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Biomedical subjects

S M Anderson

Publications and source records attributed to S M Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Comparison of nucleic acid hybridization and cytologic examination for detection of human papillomavirus infection, with evaluation of two commercially available hybridization kits.

Human papillomavirus (HPV) infections were detected by analyzing exfoliated cervical cells for HPV DNA by use of nucleic acid hybridization; the results were correlated with cytologic findings on Papanicolaou smears. HPV infection was diagnosed in 154 women (20%) by either morphologic evidence on cervical smears or nucleic acid hybridization. Many of these women (38%; 58/154) exhibited Papanicolaou smears with no morphologic evidence of HPV infection. In those patients with cytologic evidence of HPV infection, only 28% were positive for HPV DNA. HPV 16 and (or) 18 were the most common types (27%) detected in women with cervical intraepithelial neoplasia, whereas all HPV groups tested were equally represented in patients with normal cervical smears. We also present an assessment of 17,000 clinical specimens submitted to this laboratory for analysis of HPV DNA.

Adolescent↗
PubMed1991

Transformation of human kidney proximal tubule cells by a src-containing retrovirus.

Analysis of the cell-surface antigenic phenotypes of normal and malignant renal cells demonstrates that approximately 90% of cultured normal human kidney cells and virtually all renal cell carcinomas (RCC) derive from the proximal tubule (PT) cell of the nephron. In the present study, the v-src oncogene was introduced into cultured normal human PT cells, and the effects of the v-src-encoded protein (pp60v-src) on the biologic and genetic phenotype of these cells were determined. V-src-containing PT cells underwent a series of phenotypic changes characteristic of renal cells in vivo. These included (i) alterations in morphology, (ii) an increase in proliferative capacity, (iii) loss of contact inhibition, (iv) immortalization and (v) tumorigenicity. Moreover, v-src-infected PT cells developed non-random clonal karyo-typic abnormalities which are commonly observed in RCCs, including a deletion of chromosomal region 3p14-21, one of the most frequent deletions observed in human renal tumors. These results indicate that pp60v-src can initiate a complex process leading to the transformation of PT cells. This process includes the induction of genetic instability. Finally, these data provide experimental evidence corroborating cytogenetic and molecular data that a deletion of genes on chromosome 3p is a critical event in the transformation of the human renal cell.

Animals↗
PubMed1990

Effects of carbamazepine on 5-hydroxytryptamine function in rodents.

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of postsynaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed by L-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 microM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Abrogation of IL-3 dependent growth requires a functional v-src gene product: evidence for an autocrine growth cycle.

We have investigated the ability of the v-src oncogene to abrogate growth factor dependent growth in the interleukin-3 dependent myeloid progenitor cell line 32D c13. Growth factor independent clones were isolated following infection of 32D c13 cells with murine retroviruses containing the v-src oncogene. v-src was demonstrated to be directly responsible for growth factor independence in experiments utilizing temperature-sensitive v-src mutants. The v-src infected cells released a growth factor capable of stimulating the proliferation of normal 32D c13 cells. Analysis of the mRNA from v-src infected 32D c13 did not identify the putative autocrine growth factor as one of the currently identified murine or human hematopoietic growth factors.

Animals↗
PubMed1989

Synthetic Medium for Acetobacter xylinum That Can Be Used for Isolation of Auxotrophic Mutants and Study of Cellulose Biosynthesis.

Acetobacter xylinum is a bacterium that can synthesize cellulose when grown in an undefined medium containing glucose. We developed a defined minimal medium for A. xylinum that contains 1% glucose, 0.1% NH(4)Cl, 0.115% citric acid, 0.33% Na(2)HPO(4), 0.01% KCl, 0.025% MgSO(4). 7H(2)O, and 7.5 mg of nicotinamide per liter which both allows cellulose synthesis and can be used to isolate a variety of auxotrophic mutants.

Journal Article↗
PubMed1989

Activity of rhodopsin in vitamin A-deprived rats: light-dependent binding of G-protein.

Levels of rhodopsin in the photoreceptors of Long-Evans rats were reduced by approximately 55% through dietary deprivation of vitamin A. The interaction of visual pigment with G-protein was examined in receptor outer segment (ROS) membranes obtained from these animals. A binding assay was used to quantitate affinity of the visual pigment in unbleached and bleached ROS membranes for the alpha and beta subunits of exogenous G-protein. Extents of binding were similar to those observed for ROS membranes of rats raised on a normal (vitamin A-supplemented) diet. The results are consistent with a normal capacity for G-activation by photoactivated rhodopsin (R*) in vitamin A-deprived animals. They further indicate that "free opsin" arising in vitamin A deficiency, unlike R*, has relatively low affinity for G-protein.

