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S J Smith

Publications and source records attributed to S J Smith.

At least 145 records · Page 8Linked to original sources
PubMed1996

Isotope dilution--mass spectrometric quantification of specific proteins: model application with apolipoprotein A-I.

An enzymatic hydrolysis isotope dilution-mass spectrometric method was developed for reference quantification of specific proteins. The analytical procedure involved measuring a reproducibly hydrolyzed peptide (serving as the primary standard) unique to a specific protein. This new mass spectrometric method was evaluated by assessing the concentration of apolipoprotein (apo) A-I in the European Community Bureau of Reference (BCR) lyophilized Certified Reference Material (CRM 393). We used the method to make 96 measurements (4 replicate analyses of 4 enzymatic digests of 6 vials of BCR-CRM 393), which gave an average total protein mass of 1.048 mg (+/- 1.0% at 99% confidence limits). The total overall analytical CV was 3.95%. The results of this evaluation of our model approach to determine the concentration of a specific protein in a purified preparation demonstrated that our new mass spectrometric method can be used to measure apolipoproteins and other specific proteins without the use of epitopic immunoassay methods.

Amino Acid Sequence↗
PubMed1995

Early functional neural networks in the developing retina.

In the adult mammalian retina, the principal direction of information flow is along a vertical pathway from photoreceptors to retinal interneurons to ganglion cells, the output neurons of the retina. We report here, however, that initially in development, at a time when the photoreceptors are not yet even present, there are already functionally defined networks within the retina. These networks are spontaneously active rather than visually driven, and they involve horizontal rather than vertical pathways. By means of optical recording using the calcium-sensitive dye Fura-2, we have found that sets of retinal ganglion cells and amacrine cells, a type of retinal interneuron, undergo synchronized oscillations in intracellular calcium concentration. These oscillations are highly correlated among subgroups of neighbouring cells, and spread in a wave-like fashion tangentially across the retina. Thus, in development of retinal circuitry, the initial patterning of neuronal function occurs in the horizontal domain before the adult pattern of vertical information transfer emerges.

Animals↗
PubMed1995

The triggering of astrocytic calcium waves by NMDA-induced neuronal activation.

It has been well established that astrocytes possess functional receptors for the excitatory neurotransmitter glutamate and respond to physiological concentrations of this substance with oscillations in cytoplasmic Ca2+ concentrations and spatially propagating Ca2+ waves. These findings strongly suggest that glutamate released during synaptic transmission triggers such phenomena within the perisynaptic astrocyte in situ. We test this hypothesis in two preparations, the organotypic hippocampal slice and hippocampal neuron-astrocyte co-cultures, using the Ca2+ indicator fluo-3 and confocal laser microscopy. An agonist for the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor is employed to stimulate neuronal populations specifically, leaving the astrocytic population unaffected as these cells appear to lack this glutamate receptor subtype. Such pharmacological stimulation initially elicits large Ca2+ transients within the neuronal populations, followed by Ca2+ spikes in surrounding astrocytes, presumably as the result of neuronal glutamate release. During continuous neuronal stimulation, the astrocyte's Ca2+ response becomes oscillatory, with a period averaging 33 s and ranging from 15 to 50 s at 21 degrees C. These findings establish another form of communication within the brain, that between neurons and astrocytes, which perhaps acts to couple astrocytic regulatory responses to neuronal activity.

Animals↗
PubMed1995

First seizures associated with playing electronic screen games: a community-based study in Great Britain.

Active surveillance by virtually all electroencephalographic departments throughout Great Britain identified 118 patients who had a first seizure while playing an electronic screen game during two 3-month periods. Patients were divided into Group A (46 patients)--those for whom there was thought to be a definite causal relationship (type 4 photoparoxysmal response); Group B (25 patients)--those for whom there was a probable causal relationship (types 1-3 photoparoxysmal response, clinical evidence of photosensitivity, subsequent recurrent seizures on repeat exposure to electronic screen games, and/or occipital spikes in the resting electroencephalogram); and Group C (47 patients)--those for whom there was no apparent causal relationship. The number of patients in Group C did not exceed that expected by the chance occurrence of two common events (playing electronic screen games and incidence of epilepsy). Most (103/118) of the patients were in the age range of 7 to 19 years. Within this age group the annual incidence of first seizures triggered by playing electronic screen games (Groups A and B combined) was estimated to be 1.5/100,000.

