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Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 19 recordsLinked to original sources

How important is race/ethnicity as an indicator of risk for specific AIDS-defining conditions?

In order to examine differences in the prevalence of AIDS-defining conditions by race/ethnicity, we analyzed U.S. surveillance data for 203,470 adolescents and adults diagnosed with AIDS from 1988 through 1992. A number of AIDS-indicator conditions were more common among certain racial/ethnic groups. The prevalence of extrapulmonary tuberculosis was higher among blacks, Hispanics, Asians/Pacific Islanders, and American Indians/Alaskan Natives than among whites. The prevalence of isosporiasis and toxoplasmosis was higher among Hispanics than among blacks or whites. Furthermore, the likelihood of being diagnosed with extrapulmonary tuberculosis (TB), toxoplasmosis, or isosporiasis was generally higher among foreign-born than among U.S.-born persons of all racial/ethnic groups. The prevalence of all malignancies was higher among whites than among blacks or Hispanics. However, the magnitude of prevalence differences by race/ethnicity was reduced when we controlled for other demographic and exposure risk categories. Although race/ethnicity was significantly associated with the prevalence of a number of conditions, the relative frequency and patterns of AIDS-indicator conditions in different populations are probably most influenced by differences in (1) underlying prevalence or exposure to various etiologic agents causing these conditions, (2) diagnosis and reporting of conditions, and (3) access to care and therapy for HIV-related conditions.

Acquired Immunodeficiency Syndrome

Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay.

The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products, were tested in an in vitro disk diffusion assay against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelial cell line (I18). The results demonstrate a dose-dependent inhibition of cancerous cell growth, while non-cancerous cell growth is not inhibited by the same dosages. All of the acetogenins, irrespective of their various structural types, inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. These results show that the Annonaceous acetogenins are an extremely potent class of compounds, and their inhibition of cell growth can be selective for cancerous cells and also effective for drug resistant cancer cells, while exhibiting only minimal toxicity to 'normal' non-cancerous cells.

Adenocarcinoma

Adenine nucleotide depletion in cryopreserved human cardiac valves: the "stunned" leaflet interstitial cell population.

Preparation protocols for human cardiac valves are intended to minimize cytotoxicity because it has been thought that viable leaflet interstitial cells may enhance homograft durability. Preimplantation factors influencing the status of these cells at the time of transplantation include ischemia, disinfection, and cryopreservation freezing programs. In these experiments, adenine nucleotide quantitation was undertaken to assess metabolic consequences of preparation; preharvest ischemia served as an independent variable to examine the relationship between time of procurement (postmortem) and high-energy phosphate status of the cryopreserved leaflets at thaw. Nucleotides were measured using high-performance liquid chromatography performed on extracts of semilunar cusps from 25 cryopreserved human valves with documented ischemic times. Results indicate total adenine nucleotides (TAN; [ATP] + [ADP] + [AMP], in nmol TAN/mg leaflet protein) are higher (P < 0.05) after < 2 h of harvest ischemia (1.16 +/- 0.36) than with ischemic times of 3-6 h (undetected), 7-12 h (0.18 +/- 0.07), and 13-20 h (0.06 +/- 0.06). Depletion of ATP was similar, with many leaflets devoid of detectable levels. Net utilization of leaflet energy stores demonstrates time dependency when assayed after completed processing. However, relatively elevated catabolites, even with brief ischemia, and infrequently identified ATP, ADP, and AMP, suggest a consumption so accelerated that the following cryopreservation it is virtually independent of procurement-associated ischemia. We conclude resumption of a functional cell population obligates significant de novo phosphoanhydride boned reformation or a repopulation of dead/dying interstitial cells from a subset surviving the apparently severe rigors of valve preparation.

Adenine Nucleotides

Contraception. A clinical review for the internist.

Effective use of contraception allows couples to control their fertility and, in certain instances, is associated with important noncontraceptive benefits. Surgical sterilization offers safe, effective, and permanent contraception for women and men. Low-dose OCPs offer safe, effective contraception for most women able and willing to take pills consistently. In addition, their use confers a variety of important noncontraceptive benefits. The availability of long-acting progestin injectable and implantable methods has made highly effective and convenient birth control available for women who are not good pill takers as well as for those for whom contraceptive doses of estrogen are contraindicated. Barrier methods are readily available and provide protection against STDs; unfortunately, erratic use is all too often associated with inadequate contraceptive efficacy. IUDs offer convenient, highly effective contraception for appropriate candidates.

