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Biomedical subjects

N Taylor

Publications and source records attributed to N Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Impact of polydonor mixed lymphocyte culture media on quantity and quality of myeloid metaphases.

A novel mitotic stimulator of myeloid hematopoietic cells was prospectively evaluated to detect enhanced quantity and quality of metaphases from bone marrow (BM) cultures for cytogenetic analysis. This polydonor mixed lymphocyte conditioned (PMLC) media decreased the culture failure rate, improved detection of chromosomal aberrations, and reduced technologists' analysis time. The conditioned media is recommended as a highly effective culture system for normal and neoplastic cells of myeloid lineage.

Bone Marrow↗
PubMed1992

Cyclic AMP produces desensitization of prostacyclin and adenosine A2 receptors in hybrid cell lines but does not affect Gs function.

Prostacyclin and adenosine A2 receptors stimulate adenylate cyclase activity in the related somatic hybrid cell lines NG108-15 and NCB20. The role of cAMP in the desensitization of these receptors has been examined. Pretreatment for 17 h with forskolin or 8-bromo-cAMP had the same effect in both cell lines. There was no change in the response to sodium fluoride or forskolin, suggesting that the function of Gs and adenylate cyclase were unaffected by increased levels of cAMP. Receptor responses were affected however; the maximum response to N-ethylcarboxamidoadenosine (an A2 receptor agonist) was reduced by 30-40%, there was a small but consistent shift to the right of the dose-response curve for iloprost (a stable analogue of prostacyclin) and [3H]iloprost binding studies revealed a loss of prostacyclin receptors. However, the loss of receptor responsiveness was much smaller than that which occurs following pretreatment with prostacyclin or adenosine A2 receptor agonists (Keen et al. (1989) Biochem. Pharmacol. 38, 3827-3833; Kelly et al. (1990) Br. J. Pharmacol. 99, 309-316) suggesting that cAMP may not play a major role in agonist mediated desensitization.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Viral proteins associated with the Epstein-Barr virus transactivator, ZEBRA.

The BamHI Z Epstein-Barr replication activator (ZEBRA) mediates disruption of latency and induction of Epstein-Barr virus (EBV) early gene expression in latently infected lymphocytes. Polyclonal rabbit sera raised against ZEBRA were used to immunoprecipitate ZEBRA-associated proteins (ZAPs). ZAPs of 19, 21, 23, and 42 kDa were coimmunoprecipitated with ZEBRA from extracts of EBV-producing lymphoid cell lines. ZAPs were not recognized directly by the rabbit sera, but they were antigenic for EBV+ human sera. Immunoprecipitation of ZAPs by ZEBRA-specific antisera required the presence of ZEBRA. ZAPs were not coprecipitated with ZEBRA from mouse cells expressing only ZEBRA, from Raji (a cell line in which EBV is unable to complete lytic replication), or from cells treated with inhibitors of viral DNA synthesis. Thus, ZAPs are late EBV-encoded proteins. ZEBRA and ZAPs colocalized to a salt-insoluble nuclear fraction, and both were found extracellularly in crude preparations of virions. ZAPs might function to affect the cellular localization of ZEBRA, to alter its capacity to transactivate, or to influence its target gene specificity.

Cell Line↗
PubMed1991

Misinformation about medications in rural Ghana.

Misuse of medications is a serious problem in developing countries where drug sales are not regulated. This study assessed drug knowledge and use in a rural Ghanaian town. We surveyed health care workers and a community population sample regarding knowledge and use of available drugs. Although drugs were used by a large percentage of the population, only a small percentage correctly described their recommended use. Doctors and medical assistants were knowledgeable in the correct use of drugs, while chemists were poorly informed. However, the majority of the non-health care worker (NHCW) population bought drugs from chemists without a prescription. We conclude that in this rural setting, chemists contributed to drug misuse by providing misinformation about drugs and selling drugs according to popular demand. Educational programs for chemists and the population regarding drug use and regulation of drug sales by chemists will be critical to drug reform in Ghana.

Adult↗
PubMed1991

ZEBRA and a Fos-GCN4 chimeric protein differ in their DNA-binding specificities for sites in the Epstein-Barr virus BZLF1 promoter.

