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Biomedical subjects

A King

Publications and source records attributed to A King.

At least 19 recordsLinked to original sources
PubMed1995

Accuracy of a saliva test for HIV antibody.

The accuracy of a saliva collection and testing protocol for determination of HIV-1 antibody status was assessed under realistic field conditions. The 1,256 study participants came from two lower-prevalence settings--a self-referral testing clinic (478) and a street-based outreach program (431)--and two high-prevalence clinics--an HIV/AIDS treatment clinic (337) and a hemophilia clinic (10). Saliva was collected using the Omni-Sal collection device and was tested by technicians blind to serum status using a modified protocol that employed the Recombigen HIV-1 EIA. Serum was tested using standard methods. A single saliva enzyme immunoassay (EIA) correctly identified 358 of 368 seropositive individuals, for a sensitivity of 97.3% (95% CI: 95.1%-98.7), and 888 of 888 seronegative individuals, for a specificity of 100% (95% CI: 99.6-100). Confirmation of saliva EIA positives with a repeat saliva EIA and an in-house saliva radioimmunoprecipitation assay resulted in a substantial drop in sensitivity to 85.3% (95% CI: 81.0-89.0). We conclude that a single saliva EIA using the modified test protocol described is sufficiently accurate for surveillance purposes, but we do not recommend it for diagnostic purposes or screening.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Concurrent radiation therapy and chemotherapy in the treatment of primary squamous cell carcinoma of the vulva.

BACKGROUND: Interest in combined modality treatment and in quality of life issues may affect the choice of radical vulvectomy as the treatment of choice in many vulvar carcinomas. To evaluate the potential role of combined radiation and chemotherapy with or without local excision as primary treatment for squamous cell carcinoma of the vulva, the outccomes of 19 patients with this disease treated with combination therapy were reviewed. METHODS: Nineteen patients were treated between September 1987 and October 1992. Fifteen patients had American Joint Committee on Cancer Stage III disease; 4 had Stage II. All had clinically negative inguinal lymph nodes with the exception of two patients who had positive ipsilateral inguinal nodes that were removed before treatment. The patients received 45-50 Gy to the pelvis and inguinal nodes with concurrent chemotherapy that consisted of 5-fluorouracil given as a 96-hour continuous infusion (1000 mg/m2/d) during weeks 1 and 5 of radiation. A single dose of mitomycin-C (10 mg/m2) during the first day of chemotherapy has been used since November 1991. Ten patients were boosted with implants or electrons and 6 others underwent local excision. RESULTS: The median follow-up was 34 months. Responses were determined clinically 1 month after completion of the radiation and chemotherapy. Clinically, complete responses were obtained in 10 patients (53%), partial responses in 7 (37%), and no response in 1; 1 patient progressed during treatment. The combined modality therapy (radiation/chemotherapy/with or without wide local excision) resulted in a local control rate of 74% (14/19). All five treatment failures occurred within 6 months of treatment. Four of these patients were rendered disease free by radical vulvectomy and/or exenteration, for an overall local control rate of 95% (18/19). CONCLUSION: Concurrent radiation therapy and chemotherapy with local excision performed as needed, appears to be a reasonable alternative to radical vulvectomy in patients with primary squamous cell carcinoma of the vulva. Radical surgery remains a viable option for patients in whom primary therapy has failed.

Adult↗
PubMed1995

The role of integrins in adhesion of decidual NK cells to extracellular matrix and decidual stromal cells.

At the time of implantation, the decidua is infiltrated by a unique population of NK cells with large granular lymphocyte morphology, which are thought to influence placental trophoblast invasion and differentiation. The mechanisms used by these cells to migrate within decidua are not known, but in other biological processes such as wound healing and tumor invasion cell-matrix interactions are important. These interactions are mediated by specific receptors, mostly belonging to the family of integrins. Decidual NK cells are observed to bind to type IV collagen and fibronectin, but not to laminin. Adhesion to collagen was inhibited with an anti-alpha 1 integrin subunit mAb, whereas adhesion to fibronectin was blocked with anti-alpha 4, -alpha 5, and -beta 1 integrin subunit mAbs. Binding of decidual NK cells to decidual stromal cells was partially blocked with mAbs to the alpha 4 and alpha 5 integrin subunits. These results provide insight into the possible mechanisms utilized by decidual NK cells for migration and retention within the pregnant uterine mucosa.

