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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 271 records · Page 15Linked to original sources
PubMed1990

High-performance liquid chromatographic analysis of imidazolium and pyridinium oximes in plasma and urine.

Imidazolium oximes are useful in the treatment of organophosphorus agent poisoning. However, the extant methods for analyzing oximes in plasma and urine samples are not adequate. A unique high-performance liquid chromatographic assay method was developed for quantitating either imidazolium or pyridinium oximes. Plasma or urine samples can be injected directly onto the column after a centrifugation filtration step. This method demonstrates a different approach in the method development for quaternary ammonium compounds using non-end-capped reversed-phase columns and a mobile phase containing competing cations. In addition, a preliminary pharmacokinetic study of the imidazolium oxime in rabbits was carried out using this method.

Animals↗
PubMed1990

Identification of nucleotides responsible for enhancer activity of sterol regulatory element in low density lipoprotein receptor gene.

Sterol-dependent regulation of the low density lipoprotein (LDL) receptor promoter has been localized previously to a 16-base pair sequence, designated repeat 2, in the 5'-flanking region of the gene. In the current study, we show that the central 10 nucleotides of repeat 2 are crucial for the sterol regulatory activity. This sequence includes an octamer, designated sterol regulatory element 1 (SRE-1), which was identified previously in the promoter of the gene for 3-hydroxy-3-methylglutaryl coenzyme A synthase, a sterol-regulated enzyme of cholesterol biosynthesis. We made a series of single-base substitutions within a 1471-base pair fragment of the intact LDL receptor promoter, introduced the mutant plasmids into hamster cells by transfection, and measured mRNA levels in the absence and presence of sterols. Substitutions within the 10-base pair sequence in repeat 2 largely prevented the induction of transcription which occurs in the absence of sterols. None of these point mutations affected transcription in the presence of sterols. Like an enhancer, the SRE-1 in repeat 2 functioned in an orientation-independent manner. We interpret these findings to indicate that the SRE-1 of the LDL receptor promoter is a conditional positive element that cooperates with other elements to enhance transcription in the absence of sterols and loses its function in the presence of sterols.

Animals↗
PubMed1990

Novel monoclonal antibodies identify antigenic determinants unique to cellular senescence.

Normal human diploid fibroblasts exhibit a limited lifespan in vitro and are used as a model to study in vivo aging. Monoclonal antibodies were generated against partially purified surface membranes from human diploid fibroblasts at the end of their lifespan (senescent). Three hybridomas were isolated that secreted antibodies reacting to cellular determinants expressed specifically on senescent human fibroblasts of different origin, including neonatal foreskin, embryonic lung, and adult skin punch biopsy, but not expressed on matched young cells. The antibodies did not bind to immortal human cells and normal young cells made reversibly nondividing, indicating the antigens are not expressed in cells that are not senescent. The antibodies identified senescent cells in a mixed cell population and expression of the senescent cell antigens correlated strongly with the cells inability to synthesize DNA at the onset of senescence. The antigens appeared to be cell surface or extracellular matrix associated, and the epitopes were destroyed by mild trypsin treatment. Western analysis indicated all three antibodies reacted with fibronectin. Though the antigenic determinants on the fibronectin molecule were not accessible in the intact young cell, the epitopes were present in fibronectin extracted from both senescent and young cells, as well as purified human plasma fibronectin. These antibodies and the senescent specific expression of the antigens provide powerful tools to investigate the mechanisms leading to in vitro senescence. This may enable us to investigate directly the relationship between cellular aging and aging of the individual.

Aging↗
PubMed1990

Adaptive smoothing: an improved method for spectral analysis and its application to seizure EEG.

We describe the data adaptive smoothing method, an improved method for multichannel spectral analysis of seizure EEG. After Fast Fourier Transform of EEG data, spectra were computed by smoothing over adjacent frequency components. Using cross-validatory maximum likelihood criteria, unsmoothed spectral data were used to select the level of smoothing (spectral window effective bandwidth) required to minimize bias and variance errors. The statistical assumptions of this method are consistent with the statistical properties of seizure EEG. On computer simulation of seizure EEG, the smoothing level predicted by this method correlates strongly with the optimum smoothing level. The utility of the method is demonstrated by application to seizure EEG. The consistency of the method's statistical assumptions, the success in selection of the optimum smoothing level, and the variability in optimum smoothing required for seizure EEG suggest that the adaptive smoothing method is a useful method for multichannel spectral analysis.

Electroencephalography↗
PubMed1990

Cerebral language lateralization: evidence from intracarotid amobarbital testing.

Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable.

Amobarbital↗
PubMed1990

Blocking enzyme-linked immunosorbent assay for detection of antibodies against bovine enterovirus.

