Search PubMed⌕ Search

Biomedical subjects

M A Taylor

Publications and source records attributed to M A Taylor.

At least 73 records · Page 4Linked to original sources

cDNA cloning and characterisation of an alpha-glucosidase gene from potato (Solanum tuberosum L.).

Using an Arabidopsis thaliana expressed sequence tag with sequence similarity to human lysosomal alpha-glucosidase as a probe, a potato cDNA was isolated. The cDNA encodes a polypeptide with an Mr value of 105,400 and the most significant matches of the deduced amino acid sequence are with members of family 31 of glucosyl transferase. The potato cDNA was expressed in a strain of Saccharomyces cerevisiae that is deficient in maltase activity and unable to grow using maltose as a carbon source (ABYSMAL81). Expression of the potato cDNA in the mutant yeast strain restores its ability to use maltose as a carbon source for growth. Additionally, alpha-glucosidase activity could be measured in extracts of the yeast cells following complementation. A range of maltodextrins were substrates for this activity. The steady-state expression level of the potato alpha-glucosidase gene was low in most tissues examined, the highest levels occurring in sprouting tubers and source leaves.

Amino Acid Sequence↗

Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands.

The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (>80%). Partial generalization (defined here as 40% maximal generalization) was seen with the D1 receptor antagonist SCH 23390 (43% maximal generalization), the alpha1-adrenoceptor antagonist prazosin (67%) and the alpha2-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced <25% maximal generalization, including the alpha2-adrenoceptor antagonist yohimbine (24%), the histamine H1 receptor antagonist mepyramine (21%), the D2 antagonist typical neuroleptic haloperidol (23%), the D4 receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2A receptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2C receptor antagonists SB 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3 receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D1 receptor antagonist SCH 23390, or by the 5-HT1A receptor antagonist WAY 100635, when given concomitantly with clozapine. Although the results suggest that muscarinic antagonism plays a major role in the clozapine cue, the results have to be considered in the light of the full generalization to clozapine seen with various antipsychotic agents which have very low affinity for muscarinic receptors, including zotepine, quetiapine, JL13 and PNU 96415 (a finding replicated in rats from the same breeding colony as those which generalized to scopolamine). Thus, generalization to clozapine for antipsychotics with multiple affinities but with low muscarinic affinity is probably mediated by additive or perhaps supra-additive actions at other receptors, although extensive studies with various combinations of drug mixtures are required to validate this hypothesis.

Adrenergic alpha-Antagonists↗

A feedforward and feedback framework for analysing an organisation's resources, capabilities and development needs.

The success of an organisation is measured by the progress its people make towards its goals and objectives. But, most organisations today operate in fast changing and competitive environments. In turn, these unpredictable conditions impact on the organisation's internal operations. As a result, established skills and competences can become obsolete. Strong and appropriate competences can enhance an organisation's performance. Strategic managers then need to ensure that their organisational skills and competences remain of an appropriate mix and measure. They need to continuously develop and/or renew the skills and capabilities of their workforce. Identifying what skills need renewing is not easy but very necessary. Identifying them quickly is harder still. An easy to follow framework that can be adapted at the various levels within the organisation's structure could prove useful as a consistent and relatively speedy format for analysing the organisation's resources, capabilities and development needs. This paper supports the use of such a framework.

Efficiency, Organizational↗

Cognitive deficits, psychopathology, and psychosocial functioning in bipolar mood disorder.

The objective of this study was to study the relationship of poor functioning, cognition, and psychopathology in bipolar mood disorder. The authors assessed 36 patients with bipolar mood disorder (23 VA, 13 community) for the presence of psychopathology, cognitive deficits, and psychosocial impairment. The authors assessed psychopathology using screening and follow-up questions based on the schedule for affective disorder and schizophrenia, lifetime version (SADS-L), schedule for the assessment for negative symptoms (SANS), and schedule for the assessment of positive symptoms (SAPS), and psychosensory features using the "Profile of Psychomotor Symptoms." They tested cognitive functioning in the following domains: 1) general intelligence and language, 2) verbal and visual memory, and 3) visuospatial functioning. They also assessed psychosocial functioning using a structured scale to assess maladjustment and an impairment rating scale. Patients with bipolar disorder showed significant impairment compared to age equivalent normals in several cognitive domains. Anhedonia was related to memory deficits. Memory deficits were also associated with poor psychosocial functioning. This study demonstrates that nondemented, asymptomatic patients with bipolar disorder exhibit substantial cognitive deficits that are associated with poor functioning, and anhedonia and avolition best predict this outcome.

Adult↗

Trypsin isolated from the midgut of the tobacco hornworm, Manduca sexta, is inhibited by synthetic pro-peptides in vitro.

