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Biomedical subjects

D W Taylor

Publications and source records attributed to D W Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1988

Factors that may effect the reduction of hunger and body weight following d-fenfluramine administration.

Three studies have been undertaken to investigate why there are individual differences in the response to d-fenfluramine with respect to food intake and hunger in the short term and on body weight loss in the long term. Fenfluramine and norfenfluramine plasma levels have been used as probes to help detect and normalize these variances. In a single dose ranging volunteer study (0, 30, 40, and 60 mg), d-fenfluramine levels were significantly related to caloric intake and hunger rating scales when compared individually, and the slopes of the regression lines showed intersubject variation. These slopes, an index of each subject's response to fenfluramine, appear to be related to both the percentage underweight and more weakly to the percentage overweight. Those subjects at the extremes of weight showed a greater response to a given drug level. In two placebo-controlled 3 month studies (30 mg/day), the variances in weight loss were not explained by steady state drug levels, the percentage overweight, initial weight, duration of obesity, or caloric intake even when weight loss was normalized for differences in drug levels. Age, however, was significantly related to weight loss, with each additional 10 years increasing weight loss by approximately 1 kg. If confirmed, the sensitivity of fenfluramine anorexia may be an objective acute test of the central control of food intake. However, in long term clinical studies, drug levels were only weakly related to weight loss and other undefined factors seem to determine which patients responded better to fenfluramine treatment.

Adult↗
PubMed1987

Functional status changes following medical or surgical treatment for cerebral ischemia. Results of the extracranial-intracranial bypass study.

To determine the value of extracranial-intracranial arterial anastomosis (EC/IC bypass), we randomly allocated 1377 patients with symptomatic atherosclerosis of the internal carotid or middle cerebral arteries to medical care alone or to EC/IC bypass with continuing medical care. As previously reported, surgery did not reduce--or significantly increase--the risk of stroke. Functional status data collected during the trial provide new information. Six weeks following entry, surgical patients showed greater dysfunction in the following activities: fluency of speech, getting in and out of bed, sitting down and standing up, toileting, cutting food and pouring beverages, and dressing and undressing. At 4.5 months, surgical patients still exhibited greater dysfunction in toileting, with nonsignificant trends in several other activities. From six months onward, there were no significant differences between the groups. Thus, EC/IC bypass results in transient worsening of functional status beyond the immediate perioperative period.

Activities of Daily Living↗
PubMed1987

Possible eggshell protein gene from Schistosoma mansoni.

We have identified and sequenced a cDNA clone of a mRNA found only in mature female schistosomes. This mRNA is not detectably synthesized by female worms from single sex infections (unisexual females), by males or by the developing miracidia in the eggs. The clone hybridises to a highly abundant polyadenylated mRNA of approximately 1500 nucleotides. The nucleotide sequence of the clone predicts a polypeptide comprising two repetitive regions. A pentapeptide repeat with the consensus sequence Gly-Tyr-Asp-Lys-Tyr, and a region rich in histidine residues. Hybrid selected mRNA translated in vitro with [3H]tyrosine as labelled amino acid yields a polypeptide of 48 kDa (p48) that corresponds to the major [3H]tyrosine labelled translation product of female worm total mRNA. p48 does not label with [35S]methionine and is absent from the translation products of male and unisexual female mRNAs. The amino acid sequence of p48 has significant homologies to silk moth chorion proteins and we suggest that it is one of the major components of the schistosome eggshell probably accounting for the high level of [3H]tyrosine incorporation into the vitellaria of Schistosoma mansoni. The tyrosine content of the polypeptide suggests that it may play a role in phenol oxidase mediated cross-linking of the schistosome eggshell and in support of this we find that mushroom phenol oxidase will cause the specific cross-linking of p48 in in vitro translation products.

Animals↗
PubMed1987

Plasmodium falciparum: fine structural changes in the cytoskeletons of infected erythrocytes.

