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Biomedical subjects

R J Weber

Publications and source records attributed to R J Weber.

At least 19 recordsLinked to original sources
PubMed2006

Variability in nocturnal nitrogen oxide processing and its role in regional air quality.

Nitrogen oxides in the lower troposphere catalyze the photochemical production of ozone (O3) pollution during the day but react to form nitric acid, oxidize hydrocarbons, and remove O3 at night. A key nocturnal reaction is the heterogeneous hydrolysis of dinitrogen pentoxide, N2O5. We report aircraft measurements of NO3 and N2O5, which show that the N2O5 uptake coefficient, g(N2O5), on aerosol particles is highly variable and depends strongly on aerosol composition, particularly sulfate content. The results have implications for the quantification of regional-scale O3 production and suggest a stronger interaction between anthropogenic sulfur and nitrogen oxide emissions than previously recognized.

Journal Article↗
PubMed2006

The UCSC Genome Browser Database: update 2006.

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

Amino Acid Sequence↗
PubMed2004

Immune, neuroendocrine, and somatic alterations in animal models of human heroin abuse.

We investigated immune, endocrine, and somatic alterations using two animal models of human heroin administration. In a heroin self-administration paradigm, we observed changes in immune function which suggest that the cycle of intermittent drug use is actually a stressor, which in turn not only exacerbates craving and drug-seeking behavior but also collaterally causes suppression of immune function and therefore susceptibility to disease. In another model of rats made physically dependent to heroin, we show that immune function is more broadly compromised, leading to evidence of infection, followed by chronic activation of innate immune function, cachexia, and weight loss.

Animals↗
PubMed2003

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗
PubMed2003

The UCSC Genome Browser Database.

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.

Animals↗
PubMed2001

Increased tumor necrosis factor-alpha and nitric oxide production by rat macrophages following in vitro stimulation and intravenous administration of the delta-opioid agonist SNC 80.

Opioids alter immune function by binding to opioid receptors on cells of the immune system, or indirectly by acting on receptors within the central nervous system. Mu-selective opioid agonists are generally associated with immunosuppression, whereas delta-opioid receptor-selective agonists are commonly associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the nonpeptide delta-opioid receptor agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC 80) did not alter certain parameters of immunocompetence. In the present study, we studied the in vitro and ex vivo effects of SNC 80 on rat macrophage and lymphocyte functions. We showed that SNC 80 at concentrations of 10(-7) M and 10(-6) M, significantly (P < 0.01) stimulated the in vitro production of tumor necrosis factor-alpha (TNF-alpha) (60-100% increase) and nitric oxide (34-67% increase) by resident and LPS-stimulated peritoneal macrophages. Similarly, intravenous administration of SNC 80 (6.8 mg/kg) significantly (P < 0.01) increased the production of TNF-alpha and nitric oxide (2- and 1.5-fold increases respectively, compared with saline-injected control) by LPS-stimulated splenic macrophages. In addition, intravenous injection of SNC 80 plus Con A potentiated ex vivo LPS-stimulated macrophage functions. SNC 80 could potentially be utilized in various clinical situations where immunosuppression is undesirable.

Adjuvants, Immunologic↗
PubMed2001

Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions.

Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opioid agonists such as morphine are immunosuppressive, whereas certain delta-opioid receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the non-peptidic delta-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanavalin A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reduction) by peritoneal macrophages, compared with untreated control. The mu-opioid receptor selective antagonist CTOP used at equimolar doses, significantly suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (CTOP alone did not show any effect on lymphocyte or macrophage functions). In summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu-opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathways depending on the cell type and effector function being analyzed. The mechanism (s) associated with the differential effect of CGPM-9 on these immune cells remains to be elucidated. The pharmacotherapeutic potential for compounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppress production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine.

Animals↗
PubMed2001

The health of women with cerebral palsy.

Over the past 10 years, there has been interest in describing the health and functional status of persons with CP. More recently, information specific to women with CP has become available. From these studies a better appreciation of the affect a lifelong primary disability such as CP has on an individual's life has developed. An understanding of aging with a disability, secondary conditions, associated conditions, comorbidities, and health have promoted a health and wellness agenda for women and men with CP. Women with CP are generally healthy. There appears to be no significant risk for any specific comorbiditv from CP. Women may note a modest change in function over time that may represent issues of aging, but there should be no dramatic loss of function. Any loss of function must be evaluated further for cause, and cannot be attributed to aging alone. Common secondary conditions and health issues include pain and musculoskeletal issues, bladder and bowel problems, poor dental hygiene, and possibly gastroesophageal reflux. Osteoporosis at all ages from limited mobility (secondary osteoporosis) likely is common, but only recently has bone densitometry been used for more routine evaluations; consequently, no data are available in women with CP regarding this. All health issues should be evaluated and appropriate intervention prescribed. There appear to be no significant reproductive health issues for women with CF. Women should engage in all decisions regarding diagnosis and treatment. Women with CP likely participate in some healthy behaviors. However implementing health promotion programs requires some understanding of health behavior theories and models. It may not be enough to modify existing programs for accessibility (e.g., transportation, cost. environment). Engagement in health promotion programs by women with CP must take into account individual perceptions and values, social networks, a sense of personal control, and a readiness to change attitude toward changing lifestyles.

