Effects of amphetamine on locomotor activity in adult and juvenile alcohol-preferring and -nonpreferring rats.

The objective of this study was to determine whether functional differences exist in amphetamine-induced locomotor activity between alcohol-naive alcohol-preferring (P) and -nonpreferring (NP) rats during postnatal development and during adulthood. Using a between-subjects design, 20- and 28-day-old P and NP rats (male and female counterbalanced, n=11-16/line) were habituated for 30 min in a photocell activity field. Each rat received subcutaneous injections of saline or 0.

Serosurvey of Borrelia burgdorferi infection among U.S. military personnel: a low risk of infection.

A serosurvey of 9,673 United States military personnel was conducted to estimate infection rates with Borrelia burgdorferi sensu stricto, which is the cause of Lyme disease in the United States. Initial screening of sera from 9,673 military personnel on active duty in 1997 was performed by enzyme-linked immunosorbent assay (ELISA); supplemental testing of all ELISA-positive sera was performed by Western blot. Initial screening identified 1,594 (16.

The role of tumor necrosis factor signaling pathways in the response of murine brain to irradiation.

Late effects after radiotherapy for brain tumors can be severe and tend to limit the efficacy of this treatment modality. The mechanisms governing the development of late radiation-induced lesions in the brain are not clear, but they are preceded by cycles of molecular and cellular events including production of cytokines, one of which is tumor necrosis factor (TNF)-alpha. There is literature to support possible roles for TNF-alpha as a contributor to edema, gliosis, and demyelination in the brain, all of which are histopathologically associated with radiation-induced brain damage.

CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells.

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking.

alpha-Fetoprotein-specific tumor immunity induced by plasmid prime-adenovirus boost genetic vaccination.

alpha-Fetoprotein (AFP) is a potential target for immunotherapy in hepatocellular carcinoma; both the murine and human T-cell repertoires can recognize AFP-derived epitopes in the context of the MHC. Protective immunity can be generated with AFP-engineered dendritic cell-based vaccines. We now report a DNA-based immunization strategy using a prime-boost approach: coadministration of plasmid DNA encoding murine AFP and murine granulocyte-macrophage colony-stimulating factor followed by boosting with an AFP-expressing nonreplicating adenoviral vector.

Regional central nervous system densities of delta-opioid receptors in alcohol-preferring P, alcohol-nonpreferring NP, and unselected Wistar rats.

The densities of delta-opioid receptors in the central nervous system of alcohol-naive, adult, male, alcohol-preferring P, alcohol-nonpreferring NP, and Wistar rats were examined with the use of quantitative autoradiography. Slides with coronal 20-microm sections through the regions of interest were incubated in 5 nM [3H]-[D-Pen(2),D-Pen(5)]enkephalin (DPDPE) to label delta(1)-opioid receptor sites. Nonspecific binding was determined in the presence of 10 microM naloxone.

The proteasome in cancer biology and treatment.

During the last 30 years, investigation of the transcriptional and translational mechanisms of gene regulation has been a major focus of molecular cancer biology. More recently, it has become evident that cancer-related mutations and cancer-related therapies also can affect post-translational processing of cellular proteins and that control exerted at this level can be critical in defining both the cancer phenotype and the response to therapeutic intervention. One post-translational mechanism that is receiving considerable attention is degradation of intracellular proteins through the multicatalytic 26S proteasome.

Molecular pathways that modify tumor radiation response.

Aberrant expression of signal transduction molecules in pathways controlling cell survival, proliferation, death, or differentiation are a common feature of all tumors. The identification of the molecules that are involved allows the development of novel tumor-specific strategies. Not surprisingly, targeting these pathways often also results in radiosensitization.

Alcohol-naïve alcohol-preferring (P) rats exhibit higher local cerebral glucose utilization than alcohol-nonpreferring (NP) and Wistar rats.

Background: The present study determined local cerebral glucose utilization (LCGU) rates in alcohol-naïve alcohol-preferring (P), alcohol nonpreferring (NP), and outbred Wistar rats to test the hypothesis that innate differences in functional neuronal activity are present in limbic regions as a result of selective breeding for high-alcohol drinking behavior.

Methods: All procedures were conducted during the dark cycle. 2-[14C]deoxyglucose ([14C]2-DG; 125 microCi/kg) was injected intravenously and timed arterial blood samples were collected during the following 45 min and assayed for glucose and [14C]2-DG content.

Prospective study of respiratory infections at the U.S. Naval Academy.

Midshipmen at the U.S. Naval Academy have recently suffered epidemics of upper respiratory tract infections.

Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes.

Methods And Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-alpha, mIL-1 alpha, mIL-1 beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-gamma) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay.

Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation.

Long-term effects of alcohol drinking on cerebral glucose utilization in alcohol-preferring rats.

