Pharmacist compounding of analgesic medication: the risk of a little-known practice.
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Analgesics↗
Biomedical subjects
P Johnson
Publications and source records attributed to P Johnson.
Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels.
Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p < 0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p < 0.05) more common.
ABO Blood-Group System↗
XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro.
The DNA repair proteins XRCC1 and DNA ligase III are physically associated in human cells and directly interact in vitro and in vivo. Here, we demonstrate that XRCC1 is additionally associated with DNA polymerase-beta in human cells and that these polypeptides also directly interact. We also present data suggesting that poly (ADP-ribose) polymerase can interact with XRCC1. Finally, we demonstrate that DNA ligase III shares with poly (ADP-ribose) polymerase the novel function of a molecular DNA nick-sensor, and that the DNA ligase can inhibit activity of the latter polypeptide in vitro. Taken together, these data suggest that the activity of the four polypeptides described above may be co-ordinated in human cells within a single multiprotein complex.
Base Sequence↗
Cellulose-binding domains. Versatile affinity tags for inexpensive large-scale purification, concentration, and immobilization of fusion proteins.
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Actinomycetales↗
Emergency hospital visits for asthma.
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Asthma↗
Intracellular immunization against SIVmac utilizing a hairpin ribozyme.
A hairpin ribozyme targeting the 3' LTR region (9456) of SIVmac238 was cloned into a murine retroviral vector. This target sequence is conserved among various SIV, as well as most HIV-2, strains. The ribozyme cassette is driven from a polymerase III promoter, that of the human tRNAval gene. Hybrid human B-/T-cell lines (CEM/174) were transduced with the retroviral constructs and selected for G418 resistance. Cells stably expressing the 9456 ribozyme exhibited long-term resistance to infection by a pathogenic molecular clone of SIV and two strains of HIV-2. The ribozyme was also able to effectively reduce the proviral DNA burden. Its efficient protection against SIV/HIV-2 infection constitutes an important step toward evaluating ribozyme gene therapy in a primate model.
Animals↗
Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro.
p56lck is a potential in vivo substrate for the tyrosine-specific phosphatase, CD45. In this study, recombinant purified p56lck was found to specifically associate with recombinant CD45 cytoplasmic domain protein, but not to the cytoplasmic domain of another related tyrosine phosphatase, receptor protein-tyrosine phosphatase alpha. Under equilibrium binding conditions, the binding was saturable and occurred at a 1:1 molar stoichiometry. A fusion protein containing only the amino-terminal region of p56lck (residues 34-150) also bound to recombinant CD45, and further analysis of this region indicated that glutathione S-transferase fusion proteins of the unique amino-terminal region and the SH2 domain, but not the SH3 domain of p56lck, bound to recombinant CD45. The SH2 domain protein bound with a higher affinity than the amino-terminal region, but both were able to compete for the binding of p56lck to CD45, and when added together worked synergistically to compete for p56lck binding. The SH2 domain interaction with CD45 was specific as glutathione S-transferase-SH2 fusion proteins from p85 alpha subunit of phosphatidylinositol 3-kinase and SHC did not bind to CD45. In addition, this interaction occurred in the absence of any detectable tyrosine phosphorylation on CD45, suggesting a nonconventional SH2 domain interaction.
Blotting, Western↗
Barriers to return to work among persons unemployed due to arthritis and musculoskeletal disorders.
OBJECTIVE: To identify barriers to return to work (RTW) among persons likely to be seen in a clinician's practice who are unemployed due to arthritis and musculoskeletal disorders. METHODS: Two hundred eighteen persons unemployed due to arthritis and musculoskeletal disorders were interviewed at baseline and followed up for 1 year, at which time their work status was ascertained. Backward stepwise logistic regression was used to determine the association of baseline clinical, sociodemographic, and work-related factors to their work status at 1 year of followup. RESULTS: Fifty-one (24%) of 216 initially unemployed subjects had returned to permanent paid employment of > or = 20 hours/week after 1 year. Having rheumatoid arthritis, Social Security Disability Insurance (SSDI) status, a high pain level, older age, and lower education were barriers to reemployment. CONCLUSION: This study establishes the importance of chronic pain and having rheumatoid arthritis as factors independently associated with failure to RTW among persons unemployed due to arthritis and musculoskeletal disorders. The importance of SSDI beneficiary status, age, and education level in RTW is further confirmed. Duration of unemployment or previous work factors were not predictors of RTW in this group.
Adult↗
An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence.
