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Biomedical subjects

A M Smith

Publications and source records attributed to A M Smith.

At least 235 records · Page 13Linked to original sources
PubMed1994

A dipeptidylpeptidase secreted by Fasciola hepatica.

A dipeptidylpeptidase (DPP) was isolated from Fasciola hepatica by gel-filtration and ion-exchange chromatography. The exoproteinase is secreted by newly excysted juveniles, immature and mature flukes. The liver fluke DPP is a serine proteinase of molecular weight > 200 kDa and differs from previously characterized mammalian DPPs in its substrate preference and susceptibility to inactivation by inhibitors. The parasite DPP may function in the latter stages of the proteolytic digestion of host macromolecules. In this manner, the enzyme may be important in providing the parasite with dipeptides that could be absorbed through the intestine as nutrient.

Animals↗
PubMed1994

Palliative medicine education for medical students: a survey of British medical schools, 1992.

The new specialty of palliative medicine is now recognized as making a significant contribution, not only to the practice of cancer medicine, but also to the care of terminal disease. This article reports an enquiry into the current teaching of palliative medicine in undergraduate curricula in Britain. A questionnaire concerning palliative medicine teaching was sent in December 1992 to undergraduate deans of all medical schools, colleges and faculties (hereafter referred to as schools). Replies were received from all and were analysed. Most of the subjects represented by palliative medicine were taught in all schools by palliative medicine specialists or in sessions of other specialisms, or both. Many schools gave opportunity for students to visit local palliative care units or hospices; a few required it as part of the syllabus. The amount of time devoted to this subject in the curricula varied considerably. Eleven per cent of schools regularly asked questions on palliative medicine in final examinations; half occasionally did so, but 30% reported that there was never a question on palliative medicine in finals. In the light of recent publications by the General Medical Council and the Standing Medical Advisory Committee and Standing Nursing and Midwifery Advisory Committee, I urge that increasing attention be paid to teaching the subjects represented by palliative medicine and to examining it. I suggest that the recently published core curriculum will enable this to be carried out more effectively.

Curriculum↗
PubMed1994

Neutralization of the activity of a Fasciola hepatica cathepsin L proteinase by anti-cathepsin L antibodies.

Fasciola hepatica secretes a cathepsin L proteinase that is suggested to play an in vivo role in immunoprotection since the enzyme can cleave host immunoglobulin. In the present report, rabbit anti-cathepsin L IgG was shown to bind to the cathepsin L enzyme and inhibit its ability to cleave IgG molecules. Cathepsin L can prevent the antibody-mediated attachment of eosinophils to newly excysted juveniles in in vitro assays; however, if anti-cathepsin L IgG are mixed with the cathepsin L prior to the addition of the enzyme to the assay, eosinophils attach to the newly excysted juveniles. Thus it is possible to prepare antibodies that can bind and disrupt the biological activity of the F. hepatica cathepsin L.

Animals↗
PubMed1994

Some shear facts and pure friction related to roughness discrimination and the cutaneous control of grasping.

The question of whether friction contributes to the perception of roughness has been overdebated and underinvestigated. A review of the psychophysical literature suggests that roughness and friction can be subjectively distinguished very effectively, although the same rapidly adapting Meissner corpuscles (RA1s) and slowly adapting Merkel receptors (SA1s) are stimulated by both stimuli. It appears that to achieve the subjective appreciation of roughness, the brain must learn to ignore variations in the speed of movement over the skin, the perpendicular force applied to the receptor surface, and the shear forces tangential to the skin generated by friction. Similarly, the subjective appreciation of slipperiness requires selective attention to tangential forces to the exclusion of speed, perpendicular force, and surface texture. A clearer picture is gradually emerging concerning the detection and appreciation of shear forces from investigations of the grasping and lifting of objects of different surfaces against the force of gravity. Although high shear forces provoke larger responses in almost all skin mechano-receptors, some neurons in both the sensory and motor cortex discharge more vigorously with smooth textures and lower coefficients of friction. Although populations of such neurons sensitive to smooth surfaces and low friction would be very useful in detecting both potential and real slips, just how the afferent signals are derived remains puzzling.

Discrimination Learning↗
PubMed1994

Palliative care services in Britain and Ireland--update 1991.