Contraception

Coccidioidomycosis among persons with AIDS in the United States.

Adults and adolescents diagnosed with AIDS from 1987 through 1992 residing in counties endemic (selected counties in California, Arizona, Texas, New Mexico, Nevada, Utah) and not endemic for Coccidioides immitis were assessed to determine the frequency of and risk factors for disseminated coccidioidomycosis. Of 602 AIDS patients reported with disseminated coccidioidomycosis, 323 (1.1% of AIDS patients) resided in C. immitis-endemic counties and 279 (0.1% of AIDS patients) resided in C. immitis-nonendemic counties in 35 states. In multivariate analysis, patients with disseminated coccidioidomycosis in C. immitis-endemic counties were more likely to be injecting drug users (odds ratio, 2.6; 95% confidence interval, 1.8-3.7) and blood product recipients (odds ratio, 3.6; 95% confidence interval, 1.5-8.3) than to be homosexual or bisexual men. Of patients with disseminated coccidioidomycosis, 63% had died by 1 year after AIDS diagnosis. Disseminated coccidioidomycosis should be considered in AIDS patients in all areas of the United States.

AIDS-Related Opportunistic Infections

Amrinone combined with dobutamine improves hemodynamics and oxygen delivery without down-regulation of cardiac beta-adrenergic receptor density in porcine endotoxemia.

Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O2 delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia coli lipopolysaccharide (endotoxin) or equivolumetric .9% NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T = 120-240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 micrograms/kg/min) (AMRlow); DOB (10 micrograms/kg/min) (DOB); AMR infusion (40 micrograms/kg/min) + DOB (AMRlow+DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 micrograms/kg/min) (AMRhigh); or AMR bolus (.75 mg/kg) followed by infusion (40 micrograms/kg/min) + DOB (AMRhigh+DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for beta-adrenergic receptor analysis. Endotoxin significantly (p < .05) decreased cardiac index, right ventricular ejection fraction, stroke volume index, maximum rate of rise of left ventricular pressure (dP/dtmax), mean arterial pressure, and O2 delivery, and increased pulmonary vascular resistance and mean pulmonary arterial pressure (p < .05). AMRlow+DOB significantly (p < .05) increased cardiac index, dP/dtmax, right ventricular ejection fraction, stroke volume index, O2 delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. beta-Adrenergic receptor density (Bmax) and binding equilibrium dissociation constant (KD) for [3H]dihydroalprenolol were not affected by endotoxin or any treatment (p < .05). Endotoxin-induced hemodynamic deterioration and decreased O2 delivery was attenuated by AMRlow+DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O2 delivery complicated by pulmonary hypertension.

Amrinone

Biphasic defibrillation waveforms reduce shock-induced response duration dispersion between low and high shock intensities.

Mechanisms underlying defibrillation threshold reduction with biphasic waveforms remain unclear. The interaction of local shock-induced voltage gradients, which change with distance from the shocking electrode, and the state of membrane repolarization results in different cellular responses that may influence the success of defibrillation. We used intracellular microelectrodes and S1S2 pacing protocols in myocardial cell aggregates to determine the effects of shock intensity and waveform on refractory period responses during simulated fibrillation (3 s of S1 pacing at 180-ms cycle length). We simulated defibrillation by electric field stimulation S2 using 8-ms monophasic (MS2) and 4/4 biphasic (BS2) waveforms (65% total tilt) delivered at intensities of 1.5, 3, and 5 times S1 diastolic threshold, or approximately 2 to 7 V/cm. Responses following MS2 varied with S2 intensity and coupling interval (P < .001). When averaged over the last 10 ms of the refractory period, MS2 produced a negligible response (8.8 +/- 1.4 ms) at 1.5 times diastolic threshold and a prolonged response (53.0 +/- 3.1 ms) at 5 times diastolic threshold (P < .01). In contrast, BS2 response duration did not change significantly (P - NS) between 1.5 times diastolic threshold (35.1 +/- 12.6 ms) and 5 times diastolic threshold (46.2 +/- 2.7 ms). Our results suggest that biphasic waveforms not only prolong response duration at low shock intensity but reduce dispersion of refractoriness produced by differing local potential gradients generated by defibrillation shocks compared with monophasic waveforms. Preventing dispersion of refractoriness and prolonging shock-induced responses may improve biphasic waveform efficacy at low shock intensity.

