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Biomedical subjects

J A Rush

Publications and source records attributed to J A Rush.

At least 19 recordsLinked to original sources
PubMed2000

Gambling behavior of Louisiana students in grades 6 through 12.

OBJECTIVES: The prevalence of problem and gambling behavior, the average age of onset of gambling behavior, and the co-occurrence of gambling disorder with substance use were determined in the Louisiana student population grades 6 through 12. METHODS: A stratified randomized sample of 12,066 students in Louisiana schools during the 1996-1997 school year was surveyed about gambling behavior using the South Oaks Gambling Screen--Revised for Adolescents (SOGS-RA). RESULTS: Fourteen percent of the students never gambled, 70.1 percent gambled without problems, 10.1 percent indicated problem gambling in the past year (level 2 according to the SOGS-RA), and 5.8 percent indicated pathological gambling behavior in the past year (level 3). Weekly or more frequent lottery play was reported by 16.5 percent. The average age of onset of gambling behavior was 11.2 years. Fifty-nine percent of the students with problem and pathological gambling behavior reported frequent alcohol and illicit drug use. CONCLUSIONS: A significant minority of Louisiana students in grades 6 through 12-15.9 percent--acknowledged gambling-related symptoms and life problems. The association of problem and pathological gambling with use of alcohol, tobacco, and marijuana provides preliminary support for the inclusion of gambling among other adolescent risk behaviors.

Adolescent↗
PubMed1998

Gambling behavior of adolescents in residential placement in northwest Louisiana.

BACKGROUND: The rapid expansion of legalized gambling in the United States necessitates evaluation of its impact on vulnerable populations, especially adolescents. METHODS: Gambling behavior in 135 adolescents in residential placement in northwestern Louisiana was measured using the South Oaks Gambling Screen-Revised for Adolescents. RESULTS: During the past year, 41% of these adolescents reported minimal problems with gambling, 21% reported level 2 or problem gambling, and 38% reported level 3 or pathologic gambling. In this population, the first drink of alcohol, the first cigarette, and the first experience with gambling began on average at 11 years of age, with the first use of marijuana and the first episode of alcohol intoxication occurring a year later. CONCLUSION: The level 2 rate of gambling exceeded the upper extreme of the adolescent community sample range, and the level 3 rate was approximately six times the reported level 3 community prevalence rate for adolescents. Residential placements sites should be considered when developing prevention programs for gambling disorders.

Adolescent↗
PubMed1998

SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: in vitro anti-inflammatory actions.

First-generation phosphodiesterase 4 (PDE4) inhibitors, such as rolipram, inhibit the activation of immune and inflammatory cells. The clinical use of these compounds is limited by gastrointestinal side effects, such as increased acid secretion and nausea. Consequently, the challenge has been to design novel PDE4 inhibitors that maintain the anti-inflammatory actions of rolipram while achieving an improved side effect profile. Among the first of this new class of PDE4 inhibitors specifically designed to have an improved therapeutic index relative to earlier compounds is SB 207499 (Ariflo) [c-4-cyano-4-(3-cyclopentyloxy-4-methoxy-phenyl)-r-1-cyclohexanecarboxyl ic acid]. In this study, we compared the anti-inflammatory and gastric secretogogue activities of SB 207499 with those of rolipram. The cellular models used were (1) histamine release from human basophils, (2) tumor necrosis factor-alpha generation in human monocytes, (3) degranulation of human neutrophils, (4) antigen-driven proliferation and cytokine synthesis from human T cells and (5) acid secretion from isolated rabbit gastric glands. SB 207499 inhibited the activation of a variety of immune and inflammatory cells in a concentration-dependent manner: (1) histamine release in basophils [-log IC25 = 6.6 +/- 0.3 vs. 8.0 for (R)-rolipram], (2) lipopolysacchride-induced TNF-alpha formation in monocytes [-log IC50 = 7.0 +/- 0.1 vs. 7.2 +/- 0.1 for (R)-rolipram], (3) fMLP-induced degranulation in neutrophils [-log IC15 = 7.1 +/- 0.2 vs. 6.4 +/- 0.5 for (R)-rolipram], (4) house dust mite induced-proliferation of peripheral blood mononuclear cells [-log IC40 = 6.5 +/- 0.3 vs. 6.4 +/- 0.3 for (R)-rolipram] and (5) ragweed-induced production of interferon-gamma [-log IC50 = 5.4] and interleukin-5 [-log IC50 = 5.0]. Although SB 207499 inhibits the activation of a variety of immune and inflammatory cells with a potency equal to that of rolipram, it is > 100-fold less potent than the latter compound as an acid secretagogue [-log EC50 = 6.1 +/- 0.1 vs. 8.3 +/- 0.2 for (R)-rolipram]. Collectively, these data indicate that SB 207499 retains the anti-inflammatory activity of the prototypical PDE4 inhibitor rolipram but is substantially less likely to stimulate gastric acid secretion.

