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Biomedical subjects

C J Nelson

Publications and source records attributed to C J Nelson.

At least 19 recordsLinked to original sources
PubMed2000

Phenotypic and functional assessments of immune status in the rat spleen following acute heroin treatment.

Heroin use is associated with an increased incidence of several types of infections, including HIV. Yet few studies have assessed whether heroin produces pharmacological alterations of immune status that might contribute to the increased rate of infections amongst heroin users. The present study investigated whether a single administration of heroin to rats produces dose-dependent alterations in functional measures of immune status and in the distribution of leukocyte subsets in the spleen. The results showed that heroin produces a dose-dependent, naltrexone-reversible suppression of the concanavalin A-stimulated proliferation of T cells, lipopolysaccharide-stimulated proliferation of B cells, production of interferon-gamma and cytotoxicity of natural killer (NK) cells in the spleen. Heroin's suppressive effect on NK cell activity results in part from a heroin-induced decrease in the relative number of NKR-P1A(hi) CD3- NK cells in the spleen. Heroin also decreases the percent of a splenic granulocyte subset, the CD11b/c+ HIS48(hi) cells, whose function currently is unknown. In contrast, heroin does not alter relative numbers of CD4+ CD3+ T cells, CD8+ CD3+ T cells, CD45+ B cells, NKR-P1A(lo) CD3+ T cells, CD11b/c+ ED1+ (or CD11b/c+ HIS48-) monocytes/macrophages or CD11b/c+ ED1- (or CD11b/c+ HIS48+) total granulocytes in the spleen. Collectively, these findings demonstrate that heroin produces pharmacological effects on functional and phenotypic measures of immune status.

Animals↗
PubMed1999

Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.

The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory.

Animals↗
PubMed1998

Gender differences in factor structure of the Self-Administered Alcoholism Screening Test.

Recent studies have revealed differences between men and women alcoholics in symptoms, consequences, and help-seeking behavior related to alcohol usage. Based on these findings, it was hypothesized that gender differences also would appear on alcohol screening instruments. The Self-Administered Alcoholism Screening Test (Colligan, Davis, & Morse, 1988: SAAST: Swenson & Morse, 1975) of 1,920 men and 1,775 women was subjected to a within-gender, principle-components, factor analysis with a varimax rotation. Gender differences at the component level were revealed. Men endorsed the "help-seeking for alcohol-related problems" component while women endorsed the "help-seeking for emotional problems" component. In addition, men expressed concern about receiving a psychiatric label while women expressed concern about receiving a drinker label. The results suggest that different items need to be used in screening women for alcohol-related problems.

Adult↗
PubMed1998

Severity, time, and beta-adrenergic receptor involvement in surgery-induced immune alterations.

Although investigations of surgical stress in animals have reported immune alterations, surprisingly little is known about the variables or mechanisms contributing to the effect. Thus, we completed a series of experiments investigating the immune-altering effects of surgery severity, time of maximal immune alterations, and recovery, as well as the involvement of beta-adrenergic receptors in surgery-induced immune alterations in Lewis rats. Immune alterations included natural killer (NK) cell cytotoxicity as well as B- and T-cell proliferation. Results showed increased immune suppression with larger incisions (6 cm > 3 cm > anesthesia > saline). In addition, maximal immune alterations induced by surgery occurred after 24 h; anesthesia effects predominated at the earlier time points. Recovery of immune status varied depending on the immunological measure of interest. Although NK cell cytotoxicity returned to control values within 2 days, B-cell proliferation remained suppressed for at least 8 days, and T-cell proliferation did not begin to recover until 4-8 days following the surgical procedure. To assess the mechanisms involved in surgery-induced immune alterations, follow-up assessments evaluated the effect of nadolol, a beta-adrenergic receptor antagonist, on surgery-induced immune alterations. Results show that nadolol blocks the surgery-induced reduction in B- and T-cell proliferation but has no effect on the suppression of NK cell cytotoxicity. These results indicate the need to consider surgical severity and postoperative time of immune assessment when investigating the immune-altering effects of surgery. Importantly, activation of beta-adrenergic receptors appears to play a modulatory role in surgery-induced immune alterations.