Adult↗
PubMed2000

Differential effects of buprenorphine and morphine on immune and neuroendocrine functions following acute administration in the rat mesencephalon periaqueductal gray.

The effects of the mu-opioid receptor agonists buprenorphine and morphine on immune and neuroendocrine functions through acute action in the rat mesencephalon periaqueductal gray (PAG) were evaluated. Buprenorphine is an analgesic recently approved for the treatment of drug dependency. In this study, it was shown that injection of an equianalgesic dose of buprenorphine (related to morphine) into the ventral-caudal PAG did not alter splenic NK cell, T cell, and macrophage functions, whereas morphine significantly (p<0.001) suppressed splenic NK cell cytotoxic activity (14-50% reduction), splenic and thymic T cell proliferation to concanavalin A (Con A, 43-76% reduction), antiTCR (T cell receptor) (85% reduction) and IL-2 (36-48% reduction), and macrophage functions including nitric oxide (36-41% reduction) and TNF-alpha production (26%), and phagocytosis of Candida albicans (39%). In addition, buprenorphine was associated with significant (p<0.0001) reductions in adrenocorticotropic hormone (ACTH) and corticosterone (CSO) plasma levels, without altering norepinephrine (NE) and serotonin splenic dialysate levels. In contrast, morphine significantly (p<0.0001) increased glucocorticoid and catecholamine levels in plasma and spleen dialysates, respectively. These results indicated that buprenorphine did not activate either the hypothalamic-pituitary-adrenal (HPA) axis with glucocorticoid release, or the sympathetic nerve (SNS) activity with bioamine production, and was not associated with immunosuppression. The lack of effects of buprenorphine on neuroendocrine systems may be related to its partial agonist properties, the absence of effects on immune system function, and may be associated with the reduction in craving observed in addictive disorders.

Adrenocorticotropic Hormone↗
PubMed2000

Immunoenhancing properties of Plantago major leaf extract.

Plantago major (PM), also known as plantain, is a weed found in temperate zones worldwide. PM leaves have been associated with various biological properties ranging from antiinflammatory, antimicrobial and antitumour to wound healing. However, its mechanism of action associated with boosting of the immune function remains to be elucidated. We found that endotoxin-free methanol extracts from PM leaves, at doses of 50, 100, 250, and 500 microg/mL, were associated with 4.4 +/- 1, 6 +/- 1, 12 +/- 0.4, and 18 +/- 0.4-fold increases of nitric oxide (NO) production, and increased TNF-alpha production (621 +/- 31, 721 +/- 36, 727 +/- 36, and 1056 +/- 52 U/mL, respectively) by rat peritoneal macrophages, in the absence of IFN-gamma or LPS. NO and TNF-alpha production by untreated macrophages was negligible. In addition, PM extracts potentiated Con A-induced lymphoproliferation (3- to 12-fold increases) in a dose-dependent fashion, compared with the effect of Con A alone. The regulation of immune parameters induced by plant extracts may be clinically relevant in numerous diseases including chronic viral infections, tuberculosis, AIDS and cancer.

Animals↗
PubMed2000

Activation of rat splenic macrophage and lymphocyte functions by fumonisin B1.

Fumonisins represent a family of toxic, structurally related metabolites produced by fungi that are found in corn worldwide. We investigated the effects of the mycotoxin, fumonisin B(1), on rat splenic macrophage and lymphocyte functions. Pretreatment (24 h) of resident macrophages with fumonisin B(1) (1, 10, and 100 microg/ml) significantly (p<0.01) stimulated nitric oxide production (0.48, 2. 60, and 4.40 nmol nitrite/well, respectively), compared with the response of untreated macrophages (no nitrite detected), after 72 h of culture. Fumonisin B(1) (1 and 10 microg/ml) and IFN-gamma acted in an additive manner to activate nitric oxide production. The response of IFN-gamma (50 U/ml)-activated macrophages (1.68 nmol nitrite/well) was potentiated (3.52, 4.96, and 4.44 nmol nitrite/well) by fumonisin B(1) (1, 10, and 100 microg/ml, respectively). In addition, fumonisin B(1) significantly (p<0.05) potentiated Con A (1.25 to 5 microg/ml) (1.46- to 2.62-fold increases)- and antiTCR, IL-2 or antiTCR+IL-2 (1.72- to 2.60-fold increases)-induced proliferation of splenic cells in the presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (NMA). These results show two distinct and separate effects of fumonisin B(1): it induces nitric oxide production by macrophages and it stimulates T cell proliferation.