The 2-[14C]deoxyglucose (2-DG) quantitative autoradiography technique was used to determine rates of local cerebral glucose utilization (LCGU) in discrete brain regions in alcohol-chronic (A-C), alcohol-deprived (A-D) and alcohol-naïve (A-N) adult, male alcohol-preferring (P) rats. The hypothesis to be tested is that neuronal alterations occur as a result of chronic alcohol drinking and some of these alterations persist for long periods in the absence of alcohol. Following 6 weeks of daily 4-h scheduled access sessions to 15% (v/v) ethanol and water, group A-D received only water during the sessions over the next 2 weeks, whereas groups A-C and A-N continued to receive ethanol-water and water-water, respectively.

Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of alcohol-preferring rats.

Background: The alcohol deprivation effect (ADE) is a temporary increase in the voluntary intake of ethanol solutions following a period of alcohol deprivation. Multiple deprivations can prolong the expression of an ADE. This study examined the effects of initial deprivation length, concurrent exposure to multiple ethanol concentrations, and number of deprivation exposures on the magnitude and duration of the ADE in alcohol-preferring (P) rats.

Effects of ethanol on the dorsal raphe nucleus and its projections to the caudate putamen.

The objective of this study was to examine the effects of intraperitoneal injection of ethanol on the activity of the dorsal raphe nucleus (DRN) serotonin (5-hydroxytryptamine [5-HT]) system and its projections to the rostral caudate putamen (CPu) and determine whether rapid tolerance to the effects of ethanol develops in this system. Adult, male, Wistar rats were used in these experiments. In experiment 1, a microdialysis procedure was used to determine (a) the effects of acute intraperitoneal administration of ethanol (1.

Fine specificity analysis of an HLA-A2.1-restricted immunodominant T cell epitope derived from human alpha-fetoprotein.

Human alpha-fetoprotein (AFP) is a potentially important target for the immunotherapy of hepatocellular carcinoma (HCC). AFP(542-550) (GVALQTMKQ) is one of several HLA-A2.1-restricted immunodominant AFP peptides that consistently generate AFP-specific T cell responses in human T cell cultures and in HLA-A2.

Alcohol reinforcement and voluntary ethanol consumption.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The organizer/chair was Ting-Kai Li and the co-chair was Rainer Spanagel. The presentations were (1) Genetic differences in alcohol drinking and reinforcement: The sP and sNP Rats, by Giancarlo Colombo; (2) Ventral tegmental area-Neuroanatomical substrate for alcohol reinforcement, by William J.

D1-D2 dopamine receptor interaction within the nucleus accumbens mediates long-loop negative feedback to the ventral tegmental area (VTA).

The objective of the present study was to examine the effects of perfusion of dopamine (DA) D1- and D2-like receptor agonists in the nucleus accumbens (ACB) on the long-loop negative feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats employing ipsilateral dual probe in vivo microdialysis. Perfusion of the ACB for 60 min with the D1-like receptor agonist SKF 38393 (SKF, 1-100 microM) dose-dependently reduced the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA were not changed. Similarly, application of the D2-like receptor agonist quinpirole (Quin, 1-100 microM) through the microdialysis probe in the ACB reduced the extracellular levels of DA in the ACB in a concentration-dependent manner, whereas extracellular levels of DA in the VTA were not altered.

Responsivity and development of tolerance to the motor impairing effects of moderate doses of ethanol in alcohol-preferring (P) and -nonpreferring (NP) rat lines.

Background: Research comparing the alcohol-preferring (P) and -nonpreferring (NP) rat lines has detected an apparent association between ethanol preference and lower responsivity to ethanol, as well as the capacity to develop and maintain tolerance to ethanol's effects. However, past studies of tolerance to ethanol's effects generally involved relatively high doses. The present study examined recovery from functional impairment induced by moderate doses of ethanol after a single dose (responsivity) and after multiple doses (development of tolerance) in the P and NP rat lines.

Quantitative autoradiography of mu-opioid receptors in the CNS of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats.

Background: The binding of [3H]DAMGO to mu-opioid sites was measured in the CNS of selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats to test the hypothesis that high alcohol preference is associated with higher densities of mu-opioid receptors.

Methods: Adult, alcohol-naïve male HAD and LAD rats from replicate line 1 were decapitated and their brains frozen in isopentane. Brain sections were incubated with 5 nM [3H]DAMGO, and nonspecific binding was determined in the presence of unlabeled DAMGO.

Local cerebral glucose utilization rates in alcohol-naïve high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats.

Background: The present study compared baseline local cerebral glucose utilization (LCGU) values within reward-relevant brain regions in alcohol-naïve, adult male high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats from replicate lines 1 and 2.

Methods: 2-[14C]Deoxyglucose ([14C]2-DG) was injected (125 microCi/kg) intravenously during the rats' dark cycle. Timed arterial blood samples were collected over 45 min and assayed for glucose as well as [14C]2-DG content.

Ionizing radiation affects 26s proteasome function and associated molecular responses, even at low doses.

Background And Purpose: Ionizing radiation is known to activate certain signal transduction pathways, the regulation of which could involve post-transcriptional as well as transcriptional mechanisms. One of the most important post-transcriptional pathways in eukaryotic cells is the ATP- and ubiquitin-dependent degradation of proteins by the 26s proteasome. This process controls initiation of many cellular stress responses, as well as inflammatory responses under control of the transcription factor NF-kappaB.