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Biomedical subjects

D Wells

Publications and source records attributed to D Wells.

At least 109 records · Page 6Linked to original sources
PubMed1988

Tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts.

PURPOSE: The intralesional administration of recombinant interferon alpha has led to resolution of genital warts in 50 to 70 percent of cases. However, continuous warts do not respond to such treatment, and human papillomavirus (HPV) infection of other anatomic sites remains untreated, so infection may continue to be transmitted. Since interferons have shown promise as effective therapies for genital warts, we decided to investigate the tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts. PATIENTS AND METHODS: Nineteen women and nine men with refractory genital warts were treated in an open-label, dose-response trial of intramuscular recombinant human interferon gamma. RESULTS: Complete responses were seen in two (7 percent) and partial responses were seen in 13 (46 percent). Of 12 women with concomitant cervical HPV infection, eight demonstrated resolution with therapy. Response rates were higher in those patients who had warts less than nine months (73 percent) prior to therapy and in women (63 percent). Responses were not associated with HPV type. Flu-like symptoms during treatment were frequent but well tolerated. Transient abnormal laboratory results were more frequent with daily administration than with three times weekly therapy. Eleven of 16 subjects treated with cryotherapy after treatment with interferon experienced long-term remissions. CONCLUSIONS: In ambulatory patients with refractory genital warts, recombinant human interferon gamma appears to be biologically active and to have few adverse effects. The high efficacy rate achieved in subjects treated with cryotherapy after treatment with interferon suggests that further studies of combination therapy with these modalities are warranted.

Adolescent↗
PubMed1987

Identification of intrinsic termination sites in vitro for RNA polymerase II within eukaryotic gene sequences.

We have identified and mapped several DNA sequences within a human histone gene (H3.3) at which in-vitro transcription by highly purified RNA polymerase II is efficiently terminated. Since transcription in our system involves only RNA polymerase II acting on a linear DNA template, these sequences contain "intrinsic" termination signals recognized by the polymerase protein itself. The existence of such signals within a gene suggests that efficient antitermination systems probably exist for mammalian transcription units. Alternatively, there could be a high frequency of premature transcription termination, or "polarity" for genes such as H3.3. Intrinsic transcription termination sites in H3.3 are located in sequences of consecutive thymidylate residues (5 to 8 nucleotides) on the non-transcribed DNA strand (T-runs), from which it is likely that such T-runs are elements of the intrinsic termination signal for RNA polymerase II. However, transcription proceeds without significant termination through many similar T-runs, from which it follows that these intrinsic termination signals include other elements. Since transcription is also terminated efficiently at these sites when the transcript remains bound along its full length as a DNA-RNA hybrid, it is unlikely that formation of specific RNA secondary structures in the transcript is a general element of the intrinsic termination signal. Although DNA sequences downstream from the coding portion of the mouse beta-globin gene have been implicated as sites of transcription termination in vivo, these regions do not contain strong intrinsic termination signals, and transcription in vitro proceeds through these regions almost undiminished. Transcriptional termination in this region in vivo may depend on the presence of termination factors or other intracellular elements, and there may be multiple classes of DNA signals that control eukaryotic termination.

Animals↗
PubMed1987

Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the human H3.3 histone multigene family.

The genomic organization of the replication-independent, basally expressed, human H3.3 gene is atypical of traditional histone gene organization. The gene contains 3 introns totalling 7.8 kb and unusual direct repeats flank all three intron-exon splice junctions. The transcription initiation site was mapped by S1 nuclease protection analysis and confirms that cDNA clones previously reported were full length. Sequence similarities between regions at the 5' and 3' termini of this human gene and a chicken H3.3 gene lead us to propose that either the previous assignments of termini of the chicken gene are in error, or there are alternative transcription start and polyadenylation sites. The 85% base matching of human and chicken H3.3 3'UTR sequences for 520 bases is unprecedented among homolog 3'UTR segments, especially considering that these species are separated by over 250 Myr of evolution. We also present the sequence of three related processed human H3.3 pseudogenes and provide evidence demonstrating that most of the 20 to 30 copies of the H3.3 gene within the human genome are in fact processed pseudogenes.

Amino Acid Sequence↗
PubMed1986

Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships.

