Search PubMed⌕ Search

Biomedical subjects

K A Ryan

Publications and source records attributed to K A Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1998

The Open Artery Hypothesis: Past, Present, and Future.

The survival benefit following a reperfusion strategy, be it pharmacologic or mechanical, appears to be due to both full and early reperfusion. While the TIMI Flow Grade classification scheme has been a useful tool to assess coronary blood flow in acute syndromes, it has several limitations. A newer method of assessing coronary blood flow called the Corrected TIMI Frame Count method has the following advantages: (1) it is a continuous quantitative variable rather than a categorical qualitative variable; (2) the flow in the non-culprit artery is not assumed to be normal as it is in the assessment of TIMI Grade 3 Flow; (3) there is simplified reporting of reperfusion efficacy through the use of a single number instead of expressing the data in 2 to 4 categories; (4) because a single number rather than 4 categories is used to report the data, there is more efficient use of the dataset by increasing the statistical power; and finally (5) coronary flow can be expressed in intuitive terms (e.g. time or cm/sec for strategy A versus time or cm/sec for strategy B). This paper reviews the history of the open artery hypothesis and recent advances in the field.

Journal Article↗
PubMed1998

A randomized controlled trial comparing nonoxynol-9 lubricated condoms with silicone lubricated condoms for prophylaxis.

OBJECTIVE: We tested the effect of nonoxynol-9 (N-9) in condom lubrication on the risk of acquiring STD and genital discomfort. METHODS: The study was a triple masked, randomised controlled trial comparing N-9 lubricated condoms with plain silicone lubricated condoms among Dominican female sex workers. RESULTS: Randomisation provided two groups (313 for N-9 and 322 for plain) similar in baseline characteristics, but extensive loss to follow up occurred (56 women in each group completed the 24 week follow up). Most vaginal acts with clients were protected with condoms (99% of vaginal sex) but fewer acts with non-clients were protected (43% of vaginal sex). No significant differences occurred in rates of cervical infections (N-9 = 3.4 per 100 person months v plain = 2.8), trichomoniasis (N-9 = 2.8 v plain = 3.6), or discomfort rates (N-9 = 0.82 v plain = 0.92). CONCLUSIONS: Plain silicone lubricated condoms are as effective as N-9 lubricated condoms, cost less, have longer expected shelf life, and therefore may be the better condom to provide.

Adolescent↗
PubMed1998

Characteristics associated with prevalent HIV infection among a cohort of sex workers in Cameroon.

OBJECTIVE: To determine prevalence of HIV infection in a cohort of female sex workers in Cameroon, and to describe characteristics associated with HIV infection in this population. METHODS: In a cross sectional study, 2260 female sex workers in Cameroon were interviewed and screened for HIV serostatus. A standardised questionnaire was used to collect information on sociodemographic characteristics and sexual and health behaviours. RESULTS: Seropositive participants (18%) were more likely to be over age 25, have four or more children, live in Yaoundé or Douala for 5 years or less, solicit clients in their homes or on the street, have a low educational level, earn a weekly income of less than $24, and have no other occupation outside of sex work. A logistic regression model of selected sociodemographic characteristics indicated that women at particularly high odds of HIV infection were older, poorer, and new immigrants to their city of residence. CONCLUSION: This seroprevalence study found a lower HIV prevalence than had been previously reported. Although our results are different, this group is still at much higher risk of HIV infection than the population as a whole.

Adolescent↗
PubMed1998

Prevalence and prediction of sexually transmitted diseases among sex workers in Cameroon.

The aim of the study was to determine the prevalence of sexually transmitted diseases (STDs), describe the frequency of genitourinary symptoms and signs, and to assess the accuracy of clinical diagnoses of STD in a cohort of Cameroonian sex workers. Physical examinations were conducted on 1233 sex workers in Yaoundé and Douala, Cameroon. Symptoms experienced within the 14 days prior to examination were collected. Women were tested for gonorrhoea, chlamydia infection, and trichomoniasis. Doctors' clinical impressions were compared with laboratory tests. Prevalence of cervical infection and trichomoniasis was 20%. A high percentage of abnormal signs and symptoms was found in this cohort. Clinical diagnosis for cervicitis and trichomoniasis had low sensitivities (<50%) while specificity remained high (>65%). In conclusion STDs are common among sex workers in Cameroon. Clinical diagnosis was not an accurate predictor of infection at the individual level in this population at risk of STD.

