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Biomedical subjects

J Webb

Publications and source records attributed to J Webb.

At least 127 records · Page 7Linked to original sources

Antiphospholipid antibodies in systemic lupus erythematosus: clinical and laboratory associations in 111 patients.

An enzyme linked immunosorbent assay (ELISA) was used to evaluate the prevalence and disease associations of antibodies to a range of negatively charged phospholipids in 111 patients with systemic lupus erythematosus (SLE). The frequency of one or more isotypes of different antiphospholipid antibodies (APLs) was similar (range 33%-45%). When individual isotypes were considered alone there was considerable variation (range 5%-32%). There were significant associations between thrombosis, thrombocytopenia, and central nervous system (CNS) disease but not abortion with elevated APL. Strong associations were found between raised anti-ds-DNA (Farr assay) and a positive direct Coomb's test with raised APL. Thus, APLs are common in SLE and are associated with discrete clinical and laboratory features. However, detection of antibodies to a range of negatively charged phospholipids added little clinically useful information to that obtained by measuring anticardiolipin antibody (ACL) alone. We cannot recommend the use of APLs other than ACL for routine testing.

Adolescent↗

The 54-kD protein of signal recognition particle contains a methionine-rich RNA binding domain.

Signal recognition particle (SRP) plays the key role in targeting secretory proteins to the membrane of the endoplasmic reticulum (Walter, P., and V. R. Lingappa. 1986. Annu. Rev. Cell Biol. 2:499-516). It consists of SRP7S RNA and six proteins. The 54-kD protein of SRP (SRP54) recognizes the signal sequence of nascent polypeptides. The 19-kD protein of SRP (SRP19) binds to SRP7S RNA directly and is required for the binding of SRP54 to the particle. We used deletion mutants of SRP19 and SRP54 and an in vitro assembly assay in the presence of SRP7S RNA to define the regions in both proteins which are required to form a ribonucleoprotein particle. Deletion of the 21 COOH-terminal amino acids of SRP19 does not interfere with its binding to SRP7S RNA. Further deletions abolish SRP19 binding to SRP7S RNA. The COOH-terminal 207 amino acids of SRP54 (M domain) were found to be necessary and sufficient for binding to the SRP19/7S RNA complex in vitro. Limited protease digestion of purified SRP confirmed our results for SRP54 from the in vitro binding assay. The SRP54M domain could also bind to Escherichia coli 4.5S RNA that is homologous to part of SRP7S RNA. We suggest that the methionine-rich COOH terminus of SRP54 is a RNA binding domain and that SRP19 serves to establish a binding site for SRP54 on the SRP7S RNA.

Animals↗

Polyarthritis. A diagnostic approach.

The authors discuss the general classification of rheumatic disorders and the likely diagnosis of polyarthritis based on the mode of presentation, the patient's clinical situation and appropriate investigations. There is no simple formula that will lead to the correct diagnosis and specific therapy for every patient.

Arthritis, Rheumatoid↗

Extended perinatal outreach.

The perinatal outreach plan of the Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, and the Naples Community Hospital is described. From June 1988 through May 1989, 79 high-risk pregnant patients were evaluated at a monthly clinic at the hospital. The main indications for referral were intrauterine growth retardation (10), twin gestation (9), gestational diabetes (9) and possible fetal anomaly (8). With one exception, all babies were delivered at Naples. The high-risk patients had a 21% incidence of newborns less than 2500 gr, cesarean section rate of 30%, average maternal hospital charge of $2,403/patient, and an average neonatal hospital charge of $1,777/patient. There was a definite change in transport trends from Naples with three more maternal transports and seven fewer neonatal transports over the preceding year. Comprehensive perinatal outreach programs can be implemented at a reasonable cost and provide support and services that strengthen the entire local perinatal health delivery system.

Adult↗

Homology of 54K protein of signal-recognition particle, docking protein and two E. coli proteins with putative GTP-binding domains.

Most proteins exported from mammalian cells contain a signal sequence which mediates targeting to and insertion into the membrane of the endoplasmic reticulum (ER). Involved in this process are the signal-recognition particle (SRP) and docking protein (DP), the receptor for SRP in the ER membrane. SRP interacts with the signal sequence on nascent polypeptide chains and retards their further elongation, which resumes only after interaction of the arrested ribosomal complex with the docking protein. SRP is a ribonucleoprotein particle comprising a 7S RNA and six polypeptides with relative molecular masses (Mr) of 9,000 (9K) 14K, 19K, 54K, 68K and 72K (ref. 1). The 9K and 14K proteins are essential for elongation arrest and the 68K-72K heterodimer is required for docking to the ER membrane. The 54K protein binds to the signal sequence when it emerges from the ribosome. Docking protein consists of two polypeptides, a 72K alpha-subunit (DP alpha) and a 30K beta-subunit (DP beta). No components structurally homologous to SRP and docking protein have yet been found in yeast or Escherichia coli. To understand the molecular nature of the interaction between the signal sequence and its receptor(s) we have characterized a complementary DNA coding for the 54K protein of SRP. Significant sequence homology was found to part of DP alpha and two E. coli proteins of unknown function. The homologous region includes a putative GTP-binding domain.

Amino Acid Sequence↗

Antihistone antibodies in rheumatoid arthritis and Felty's syndrome.

