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Biomedical subjects

S J Smith

Publications and source records attributed to S J Smith.

At least 19 recordsLinked to original sources
PubMed1992

Diverse migratory pathways in the developing cerebral cortex.

During early development of the mammalian cerebral cortex, young neurons migrate outward from the site of their final mitosis in the ventricular zone into the cortical plate, where they form the adult cortex. Time-lapse confocal microscopy was used to observe directly the dynamic behaviors of migrating cells in living slices of developing cortex. The majority of cells migrated along a radial pathway, consistent with the view that cortical neurons migrate along radial glial fibers. A fraction of cells, however, turned within the intermediate zone and migrated orthogonal to the radial fibers. This orthogonal migration may contribute to the tangential dispersion of clonally related cortical neurons.

Animals↗
PubMed1992

Neurally evoked calcium transients in terminal Schwann cells at the neuromuscular junction.

We examined the effects of motor-nerve stimulation on the intracellular Ca2+ levels of Schwann cells, the glial cells at the frog neuromuscular junction. Schwann cells, which were loaded with the fluorescent Ca2+ indicator fluo-3 and examined by confocal microscopy, showed a transient increase in free Ca2+ within a few seconds of the onset of tetanic stimulation of the motor nerve. The Ca2+ response was specific to the synapse in that it was found in the terminal Schwann cells at the junction but not in the myelinating Schwann cells along the axon. The Ca2+ transients occurred in the presence of d-tubocurare, indicating that they were not mediated by nicotinic acetylcholine receptors and recurred when the stimulus was repeated. The Ca2+ response persisted after degeneration of the postsynaptic muscle fiber, demonstrating that the terminal Schwann cell was stimulated directly by presynaptic activity. The finding that terminal Schwann cells at the neuromuscular junction respond to presynaptic activity suggests that glial-cell function is modulated by synaptic transmission.

Animals↗
PubMed1992

Performance characteristics of a composite multivariate quality control system.

We present the results of an evaluation of the performance characteristics of a composite multivariate quality control (CMQC) system that incorporates quality control rules for univariate, multivariate, and correlation conditions. The CMQC system evaluated is designed to help analysts detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure of any pair of variables. It is also designed to be tolerant of missing data, to allow analysts to reject as few as one or as many as all variables in a run, and to provide analysts with control statistics and graphics that logically relate to sources of analytical error. We show that the various components of the CMQC system have adequate statistical power to detect systematic errors, random errors, and correlation changes under the conditions likely to be encountered with multivariate analytical measurement systems: (1) a single variable with increased systematic or random error; (2) all variables or a subgroup of variables affected by a common problem that increases systematic or random error; and (3) missing data for one or more variables in a run. We also show that the power of the multivariate component of the CMQC system to detect systematic and random errors is higher than the power of an alternative multivariate test criterion.

Chemistry Techniques, Analytical↗
PubMed1992

Genetic diagnosis of Gaucher's disease.

The inherited disorder Gaucher's disease can be caused by various mutations in the glucocerebrosidase gene. Some mutations may be associated with greater severity, and there is a need for methods of gene analysis that would facilitate screening and diagnosis. We have studied the molecular basis of Gaucher's disease in twelve unrelated patients of diverse ethnic origin by means of the amplification refractory mutation system (ARMS). Primers for the polymerase chain reaction were designed to discriminate between mutant and wild-type alleles of glucocerebrosidase and to allow separation from products of the related pseudogene. The nucleotide 1226 mutation (asparagine 370----serine) and 84GG (an insertional frameshift mutation) were found exclusively in five patients of Ashkenazi Jewish descent (7 and 2 of the 10 disease alleles, respectively). Two point mutations, at nucleotides 1448 (leucine 444----proline) and 1504 (arginine 463----cysteine), were found in 4 and 3 alleles, respectively; they were associated with rapidly progressive disease and neurological involvement in non-Jewish patients. The ARMS procedure for direct detection of common mutations in glucocerebrosidase will facilitate genetic counselling and screening programmes for individuals at risk of Gaucher's disease.

Adolescent↗
PubMed1992

Blood lipid measurements. Variations and practical utility.