Animals↗
PubMed1988

Neuroendocrine correlates of sustained stress: the activity-stress paradigm.

Rats sacrificed after 4 days in the activity-stress paradigm or after 4 days of food restriction had significantly elevated levels of plasma corticosterone as compared to control rats. The approximately 5 fold increase in corticosterone in the stressed treatment groups was consistently found in all experiments. ACTH levels were elevated in activity-stress and food-restricted groups in some experiments but these increases were not statistically significant. Prolactin levels were significantly elevated in food-restricted group rats as compared to controls or activity-stress group animals in one experiment but this finding was not repeated in further experiments. In a second series of experiments, rats from activity-stressed and food-restricted treatment groups and controls were exposed to an acute stressor for 15 min prior to sacrifice to assess the effects of prior sustained stress on hormonal responses to an acute stressor. Exposure to 15 min of immobilization or intermittent footshock immediately prior to sacrifice increased plasma levels of corticosterone, ACTH and prolactin in control, food-restricted and activity-stressed rats. Generally, hormonal responses to the acute stress were similar in all treatment groups. However, in two experiments where the resting levels of corticosterone were especially elevated in the activity-stress group, the acute stress-induced rise in corticosterone was less than that seen for the other two treatment groups. In another experiment, administration of dexamethasone suppressed acute stress-evoked levels of ACTH and corticosterone in control, activity-stressed and food-restricted rats. Thus, rats exposed to 4 days of sustained stress were found to have consistently elevated resting levels of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Chronic stress increases the binding of the A1 adenosine receptor agonist, [3H]cyclohexyladenosine, to rat hypothalamus.

We previously reported an increase in the binding of [3H]cyclohexyladenosine ([3H]CHA) to brain membranes from the hypothalamus of rats sacrificed following three days of chronic stress in an around-the-clock intermittent footshock avoidance/escape paradigm ("sustained performance" stress). Here we report stress-induced increases in [3H]CHA binding to hypothalamic membranes from rats stressed for 14 days in that escape/avoidance paradigm, in rats exposed to repeated restraint (3 hr/day for 10 days) and in rats exposed to four days of "activity-stress." Data from saturation binding experiments indicate that this up-regulation was due to an increase in the apparent number of [3H]CHA binding sites without change in affinity for [3H]CHA. Neither restraint for one three-hr period nor one 15-min exposure to intermittent footshock resulted in significant changes in [3H]CHA binding to hypothalamic membranes. Our present data demonstrate small but consistent increases in the number of [3H]CHA binding sites in hypothalamic membranes from rats stressed in several different chronic stress models but no change by acute stress.

Adenosine↗
PubMed1987

Effects of chronic stress on plasma corticosterone, ACTH and prolactin.

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the "stressed" group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.

Adrenocorticotropic Hormone↗
PubMed1987

Isolation of a murine retrovirus with a temperature-sensitive src gene.

A murine retrovirus containing the src gene of avian sarcoma virus ts LA31A was generated. In contrast to the avian sarcoma virus, our recombinant murine retrovirus can efficiently infect mammalian cells. Transformation of NIH3T3 cells by the recombinant murine retrovirus is temperature sensitive. At the permissive temperature of 34 degrees, cells form foci of rounded cells. At the nonpermissive temperature of 39 degrees, the infected cells remain flat and exhibit contact inhibition. No disease was observed following infection of newborn NFS/n mice with the ts mutant virus. In contrast, infection of newborn NFS/n mice with a recombinant murine retrovirus containing the wild-type src gene causes fibrosarcomas and hepatosplenomegaly.

Animals↗
PubMed1987

Effects of stress on [3H]cyclohexyladenosine binding to rat brain membranes.