Although antihistone antibodies are frequently detected in patients with systemic lupus erythematosus, they appear to be uncommon or present only at low levels in rheumatoid arthritis (RA) patients. We used an enzyme-linked immunosorbent assay to study sera from 42 patients with RA, and we confirmed that antihistone antibodies mainly occurred at low levels in these patients. In contrast, 83% of 24 patients with Felty's syndrome had antihistone antibodies, often at high levels. Thus, antihistone antibodies may be a common autoimmune abnormality in patients with Felty's syndrome but not in other patients with RA. In addition, we demonstrated that some rheumatoid factors have cross-reactive antihistone antibody activity.

Arthritis, Rheumatoid↗

Pyridoxal isonicotinoyl hydrazone and analogues. Study of their stability in acidic, neutral and basic aqueous solutions by ultraviolet-visible spectrophotometry.

The ultraviolet-visible absorption spectra of the orally effective iron chelator, pyridoxal isonicotinoly hydrazone (PIH), and three analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone (PpMBH) and pyridoxal m-fluorobenzoyl hydrazone (PmFBH) have been measured in aqueous solution with various concentrations of added acid or alkali. Assignment of absorption bands to various molecular species in equilibrium in aqueous solution is made by reference to their acid ionisation constants. All four hydrazones were stable at physiologial pH, but hydrolysed in strongly acidic and basic solutions, resulting in the liberation of pyridoxal and the acid hydrazide. In acidic solutions this resulted in a dramatic decrease in the intensity of absorption at wavelengths of 225 nm and above 300 nm, allowing a quantitative estimate of the degree of acid-catalysed hydrolysis of the ligands. These results indicate that for oral administration the chelator should be administered with calcium carbonate or provided with an enteric coating to minimise acid-catalysed hydrolysis in the stomach. At high pH, base-catalysed hydrolysis occurred, resulting in a decrease in the absorption at a wavelength of 387 nm.

Drug Stability↗

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II).

Formation constants for the calcium(II), magnesium(II) and zinc(II) complexes of the orally effective iron chelator, pyridoxal isonicotinoyl hydrazone (PIH) and three analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone (PpMBH) and pyridoxal m-fluorobenzoyl hydrazone (PmFBH) have been determined by potentiometry at 25 degrees C and I = 0.1 M [KNO3]. The four ligands bind calcium(II) weakly and magnesium(II) only slightly more strongly, as a 1:1 complex which is formed at pH greater than 8. The chelation of zinc(II) for all the ligands studied was greater than that for calcium(II) and magnesium(II), with complexation generally becoming significant at about pH 5. Thus, chelation of zinc(II) but not calcium(II) or magnesium(II) at physiological pH, 7.4 may be expected. Calculated values of the concentration of uncomplexed metal ion indicate that the selectivity of these ligands towards Fe(III) is comparable to that of the clinically used chelator desferrioxamine.

Calcium↗

Use of antibiotic resistance mutations to track strains of obligately anaerobic bacteria introduced into the rumen of sheep.

Selective plating procedures were used to follow the fate of rifampicin-resistant mutant strains of the obligately anaerobic species Bacteroides multiacidus and Selenomonas ruminantium after their introduction at numbers around 10(7)/ml into the rumen of sheep. Bacteroides multiacidus strain F100 showed an initially rapid rate of loss (49%/h) but subsequently numbers declined more gradually approaching the limits of detection (less than 10(3)/ml) after 100 h. Viable cell numbers also decreased in vitro upon addition of F100 cells to whole rumen contents, but remained stable upon addition to cell-free rumen fluid, suggesting protozoal predation. F100 cells were able to grow in vitro in whole rumen contents in the presence of an added utilizable substrate such as sorbitol, but addition of sorbitol to the rumen failed to enhance survival in vivo. In the case of S. ruminantium, introduced rifR strains persisted in the rumen at levels around 10(6) ml for at least 30 days.

Animals↗

Preliminary results of a district call scheme for cervical screening organised in general practice.

A recognised problem with the cervical screening programme in the United Kingdom is the failure to include women who have never had a cervical smear test, who are a high risk group. The implementation of a district based call scheme in East Berkshire in 1986 is described whereby women aged 20-64 with no record of a cervical smear test who were judged to be eligible for testing by their general practitioner were sent a personal invitation from their general practitioner to attend for a test. A list of high risk unscreened women was kept by each practice, and a duplicate sent to the cytology laboratory to update the central records. Six months after each batch of invitations had been sent the resulting number of women having a smear test was assessed. Forty three of 51 practices approached agreed to participate in the five year scheme. During the first year lists were sent to the 43 participating practices. The first list was returned to the cytology laboratory by 37 practices and the second by 33; practices varied in their responses, however, some needing considerable persuasion to return the lists. Of 972 identified unscreened women from the total 3757 women listed in the lists of the family practitioner committee, 247 (25%) had a cervical smear test in response to the invitation, representing an overall increase of 7% in the screened population. The preliminary findings of the five year study have shown that screening can be improved by a systematic call scheme. Coordinated support from the area health authority in health education, monitoring of screening, and feedback of data from the scheme to practices is required to reduce the proportion of unscreened women.

Adult↗