Animals↗
PubMed1997

Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function.

A growing family of proteins, known as the chemokines, play an important role in the recruitment and activation of inflammatory cells. The purpose of these studies was to characterize the chemokine receptors present on human sodium butyrate differentiated EoL-3 cells (dEoL-3 cells). Using a combination of 3' rapid amplification of cDNA ends and nested polymerase chain reaction, we detected mRNA for CC chemokine receptor (CCR)1, CCR2, CCR3 and low level of CCR5. Radioligand binding studies demonstrated high-affinity saturable binding for both 125I-macrophage inflammatory protein (MIP)-1alpha and 125I-regulated upon activation normal T cell expressed and secreted (RANTES) with Kd values of 1.4 and 7 nM, respectively. Competition binding with chemokines demonstrated exactly the same rank order of potency for displacement of both ligands: MIP-1alpha approximately monocyte chemoattractant protein (MCP)-3 approximately RANTES > MIP-1beta >> MCP-1 >>> IL-8. RANTES, MCP-3 and MIP-1alpha all produced concentration-dependent transient increases in intracellular calcium concentrations in dEoL-3 cells. Desensitization studies indicated that RANTES, MIP-1alpha and MCP-3 interacted at the same receptor, which is identical in characterization to the cloned CCR1. 125I-MCP-1 also demonstrated high-affinity satuable binding to dEoL-3 cells with a Kd value of 0.4 nM. Competition studies showed that MCP-3 was slightly more potent than MCP-1 and MCP-2. MIP-1alpha, MIP-1beta and RANTES were unable to displace 125I-MCP-1. Addition of either MCP-1 or MCP-3 produced a concentration-dependent elevation of intracellular calcium with a maximun response 2-fold higher than that seen with RANTES or MIP-1alpha. Desensitization studies indicated that MCP-1 and MCP-3 function through CCR2 on these cells. Thus binding and functional studies indicate that dEoL-3 cells express functional CCR1 and CCR2 and that these cells may serve as an important system with which to study the regulation and role of these receptors.

Chemokine CCL2↗
PubMed1996

Association of the anti-inflammatory activity of phosphodiesterase 4 (PDE4) inhibitors with either inhibition of PDE4 catalytic activity or competition for [3H]rolipram binding.

Phosphodiesterase 4 (PDE4) inhibitors are novel anti-inflammatory compounds. Unfortunately, the archetypal PDE4 inhibitor rolipram produces central nervous system and gastrointestinal side-effects. To exploit these agents, we need to identify PDE4 inhibitors that retain the anti-inflammatory activity with a reduced potential to elicit unwanted side-effects. PDE4 possesses both cyclic AMP catalytic activity that is inhibitable by rolipram and a high affinity binding site for rolipram. The function of this high affinity rolipram binding site is unclear; however, certain pharmacological effects of PDE4 inhibitors are associated with competition for this site. Since PDE4 inhibitors suppress both monocyte and neutrophil activation, the present experiments were carried out to establish a correlation between suppression of monocyte activation [tumor necrosis factor alpha (TNF alpha) formation] or suppression of neutrophil activation (degranulation) with inhibition of either PDE4 catalytic activity or [3H] rolipram binding. Suppression of TNF alpha formation demonstrated a strong correlation with inhibition of PDE4 catalytic activity (r=0.87; P<0.01; Spearman's Rho = 0.79, P<0.05), whereas there was no correlation with inhibition of [3H]rolipram binding(r=0.21, P>0.5; Spearman's Rho=0.16, P>0.5). Suppression of neutrophil degranulation was not associated with inhibition of PDE4 catalytic activity (r=0.25, P>0.4; Spearman's Rho=0.33, P>0.2), but was associated with inhibition of [3H]rolipram binding (r=0.68, P<0.05; Spearman's Rho=0.6, P=0.06). These results indicate that anti-inflammatory effects of PDE4 inhibitors can be associated with either inhibition of PDE4 catalytic activity or high affinity rolipram binding.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Epidemiology of early primary hypertension and implications for prevention: the Bogalusa Heart Study.