Adrenergic beta-Antagonists↗
PubMed1998

Characterization and use of a recombinant retroviral system for the analysis of drug resistant HIV.

A recombinant retroviral system was used for the analysis of early HIV breakthrough infection in the presence of antiviral drugs. The use of replication-defective HIV allowed a quantitative analysis of a single cycle of infection. This report characterizes this recombinant HIV system and demonstrates it's validity in comparison to standard assays. It is demonstrated that the protease inhibitor XM323 inhibits both early and late events in the HIV life-cycle, while dextran sulphate inhibits only early events. In addition, it is shown that this system can be used for detecting and quantitating drug resistant HIV. Thus, the use of this system may provide both novel information about the stage of the viral life-cycle inhibited and a preliminary assessment of the mechanism(s) responsible for breakthrough infection in the presence of antiretroviral drugs.

Anti-HIV Agents↗
PubMed1998

Dose-dependent effects of multiple acute cocaine injections on maternal behavior and aggression in Sprague-Dawley rats.

Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towards 8 surrogate male pups on PPD 1 and PPD 3 and for aggression towards a male or female intruder in the presence of their litter on PPD 6 and PPD 10. Compared to saline and untreated controls, cocaine-treated dams exhibited more disruptions in MB on both PPD 1 and PPD 3 and were less aggressive towards an intruder, regardless of intruder sex, on PPD 6 and PPD 10. In most cases MB was altered in a dose-dependent manner with the higher doses of cocaine resulting in a greater disruption of behavior.

Aggression↗
PubMed1997

Daily fluoxetine administration impairs avoidance learning in the rat without altering sensory thresholds.

1. Male rats given daily intraperitoneal injections of fluoxetine (10 mg/kg) were slower to escape foot shock by jumping a low barrier. 2. When switched to a shuttle task requiring two crosses to terminate shock, the FLU-treated animals failed to learn in 55 trials. 3. A second experiment found FLU-treated animals could learn a one-way avoidance response, but were significantly slower to learn than control animals. 4. FLU-treated animals were no different than controls on tests of sensory thresholds for foot shock or heat. 5. Tests of motor behaviors revealed no differences in latency to traverse a narrow beam to reach a goal box, however FLU-treated animals were less active in an open field. 6. Several hypotheses can account for these data, the most promising being that a central motivational system (fear) is less active in FLU-treated animals.

Analgesia↗
PubMed1997

Comparison of the time course of morphine's analgesic and immunologic effects.

UNLABELLED: Morphine, an opioid analgesic commonly prescribed and abused, produces immune-altering effects. Whether morphine's antinociceptive and immunologic effects occur concurrently is unknown. Therefore, we investigated the time course of morphine's immunologic and antinociceptive effects. Rats were given a 15-mg/kg morphine injection (subcutaneously), and experimental assessments were taken at 30 min, 1 h, 2 h, 6 h, 12 h, and 24 h after treatment. Immune measures included natural killer (NK) cell activity, proliferation of splenic T and B lymphocytes, and cytokine production. Antinociception was assessed by using the tail withdrawal assay. Results show that morphine's immunomodulatory effects on NK cell activity begin within 30 min, continue for at least 12 h, and return to control values by 24 h. In contrast, proliferation of splenic T and B cells and interferon-gamma production are not altered within 30 min; maximal suppression occurs at 1 h, and recovery begins within 2 h. In all immune measures, therefore, maximal suppression is present at the 1-h time point, and recovery is complete within 24 h. Morphine induces antinociception 30 min to 2 h after drug administration; recovery is complete within 6 h. These results suggest the possibility that different mechanisms modulate morphine's immunologic and analgesic effects. IMPLICATIONS: Acute morphine treatment in rats produces immune alterations and antinociception. Although there are slight differences in morphine's maximal immunological and antinociceptive effects, morphine suppresses immune status at time points concordant with its antinociceptive effects. These effects should be considered when administering morphine to patients whose systems are immunocompromised.

Analgesia↗
PubMed1997

Epidemiology, preventive services, and illnesses of international travelers.