OBJECTIVE: To describe the magnitude and impact of the major biological and analytical sources of variation in serum lipid and lipoprotein levels on risk of coronary heart disease; to present a way to qualitatively estimate the total intraindividual variation; and to demonstrate how to determine the number of specimens required to estimate, with 95% confidence, the "true" underlying total cholesterol value in the serum of a patient. DATA SOURCES: Representative references on each source of variation were selected from more than 300 reviewed publications, most published within the past 5 years, to document current findings and concepts. Most articles reviewed were in English. STUDY SELECTIONS: Studies on biological sources of variation were selected using the following criteria: representative of published findings, clear statement of either significant or insignificant results, and acquisition of clinical and laboratory data under standardized conditions. Representative results for special populations such as women and children are reported when results differ from those of adult men. DATA EXTRACTION: References were selected based on acceptable experimental design and use of standardized laboratory lipid measurements. DATA SYNTHESIS: The lipid levels considered representative for a selected source of variation arose from quantitative measurements by a suitably standardized laboratory. Statistical analysis of data was examined to assure reliability. The proposed method of estimating the biological coefficient of variation must be considered to give qualitative results, because only two or three serial specimens are collected in most cases for the estimation. CONCLUSIONS: Concern has arisen about the magnitude, impact, and interpretation of preanalytical as well as analytical sources of variation on reported results of lipid measurements of an individual. Preanalytical sources of variation from behavioral, clinical, and sampling sources constitute about 60% of the total variation in a reported lipid measurement of an individual. A technique is presented to allow physicians to qualitatively estimate the intraindividual biological variation of a patient from the results of two or more specimens reported from a standardized laboratory and to determine whether additional specimens are needed to meet the National Cholesterol Education Program recommendation that the intraindividual serum total cholesterol coefficient of variation not exceed 5.0. A National Reference Method Network has been established to help solve analytical problems.

Analysis of Variance↗
PubMed1992

Comparison of lymphocyte immunophenotypes obtained simultaneously from two different data acquisition and analysis systems on the same flow cytometer.

Immunophenotyping of different lymphocyte populations was carried out in parallel on 113 consecutively received specimens of human peripheral blood using 2 different data acquisition and analysis systems (EPICS C and 4Cyte-Acmecyte) on the same flow cytometer (EPICS C). The phenotypes analyzed were CD3+, CD4+, CD8+ CD56+ CD16+ CD3-, TCR-gamma delta+ CD8-, and TCR-gamma delta+ CD8+. Both HIV- and HIV+ specimens were used for this study, including some with CD4 levels as low as 2% of all lymphocytes. Despite differences in gating procedures and shapes of bitmap (rectilinear vs. "amorphous"), the 2 methods agreed to within 2% positive cells in 97% of the cases. Although some statistically significant biases in the methods were observed, these were small and not biologically important. We conclude that both methods of data acquisition and analysis, as employed by experienced operators on the EPICS C flow cytometer, gave essentially equivalent results for lymphocyte sub-populations in peripheral blood preparations.

Electronic Data Processing↗
PubMed1992

Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy?

The sex ratio, age at onset, and ictal features of nine patients with nocturnal paroxysmal dystonia were compared with those of eight patients with daytime frontal lobe seizures and eight patients with nocturnal motor attacks of known epileptic origin. All patients underwent video electroencephalography telemetry. There were no clinical features that would allow distinction between the groups and no single phenomenon was uniquely seen in nocturnal paroxysmal dystonia. This study provides no evidence that nocturnal paroxysmal dystonia is a separate diagnostic entity.

Adolescent↗
PubMed1992

A real-time analysis of growth cone-target cell interactions during the formation of stable contacts between hippocampal neurons in culture.

Mechanisms of cell-cell recognition and structural changes of growth cones (g.c.) and target membranes during contact formation are poorly understood. To examine these issues, we obtained a high magnification, real-time record of stable contact formation in cultured cells from the hippocampal CA1 area in the newborn rat. We used differential interference contrast (DIC) optics coupled to a video microscope for periods of over 24 h of continuous time-lapse recording. Our goal was to observe the sequential changes exhibited by afferent and target cells as they form a stable contact. Understanding the process of how stable contacts are made is important because such contacts are the first step in synapse formation. Four principal observations emerged from our study: (1) The target cell was receptive to a contact on a specific patch on its surface defined by the presence of lamellae and filopodia. This specific patch (named target site) was invariably present on the target cell surface before the time the growth cone arrived. (2) Stable adhesion between filopodia on the two cells initiated events leading to cell-cell contact formation. Specifically, the remaining filopodia on the growth cone and target cell were redirected toward the adhering filopodia, and the growth cone size decreased dramatically. (3) The axonal process then grew at a significantly accelerated rate (up to 50 times its baseline growth rate). (4) In addition, a number of observations were obtained on axonal turns towards the target cell, induction of target sites, and architectural remodelling of cells after the formation of a new contact. Our findings indicate that in this neuronal system, filopodia are the means used by cells to interact at stages prior to and during contact formation. We speculate that the molecules involved in cell recognition and the machinery that initiates contact formation are embedded in the fine structure of filopodia. Finally, our results provide possible clues as to some of the stages that may be involved in synapse formation in the mammalian central nervous system.