Adolescent↗
PubMed1995

Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a cancer and leukemia group B study.

The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) microM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2, P = 0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment blast count (P = 0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P = 0.315, P = 0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin.

Acute Disease↗
PubMed1995

Biochemical and physiological effects of sterol alterations in yeast--a review.

Considerable progress has been made in the selection and characterization of mutants that are defective in the synthesis of ergosterol in the yeast, Saccharomyces cerevisiae. Mutations in nearly every step of the yeast sterol biosynthetic pathway have been induced and selected. These mutants have been used to elucidate the sequential order of steps in sterol synthesis, to study the mode of action of antifungal agents and to determine the method of resistance of some pathogenic fungi, and to answer questions on the role of sterols in general cell biology. Physiological examination of ergosterol null mutants, lacking all biochemical activity attributed to the particular gene, supports a role for ergosterol in a number of critical functions in the organism. Among the physiological functions attributed to ergosterol are sparking and bulking requirements, involvement in amino acid and pyrimidine transport, resistance to antifungal agents and certain cations, and a requirement for respiratory activity. Those genetic null alleles discussed in this review are erg24, lacking the ability to reduce the delta 14 double bond; erg6, unable to methylate C-24; and erg3, defective in the C-5 desaturase. The different biochemical activities that are disrupted in the ergosterol mutants support a role for ergosterol in a number of critical functions in yeast.

Genes, Fungal↗
PubMed1995

Cortical dysgenesis: serial EEG findings in children and adults.

Cortical dysgenesis (CD) is becoming increasingly recognised as a cause of epilepsy in otherwise cryptogenic cases. We describe the serial EEG findings in 22 patients with focal/localised CD. The EEGs covered a minimum period of 5 years in each case (median = 13 years, range: 5-30 years), beginning in childhood. Median age at seizure onset was 3 years (range: 3 weeks-10 years, n = 21). The EEG was normal in the one patient, a 6 year old, who did not have epilepsy. Background rhythms appropriate for age were preserved in the majority of patients (18/22). Slow activity localised to the area of CD was seen in 11 patients; in 3 patients, this did not appear until the second decade of life. Epileptiform discharges were seen in at least one EEG in 20 patients: these were continuous or near-continuous (6 patients) or occurred recurrently in short runs (6 patients). In 6 patients, these discharges appeared only after the second decade of life and in 11 patients, they became more widespread over time. In the remaining patients, the EEG changes did not evolve. Sleep failed to produce new abnormalities (n = 15). None of the patients showed EEG features characteristic of lissencephaly or evolution to the Lennox-Gastaut syndrome. Even in this selected cohort of patients who had undergone serial clinical EEGs, the EEG abnormalities in focal/localised CD appeared relatively stable and showed only moderate changes over time. CD must be included in the differential diagnosis of any patient who presents with localised slow activity on EEG.

Adolescent↗
PubMed1995

Incidence of photosensitive epilepsy: a prospective national study.

We undertook a prospective nationwide study to determine the incidence of photosensitive epilepsy (PE). Virtually all EEG departments in Great Britain (providing approximately 90% coverage of all EEGs performed on people with newly diagnosed seizures) screened cases referred to them over a 3 month period and identified all new cases of epilepsy (defined as one or more recognised seizures) whose first EEG showed a photoparoxysmal response (PPR) on intermittent photic stimulation (IPS). 191 cases were identified, 143 of whom had type 4 PPRs (generalised spike and wave on IPS) on their first EEG. The annual incidence of cases of epilepsy with type 4 PPRs on their first EEG was conservatively estimated to be 1.1 per 100,000, representing approximately 2% of all new cases of epilepsy. When restricted to the age range 7-19 years, the annual incidence rose to 5.7 per 100,000-approximately 10% of all new cases of epilepsy presenting in this age range. To ascertain if there was a significant seasonal variation in PE, 5 EEG departments (which together contributed 15% of cases in the first study period) were visited during a second 3 month study period to identify all new cases of epilepsy with type 4 PPRs on their first EEG. No significant seasonal variation in incidence between summer and winter was found.

