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Biomedical subjects

R L Montgomery

Publications and source records attributed to R L Montgomery.

At least 19 recordsLinked to original sources

Regulation of rat ornithine decarboxylase promoter activity by binding of transcription factor Sp1.

Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine biosynthesis. We investigated the transcriptional regulation of the rat ODC gene using transient expression assays. The 5'-flanking region (-1156 to +13) of the ODC gene was sufficient to mediate strong basal expression of a luciferase reporter. Sequences between -345 and -93 contributed to basal promoter activity. This region, containing five potential Sp1 binding sites, was analyzed by electrophoretic mobility shift assays. Three specific DNA-protein complexes were identified using H35 nuclear extracts and the -345/-93 ODC probe. Binding to all three was eliminated by competition with an oligonucleotide containing an Sp1 binding site, but not by a mutant Sp1 oligonucleotide. Preincubation with an antibody against Sp1 supershifted complexes associated with one or more of Sp1 binding sites 1-4 as well as with site 5. DNase I footprinting revealed two protected regions: PR-I (-92 to -130) and PR-II (-304 to -332). PR-I contains a putative binding site for Sp1 that was protected by recombinant Sp1 protein. Transfection studies in Schneider SL2 cells demonstrated that the ODC promoter is transactivated up to 350-fold by Sp1 and that this transactivation is dependent on the presence of Sp1 binding sites 1-4. Thus, although the ODC promoter binds multiple nuclear proteins, Sp1 or a related protein appears to be a critical determinant of ODC transcription, possibly through cooperative interactions between Sp1 and additional transcription factors.

Animals

Expression of epidermal ornithine decarboxylase and nuclear proto-oncogenes in phorbol ester tumor promotion-sensitive and -resistant mice.

This study was undertaken to assess the effects of a single or two sequential topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of c-fos, c-jun, junB, c-myc, and ornithine decarboxylase (ODC) in promotion-sensitive SSIN mice and the relatively promotion-resistant C57BL/6 strain. Northern blot analysis demonstrated that a single promoting dose of TPA induced ODC mRNA expression 10- to 15-fold in both strains. Treatment of each strain with a second dose of TPA, 48 h (in C57BL/6 mice) or 72 h (in SSIN mice) after the first, led to hyperinduction of ODC activity. Although this involved transcription of new ODC mRNA, the hyperinduction of ODC enzyme activity was primarily posttranscriptional. Induction of c-fos mRNA or protein was maximal about 3 h after a single treatment in either strain but was sustained for at least 6 h in C57BL/6 mice. In contrast, two treatments of SSIN mice with TPA caused a rapid, strong c-fos induction 1-2 h after treatment, whereas C57BL/6 mice responded no more strongly than after a single treatment. c-jun mRNA and protein were induced only slightly in either strain, but junB was induced about fivefold in SSIN mice and tenfold in C57BL/6 mice. Although c-myc was induced to comparable levels in both strains, the response was more prolonged in C57BL/6 mice. Compared with SSIN mice, C57BL/6 mice responded to TPA treatment, in general, with changes in proto-oncogene mRNA to a higher level or for longer or both. Thus, although small differences in the expression of these genes were observed, they were not positively correlated with the differential sensitivity of SSIN and C57BL/6 mice toward tumor promotion by phorbol esters, with the possible exception of c-fos.

Animals

Age of first use and present use of alcohol by undergraduates.

This study assessed age of first experimentation with alcohol and its present use and consequences of use by 231 college students at a midwestern university. Early alcohol use was significantly associated with present use of alcohol, negative consequences of present alcohol use, and several measures of adjustment including academic and personal-emotional adjustment.

Adolescent

Late rupture of the posterior cruciate ligament after total knee replacement.

To our knowledge there have been no reports of late rupture of the posterior cruciate ligament (PCL) as a cause of instability in PCL-retaining total knee prostheses. In our experience of 150 total knee replacements using PCL-retaining prosthesis, three cases (2.0%) of late rupture of the posterior cruciate ligament have occurred, each leading to chronic instability, disabling pain, and revision arthroplasty. In each case rupture of the posterior cruciate ligament was confirmed at the time of revision arthroplasty. The use of a more constrained prosthesis led to a successful outcome in each case.

Aged

Isoniazid as preventive therapy in HIV-infected intravenous drug abusers. A decision analysis.

