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J R Smith

Publications and source records attributed to J R Smith.

At least 289 records · Page 16Linked to original sources
PubMed1990

Human hippocampal EEG: effects of behavioral activation.

We studied spectral components of human hippocampal EEG in relation to behavioral status in 19 patients with intractable complex partial seizures who had depth electrodes implanted into the anterior hippocampi as a part of their preoperative evaluations. Behavioral conditions included: eyes closed resting, eyes open resting, eyes open with a verbal task, and eyes open with a visuospatial task. Hippocampal EEG spectral power uniformly decreased during behavioral activation. EEG activation was quantitatively different among the 3 activated conditions, with the most prominent change occurring during the visuospatial task. The degree of EEG activation corresponded inversely with the site of epileptic focus during the verbal task. The results demonstrate the response of human hippocampal EEG to behavioral activation. The magnitude of EEG change may reflect the degree of functional activation of the given hippocampus.

Adult↗
PubMed1990

MR imaging in patients with intractable complex partial epileptic seizures.

Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis.

Adolescent↗
PubMed1989

Isolation of a cDNA that hybrid selects antiproliferative mRNA from rat liver.

Studies of chromosome loss in inherited cancers, of fusions between proliferating and quiescent cells, and of microinjection of RNA from quiescent cells into proliferation competent cells have all provided evidence for antiproliferative genes in mammalian cells. In this report, we describe a partial cDNA clone isolated on the basis of its preferential hybridization to RNA from normal versus regenerating rat liver. The corresponding mRNA, enriched by hybrid selection, was microinjected into normal human diploid fibroblasts in cell culture, resulting in a 53% decrease in the fraction of nuclei incorporating tritiated thymidine. This mRNA is 2 kb in size and is expressed in eight tissues examined.

Animals↗
PubMed1989

Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity.

The atrophy of extracellular matrix is a common event during the aging of connective tissues. In this study, we tested the hypothesis that the altered ability of senescent cells to be modulated by serum growth factors correlated with a loss of regulation of collagenase synthesis. We examined the levels of immunoreactive procollagenase and collagenase inhibitor (the tissue inhibitor of metalloproteinases, TIMP) associated with young and senescent fibroblasts cultured in vitro. Young fibroblasts cultured in low (0.5%) concentrations of fetal bovine serum respond to increased (10%) serum by increasing levels of procollagenase and TIMP beginning 4.0 h after serum stimulation. In contrast, senescent fibroblasts constitutively produce relatively high levels of procollagenase even when cultured in low levels of serum and do not respond to serum stimulation by increasing procollagenase synthesis. In addition, senescent fibroblasts constitutively express a relatively small amount of TIMP which is not induced upon serum stimulation. This altered expression of collagenase and TIMP appears unique to the senescent phenotype and not merely a result of growth inhibition, since young cells growth arrested by density-dependent growth inhibition displayed a temporal pattern of procollagenase and TIMP expression upon serum stimulation similar to that of subconfluent young cultures. An assay of net collagenase activity revealed a greater than 20-fold elevation of activity in trypsin-activated extracts from senescent versus young fibroblasts when cultured in a low concentration of fetal bovine serum. These results demonstrate for the first time a direct correlation between alterations in the molecular pathways regulating connective tissue homeostasis and those of replicative senescence. The increased collagenolytic activity of senescent compared to young fibroblasts cultured in the presence of a low serum concentration suggests that aging fibroblasts may become increasingly fibroclastic causing many of the age-associated alterations in dermal collagen observed during aging in vivo.

Blotting, Western↗
PubMed1989

The inhibitory effects of nitrous oxide and methylmercury in vivo on methionine synthase (EC 2.1.1.13) activity in the brain, liver, ovary and spinal cord of the rat.

