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Biomedical subjects

A King

Publications and source records attributed to A King.

At least 307 records · Page 17Linked to original sources
PubMed1992

Uptake of exogenous human papilloma virus L1 DNA by oocytes and detection by the polymerase chain reaction.

OBJECTIVE: The purpose of this study was to determine if oocytes were capable of taking up exogenous DNA such as human papillomaviral (HPV) DNA and evaluate the zona pellucida as a barrier to the entry of foreign DNA into the oocyte. METHODS: The experiment consisted of four groups of hamster oocytes exposed to HPV DNA fragments: Group A, zona-free oocytes (n = 5); Group B, oocytes with an intact zona pellucida (n = 5); Group C, oocytes fixed in 4% buffered formalin solution for 20 min (n = 5); and Group D, zona-free oocytes (n = 4). Group C oocytes served as an internal control to ensure adequate washing of the oocytes after incubation. RESULTS: The zona pellucida was not a barrier to foreign DNA molecules. The PCR did not detect L1-HPV and beta-globin gene sequences in the untreated hamster oocyte. Uptake of the smaller DNA fragments such as that amplified from the beta-globin region was independent of active oocyte cell processes. CONCLUSION: Oocytes cultured in vitro can passively take up exogenous DNA fragments. The results suggest a possible role of oocytes as vectors for foreign DNA.

Animals↗
PubMed1992

Antibiotic sensitivity of the Bacteroides fragilis group in Europe. European Study Group.

Rates of resistance to 12 antibiotics were determined for 1,289 isolates of Bacteroides fragilis group submitted in 1988-1989 by 22 laboratories in 15 European countries. There was no resistance to metronidazole (breakpoint 8 mg/l) and only one isolate was resistant to chloramphenicol (breakpoint 8 mg/l). Resistance was uncommon for imipenem (0.3% at greater than 4 mg/l), amoxicillin/clavulanate (1% at greater than 8 mg/l), cefoxitin (3% at greater than 32 mg/l), mezlocillin (6% at greater than 64 mg/l) and clindamycin (9% at greater than 4 mg/l). Resistance was the rule for ampicillin (93% at greater than 4 mg/l), ciprofloxacin (56% at greater than 4 mg/l) and tetracycline (64% at greater than 4 mg/l). Bacteroides fragilis, the commonest species, was generally the most sensitive: resistance of this organism was uncommon for cefotetan (4% at greater than 32 mg/l) and ceftazidime (12% at greater than 32 mg/l) to which the other species were more often resistant. There were small but significant differences between laboratories and countries for many of the antibiotics. Regionally the most striking differences were for clindamycin where resistance in Bacteroides fragilis was most common in the South and for tetracycline where resistance in Bacteroides fragilis, Bacteroides thetaiotaomicron and Bacteroides uniformis was least common in the North.

Anti-Bacterial Agents↗
PubMed1992

The response of human decidual leukocytes to IL-2.

The phenotype of human decidual leukocytes, composed predominantly of CD3-CD16(-)-CD56bright cells, was examined after culture with IL-2 by immunofluorescence and flow cytometry. After IL-2 stimulation the phenotype became like that found on classical NK cells, with an increased proportion of cells expressing CD16. The IL-2R alpha was absent before and after IL-2 stimulation. However, the intermediate affinity receptor, IL-2R beta, was expressed by CD56bright decidual cells, but this receptor was downregulated after IL-2 stimulation. IL-2-induced proliferation of CD56+ decidual cells could be blocked using TU27, a monoclonal antibody to the IL-2R beta. These findings indicate activation of decidual leukocytes by IL-2 occurs through the IL-2R beta alone.

Antigens, CD↗
PubMed1992

Evidence for the expression of granulocyte-macrophage colony-stimulating factor receptors by human first trimester extravillous trophoblast and its response to this cytokine.

