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Biomedical subjects

R D Anderson

Publications and source records attributed to R D Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Excision repair reduces doxorubicin-induced genotoxicity.

LacI mutations induced by doxorubicin in a wild-type, uvr(A)BC repair-proficient E. coli strain were analyzed by DNA sequencing. These mutations were contrasted with mutations previously recovered from doxorubicin-treated uvrB- organisms in order to assess the role of excision repair in doxorubicin-induced genotoxicity. After a 30-min exposure of wild-type E. coli to 330 microM doxorubicin, survival was 34% and the overall lacI mutation frequency increased 1.8-fold to 340 x 10(-8). The distribution of doxorubicin-induced mutants among subclasses of mutation involving the i-d and lac operator regions differed significantly between repair-proficient and -deficient strains. Distributional differences appeared to result both from a decrease in deletions involving the lac operator and an increase in base substitutions involving the i-d region in repair proficient organisms. However, elements of the doxorubicin-induced mutation spectrum in uvrB- E. coli are still discernable in wild-type organisms. These elements include the remarkable shift of 3'-deletion endpoints to palindromic sequence within the lac operator and the recovery of multiple isolates of T:A-->A:T transversions at position 96 in doxorubicin-treated cultures. These observations suggest that components of the uvr(A)BC nucleotide excision repair system function through a general mechanism prior to fixation of mutations to reduce, but not completely eliminate, the genotoxic effects of doxorubicin.

Base Sequence↗
PubMed1993

Genetic heterogeneity for Duchenne-like muscular dystrophy (DLMD) based on linkage and 50 DAG analysis.

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive (AR) muscular dystrophy which presents a clinical course indistinguishable from the Xp21 Duchenne muscular dystrophy or DMD. Recently, Othmane et al., based on a linkage study with 13q12 markers in 3 highly inbred DLMD families from Tunisia, suggested that the gene for this myopathy lies in the pericentromeric region of chromosome 13q. It is unknown if there is genetic heterogeneity causing the DLMD phenotype. Therefore, the aim of the present report is to describe the results of linkage analysis in 4 Brazilian DLMD families with 13q12 markers (D13S115 and D13S120), which were also tested for 50DAG. It was possible to exclude the 13q gene at theta = 0.10 as responsible for the DLMD phenotype in our families using both 13q12 markers, if the lod scores of each family were added up. Interestingly, 3 families were deficient for 50 DAG while one showed a positive pattern for this glycoprotein. Therefore, these results suggest: a) the DLMD phenotype is caused by more than one recessive gene; b) a gene, not located at 13q, causes deficiency of 50 DAG as a primary or secondary defect.

Brazil↗
PubMed1993

The expanded "BAT" flap for treatment of male pattern baldness.

A new combination of expanded simultaneous transposition and advancement flaps is reported for the treatment of extensive male pattern baldness. Although vertical transposition and parieto-occipital advancement flaps in themselves are not new, their combination and simultaneous bilateral use combined with the use of expansion is new. The advantages of the expanded bilateral advancement transposition flap procedure are presented, along with the technique and results. The results are predictable, providing a more pleasing result, with a natural immediate temporal recession, avoidance of temporal dog-ears, and desirable anterior-superior direction of hair growth. Although flaps do require surgical skill and training, and there are risks and possible complications involved, the results are achieved in a relatively short time compared with grafting techniques. Flaps also provide the advantages of a full and natural hairline contrasted with the sparse look afforded by multiple grafts. The described procedures are very effective and reliable when properly planned and properly executed.

Adult↗
PubMed1993

Deficiency of dystrophin-associated proteins in Duchenne muscular dystrophy patients lacking COOH-terminal domains of dystrophin.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a cytoskeletal protein tightly associated with a large oligomeric complex of sarcolemmal glycoproteins including dystroglycan, which provides a linkage to the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix which, in turn, may render muscle cells susceptible to necrosis. The COOH-terminal domains (cysteine-rich and carboxyl-terminal) of dystrophin have been suggested to interact with the sarcolemmal glycoprotein complex. However, truncated dystrophin lacking these domains was reported to be localized to the sarcolemma in four DMD patients recently. Here we report that all of the dystrophin-associated proteins are drastically reduced in the sarcolemma of three DMD patients in whom dystrophin lacking the COOH-terminal domains was properly localized to the sarcolemma. Our results indicate that the COOH-terminal domains of dystrophin are required for the proper interaction of dystrophin with the dystrophin-associated proteins and also support our hypothesis that the loss of the dystrophin-associated proteins in the sarcolemma leads to severe muscular dystrophy even when truncated dystrophin is present in the subsarcolemmal cytoskeleton.

Biopsy↗
PubMed1993

Screening for psychiatric symptoms and illness behaviour in a pain clinic.