Epidemiological studies of BPs in children and young adults over the past 20 years have contributed considerably to understanding the early onset of primary hypertension. Observations from autopsies and echocardiographic studies, together with long-term BP studies, of children clearly indicate that primary hypertension begins in early childhood. Although abnormal BP levels in children are much lower than the adult criteria used for clinical diagnosis of hypertension, essential hypertension is identifiable in early life. Complex haemodynamic and metabolic mechanisms related to essential hypertension are also being identified in childhood. The development of intervention programs in an attempt to prevent hypertension in its early phases suggests hypertensive cardiovascular disease is preventable. Environmental factors (improved dietary factors, altering electrolyte intake, prevention of obesity and increased activity levels) are critical elements to prevention. Children and young adults identified as high risk for hypertension need to be targeted for prevention of early cardiovascular renal disease. Also, as hypertension is so prevalent, attempts should be made to control environmental factors in the general public. Preventive programmes established by primary healthcare physicians, paediatricians and para-professionals can have a major impact on the reduction of hypertension and its complications of cardiovascular renal disease in the future.

Adolescent↗
PubMed1986

DA1 receptor mediates dopamine-induced relaxation of opossum lower esophageal sphincter in vitro.

The objective of the present experiments was to determine the specific receptor subtype through which dopamine (DA) receptor agonists relax the lower esophageal sphincter in vitro. Opossum lower esophageal sphincter smooth muscle strips were placed in oxygenated Krebs' solution containing propranolol and cocaine. The tissues were placed at a tension that gave maximum relaxation to electrical field stimulation and were then pretreated with phenoxybenzamine. The effects of DA, and the DA receptor agonists epinine and apomorphine were determined. In addition, agonist responses were studied in the presence of the selective DA2 receptor antagonist domperidone, a mixed DA1/DA2 receptor antagonist metoclopramide, and the selective DA1 receptor antagonists bulbocapnine and SK&F 83566. The DA agonists relaxed the smooth muscle strips in the following order of potency: DA greater than epinine greater than apomorphine. Domperidone did not antagonize DA- or apomorphine-induced relaxation. Metoclopramide failed to alter DA-induced relaxation. Bulbocapnine and SK&F 83566 significantly inhibited the relaxation induced by DA. These data indicate that DA-induced lower esophageal sphincter relaxation in vitro is mediated by DA1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1984

Leucopenia as an adverse reaction to carbamazepine therapy.

Carbamazepine is a commonly used anticonvulsant agent, particularly in the management of partial seizures. Because of the low incidence of adverse effects associated with this drug, these are often ignored or forgotten. The cases of two patients in whom neutropenia has developed after prolonged therapy with carbamazepine, which illustrate the dose-related nature of this adverse reaction, are reported.

Adult↗
PubMed1983

Kinetic analysis of the accumulation of gamma-aminobutyric acid by particulate fractions of rat brain: comparison of the effects of nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid.

Kinetic analyses indicate that nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid (cis-3-ACHC) inhibit GABA accumulation by similar mechanisms of action. Both amino acids are competitive inhibitors of particulate GABA accumulation when GABA and the inhibitor are added simultaneously to tissue fractions. However, preincubating the tissue with either amino acid produces noncompetitive inhibition of GABA accumulation at low concentrations of inhibitor and mixed inhibition at higher concentrations. The possible roles of intrasynaptosomal mechanisms and of astroglia in producing these effects are discussed. The most notable difference between cis-3-ACHC and the other amino acid inhibitors of GABA accumulation, such as nipecotic acid, cis-4-OH-nipecotic acid, guvacine, beta-proline, homo-beta-proline, and 2,4-diaminobutyric acid (DABA), is that cis-3-ACHC is approximately 3.5 times more potent as an inhibitor following preincubation. Thus, while cis-3-ACHC does inhibit GABA transport, its major site of action in the synaptosome may be intracellular.

Amino Acids↗