The seven residue synthetic peptides VPAYPQR and VPANPQR, identical to the pro-regions of midgut trypsins from Manduca sexta, inhibit the peptidase activity of the mature enzymes. The inhibitory potencies of these peptides towards purified insect trypsin were determined and were found to be more potent at pH 7.0 than at pH 10.0. These peptides did not inhibit porcine trypsin, nor were they degraded rapidly by purified insect trypsin. We suggest that these particular peptides, and insect proregions in general, may be suitable for use in genetically engineered plants as insect specific inhibitors of digestive proteases.

Amino Acid Sequence↗

Evaluation and management of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder is the most common pediatric psychiatric disorder, involving one of every 20 children. It is often a disabling condition and is frequently accompanied by high levels of frustration and comorbidity. Diagnosis of attention-deficit hyperactivity disorder requires a detailed history from the family and use of rating scales to collect observations from two or more settings. Effective treatment, including behavior management, appropriate educational placement and stimulant medication, will improve academic performance and behavior in most patients. Armed with an organized approach and a broad general knowledge of stimulant therapy, the family physician can effectively evaluate and coordinate the initial therapy for many of these troubled children within the office setting. Children in whom initial management fails or for whom the diagnosis is unclear or complicated should be referred to appropriate mental health professionals.

Attention Deficit Disorder with Hyperactivity↗

The isolation of RNA from raspberry (Rubus idaeus) fruit.

Previous attempts to extract high-quality, total RNA from raspberry (Rubus idaeus) fruits using published protocols have proven to be unsuccessful. Even the use of protocols developed for the extraction of RNA from other fruit tissue has resulted in low yields (1) or the isolation of degraded RNA (2). Here, we report on the development of a quick and simple method of extracting total RNA from raspberry fruit. Using this method, high yields of good quality, undegraded RNA were obtained from fruit at all stages of ripening. The RNA is of sufficient quality for northern analysis and cDNA library construction.

Fruit↗

Isolation of RNA from blackcurrant (Ribes nigrum L.) fruit.

Extraction of high-quality RNA from blackcurrant fruit has hitherto proved difficult, probably owing to high levels of phenolic and polysaccharide components in the berries. The procedure described here is a modification of one described for grape berries, and yields RNA suitable for in vitro translations, RNA blot analysis, and cDNA library construction.

Fruit↗

The sensitization hypothesis and importance of psychosensory features in mood disorder: a review.

The sensitization model of mood disorders, articulated 10 years ago, predicts symptoms, course, and treatment response relationships. However, clinical data testing this model have not been reviewed. The authors reviewed all English-language publications characterizing psychosensory features (clinical phenomena hypothesized to reflect temporolimbic sensitization) and the relationship of these features to mood disorder, course, and treatment. They found that 20% to 80% of bipolar and 80% of epileptic patients experience psychosensory phenomena. Although these features do not identify a specific subgroup of mood disorders, their prevalence is highest in schizoaffective bipolar patients. The value of psychosensory features in predicting treatment response or chronicity is unclear.

Humans↗

The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.

BACKGROUND: Cysteine proteases are involved in a variety of cellular processes including cartilage degradation in arthritis, the progression of Alzheimer's disease and cancer invasion: these enzymes are therefore of immense biological importance. Caricain is the most basic of the cysteine proteases found in the latex of Carica papaya. It is a member of the papain superfamily and is homologous to other plant and animal cysteine proteases. Caricain is naturally expressed as an inactive zymogen called procaricain. The inactive form of the protease contains an inhibitory proregion which consists of an additional 106 N-terminal amino acids; the proregion is removed upon activation. RESULTS: The crystal structure of procaricain has been refined to 3.2 A resolution; the final model consists of three non-crystallographically related molecules. The proregion of caricain forms a separate globular domain which binds to the C-terminal domain of mature caricain. The proregion also contains an extended polypeptide chain which runs through the substrate-binding cleft, in the opposite direction to that of the substrate, and connects to the N terminus of the mature region. The mature region does not undergo any conformational change on activation. CONCLUSIONS: We conclude that the rate-limiting step in the in vitro activation of procaricain is the dissociation of the prodomain, which is then followed by proteolytic cleavage of the extended polypeptide chain of the proregion. The prodomain provides a stable scaffold which may facilitate the folding of the C-terminal lobe of procaricain.

Amino Acid Chloromethyl Ketones↗

Crystal structure of a caricain D158E mutant in complex with E-64.

The structure of the D158E mutant of caricain (previously known as papaya protease omega) in complex with E-64 has been determined at 2.0 A resolution (overall R factor 19.3%). The structure reveals that the substituted glutamate makes the same pattern of hydrogen bonds as the aspartate in native caricain. This was not anticipated since in the native structure there is insufficient room to accommodate the glutamate side chain. The glutamate is accommodated in the mutant by a local expansion of the structure demonstrating that small structural changes are responsible for the change in activity.