The present study has demonstrated that human extravillous trophoblast cells isolated from first trimester placentae can bind granulocyte-macrophage colony-stimulating factor (GM-CSF). We have used a technique which incorporates a phycoerythrin (PE)-conjugated GM-CSF in association with a monoclonal antibody against trophoblast (BC-1) in single and double flow cytometric analysis. Trophoblast cells are also observed to show increased DNA synthesis in response to GM-CSF as assayed by [3H]thymidine incorporation and proliferative activity as demonstrated by double immunocytochemical staining of cells with a trophoblast cytokeratin marker (PKK1) and for the nuclear proliferation antigen (Ki-67). These findings provide evidence that human extravillous trophoblast expresses receptors for GM-CSF and responds to this cytokine.

Antibodies, Monoclonal↗
PubMed1992

Prevalence of resistance to beta-lactam antibiotics in Escherichia coli isolated from blood from 1969-1991.

MICs of beta-lactam antibiotics were determined for blood culture isolates of Escherichia coli from patients in St. Thomas' Hospital, London between 1969 and 1991. There was correlation between MICs of carbenicillin and those of amoxycillin (Kendall's coefficient of rank correlation, tau = 0.67), mezlocillin (tau = 0.73), cephaloridine (tau = 0.64) and amoxycillin/clavulanic acid (tau = 0.72), but less correlation between MICs of carbenicillin and cefuroxime (tau = 0.31). During the two decades, the geometric mean MICs increased for carbenicillin (6.6-fold increase in mean MIC), mezlocillin (3.4-fold increase in mean MIC), cephaloridine (two-fold increase in mean MIC) and, to a smaller extent, amoxycillin/clavulanic acid (1.2-fold increase in mean MIC), but not for cefuroxime. These changes were the result of increases in the proportion of isolates that were resistant to carbenicillin and not of changes in the phenotype of carbenicillin-resistant isolates.

Amoxicillin↗
PubMed1992

Macrolactams: a novel class of antifungal antibiotics produced by Actinomadura spp. SCC 1776 and SCC 1777.

Three novel antifungal antibiotics, Sch 38518, Sch 39185 and Sch 38516 were isolated from the fermentation broths of two actinomycetes identified by chemical, morphological and physiological analysis as a new species of Actinomadura. The compounds were isolated from broth by solvent extraction and purified by silica gel chromatography. Physico-chemical properties, mass spectral analysis, IR and UV suggested the compounds were similar. Sch 38518 and Sch 39185 have a molecular formula of C25H48N2O5. 1H NMR, 13C NMR and hydrolysis indicated the aglycones were identical, however the compounds differed in containing isomeric sugar moieties. Sch 38518 contains mycosamine while Sch 39185 contains 3,6-dideoxy-3-amino-L-talopyranose. Sch 38516 has a molecular formula of C24H46N2O5 and is a lower homolog of Sch 39185. The three compounds, Sch 38518 (1), Sch 39185 (2), and Sch 38516 (3) exhibit similar activity against Candida spp. with geometric mean MICs of 1.81, 2.00 and 0.91 micrograms/ml, respectively.

Actinomycetales↗
PubMed1992

Discordant segregation of Na+,K(+)-adenosine triphosphatase alleles and essential hypertension.

OBJECTIVES: To determine whether the alpha 2 and or beta 1 isoforms of the Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) are involved in the pathogenesis of essential hypertension. DESIGN: Segregation analysis of polymorphic DNA markers was used to test the involvement of Na+,K(+)-ATPase in essential hypertension. PARTICIPANTS: Children with persistent hypertension having one parent with essential hypertension were included in the study. Criteria for persistent hypertension were blood pressure readings with systolic and/or diastolic levels exceeding the 95th percentile based upon age and sex. The diagnosis of hypertension for adults, including parents and older siblings, was confirmed using criteria recommended in the 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. RESULTS: In three essential hypertensive families consisting of 18 members including 11 hypertensives, several obligate recombinants between the Na+,K(+)-ATPase alpha 2 isoform marker and the hypertension phenotype were observed. Similarly, in one hypertension family consisting of four members, obligate recombinants between the beta 1 isoform marker and the disease were observed. CONCLUSIONS: The discordant segregation of the alpha 2 and beta 1 isoform markers and essential hypertension suggests that neither the Na+,K(+)-ATPase alpha 2 nor beta 1 isoform genes play a primary role in the pathogenesis of hypertension in the families studied.