Medical preparation of travelers to overseas locations is an important part of military medical care. We reviewed pre-travel records of patients attending the travel clinic at the National Naval Medical Center (NNMC) and used a post-travel questionnaire to determine the most frequent medical problems associated with international travel. Among 1,416 individuals who received pre-travel care at NNMC, there were 760 (54%) males and 656 (46%) females, the median patient age was 48 years, the most common reason for travel was pleasure, and the median duration of travel was 21 days. The most common destinations were Asia (27%), Africa (15%), Europe (13%), Central America/Caribbean (12%), and South America (11%). The median number of immunizations prescribed was three. Malaria chemoprophylaxis was prescribed to 45%. The average cost of vaccines and medications to medically prepare a traveler was $67. Among 271 (82%) who returned the post-travel questionnaire, the most common illnesses reported were diarrhea (23%) and upper respiratory infections (19%); medical treatment was sought by 9%. Properly informed, military physicians can provide a valuable service at a reasonable cost to reduce the risk of travel-acquired medical problems and illnesses.

Adult↗
PubMed1995

Sanctuary growth of human immunodeficiency virus in the presence of 3'-azido-3'-deoxythymidine.

Human immunodeficiency virus (HIV) resistance to the nonnucleoside reverse transcriptase inhibitors emerges very rapidly under selection in culture and in patients. In contrast, zidovudine (3'-azido-3'-deoxythymidine [AZT])-resistant HIV generally emerges in patients only after more-prolonged therapy. Although HIV can be cultured from many patients shortly after the initiation of AZT treatment, characterization of the virus that is cultured generally indicates that it is sensitive to AZT. To initiate an evaluation of the mechanisms contributing to early HIV breakthrough in the presence of AZT and other nucleoside analogs, we have utilized replication-defective HIV encoding reporter genes. These recombinant HIV allow a quantitative analysis of a single cycle of infection. Results with these defective HIV indicate that early infection in the presence of AZT often results from the infection of a cell which is refractory to the antiretroviral effects of AZT. Characterization of a cell line derived from one such cell has demonstrated decreased accumulation of AZT triphosphate, increased phosphorylation of thymidine to thymidine triphosphate, and increased levels of thymidine kinase activity. In addition, AZT inhibition of replication-competent HIV infection is also significantly impaired in this cell line. Attempts to detect and characterize the mechanisms responsible for early viral infection after initiation of AZT therapy may result in the development of new strategies for prolonged suppression of viral infection prior to the emergence of drug-resistant virus.

Cell Line↗
PubMed1993

Recombinant retroviral systems for the analysis of drug resistant HIV.

Two recombinant retroviral systems are described that can be used to analyze antiretroviral drug activity and HIV breakthrough (replication in the presence of the drug). The first system utilizes a recombinant HIV encoding beta-galactosidase as a reporter gene (HIV-LacZ). The defective HIV-LacZ virus is produced in COS cells after co-transfection of a plasmid encoding the HIV-LacZ genome with a plasmid encoding HIV proteins necessary for packaging and infectivity. Subsequent infection of CD4+ target cells, followed by assay for LacZ expression, permits the rapid identification of individual virus-infected cells. This system can be used to quantitate the inhibition of early events in the HIV replicative cycle and is suitable for the screening of compounds for anti-HIV activity. However, this system cannot be used to analyze HIV drug resistance because of the limited genetic heterogeneity of the virus that is produced in COS cells. To circumvent this problem, a second system has been developed in which heterogenous recombinant HIV is produced by rescue with replication-competent 'helper' HIV. This system required the production of CD4+ cell lines containing defective proviruses encoding either LacZ or guanosine phosphoribosyl transferase (gpt). The defective proviruses are rescued by infection of the cell lines with 'helper' HIV and used to infect target cells in the presence of antiretroviral agents. Subsequent reporter gene assay is used to identify virus-infected cells. This system has been used to detect rare HIV breakthrough infection of cells in the presence of the non-nucleoside reverse transcriptase inhibitor TIBO R82150. Similar analyses with other antiretroviral agents, alone and in combination, may help identify therapeutic strategies that minimize breakthrough replication of HIV.

