The coexistence of classic RA and AIDS.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
A Black
Publications and source records attributed to A Black.
The biochemistry and pharmacology of PD 116124 (8-amino-2'-nordeoxyguanosine), an inhibitor of purine nucleoside phosphorylase (PNP).
PD 116124 (8-amino-2'-nordeoxyguanosine; 2,8-diamino-1,9-dihydro-9- ([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)-6H-purin-6-one) is a competitive, reversible inhibitor of human purine nucleoside phosphorylase with an apparent inhibition constant of 0.41 microM. In a cell line system using human MOLT-4 and CEM T lymphoblasts and human MGL-8 and NC-37 B lymphoblasts, PD 116124 failed to inhibit [3H]thymidine uptake at concentrations up to 500 microM. However, in the presence of 10 microM 2'-deoxyguanosine (dGuo), a noninhibitory dGuo concentration by itself, PD 116124 produced potent inhibition of growth of both T cell lines but not of either B cell line. Significant elevation of intracellular 2'-deoxyguanosine triphosphate was observed in both inhibited T cell lines but not in either B cell line. Greater and more sustained accumulation of 2'-deoxyguanosine triphosphate was observed in T lymphoblasts cultured with PD 116124 plus dGuo than with dGuo only. PD 116124 was only weakly inhibitory in human mixed lymphocyte cultures (IC50 approximately equal to 1420 microM), but in the presence of 10 microM dGuo, the IC50 for PD 116124 was reduced to 108.7 microM. Administration of PD 116124 p.o. to normal male Wistar rats caused dose-dependent elevation of plasma inosine up through 500 mg/kg. Maximal inosine elevation occurred at 30 min after dosing, and elevation was significant even 24 hr after dosing. Guanosine was also elevated, although not in a dose-dependent manner. Administration of PD 116124 i.v. produced marked and statistically significant elevation of both inosine and guanosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Pain mechanisms and the management of neuropathic pain.
The nociceptive system is not fixed, but changes in response to its input and activity. This 'plasticity' comprises dynamic developments of both pro- and antinociceptive processes. Recent advances in the understanding of these processes have important implications for the treatment of persistent neuropathic pain.
Afferent Pathways↗
Physical fitness and occupational demands of the Belfast ambulance service.
The objectives of this study were to evaluate the current fitness of an area ambulance service based in Belfast and to quantify the physiological demands of accident and emergency work. From a total staff of 230, 105 (46%) volunteered to undergo a series of fitness tests subject to health state. Results based on body mass indices showed that 52% of subjects could be classified as overweight and 10% of subjects as obese. Fitness levels were similar to other comparable samples and showed the expected but not inevitable decrease with age. A simple work related task (walking at 6 km/h) performed in the laboratory showed that 54% of men over 40 years of age and 24% under 40 found it taxing. This would favour selection for accident and emergency work on the basis of functional capacity rather than chronological age. Accident and emergency work consisted of long periods of inactivity interspersed with shorter periods of relatively intense activity, often above the anaerobic threshold. Lactate concentrations measured during a staged emergency incident also suggested that personnel may work at intensities exceeding their anaerobic threshold. The incorporation of physical fitness standards in the ambulance service may be appropriate and consideration should be given to a reduced age of retirement.
Adult↗
Increased demands on services as a result of screening elderly people.
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Aged↗
Two Ig framework I epitopic specificities recognized by a rabbit antiserum and a monoclonal antibody to mouse VH chains.
The reactivity of 23 mouse monoclonal Ig with a rabbit polyclonal antiserum to VH of anti-alpha(1----6)dextran 19.22.1 and with a monoclonal anti-VH of anti-DNP MOPC315, when correlated with amino acid sequence, identified several residues in the first and third framework regions as being of potential importance in forming the epitope. Inhibition studies using synthetic peptides corresponding to residues 1-15 of the monoclonal Ig used to produce the poly- and monoclonal reagents provide evidence that the epitopes are predominantly, if not exclusively, specific for the N-terminal strand of the domain. Examination of known x-ray structures of mouse VH suggests that the primary difference between the two epitopes in the N-terminal strands is determined by the peptide chain structure due to Pro at position 9. Pro 9 appears essential for the epitope reactive with anti-VH MOPC315.