Tuberculin skin testing is a notoriously poor marker of tuberculosis infection in patients who are serologically positive for the human immunodeficiency virus. A decision analysis was performed to determine if and when isoniazid should be prescribed to prevent tuberculosis in these patients. The decision was analyzed for an intravenous drug abuser who may have been anergic, while tuberculin test status, race, and gender were varied. The assumptions and parameter estimates selected for this investigation represent a highly conservative vantage point opposing the use of isoniazid as a preventive therapy. Nevertheless, results showed a benefit from the use of isoniazid as a preventive therapy for all groups, even without tuberculin testing, except tuberculin-negative black women. This benefit of isoniazid therapy increased patient life expectancy as much as 285 days. Further, the decisions continue to favor prescribing isoniazid even when the suspected incidence of tuberculosis infection falls as low as 3% to 8%. Tuberculin testing appears important primarily for black women, since those who have negative tuberculin skin tests may not be candidates for isoniazid therapy.

Adult

Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C-kinase-deficient rat hepatoma cells.

Tumor-promoting phorbol esters and insulin produce similar effects in Reuber H35 rat hepatoma cell proliferation, including increased ornithine decarboxylase (ODC) enzyme activity, DNA synthesis, and mitogenesis. We investigated ODC mRNA accumulation in cells treated with either insulin or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Both agents caused rapid accumulation of ODC mRNA: for TPA, it was maximal 3 hr after treatment (4-6-fold greater than control cells) and returned quickly to control levels; for insulin, it was significantly longer, continuing to increase for at least 6 hr. Simultaneous treatment with TPA and insulin led to additive effects on ODC mRNA. Induction of ODC by TPA was blocked by down-regulation or inhibition of protein kinase C (PKC), consistent with a PKC-mediated mechanism. In contrast, PKC down-regulation had little effect on ODC induction by insulin. Furthermore, although both agents stimulated ribosomal S6 protein phosphorylation in cells containing normal amounts of PKC, the response to TPA was abolished in PKC-depleted cells; the effect of insulin was only slightly inhibited. TPA caused a rapid redistribution of essentially all of the PKC activity from the cytosolic to the membrane fraction of the cells, whereas insulin had no effect on PKC distribution. These results suggest that although insulin and TPA share some common cytoplasmic signalling pathways, their effects on phosphorylation of nuclear proteins and transcription of ODC may be mediated by distinct factors.

Animals

Social support, perceptions of attractiveness, weight, and the CPI in socially anxious males and females.

To see how socially anxious people function in a number of domains, Watson and Friend's (1969) Social Avoidance and Distress Scale (SAD) was administered to 101 undergraduates along with the California Personality Inventory (CPI) and the Psychosocial Support Inventory (PSI), a measure of social support. Additionally, a perceived attractiveness measure and various measures related to being overweight were taken. SAD scores correlated significantly in a negative direction with 13 of the 18 CPI scales, and those with high SAD scores had poorer social support networks. High SAD scores also were related to the perception of being overweight, but not to perceived physical attractiveness or to actually being overweight. Gender differences showed that females had more intimate social interactions and that socially anxious females relied more on their family for social support than did other people. Overall, the results suggested that the socially anxious person may have deficits in a variety of personal and interpersonal domains.

Adult

Demography and pathology of an urban slave population from New Orleans.

Twenty-nine skeletons from the first cemetery in New Orleans provide significant new information about urban slavery in America. Dating as early as 1720 and used perhaps as late as 1810, the cemetery provided an identifiable sample of two whites, 13 blacks, one individual of possible Indian-white ancestry, and two possibly mulatto individuals. Numerous skeletal and dental lesions were noted in the series, and historical information was used in conjunction with the physical data to draw conclusions about rates and patterns of mortality. Pathological changes indicate that the cemetery contained individuals representing two slave occupational groups, house servants and laborers. This research provides information in the expanding area of Afro-American biohistorical research.

Black or African American

An X-ray diffraction comparison of myelins from the human nervous system.

Earlier small-angle X-ray diffraction studies have indicated that central and peripheral nerve myelins may be significantly different structurally, although relatively few examples for each system and for individual species have been examined. In order to understand better the intra- and inter-system relationships, this study has developed more extensive information for a single species: six cases centrally and ten peripherally, featuring cranial nerves and a few others of the human nervous system. Peripheral myelin spacings (membrane pair thicknesses) are relatively similar, 184.4 +/- 1.40 A, and the ratios of diffraction peak height intensities of the second to fourth orders are also closely bunched: 1.85 +/- 0.216. Central myelin spacings and intensity ratios are distinctly different and more variable: spacings 160.3-165.8 A and intensity ratios 2.81-4.46. It appears that within a given species or between closely related (e.g., mammalian) species peripheral myelins possess relatively invariant structures, though significant spacing declines are encountered for both systems as phylogenetic relationships become more distant. The observed greater variability of CNS structures within a single species may correspond to known compositional differences between CNS regions or result from observational difficulties. In any case there is a marked discontinuity between the myelin structures of CNS and PNS nerves.

Adolescent