Adolescent↗
PubMed1998

Measuring condom use: asking "do you or don't you" isn't enough.

This article compares cross-sectional measures of condom use among 2,269 female sex workers in Cameroon randomly assigned to receive one of five different questionnaires measuring condom use. We found that the level of reported condom use varied depending on the type of survey questions used. Measures based on 2-week coital logs or the past 10 acts categorized more women as "100%" or "0%" users than always-to-never scales categorized women as "always" or "never" users. Consistency of use also varied by type of partner. Internal consistency of responses was high. Future studies should assess differences in prospective measures of condom use and the level of association between various measures and infection with sexually transmitted disease.

Adolescent↗
PubMed1997

Antiviral properties of 3-quinolinecarboxamides: a series of novel non-nucleoside antiherpetic agents.

Novel antiherpetic 3-quinolinecarboxamides were discovered as part of a drug discovery program at Sterling Winthrop Inc. A major goal of this research was to identify novel non-nucleoside agents possessing activity against acyclovir resistant herpes simplex virus. From screening compound libraries in an HSV-2 plaque reduction assay, 1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarboxamide (1) emerged as an attractive lead structure. By modifying the quinoline ring at the 1-, 2-, 3-, 4-, and 7-positions, analogues were identified that have up to 5-fold increased in vitro potency relative to acyclovir. In a single dose mouse model of infection the 1-(4-FC6H4) analogue 17, one of the most potent derivatives in vitro, displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple dose regimen, however, it was 2-fold less potent. Mechanism of action studies indicate that these new compounds interact with a different, as yet undefined, molecular target than acyclovir.

Acyclovir↗
PubMed1995

Keto/enol epoxy steroids as HIV-1 Tat inhibitors: structure-activity relationships and pharmacophore localization.

Inhibition of the HIV-1 nuclear regulatory protein tat could potentially yield particularly useful drugs because it functions as an activator of transcription. It has no known cellular counterpart, and deletions in the tat gene destroy the ability of HIV-1 to replicate. We recently reported that a structurally unique class of tat inhibitors, 3-keto/enol 4,5-alpha-epoxy steroids bearing electron-withdrawing substituents at position 2, specifically inhibit tat-induced gene expression in virus free transfected SW480 cells. In this paper, we report on additional SAR (structure-activity relationships) for the steroid series and the localization of the pharmacophore to the A-ring functionality. There is a weak enantioselective preference for the natural steroid stereochemistry and hints of additional SAR in the electron-withdrawing group. Compound 34a is of particular interest in that it inhibits HIV replication in H9 cells at a concentration equivalent to its inhibitory level in the primary tat assay.

Cell Line↗
PubMed1995

Cyclic variations of 3-quinolinecarboxamides and effects on antiherpetic activity.

Supported by the antiherpetic properties of 3-quinolinecarboxamides and the importance of the planar intramolecular H-bonded beta-keto amide pharmacophore, a series of novel conformationally rigid analogues that contain a heterocyclic bridge between the 3- and 4-positions of the quinoline ring have been evaluated. Two isoxazolo-fused derivatives 17 and 23 displayed good in vitro antiherpetic potency that was similar to that of 1, the 3-quinolinecarboxamide that served as the comparison structure for this study. The pyrazolo, pyrrolo, and pyrimido derivatives showed considerably less or no activity. In vitro activity did not translate to in vivo efficacy. For 17, the lack of in vivo activity is likely a consequence of insufficient plasma drug levels (both Cmax and duration) in mice relative to the MIC versus HSV-2.

Animals↗
PubMed1994

Studies of the conformation-dependent neutralizing epitopes of simian immunodeficiency virus envelope protein.

It has been shown previously that the major neutralizing epitopes in simian immunodeficiency virus (SIV) are discontinuous and conformation dependent and that the V3 loop, in contrast to that of human immunodeficiency virus (HIV) type 1, does not by itself elicit neutralizing antibodies (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 89:1418-1422, 1992). We now present data showing that on the basis of fractionation of infected macaque sera, protease digestion of the envelope, and binding properties of two neutralizing monoclonal antibodies to SIV and SIV-HIV chimeric envelope proteins, changes in V3 can disrupt the conformation-dependent neutralization region. The chimeric protein did not produce significant neutralizing antibodies against either SIV or HIV. We also report that neutralizing antibodies elicited by recombinant SIV envelope proteins of mac251 and B670 isolates cross-neutralize. Finally, we show that deglycosylation of the SIV envelope results in a molecule which binds neither soluble CD4 nor the neutralizing monoclonal antibodies being investigated here and does not elicit sera with a significant neutralizing titer.

