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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 199 records · Page 11Linked to original sources
PubMed1995

Protective effects of doxycycline in mesenteric ischemia and reperfusion.

In rats splanchnic artery occlusion (SAO) of the celiac and superior mesenteric arteries for 1 hr., followed by a period of reperfusion initiates a severe form of circulatory shock, which typically leads to death within 2 hrs, characterized by multiorgan failure in which neutrophils play a central role. Doxycycline (Dc) pretreatment (10mg/kg; 2 hrs. prior to occlusion) significantly increased the survival time and leukocytes retention in circulation and decreased the hemoglobin levels in the contents of the small intestine. Dc did not influence serum alanine aminotransferase or amylase levels (marker enzymes for liver and pancreas damages respectively) at the time of death. Creatinine phosphate kinase, a marker of cardiotoxicity, was significantly increased in serum from Dc-treated rats. We conclude that pretreatment with Dc has a protective effect in the SAO rat model and this protection cannot be ascribed directly to a specific sparing influence on the liver, pancreas, or heart.

Animals↗
PubMed1994

Increased transcription and coordinate stabilization of mRNAs for secreted immunoglobulin alpha heavy chain and kappa light chain following stimulation of immunoglobulin A expressing B cells.

Immunoglobulin A (IgA) plays a key role in host protection at mucosal surfaces, yet little is known regarding the molecular mechanisms that govern the expression of this isotype. The studies herein investigated mechanisms that control IgA secretion in response to stimulation with interleukin-4 and interleukin-5, cytokines which are known to regulate IgA responses, and to bacterial lipopolysaccharide. Two mechanisms were shown to govern agonist induced IgA expression in a murine IgA expressing B cell line. In the initial period after stimulation, increased mRNA levels for the secreted form of alpha heavy chain (alpha s), and kappa light chain were paralleled by a transient increase in transcription rates of the corresponding genes. However, with prolonged agonist stimulation, gene transcription rates decreased to near control levels, and increased mRNA levels were associated with a coordinate increase in alpha s and kappa mRNA stability. In striking contrast, these agonists did not affect levels or stability of mRNA for the membrane form of alpha heavy chain (alpha m). Alpha s mRNAs contained multiple poly(A) addition sites located 13-32 nucleotides downstream of a single AAUAAA sequence. Nonetheless, the differential usage of these sites as a mechanism for controlling alpha s mRNA stability could be excluded, since the relative abundance of these different alpha s mRNAs did not differ significantly after agonist stimulation. These data, taken together, suggest that sequences within 107 nucleotides of the 3' end of alpha s mRNA, which are absent in alpha M mRNA, are required for the regulation of alpha s mRNA stability, possibly by acting as targets for regulated trans-acting cellular factors.

Animals↗
PubMed1994

Stimulus timing effects on Wada memory testing.

OBJECTIVE: To determine the effects of presenting Wada memory stimuli at different times after intracarotid amobarbital injection on Wada memory asymmetries. DESIGN: Wada memory asymmetries from three timing series were related to the laterality of eventual temporal lobectomy. SETTING: Academic institution epilepsy surgery program. PATIENTS: Forty-three patients with complex partial seizures who later underwent anterior temporal lobectomy (left temporal lobectomy, 24 patients; right temporal lobectomy, 19 patients). No patient included had abnormalities on magnetic resonance imaging scans to suggest a lesion other than gliosis. RESULTS: Memory performance for objects whose presentation began approximately 45 seconds after amobarbital administration differentiated laterality of seizure onset. Memory for items presented later and after partial return of language (on average 3 minutes 40 seconds postinjection) also differed as a function of ipsilateral vs contralateral injection, but at a lower level of statistical significance. Memory for items presented last during the procedure (on average 6 minutes postinjection) discriminated seizure groups at a still lower level of statistical significance. When used to predict lateralized temporal lobe impairment in individual patients, early object memory performance was significantly better than memory performance employing either middle (56%) or late (43%) stimulus presentation timings. CONCLUSION: The results of early object memory testing are superior to those obtained from stimulus presentation later in the procedure in documenting temporal lobe dysfunction associated with a lateralized seizure onset.

Adult↗
PubMed1994

Evidence for a p53-independent pathway for upregulation of SDI1/CIP1/WAF1/p21 RNA in human cells.

SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent contact-inhibited or serum-deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth-arrest-inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of gamma-radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild-type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis.

Antimetabolites↗
PubMed1994

A method for imaging of intracranial EEG electrodes using magnetic resonance imaging.

In this study, we describe a method for imaging intracerebral electrodes within a three-dimensional reconstructed image of the brain. A three-dimensional image of the brain was reconstructed from serial magnetic resonance images. The locations of intracerebral electrodes were determined from anterior-posterior and lateral skull X-rays performed after intracerebral electrode implantation. The three-dimensional reconstruction of the brain including electrode locations was displayed using IRIS Explorer Software (Silicon Graphics, Mountainview, CA). This method might improve the interpretation of electrical patterns of seizure activity recorded from intracerebral electrodes.