The object was to study prospectively the results of a modified intravaginal slingplasty for the surgical treatment of female stress incontinence, carried out under local anesthesia as a day procedure. Seventy five patients with genuine stress incontinence were operated upon and followed for a 2-year period. All patients were diagnosed urodynamically to have genuine stress incontinence. Pad tests and quality of life assessments were carried out in all patients both pre- and postoperatively. There were no intra- or postoperative complications and 63 patients (84%) were completely cured throughout the 2-year follow-up period. Six patients (8%) were significantly improved, i.e. they did not loose urine apart from an occasional leakage during severe cold etc. In the remaining 6 patients (8%) no improvement was seen. These failures were obvious at the first postoperative check-up after 2 months. Thus, there were no relapses after 2 months. All but 5 patients were able to void properly directly after surgery. These 5 needed an indwelling catheter during the night directly after the operation. All 75 patients were released from the hospital the same day or the day after surgery without catheterization. Mean sick leave was 10 days and mean operation time 22 minutes. No defect healing or rejection of the sling occurred. It is concluded that the procedure described is a promising new technique for the surgical treatment of female stress incontinence. Prospective long-term studies including more patients are in progress to establish the definitive place of this technique in the clinical routine.
Adult↗
Hartmann's pouch, the Hartmann operation, the Hartmann procedure. An enigma of terminology.
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Cholecystectomy↗
Increase in the specific activity of p50csk in proliferating T cells correlates with decreased specific activity of p56lck and p59fyn and reduced phosphorylation of CD3 subunits.
Depending on their prior antigen recognition history, mature T cells respond with different functional outcomes to T cell receptor (TCR) stimulation. These functional outcomes include proliferation, anergy and cell death. The biochemical basis underlying differential responses by mature T cells at different stages of their developmental pathway to TCR stimulation remains to be determined. We have previously shown that proliferating but not naive T cells were susceptible to apoptosis after TCR stimulation and that the tyrosine phosphorylation of TCR zeta, CD3 gamma, and CD3 epsilon in proliferating T cells was decreased after TCR stimulation. In this study. We determined whether differences in phosphorylation between naive and proliferating T cells were due to altered regulation of p56lck (Lck) or p59fyn (Fyn) by their positive or negative regulators, CD45 or p5Ocsk (Csk), respectively. We found that Lck was expressed at the same level and had the same phosphotyrosine content in naive and proliferating T cells. However, its autophosphorylation activity was lower in proliferating cells, corresponding to a 2-fold decrease in its specific kinase activity. Similarly, the specific kinase activity of Fyn was also decreased by about 2-fold in proliferating T cells. In contrast, although Csk was expressed at the same level in both cell types its specific kinase activity was increased by 6-fold in proliferating T cells. The tyrosine phosphatase CD45, a positive regulator of src-family kinases, was overexpressed by 3- to 6-fold in proliferating cells. However, the specific activity of CD45 in naive and proliferating T cells was the same. Therefore, although the protein expression level of CD45 was increased in proliferating T cells it only partially compensated for the hyperactivity of Csk resulting in a 2-fold reduction in the specific activity of Lck and Fyn in proliferating T cells.
Animals↗
Community volunteers as recruitment staff in a clinical trial: the systolic hypertension in the elderly program (SHEP) experience.
During the recruitment phase of a trial it is often found that recruitment is not proceeding as quickly as projected. Budget limitations require innovative methods, such as use of volunteers, to increase recruitment yields without increasing cost. In the Systolic Hypertension in the Elderly Program (SHEP), volunteer staff at 12 of the 16 clinical centers (CCs) performed a range of tasks such as mailings, telephoning, and clerical work. SHEP volunteers donated almost 40,000 hours, at an estimated cost savings to the program of more than $368,000. Staff volunteers appear to require more training and supervision than regular staff and may require flexible work schedules. These limitations can be obviated by careful planning. This paper describes the SHEP experience with staff volunteers and provides suggestions for their use in other trials.
Aged↗
Marked hypocalcemia and ventricular fibrillation in two pediatric patients exposed to a fluoride-containing wheel cleaner.
In two separate cases, pediatric patients exposed to Armor-All Quicksilver Wheel Cleaner exhibited systemic toxicity including mental status changes, marked hypocalcemia, and ventricular fibrillation. One child also demonstrated profound hypomagnesemia. These are the first pediatric reports of near-fatal outcomes after ingestion or inhalation of a hydrofluoric acid-like product, namely, ammonium bifluoride.
Ammonium Compounds↗
Fluorescent polymerase chain reaction of a panel of CA repeats on chromosome 6 in the indolent phase of follicular centre cell lymphoma.
Twenty-four cases of histologically defined follicle centre cell (FCC) lymphoma have been examined for allele imbalance at 19 microsatellite loci spanning the length of chromosome 6, including six markers within the major histocompatibility complex (MHC), using fluorescent polymerase chain reaction (PCR) to amplify microsatellites. Nineteen cases were observed in which imbalance of one or more markers on chromosome 6 had occurred (79%). The frequency of allele imbalance was significantly higher on 6p than 6q, and two regions of deletions, 6p24-25 and 6p21.3-23, were identified in which the loci showed a significantly high allele imbalance frequency.