Acids↗
PubMed1993

Selective inactivation of eukaryotic beta-galactosidase in assays for inhibitors of HIV-1 TAT using bacterial beta-galactosidase as a reporter enzyme.

Bacterial beta-galactosidase is one of several reporter enzymes used in studying the transcriptional activity of eukaryotic promoters. Although it is one of the easiest and least expensive enzymes to assay, its use has been limited because of its low sensitivity, which is due in part to endogenous levels of beta-galactosidase in many eukaryotic cells. In this study, we compared the pH and salt requirements, as well as the heat stability, of bacterial and eukaryotic beta-galactosidase in order to identify conditions which would inhibit the beta-galactosidase enzyme endogenous to eukaryotic cells without adversely affecting the activity of either purified bacterial beta-galactosidase or reporter beta-galactosidase produced after transfection of expression vectors into eukaryotic cells. Heat treatment at 50 degrees C for 1 h inactivated the beta-galactosidase activity endogenous to several eukaryotic cell lines by as much as 40-fold without adversely affecting the activity of bacterial beta-galactosidase. This treatment increased the sensitivity of this reporter enzyme and allowed the development of a rapid and quantifiable screening assay for HIV-1 tat inhibitors.

Animals↗
PubMed1993

Isolation of virulence genes directing surface glycosyl-phosphatidylinositol synthesis by functional complementation of Leishmania.

Trypanosomatid parasites of the genus Leishmania cause a spectrum of widespread tropical diseases. In the vertebrate host they reside within the macrophage phagolysosome; however, the mechanisms employed in this remarkable survival strategy are not well understood. Recent advances in the molecular genetics of these parasites prompted us to develop methods of functional genetic complementation in Leishmania and apply them to the isolation of genes involved in the biosynthesis of the virulence determinant lipophosphoglycan, an abundant glycosyl-phosphatidylinositol-anchored polysaccharide. LPG1, the gene product identified by complementation of the R2D2 mutant, appears to be a glycosyltransferase responsible for the addition of galactofuranosyl residues to the nascent lipophosphoglycan chain. As galactofuranose is not found in mammalian cells, inhibition of the addition of this sugar could be exploited for chemotherapy. Overall, the success of the functional complementation approach opens the way to the identification of a variety of genes involved in pathogenesis and parasitism.

Agglutination↗
PubMed1993

Shuttle cosmid vectors for the trypanosomatid parasite Leishmania.

We have developed two shuttle cosmid vectors for the trypanosomatid protozoan parasite Leishmania. Cosmids cLHYG and cLNEO contain hyg and neo markers, conferring resistance to hygromycin B and G418, respectively, replicate extrachromosomally after transfection into promastigotes, and bear a unique BamHI cloning site. To ensure the representation of telomeric sequences, which represent about 5% of the Leishmania genome, random insert DNAs were prepared by shearing followed by blunt-end ligation with BamHI adapters. Representative genomic libraries from Leishmania species representing the four major pathogenic complexes were prepared using cosmid cLHYG. The cosmid libraries were efficiently transfected into Leishmania, and individual cosmids were readily recovered by transformation back into Escherichia coli. The relatively small size of the Leishmania genome (50 Mb) combined with the capacity and transfection efficiency of these cosmid libraries (> 1000 Leishmania transfectants/plate) suggests the feasibility of functional genetic complementation in this parasite.

Animals↗
PubMed1993

Mothers of adult children with schizophrenia: an ethnographic study.