Adolescent↗
PubMed1995

Vesicle pool mobilization during action potential firing at hippocampal synapses.

Using the fluorescent membrane label FM 1-43, we have measured the release, reuptake, and repriming of synaptic vesicles in response to action potential stimulation of cultured hippocampal neurons. We find that approximately 90% of a recycling vesicle pool is released during 60 s of 10 Hz action potential firing, and that a single action potential releases approximately 0.5% of that pool. Our data also indicate that endocytic reuptake of vesicle membrane externalized by 10 Hz action potentials lags exocytosis, with a half-time on the order of 20 s, and that the minimum time for repriming of an endocytosed vesicle is on the order of 15 s. Finally, we find that once vesicles have undergone this repriming period, they become functionally mixed in the vesicle pool within a few minutes; the probability of release for recently recycled vesicles is indistinguishable from that of vesicles that have resided within the bouton for much longer periods.

Action Potentials↗
PubMed1995

Do autoantibodies to IgE play a role in IgE-mediated events?

Elevated blood levels of IgG anti-IgE are detectable in individuals exhibiting enhanced IgE production, namely those with allergic conditions and helminthic parasite infections. The fact that there are epitope-specific subpopulations of autoanti-IgE suggests that this autoantibody could potentially have multiple effects in immunological events involving IgE.

Animals↗
PubMed1995

Optic nerve decompression in cranial base fibrous dysplasia.

Fibrous dysplasia of the anterior cranial base involves the bony orbit and optic canal. Although fibrous dysplasia is benign, it may produce a mass effect along the course of the optic nerve, inducing visual disturbances. Optic canal decompression in patients without clinical signs of optic neuropathy is controversial. We describe five patients with extensive fibrous dysplasia of the anterior cranial base involving the orbit and optic canal. These patients underwent transcranial optic canal decompression before signs of severe visual loss during correction of dystopias and craniofacial deformity induced by fibrous dysplasia. Cranial orbital reconstruction was performed by means of split rib and cranial bone grafts. Postoperative follow-up did not reveal disturbances in visual function, extraocular motility, or evidence of cerebrospinal fluid fistulas. This suggests that early, radical resection of orbital fibrous dysplasia with optic canal decompression may be effective in preventing visual loss with minimal risk of other neurological sequelae. Subsequent orbital reconstruction involving split-thickness rib and cranial bone grafting yields satisfactory cosmetic results.

Adolescent↗
PubMed1995

The intensive care treatment of convulsive status epilepticus in the UK. Results of a national survey and recommendations.

Six hundred and ninety-four members of the Intensive Care Society working in the UK were surveyed by postal questionnaire between May and November 1993 to determine their management of convulsive status epilepticus resistant to initial therapy with intravenous diazepam and phenytoin. Four hundred and eight forms were completed and returned (58.8%). The survey revealed that, following failure of initial management, a benzodiazepine infusion (35%) or anaesthetic induction agent (32%) were the preferred second lines of treatment in intensive care units. In paediatric intensive care units, phenobarbitone (31%) was the agent of choice. Most respondents (57%) gave anaesthetic induction agents within 60 min of the start of status epilepticus, the majority choosing thiopentone (82%). Patients were usually monitored using clinical assessment only (45%), except in paediatric intensive care units and specialist neurological or neurosurgical units where the majority used a cerebral function monitor. Only 12% of the respondents were aware of a protocol for status epilepticus in their intensive care units. The most frequently used therapeutic and monitoring strategies in the management of refractory status epilepticus in the UK are insufficient and need re-evaluation.

Anesthetics, General↗
PubMed1995

The prevalence of IgG1 and IgG4 autoantibodies to IgE in patients with allergic and non-allergic rhinitis.