Chromosomes, Human, Pair 6↗
Microsatellite instability in follicle centre cell lymphoma.
Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.
Chromosomes, Human, Pair 14↗
Denaturing gradient gel electrophoresis: a novel method for determining Rh phenotype from genomic DNA.
Denaturing gradient gel electrophoresis (DGGE) was carried out on PCR products amplified from exons 2 and 5 of RHD and RHCE. Exon 2 of RHD and exon 2 of the C allele of RHCE have an identical sequence, which differs from that of the c allele of RHCE. One band representing D and/or C, and another representing c, could be distinguished by DGGE of exon 2 amplifications of genomic DNA from individuals with the appropriate Rh phenotype. C and c could only be distinguished in D-negative samples. Exon 5 of RHD and exon 5 of the E and e alleles of RHCE all have different nucleotide sequences. Bands representing D, E and e could be distinguished following DGGE of the products of exon 5 amplification of genomic DNA from individuals with red cells of the appropriate Rh phenotype. In samples from individuals with VS+ red cells (V+ or V-) there was a shift of the band representing e. Sequencing demonstrated that VS is associated with a RHCE e sequence with a single base change predicting a Leu245 --> Val substitution in the Rh polypeptide. This substitution may be responsible for the VS and e5 antigens.
Base Sequence↗
MIB-1 and involucrin expression in laryngeal squamous carcinoma: the relationship to host and tumour factors and survival.
MIB-1 is an antibody which attaches to the Ki67 antigen expressed by proliferating cells. MIB-1 immunoreactivity may be used to quantify the proliferative component of a tumour. Involucrin is a protein expressed by mature keratinocytes and may be used as a marker of differentiation. The present paper studies the expression of these two markers in a group of patients with squamous carcinoma of the larynx. Tumour cell kinetics were studied in 49 patients with squamous cell carcinoma of the larynx using antibodies to "Ki67' and involucrin. The median potential follow-up for the group was 8.1 years with a minimum follow-up of 5 years. The median MIB-1 index was 32%. The median involucrin index was 56%. Fifteen patients had no or only slight involucrin staining whereas 34 stained intensely for this protein. Involucrin expression was found to be associated with histological grade with those patients expressing involucrin tending to have well differentiated tumours and those not expressing this parameter tending to have poorly differentiated tumours (P = 0.045). There were no other associations between host and tumour factors and the various biological parameters. Survival analysis demonstrated that patients with an involucrin count above the median value had a better 5-year survival than those below the median (89% and 56% respectively) (P < 0.05). In addition, patients with no (or poor) involucrin expression had an increased risk of developing a recurrence at the primary site (P < 0.05). Involucrin appears to be a promising marker of tumour differentiation and survival in squamous carcinoma of the larynx.
Biomarkers, Tumor↗
Accessory cells in physiological lymphoid tissue from the intestine: an immunohistochemical study.
We report a study of the organization of accessory cell populations, in normal mucosal lymphoid tissue from small intestine (8 cases), large intestine (6) and appendix (9) using a panel of monoclonal antibodies and polyclonal antisera in paraffin-embedded tissue. Two populations were identified in dome areas, one positive for acid cysteine proteinase inhibitor and HLA class II (WR18) only and the second positive for S-100 protein, CD68, and WR18 and negative for acid cysteine proteinase inhibitor and factor XIIIa. Superficial colonic mucosal and small intestinal villous tip macrophages stained positively with CD68 and WR18 only, while deeper cryptal and submucosal populations exhibited additional positivity for factor XIIIa, but both populations were negative for acid cysteine proteinase inhibitor and S-100 protein. Germinal centre macrophages were positive for CD68, WR18 and acid cysteine proteinase inhibitor and negative for factor XIIIa, and S-100 protein. T zone dendritic cells included a population which stained positively for S-100 protien, WR18 and were negative for factor XIIIa, CD68 and acid cysteine proteinase inhibitor, an immunophenotype typical of interdigitating dendritic reticulum cells. This distribution of phenotypically identifiable accessory cell subpopulations was apparent at all three sites examined. We suggest that the specialized subpopulations of dendritic cells staining for S-100 protein and for acid cysteine proteinase inhibitor which are restricted to the dome areas, may have a potential role in the transfer of antigen across the epithelium to the germinal centres, while factor XIIIa appears to identify a tissue macrophage population with a potential role in stromal modulation distant from direct antigen challenge.
Antigen-Presenting Cells↗