Animals↗
PubMed1992

Open stereotactic selective amygdalo-hippocampectomy for drug resistant epilepsy.

Selective removal of the medio-basal temporal structures has been introduced as an alternative to standard temporal lobectomy in the treatment of intractable temporal lobe epilepsy not related to gross structural lesions. Various approaches have been described for the surgical excision of the amygdalo-hippocampal complex, each of them presenting advantages and limitations. The recently introduced computer-assisted technique of volumetric stereotactic excision of deep-seated intracerebral lesions combines precision of targeting with elimination of unnecessary cortical trauma and may potentially provide an alternative method in the treatment of temporal lobe epilepsy. We present our experience of stereotactic volumetric selective amygdalo-hippocampectomy in six patients with medically intractable temporal lobe epilepsy. The criteria for selection, the pre-operative evaluation and the operative technique are discussed. All patients had a cessation or considerable reduction in seizure frequency while the morbidity was minimal.

Adolescent↗
PubMed1992

Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy.

Intracerebral EEG (SEEG) recordings showing the development of fast rhythmic activity at seizure onset provide important evidence for the localisation of an epileptic focus. However, very high-frequency activity (greater than 50 Hz) of low amplitude relative to the background may not be apparent on the paper record due to the limited bandwidth and dynamic range of conventional SEEG recording and display methods. The use of a digital telemetry system with a fast sampling rate (400 Hz) and a wide dynamic range (1 microV resolution, 4 mV range) has allowed us to utilize expanded time scale SEEG plots and autoregressive spectral estimation to identify this activity in chronic SEEG studies. This may be particularly useful in frontal lobe epilepsy, where rapid propagation often prevents adequate localization using conventional methods of analysis.

Adult↗
PubMed1992

Measurement of interhemispheric time differences in generalised spike-and-wave.

We have compared interhemispheric time differences (ITD) calculated by coherence/phase and linear and non-linear correlation analyses of generalised spike-wave episodes in 30 patients (15 with primary generalised epilepsy (PGE), 5 with secondary generalised epilepsy (SGE) and 10 with a lateralised epileptogenic area). Most cases were recorded during routine departmental EEGs. No significant difference was found between measures of interhemispheric synchrony (IS) (proportion of ITDs that are synchronous) calculated using the linear and the non-linear correlation techniques, although the latter gave slightly more (average 7%) valid ITD estimates. This suggests that the non-linear correlation technique does not provide significantly more time difference information than its linear counterpart. Similarly, no significant differences in IS values were identified between the coherence/phase and the correlation techniques. For all 3 techniques, IS values greater than 50% were derived for most patients with PGE and SGE; the proportion of patients with a lateralised epileptogenic area showing this was smaller. However, broad overlap in the distribution of IS values between the 3 groups suggests that individual patients cannot reliably be distinguished using these methods.

Action Potentials↗
PubMed1992

Neuronal activity triggers calcium waves in hippocampal astrocyte networks.

The recent discovery that the neurotransmitter glutamate can trigger actively propagating Ca2+ waves in the cytoplasm of cultured astrocytes suggests the possibility that synaptically released glutamate may trigger similar Ca2+ waves in brain astrocytes in situ. To explore this possibility, we used confocal microscopy and the Ca2+ indicator fluo-3 to study organotypically cultured slices of rat hippocampus, where astrocytic and neuronal networks are intermingled in their normal tissue relationships. We find that astrocytic Ca2+ waves are present under these circumstances and that these waves can be triggered by the firing of glutamatergic neuronal afferents with latencies as short as 2 s. The Ca2+ waves closely resemble those previously observed in cultured astrocytes: they propagate both within and between astrocytes at velocities of 7-27 microns/s at 21 degrees C. The ability of tissue astrocyte networks to respond to neuronal network activity suggests that astrocytes may have a much more dynamic and active role in brain function than has been generally recognized.

Animals↗
PubMed1992

Gibberellin perception and the Avena fatua aleurone: do our molecular keys fit the correct locks?