The objective of this study was to repeat part of a survey carried out the previous year and to describe and quantify the hospice and palliative care inpatient units throughout Great Britain and Ireland for the year 1991, this also to include a survey of palliative care day centres and hospital support services. Questionnaires were sent to 346 hospice and palliative care services in Great Britain and Ireland. Replies were analysed by the Hospice Information Service. A total of 293 replies were received (84% response). The report details bed usage, length of stay and admissions, deaths and discharges in inpatients units. It also describes provision of day centre places and types of services offered. An initial assessment is made of the different types of hospital palliative care support services available. An estimate of the number of patients receiving palliative care in inpatient units and in day care centres is made.

Day Care, Medical↗
PubMed1994

Divergent dimerization properties of mutant beta 1 thyroid hormone receptors are associated with different dominant negative activities.

Syndromes of resistance to thyroid hormones are caused by mutations in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene. The S receptor (deletion of THR332) is a potent dominant negative protein cloned from a kindred with generalized resistance to thyroid hormones. The G-H receptor (ARG311HIS) has compromised dominant negative function and was found in both normal individuals and in a patient with severe pituitary resistance to thyroid hormones. We have investigated the mechanism responsible for the difference in receptor phenotypes by analyzing the binding of S and G-H receptors to thyroid hormone response elements with electrophoretic mobility shift analysis. Wild-type human c-erbA beta 1 (WT), S, and G-H receptors were synthesized in reticulocyte lysate, reacted with a thyroid hormone response element consisting of a direct repeat with 4 base pairs (DR+4; AGGTCA CAGG AGGTCA), and the products analyzed by gel shift. G-H receptor homodimerization was greatly impaired; G-H formed predominantly monomeric complex compared with monomeric and homodimeric WT complexes. The G-H receptor was able to form heterodimeric complexes with cellular thyroid hormone receptor auxiliary protein (TRAP) factors including the human retinoid X receptor-alpha. When TRAP was limiting, the levels of G-H heterodimeric complex were 2- to 3-fold reduced compared with WT receptor. In contrast to the WT and G-H receptors, the S receptor formed almost exclusively homodimeric complex with DR+4; the approximate ratio of S:WT:G-H homodimeric complexes at equivalent concentrations of receptors was 60:20:1. A measurable increase (1.2- to 2.6-fold) in heterodimeric complex formation was observed with the S receptor relative to WT when TRAP was at limiting concentration. As reported previously by others, thyroid hormone significantly reduced the WT homodimeric complex with DR+4. There was no effect on the S homodimeric complex. Finally, the WT, S, and G-H receptors formed different complexes with the element consisting of an inverted repeat with 5 base pairs (IR+5; AGGTCA ACAGT TGACCT) and the IR element (AGGTCA TGACCT), which were differently regulated by thyroid hormone. The S receptor bound as a homodimer with IR+5, whereas the WT receptor bound as a homodimer only with thyroid hormone. No homodimeric complex formed with IR+5 and the G-H receptor. Qualitatively similar results were observed with the IR element. We conclude that the ARG311HIS mutation severely perturbs the homodimerization and, to a much less degree, heterodimerization functions of the c-erbA beta 1 receptor. Furthermore, the THR332 deletion mutation augments homodimerization of the c-erbA beta 1 receptor. These results indicate that different mutations in the c-erbA beta 1 thyroid hormone receptor have divergently affected dimerization activities which seem to influence the level of dominant negative activity in man.

Amino Acid Sequence↗
PubMed1994

Sexuality and the menopause.

Sexual problems are often reported to clinicians by women in the midlife years. Yet few of the epidemiological studies of women in midlife have investigated the relationship of the menopause to sexual functioning. This paper reports the results of a cross-sectional telephone survey of 2001 randomly selected Australian-born women aged between 45 and 55 years. The major outcome variables were questions relating to changes in sexual interest over the prior 12 months, reasons for any changes, occurrence of sexual intercourse, and of unusual pain on intercourse. Logistic regression was used to identify explanatory variables for change in sexual interest. The majority of women (62%) reported no change in sexual interest, although 31% reported a decrease. Decline in sexual interest was significantly and adversely associated with natural menopause (p < 0.01) rather than age, decreased well-being (p < 0.001), decreasing employment (p < 0.01) and symptomatology (vasomotor p < 0.05, cardiopulmonary p < 0.001 and skeletal p < 0.01). Eleven to twelve years of education was associated with a lowered risk of decreased sexual functioning (p < 0.01). Heterogeneous results were reported by users of hormone replacement therapies. Longitudinal studies of large and representative samples are needed to determine the etiology of adverse sexual changes with the menopause and the role of hormone replacement therapies.