A blocking enzyme-linked immunosorbent assay (ELISA) was developed for detecting antibodies against bovine enterovirus (BEV) in bovine sera. In this ELISA, bovine serum samples were allowed to react with captured viral antigens (by specific chicken IgG), before the addition of specific mouse IgG for measuring non-occupied viral epitopes. The ELISA was slightly more sensitive and required a shorter time period than traditional serum neutralisation (SN). Among the 871 bovine serum samples tested so far, the titres produced by this assay had a significant correlation with those recorded by SN. The ELISA could be used as an alternative assay for SN in a large-scale BEV antibody investigation.

Animals↗
PubMed1990

Material specific learning during electrical stimulation of the human hippocampus.

Material specific learning was assessed during unilateral electrical stimulation of the hippocampus through intracerebrally implanted electrodes in 30 patients with unilateral temporal lobe epilepsy (TLE). Verbal learning significantly decreased in patients with right TLE after stimulation of the left, but not the right, hippocampus. No verbal learning impairment was observed in left TLE patients following stimulation of either hippocampus. Visuospatial memory performance significantly decreased following stimulation of the right hippocampus regardless of the side of seizure onset. Results suggest that the contralateral "nonepileptic" hippocampus does not assume the material specific mnestic functions of the dysfunctional hippocampus associated with longstanding epilepsy.

Analysis of Variance↗
PubMed1990

Crossed aphasia in a patient with complex partial seizures: evidence from intracarotid amobarbital testing, functional cortical mapping, and neuropsychological assessment.

We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Preoperative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.

Adult↗
PubMed1990

TDAT--time domain analysis tool for EEG analysis.

An interactive design and analysis tool for displaying and quantifying multiple channels of data is presented. The system allows one to easily visualize multiple data channels and simultaneously observe the effects of filters on the data and to evaluate signal detection algorithms. The software is designed for a workstation environment; it will find application in a variety of applications where one needs to simultaneously visualize multiple data channels. TDAT is being used for the design and evaluation of filters and detection algorithms for electroencephalogram (EEG) waveforms, and it is serving as a prototype of a paperless system to be used by electroencephalographers. This paper describes the general software structure of the system and illustrates many of the system features with examples.

Algorithms↗
PubMed1990

Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour.

The use of prostaglandin synthetase inhibitors (indomethacin and ibuprofen) for greater than 72 h in women with preterm labour (n = 67) was significantly (P less than 0.001) associated with ultrasound-recorded oligohydramnios compared with the use of ritodrine or magnesium sulphate (control group, n = 67). Oligohydramnios developed in 26 of 37 women (70%) treated with indomethacin and 8 of 30 women treated with ibuprofen (27%) (P less than 0.01). Oligohydramnios developed in only two control subjects and one of these pregnancies was associated with intrauterine growth retardation. All 34 cases of oligohydramnios in the treatment group resolved after stopping medication, whereas the two in the control group did not resolve. No instances of renal failure, premature closure of the ductus arteriosus, pulmonary hypertension, or bleeding disorders were noted in any of the treated or control infants.

Adult↗
PubMed1990

An 8-year experience with depth electrodes in the evaluation of ablative seizure surgery candidates.

Stereotactically implanted depth electrodes are one means of localization of seizure foci. Unilateral seizure focus localization was obtained in 72.7% mesial temporal (MT) implants and 50% of focus/extramesial temporal (MT-XMT) implants. Recent increase in localization to over 80% in MT implants was possible because a larger percentage of patients had MT-XMT implants. Increased localization to 60% in MT-XMT implants was related to using more XMT electrodes per patient and to orienting electrodes to monitor larger limbic XMT and neocortical areas. Since MT foci were localized in 25% of MT-XMT cases, MT electrodes should be included with all MT-XMT implants. Depth electrography can also be used to rule out certain patients as surgical candidates. Therefore, a surgical decision can be reached in a very high percentage of patients undergoing depth implantation. Surgical results are comparable to those in our overall series.

Brain Mapping↗
PubMed1990

Risk factors of female HIV-seropositive patients attending the clinic for sexually transmitted diseases at St Mary's Hospital, London.

Of 3450 women tested for antibodies to human immunodeficiency virus HIV-1 and HIV-2 between September 1985 and July 1989, 61 were positive (1.8%). Twenty-seven of these (44%) were presumed to have acquired their HIV infection by heterosexual contact and 23 (38%) were intravenous drug addicts. In geographical origin, 23 (38%) of the patients were from the UK and 19 (31%) from Africa. Amongst these 61 women, 2 (3%) have since died, one committed suicide and one was suspected of committing suicide.

Adolescent↗
PubMed1990

The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy.

We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option.

Amnesia↗