Evolution of a multidisciplinary pain clinic in a rehabilitation hospital is described. The assessment process was facilitated, particularly with respect to psychiatric and psychological evaluation, by the preliminary administration of two well established but simple self-administered questionnaire instruments, the Illness Behaviour Questionnaire (IBQ) and the Crown-Crisp Experiential Index (CCEI). The characteristics of our pain clinic population are described. They demonstrate questionnaire profiles which are typical of pain patients. Attention is drawn to the CCEI profile now shown in three studies of pain patients, predominance of the somatic anxiety (S) scale occurring in all. Correlations between the IBQ and CCEI showed, inter alia, that the S scale is a measure of somatisation in pain patients. This paper aims to describe the changes in the clinic since previously published descriptions, to note the characteristics of our patient on the questionnaire instruments and to comment on the value of these questionnaires in the assessment of psychiatric symptoms and somatisation in pain clinic patients.

Adult↗
PubMed1992

Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells.

The human papillomavirus (HPV)-16 oncogenes, E6 and E7, are transcribed preferentially in keratinocytes and cervical carcinoma cells due to a 5' enhancer. An abundant peptide binding to a 37 nt enhancer element was purified from human keratinocytes by sequence-specific DNA chromatography. This protein was identified as transcriptional enhancer factor (TEF)-1 by complex mobility, binding to wild-type and mutant SV40 and HPV-16 enhansons and antigenic reactivity with two anti-TEF-1 antibodies. TEF-1 is cell-specific, but its transactivation also depends on a limiting, cell-specific TEF-1 'co-activator'. We show that both TEF-1 and the TEF-1 co-activator are active in human keratinocytes and essential for HPV-16 transcription. TEF-1 binding in vivo was necessary for HPV-16 P97 promoter activity. Excess TEF-1 and chimeric GAL4-TEF-1 specifically inhibited the P97 promoter by 'squelching', indicating that HPV-16 transcription also requires a limiting TEF-1 co-activator. TEF-1 and the TEF-1 co-activator functions mirrored HPV-16 transcription by their presence in keratinocytes and cervical carcinoma cells and their absence from lymphoid B-cells, but also functioned in liver cells where the HPV-16 promoter is inactive. TEF-1 and its associated co-activator are thus part of a complex mechanism which determines the restricted cell range of the HPV-16 E6 and E7 oncogene promoter.

Antibodies↗
PubMed1992

Mirror to ASHP: 1942-1992.

Highlights from the history of ASHP are presented on the occasion of the Society's 50th anniversary. Efforts to organize a formal group representing hospital pharmacists, begun in the 1920s, resulted in the formation of a subsection on hospital pharmacy of the American Pharmaceutical Association in 1936. In 1942, ASHP became a distinct organization affiliated with APhA. The body's goals were to establish minimum standards for pharmaceutical services, ensure a supply of well-qualified hospital pharmacists by providing hospital internships, facilitate information exchange, and foster cost-effective use of medicines. The development of practice standards and periodic surveys of hospital pharmaceutical services, educational efforts and accreditation programs, publications, and ASHP's role in the development of principles for hospital formulary systems are described. ASHP's endorsement of unit dose drug distribution and systems for preparation of intravenous admixtures is discussed. The evolution of pharmacists' clinical roles, their increased involvement in drug therapy decisions and the provision of drug information to patients, and the expanded responsibility implicit in the pharmaceutical care concept are traced. Today's ASHP members can build on the work of yesterday's members to provide better pharmaceutical care.

History, 20th Century↗
PubMed1991

DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli.

In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-fold increase in overall mutation frequency. The 5'-endpoints of doxorubicin-induced lacO and lacI/lacO deletions occurred at the DNA sequence 5'-pyTAA or 5'-AATpy (where py is pyrmidine) (16%), at runs of purines or pyrimidines (41%) and adjacent to 5'-dGdC or 5'-dCdG doublets (34%). Ninety % (27 of 30) of the doxorubicin-induced deletions involving the region of the lacO palindrome had 3'-endpoints within the palindrome sequence as compared with 40% (4 of 10) spontaneous deletions in an untreated set. Doxorubicin-induced single base substitutions were highly focused at one site (4 of 6) in the i-d region of lacI, in contrast to the spontaneous distribution of point mutations, where 16 mutants were recovered at 12 different sites. An increased frequency (3-fold) of highly focused base substitutions was also observed at 2 sites in the lac operator region (at lacO +6, which is a transition "hotspot" in the spontaneous spectra of both wild type and uvrB- organisms and at the adjacent +5 site). Notably, the frequency of 1- and 2-base frameshifts did not increase in the doxorubicin-induced spectrum, relative to the spontaneous mutation spectrum. These in vivo observations in E. coli suggest that in the absence of excision repair, doxorubicin causes highly focused deletions and base substitutions. These mutations occur adjacent to DNA sequences identified in previous in vitro studies as preferential sites of doxorubicin binding.

Base Sequence↗
PubMed1991

The association between pregnancy and human papilloma virus prevalence.