Adaptation, Psychological↗
PubMed1994

Injured athletes and the risk of suicide.

Research on the emotional responses of athletes to injury shows significant depression that may be profound and may last a month or more, paralleling the athlete's perceived recovery. Injured athletes cared for by athletic trainers are often between the ages of 15 to 24, the high-risk age group for suicide, which is currently a leading cause of death for young Americans. The purposes of this paper are to discuss postinjury depression, the incidence and risk factors of suicide, athletic injury as a psychosocial risk factor, the features common to suicide attempts in case studies of five injured athletes, and the motivation of athletes for sport participation. We also suggest ways in which athletic trainers can assess injured athletes for depression and risk of suicide. The five injured athletes who attempted suicide shared several common factors. All had experienced 1) considerable success before sustaining injury; 2) a serious injury requiring surgery; 3) a long, arduous rehabilitation with restriction from their preferred sport; 4) a lack of preinjury competence on return to sport; and 5) being replaced in their positions by teammates. Also, all were in the highrisk age group for suicide. As a primary care provider, the certified athletic trainer is in an ideal position to detect serious postinjury depression and to determine whether the injured athlete is at risk for suicide.

Journal Article↗
PubMed1994

Emergencies in palliative care.

Five groups of events are here considered as emergencies in palliative care: haemorrhage, convulsions, fractures, spinal cord compression and acute confusion. Incidence, causes and management of these form the major part of this article. Emergencies in palliative care also include sudden severe exacerbation of symptoms. Therefore, onset of severe pain, exacerbation of breathlessness, and worsening of other symptoms are also discussed with their appropriate treatment. A small armamentarium of appropriate medications is thus shown to cover treatment of the various emergencies that may arise. As palliative care deals with patients who are suffering from progressive fatal conditions, death is the expected end. Nevertheless, however well the family are prepared, death often appears for them as an emergency. Comment is made regarding this family emergency in the care of terminally ill people. Attention in this article is focussed on medical treatment. In the care of the emergency event, however, and in all palliative care, management includes making the patient comfortable, thinking of the needs of other patients and relatives observing the event, explaining what is happening and is being done, involving other members of the team, and communicating reassurance to the patient and the relatives as well as to other observers.

Acute Disease↗
PubMed1994

Kinetic modeling of teboroxime using dynamic SPECT imaging of a canine model.

UNLABELLED: The tomographic utility of 99mTc-labeled teboroxime has been limited because of its fast washout from the heart, which requires rapid data acquisitions that have not been feasible until the recent development of multidetector SPECT systems. METHODS: Using a three-detector SPECT system to acquire dynamic tomographic data every 10.2 sec, we investigated the potential of modeling the kinetics of teboroxime to develop a sensitive and quantitative measure of cardiac perfusion. Seven studies were performed on four dogs; in three of the studies the LAD artery was occluded. The three-dimensional activity distributions were reconstructed and were corrected for attenuation using a transmission scan. Time-activity curves from the blood and tissue were fit to a two-compartment model with two-way exchange. RESULTS: Performing attenuation correction during the reconstruction process affected the washin parameter k21 significantly (p < 0.0001). The washin parameter k21 also decreased significantly (p < 0.002) when the LAD was occluded. CONCLUSIONS: The results indicate that the washin of teboroxime in myocardial tissue (k21) measured using dynamic SPECT imaging and kinetic modeling is an indicator of myocardial blood flow.

Algorithms↗
PubMed1993

Menopausal symptoms in Australian women.