Most recent investigations of families of individuals with schizophrenia have been concerned with the negative impact of the family on the outcome for the ill relative. Although several investigators have documented the consequences of living with a mentally ill relative to family members, there is still a lack of research exploring the broader experience of family members including how they perceive and define the illness experience, and how they actively manage the situation. While mothers have been frequently identified as primary caregivers of mentally ill children, few investigators have explored the mother's perspective. A qualitative descriptive study was conducted to gain an understanding of the experience of mothers living with schizophrenic adult children. Ethnographic interviews conducted with five mothers were transcribed and subjected to qualitative analysis. The overall theme that emerged was a lifetime of mothering consisting of two major components, disruption and loss. Disruption was experienced in the mother's relations with the ill child, and in her own life. A lifetime of mothering involved two dimensions of loss: loss of the child's potential to lead a 'normal' life, and loss of freedom in the mother's own life. Central to mothers' descriptions was how they actively managed disruption and loss on a day-to-day basis.

Activities of Daily Living↗
PubMed1989

Expression of the four subunits of the Torpedo californica nicotinic acetylcholine receptor in Saccharomyces cerevisiae.

Yeast expression vectors were constructed containing complementary DNA encoding the alpha-, beta-, gamma-, and delta-subunits of the Torpedo californica nicotinic acetylcholine receptor under the control of the Saccharomyces cerevisiae alcohol dehydrogenase promoter. All four plasmids were integrated into the yeast genome of a single yeast cell. The resulting yeast strain synthesized polypeptides novel to yeast that had the molecular weights and antigenic properties similar to the authentic T. californica receptor alpha-, gamma, and delta-subunits. The beta-subunit polypeptide could not be detected in this yeast strain, even though the poly(A)+ RNA from this strain contained all the information necessary for the expression of functional acetylcholine receptors in Xenopus laevis oocytes. The replacement of the beta-subunit mRNA 5'-untranslated leader and its N-terminal signal sequence by the corresponding alpha-subunit sequences, however, resulted in the expression of the beta-subunit polypeptide in yeast grown at 5 degrees C.

Animals↗
PubMed1989

Replication of kinetoplast DNA in Trypanosoma equiperdum. Minicircle H strand fragments which map at specific locations.

The mitochondrial DNA of trypanosomes, kinetoplast DNA, is a network containing thousands of topologically interlocked minicircles. Minicircles are replicated as free molecules after being detached from the network. The minicircle L strand appears to be synthesized continuously and the H strand discontinuously. This paper describes properties of Trypanosoma equiperdum minicircle H strand fragments which could be Okazaki fragments. These fragments constitute a family of molecules of discrete sizes (ranging from about 70 to 1000 nucleotides) which map to specific locations. Three of the most prominent fragments, a 73-mer, 83-mer, and 138-mer, map at contiguous or overlapping sites. Based on their position relative to the initiation site for L strand synthesis, the 73-mer may be the first Okazaki fragment to be synthesized and either the 83-mer or the 138-mer may be the second. The 5' end of the 73-mer lies within a sequence, GGGCGT, found at a similar location in minicircles of all trypanosomatid species. During the maturation of free minicircles and after their reattachment to the networks there appears to be continued extension and ligation of the H strand fragments. However, the ligation of the 73-mer, 83-mer, and 138-mer to the rest of the H strand is delayed; their eventual ligation results in covalent closure of the minicircles.

Animals↗
PubMed1989

Synthesis and processing of kinetoplast DNA minicircles in Trypanosoma equiperdum.

Kinetoplast DNA, the mitochondrial DNA in trypanosomes, is a giant network containing topologically interlocked minicircles. Replication occurs on free minicircles that have been detached from the network. In this paper, we report studies on the synthesis and processing of the minicircle L and H strands. Analysis of free minicircles from Trypanosoma equiperdum by two-dimensional agarose gel electrophoresis indicated that elongating L strands are present on theta structures. Hybridization studies indicated that L-strand elongation is continuous and unidirectional, starting near nucleotide 805 and proceeding around the entire minicircle. The theta structures segregate into monomeric progeny minicircles, and those with a newly synthesized L strand have a 8-nucleotide gap between nucleotides 805 and 814 (J. M. Ntambi, T. A. Shapiro, K. A. Ryan, and P. T. Englund, J. Biol. Chem. 261:11890-11895, 1986). These molecules are reattached to the network, where repair of the gap takes place. Of the molecules labeled during a 10-min pulse with [3H]thymidine, gap filling occurred on half within about 15 min and on virtually all by 60 min; however, there was no detectable covalent closure of the newly synthesized L strand by 60 min.

Animals↗