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Biomedical subjects

C Anderson

Publications and source records attributed to C Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Violence in television commercials during nonviolent programming. The 1996 Major League Baseball playoffs.

OBJECTIVE: To identify the frequency of violent television commercials aired during major league baseball playoffs, traditionally thought to be a family-oriented viewing time. DESIGN AND SETTING: All 6 World Series games televised on the Fox Television Network (Fox), all 5 American League Championship Series playoff games televised by the National Broadcasting Company (NBC), and 4 first-round playoff games televised by ESPN Sports Television Network (ESPN) were videotaped in October 1996. RESULTS: During the 15 televised games reviewed, 104 (6.8%) of the 1528 commercials contained violent content. Sixty-one commercials (10 per game) that included violent interactions were noted during the World Series, 30 (6 per game) during the American League Championship Series, and 13 (3 per game) during the 4 first-round playoff games for a total of 104. In these 104 violent commercials, 69 contained at least 1 violent act, 90 contained at least 1 violent threat, and 27 contained evidence of at least 1 violent consequence. Seventy (67.3%) of the violent commercials were promotions for television programs, 7 (6.7%) were cable television program advertisements, and 20 (19.2%) were big-screen movie promotions. Twenty (71.4%) of 28 big-screen movie promotions were violent. Twenty-two (21.2%) of the 104 violent commercials and 7 "nonviolent" commercials contained blood or other graphic content, all of which were televised during the Fox presentation of the World Series. Fox also accounted for all 24 violent commercials that used a knife. Guns were involved in 25 violent commercials on NBC (5.0 per game), in 20 on Fox (3.33 per game), and in 7 on ESPN (1.75 per game). CONCLUSION: Overt violent content in commercials during the 1996 major league playoffs was common and consisted mainly of promotions for television programs and big-screen movies. It is counterintuitive to find such commercials in nonviolent programming and makes it difficult for parents to avoid exposing their children to this form of violence.

Advertising↗
PubMed1997

Insulin signal transduction by a mutant human insulin receptor lacking the NPEY sequence. Evidence for an alternate mitogenic signaling pathway that is independent of Shc phosphorylation.

The cytoplasmic juxtamembrane domain of the human insulin receptor (hIR) contains a single copy of the tetrameric amino acid sequence Asn-Pro-Glu-Tyr (NPEY) (residues 969-972 in the exon 11-containing B-isoform), which exists in the context of NPXY. In this study, we examined the role of NPEY972 in mediating insulin signal transduction and cellular biological effects. Transfected Chinese hamster ovary cell lines expressing either the wild-type hIR-B isoform (hIR.WT) or a mutant receptor lacking the NPEY972 sequence (hIRDeltaNPEY) and control Chinese hamster ovary.Neo cells were used to comparatively analyze the following insulin effects: in vivo receptor tyrosine autophosphorylation and kinase activity, signal transduction to downstream signaling molecules, and stimulation of glycogen and DNA synthesis. The results showed that in comparison to hIR.WT, the hIRDeltaNPEY mutant demonstrated the following: (a) normal insulin-mediated receptor tyrosine phosphorylation, but approximately 50% reduction in phosphorylation of p185-(insulin receptor substrate-1) and binding of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase), (b) an enhanced stimulation of PI 3-kinase enzymatic activity, (c) a complete inability to phosphorylate Shc, (d) minimal impairment of insulin sensitivity for glycogen synthesis, and (e) an augmented response to insulin-stimulated DNA synthesis via a high capacity, low sensitivity pathway. These results demonstrate the following: 1) the NPEY972 sequence is important but not absolutely essential for coupling of hIR kinase to insulin receptor substrate-1 and p85 or for mediating insulin's metabolic and mitogenic effects, 2) the NPEY972 sequence is necessary for Shc phosphorylation, and 3) the absence of Shc phosphorylation releases the constraints on maximal insulin-stimulated mitogenic response, thus indicating that alternate signaling pathway(s) exist for this insulin action. This alternate pathway appears to be associated with enhanced activation of PI 3-kinase and is of high capacity and low sensitivity.

Animals↗
PubMed1997

Estrone sulfatase: probing structural requirements for substrate and inhibitor recognition.