Brain↗
PubMed1994

Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen.

We here describe a rapid and simple expression screen method that has allowed us to isolate cDNAs coding for inhibitors of DNA synthesis from senescent human diploid fibroblasts. The assay involved transient transcriptional overexpression of a gene product encoded by a cDNA in a proliferating cell, on the assumption that this would be sufficient to block DNA synthesis in a short-term assay using tritiated thymidine autoradiography. Three cDNAs, referred to as senescent cell-derived inhibitors (sdi), that exhibit DNA synthesis-inhibitory activity when introduced into young cycling cells, were successfully identified. Expression of one of the cDNAs, sdi1, increased 10- to 20-fold in senescent compared with young cells and the increase in RNA closely paralleled the onset of the senescent phenotype and loss of cell proliferation. sdi1 expression was also increased in young cells made nondividing (quiescent) by deprivation of growth factors or contact inhibition. Following serum stimulation, RNA levels of sdi1 in quiescent cells were initially increased, but then declined to low levels just prior to the entry of the cells into S phase. In contrast, RNA levels of sdi1 in senescent cells failed to decline, suggesting a role for this gene in maintaining the senescent phenotype. The sdi1 gene has been mapped to the p arm of chromosome 6.

Amino Acid Sequence↗
PubMed1994

Doxycycline suppression of ischemia-reperfusion-induced hepatic injury.

Leukocytes, in particular polymorphonuclear neutrophils (PMNs), are believed to play a central role in ischemia-reperfusion (I/R)-induced tissue injury. Changes in endothelial cells occurring during ischemia promote PMN binding to these cells during reperfusion, which primers PMN synthesis of oxygen radicals and release of cytotoxic proteins. These events lead to vascular damage and subsequent tissue injury. Recently we have shown that doxycycline (Dc), a member of the tetracycline family of antibiotics, inhibits PMN superoxide (O2) synthesis and degranulation in vitro. It also suppresses PMN-mediated RBC, fibroblast, and endothelial cytotoxicity, properties of the drug that may make it of use to protect tissues from I/R-induced injury. In this study we demonstrate that Dc administration either prior to clamping of the portal circulation, or 1 h after the reperfusion, significantly suppressed liver damage as assessed by serum levels of a marker of hepatic injury, alanine aminotransferase (s-ALT). The reduction in s-ALT was not a result of reduced reflow in the Dc-treated rats as indicated by Evans' blue perfusion data. The findings suggest that Dc and possibly other tetracyclines may be of value in protecting tissues and organs from I/R-mediated damage even if the drug is given after the ischemic event has occurred.

Alanine Transaminase↗
PubMed1994

Do dichotic word listening asymmetries predict side of temporal lobe seizure onset?

Dichotic word listening asymmetries are thought to be useful in predicting side of temporal lobe dysfunction. However, little direct evidence exists to support this assumption in practice, especially in patients with subtle epileptogenic lesions. To determine if word listening ear asymmetries are valid predictors of side of temporal lobe seizure onset, we examined the preoperative dichotic word listening performance of 80 patients with either left (N = 41) or right (N = 39) temporal lobe (TL) seizure foci. On a group level, patients showed a statistically significant 'lesion effect' as evidenced by a relative deficit in the ear contralateral to the side of lesion. Prediction of side of seizure focus in individual cases, however, was poor: depending upon the criteria used, 61% to 80% of epileptics with unilateral temporal lobe foci did not show the expected contralateral ear deficit. Results suggest that caution be exercised when inferring side of temporal lobe seizure focus through dichotic word listening asymmetries in individual temporal lobe epilepsy cases.

Adult↗
PubMed1994

Use of scalp-sphenoidal EEG for seizure localization in temporal lobe epilepsy.

We determined the accuracy and sensitivity of scalp-sphenoidal EEG for seizure focus localization in 50 patients who became seizure-free or had rare seizures following temporal lobectomy. EEG localization was based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters. All patients became seizure-free or had rare seizures following temporal lobectomy. Localization from EEG disagreed with the side of surgery in only 1 (2%) of 50 patients. We identified 3 distinct patient groups with a low, moderate, and high likelihood of having a focal ictal EEG pattern during a seizure. These groups comprised 31% (low likelihood), 44% (moderate likelihood), and 25% (high likelihood) of patients. A model based on these results suggests that with multiple ictal EEG recordings, accurate localization from scalp-sphenoidal EEG is possible in approximately up to 65-70% of patients with temporal lobe epilepsy.

Brain↗
PubMed1994

Molecular genetic approaches to the study of cellular senescence.

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Fusion↗
PubMed1994

Role of multichannel magnetoencephalography in the evaluation of ablative seizure surgery candidates.

