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Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 127 records · Page 7Linked to original sources

Comparative effects of fluoxetine, amitriptyline and serotonin on functional motor recovery after sensorimotor cortex injury.

A recent investigation of the effects of the antidepressants desipramine and trazodone on behavioral recovery in brain-injured animals suggested that antidepressants, which act to increase noradrenergic activity in the brain, may facilitate the rate of recovery, whereas those that act to increase serotonergic (5-HT) activity may hinder recovery and reinstate deficits in recovered animals. The present study was designed to evaluate these findings further by assessing the effect of a single intraperitoneal injection of fluoxetine (a relatively pure 5-HT reuptake blocker), amitriptyline (a mixed 5-HT and noradrenergic reuptake blocker with alpha 1-adrenergic receptor blocking activity) or a single intraventricular infusion of 5-HT on recovery of beam-walking ability in animals with a unilateral sensorimotor cortex injury. None of the drugs significantly affected the rate of recovery. Although fluoxetine was ineffective in reinstating the motor deficit in recovered animals, amitriptyline reinstated the deficit in a dose-dependent fashion. Infusion of 5-HT resulted in an extremely transient reinstatement of the deficit, which was largely attributable to its short-term sedative properties. These results suggest that 5-HT may be less involved in functional recovery than previously thought. They also add further support to previous findings that indicate that drugs which act to antagonize alpha 1-adrenergic activity (e.g., phenoxybenzamine) may interfere with motor recovery after sensorimotor cortex injury. An appreciation of the potential impact of certain antidepressants on functional recovery in brain-injured patients appears warranted.

Amitriptyline↗

Comparison of individuals receiving anonymous and confidential testing for HIV.

We assessed the magnitude, demographics, seroprevalence, and reasons for site selection among South Carolina residents who chose to be tested in bordering states offering anonymous testing for human immunodeficiency virus (HIV). Residents tested from July 1990 through July 1991 at selected HIV testing sites in bordering states were surveyed and HIV test results were recorded. Of the 75 residents tested at these sites, 66 (88%) were white, 44 (59%) were male, and 9 (12.3%) of the 73 whose test results were recorded were HIV infected. During the same period, 57,137 individuals were HIV tested in-state by the state health department, of which 1,752 (3.1%) were positive. Residents tested outside the state were more likely to be HIV infected, male, and white than individuals tested within the state. Our findings suggest that although large numbers of South Carolinians are not HIV tested anonymously in other states, those tested anonymously out of state have a different demographic and risk profile than those tested confidentially in state.

Adolescent↗

Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential.

Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, we used the Beeler-Reuter ventricular action potential computer model with the Drouhard-Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm2. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities.

Action Potentials↗

Dysfunction and safety factor strength-duration curves for biphasic defibrillator waveforms.

Newly developed biphasic waveforms significantly lower defibrillation threshold in animal and clinical models. However, underlying mechanisms and optimum waveform shape are unknown. Defibrillation shocks produce dysfunction; safety factor, the ratio of shock intensity inducing dysfunction to that producing stimulation of partially refractory cells, is an important parameter for defibrillator waveforms. We determined dysfunction and safety factor strength-duration curves for symmetric and asymmetric (50% undershoot) monophasic and biphasic rectangular (0%-tilt) waveforms. Dysfunction threshold, defined as the voltage producing a 4-s postshock contractile arrest, was determined for waveforms with total durations from 1 to 40 ms. For all waveforms, dysfunction threshold decreased with waveform duration. At all durations, dysfunction threshold was similar for symmetric monophasic and biphasic waveforms with the same total duration. In contrast, asymmetric biphasic waveforms increased dysfunction threshold 14 +/- 3% (P < 0.005) compared with monophasic control waveforms. Because long-duration, low-tilt, biphasic waveforms improve excitation threshold for refractory cells, they should improve defibrillation threshold. Asymmetric waveforms have the additional advantage of improving safety factor by reducing postshock dysfunction.

Animals↗

Completeness of reporting of diagnosed HIV-infected hospital inpatients.