The enzyme-catalyzed desulfation of steroids is a transformation that plays an important role in steroid biosynthesis. Conversion of steroid sulfates to unconjugated steroids may provide a source of steroids for processes such as steroid transport and the growth and proliferation of breast cancer. Steroid sulfatase catalyzes the hydrolysis of 3beta-hydroxysteroid sulfates. To identify structural features important in enzyme-inhibitor interaction, a variety of steroidal and non-steroidal phosphate esters were synthesized and tested as inhibitors of steroid sulfatase activity. We report that the basic structure for enzyme-inhibitor binding does not include the steroid nucleus. Furthermore, the hydrophobicity of the non-steroidal phosphates was determined to be an important factor for optimal inhibition. The monoanionic form of the phosphorylated compounds was found to be the inhibitory species. The best non-steroidal inhibitor of steroid sulfatase activity was n-lauroyl tryamine phosphate with a Ki of 3.6 microM and 520 nM at pH 7.5 and 7.0. The poorest non-steroidal based inhibitor of sulfatase activity was tetrahydronaphthyl phosphate with a Ki of 870 and 360 microM at pH 7.5 and 7.0.

Chromogenic Compounds↗
PubMed1997

Risk factors for post-stroke depression.

OBJECTIVE: To examine possible risk factors in post-stroke depression (PSD) other than site of lesion in the brain DATA SOURCES: 191 first-ever stroke patients were examined physically shortly after their stroke and examined psychiatrically and physically 4 months post-stroke. SETTING: A geographically defined segment of the metropolitan area of Perth, Western Australia, from which all strokes over a course of 18 months were examined (the Perth Community Stroke Study). MEASURES: Psychiatric Assessment Schedule, Mini Mental State Examination, Barthel Index, Frenchay Activities Index, physical illness and sociodemographic data were collected. Post-stroke depression (PSD) included both major depression and minor depression (dysthymia without the 2-year time stipulation) according to DSM-III (American Psychiatric Association) criteria. Patients depressed at the time of the stroke were excluded. PATIENTS: 191 first-ever stroke patients, 111 M, 80 F, 28% had PSD, 17% major and 11% minor depression. RESULTS: Significant associations with PSD at 4 months were major functional impairment, living in a nursing home, being divorced and having a high pre-stroke alcohol intake (M only). There was no significant association with age, sex, social class, cognitive impairment or pre-stroke physical illness. CONCLUSION: Results favoured the hypothesis that depression in an unselected group of stroke patients is no more common, and of no more specific aetiology, than it is among elderly patients with other physical illness.

Activities of Daily Living↗
PubMed1997

Hepatotoxicity of an HIV protease inhibitor in dogs and rats.

Oral administration of the HIV protease inhibitor L-689,502 caused cholestasis and hepatocyte injury in rats and dogs. These changes occurred rapidly, with elevations in serum transaminase observed as early as 6 hr after oral dosing in dogs. The acute phase of this hepatotoxic response was characterized in more detail in rats. Following intravenous administration, bile flow was decreased in a dose-dependent manner with greater than 90% decrease in less than 30 min at a dose of 5 mg/kg. The decrease in bile flow was associated with a decrease in erythritol clearance. The decrease in bile flow was not due to disruption of biliary tight junctions. Sucrose clearance was not increased and biliary bile acid concentrations in treated animals were not different from controls. Unlike control animals, bile flow was not stimulated by infusion of the bile acid tauroursodeoxycholic acid in animals treated with L-689,502. These cholestatic effects may be due, in part, to direct hepatocyte injury. Histological examination of perfusion-fixed livers 30 min after L-689,502 administration revealed periportal changes including hepatocyte vacuolation and occasional single cell necrosis. On a subcellular level, the nucleus and mitochondria were intact in less-severely affected cells. However, extensive vacuolation with multilamellar inclusions was pronounced in these cells. In addition, canalicular ectasia was also observed which was consistent with the cholestatic changes that were seen. In summary, L-689,502 is a potent, rapid acting hepatotoxin in dogs and rats. The mechanism by which this agent induces cholestasis is novel compared to other well-characterized cholestatic agents such as alpha-naphtylisothiocyanate and ethinyl estradiol.

Animals↗
PubMed1997

Tumour biological features of BRCA1-induced breast and ovarian cancer.

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.

Adult↗
PubMed1997

Phthalocyanine photodynamic therapy: disparate effects of pharmacologic inhibitors on cutaneous photosensitivity and on tumor regression.