Adult↗
PubMed1992

Benefits and weaknesses of a cardiac rehabilitation programme.

The British Heart Foundation and the Chest, Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes. We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infarction. Patients admitted to the Plymouth cardiac care unit were randomised into groups: a control group to receive standard hospital care, and a rehabilitation group who, in addition, received an exercise programme reinforced with advice. Patients were assessed at entry to the study and at intervals thereafter. Assessment was by questionnaire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry. In the rehabilitation group patients were able to walk further and faster, return to work earlier, undertake more housework, and resume normal sexual activity; they were less short of breath and did not experience more angina. However, the rehabilitation course brought little benefit to the patients' perception of well-being and their anxiety about health or their outlook on life. Exercise and advice are important components of a rehabilitation programme, but more attention needs to be given to the psychological aspects of recovery from a heart attack.

Adult↗
PubMed1991

The mouse androgen receptor. Functional analysis of the protein and characterization of the gene.

Screening a mouse genomic DNA library with human androgen-receptor (hAR) cDNA probes resulted in the isolation and characterization of eight genomic fragments that contain the eight exons of the mouse androgen-receptor (mAR) gene. On the basis of similarity to the hAR gene, the nucleotide sequences of the protein-coding parts of the exons as well as the sequences of the intron/exon boundaries were determined. An open reading frame (ORF) of 2697 nucleotides, which can encode an 899-amino-acid protein, could be predicted. The structure of the mAR ORF was confirmed by sequence analysis of mAR cDNA fragments, which were obtained by PCR amplification of mouse testis cDNA, using mAR specific primers. A eukaryotic mAR expression vector was constructed and mAR was transiently expressed in COS-1 cells. The expressed protein was shown by Western blotting to be identical in size with the native mAR. Co-transfection of HeLa cells with the mAR expression plasmid and an androgen-responsive chloramphenicol acetyltransferase (CAT) reporter-gene construct showed mAR to be able to trans-activate the androgen-responsive promoter in a ligand-dependent manner. Transcription-initiation sites of the mAR gene were identified by S1-nuclease protection experiments, and the functional activity of the promoter region was determined by transient expression of mAR promoter-CAT-reporter-gene constructs in HeLa cells. Structural analysis revealed the promoter of the mAR gene to be devoid of TATA/CCAAT elements. In addition, the promoter region is not remarkably (G + C)-rich. Potential promoter elements consist of a consensus Sp1 binding sequence and a homopurine stretch. The polyadenylation sites of mAR mRNA were identified by sequence similarity to the corresponding sites in the hAR mRNA.

Amino Acid Sequence↗
PubMed1991

Protective antibodies to hepatitis B virus in haemophiliacs.

Haemophilic patients are at increased risk from hepatitis B virus infection because of their need for blood product therapy. They are potentially poor responders to hepatitis B vaccine due to immunological abnormalities resulting from two causes: infection with the human immunodeficiency virus and treatment with clotting factor concentrates. The protective antibody response to hepatitis B virus in vaccinated haemophiliacs was investigated using a competitive enzyme-linked immunosorbent assay which employs a monoclonal antibody, RF-HBs-1, that recognises a virus-neutralising epitope on HBsAg. Serum samples from 55 haemophilic patients were studied at 7, 12, and 24 months after the first injection with HB vaccine. Twenty-four vaccinated normal subjects were used as controls. The level of neutralising antibody was found to correlate with the polyclonal anti-HBs response in the majority of subjects in both the control and patient groups. There was a small but statistically significant reduction in both antibody responses in the patients compared with the normal controls. Treatment with FVIII or FIX concentrate did not influence the antibody response in the patients. Eleven of the haemophilic patients were anti-HIV seropositive. This group had a significantly lower antibody response than anti-HIV negative patients, and this correlated with the duration of anti-HIV seropositivity, rather than with their T4 counts. We conclude that, following vaccination, the majority of haemophiliacs are able to mount a protective antibody response to hepatitis B virus. HIV infection was found to be the sole cause of immunological suppression of this response.