Following parasitization by Plasmodium falciparum, numerous changes take place in the host erythrocyte membrane. In this study, we used the technique of whole cell mount electron microscopy to determine if the ultrastructure of the erythrocyte cytoskeleton changed following parasitization with knobby and knobless strains of P. falciparum. Using this technique, a network of spectrin filaments (3-10 X 45-120 nm) branching from electron dense junctions (15-25 nm in diameter), the presumed site of bands 4.1 and actin, were visualized. The overall architecture of normal and parasitized erythrocyte cytoskeletons was the same: however, additional patches (35 to 60 nm in size) and aggregates (30 X 150 nm) of electron dense material were present in parasitized skeletons. The ultrastructure of knobby and knobless cytoskeletons was similar, except knobless skeletons usually did not possess the larger aggregates of material. Antigens associated with the erythrocyte cytoskeleton of cells infected with knobby and knobless strains, but not uninfected cells, were demonstrated by indirect immunofluorescence. Results suggest that antigens, associated with the erythrocyte cytoskeleton, may contribute to perturbations in the host erythrocyte membrane.

Animals↗
PubMed1987

Localization of Plasmodium falciparum histidine-rich protein 1 in the erythrocyte skeleton under knobs.

Plasmodium falciparum parasites that induce knobs in the host erythrocyte membrane (K+ phenotype) synthesize a 90 kDa histidine-rich protein (PfHRP-1), whereas knobless variants do not. A monoclonal antibody (mAb 89) to PfHRP-1, in combination with cryo-thin section immunoelectron microscopy, localized the antigen in the parasitophorous vacuolar space and vesicles within the erythrocyte cytosol. Additional immunoelectron microscopic studies showed that PfHRP-1 was also associated with submembranous electron-dense material under knobs and with microfilaments of the host erythrocyte skeletal network. Immunofluorescence and immunoelectron microscopy of intact, non-fixed K+ infected erythrocytes using mAb 89 and a rabbit antiserum raised against purified PfHRP-1, failed to identify any surface exposed epitopes. These antibodies also failed to block cytoadherence of infected erythrocytes to C32 melanoma cells or to affect macrophage phagocytosis of infected erythrocytes.

Animals↗
PubMed1987

Comparative analysis of the Plasmodium falciparum histidine-rich proteins HRP-I, HRP-II and HRP-III in malaria parasites of diverse origin.

Plasmodium falciparum-infected erythrocytes (IRBC) synthesize 3 histidine-rich proteins: HRP-I or the knob-associated HRP, HRP-II and HRP-III or SHARP. In order to distinguish these proteins immunochemically we prepared monoclonal antibodies which react with HRP-I, HRP-II and HRP-III, and rabbit antisera against synthetic peptides derived from the HRP-II and HRP-III sequences. A comparative analysis of diverse P. falciparum parasites was made using these antibodies and immunoprecipitation or Western blotting. HRP-I (Mr 80,000-115,000) was identified in all knob-positive P. falciparum parasites including isolates examined directly from Gambian patients. However, this protein was of lower abundance in these isolates and in 6 knob-positive, culture-adapted parasites compared to Aotus monkey-adapted parasites or culture-adapted parasites studied previously. HRP-II (Mr 60,000-105,000) was identified in all P. falciparum parasites regardless of knob-phenotype, and was recovered from culture supernatants as a secreted water-soluble protein. Within IRBC, HRP-II was found as a complex of several closely spaced bands. Cell surface radio-iodination of IRBC from several isolates and immunoprecipitation with a rabbit antiserum against the HRP-II repeat sequence identified HRP-II as a surface-exposed protein. Like HRP-I, the abundance of HRP-II was lower in the Gambian isolates than with Aotus monkey-adapted parasites studied earlier. Neither HRP-I nor HRP-II were identified in a knob-positive isolate of P. malariae collected from a Gambian patient. Analogues of these HRP were also absent from asexual parasites of diverse primate and murine malaria species screened with this panel of antibodies. HRP-III (Mr 40,000-55,000) was distinguished by its lower apparent size and by specific reaction with rabbit antibody against its 5-mer repeat sequence. HRP-III was of lowest abundance compared with the other two HRP. These antibody reagents and distinguishing properties should prove useful in studies on the separate functions of the 3 P. falciparum HRP.