The phthalocyanines are promising second-generation photosensitizers that are being evaluated for the photodynamic therapy (PDT) of malignant tumors. In vivo studies with the silicon phthalocyanine Pc 4 have shown that it is highly effective at causing regression of RIF-1 tumors in C3H/HeN mice in PDT protocols. Because cutaneous photosensitivity is the major complication of photosensitizers used for PDT, experiments were performed to evaluate the effect of inhibitors of the inflammatory response (cyproheptadine, dexamethasone, pentoxifylline, and tumor necrosis factor alpha [TNF-alpha] antibodies) on Pc 4-induced cutaneous photosensitivity and tumor regression. The C3H/HeN mice were injected with either Pc 4 or Photofrin and were exposed to 86 J/cm2 of filtered radiation emitted from a solar simulator. Animals were irradiated at 1, 3, 7, 10, 14 and 28 days postinjection. Cutaneous photosensitivity was assessed using the murine ear-swelling response. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies were administered prior to illumination to assess their ability to block Pc 4-induced cutaneous photosensitivity and to evaluate whether such treatment adversely influenced Pc 4 PDT-induced tumor regression. Compared to Photofrin, Pc 4 produced cutaneous photosensitivity that was transient, resolving within 24 h, and that could be elicited for only 10 days after administration. In contrast, Photofrin caused photosensitivity that required 4 days to resolve and could be elicited for at least 1 month after it was administered. The Pc 4-induced cutaneous photosensitivity could be blocked by corticosteroids and an inhibitor of vasoactive amines (cyproheptadine). The TNF-alpha gene transcription was found to increase in keratinocytes following treatment with Pc 4 and light. The anti-TNF-alpha antibodies and pentoxifylline, an inhibitor of cytokine transcription, also prevented cutaneous photosensitivity, implicating TNF-alpha in the pathogenesis of Pc 4-induced cutaneous photosensitivity. None of these agents had any effect on Pc 4 PDT-induced tumor regression. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies may be valuable pharmacologic agents in the management of cutaneous photosensitivity associated with PDT without altering the efficacy of this new therapeutic modality. The findings suggest that it should be possible to devise PDT protocols that block cutaneous photosensitivity without impairing the anti-tumor response to the agents.

Animals↗
PubMed1997

Effectiveness and economic impact of antidepressant medications: a review.

This article reviews the existing literature on the pharmacoeconomics and effectiveness of antidepressant medications. Although selective serotonin reuptake inhibitors (SSRIs) have not proved to be more efficacious than the older tricyclics, and their prescription costs are significantly higher, they provide superior effectiveness; ie, patients are less likely to discontinue taking them or switch antidepressants. Pharmacoeconomic studies consistently demonstrate a relationship between this superior effectiveness and reductions in overall treatment costs, often through decreased utilization of medical and hospital services. The most conservative study found a cost offset that more than negated the extra cost of drugs, although the cost savings were not statistically significant. Other studies found statistically significant lowering of utilization costs by using SSRIs rather than tricyclics. Studies comparing SSRIs with each other present conflicting findings, although fluoxetine appears to have an edge over sertraline and paroxetine with regards to effectiveness and pharmacoeconomics. More studies employing a prospective outcome design and naturalistic study setting need to be conducted with SSRIs and other new antidepressants.

Antidepressive Agents, Second-Generation↗
PubMed1996

Insulin internalization in the absence of the insulin receptor tyrosine kinase domain is insufficient for mediating intracellular biological effects.

The intracellular portion of the human insulin receptor (hIR) beta-subunit contains distinct functional domains including the exon 16-encoded juxtamembrane (JM) domain that mediates endocytosis, and the tyrosine kinase (TK) domain that mediates insulin's metabolic and mitogenic actions. To explore the functional relationship between these domains and to determine the role of insulin internalization in insulin action, we constructed and studied the endocytic and signaling properties of an hIR mutant truncated at Glu-1012. This truncation removes the carboxyl-terminal 343 amino acids containing essentially all of the TK domain but leaves behind the exon 16-encoded JM domain that is necessary for endocytosis, plus an additional 35 amino acids downstream. The wild-type (hIR-WT) and mutant (hIR delta 343) receptors were stably expressed in CHO cells and their abilities to mediate various insulin-stimulated functions were comparatively analyzed. In cells expressing hIR-WT, insulin markedly enhanced tyrosine phosphorylation of the beta-subunit and of the endogenous 185 kDa substrate whereas these effects were completely absent in cells expressing hIR delta 343. The hIR delta 343 receptors retained the ability to internalize a significant amount of surface-bound insulin at 37 degrees C. However, they were unable to mediate either the short or long-term biological effects of insulin as determined by assaying insulin-stimulated glucose uptake (assessed by 2-deoxyglucose uptake), protooncogene expression (measured by Northern blot analysis of c-fos mRNA) and DNA synthesis (measured by 3H-thymidine incorporation). These results indicate that the hIR beta-subunit JM and TK domains can be functionally uncoupled, and that insulin internalization in the absence of hIR TK domain and kinase activity is insufficient for mediating intracellular insulin action.