Amino Acid Sequence↗
Rabbit antisera to the variable region domains of an anti-alpha(1----6) dextran using E. coli-produced VL and VH fusion proteins as immunogens.
Bacteria were engineered for the expression of mouse immunoglobulin light chain variable region (VL) and heavy chain variable region (VH) fusion proteins. cDNAs encoding the VL and VH of anti-alpha(1----6)dextran hybridoma protein 19.22.1 were inserted into the pATH 10 prokaryotic expression vector downstream of trp operon sequences. V domains joined to approximately 330 amino acids of the trp E gene product encoded by the expression plasmids accumulated at high levels in E. coli. In addition, the VL domain was expressed with a 15 amino acid extension at low levels in lon mutant bacteria. The trp E-VL and trp E-VH proteins were used to raise antisera in rabbits and the V specificity of the sera demonstrated.
Animals↗
Vitamin B-12: low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduria in their infants.
In a group of 13 strict vegetarian and 6 omnivorous lactating women, relationships were studied among maternal milk and serum vitamin B-12, and milk vitamin B-12 and infant urinary methylmalonic acid (MMA) excretion. Milk vitamin B-12 concentrations were lower in women consuming a strict vegetarian diet compared with an omnivorous diet. Milk vitamin B-12 was inversely related to length of time on a vegetarian diet and positively correlated with maternal serum vitamin B-12 concentrations. Infant urinary MMA excretion was inversely related to milk vitamin B-12 concentrations less than 362 pmol/L. The 1989 recommended dietary allowance for vitamin B-12 of 221 pmol/d for infants is close to the intake below which infant urinary MMA excretion is increased. We conclude that the current RDA for infants provides little margin of safety.
Adult↗
Tolerance and safety of ciprofloxacin in paediatric patients.
The Cystic Fibrosis Clinic at the Royal Belfast Hospital for Sick Children has treated 31 children with ciprofloxacin, for serious pseudomonas infection in cystic fibrosis, and carefully monitored the safety and acceptability of the drug. Initially, eight very ill children were treated on a named-patient basis, with an encouraging clinical response and few adverse effects. Children aged 10-18 years were included in a study of four consecutive exacerbations of respiratory disease, comparing (i) oral ciprofloxacin in each episode with (ii) ciprofloxacin alternating with intravenous azlocillin and tobramycin. Other children with cystic fibrosis were subsequently treated with ciprofloxacin, as the need arose. In all the groups very few adverse reactions were found; in particular only one child developed arthralgia. A total of 202 children in the UK have been treated with ciprofloxacin on a named-patient basis, and their clinicians have reported 46 adverse events that may have been drug-related. Overall ciprofloxacin appears to be safe and effective in children but concern about the possible occurrence of arthropathy remains and long term follow-up of these children may be necessary.
Adolescent↗
The general practitioner's use and expectations of an accident and emergency department.
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Communication↗
Jonestown--two faces of suicide: a Durkheimian analysis.
This paper takes exception to much of the literature on Jonestown. The authors of this literature claim that an explanation of the mass suicide in Jonestown requires an understanding of how its residents came to a common consciousness. Such an analysis implies that the residents of Jonestown died for essentially the same reason. This paper, using Durkheim's typology of suicides, demonstrates that the residents of Jonestown died for very different reasons and that two types of suicide occurred simultaneously on November 18, 1978: altruistic and fatalistic. Some of the residents of Jonestown died because they put the group above the self; they committed altruistic suicide. The majority, however, died for fatalistic reasons. Jonestown in fact had become a hopeless, demeaning, and antagonistic environment. The analysis here suggests caution to those who assume that a mass suicide is necessarily a homogeneous event.
Emigration and Immigration↗
Isolation and characterization of complementary DNA to proliferating cell nucleolar antigen P40.
