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Biomedical subjects

L A Williams

Publications and source records attributed to L A Williams.

At least 73 records · Page 4Linked to original sources
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

MEDLINE and PsycLIT on CD-ROM: a survey of users in an academic medical library.

A survey of users of PsycLIT and MEDLINE on CD-ROM was performed at an academic medical library. The questionnaire was designed to gather information about the user population, satisfaction of the users, the assistance needed to use the systems, and the type of searches being performed. The majority of users were graduate students in the schools of medicine, nursing, and pharmacy. In general, users were satisfied with the performance of the systems. Assistance from a librarian, printed documentation, or another patron was required by 85% of users, and they were generally satisfied with this assistance. Most searches were performed to obtain information on a subject. The results were remarkably similar for both databases.

Consumer Behavior↗
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↗
PubMed1988

The management of congenital dislocation of the hip in the newborn.

We describe the results of a policy of highly selective splintage for CDH, using knee plasters. No child suffered because splintage was withheld. In those who were treated the results were satisfactory and the proportion who required a subsequent operation was extremely low. Avascular necrosis was not a significant problem. The method, although a little more time consuming, appears to offer significant advantages over current alternatives.

Hip Dislocation, Congenital↗
PubMed1987

HbXL99 alpha: a hemoglobin derivative that is cross-linked between the alpha subunits is useful as a blood substitute.

Under deoxygenated conditions, bis(3,5-dibromosalicyl) fumarate reacts with hemoglobin selectively to cross-link the alpha subunits between Lys-alpha 1 99 and Lys-alpha 2 99. We have characterized further the properties of this recently described hemoglobin and have demonstrated its utility as a blood substitute. The oxygen transport characteristics of the cross-linked derivative are very similar to those of whole blood. Under physiological conditions, the partial pressure of oxygen at half-saturation of hemoglobin is increased to 29 mm Hg (1 mm Hg = 133.3 kPa), compared to 12 mm Hg for hemoglobin A, fully compensating for the absence of 2,3-bisphosphoglycerate outside of the erythrocyte. The Hill coefficient is 2.9. The dependence of the oxygen affinity of HbXL99 alpha on CO2 is also identical to that of hemoglobin A. The cross-link between the alpha subunits blocks dissociation of oxyhemoglobin into alpha beta dimers and thereby prevents renal excretion of the modified hemoglobin. In the rat, the half-life of HbXL99 alpha in plasma, at a 15% volume exchange, is increased to 3.3 hr, compared to 90 min for hemoglobin A. Cross-linking HbXL99 alpha intermolecularly with bis(sulfosuccinimidyl) suberate to form predominantly a mixture of dimers and trimers further increased the half-life of the hemoglobin within the circulation by about 2-fold. The rate of autooxidation of the transfused hemoglobin was found to be markedly reduced because of the presence of an endogenous reducing system in plasma.

Animals↗