Animals↗
PubMed1996

Comparison of transrectal ultrasound prostatic volume estimation with magnetic resonance imaging volume estimation and surgical specimen weight in patients with benign prostatic hyperplasia.

There are relatively few reports in the literature comparing transrectal ultrasound (TRUS) to magnetic resonance imaging (MRI) in estimating the volume of the prostate in the management of benign prostatic hyperplasia (BPH). In this study, we compared volumes determined by TRUS with MRI and TRUS-estimated weights with surgical specimen weights. The main findings of this study were (a) TRUS and MRI measurement of prostate volumes are quite similar; and (b) TRUS underestimates (by 10%) the prostatic weight as determined from the surgical specimens. A better volume estimate can thus be obtained by multiplying the TRUS measurement by a factor of 1.10. We conclude that because TRUS is cheap, user-friendly, noninvasive, and equally as accurate as MRI, it should be the preferred modality in the follow-up of BPH patients.

Humans↗
PubMed1996

Methylation of the glial fibrillary acidic protein gene shows novel biphasic changes during brain development.

The gene for glial fibrillary acidic protein (GFAP) was analyzed in the rat for developmental changes in methylation of cytosine at CpG sequences as a correlate of the onset of GFAP mRNA expression and for the effect of methylation on GFAP promoter activity. The methylation of nine CpG sites in the GFAP promoter and ten sites in exon 1 was analyzed in F344 rats by a quantitative application of ligation-mediated polymerase chain reaction. Whole rat brain poly(A)+ RNA showed an exponential increase of GFAP mRNA after embryo day 14 that reached stable adult levels by postnatal day 10. During development, only the seven CpG sites in the far-upstream promoter showed large changes in methylation; these sites constitute the brain-specific domain of methylation described in adult rats (Teter et al: J Neurosci Res 39:680, 1994). These seven CpG sites showed a cycle of demethylation during the onset of GFAP transcription in the embryo (between embryonic day 14 and postnatal day 10) followed by remethylation at later postnatal ages when GFAP mRNA remains prevalent. The minimum levels of methylation across these CpG sites displayed a gradient with the lowest minima at the 3' sites. This demethylation/remethylation cycle is a novel phenomenon in DNA methylation during perinatal development. The demethylation/remethylation cycle during development was also shown by the opposite-strand cytosines. Two cytosines in this region that are conserved in rat and mouse also undergo the same demethylation/remethylation cycle in the mouse GFAP gene during development, implying evolutionary conservation and functional significance. As a further test of functional significance, a Luciferase reporter gene assay was evaluated in primary cultured astrocytes; the activity of the GFAP promoter was reduced when it was methylated at one or all CpG sites. Therefore, the GFAP promoter may be activated in rodent development by transient demethylation of a conserved brain-specific methylation domain.

Animals↗
PubMed1996

Effect of continuously warmed i.v. fluids on intraoperative hypothermia.

The investigators examined the effect of infusing continuously warmed (ie, 37.0 degrees C [98.6 degrees F]) i.v. fluids in two groups of middle-aged female patients undergoing laparoscopic cholecystectomy procedures. They hypothesized that increasing i.v. fluid temperature during surgery would decrease patients' risk for hypothermia. One group of patients received prewarmed i.v. fluids that cooled to room temperature during surgery. The second group received i.v. fluids that were warmed continuously by a fluid warmer during the surgical procedures. Analyses of covariance, with the first intraoperative temperature measurement treated as the covariate, revealed nonsignificant results at the P < .05 level. The results suggest that administering continuously warmed i.v. fluids intraoperatively has no significant effect on maintaining patients' body temperatures during short laparoscopic surgical procedures.

Adult↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