The nucleic acid sequences coding for 23 H3 histone genes from a variety of species have been analyzed using a computer assisted alignment and analysis program. Although these histones are highly conserved within and between highly divergent species, they represent various classes of histones whose patterns of expression are distinctively regulated. Surprisingly, in dendrograms derived from these comparisons, H3 sequences cluster according to their modes of regulation rather than phylogenetically. These clusters are generated from highly distinctive patterns of codon usage within the functional gene classes. We suggest that one factor involved in specifying the differing codon usage patterns between functional classes is a difference in requirements for rapid translation of mRNA. In addition, the data presented here, together with structural and sequence information, suggest a heterodox evolutionary model in which genes related to the intron-bearing, basally expressed H3.3 vertebrate genes are the ancestors of the intronless H3.1 class of genes of higher eukaryotes. The H3.1 class must have arisen, therefore, following duplication of a primitive H3.3 gene, but prior to the plant-animal divergence. Implications of the data presented are discussed with regard to functional and evolutionary relationships.

Amino Acid Sequence↗
PubMed1986

Oxitropium bromide, a new anticholinergic bronchodilator.

Oxitropium bromide (OB) is a quaternary ammonium congener of hyoscine with anticholinergic properties. We studied its bronchodilating properties in 14 patients with chronic obstructive lung disease without features of asthma in whom theophylline and other bronchodilators were withheld. Five doses of OB(20, 40, 100, 200, and 400 micrograms) as well as 150 micrograms of isoproterenol (ISO) and placebo were administered by metered-dose inhaler on separate occasions in a double-blind fashion. Pulmonary function (flow volume loops and airways resistance), blood pressure, and pulse rate were measured at baseline and periodically for eight hours after drug administration. Onset of bronchodilator effect was within five minutes for OB (P less than .025). Duration of action of OB was at least eight hours (P less than .025). The dose response characteristics of OB were examined by correlating the log dose with the areas under the time-FEV1 curve (r = .97, P less than .01), the time-forced vital capacity curve (r = .98, P less than .01), and the time-SGAW curve (r = .83, P less than 0.1). For FEV1, doses of 40 to 400 micrograms were significantly better than placebo and 100 to 400 micrograms were better than ISO (P less than .01). For forced vital capacity, all doses of OB were better than placebo (P less than .05). For SGAW, the response to the 100- and 400-micrograms doses were significantly better than placebo and isoproterenol (P less than .05). There were no significant effects of OB on pulse, blood pressure, or electrocardiogram. No side effects were noted from the use of OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylylated mRNAs.

We have isolated and sequenced full-length cDNA clones encoding the human basally expressed H3.3 histone from a human fibroblast cDNA library. Several features of this atypical cDNA distinguish it and its gene from the well-characterized cell-cycle regulated histone genes and their RNA transcripts. The H3.3 mRNA is approximately equal to 1200 bases long, contains unusually long 5' and 3' untranslated regions, and has a 3' polyadenylylated terminus. In addition, we have isolated and characterized a cDNA clone that is a precursor to the H3.3 mRNA and contains an intervening sequence interrupting its 5' untranslated region. Hybridization of subsegments of the cDNA to human genomic DNA reveals a complex multigene family. The differences in the structures of basal and cell-cycle histone genes suggest a model to explain the differences in their expression.

Base Sequence↗
PubMed1984

Opening address.

Explore the source record for details and available documents.

Australia↗
PubMed1983

In vitro fertilisation: the major issues.

In vitro fertilisation is now an established technique for treating some forms of infertility, yet it remains ethically controversial. New developments, such as embryo donation and embryo freezing, have led to further discussion. We briefly discuss the ethical aspects of IVF, focusing on the issues of resource allocation, the 'unnaturalness' of the procedure, the moral status of the embryo, surrogate motherhood, and restrictions on access to IVF. We argue that, on the whole, IVF is an ethically justifiable method of assisting infertile couples.

Adoption↗
PubMed1982

Characteristics of teachers of emotionally disturbed adolescents.

The National Secondary Society School Survey was conducted to obtain information regarding the "state-of-the-art" in service delivery to learning disabled and emotionally disturbed adolescents. Volunteer teachers in all fifty states completed a survey instrument regarding their own characteristics and those of their students and educational programs. The results of analyses of the responses of 320 secondary level teachers of emotionally disturbed adolescents to questionnaire items regarding their personal and educational characteristics are presented and discussed.

Adolescent↗