Adolescent↗
PubMed1991

Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.

Adult↗
PubMed1991

In vitro activity of cefpodoxime, a new oral cephalosporin, compared with that of nine other antimicrobial agents.

The in vitro activity of the compound RU-51746, the sodium salt of cefpodoxime (which is administered orally as the ester cefpodoxime proxetil) was compared with that of other commonly used oral antibiotics against a selection of clinical isolates of common bacteria from patients with urinary tract, soft tissue and respiratory tract infections. RU-51746 was found to inhibit 90% of Enterobacteriaceae at less than 1 mg/l; pneumococci, pyogenic streptococci (Lancefield groups A, C and G) and Streptococcus agalactiae were almost all inhibited by concentrations of less than 0.06 mg/l; Haemophilus influenzae (including beta-lactamase producers) were inhibited by less than 1 mg/l; 90% of Branhamella catarrhalis were inhibited at less than 2 mg/l. Activity against Acinetobacter spp. and staphylococci was variable and enterococci were all resistant.

Acinetobacter↗
PubMed1991

Endometrioid carcinoma of the oviduct.

Endometrioid carcinoma is a malignant tumor which microscopically resembles endometrial adenocarcinoma, but arises from extrauterine sites, most commonly the ovary. Although its association with endometriosis has received considerable discussion, it appears that most of the malignant endometrioid tumors arise de novo. We present a case of endometrioid carcinoma which is outstanding for its primary site in the oviduct and for its histologic appearance, which incorporated a close interplay between both stromal and epithelial elements. The neoplasm was found incidentally, when the woman presented with postmenopausal bleeding due to adenomatous hyperplasia of the endometrium. The patient presented with a stage I, grade I tumor which did not invade the wall of the oviduct. Twelve years following a TAH-BSO and postoperative radiation, the tumor recurred, requiring additional surgery and chemotherapy. The patient is currently disease free, 2 years from her recurrence.

Adenocarcinoma↗
PubMed1991

On the nature and function of human uterine granular lymphocytes.

The 'foetal allograft' concept of the maternal-foetal relationship is currently being questioned. This is partly due to the increasing awareness of uterine large granular lymphocytes, a subset of natural killer cells found in the human endometrium at the time of placentation. Analogous cells are present in several species. The possible role of these cells in the regulation of the trophoblast-maternal interface is discussed here by Ashley King and Yung Wai Loke.

Animals↗
PubMed1991

A comparison of the in-vitro activity of clarithromycin, a new macrolide antibiotic, with erythromycin and other oral agents.

On the basis of minimum inhibitory concentrations clarithromycin (6-O-methylerythromycin), a new macrolide, was found to be slightly more active than erythromycin against Staphylococcus aureus, enterococci. Moraxella catarrhalis, Gardnerella vaginalis, Bacteroides fragilis (sensu stricto) and B. ureolyticus and slightly less active against coagulase-negative staphylococci, alpha- and beta-haemolytic streptococci, Haemophilus influenzae, Campylobacter coli/jejuni and the B. melaninogenicus/oralis groups. There was complete cross-resistance between the two agents. Reports of potentiation of the activity against Haemophilus influenzae of clarithromycin by its own metabolite and by human serum appear to operate in vivo, and therefore the new agent shows great promise, especially for the treatment of respiratory tract infections.

Administration, Oral↗
PubMed1991

A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy.

We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed cases of CO poisoning occurring during pregnancy between December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), car fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomographic findings consistent with ischemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehavioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P less than 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcome.

Abnormalities, Drug-Induced↗