The investigation of stress-induced changes in neuronal functioning is important to our understanding of mental disorders, stress-induced psychological impairment, and the emotional reactions of fear and anxiety. Data from previous animal studies have demonstrated various pituitary-adrenal responses to stress and also changes in brain neurotransmitters. We are investigating whether stress-induced neuroendocrine and brain monoamine changes are accompanied by concomitant changes in brain neurotransmitter and/or neuromodulator receptors. We have developed a behavioral paradigm of chronic stress which incorporates sustained stress, continuous performance, and disruption of sleep. Animals which are habituated to press a lever to receive food are trained in an active shock escape task. A matched set of animals housed in identical operant chambers but not exposed to footshock are used as comparative controls. [3H]Cyclohexyladenosine ([3H]CHA) (5-7 nM) binding to A1 adenosine receptors in hypothalamic membrane preparations from rats stressed for three days was fifteen percent higher than in matched controls. However, no differences in [3H]CHA binding were found in tissue preparations from frontal cortex, hippocampus, or striatum, when comparing stressed and matched control rats. Plasma corticosterone levels were higher in stressed rats than in matched controls.

Adenosine↗
PubMed1987

Interaction of visual pigment with G-protein: effects of bleaching in native and reconstituted ROS preparations.

Native and reconstituted preparations of bullfrog rod outer segment (ROS) membranes were analysed for the binding of the alpha and beta subunits of G-protein. Following incubation at 22-28 degrees C under varying conditions of illumination and chemical treatment, preparations were chilled and extracted with hypotonic medium lacking-vs.-containing GTP (H and HG extracts, respectively). The extent of binding of G alpha,beta ('percentage G bound') was determined by measurement of the relative abundance of G alpha, beta in the H and HG extracts. The addition of G to unbleached, G-depleted membranes (D-ROS) yielded relatively little binding of the G (14 +/- 13%). G reintroduced at congruent to 1 min vs. congruent to 90 min after major bleaching yielded, respectively, levels of binding of 88 +/- 8% and 24 +/- 8%. Native G, extracted at congruent to 90 min post-bleach and added to freshly bleached D-ROS, exhibited binding exceeding that in the parent (bleached +90 min) sample. Supplementation of reconstituted suspensions with all-trans retinal, and subsequent incubation in darkness, yielded 30-35% G-binding; similar treatment with 11-cis retinal yielded binding in the range of 0-32%. Upon irradiation, suspensions previously supplemented with either isomer exhibited approximately 60% binding. Incubation with 11-cis retinal had no substantial effect on the condition of tight binding observed shortly after bleaching. The data are discussed in relation to previous studies of visual pigment bleaching and regeneration.

Animals↗
PubMed1987

Effects of an anxiogenic benzodiazepine receptor ligand on motor activity and dopamine release in nucleus accumbens and striatum in the rat.

The effects of the anxiogenic beta-carboline FG 7142 (N-methyl-beta-carboline-3-carboxylate) on motor activity and dopamine release in nucleus accumbens and striatum were measured in the rat. Changes in extracellular homovanillic acid (HVA) concentration, monitored by computer-controlled linear sweep voltammetry with carbon-paste electrodes, were used as an index of changes in dopamine release. An intraperitoneal injection of FG 7142 was followed by an inhibition of the nocturnal rise in motor activity and in dopamine release in nucleus accumbens, but not striatum. Two days after the drug injection, dopamine release in nucleus accumbens returned to control level and then increased on days 3-6 after the injection; there was no delayed change in motor activity or in striatal dopamine release. In parallel experiments using ex vivo changes in the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to dopamine as an index of changes in dopamine turnover, a similar early depression and delayed increase of dopamine turnover in nucleus accumbens, with no change in striatum, was found after an intraperitoneal injection of FG 7142. Regression analysis of motor activity versus dopamine release showed a decrease in correlation between these 2 parameters for nucleus accumbens but not striatum after FG 7142 injection. These results suggest that the inverse benzodiazepine receptor agonist FG 7142 has a biphasic effect on dopamine release from mesolimbic neurons and support the hypothesis that dopamine release in nucleus accumbens and striatum has a modulatory effect on the control of motor activity but does not play a determining role in the regulation of movement.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Dopamine stimulated increase of GTP levels in the rat retina.

Dopamine stimulates a 7-10-fold increase of GTP concentration in whole rat retina maintained in vitro. Half-maximal stimulation of GTP levels were obtained with 10(-6) M dopamine, and significant increases in GTP levels were seen with 10(-7) M dopamine. Intracellular GTP levels were significantly increased within 4 min after exposure to dopamine and maximal effects were reached within 30 min. Dopamine agonists, apomorphine and bromocriptine, also stimulate a 7-10-fold increase in GTP concentration, whereas other catecholamines (norepinephrine, epinephrine, and isoproterenol) were less potent. Several other neurotransmitters present in rat retina (gamma-aminobutyric acid, glycine, glutamine, and taurine) had no effect on GTP levels. Although dopamine also stimulates increases in cyclic AMP levels in the retina, dibutyryl cyclic AMP and 8-bromo-cyclic AMP had no effect on GTP levels, indicating that the dopamine-stimulated increase of GTP is independent of the catalytic production of cyclic AMP by adenylate cyclase. Since dopamine-stimulated adenylate cyclase activity requires GTP, the dopamine-stimulated increase in GTP concentration described in this report may serve to facilitate dopamine stimulation of adenylate cyclase activity.