Magnetic source imaging (MSI) was performed on 30 ablative epilepsy surgery candidates. The technique involved high resolution multiplanar MRI images with lipid fiducials attached to the patient's head to define a head-based 3D coordinate space. Magnetoencephalography (MEG) was performed after digitizing the same fiducial points. A 37-channel magnetometer obtained data at two to five sites over each hemisphere. MEG epileptiform data were obtained with and without EEG triggering. A single equivalent current dipole model was used to determine orientation and location of a dipole generator whose surface isocontour map most closely fits the measured dipolar data for each event. The MEG data were then transformed to MRI images for source localization. In five of seven cases with ictal anterior temporal lobe foci, MSI data were localized to the same temporal lobe but did not provide additional spatial data. In 10 of 11 cases with convexity foci, MSI provided additional spatial localizing data. MSI did not verify depth electrode localization in one anterior temporal-orbital frontal and three orbitofrontal cases. In seven of eight cases in which depth EEG recordings were nonlocalizing, MSI provided insufficient localizing data. MSI appears to provide additional spatial localizing data in most cases with a convexity epileptic focus.

Analog-Digital Conversion↗
PubMed1994

Multichannel magnetoencephalographic mapping of sensorimotor cortex for epilepsy surgery.

Preliminary reports have shown a close correlation between the anatomic location of evoked magnetic somatosensory fields and intraoperative evoked somatosensory potentials in patients with mass lesions. We have performed magnetic source imaging (MSI) of sensory and motor (MER) evoked responses or fields on 4 patients with frontal convexity epileptic foci. The method involves (1) graphic overlaying of magnetoencephalography evoked field data and three-dimensional (3D) phase contrast magnetic resonance angiographic data on 3D MRI surface cortical renderings, and (2) correlating these data with intraoperative stimulation-mapped sensory and/or motor responses and local cortical venous anatomy. Our initial results indicate that the location of MSI evoked sensory data correlates closely with the results of intraoperative stimulation mapping. MSI MERs have tended to show a less discrete spatial topography, involving areas of cortex extending beyond the motor strip.

Brain Mapping↗
PubMed1994

Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment.

BACKGROUND AND PURPOSE: Activated leukocytes appear to potentiate central nervous system reperfusion injury, and agents that block leukocyte adhesion have shown neuroprotective efficacy in experimental models. Doxycycline, a tetracycline antibiotic, inhibits leukocyte function in vitro, presumably through divalent cation binding. We used a model of focal central nervous system reperfusion injury to determine the efficacy of doxycycline treatment in preserving neurological function. METHODS: Rabbits randomly received 10 mg/kg i.v. doxycycline 30 minutes before ischemia (pretreatment group) or 45 minutes after ischemia (posttreatment group) or received phosphate-buffered saline vehicle (control group) followed by 10 mg/kg q 8 hours times two. The average length of reversible spinal cord ischemia required to produce paraplegia (P50) at 18 hours was calculated for each group. RESULTS: For the control group (n = 13), the P50 was 22.8 +/- 2.2 minutes; for the pretreatment group (n = 14), 35.5 +/- 2.4 minutes (P < .01; t = 3.8); and for the posttreatment group (n = 13), 31.4 +/- 4.2 minutes (not significant; t = 1.6). Doxycycline also attenuated postischemic decreases in vivo leukocyte counts and inhibited in vitro leukocyte adhesion. Therapeutic doxycycline levels at 24 hours were confirmed in the plasma and spinal cord. CONCLUSIONS: This significant protective effect suggests that doxycycline, a safe and readily available agent, may play a role in reducing clinical central nervous system reperfusion injury.

Animals↗
PubMed1994

Wada memory performance predicts seizure outcome following anterior temporal lobectomy.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.

Adult↗
PubMed1994

CD8+ polylobated T-cell leukemia/lymphoma. A case report with immunophenotypic, ultrastructural, gene rearrangement, karyotypic, and DNA content analysis and autopsy description.

Polylobated lymphoma is a morphologic variant of malignant lymphoma characterized by large pleomorphic neoplastic cells with polylobated nuclei. We report an unusual case in a 57-year-old man with a 9-year history of an antecedent low-grade peripheral T-cell lymphoma with dermal involvement. The polylobated lymphoma expressed the CD2, 8, 45, and DR surface antigens and had a clonally rearranged T-cell receptor beta-chain gene. The DNA content analysis indicated that most of the neoplasm was DNA diploid and tetraploid, with a high S phase. Cytogenetic analysis demonstrated the presence of a clone with an abnormal karyotype 45, X, -Y, -1, -10, -10, -17, -19, +5 mar. Serology and polymerase chain reaction analysis showed no evidence of retroviral infection (human immunodeficiency virus types 1 and 2 and human T-cell lymphotropic virus types I and II). We review the literature on polylobated T-cell lymphoma.

CD8 Antigens↗