1. Baseline levels of methionine synthase (MS) activity in spinal cord and ovary from female rats were comparable to activities seen in brain and liver. 2. Exposure (1 hr) of female rats to 50% nitrous oxide (N2O) caused significant decreases in MS in brain, liver, and spinal cord and a sharp drop in ovary. 3. Four daily injections of 6 mg/kg methylmercury (MM) caused a significant decrease in MS activity in brain and a decrease in mean MS activity in ovary and spinal cord. 4. Results from a combined treatment with MM and N2O suggests additive inhibition of MS by these agents.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1989

Further studies on the genetic and biochemical basis of cellular senescence.

Cell fusion analysis, exploiting the fact that the phenotype of immortality is recessive in hybrids, has allowed the assignment of 26 different immortal human cell lines to at least four complementation groups for indefinite division. This indicates that there are at least four sets of genes or processes involved in the mechanisms leading to cellular senescence. We have also observed alterations in gene expression accompanying senescence that induce the expression of a protein inhibitor of DNA synthesis, expression of new cell surface epitopes as identified by monoclonal antibodies specific to senescent cells, and changes in the extracellular matrix. We have yet to determine whether these changes in gene expression are casual or the result of senescence. The assignment of immortal cell lines to specific complementation groups now allow for a focused approach to identify the normal growth regulatory genes that have been modified to yield immortal cells and determine whether certain senescent cell specific patterns of gene expression continue to be expressed in immortal cells within a group. In addition, the isolation of senescent cell-specific antibodies provides for the first time the tools with which to probe the relationship between in vitro and in vivo aging.

Cell Fusion↗
PubMed1989

Approach to the isolation of antiproliferative genes.

Poly(A) RNAs from normal rat liver and senescent human fibroblasts appear to have more antiproliferative activity than RNAs from regenerating rat liver and early passage human fibroblasts. We have screened two rat liver and one human liver library by differential hybridization and isolated four candidate cDNAs for this antiproliferative activity; one is fibronectin and three others do not match to any sequence in the mammalian portion of the GENBANK database. We are currently testing the antiproliferative nature of these cDNAs by microinjection of hybrid-selected RNA, and we describe an alternative strategy for cloning such genes based on construction of a cDNA library in an RNA expression vector.

Animals↗
PubMed1989

Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial.

To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Surgical management of epilepsy.

About 300,000 people in the United States suffer from medically uncontrolled focal epilepsy. It is estimated that about 40,000 of these patients are candidates for surgery. Underuse of surgical treatment of epilepsy is reflected by the fact that only about 1% of these candidates are operated on. Candidates for ablative surgery (ie, removal of seizure focus) must have a focus demonstrated by either extracranial or intracranial electrode recordings. Nearly half of the patients who have ablative surgery become seizure-free, and nearly two thirds have no seizures or only rare ones. Candidates for corpus callosotomy are those patients with multiple seizure types and nonfocal EEG abnormalities. Almost half of these patients have at least a 50% reduction in seizure frequency. Patients with infantile hemiplegia and seizures may have marked improvement in seizure control after physiologic hemispherectomy.

Corpus Callosum↗
PubMed1989

Altered gene expression during cellular aging.

The limited division potential of normal human diploid fibroblasts in culture represents a model system for cellular aging. Observations indicate cellular senescence is an active process. Senescent cells, although unable to divide, are actively metabolizing. Hybrids from fusion of normal and immortal human cells exhibit limited division potential, suggesting that the phenotype of cellular senescence is dominant and supporting the hypothesis that senescence is genetically programmed. Fusion of immortal human cell lines with each other has identified four complementation groups for indefinite division. This indicates that a limited number of specific genes or processes are involved in senescence. Senescent cells express highly abundant DNA synthesis inhibitory messenger RNAs and produce a surface membrane associated protein inhibitor of DNA synthesis not expressed in young cells. Senescent cell membranes were used as immunogen to generate three monoclonal antibodies reacting specifically with senescent but not young cells in several normal human cell lines. We have also found that fibronectin messenger RNA accumulates to high levels in senescent cells. The role of these changes in gene expression in senescence is being explored.

