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Biomedical subjects

L A Williams

Publications and source records attributed to L A Williams.

At least 19 recordsLinked to original sources
PubMed1991

Covert bacteriuria: long term follow up.

In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In girls with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment.

Bacteriuria↗
PubMed1991

Pitfalls of bone scintigraphy in suspected hip fractures.

In a review of 2617 patients who were admitted with a suspected fractured neck of femur over a period of five years, 213 had normal or equivocal plain radiographs, and were subsequently investigated by bone scintigraphy. Normal scans were obtained in 127 (60%) cases. Of the remaining 86 cases, 82 (38%) were reported to show fractures of the proximal femur, three showed pubic ramus fractures, and one acetabular fracture was demonstrated. Review and follow-up has revealed eight false positive and two false negative scans. The various factors accounting for these errors are considered, and the clinical implications discussed. Careful analysis of accompanying plain radiographs is stressed when interpreting scintigrams.

Aged↗
PubMed1991

Labelling of tumour cells with a biotinylated inhibitor of a cell surface protease.

Our objective has been to prepare a biotinylated affinity probe for the active centre of a protease associated with the surface of tumour cells. We employed three model systems in which easily recognisable tumour cells containing the active protease were used as targets for the biotinylated affinity probe. These were: squamous cell carcinoma, leukaemia cells in muscle and outgrowths of prostate carcinoma cells grown in three dimensional collagen gels. The presence of the bound biotinylated affinity probe was demonstrated by its ability to bind Texas-red labelled streptavidin with the results that the tumour cells exhibited red fluorescence. This binding was shown to be competitive with 9-amino acridine, a compound known to bind to the active centre of the target protease. This technique depends upon the affinity of the active centre of an enzyme for a competitive inhibitor and therefore should be applicable to other enzyme systems employing suitable ligands for their active centres.

Affinity Labels↗
PubMed1990

The status of trypsin-like enzymes in squamous-cell carcinoma of the head and neck region.

The activity of two proteases associated with tumour cells was studied using frozen sections of squamous-cell carcinoma and fluorescent probes for the enzymes. Four fluorescent probes were used to define the enzymic status of guanidinobenzoatase on the surface of the squamous carcinoma cells. Each of four probes demonstrated the location of cells possessing inactive guanidinobenzoatase, whereas adjacent cells of the same tumour exhibited active enzyme. It was shown that the inactive form of the enzyme was an inhibitor-enzyme complex that could be dissociated. In contrast, all of the squamous carcinoma cells possessed active trypsin-like enzymes that were recognised by fluorescent aprotinin molecules. The observed variation in enzymic status of these two tumour-associated enzyme systems is discussed in the context of a possible biological control mechanism for cell migration.

Aminacrine↗
PubMed1990

Single-dose cyclosporine pharmacokinetics in various biological fluids of patients receiving allogeneic marrow transplantation.

The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population.

Adult↗
PubMed1990

The protective role of a natural inhibitor in the fluorescent location of cells possessing a latent form of cell surface protease.

Leukaemia cells possess a latent form of a cell surface protease referred to as guanidinobenzoatase. Latency is due to complex formation between an inhibitor protein and the cell surface enzyme which is stable under acid conditions but is dissociated with formaldehyde treatment. The latent form of the cell surface protease has been used as a protecting mechanism during a preliminary step to stain all the nuclei of cells with haematoxylin. The enzyme-inhibitor complex was then dissociated and a combination of 9-amino acridine and propidium iodide employed to enable the fluorescent location of cells possessing active guanidinobenzoatase. We were thus able to visualise the nuclei by conventional light microscopy and simultaneously visualise the cell surface of leukaemia cells by fluorescent microscopy. This simple model system has provided technology applicable to the more complex analysis of neoplastic cells in cervical smears.

Animals↗
PubMed1990

Inactivation of strongyloides stercoralis filariform larvae in vitro by six Jamaican plant extracts and three commercial anthelmintics.

In vitro bioassay of (a) aqueous methanol extracts (AME) of the green leaves of mimosa (Mimosa pudica), love weed (Cuscuta americana), vervine (Stachytarpheta jamaicensis), chicken weed (Salvia serotina) and breadfruit (Artocarpus altilis); (b) methanol-water fraction (MWF) of breadfruit leaves, and (c) commercially available drugs albendazole, thiabendazole and levamisole were assayed for nematode inactivating potential, using filariform larvae of Strongyloides stercoralis. Test larvae were obtained from a 10-day-old charcoal coproculture. Bioassays were conducted in Locke's solution, using 100 larvae in each of three replicates. Inactivation was recorded microscopically at 1, 3, 6 and 12 hours, then every 24 hours up to 5 days' incubation. It50 (time for inactivation of 50% of larvae) values read: levamisole and mimosa extract less than 1 hour; love weed extract, approximately 2 hours; breadfruit (MWF), 9.5 hours; chicken weed, 20 hours; albendazole, 35 hours; breadfruit (AME), 49 hours; thiabendazole, 74 hours and vervine extract, 81.5 hours. It95 values followed a similar, trend, and were approximately double the It50 measures. A potential role for locally available natural products in the treatment of strongyloidiasis is highlighted.

