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Biomedical subjects

A M Smith

Publications and source records attributed to A M Smith.

At least 325 records · Page 18Linked to original sources
PubMed1987

Optical biosensors for immunoassays: the fluorescence capillary-fill device.

This paper reports, for the first time, details of a novel type of optical biosensor for immunoassays, the fluorescence capillary-fill device (FCFD). This is based on a straightforward adaptation of the technology used to mass manufacture liquid-crystal display (LCD) cells to give cheap disposable immunosensors. These merely require contact by the sample to give a result in about a minute, and use certain principles of optical fibres and waveguides to avoid the need for operator attention, for physical separation methods or for washing steps. After a very brief introductory review and classification of optical biosensors, the main features of the FCFD and its associated instrumentation are described. The optical characteristics of the FCFD are then described, followed by accounts of the immunoassay method, the measurement system used in the experiments, the fabrication of FCFD sensors and a detailed description of the design of a competitive immunoassay for human immunoglobulin G (hIgG). The experimental details and the results of a first attempt at such an assay are then presented and discussed. It is concluded that the demonstration of this assay is a significant achievement, because the format of the FCFD, its manufacturing process and its instrumentation are completely novel. Certain problem areas have been identified and quantified; intended further work on these is outlined.

Animals↗
PubMed1987

Locomotor deficits in the mutant mouse, Lurcher.

The effect of total Purkinje cell degeneration on treadmill locomotion was studied in the cerebellar mutant mouse Lurcher. Other movements such as swimming and scratching were also studied in order to evaluate the cerebellar control of rhythmic actions. Cinematographic and electromyographic recordings were taken from normal and Lurcher mice that were subsequently perfused to obtain a Purkinje cell count. Walking deteriorated progressively and was clearly abnormal in 30 day old Lurchers with 90% Purkinje cell degeneration. In adult Lurcher mice in which Purkinje cells were totally absent, walking was characterized by short steps with exaggerated hindlimb flexion in the swing phase. Also, both the interlimb step ratio, defined as the step length of the reference limb divided by the step length of the opposite limb, and the interlimb coupling, defined as the temporal relation of one footfall with respect to the footfall of another limb, varied more than in normal mice. Furthermore, the locomotion of Lurcher mice displayed increased vertical displacement of the hip and an inability to produce continuous step cycles without stumbling. Both the EMG onset relative to foot contact and the EMG burst duration were highly variable, and a greater overlap in the activities of antagonist muscles at the transition from ankle extension to flexion was evident. Although both walking and swimming involve cyclical limb movements, the disorganization of the cycle and the irregular EMG pattern seen in the Lurcher during walking were not observed during swimming. Furthermore, scratching was well executed in the Lurcher mice. However, a consistently higher tonic extensor activity at the ankle appeared during walking, swimming and scratching. These results suggest that, in contrast to swimming and scratching, the requirements of walking depend to a greater degree on a functional cerebellar cortex for successful performance.

Age Factors↗
PubMed1987

Relative bioavailability of seleno-compounds in the lactating rat.

Bioavailability of the organic forms of selenium (Se), selenomethionine (Se-methionine) and Se-yeast was determined relative to that of an inorganic form, selenite, in the lactating rat. A purified, casein-based diet without added Se was fed to nine groups of rats throughout pregnancy to produce a marginal Se deficiency. During lactation, groups (n = 8) were fed experimental diets containing either 0.1, 0.25 or 0.5 ppm Se as selenite, Se-methionine, or Se-yeast. On d 18 of lactation, tissue Se and glutathione peroxidase (GSH-Px) activities of dams and pups were determined. Based on slope-ratio analyses, the bioavailability of Se-methionine and Se-yeast was greater than that of selenite in both lactating dams and their nursing pups. The greater availability of organic Se to pup tissues may be a direct result of the greater concentration of Se in the milk of dams fed organic Se. A dietary level of 0.25 ppm Se as Se-methionine ensured maximal GSH-Px activity in both dam and pup tissues, but 0.5 ppm Se was necessary when selenite or Se-yeast was fed. These results indicate that, regardless of form, the National Research Council recommendation for growing rats of 0.1 ppm Se is not adequate to replete lactating dams and maintain maximal tissue GSH-Px in nursing pups.

Animals↗
PubMed1987

Hereditary angioedema and thyroid autoimmunity.

Sera from 91 patients with hereditary angioedema were screened for thyroid antibodies. The results for the 77 patients more than 17 years old were compared with previously published data for the prevalence of thyroid disease in a large community (Whickham). Of the female patients with hereditary angioedema, the prevalence of thyroglobulin antibodies (TGA) was 14.0%, higher than the expected 3% (p less than 0.001). The prevalence of thyroid microsomal antibodies (TMA) was 20%, also higher than the expected 7.6% (p less than 0.01). The age distributions of the females in both groups differed: in the group with hereditary angioedema there was a greater proportion of younger patients which should have resulted in a lower prevalence of thyroid antibodies. Adjusting for related patients with hereditary angioedema, there was still an increased prevalence of TGA (p less than 0.01) and TMA (p less than 0.01).