In this study we have compared the levels of IgG1 and IgG4 autoantibodies to IgE in the sera of patients with allergic rhinitis and non-allergic rhinitis. A group of patients undergoing cosmetic nasal surgery, but who did not have rhinitis or any history of atopy, acted as control. The frequency of positive titres of IgG1 and/or IgG4 anti-IgE was 70% (14/20) in patients with allergic rhinitis, 50% (10/20) in patients with non-allergic rhinitis and 20% (4/20) in the control group. The mean titres of IgG1 anti-IgE and IgG4 anti-IgE were in the order allergic rhinitis > non-allergic rhinitis > controls. In the allergic rhinitis group levels of IgG1 anti-IgE (P = 0.0055) and IgG4 anti-IgE (P = 0.0028) were significantly higher than those found in the control group. The non-allergic rhinitis group also showed significantly higher levels of IgG1 anti-IgE (P = 0.0182) and IgG4 and anti-IgE (P = 0.0359) than the control group. The existence of IgG autoantibodies to IgE in both allergic and non-allergic rhinitis suggests a possible role for these antibodies in the disease process, particularly in patients whose symptoms are not due to an allergic trigger.

Adolescent↗
PubMed1995

The effect of social deprivation on birthweight, excluding physiological and pathological effects.

OBJECTIVE: To study the effect of social deprivation on birthweight, excluding the effect of known physiological factors and exploring the effect of possible pathological factors. DESIGN: Retrospective analysis of computerised obstetric database. SETTING: Two teaching hospitals and an associated district general hospital which provided a defined catchment area in the East Midlands. SUBJECTS: The final analysis included 7493 women with complete datasets and gestations of between 259 and 300 days at delivery, dated by ultrasound scan. MAIN OUTCOME MEASURES: Smoking habit, alcohol consumption, weight gain during pregnancy, systolic and diastolic blood pressures at booking, bleeding during pregnancy and Jarman score; also, the effect of these variables on birthweight, adjusted for the effects of physiological factors using the individualised birthweight ratio. RESULTS: Smoking during pregnancy reduced birthweight but the effect is not linear, becoming less marked as the number of cigarettes smoked increases. Alcohol intake, diastolic and systolic blood pressures at the booking visit and vaginal bleeding during early pregnancy were not significantly related to birthweight. Pregnancy weight gain was significantly positively related to birthweight especially in the normal weight range (60-99 kg). A multivariate analysis including physiological and pathological factors found increasing Jarman score to be negatively related to birthweight. CONCLUSIONS: In this central British population social deprivation is correlated negatively with birthweight: the most socially deprived mothers have the smallest babies. This association cannot be explained in terms of physiological differences in the population nor in a higher prevalence of known pathological factors.

Alcohol Drinking↗
PubMed1995

Case of simple partial status epilepticus in occipital lobe epilepsy misdiagnosed as migraine: clinical, electrophysiological, and magnetic resonance imaging characteristics.

An 31-year-old man had a unique form of occipital lobe epilepsy. Since age 13 years, he has had episodes of simple partial status epilepticus (SE) occurring twice a month. These typically consisted of elementary visual hallucinations of flashing lights obscuring his left visual field for a period of 2 days, associated with a severe frontal headache initially diagnosed as migraine. These episodes of simple partial SE then evolved to a complex partial seizure (CPS) or secondarily generalized seizure. There were unique EEG features, including: (a) the perception of a flash of light in the left visual field with a single sharp/slow wave discharge over the right occipital lobe, (b) right occipital lobe epileptiform activity during the prolonged aura, and (c) an abnormal response to photic stimulation, with occipital lobe discharges during low rates of stimulation (3-5 Hz), time-locked to the stimulus. High-resolution magnetic resonance imaging (MRI) with quantitative morphometry demonstrated that the right hemisphere and right caudate nucleus were smaller than those on the left. An abnormal gyral pattern was also noted over the right parietal region. Occasionally, distinguishing occipital lobe epilepsy from migraine may be difficult.

Adult↗