Crystallography, X-Ray↗

Autocatalytic processing of pro-papaya proteinase IV is prevented by crowding of the active-site cleft.

The DNA coding for pro-papaya proteinase IV (PPIV) has been cloned and expressed in Escherichia coli. Heterologous expression of the protein, followed by refolding in vitro, yields an enzymatically active pro-enzyme which fails to autodigest to form the mature protein. Mutagenesis of the active site of papain to simulate that of PPIV yields a proenzyme which also fails to autoactivate. Complementary mutagenesis of the pro-region/mature boundary of PPIV, to introduce its own substrate recognition sequence, has, however, produced a pro-enzyme that will autocatalytically cleave. This is the first report of enzymatic activity in a recombinant pro-cysteine proteinase, and the first time that such a protein has been shown to fail to autocatalytically cleave because of its stringent substrate specificity.

Amino Acid Sequence↗

Brace-free rehabilitation, with early return to activity, for knees reconstructed with a double-looped semitendinosus and gracilis graft.

Forty-one patients in whom operative reconstruction of a torn anterior cruciate ligament had been performed by one surgeon with use of a double-looped semitendinosus and gracilis hamstring graft were studied to determine (1) if a brace-free rehabilitation program compromised the early stability of the knee; (2) if the stability of the knee deteriorated between four months, when the patient returned to unrestricted activities, and two years; and (3) if the function of the treated knee was completely restored by four months after the operation. The graft was placed arthroscopically, without impingement by the intercondylar roof, and was fixed within the tibial tunnel to conserve the length of the graft. The stability and function of thirty-seven of the knees were assessed at four months as part of a larger prospective study. Four patients chose not to return for the four-month evaluation. The patients returned to unrestricted sports and work activities after the four-month evaluation. At two years, all forty-one patients were evaluated. At four months, after completion of the brace-free rehabilitation program, thirty-three (82 per cent) of the thirty-seven patients had an absent pivot shift and a normal Lachman test. Twenty-eight (88 per cent) of thirty-four knees had less than three millimeters of difference in laxity compared with the contralateral knee, as determined by testing at the maximum manual force with use of a KT-1000 arthrometer. Stability remained unchanged at two years, justifying the early return to vigorous activities at four months. The girth of the thigh, the extension of the knee, and the Lysholm and Gillquist score were the same at four months as at two years, verifying the success of the brace-free intensive rehabilitation program in the restoration of early function to the treated knee. However, some continued improvement was observed in the performance of the one-leg-hop for distance test between four months and two years.

Activities of Daily Living↗

The characterization of liposomal glucose oxidase electrodes for the measurement of glucose.

Many biosensors have been described for the measurement of glucose in order to monitor diabetic patients. Glucose oxidase has been used commonly in the construction of glucose sensors but the performance of this enzyme is limited by enzyme saturation kinetics, which restrict the measurement of clinically relevant glucose concentrations (0 to 25 mM). Diffusion limiting membranes have been described that result in the exposure of the enzyme to lower concentrations of glucose than are present in the bulk test solution. Recently a liposomal enzyme electrode was reported whereby glucose oxidase was encapsulated within liposomes so that the lipid bilayer was the diffusion limiting membrane. It was shown that the electrode response was defined by the lipid constituents of the liposome, and that a linear response to glucose could be achieved up to 40 mM. This paper describes research undertaken to improve the methods of production of a liposomal enzyme electrode. Improved immobilization of liposomes is demonstrated with the use of poly-L-lysine solution. The variation in electrode response with respect to the amount of glucose oxidase liposomally encapsulated is reported. The new method allows a greater number of sensors to be produced from a single batch of liposomes. Studies also show the biofouling effects of the lipid constituents of ruptured liposomes on the response of the electrode to glucose over time.

Biosensing Techniques↗

Predictors of planned retirement age: an application of Beehr's model.

Given the aging workforce, understanding the retirement process is an area of increasing interest to organizations. T. A. Beehr's (1986) model of retirement behavior was used in this study as a basis for selecting personal, psychological, and organizational predictors of subsequent planned retirement age. In addition, potential differences in predictors of the planned retirement age of retirement-eligible and retirement-ineligible respondents were explored. Two hundred sixty-four respondents working for a large multinational firm completed 2 surveys on their attitudes toward work and retirement. Results showed that chronological age, employee health, and self-perceptions of the ability to adjust to retirement predicted subsequent planned retirement age. Interactions of the predictors with retirement eligibility are reported along with implications for retirement-planning programs.

Adaptation, Psychological↗