipid in the liver in this model is regarded to have been caused by the simultaneous occurrence of increased lipolysis and increased hepatic TG synthesis owing, in part, to diversion of activated FA by CPT, which is reduced in activity due to the regulatory action of insulin. These findings may have pathophysiologic relevance for the lipid changes that occur in Reye's syndrome and to fatty liver formation in hyperinsulinemic states.

Adipose Tissue↗
PubMed1988

Effect of efrotomycin in feed on the quantity, duration, and prevalence of shedding and antibacterial susceptibility of Salmonella typhimurium in experimentally infected swine.

The influence of efrotomycin administered at the rate of 16 mg/kg of feed in 10 Salmonella typhimurium-inoculated pigs was determined by comparing this group with a group of 10 pigs inoculated with S typhimurium that were given nonmedicated feed. Two control groups of 4 noninoculated pigs each, 1 group medicated with efrotomycin at 16 mg/kg of feed, the other nonmedicated, also were evaluated. An inoculum of 1.7 x 10(10) colony-forming-units/pig induced colonization of S typhimurium in all 20 pigs. Evaluation of the quantity of shedding did not reveal a clear or consistent treatment-related increase in S typhimurium counts; mean differences between the nonmedicated and medicated groups never exceeded 1 log unit. On the last day of the study (day 56 of the medication), 8 nonmedicated and 9 medicated pigs were determined to be infected with S typhimurium via enrichment procedures, so there was no difference in duration of shedding, and there were no significant differences in prevalence of shedding between the nonmedicated and medicated groups at any of the sampling times. Of 1,340 S typhimurium colonies isolated from the nonmedicated and medicated groups, 1,330 were susceptible to all 12 antibacterials tested, indicating no treatment-related effect on susceptibility. At necropsy, S typhimurium was not isolated from any liver or spleen specimens, and was isolated from only 2 of 20 lymph nodes. However, S typhimurium was isolated via enrichment from the cecal contents from all 20 pigs. There were no treatment-related differences in feed consumption, weight gain, or feed efficiency. Appreciable differences in the measurements were not found between the efrotomycin-medicated and nonmedicated pigs.

Animal Feed↗
PubMed1987

The carcinogenicity of trichloroethylene and its metabolites, trichloroacetic acid and dichloroacetic acid, in mouse liver.

Trichloroethylene (TCE) has previously been shown to be carcinogenic in mouse liver when administered by daily gavage in corn oil. The metabolism of TCE results, in part, in the formation of trichloroacetic acid (TCA) as a major metabolite and dichloroacetic acid (DCA) as a minor metabolite. These chlorinated acetic acids have not been shown to be genotoxic, although they have been shown to induce peroxisome proliferation. Therefore, we determined the ability they have been shown to induce peroxisome proliferation. Therefore, we determined the ability of TCE, TCA, or DCA to act as tumor promoters in mouse liver. Male B6C3F1 mice were administered intraperitoneally 0, 2.5, or 10 micrograms/g body wt ethylnitrosourea (ENU) on Day 15 of age. At 28 days of age, the mice were placed on drinking water containing either TCE (3 or 40 mg/liter), TCA (2 or 5 g/liter), or DCA (2 or 5 g/liter). All drinking waters were neutralized with NaOH to a final pH of 6.5-7.5. The animals were killed after 61 weeks of exposure to the treated drinking water (65 weeks of age). Both DCA and TCA at a concentration of 5 g/liter were carcinogenic without prior initiation with ENU, resulting in hepatocellular carcinomas in 81 and 32% of the animals, respectively. DCA and TCA also increased the incidence of animals with adenomas and the number of adenomas/animal in those animals that were not initiated with ENU. While 2.5 micrograms/g body wt ENU followed by NaCl in the drinking water resulted in only 5% of the animals with hepatocellular carcinomas, 2.5 micrograms/g body wt ENU followed with 2 or 5 g/liter DCA resulted in a 66 or 78% incidence of carcinoma, respectively, or, followed with 2 or 5 g/liter TCA, resulted in a 48% incidence at either concentration. None of the untreated animals had hepatocellular carcinomas. Therefore our results demonstrate that DCA and TCA are complete hepatocarcinogens in B6C3F1 mice.

Acetates↗