Adolescent↗
PubMed1987

Is there more dementia, depression and neurosis in New York? A comparative study of the elderly in New York and London using the computer diagnosis AGECAT.

A computerised diagnosis, AGECAT, is applied to data from random community samples of the elderly in New York and London in order to examine the prevalence of mental illness in the two cities, especially the result reported from the same study, using a different diagnostic procedure, that the proportion of dementia was higher in New York. The greater proportion of dementia in New York is confirmed for all AGECAT's levels of diagnostic confidence, for both sexes and at all half-decades over 65 years. Provided that this difference is upheld and genetic differences can be discounted, these findings would seem to support a contributory environmental cause for dementia. Proportions of depression as a whole are similar in both cities. Syndrome case and sub-case levels of neurotic disorder are generally higher in London.

Aged↗
PubMed1986

Spontaneous alternation and habituation in lurcher mutant mice.

There is a spontaneous degeneration of Purkinje cells, granule cells and inferior olivary neurons in lurcher mutant mice. It was found that, in comparison to littermate controls, the lurcher mutants alternated less often in a discrete two-trial procedure of spontaneous alternation and did not habituate to maze stimuli in a T-maze. Results are discussed in terms of a possible role for the cerebellum in spatial learning.

Animals↗
PubMed1986

Surgical biopsy for persistent generalized lymphadenopathy.

Lymph node biopsy was performed in 39 homosexual men with unexplained persistent generalized lymphadenopathy (PGL). Thirty-seven (95 per cent) of these patients had antibodies to human T-lymphotropic virus type III (HTLV-III), at the time of biopsy. Histology in all but one showed only follicular hyperplasia, the exception showed caseating granulomata typical of tuberculosis. Clinical differentiation between lymphadenopathy associated with HTLV-III and other causes of generalized lymphadenopathy is difficult; however, the presence of antibodies to HTLV-III probably identifies patients in whom surgical biopsy will only occasionally reveal a specific histological diagnosis. It is suggested that the presence of antibodies to HTLV-III in patients with PGL justifies a more selective approach to lymph node biopsy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Production of cobalt-55, a short-lived, positron emitting radiolabel for bleomycin.

The production and radiochemical separation of 55Co from deuteron irradiation of enriched 54Fe target is described. Methods used for the recovery and reuse of the target material (54Fe) are also described. The yield of 55Co at 12 MeV incident deuteron energy is 1.7 mCi per mu Ah at end of bombardment and the contamination with 57Co is 0.016%. The 55Co produced is chelated to bleomycin and used for tumour imaging with a positron emission tomographic camera based on multi-wire proportional chamber detectors.

Bleomycin↗
PubMed1986

Rapid isolation of monoclonal antibodies specific for cell surface differentiation antigens.

Two immunization procedures were compared for their ability to yield monoclonal antibodies that react with plasma membrane-bound differentiation antigens of Dictyostelium. In the first method, hybridomas prepared from BALB/c mice immunized with aggregating amoebae produced monoclonal antibodies that recognized antigens present on both growing and aggregating Dictyostelium amoebae. None of the monoclonal antibodies reacted with only the injected aggregation-stage cell type. In contrast, monoclonal antibodies that reacted with differentiation antigens were easily obtained by primary immunization of BALB/c mice with living aggregation-stage cells, followed by secondary immunization with a preparation of plasma membrane from aggregating cells or intact aggregating cells mixed with polyclonal BALB/c antiserum raised against undifferentiated cells. By this method, approximately 20% of all anti-Dictyostelium monoclonal antibodies obtained in a fusion are specific for differentiation antigens. The properties and developmental regulation of several of these antigens are described. The possible uses of this immunological method to detect unique determinants on other kinds of cells and the likely immune mechanisms that make it successful are discussed.

Animals↗
PubMed1986

Evidence for increased selenium requirement for the rat during pregnancy and lactation.

Adequacy of the National Research Council (NRC) selenium (Se) requirement for growth (0.1 ppm Se) was assessed in reproducing Sprague-Dawley rats. Either a casein-based diet with no added Se or the same diet supplemented with selenite to contain 0.05, 0.1, or 0.2 ppm Se was fed during pregnancy and lactation and to nonreproducing controls. Only 0.05 ppm Se was necessary to maintain maximal red blood cell (RBC) and liver Se concentrations and glutathione peroxidase (GSH-Px) activities in controls, whereas 0.2 ppm Se was necessary to maintain comparable RBC Se during pregnancy and tissue Se and GSH-Px activities during lactation. On d 2 of lactation, no differences in pup tissue Se or GSH-Px activities could consistently be related to maternal Se intake. By d 18 of lactation, however, Se status of nursing pups reflected maternal Se intake. Pups of dams fed 0.2 ppm Se had tissue Se and GSH-PX activities significantly greater than those of all other pups. Milk Se content correlated significantly with maternal Se intake and plasma Se and with pup tissue Se and GSH-Px activities. These results indicate that during reproduction 0.1 ppm Se is not adequate to maintain maternal tissue Se or GSH-Px activities comparable to those of normal controls; 0.2 ppm dietary Se is more appropriate, resulting in maternal GSH-PX activities similar to those of controls fed 0.1 ppm Se and milk Se concentrations that result in greater pup tissue GSH-Px activities.