Action Potentials

Transforming growth factor-beta 1 inhibits inflammatory cytokine-induced C3 gene expression in astrocytes.

In this report, we show that transforming growth factor-beta (TGF-beta) can significantly inhibit the capacity of IFN-gamma, IL-1 beta, and TNF-alpha to augment expression of the central component of complement C3 in the human astroglioma cell line D54-MG. Treatment of D54-MG cells with TGF-beta alone had no dose- or time-dependent effect on basal C3 protein or mRNA levels. However, TGF-beta suppressed induction of C3 expression at both the protein and mRNA level in D54-MG cells treated with inflammatory cytokines. The extent of TGF-beta-mediated suppression was cytokine-specific, and suppression of protein production did not necessarily correspond to reductions in steady-state mRNA levels for each cytokine. Similar findings were obtained at the mRNA level using primary rat astrocytes, indicating that TGF-beta can modulate C3 gene expression in nontransformed astrocytic cells. Kinetic studies demonstrated that TGF-beta mediates its suppressive effect for at least 72 h, and that pretreatment of cells with TGF-beta for as little as 2 h significantly reduced the ability of all three inflammatory cytokines to enhance C3 expression. Our results suggest that TGF-beta may play an important role in modulating the endogenous synthesis of complement by astrocytes under inflammatory conditions.

Animals

Sparing of motor function after cortical injury. A new perspective on underlying mechanisms.

Historically, many theories have been offered to explain recovery of function following permanent brain injury. Because specific functional deficits often occur after injury to certain neuroanatomical locations, it has been tempting to suggest that within the brain, structure equals function (this interpretation, of course, has its roots in "phrenology", the 19th-century practice of detecting mental and behavioral traits by examining the skull's shape). Views that were common until recently emphasized structural and functional rigidity in the brain, which would seem to provide little opportunity for the occurrence of compensation. However, the observation that a considerable amount of spontaneous functional recovery occurs after many permanent brain lesions requires some explanation for the recovery that involves modification of intact portions of the brain. Recent research has provided data that reveal several forms of brain plasticity, including changes in neurotransmitter sensitivity, collateral sprouting, and diaschisis. Evidence supporting claims that beneficial behavioral recovery occurs through such physiological modifications in the brain are abundant in the literature, although, in general, there has not been any empirical establishment of causality.

Animals

Assessment of epidermal dendritic cell markers and T-lymphocytes in psoriasis.

Epidermal dendritic and T-cell counts have been performed in lesional and non-lesional skin from 35 psoriatic patients. The aims were to investigate absolute changes and interrelationships between these cellular elements in psoriasis and to explain apparent discrepancies between these results and reports in the literature. In non-lesional skin, the most frequently expressed dendritic cell marker was CD1a. HLA-DR+ and alpha-mannosidase+ dendritic cells were approximately 50 per cent and S100+ cells were 25 per cent as frequent. T-lymphocytes were rare, CD4+ cells predominating. In lesional psoriatic epidermis, there was a definite increase (approximately two-fold) in the absolute number of CD1a+ dendritic cells. This differs from the conclusions from the majority of previous studies. However, when cell counts were expressed per unit area of vertical section, there was a decrease in CD1a+ cells in lesional skin, which is an explanation for this discrepancy. There was a greater increase in absolute HLA-DR+ cell counts, so that the numbers of cells expressing CD1a and HLA-DR were similar in lesional skin. S100 expression increased proportionately with CD1a+, but there was no absolute increase in alpha-mannosidase+ cells, which might represent a separate sub-population of dendritic cells. The greatest cellular increase was in T-lymphocytes, particularly CD8+. In lesional skin, direct correlations have been demonstrated between epidermal thickness, HLA-DR+ dendritic cells and T-lymphocytes, particularly CD8+ cells. We would suggest that the present method of quantification is of value for the analysis of absolute changes in epidermal infiltrates, particularly psoriasis, and could be applied to other epidermal pathologies.