Epstein-Barr virus (EBV) encodes a protein, ZEBRA, which enables the virus to switch from a latent to a lytic life cycle. The basic domain of ZEBRA is homologous to the Fos/Jun oncogene family, and both proteins bind the canonical AP-1 site (TGAGTCA). However, ZEBRA does not contain a leucine zipper dimerization domain which has been shown to be necessary for DNA binding of Fos/Jun proteins. Additionally, ZEBRA binds to sites which deviate from the AP-1 consensus sequence. Thus, it was of interest to define the domain of the ZEBRA protein required for DNA binding. We have determined by mutagenesis that ZEBRA residues 172 to 227, representing the basic domain and a putative dimerization domain, are required for specific binding to AP-1 and divergent sites. Mutagenesis of the basic amino acids 178 to 180 or 187 to 189 abrogates ZEBRA binding to all DNA target sequences. These residues are conserved in Fos and are also necessary for Fos DNA-binding activity. We have found that a Fos-GCN4 chimera and ZEBRA have different cognate binding specificities. The autoregulated BZLF1 promoter contains three divergent AP-1 sequences, ZIIIA (TGAGCCA), ZIIIB (TTAGCAA), and Z-AP-1-octamer (TGACATCA). ZEBRA binds with high specificity to ZIIIA and ZIIIB but weakly to the Z-AP-1 octamer. Conversely, the Fos-GCN4 chimera recognizes only the Z-AP-1 octamer. ZEBRA binds the ZIIIA and ZIIIB sites together in a noncooperative fashion, while Fos-GCN4 binds these sites as a higher-order complex. Additionally, we have found that flanking sequences influence binding of Fos-GCN4 to a degenerate AP-1 site (TGAGCAA). The characteristic binding specificities of ZEBRA and cellular AP-1 proteins suggest that they differentially affect viral and cellular transcription.

Amino Acid Sequence↗
PubMed1991

Exploring the use of antisense, enzymatic RNA molecules (ribozymes) as therapeutic agents.

Antisense catalytic RNAs that specifically base-pair with and cleave target RNA sequences have potential for use as therapeutic agents against viral as well as endogenous gene expression. With the ultimate goal of developing anti-human immunodeficiency virus type 1 (HIV-1) ribozymes for therapeutic use, we have been exploring ways to improve upon the functional activity of ribozymes in living cells. This is being done by the systematic exploration of parameters that affect antisense, and hence ribozyme, function. These include target accessibility, stability of the catalyst, methods for delivery, and intracellular localization of the ribozyme. In addition, we have been examining the kinetic consequences of having extra, nontargeted sequences appended to the ribozyme flanking sequences. Perhaps the single most important consideration for ribozyme effectiveness in an intracellular environment is the accessibility of the target RNA for cleavage. By exploiting the mechanisms by which naturally occurring antisense RNAs interact with their target sequences, we hope to be able to address this problem of targeting and fully capitalize upon the potential of ribozymes as therapeutic agents.

Antiviral Agents↗
PubMed1990

Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks.

This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.

Adolescent↗
PubMed1990

Differences in the extent of activation of Epstein-Barr virus replicative gene expression among four nonproducer cell lines stably transformed by oriP/BZLF1 plasmids.

Lymphoid cell lines were established which stably carry the Epstein-Barr viral (EBV) BZLF1 gene on an extrachromosomal plasmid. These lines, which spontaneously synthesize the BZLF1 gene product, ZEBRA, were examined for expression of EBV genes which were activated by ZEBRA. Cell lines which acquired oriP plasmids without BZLF1 served as controls. The extent of activation differed among derivatives of four cell lines. X50-7 cells, which harbor a standard latent EBV, could be induced by ZEBRA to produce transforming virus; a cellular subclone of this line was induced to express EBV late antigens but did not release transforming virus. In two other cell lines, Raji and ER, ZEBRA activated only a group of early antigens. Using immunofluorescence and immunoblotting with monoclonal antibodies and Northern analysis five EBV early genes were shown to be induced in cells stably transformed by oriP/BZLF1 plasmids. ZEBRA itself was activated; thus BZLF1 is autostimulatory. Four other activated genes were components of the diffuse (EA-D) and restricted (EA-R) early antigens (BMRF1, BMLF1, BHRF1, and BORF2). Stable cell lines with extrachromosomal BZLF1 expression vectors will ultimately be useful in a variety of experiments designed to study regulation of this gene, to analyze the effects of mutations on ZEBRA protein function, and to define the full spectrum of viral and cellular genes which are activated by and interact with the ZEBRA protein.

Cell Line↗
PubMed1990

Measuring malnutrition in famines: are weight-for-height and arm circumference interchangeable?

Data from two surveys in Sudan have been used to examine whether weight-for-height (WFH) and mid-upper arm circumference (MUAC) can be used interchangeably at a population level to define the proportion of children aged one to four years that are malnourished, whether they identify the same individual children as malnourished, and whether the relationship between WFH and MUAC varies with age. A MUAC cut-off of 13.0 cm consistently defined approximately the same proportion of children malnourished as 80% WFH in all seven groups of children examined, even though the proportion of children with less than 80% WFH varied between 8.6% and 30.7%. However, sensitivity/specificity analysis showed that many of the children identified as malnourished by the two indices were not the same individuals. Both the MUAC cut-off defining the same proportion malnourished as 80% WFH, and the sensitivity/specificity values, varied substantially with age. Studies of other populations have revealed both different MUAC cut-offs defining the same proportion of children malnourished as 80% WFH, and different sensitivities and specificities of MUAC relative to WFH. We do not recommend the direct comparison of data from surveys using WFH and those using MUAC.