Animals↗
PubMed1985

A murine recombinant retrovirus containing the src oncogene transforms erythroid precursor cells in vitro.

A murine retrovirus (MRSV) containing the src gene of Rous sarcoma virus has been shown to cause an erythroproliferative disease in mice (S. M. Anderson and E. M. Scolnick, J. Virol. 46:594-605, 1983). We now demonstrate that this same virus can transform erythroid progenitor cells in vitro. Infection of fetal liver cells or spleen and bone marrow cells from phenylhydrazine-treated adult mice gave rise to colonies of erythroid cells which grew in methylcellulose under conditions not favorable for the growth of normal erythroid cells. The presence of pp60src in the transformed erythroid cells was demonstrated by an immune complex protein kinase assay. The time course of appearance and subsequent differentiation of erythroid colonies indicated that the target cell for MRSV was a 6- to 8-day burst-forming unit. Differentiation of the erythroid progenitors was not blocked by the presence of pp60src, and the cells retained sensitivity to the hormone erythropoietin. In fact, the transformed cells exhibited increased hormone sensitivity since the number, the size, and the extent of hemoglobinization of the colonies were all increased by the addition of small amounts of erythropoietin. MRSV was not susceptible to restriction by the Fv-2 locus, as MRSV could transform hematopoietic cells from C57BL/6 mice. These results indicate that (i) the erythroid proliferation observed in vivo is caused by a direct effect of MRSV on erythroid progenitors and (ii) the transformed erythroid precursors acquire a growth advantage over uninfected cells without losing the ability to differentiate and respond to physiologic regulators.

Animals↗
PubMed1984

Hematopoietic cell transformation by a murine recombinant retrovirus containing the src gene of Rous sarcoma virus.

A recombinant murine retrovirus (MRSV) containing the src gene of avian Rous sarcoma virus (RSV) was shown to induce hematopoietic colonies in infected mouse bone marrow. MRSV-induced colony formation followed single-hit kinetics and required mercaptoethanol in the agar medium. Cells from the colonies induced by MRSV could be established as continuous cell lines that demonstrated unrestricted self-renewal in vitro and tumorigenicity in vivo. The transformants, all of which expressed high levels of the Rous sarcoma virus transforming protein, pp60src, appeared to be at an early stage in lymphoid cell differentiation. They lacked Fc receptors and detectable immunoglobulin mu heavy chain synthesis, markers normally associated with committed B cells. The majority of the MRSV-transformed cell lines contained high levels of terminal deoxynucleotidyl transferase, an enzyme present in lymphoid progenitor cells committed to the T-cell lineage. One cell line expressed Thy-1 antigen, but none expressed Lyt-1 and Lyt-2, markers of more differentiated T cells. These findings demonstrate that the src gene is capable of transforming cells of hematopoietic origin.

Animals↗
PubMed1984

Interaction of anticonvulsant drugs with adenosine receptors in the central nervous system.

The anticonvulsant carbamazepine inhibits binding of 1 nM [3H]N6-cyclohexyladenosine to rat cerebral and cerebellar A1 adenosine receptors with an IC50 value of about 50 microM. This concentration is well within that expected for therapeutic regimens. Other anticonvulsants such as phenobarbital, phenytoin, primidone, valproate sodium, and ethosuximide had little or no effect on binding, while theophylline and caffeine caused marked inhibition. Carbamazepine had no marked effect on cyclic AMP levels in guinea pig cerebral cortical or hippocampal slices, but was a weak inhibitor (IC50 about 200 microM) of 2-chloroadenosine-elicited accumulations of cyclic AMP via an A2 adenosine receptor in cortical slices. Carbamazepine is thus a somewhat selective ligand for A1 adenosine receptors in brain. The nature of its activity at those receptors is unclear, but its lack of central stimulant effects contrasts to the stimulant properties of A1 adenosine receptor antagonist such as caffeine and theophylline.

Adenosine↗