3T3 Cells↗
PubMed1995

Blastocysts exhibit preferential uptake of DNA fragments from the E6-E7 conserved region of the human papillomavirus.

The objective of the study was to determine if embryos at the blastocyst stage differentially took up exogenous human papillomavirus (HPV) DNA derived from the different HPV types and to determine whether the capture process was active or passive. In vivo fertilized mouse embryos were cultured to the blastocyst stage in vitro. The mouse blastocysts were incubated for 2 hr in the presence of a mixture of exogenous DNA fragments derived from HPV types 6b, 11, 16, and 18. The blastocysts were rigorously washed and analyzed for differential uptake of HPV gene sequences using the polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. PCR analysis detected HPV type 18 in only 40% of the blastocyst groups while detecting the other HPV types in 100% of the blastocysts. The negative control group did not show HPV DNA after PCR ruling out possible PCR artifacts. Formalin-fixed blastocysts also showed uptake of HPV DNA. In conclusion, the data suggest a role for embryos as passive vectors for foreign DNA and that the degree of DNA uptake varies with different types of HPV DNA.

Absorption↗
PubMed1995

Comparisons of risk factors for HIV-1 infection in Jefferson and Mobile County, Alabama.

A study of the Alabama state AIDS database was conducted to determine whether differences exist in demographic and risk characteristics between patients with HIV-1 in Jefferson and Mobile County. The authors found that the age distribution of patients with HIV-1, the percent of those having AIDS, and the percent of those surviving were very similar. However, significant differences existed in patient-reported risk factors in the two counties. Homosexuality was reported as the major risk factor in both counties. However, there was proportionately more homosexuality reported in Jefferson County and, conversely, more heterosexuality reported in Mobile. There also were significant differences in race and gender distributions in the two counties. This was due in part to the proportionately higher prevalence of African American females of reproductive age with HIV-1 in Mobile County. This may pose a significantly greater risk for pediatric AIDS among African American females in Mobile County.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Paroxysmal microarousals in amygdala-kindled kittens: could they be subclinical seizures?

Amygdala-kindled kittens exhibit frequent epileptiform EEG transients, often in conjunction with phasic arousal events of sleep [k-complexes, pontogeniculo-occipital (PGO) waves, and/or sleep spindles]. In this study, paroxysmal microarousals occurred throughout the sleep-wake cycle after kindling, but were most frequent during seizure-prone states of slow-wave sleep (SWS) and the transition into rapid-eye-movement sleep (REM). Their incidence correlated with interictal sleep fragmentation as well as onset of spontaneous convulsions. Results could reflect transsynaptic kindling effects on brainstem and forebrain arousal mechanisms with which amygdala is reciprocally connected. Increased discharge rates of neural generators for normal EEG and behavioral arousal could disrupt sleep at some times and recruit epileptic neurons in the kindled focus to precipitate seizures at others. Alternatively, epileptiform EEG paroxysms were accompanied by subtle behavioral stereotypes (a head nod, limb elevation, eye twitch, lip smack, or a combination of these). Behavioral correlates were elements of partial kindled seizures, suggesting that paroxysmal microarousals may be subclinical seizures. Whether or not the microarousals are true seizures, our findings may link ictal onset and interictal sleep disorders to a subclinical paroxysmal arousal disorder and suggest a common epileptic mechanism.

Amygdala↗
PubMed1995

Embryonic activation of the myoD gene is regulated by a highly conserved distal control element.