Age Factors↗
PubMed1989

Instruments for screening for depression and dementia in a long-term care facility.

The high prevalence of mental disorders such as depression and dementia in institutionalized elderly patients warrants screening for psychiatric diagnosis in patients newly admitted to long-term care facilities. The diagnostic accuracy of the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) was evaluated against a standardized psychiatric interview. The MMSE was found to be 81% sensitive and 83% specific in screening for dementia using a previously established cutpoint of less than 24/30 points. Adjusting MMSE scores for physical disabilities precluding completion of specific tasks on the MMSE did not significantly change the diagnostic accuracy of the test. The GDS was 47% sensitive and 75% specific in screening for depression using the suggested cutpoint of greater than 13/30 points. The MMSE was significantly correlated with functional status (r = 0.48, P = .0001), but not with the scores on the GDS or the clinical diagnosis of depression. The GDS did not correlate with functional status. In summary, the MMSE is a good screening test for dementia in institutionalized elderly, but the GDS is not sensitive for depression in this population.

Activities of Daily Living↗
PubMed1989

Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837).

This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds in human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times a day, commencing 28 h before virus challenge; treatment continued for 4 days and one dose (total dose, 25 mg). This regimen suppressed symptoms until 48 h after medication ceased, at which time colds developed. In another trial, medication with R61837 commenced at 4 h before virus challenge and continued for a total of 6 days (total dose, 36 mg). The drug produced substantial reductions in both the mean daily clinical score and the mean daily nasal secretion weight compared with patients given the placebo. These differences reached statistical significance for 2 and 4 days, respectively. In a further trial, intranasal R61837 was not effective in treating colds even when given shortly after the onset of symptoms and in doses of up to 15 mg/day.

Administration, Intranasal↗
PubMed1989

Expression of the BZLF1 latency-disrupting gene differs in standard and defective Epstein-Barr viruses.

Previous experiments using gene transfer of plasmids with heterologous promoters identified an Epstein-Barr virus (EBV) gene (BZLF1) whose product (ZEBRA) switches the virus from a latent to a replicative state. We have now studied expression of ZEBRA in lymphoid cells harboring either standard virus or a mixture of standard and defective (heterogeneous [het]) viruses. A high-titer rabbit antiserum to a TrpE-BZLF1 fusion protein was used to identify ZEBRA expressed from standard and het EBV DNA. These ZEBRA proteins could be distinguished from each other on the basis of their electrophoretic mobilities. ZEBRA could not be detected in cells latently infected with standard EBV. However, within 6 h after induction of replication by sodium butyrate, ZEBRA appeared and persisted long thereafter. Synthesis of ZEBRA was insensitive to phosphonoacetic acid or acycloguanosine, behavior characteristic of an early replicative protein. ZEBRA was constitutively expressed in cells containing both defective and standard EBV genomes. ZEBRA was made predominantly from the het genome but also from the standard genome. Control of BZLF1 expression appears to occur at the transcriptional level. No BZLF1-specific transcript was detected in cells containing only standard latent EBV. BZLF1 transcripts could be detected in these cells if virus replication was induced by treatment with butyrate. Cells bearing both standard and het genomes did not require addition of an exogenous inducing agent to transcribe the BZLF1 gene. The experiments suggest that regulation of transcription of the BZLF1 gene is a pivotal event in the control of EBV replication.

Burkitt Lymphoma↗
PubMed1987

The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse.

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.

6-Ketoprostaglandin F1 alpha↗
PubMed1979

Tuberculosis.

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England↗
PubMed1978

Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis.

Tissue cultures were performed on stools from 189 patients to detect a cytopathic toxin which is neutralized by Clostridium sordellii antitoxin. Specimens satisfying these criteria were considered positive in the tissue culture assay. Stools from 26 of 27 patients with antibiotic-associated pseudomembranous colitis were positive and 16 of these specimens showed toxin titers of 10(-3) dilutions or greater. The tissue culture assay was positive with specimens from 9 of 63 patients with antibiotic-associated diarrhea without documented pseudomembrane formation. Stools from patients with neonatal necrotizing enterocolitis, ulcerative colitis, and healthy controls were uniformly negative in this assay. Cultures were performed on stools from 38 patients with antibiotic-associated diarrhea or colitis to detect clostridia which produce a cytopathic toxin in vitro. Clostridium difficile was recovered from 6 of 8 specimens which were positive in the tissue culture assay and 5 of 30 which were negative in this assay. C. sordellii was recovered in a single specimen. One hundred and nine clostridia strains were tested in the tissue culture assay and C. difficile was the only species which produced a cytopathic toxin. All strains of this organism were positive in the tissue culture assay and, in each instance, cytotoxicity was neutralized by C. sordellii antitoxin. These results indicate that C. difficile is the major cause of antibiotic-associated pseudomembranous colitis and offer an explanation for previous studies showing that the cytotoxin of stools from these patients is neutralized by C, sordellii antitoxin.

Anti-Bacterial Agents↗