Animals↗
PubMed1992

Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). I. Multireplicated dose-response studies in four inbred strains and one outbred stock of mice.

A large-scaled multireplicated developmental toxicity study was conducted in various strains/stocks of mice with the herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), by gavage on Gestational Days 6 through 14. The most important attributes of the study design were replicated test groups, a minimum of four dose levels per replicate, use of multiple stocks/strains of animals to obtain an estimate of the range in sensitivities due to genotype, complete pathological evaluation of maternal animals, and histopathological as well as teratological evaluation of the fetuses. Developmental toxicity was observed at doses below those producing discernible or measurable maternal toxicity. Regression and/or probit analyses were conducted to determine whether a dose-response relationship existed. Reduced fetal weight and increased incidence of cleft palate and embryolethality were the most significant prenatal effects of 2,4,5-T exposure observed in this study. Each strain/stock exhibited a dose-related decrease in fetal weight with the CD-1 mice having the steepest slope and the A/J mice having the shallowest slope. There was a striking similarity among the slopes of the dose-response curves for the various strains/stocks. The mean incidence of embryolethality in the A/J strain was significantly greater than that of the other strains or stocks. There was substantial variation among replicates within strains. The use of the replicated study design was logistically necessary due to the magnitude of the study and it also served to increase the statistical power of the study.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1992

Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated dose-response studies with technical and analytical grades of 2,4,5-T in four-way outcross mice.

A series of multireplicated developmental toxicity studies were conducted in four-way outcross mice and CD-1 outbred mice administered either analytical or technical grades of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) by gavage on Gestational Days 6 through 14. The formulations of 2,4,5-T differed by a factor of 10-fold in 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. Reduced fetal weight and increased incidences of cleft palate and embryolethality were the most significant prenatal effects of both formulations of 2,4,5-T observed in all strains/stocks of mice. Both the outcross and outbred mice exhibited a dose-response relationship with each of the above endpoints and the dose-response curves were parallel. There were no embryotoxic or fetotoxic differences between the technical and analytical grades of 2,4,5-T with regard to extent of fetal weight reduction, resorption rate, or cleft palate incidence. There was little difference in the results between the four-way outcross mouse and the CD-1 outbred mouse.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1991

Use of recombinant retroviruses to characterize the activity of antiretroviral compounds.

This report describes the use of a recombinant murine retrovirus encoding beta-galactosidase (PLJ beta-gal retrovirus) to study the antiretroviral activity of zidovudine (AZT) and other nucleoside analogs. The PLJ beta-gal virus permits the rapid and unequivocal identification of individual virus-infected cells arising from a single cycle of viral replication. With this model system, AZT is shown to completely and irreversibly prevent retrovirus infection of proliferating cell lines as measured by a lack of reporter gene expression. On the other hand, AZT is less effective in protecting growth-arrested cells from retroviral infection. Recombinant retroviruses such as the PLJ beta-gal virus are potentially useful reagents for the identification and characterization of antiretroviral compounds.

3T3 Cells↗
PubMed1990

Pharmacokinetics of 2,4,5-T in mice as a function of dose and gestational status.

A pharmacokinetic study was conducted in CD-1 mice with the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as a function of dose (15, 30, 60, and 90 mg/kg, iv) and gestational status (nonpregnant, day 6, 10, 13, and 17 of gestation, and postpartum). Analysis for 2,4,5-T and its metabolites was based on an electron-capture gas-liquid chromatographic method. Pharmacokinetic stimulation of the blood, urine, and feces data from each mouse was performed on an analog-digital hybrid computer system based on a two-compartment model with parallel, first-order elimination kinetics. Data analysis demonstrated dose-independent kinetics for most pharmacokinetic parameters but a gestational status-dependence. There was a tendency, as indicated by an increase in the biologic half-life and AUC and decrease in clearance and total percent recovery, for pregnant animals to eliminate 2,4,5-T more slowly as gestation progressed, resulting in potentially increasing fetal exposure during the later stages of pregnancy.

2,4,5-Trichlorophenoxyacetic Acid↗