Proliferating cell nucleolar antigen P40 is a late G1-specific protein, which was found in a variety of human tumors (A. Chatterjee, J. W. Freeman, and H. Busch. Cancer Res., 47: 1123-1129, 1987). Two overlapping complementary DNA clones for antigen P40 were isolated by immunoscreening a lambda gt11 human expression library. The complete nucleotide sequence of the clones was determined. The complementary DNAs encode the Mr 30,000 portion of the COOH-terminal portion of the protein. The mRNA for P40 was 2.8 kilobases long and was expressed maximally in G1 cells in cell cycle. A series of deletion mutants of the expressed peptide was constructed and the deletion mutants were expressed in Escherichia coli. Using these mutants, the epitope region of P40 recognized by a P40-specific monoclonal antibody was identified. The hydropathy plot based on the protein sequence revealed that this region of the protein is largely hydrophilic. This protein is unique and differs in sequence from other proliferating cell nuclear/nucleolar antigen proteins of similar molecular weight such as protein B23 and cyclin.
Antibodies, Monoclonal↗
Dosimetric equivalence of tar deposition in rodents and man.
It has proved very difficult to produce cancer in laboratory animals following the inhalation of tar from cigarette smoke. Amongst other factors, this may be due to the dose that animals get in comparison to humans. Data reported here suggest that the average dose to the bronchial region of the lung, estimated using radiotracer techniques, may be a factor of 4 lower. The local dose to the carinal is also discussed; this may be lower still.
Administration, Inhalation↗
Simultaneous immunoelectron microscopic visualization of protein B23 and C23 distribution in the HeLa cell nucleolus.
The intranucleolar distribution of phosphoproteins B23 and C23 was visualized simultaneously by post-embedding immunoelectron microscopy in HeLa cell nucleoli, using specific antibodies. The data show that proteins B23 and C23 co-localize to the same nucleolar compartments, i.e., the dense fibrillar component and the granular component. Neither of the two antibodies is significantly associated with the fibrillar centers in these cells, although the fibrillar centers appear positive after silver staining. These findings suggest that other unidentified components must be responsible for the silver staining observed in the fibrillar centers of interphase nucleoli. The results are discussed in the light of previously reported data obtained by preembedding immunolabeling techniques and by silver staining, which both suggested a localization of protein C23 inside the fibrillar centers.
Antibodies, Monoclonal↗
In vitro metabolism of isoxicam by horseradish peroxidase.
1. Disposition studies in vivo in animals and man indicate that hydroxylation of the isoxazole methyl group of isoxicam is the major route of metabolism. 2. Recently, N-methylsaccharin, saccharin, and an open-ring sulphonamide have been identified as additional isoxicam metabolites. 3. Attempts to form these metabolites in vitro with hepatic microsomal incubations were unsuccessful. However, incubations of isoxicam with purified horseradish peroxidase resulted in the formation of N-methylsaccharin and the open-ring sulphonamide in good overall yield (28% in 1 h). 4. A possible mechanism for HP-catalysed conversion of isoxicam to N-methylsaccharin and open-ring sulphonamide is presented.
Animals↗
Changes observed in the growth fraction, labeling index, duration of S phase, and total cell cycle times of HL-60 cells as they undergo differentiation in response to retinoic acid.
To assess the changes in the proliferation characteristics that occur during maturation, HL-60 cells were induced to differentiate along the granulocytic pathway by retinoic acid. Differentiation was documented by morphology, functional markers, and cytochemical staining. Durations of S phase, total cell cycle time, and the percentage of S-phase cells were determined simultaneously at each time point. In addition, the expression of two cell cycle related proteins with molecular weights of 110,000 (p110 measured by monoclonal antibody 5C2) and 145,000 (measured by monoclonal antibody p145) were measured to estimate the number of cycling cells or the "growth fraction." Our data demonstrate that as HL-60 cells undergo maturation in response to retinoic acid, a large proportion of cells exit from the cycle, the majority lose their proliferative potential, and the total cell cycle time becomes markedly longer. The slowing of the cell cycle seems to be the result of a prolongation in both S phase and the G1 phase of the cycle. We conclude that more mature myeloid cells cycle more slowly than immature cells. The clinical implications of these findings in myeloid leukemias are discussed.
Cell Cycle↗
Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.
We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.
Arthritis, Rheumatoid↗