MyoD belongs to a small family of basic helix-loop-helix transcription factors implicated in skeletal muscle lineage determination and differentiation. Previously, we identified a transcriptional enhancer that regulates the embryonic expression of the human myoD gene. This enhancer had been localized to a 4 kb fragment located 18 to 22 kb upstream of the myoD transcriptional start site. We now present a molecular characterization of this enhancer. Transgenic and transfection analyses localize the myoD enhancer to a core sequence of 258 bp. In transgenic mice, this enhancer directs expression of a lacZ reporter gene to skeletal muscle compartments in a spatiotemporal pattern indistinguishable from the normal myoD expression domain, and distinct from expression patterns reported for the other myogenic factors. In contrast to the myoD promoter, the myoD enhancer shows striking conservation between humans and mice both in its sequence and its distal position. Furthermore, a myoD enhancer/heterologous promoter construct exhibits muscle-specific expression in transgenic mice, demonstrating that the myoD promoter is dispensable for myoD activation. With the exception of E-boxes, the myoD enhancer has no apparent sequence similarity with regulatory regions of other characterized muscle-specific structural or regulatory genes. Mutation of these E-boxes, however, does not affect the pattern of lacZ transgene expression, suggesting that myoD activation in the embryo is E-box-independent. DNase I protection assays reveal multiple nuclear protein binding sites in the core enhancer, although none are strictly muscle-specific. Interestingly, extracts from myoblasts and 10T1/2 fibroblasts yield identical protection profiles, indicating a similar complement of enhancer-binding factors in muscle and this non-muscle cell type. However, a clear difference exists between myoblasts and 10T1/2 cells (and other non-muscle cell types) in the chromatin structure of the chromosomal myoD core enhancer, suggesting that the myoD enhancer is repressed by epigenetic mechanisms in 10T1/2 cells. These data indicate that myoD activation is regulated at multiple levels by mechanisms that are distinct from those controlling other characterized muscle-specific genes.

Animals↗
PubMed1995

[Adhesion molecules and trophoblastic invasion].

At the time of implantation, the extracellular matrix proteins laminin and fibronectin are abundant in the decidua and are distributed pericellularly around each individual stromal cells. First trimester human trophoblast express both laminin and fibronectin receptors, specifically the alpha 1 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrin heterodimers. We have demonstrated that in vitro adhesion of first trimester human trophoblast to purified extracellular matrix proteins and to purified decidual stromal cell monolayers can be inhibited by monoclonal antibodies directed against appropriate integrin subunits and by synthetic peptides containing an RGD sequence. We have also examined the downstream events of trophoblast matrix adhesion, such as integrin mediated signal transduction and the production of metalloproteinases. The implications of these interactions are discussed.

Cell Adhesion↗
PubMed1995

Speech perception in children using the advanced Speak speech-processing strategy.

The Speak speech-processing strategy, developed by the University of Melbourne and commercialized by Cochlear Pty Limited for use in the new Spectra 22 speech processor, has been shown to provide improved speech perception for adults in both quiet and noisy situations. The present study evaluated the ability of children experienced in the use of the Multipeak (Mpeak) speech-processing strategy (implemented in the Nucleus Minisystem-22 cochlear implant) to adapt to and benefit from the advanced Speak speech-processing strategy (implemented in the Nucleus Spectra 22 speech processor). Twelve children were assessed using Mpeak and Speak over a period of 8 months. All of the children had over 1 year's previous experience with Mpeak, and all were able to score significantly on open-set word and sentence tests using the cochlear implant alone. Children were assessed with both live-voice and recorded speech materials, including Consonant-Nucleus-Consonant monosyllabic words and Speech Intelligibility Test sentences. Assessments were made in both quiet and in noise. Assessments were made at 3-week intervals to investigate the ability of the children to adapt to the new speech-processing strategy. For most of the children, a significant advantage was evident when using the Speak strategy as compared with Mpeak. For 4 of the children, there was no decrement in speech perception scores immediately following fitting with Speak. Eight of the children showed a small (10% to 20%) decrement in speech perception scores for between 3 and 6 weeks following the changeover to Speak. After 24 weeks' experience with Speak, 11 of the children had shown a steady increase in speech perception scores, with final Speak scores higher than for Mpeak. Only 1 child showed a significant decrement in speech perception with Speak, which did not recover to original Mpeak levels.