To assess the completeness of human immunodeficiency virus (HIV) reporting among hospital inpatients whose records listed diagnostic codes for HIV infection but who did not meet the 1987 AIDS case definition, we conducted a statewide hospital study of admissions between January 1, 1986 and December 31, 1990. Of the 396 HIV-infected hospital inpatients identified, 313 (79%) had been reported to the State HIV Registry. HIV reporting was less complete for patients who were older and/or were blood product recipients. Of the 313 reported patients, 189 (60%) had been reported prior to their first hospital admission. Temporal improvements were noted in the completeness of HIV reporting among the hospital patients (1986: 65%; 1987: 81%; 1988: 64%; 1989: 82%; 1990: 86%; Chi square for linear trend 9.6, p < 0.01) and prior to their first hospital admission (1986: 31%; 1987: 34%; 1988: 49%; 1989: 64%; 1990: 72%; Chi square for linear trend 26.6; p < 0.01). Women were more likely than men to be reported prior rather than during or after their first hospital admission (71% vs. 55%; p < 0.01). Of the 155 patients with CD4+ T-lymphocyte test results, 41 had CD4+ counts < 200 mm3 and met the 1993 but not the 1987 AIDS case definition. In South Carolina most (79%) diagnosed, hospitalized, HIV-infected patients had been reported to the State HIV REgistry, with improvements in reporting occurring over time. Findings suggest that the 1993 AIDS case definition will improve our ability to monitor severe morbidity related to HIV.

Adolescent↗

Use of a thick-film capillary column for the analysis of organic acids in body fluids.

An improved method for the identification and quantification of organic acids in body fluids employing capillary gas chromatography-mass spectrometry has been developed. A thick-film capillary column, that combines the properties of a capillary column with those of a megabore column, has been successfully introduced into an existing method. Analysis over a concentration range from 1 mumol/l to 500 mumol/l body fluid is possible. This permits the assay of samples that are usually obtained in small volumes, e.g. cerebrospinal fluid.

Acids↗

Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells.

In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1 beta or TNF-alpha, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1 beta or TNF-alpha, respectively. D54-MG cells require a minimal 1 h exposure to IL-1 beta in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-alpha. Simultaneous treatment of D54-MG cells with IL-1 beta and interferon-gamma (IFN-gamma) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-alpha and IFN-gamma. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1 beta (5.3-fold increase) and TNF-alpha (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1 beta and IFN-gamma. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-gamma, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.

Animals↗

Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes.

In this report, we have shown the expression of the complement regulatory proteins decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 on human D54-MG astroglioma cells by several methods, including immunofluorescence, flow cytometry and Western blotting and Northern blot analysis. These studies demonstrate that all three proteins are structurally and antigenically similar to their counterparts expressed on HepG2 and SW480 cells (hepatocyte and epithelial cell lines, respectively). D54-MG cells express mRNA for all three proteins of the appropriate size(s). The phosphatidylinositol-specific enzyme, PIPLC, cleaved DAF from the surface of D54-MG cells, demonstrating that DAF is linked by a glycophospholipid anchor as has been shown for other cell types. Flow cytometry demonstrates that primary rat astrocytes also constitutively express all three regulatory proteins. These data are the first to demonstrate the expression of CD59 on astrocytes, and the presence of all three regulatory proteins on astrocytes suggests that regulation of complement activation in the central nervous system is important in neural host defense mechanisms.

Animals↗

A large salmonellosis outbreak associated with a frequently penalized restaurant.

Between January and June 1990, Restaurant A in Greenville, South Carolina repeatedly failed local health department inspection and was repeatedly sanctioned. In September 1990, two persons, hospitalized with salmonellosis after attending a convention catered by Restaurant A, contacted the South Carolina Department of Health and Environmental Control. We inspected Restaurant A, interviewed food handlers, and surveyed by telephone persons from every sixth business attending the convention. Of 398 persons interviewed, 135 (34%) reported gastroenteritis. Nine had culture-confirmed salmonella infection. People who ate turkey were 4.6 times more likely to become ill than those who did not eat turkey (95% confidence interval 2.0, 10.6). We estimate that of 2430 attendees, 824 became ill. Sanitarians judged Restaurant A's kitchen too small to prepare over 500 meals safely. The cooked turkey was unrefrigerated for several hours, incompletely rewarmed, and rinsed with water to reduce its offensive odour prior to serving. Stronger sanctions may be needed against restaurants that repeatedly fail local health department inspection.