The plant hormones GA, ABA, and auxin differ from the majority of animal hormones in that they are hydrophobic weak acids. They are soluble in the inter- and intra-cellular environments of plant tissues and their neutral species can cross the plasma membrane by passive diffusion. Auxin transport is mediated by specific uptake and efflux carriers in plasma membranes, and there is some evidence for carrier-mediated uptake of GA and ABA. Because these plant hormones can cross the plasma membrane it is not a prerequisite that receptors for them should be at the protoplast surface. Nevertheless, there is substantial evidence that auxin acts at the plasma membrane, and evidence suggesting that GA may be perceived at the plasma membrane of A. fatua aleurone protoplasts has been reviewed here. It is conceivable that the plant plasma membrane might provide the means to integrate, transduce, and amplify these signals, and that such properties of the plasma membrane, rather than the permeability characteristics of these ligands, may determine the site of perception. Further progress in our understanding of signal transduction pathways that may be involved in the actions of plant hormones is likely to shed light on these questions. It has been proposed that GA receptors involved in cell elongation may be soluble rather than membrane bound. The soluble 50 kDa GA-binding protein observed in aleurone by GA4 photoaffinity labelling may be a good candidate for a soluble GA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1992

Auditory function in patients infected with the human immunodeficiency virus.

A prospective study of auditory function in 18 HIV positive male patients at different CDC (Centres for Disease Control) stages was undertaken. One-third had abnormalities on either auditory evoked response testing or pure tone audiometry. No correlation was found between interwave latencies I-V, I-III, III-V and stage of disease determined either clinically or by T-cell subset. There was a weak correlation between pure tone averages at 1,2,4 kHz and 2,4,8 kHz and T-cell subset ratio in CDC Group IV disease (Rs = 0.56 and 0.57 respectively; P less than 0.05). Abnormalities of BSER were similar to those previously reported in HIV infection, and suggest isolated changes within the brain-stem.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The inferiorly based rectus abdominis myocutaneous flap for reconstruction of recurrent pressure sores.

Eight neurologically impaired patients underwent reconstruction of chronic perineal and ischial pressure sores utilizing an inferiorly based rectus abdominis myocutaneous flap. Other local and regional flap options had been previously used or were not feasible. In six patients, healing was uncomplicated. One patient required local debridement and flap readvancement. The second involved minor separation of a suture line and healed by secondary intention. All donor sites were closed directly and healed by primary intention. There was no evidence of hernia formation, and no functional deficit was detected from removal of the rectus muscle in any of the patients. In conclusion, it was felt that the inferiorly based rectus abdominis myocutaneous flap should be considered a reconstructive option in dealing with perineal and ischial pressure sores. Furthermore, for reasons discussed, we found distinct advantages to using this flap in spinal cord injury patients.

Humans↗
PubMed1991

Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man.

Heme formation in the erythron is subject to end product regulation by negative feedback, but the exact point of metabolic control in human erythroid cells is unknown. To investigate the mode of action of heme on its own formation, the effects of micromolar concentrations of hemin on de novo synthesis of protoporphyrin IX and delta-aminolevulinate (delta-ALA) by intact human reticulocytes were examined in the presence of 1 mM alpha,alpha'-bipyridyl and 200 microM 4,6-dioxoheptanoate to block their further conversion by ferrochelatase or delta-ALA dehydrase, respectively. At final concentrations (25-40 microM), hemin, which is known to reduce incorporation of [2-14C]glycine into cellular heme, significantly inhibited formation of protoporphyrin IX and total delta-aminolevulinate in situ by these cells. Since synthesis of the first committed precursor, delta-aminolevulinate, as well as protoporphyrin (which is derived from it) were diminished, the effects of hemin on delta-aminolevulinate synthase (EC 2.3.1.37) were studied. Hemin, at concentrations up to 40 microM, had no direct effect on enzymatic activity, as measured with [5-14C] alpha-ketoglutarate (in hypotonically lysed cells) or [1,4-14C]succinyl coenzyme A (in deoxycholate lysates), even after preincubation. However, when intact human reticulocytes were incubated with hemin before assay for delta-ALA synthase, there was a rapid, concentration-dependent reduction in enzymatic activity (mean 42 and 23% inhibition after 60 min for these two substrates, respectively). Hemin had no effect on steady-state levels of delta-ALA synthase mRNA, as determined by Northern blot hybridization using an erythroid-specific human cDNA probe. Thus, a mechanism for inducing feedback inhibition of the tetrapyrrole pathway exists in human erythroid cells. It controls formation of the first committed precursor of protoporphyrin IX, delta-aminolevulinate, and hence regulates heme biosynthesis by limiting the availability of the porphyrin, rather than the metal substrate for the ferrochelatase reaction. Hemin interacts with constituents of the intact reticulocyte significantly to reduce delta-aminolevulinic acid synthase activity by an indirect cellular process that does not influence the abundance of erythroid-specific synthase mRNA but may either inhibit its ribosomal translation in an unknown manner or promote degradation of the enzyme itself by specific proteolysis.

5-Aminolevulinate Synthetase↗