OBJECTIVES: To describe Australian-born women's experience of symptoms during the natural menopause transition and the relative contribution of menopausal and health status, social factors and lifestyle behaviours. DESIGN: A community based cross-sectional survey by telephone interview was carried out on a randomly derived sample of Melbourne women. PARTICIPANTS: The participants were 2000 Australian-born women, aged between 45 and 55 years. OUTCOME MEASURES: A list of 22 symptoms was used. Explanatory variables were: sociodemographic variables; menopausal and health status; lifestyle behaviours; attitudes to ageing and to menopause. RESULTS: A 70% response rate was achieved for eligible women who could be contacted during the study. Premenopausal women were the least symptomatic and perimenopausal women the most symptomatic. Factor analysis found seven common factors from the 22 symptoms studied. Menopausal status based on menstrual history was significantly related to two groups of symptoms: vasomotor symptoms, which increased through the menopausal transition; and general somatic symptoms which were more frequent in the perimenopause. Analysis of variance of factor scores found fewer symptoms with increasing years of education, better self-rated health, the use of fewer non-prescription medications, the absence of chronic health conditions, a low level of interpersonal stress, the absence of premenstrual complaints, not currently smoking, exercise at least once a week, and positive attitudes to ageing and menopause. CONCLUSIONS: Many factors unrelated to hormonal changes contributed to the symptoms. Longitudinal investigation is needed to determine the relative importance of hormonal, psychosocial and lifestyle variables in the aetiology of mid-life symptoms.

Attitude↗
PubMed1993

Potent HIV protease inhibitors: the development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands.

A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R)-tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S)-tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1.

Antiviral Agents↗
PubMed1993

Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogues.

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.

Antiviral Agents↗
PubMed1993

Monoclonal antibodies identifying subsets of ectodermal, mesodermal, and endodermal cells in gastrulating and neurulating avian embryos.

The goal of our laboratory research is to elucidate the mechanisms underlying gastrulation and neurulation, using the avian embryo as a model system. In previous studies, we used two approaches to map the morphogenetic movements involved in these processes: (1) we constructed quail/chick transplantation chimeras in which grafted quail cells could be identified within chick host embryos by the presence of nucleolar-associated heterochromatin, and (2) we microinjected exogenous cell markers. However, it would be advantageous to be able to detect endogenous markers to demarcate various subsets of cells within the unmanipulated embryo. To elucidate such a series of natural markers, we have used monoclonal antibodies to identify epitopes found on subsets of ectodermal, mesodermal, and endodermal cells. Antibodies were made by immunizing mice against either homogenized ectoderm (i.e., prospective neural plate and surface ectoderm) or primitive streak, which had been microdissected from stage 3 chick embryos. Additionally, we screened a panel of antibodies made against soluble protein obtained from isolates of cell nuclei from late embryonic chick brain. Here, we describe the labeling patterns of three monoclonal antibodies, called MAb-GL1, GL2, and GL3 (GL, germ layer), during avian gastrulation and neurulation. Our results show that labeling early avian embryos with monoclonal antibodies can reveal previously undetected distributions of cells bearing shared epitopes, providing new labels for subsets of cells in each of the three primary germ layers.

Animals↗
PubMed1993

SLAP lesions of the glenoid labrum diagnosed with MR imaging.

Tears of the superior portion of the glenoid labrum in patients without shoulder instability have recently been described. These tears, which include the "anchor" of the biceps tendon to the labrum, have been labeled "SLAP lesions" (superior labrum anterior to posterior). This study was performed to determine the magnetic resonance (MR) findings in patients with SLAP lesions. Retrospective review of the shoulder arthroscopy reports on patients who underwent MR imaging using a 1.5-T unit and subsequent arthroscopy by a single surgeon identified six patients with SLAP lesions (average age 36 years, range 17-65 years). MR images demonstrated atypical morphology indicative of tear in the superior portion of the labrum in four of the six patients, but only one tear had been identified preoperatively. Radiologists interpreting MR images of the shoulder should be aware of the MR findings of SLAP lesions as these tears can be a significant cause of patient disability and are difficult to diagnose clinically.

Adolescent↗
PubMed1993

Fasciola hepatica: a secreted cathepsin L-like proteinase cleaves host immunoglobulin.

Adult Fasciola hepatica secrete a cysteine proteinase capable of cleaving host IgG close to the papain cleaving site. The proteinase was separated by size permeation chromatography. Gelatin-substrate polyacrylamide gel electrophoresis analysis revealed that the proteinase migrates as 6 proteolytic bands in the apparent molecular size range 60-90 kDa. Based on pH profiles of activity, inhibition studies using diethylpyrocarbonate and the diazomethylketone Z-phe-ala-CHN2, and characterising the substrate specificity of the enzymes using fluorogenic peptide substrates we have shown that the 60-90-kDa proteinases are cathepsin L-like proteinases.

Animals↗