Animals↗
PubMed1986

Intravenous acebutolol raises serum potassium in acute myocardial infarction.

Hypokalaemia commonly occurs in acute myocardial infarction (AMI) and may be caused by elevated serum levels of adrenaline, allegedly by beta 2-adrenergic mediated influx of potassium (K) into cells. We investigated the effect on serum K of intravenous acebutolol (a relatively beta 1-selective agent) in 50 patients with AMI. Serum K was measured before and 1 hour after drug administration. The same measurements were made in a comparable control group of 30 patients who did not receive the drug. Mean serum K rose from 3.58 to 3.81 mEq/l (P less than 0.005) in the treated group. No significant change occurred in the control group. The rise in serum K could not be correlated with prior beta-blocker therapy, zone of infarction, prior diuretic therapy, or gender of the patient. We conclude that the administration of intravenous acebutolol after AMI raises serum K, despite the fact that this beta receptor blocking agent is relatively beta 1-selective. Since hypokalaemia is associated with an increased risk of ventricular fibrillation, it should no longer be assumed from acute intervention trials with beta-blockers in AMI which had mortality or arrhythmias as end-points, that beneficial effects were necessarily due to limitation of infarct size or to a direct anti-arrhythmic action of the drugs. Future trials should take the effect on serum K levels into consideration.

Acebutolol↗
PubMed1986

Identification and analysis of the regulation of a prestalk cell-surface antigen of Dictyostelium discoideum.

The properties of two differentiation antigens, rsa 4.2 and rsa 3.1, were examined. Both appear on the cell surface early in differentiation, but they differ with respect to their cell-type specificity. rsa 4.2 appears 1-2 h after differentiation has begun and is present on all cells during all stages of differentiation. In contrast, rsa 3.1 appears after 1-2 h on all aggregating amebae and later becomes restricted to prestalk cells. The pattern of regulation of rsa 3.1 indicates that this prestalk antigen appears on all cells early in differentiation but disappears in cells that differentiate along the prespore pathway. As a result, only cells in the anterior of migrating slugs carry this antigen. Predictions of two competing models of Dictyostelium pattern formation, i.e., position-dependent differentiation and random, position-independent differentiation, were tested by flow cytometry and immunochemical staining of sections of cells at the mound and mound-with-tip stages. Our results do not rule out either model, although they are incompatible with the simplest interpretation of the model for position-independent differentiation. The results clearly indicate that cells that ultimately differentiate along the spore pathway pass through an earlier cell state that includes the presence of a prestalk cell-surface antigen identified as rsa 3.1.

Antibodies, Monoclonal↗
PubMed1986

Cerebellar cortical activity during stretch of antagonist muscles.

Single unit activity was recorded from the anterior lobe of the cerebellum during ramp and hold stretches of limb muscles in chloralose anesthetized cats. The activity of 95 "phasic" units showed a transient response during dynamic stretch of at least one muscle usually lasting for less than 350 ms following the stimulus onset. The activity of 59 phasic-tonic units was modified not only during dynamic stretch but also during the 1 s of maintained muscle length. All Purkinje cells, identified by their complex spikes, that responded to muscle stretch demonstrated exclusively phasic changes in discharge. Fourteen of 25 Purkinje cells (56%) responded to stretch of both antagonist muscles and these responses were always similar rather than reciprocal. From the 129 units without complex spikes, 70 demonstrated phasic discharge patterns whereas 59 had tonic responses. Seventy-five (59%) of these unidentified units revealed convergent responses to stretch of both antagonists, compared with 54 which responded to stretch of one muscle only. Of the unidentified units receiving convergent afferents from antagonist muscles, 62 (83%) had similar responses and only 13 (17%) had reciprocal reactions. There appeared to be no evidence that muscle afferents alone can induce reciprocal discharge patterns in Purkinje neurons of the cerebellar cortex. The firing frequency of some phasic-tonic units was correlated with both the velocity and amplitude of muscle stretch. No Purkinje cells were found with activity related to either velocity or amplitude of muscle stretch. One phasic and seven phasic-tonic unidentified units were activated at fixed latencies following trains of electrical stimulation applied to the thoracic spinal cord at frequencies exceeding 200 Hz, implying they were terminal portions of mossy fibers originating from direct spinocerebellar tracts. A few recordings of compound potentials were presumed to arise from the cerebellar glomeruli. The changing form of one of these potentials suggested that the glomerulus might be a site at which somatosensory peripheral information is modified by the cerebellar cortex.

Action Potentials↗