Adolescent↗
PubMed1995

Sperm as a noninvasive gene delivery system for preimplantation embryos.

OBJECTIVE: To determine if sperm could be manipulated to be a noninvasive transport carrier for the delivery of gene fragments to the blastocyst. DESIGN: Sperm cells carrying foreign DNA fragments from human papillomavirus (HPV) types 16, 18, 31, and 33 were allowed to migrate from one end of an artificial reproductive tube and to come in contact with hatching mouse blastocysts at the other end of the tube. The blastocysts were then washed and analyzed for the presence of the foreign DNA fragments. SETTING: Clinical and academic research environment. MAIN OUTCOME MEASURE: Detection of amplified products from transferred foreign DNA using the polymerase chain reaction and primers targeted at the E6-E7 region for different HPV types. RESULTS: Polymerase chain reaction analyses showed transference of DNA HPV type 18 to the blastocysts. Not all types of DNA fragments were transferred equally. CONCLUSION: The results suggested the possibility of using sperm as a noninvasive gene delivery system for passing on gene fragments to preimplantation embryos. It was demonstrated that certain DNA fragments were easier to deliver than others, indicating the necessity for exploring all the factors involved in the mechanism of the transference process. The study also serves to highlight the possibility of unintentional transmission of viral or bacterial DNA to the developing embryo via the sperm.

Animals↗
PubMed1995

Factors affecting non-attendance in an ophthalmic outpatient department.

The object of the study was to establish the non-attendance rates in an ophthalmic outpatient department and any non-attendance patterns that may be useful in managing future outpatient resources. A detailed retrospective survey of monthly non-attendance rates was carried out in the outpatient department of a dedicated eye hospital over a 1 year period looking at differences in non-attendance between morning and afternoon clinics and new and review patients. A total of 43,004 scheduled outpatient appointments predominantly from the suburban population of the Merseyside region were made at St Paul's Eye Hospital from the 1 February 1990 to 31 January 1991. Five thousand four hundred and twenty-four appointments were missed giving an overall non-attendance rate of 12.6%. Non-attendance rates for morning and afternoon appointments were 12.0% and 13.0%, respectively: and for new and review patients, 11.9% and 12.8%, respectively. Logistic regression analysis showed that patients with afternoon appointments were on average 1.10 times more likely to non-attend than morning patients (P = 0.002), and that review patients were 1.09 times more likely to non-attend than new patients (P = 0.04). In order to maximize outpatient department efficiency, a reduction in non-attendance is essential. Establishing patterns for non-attendance provides us with a framework around which we can plan measures to compensate for outpatient non-attendance.

England↗
PubMed1994

Screening for cytokine messenger ribonucleic acids in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction.

At the time of human embryo implantation, large numbers of maternal CD56brightCD16- NK cells appear in the uterus. These unusual lymphocytes are believed to control the migration and differentiation of highly invasive fetally derived trophoblast cells, which infiltrate into the maternal uterus to remodel the spiral arteries during the first trimester. One possible mechanism of control is by cytokine production. In this study, highly purified (> 99%) populations of first trimester decidual CD56brightCD16- NK cells and CD3+ T lymphocytes were obtained by using a FACS. These cells were examined by reverse transcriptase PCR for their expression of mRNAs for the following cytokines: granulocyte-macrophage (GM)-CSF, CSF-1, TNF-alpha, IFN-gamma, TGF-beta 1, leukemia-inhibitory factor (LIF), and IL-2. Then, the expression was compared with that of resting PBL. The identity of the PCR products was verified by Southern blotting and hybridization with cytokine-specific probes. Both decidual CD56brightCD16- NK cells and CD3+ T cells were found to express mRNA for CSF-1, TNF-alpha, IFN-gamma TGF-beta 1, and LIF, but GM-CSF mRNA was detected only in CD56bright NK cells. IL-2 mRNA was detected in only some decidual T cell samples, and then only after at least two rounds of amplification. In contrast, peripheral blood CD56brightCD16- NK cells, CD56dimCD16+ NK cells, and CD3+ T cells expressed mRNA only for TNF-alpha and TGF-beta 1, but not for GM-CSF, CSF-1, IFN-gamma, LIF, or IL-2. These results suggest that both decidual NK cells and decidual T cells produce a variety of cytokines that may be involved in the control of trophoblast migration and differentiation during pregnancy.