This study examined the effects of pregnancy on the prevalence of HPV infection, comparing 69 pregnant and 54 nonpregnant age-frequency matched female patients. HPV prevalence was detected by DNA hybridization using the ViraPap/ViraType dot blot procedure. The prevalence of HPV among pregnant women increased with gestational age from 8.0% in the first trimester, to 16.7% in the second, and 23.1% in the third trimester. This finding suggests that HPV infection may be activated by hormonal or other effects of pregnancy and may explain why number of pregnancies is known to be associated with increased risk of cervical dysplasia and cancer. Oncogenic HPV types 16/18 and 31/33/35 were identified with almost equal frequency in the study population whereas HPV 6/11 was seen rarely. The logistic regression models indicate that there were no significant differences between HPV positive and HPV negative groups by age, income, number of sex partners, age of first intercourse, average frequency of intercourse per month, number of pregnancies, oral contraceptive duration, or pregnancy status. There were no interaction effects. A current Pap result of cervical dysplasia (OR = 8.9; 95% confidence interval: 2.1, 38.8), oral contraceptive use (OR = 0.1; 0.03, 0.6), and education (OR = 1.4; 1.1, 1.8) were significant predictors of HPV status.

Adolescent↗
PubMed1990

Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules.

The P97 promoter upstream of the oncogenic early genes of human papillomavirus (HPV)-16 is active in keratinocytes and in cervical carcinoma cells due to a 5' keratinocyte-dependent cis enhancer. In this study, we have mapped the main enhancer activity to an 88-nucleotide (nt) fragment composed of multiple cis elements. A 63-nt promoter-proximal enhancer core was sufficient for P97 activation in a human keratinocytic cell line, HaCaT, and in cervical carcinoma cells. Although the enhancer functioned poorly in hepatoma cells or in fibroblasts, nuclear extracts from different cells protected similar cis elements from DNase I digestion. Two protected half-palindromic NF-I/CTF sites within the 63-nt core were necessary for its function; one represents a "cytokeratin element" (CK), a previously described 8-nt sequence shared with cytokeratin gene promoters. Both sites formed complexes of the same apparent size and relative binding affinity with NF-I/CTF-like factor(s) present in all cells tested. Although cell-dependent P97 activation could be determined by similar, yet distinct NF-I/CTF-like proteins, adjacent cis elements in the enhancer core were also required for function, and may thus interact with additional transcription factors. A 25-nt distal module with two AP-1 sites increased enhancer activity and cooperated with cis elements of the proximal core. Each AP-1 site as well as a third AP-1 site near the promoter bound c-Jun and Jun/Fos in vitro, and was activated by c-Jun and c-Fos in transfections. In addition to cell type-dependent activation, HPV-16 P97 transcription may therefore respond to growth factors and oncogene products via the AP-1 pathway.

Base Sequence↗
PubMed1988

Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain.

The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also activate a wide range of co-transfected promoters without E2P cores to a lower extent. Analysis of multiple E2 mutants in transfected cells revealed that the C-terminal DNA binding E2 domain binds to the E2P cis sequences in the form of pre-existing nuclear dimers. The DNA binding function of E2 was required for specific trans-activation of the E2P elements, as well as for the function of the previously described C-terminal 'short E2' transrepressor. In addition to the C terminus, specific trans-activation also required an intact N-terminal half of the E2 protein. When expressed alone, the N-terminal E2 domain was found to activate heterologous promoters without E2P elements to an extent comparable to wild-type E2, and therefore represents the functional transcription activation domain of the E2 factor. In contrast to other DNA-binding activator proteins described to date, the transcriptional activation by the E2 factor can occur without specific DNA binding. Its mechanism may thus involve protein--protein interactions between common transcription factors and the N-terminal E2 domain which contains amphipathic helix motifs.

Animals↗
PubMed1987

Scalp expansion in the treatment of male pattern baldness.

Tissue expansion has been extremely valuable in the treatment of traumatic scalp defects. We have recently used expansion techniques in the treatment of male pattern baldness. Expansion has been used in conjunction with scalp-reduction procedures and pedicled hair-bearing flaps. Flaps have been designed as Juri flaps, and in one patient, a new posteriorly based flap was used. This design gives the advantage of a more natural-appearing hairline and forward-growing hair. The major advantage of tissue expansion in the treatment of male pattern baldness is that it generates new hair-bearing scalp. The increase in vascularity which occurs during expansion allows for large, safe, and predictable flaps. Donor sites are also relatively easily closed. The disadvantages of expansion include the need for two or more surgical procedures and multiple office visits. There is also some discomfort following expansion and a cosmetic defect as the expanders become larger. Complications include infection, exposure or extrusion, deflation, and hair loss. Tissue expansion combined with scalp reduction and pedicled hair-bearing flaps have proved to be a valuable technique in the treatment of male pattern baldness with a high degree of patient satisfaction.

Adult↗
PubMed1987

Expansion-assisted treatment of male pattern baldness.

Scalp expansion has been combined with scalp reduction and flap procedures for the treatment of male pattern baldness. Expansion offers the advantages of a safe and reliable procedure, as well as more coverage in a shorter period of time. The techniques described involve bilateral temporal parietal occipital (TPO) expanders followed by either a frontal TPO flap and contralateral scalp reduction or bilateral TPO flaps. Both procedures leave areas of baldness in patients with more extensive losses (Juri classes II and II). Further expansion may be used for further coverage of residual bald areas.

Adult↗