Adult

Dual structural and functional phenotypes of the porcine aortic valve interstitial population: characteristics of the leaflet myofibroblast.

The cellular properties of semilunar cardiac valve leaflets may be more complex than previously assumed. In particular, the cells of the leaflet matrix which are likely critical to proper cusp function are a poorly described population to date. We hypothesized that, similar to the matrix cells of atrioventricular valves, aortic valve leaflet interstitial cells (AoLIC's) possess characteristics of both fibroblasts (matrix secretion) and smooth muscle cells (contraction). Porcine AoLIC's were structurally examined for contractile and stress fiber protein assemblies using transmission electron microscopy and immunocytochemistry. Contractile function in response to vasoactive stimuli was directly assessed using AoLIC's cultured on flame-polymerized silicone, with cell contraction identified by the appearance of wrinkles in the substratum after challenge with each agent. The structural analyses showed cellular microfilaments were often organized into various contractile arrangements including polygonal networks, and that AoLIC's are rich in smooth muscle-specific alpha-actin. Incomplete basal laminae often associated with myofibroblasts were observed. Contraction experiments indicated a responsivity of similar latency, but variable peak and duration to 10(-7) M L-epinephrine, 3.2 x 10(-7) M angiotensin II, 110 microM carbachol, 50 mM KCl, 3.2 x 10(-7) M bradykinin, 110 microM isoproterenol, and 5 x 10(-7) M endothelin I. Soluble and insoluble matrix secretion was confirmed with FITC-conjugated monoclonal antibodies to chondroitin sulfate, fibronectin, and prolyl-4-hydroxylase. These data show that the AoLIC's are best designated as myofibroblasts. The unusual features of the myofibroblast may be central to lifelong aortic leaflet durability.

Animals

Effects of appearance-based admonitions against sun exposure on tanning intentions in young adults.

This experiment compared the effectiveness of health-based versus appearance-based messages on university students' intentions to protect their skin against the sun's damaging rays. One hundred thirty-four Ss completed a measure of appearance motivation, then responded to 1 of 3 essays about tanning and skin cancer. One essay described the health risks of excessive sun exposure, one essay discussed the deleterious effects of tanning on physical appearance, and a control essay described the process by which tanning occurs. Overall, the essay that dealt with the negative effects of the sun on appearance was most effective in promoting intentions to practice safe-sun behaviors. However, the appearance-based essay was effective primarily among Ss who were low rather than high in appearance motivation.

Adolescent

Surveillance of AIDS-defining conditions in the United States. Adult/Adolescent Spectrum of HIV Disease Project Group.

OBJECTIVE: To examine the reporting of AIDS-defining illnesses using two national surveillance systems. METHODS: Comparison of AIDS indicator diseases reported to the national AIDS reporting system (ARS) for AIDS cases diagnosed from January 1990-December 1992 among individuals aged > 13 years in 10 metropolitan areas, with that observed in the Adult/Adolescent Spectrum of HIV Disease (ASD) project, a surveillance project that monitors the clinical diagnoses of HIV-infected individuals receiving medical care. RESULTS: In the 10 metropolitan areas, 39,265 individuals with AIDS were reported to ARS, and 5969 with AIDS had medical record reviews as part of ASD. At initial AIDS diagnosis, the number of indicator diseases reported to ARS was almost identical to the number observed in ASD (mean number of diagnoses, ARS 1.3; ASD 1.2). However, ASD recorded a greater number of diagnoses over time than ARS (mean number of indicator diagnoses > 12 months after initial diagnosis, ASD 2.3; ARS 1.4). Conditions that typically occur late in the course of AIDS such as Mycobacterium avium infection and cytomegalovirus disease, were more frequently recorded by ASD than by ARS. CONCLUSION: ARS provides complete, population-based information on the frequency of AIDS-defining conditions at initial diagnosis. However, specialized surveillance projects such as ASD are needed to accurately describe subsequent AIDS-defining conditions.

AIDS-Related Opportunistic Infections

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