Animals↗
PubMed1990

Methylprednisolone, cyclosporine and methotrexate for prophylaxis of acute graft-versus-host disease.

Twenty-four patients were given the combination of methylprednisolone 100 mg i.v. on day 0, cyclosporine 2 mg/kg i.v. every 12 h starting on day -3 and methotrexate 5 mg/m2 on days 1, 3, and 6, then 10 mg/m2 on days 11 and 18 after allogeneic bone marrow transplantation for hematological malignancies for the prophylaxis of acute graft-versus-host disease. (GVHD). Methylprednisolone was given prior to the marrow infusion for its lympholytic effect. The methotrexate dose on days 1, 3, and 6 was half of that given in other studies to decrease the early toxicities. The outcome of this group is compared with patients transplanted before 1988 and given methotrexate alone, methotrexate with prednisone, or cyclosporine alone. There is no difference in relapse and survival between the groups at this time. The rate of engraftment and incidence of mucositis with the combination is not significantly different from the cyclosporine group. No patient developed greater than grade II acute GVHD with the combination. The probability of grade II or higher acute GVHD with the combination (14%) is significantly less than methotrexate, with or without prednisone or cyclosporine alone.

Adolescent↗
PubMed1989

Fluorescent location of ornithine decarboxylase employing derivatives of the specific inhibitor alpha-difluoromethyl ornithine.

Two fluorescent derivatives have been made from alpha-difluoromethyl ornithine by linking the carboxyl group of the ornithine derivatives to fluorescent amines. alpha-difluoromethyl ornithine is a potent inhibitor of ornithine decarboxylase, an enzyme which plays an essential role in cell division. We have used these fluorescent derivatives as probes for ornithine decarboxylase in frozen sections of skin to locate the epithelial cells which are known to contain ornithine decarboxylase. The probes also located squamous cell carcinoma cells in human skin.

Animals↗
PubMed1989

Inhibition of trypsin-like enzymes on cells with rhodamine-aprotinin.

Aprotinin, a polypeptide inhibitor of trypsin-like enzymes, has been labelled with rhodamine. Rhodamine-aprotinin inhibits trypsin in free solution in an identical manner to aprotinin. Rhodamine-aprotinin binds to trypsin-like enzymes on cells in formaldehyde fixed wax embedded sections. This technique has been used to locate cells possessing trypsin-like enzymes by means of fluorescent microscopy. In the present study we have used this technique to locate tumour cells.

Animals↗
PubMed1988

Acute hemodynamic effects of celiprolol.

Beta-adrenoceptor blockade is an effective treatment for ischemic heart disease and hypertension, but the more widespread use of beta antagonists is limited by their bronchoconstrictor, vasoconstrictor and negative inotropic properties. Celiprolol has been shown in preclinical studies to be a beta 1-selective antagonist with bronchosparing and vasodilating properties, but without any cardiodepressant effect. This has been confirmed by clinical studies undertaken to date. The aim of the present study was to examine the acute effects of intravenous celiprolol on the cardiac hemodynamics of patients pretreated with oral atenolol.

Adult↗
PubMed1988

Tau-crystallin/alpha-enolase: one gene encodes both an enzyme and a lens structural protein.

tau-Crystallin has been a major component of the cellular lenses of species throughout vertebrate evolution, from lamprey to birds. Immunofluorescence analysis of the embryonic turtle lens, using antiserum to lamprey tau-crystallin showed that the protein is expressed throughout embryogenesis and is present at high concentrations in all parts of the lens. Partial peptide sequence for the isolated turtle protein and deduced sequences for several lamprey peptides all revealed a close similarity to the glycolytic enzyme enolase (E.C. 4.2.1.11). A full-sized cDNA for putative duck tau-crystallin was obtained and sequenced, confirming the close relationship with alpha-enolase. Southern blot analysis showed that the duck genome contains a single alpha-enolase gene, while Northern blot analysis showed that the message for tau-crystallin/alpha-enolase is present in embryonic duck lens at 25 times the abundance found in liver. tau-Crystallin possesses enolase activity, but the activity is greatly reduced, probably because of age-related posttranslational modification. It thus appears that a highly conserved, important glycolytic enzyme has been used as a structural component of lens since the start of vertebrate evolution. Apparently the enzyme has not been recruited for its catalytic activity but for some distinct structural property. tau-Crystallin/alpha-enolase is an example of a multifunctional protein playing two very different roles in evolution but encoded by a single gene.

Amino Acid Sequence↗