Animals↗

Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart.

BACKGROUND: Recent studies examining mechanisms of defibrillation have focused on prolongation of graded cellular response duration during refractory period stimulation. This mechanism assumes that defibrillation shocks interact with ventricular cells during the process of repolarization. METHODS AND RESULTS: To test this assumption, we examined monophasic action potentials (MAPs) from 171 episodes of induced ventricular dysrhythmia associated with loss of systemic perfusion pressure in 22 patients undergoing nonthoracotomy defibrillator implantation. Ventricular fibrillation (VF)/polymorphic ventricular tachycardia (PVT), defined by an irregular limb lead I morphology, was present in 156 dysrhythmia episodes. Monomorphic ventricular tachycardia (VT), present in the remaining 15 episodes, was associated with regular limb lead morphology. All episodes were examined for MAP cycle length, variation, fractionation, and repolarization. VF/PVT cycle length was 215 +/- 28 msec, with a 14 +/- 7% (33 +/- 20-msec) cycle length variability. Nonfractionated MAP recordings were found in 122 of 156 VF/PVT episodes. Episodes characterized as VF by ECG criteria (n = 136) showed lack of MAP diastole and had a mean cycle length of 213 +/- 27 msec. Episodes characterized as PVT (n = 20) were associated with amiodarone therapy and had occasional MAP diastole and a significantly longer mean cycle length of 257 +/- 22 msec (p < 0.001). Monomorphic VT had a mean cycle length of 261 +/- 29 msec, minimal cycle length variation (1 +/- 3%), absence of MAP fractionation, and consistent degree of repolarization before restimulation. CONCLUSIONS: These results suggest that human VF cycle length is limited by cellular refractory periods so that defibrillating shocks interact with cells primarily during their refractory period.

Action Potentials↗

Inhibition of adenosine deaminase and nucleoside transport. Utility in a model of homograft cardiac valve preimplantation processing.

Human cardiac valves are increasingly used in the reconstruction of ventricular outflow tracts and offer performance advantages over porcine and mechanical prostheses; the durability of these replacements has been associated with leaflet interstitial cell viability and a presumed sustained function after implantation. Preimplantation tissue preparation entails sequential steps that are potentially cytotoxic and may therefore affect functional cell survival at thaw. We defined the metabolic consequences of each interval using semilunar cusps from 118 porcine valves to model a homograft preparation with 40 minutes of fixed cadaveric (harvest) ischemia. Fifty-eight valves served as controls and were first processed according to standard cryopreservation protocol; nucleosides were extracted at the end of each step to differentiate independent contributions to high-energy phosphate depletion. Sixty simultaneously harvested leaflets were administered the nucleoside transport inhibitor p-nitrobenzy-thionosine (NBMPR) and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) at procurement, to attempt adenosine salvage and restitution of processing-incurred adenine nucleotide losses. High-performance liquid chromatography was used to compare adenosine triphosphate, diphosphate, and monophosphate and diffusible nucleopurines of the control and EHNA/NBMPR-treated groups. Control results indicate that disruption of the adenosine triphosphate-diphosphate cycle occurs independently with antibiotic disinfection and cryopreservation. However, throughout all preparation steps, adenine nucleotides were maintained at harvest (baseline) concentrations in the EHNA/NBMPR valves. This suggests that salvage therapy may protect a significant number of cells from net high-energy phosphate catabolism. If, with further study, the durability of transplanted valves is concluded to benefit from retained leaflet interstitial cell viability, such enhancement of metabolic tolerance to the obligatory processing may facilitate functional recovery.

Adenine↗

Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients.