Adult↗
PubMed1987

Bronchodilators in chronic air-flow limitation. Effects on airway function, exercise capacity, and quality of life.

We conducted a trial of inhaled salbutamol and orally administered theophylline in patients whose acute response to inhaled salbutamol was less than 25% of their baseline FEV1. Patients underwent 4 treatment periods, each of 2 wk duration, during which they received the following combinations: placebo-placebo, placebo-salbutamol, placebo-theophylline, and salbutamol-theophylline. The 19 patient who completed the study were all males with a mean age of 65 +/- 7.4 yr, mean FEV1 of 1.02 +/- 0.38, and mean VC of 2.73 +/- 0.19. Outcomes included twice-daily recordings of peak flow rates, spirometry, the distance patients could walk in 6 min, and clinical symptoms of dyspnea, fatigue, and emotional function. Clinically important and statistically significant differences between the 4 periods were noted on both physiologic and functional outcomes. For the group as a whole, improvement with inhaled salbutamol and orally administered theophylline was comparable, and additional benefit was gained from a combination of the 2 drugs. We conclude that both inhaled salbutamol and orally administered theophylline can improve airflow obstruction, functional exercise capacity, and quality of life in patients with primarily fixed air-flow limitation.

Aged↗
PubMed1987

Measurement of quality of life in end-stage renal disease: the time trade-off approach.

The quality of life of patients with end-stage renal disease was estimated using the time trade-off technique. The sample included 103 transplant, 60 hospital hemodialysis, 57 home/self-care, and 52 continuous ambulatory peritoneal dialysis patients. Test-retest reliability was high: intra-class correlation coefficient 0.81 (p less than 0.001). The correlations of the time trade-off with the Spitzer Quality of Life index and a visual analogue scale completed by the nephrologists, nurses, friends/relatives, and the patient were positive and statistically significant, but still relatively low (r = 0.22-0.43; p less than 0.01). The time trade-off demonstrated evidence for discriminative construct validity by ordering treatment groups according to a priori prediction. The mean time trade-off values and standard deviations (where death is 0 and full health is 1) were 0.43 (0.26) for hospital hemodialysis 0.49 (0.23) for home/self-care hemodialysis, 0.56 (0.29) for continuous ambulatory peritoneal dialysis, and 0.84 (0.24) for transplant. Analysis of variance showed transplant to be different from all other groups (p less than 0.001) with age, sex, time with end-stage renal disease, and work status making no significant independent contribution. The partial correlation coefficients between time trade-off score and items in the physical, social, and emotional functioning sub-scales of the Rand questionnaire showed that physical functioning was far more important than social or emotional functioning. The time trade-off is reliable, demonstrates evidence for validity, and suggests that the quality of life for patients with end-stage renal disease is much poorer than that reported previously.

Emotions↗
PubMed1986

Conductometric monitoring of the amino acid oxidase reaction as a detector for high-performance liquid chromatography.

The deamination of L-amino acids by L-amino acid oxidase, which creates a change in the ionic strength of an HPLC eluent, is used to allow conductometric detection of L-amino acids. An example separation is given, and the conductometric method is compared to other methods of amino acid detection in the area of detection limits. Suggestions are also given for using this principle to create detectors based on other class selective enzymes.

Amino Acids↗
PubMed1986

Determining optimal therapy--randomized trials in individual patients.

Although the treatment of an individual patient in routine clinical practice has been likened to an experiment, the method is so susceptible to bias that we have come to demand multi-patient, double-blind, randomized controlled trials on matters of efficacy. Unfortunately, such trials have not or cannot be carried out for many clinical disorders; even when they have been executed their results may be difficult to extrapolate to individual patients. To resolve this problem, we have begun to use double-blind randomized trials in which a single patient undergoes a series of pairs of treatments, consisting of one active and one placebo or alternative treatment per pair, with the order determined by random allocation. Appropriate treatment targets (signs, symptoms, or laboratory tests) are used as the measure of efficacy, and the trial is continued until efficacy is established or disproved. We describe such a trial, which resulted in a dramatically beneficial modification of treatment in a patient with partially reversible airflow limitation. We have established a clinical service that facilitates the widespread use of the method in our community.