Aging↗
PubMed1989

Concentration of creatine kinase and aspartate aminotransferase in the blood of wild mallards following capture by three methods for banding.

The concentration of the enzymes creatine kinase (CK) and aspartate aminotransferase (AST), that are released from damaged muscle, was measured in the blood of wild adult male mallards (Anas platyrhynchos) captured for banding in decoy and bait traps and by rocket net. The concentration of CK and to a lesser extent AST was elevated markedly in ducks captured by all methods, indicating muscle injury. The level of CK was significantly greater in ducks captured in decoy traps and rocket net than in those captured in bait traps. This elevation appeared to be related to the length of time the birds were restrained and to the method of restraint.

Animals↗
PubMed1988

Multiple sterol regulatory elements in promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A synthase.

Through substitution mutagenesis and gene transfer experiments in cultured cells, we have identified three sequences in the 5' flanking region of the gene for hamster 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase that are required for sterol-mediated regulation of transcription. Point mutations in any one of these sequences largely prevented the increase in transcription that normally follows cellular sterol depletion. These mutations did not alter the low level of transcription that occurs in the presence of sterols. Two of the three sterol regulatory sequences contain an octanucleotide that shows a 7/8-base pair match with a sequence that was previously identified as a sterol regulatory element in the genes for HMG-CoA reductase and the low density lipoprotein receptor, both of which are induced by sterol deprivation. The third sterol regulatory region in the HMG-CoA synthase promoter shows only a low-level match with the other sterol regulatory elements. The current data suggest that the sterol regulatory elements in the HMG-CoA synthase promoter operate by a conditional positive mechanism: in the absence of sterols, regulatory proteins bind to these elements and stimulate transcription; in the presence of sterols, the regulatory proteins are inactivated and transcription decreases to the basal rate.

Animals↗
PubMed1988

Structural characterization of the major adducts obtained after reaction of an ultimate carcinogen aflatoxin B1-dichloride with calf thymus DNA in vitro.

The major adduct formed on acid hydrolysis of calf thymus DNA which has been reacted with 8,9-dichloro-8,9-dihydroaflatoxin B1, a chemical model of the ultimate carcinogen 8,9-dihydro-8,9-epoxyaflatoxin B1 (AFB1-epoxide), has been characterized by proton nuclear magnetic resonance and fast atom bombardment mass spectroscopy. This adduct has been identified as an N7-substituted guanine adduct analogous to that formed on reaction of AFB1-8,9-epoxide with DNA in vivo and in vitro, namely trans-8,9-dihydro-8-(7-guanyl)-9-hydroxy AFB1. This 8,9-dichloro-8,9-dihydroaflatoxin B1 adduct in DNA, like its equivalent B1 adduct in DNA, like its equivalent AFB1-epoxide adduct, is prone to quantitative imidazole ring opening of the substituted guanine in mildly alkaline conditions and to substantial depurination under mildly acidic conditions.

Aflatoxin B1↗
PubMed1988

Spectral power of human limbic evoked potentials: relationship to seizure onset.

Limbic evoked potentials were recorded from intracerebral electrodes bilaterally implanted in the hippocampi of 16 epileptic patients undergoing evaluation for surgical resection of a seizure focus. Spectral analysis of the limbic evoked potentials revealed consistently lower spectral power of both low-band (1-12.6 Hz) and high-band (13-20 Hz) components recorded form the hippocampus that was associated with the electrographically confirmed seizure focus as compared to the contralateral side. Limbic evoked potential recordings appear to be useful in the determination of a focal functional deficit and thus in identifying the site of epileptogenic pathology. Further, the results support the hypothesis of a local generator for limbic evoked potentials and demonstrate that limbic evoked potentials in humans include not only low-frequency, high-amplitude electric field changes, but also a high-frequency component.

Adolescent↗