OBJECTIVES: To study the incidence of eosinophilia-myalgia syndrome, the risk factors associated with the syndrome, and the clinical spectrum of illness associated with L-tryptophan use in an exposed population. DESIGN: Retrospective cohort and nested case-control studies of risk factors for eosinophilia-myalgia syndrome using inpatient and outpatient chart reviews, telephone interviews, and in-person patient interviews. Descriptive study of clinical course of L-tryptophan users. SETTING: Office practice of one psychiatrist based in a small city (population 43,467) in South Carolina. PATIENTS: Eligible subjects were all patients from the practice who used L-tryptophan during the 1989 study interval. Of these, 418 (87%) were interviewed. MAIN OUTCOME MEASURES: Clinical spectrum of illness associated with L-tryptophan use, including definite and possible cases of eosinophilia-myalgia syndrome. RESULTS: Among the 418 interviewed L-tryptophan users, we identified 47 definite cases (11%) and 68 possible cases (16%) of eosinophilia-myalgia syndrome, most of which involved patients who were using one retail brand of L-tryptophan (brand A). Among the 157 brand A users, we identified 45 definite cases (29%) and 36 possible cases (23%) of eosinophilia-myalgia syndrome, and the risk for the syndrome increased as the brand A dose increased. Fifty percent (19 of 38) of those using more than 4000 mg/day developed definite eosinophilia-myalgia syndrome, and 84% (32 of 38) developed either definite or possible eosinophilia-myalgia syndrome. On multivariate analysis, risk for definite eosinophilia-myalgia syndrome was associated with brand A dose and age of the patient; however, gender, race, and use of other medications were not associated with the syndrome. CONCLUSIONS: These results suggest that many people exposed to the agent causing eosinophilia-myalgia syndrome may develop illness, and dose of presumably contaminated L-tryptophan is the single most important predictor of eosinophilia-myalgia syndrome. The broad range of signs and symptoms reported by patients using L-tryptophan illustrates that a strict case definition may identify only about half of those affected.

Adult↗

Alteration of stromal protein and integrin expression in breast--a marker of premalignant change?

Interactions between epithelia and the extracellular matrix are important in the modulation of cellular growth, differentiation, and motility. To investigate the possible roles of these interactions in the neoplastic process, this study examines the expression of the integrin subunits a2, a6, beta 1, and beta 4 and the stromal protein tenascin in 53 breast carcinomas, non-involved breast tissue from 21 of these cases, and 32 normal/benign cases. Frozen tissue and an indirect immunoperoxidase technique were used throughout. Linear staining in relation to the basement membrane was seen for all integrins in the normal/benign cases. The carcinomas showed complete loss of reactivity in 65 per cent of cases for a2, 80 per cent for a6 and beta 4, and 90 per cent for beta 1. Those showing reactivity displayed a diffuse cytoplasmic type of staining. The non-involved breast tissue showed linear basement membrane type staining with a2 and beta 1, but for a6 and beta 4 66 per cent of cases displayed reactivity identical to that of the corresponding tumour. For tenascin, band-like staining around ducts was seen in normal/benign cases, with a diffuse coarse reactivity in all carcinomas. Most non-involved cases stained as for normal breast. The altered a6 beta 4 integrin staining in non-involved tissue in cancerous breast may be an early event in the neoplastic process, and as such, may be of use as a marker of pre-malignant change.

Basement Membrane↗

Interferon-gamma regulation of C3 gene expression in human astroglioma cells.

In this report, we show that the human astroglioma cell line, D54-MG, constitutively expresses C3 mRNA and secretes antigenically detectable C3 protein. The cytokine interferon-gamma (IFN-gamma) enhances C3 mRNA and protein expression by D54-MG cells in a dose- and time-dependent manner. C3 mRNA from both D54-MG cells and primary human adult astrocytes has the same apparent size (5.1-5.2 kb) as C3 mRNA from hepatocyte and monocyte cell lines. Constitutive C3 mRNA levels in D54-MG cells and primary human astrocytes are comparable. Primary rat astrocytes also constitutively express C3 mRNA, which is enhanced upon exposure to IFN-gamma. These data are novel since expression of C3 in other cell types is refractory to IFN-gamma. In the central nervous system (CNS), endogenous complement production by astrocytes, and enhancement by the cytokine IFN-gamma, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis (MS).

Astrocytes↗