Aged↗
PubMed1986

Single-patient randomised clinical trial. Use in determining optimum treatment for patient with inflammation of Kock continent ileostomy reservoir.

A single-patient randomised clinical trial was used to determine optimum treatment for a patient with inflammation of her continent ileostomy. The trial proved to be feasible and acceptable to both patient and clinician. As a result, both the diagnosis of inflammation and the efficacy of metronidazole in treating it were confirmed. The trial design, in which multiple courses of active and control treatments are given to one patient, may be useful in other clinical situations to determine the most effective therapy in an individual case.

Administration, Oral↗
PubMed1986

Sequence and expression of a major egg antigen from Schistosoma mansoni. Homologies to heat shock proteins and alpha-crystallins.

One of the major proteins of eggs and miracidia (p40) of Schistosoma mansoni has an apparent molecular weight of 40,000 and elicits a strong immune response in over 90% of patients. The antigen consists of a family of at least four near identical proteins, probably encoded by a multi-gene family, and expression of the p40 polypeptides is differentially regulated around the parasite's life cycle. We have isolated and sequenced cDNA clones encoding two variants of the antigen and expressed one p40 clone in Escherichia coli. The fusion protein elicits antibodies which immunoprecipitate p40 and recognise antigens of identical sizes in S. haematobium and S. bovis. The open reading frame encoding this antigen specifies a protein which shares a block of sequence homology with alpha-crystallins and Drosophila small heat shock proteins.

Amino Acid Sequence↗
PubMed1986

Identification by message selection of cDNA clones encoding antigens of Schistosoma mansoni.

cDNA clone banks have been constructed in a plasmid vector (pJSC73) using mRNA isolated from adult worms and eggs of Schistosoma mansoni. These clone banks have been screened by message selection (hybrid release translation) and clones containing fragments of genes encoding schistosome antigens have been identified by immunoprecipitation of the corresponding mRNA in vitro translation product. Over 50 clones encoding schistosome antigens have been identified including those of the 100 000, 86 000, 28 000, and 27 000 molecular weight surface antigen precursors.

Animals↗
PubMed1986

Surface components of Onchocerca volvulus.

A technique employing Sephadex G25 gel filtration has been developed for the rapid isolation and purification of live microfilariae of Onchocerca volvulus from subcutaneous nodules and skin samples. Microfilariae, adult worms and L3 larvae have been surface radiolabelled using the Iodogen technique. Two proteins have been characterised on the surface of uterine microfilariae: these have apparent molecular weights of 14,800 and 15,000. A MW 15,000 protein was the only molecule labelled on the surface of skin microfilariae. Ten proteins were labelled on adult male worms: these have molecular weights of 15,000, 17,500, 20,000, 22,000, 24,000, 29,000, 32,000, 37,000, 42,000, and 50,000. Some, if not all, of these proteins were also identified on female worms. Seven proteins were labelled on the surface of L3 larvae: these have molecular weights of 17,500, 48,000, 50,000, 52,000, 54,000, 57,000, and 105,000. Three of the adult surface proteins were precipitated by selected human infection serum: these are the MW 17,500, 32,000 and 42,000 molecules. The microfilarial surface proteins were not precipitated by human infection serum. The antiserum used in these experiments was shown by Western blot analysis to contain high levels of antibody with specificity for microfilarial and adult antigens. Indirect immunofluorescent assays showed these sera to contain antibody which bound to the surface of adult worms and eggs but not microfilariae. The possibility that skin microfilariae absorb host serum albumin was investigated: Western blot analysis and surface immunofluorescence assays using a specific anti-human albumin serum gave negative results. Fluorescent lectin binding studies revealed the presence of stage-specific carbohydrate moieties exposed on the surface of adult worms and eggs. Microfilariae do not have surface carbohydrate determinants.

Animals↗