Antigens, CD↗
PubMed1994

Protein-DNA interactions and alterations in the DNA structure upon UvrB-DNA preincision complex formation during nucleotide excision repair in Escherichia coli.

The UvrB-DNA preincision complex is a key intermediate in the repair of damaged DNA by the UvrABC endonuclease from Escherichia coli. DNaseI footprinting of this complex on DNA with a cis-[Pt(NH3)2[d(GpG)-N7(1),N7(2)]] adduct provided global information on the protein binding site on this substrate [Visse, R., et al. (1991) J. Biol. Chem. 266, 7609-7617]. By applying a method developed by Fairall and Rhodes [Fairall, L., & Rhodes, D. (1992) Nucleic Acids Res. 20, 4727-4731], who have used the size and shape of DNasI for the interpretation of a footprint, we were able to define in more detail the region where UvrB-DNA interactions in the preincision complex occur. The potential interactions with phosphate groups could be reduced to less then 14 in the damaged and to 12 in the nondamaged strand. The main UvrB-DNA interactions seem restricted to the major groove on both sides of the lesion. As a consequence UvrB crosses the minor groove just downstream of the damage. Such a binding of UvrB orients the protein away from the damage. The more detailed interpretation of UvrB-DNA interactions was supported by methylation protection experiments. The structure of the DNA in the preincision complex formed on cis-[Pt(NH3)2[GpG-N7(1),N7(2)]] is altered as could be shown diethylpyrocarbonate sensitivity of adenines just downstream of the lesion. However the adenines just downstream of another cisplatin adduct, cis-[Pt(NH3)2[d(GpCpG)-N7(1),N7(3)]], did not become diethylpyrocarbonate sensitive in the preincision complex although this complex is incision proficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1994

Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines.

The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.

Binding Sites↗
PubMed1994

The structure and antigenicity of a type C foot-and-mouth disease virus.

BACKGROUND: Picornaviruses are responsible for a wide range of mammalian diseases and, in common with other RNA viruses, show considerable antigenic variation. Foot-and-mouth disease viruses (FMDVs) constitute one genus of the picornavirus family and are classified into seven serotypes, each of which shows considerable intratypic variation. This antigenic variation leads to continuing difficulties in controlling the disease. To date the structure of only one serotype, O, has been reported. RESULTS: The three-dimensional structure of a serotype C (isolate C-S8c1) FMDV, has been determined crystallographically at 3.5 A resolution. The main chain conformation of the virion is very similar to that of type O1 virus. The immunodominant G-H loop of VP1, the presumed site of cell attachment, is disordered in both types of virus indicating a functional role for flexibility of this region. There are significant changes in the structure of other antigenic loops and in some internal regions involved in protomer-protomer contacts, including the entire amino-terminal portion of VP2, described here for the first time for a picornavirus. Antigenic sites have been identified by genetic and peptide mapping methods, and located on the capsid. The data reveal a major new discontinuous antigenic site (site D) which is located near to the three-fold axis and involves residues of VP1, VP2 and VP3 which lie adjacent to each other on the capsid. CONCLUSION: In FMDV type C, amino acid substitutions seen in mutants that are resistant to neutralization by monoclonal antibodies (MAbs) map to predominantly surface-oriented residues with solvent-accessible side-chains not involved in interactions with other amino acids, whereas residues which are accessible but not substituted are found to be more frequently involved in protein-protein interactions. This provides a molecular interpretation for the repeated isolation of the same amino acid substitutions in MAb-resistant variants, an observation frequently made with RNA viruses. This first comparison of two FMDV serotypes shows how subtle changes at antigenic sites are sufficient to cause large changes in antigenic specificity between serotypes.

Amino Acid Sequence↗