Animals↗
PubMed1999

Suppression of splenic macrophage functions following acute morphine action in the rat mesencephalon periaqueductal gray.

Morphine action in the periaqueductal gray (PAG) matter of the mesencephalon suppresses T cell proliferation and NK cell activity through actions at mu opioid receptors. We investigated the effect of acute microinjection of morphine in the rat PAG on macrophage function. We found that morphine injection in the PAG significantly (p <.01) suppressed nitric oxide production by untreated (82 +/- 23% suppression), IFN-gamma-primed (57 +/- 11% suppression), and LPS-activated (50 +/- 7% suppression) splenic macrophages and did not alter macrophage viability. In contrast, IFN-gamma- and LPS-activated macrophages from PAG-injected saline rats generated an increased output of nitric oxide, which was associated with significant (p <.01) reduction in cell viability. Morphine significantly (p <.01) inhibited TNF-alpha production by LPS-activated macrophages (28 +/- 8% inhibition compared with PAG-injected saline rats). In addition, morphine significantly (p <. 05) inhibited phagocytosis of Candida albicans by resident macrophages (40 +/- 20% inhibition compared with that of macrophages from PAG-injected saline rats). Responses of resident or activated macrophages from PAG-injected saline and untreated control groups did not differ significantly. The results of this ex vivo study suggest that suppressive effects of morphine on macrophage functions may contribute to increased susceptibility to infectious diseases and cancer associated with drug abuse.

Analgesics, Opioid↗
PubMed1999

Inhibition of interleukin-2 production and downregulation of IL-2 and transferrin receptors on rat splenic lymphocytes following PAG morphine administration: a role in natural killer and T cell suppression.

We investigated the effects of acute injection of morphine into the rat mesencephalon periaqueductal gray (PAG), on splenic natural killer (NK) cell and lymphocyte functions, interleukin-2 (IL-2) production, expression of T cell (CD3), T helper cell (CD4), T suppressor cell (CD8), and NK cell (NKR-P1) surface markers, and expression of IL-2 (CD25) and transferrin (CD71) receptors. Bilateral microinjection of 10 nmol of morphine in the PAG significantly (p < 0.001) inhibited IL-2 (31%) production by activated splenic lymphocytes compared with that of PAG saline-injected control rats. In addition, morphine significantly (p < 0.01) suppressed splenic NK cell activity (14-33%) and T lymphocyte proliferative responses (25-48%) to various mitogens compared with controls. Furthermore, morphine did not alter the expression of CD3, CD4, CD8, and NKR-P1 surface markers, but significantly (p < 0.001) downregulated the expression of CD25 and CD71 receptors following in vitro activation. These results suggested that injection of morphine in the PAG suppresses NK and T cell functions by reducing the ability of T cells to produce IL-2 and downregulating the expression of CD25 and CD71 surface activation markers.

Animals↗
PubMed1999

Polarity of the mouse embryo is anticipated before implantation.

In most species, the polarity of an embryo underlies the future body plan and is determined from that of the zygote. However, mammals are thought to be an exception to this; in the mouse, polarity is generally thought to develop significantly later, only after implantation. It has not been possible, however, to relate the polarity of the preimplantation mouse embryo to that of the later conceptus due to the lack of markers that endure long enough to follow lineages through implantation. To test whether early developmental events could provide cues that predict the axes of the postimplantation embryo, we have used the strategy of injecting mRNA encoding an enduring marker to trace the progeny of inner cell mass cells into the postimplantation visceral endoderm. This tissue, although it has an extraembryonic fate, plays a role in axis determination in adjacent embryonic tissue. We found that visceral endoderm cells that originated near the polar body (a marker of the blastocyst axis of symmetry) generally became distal as the egg cylinder formed, while those that originated opposite the polar body tended to become proximal. It follows that, in normal development, bilateral symmetry of the mouse blastocyst anticipates the polarity of the later conceptus. Moreover, our results show that transformation of the blastocyst axis of symmetry into the axes of the postimplantation conceptus involves asymmetric visceral endoderm cell movement. Therefore, even if the definitive axes of the mouse embryo become irreversibly established only after implantation, this polarity can be traced back to events before implantation.

Animals↗
PubMed1998

Opioid mediated effects on the immune system: sympathetic nervous system involvement.

Opioids have been hypothesized to suppress parameters of immune function by acting within the central nervous system to increase the activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Production of catecholamines and adrenocorticoids have been demonstrated to be responsible for many of the observed immunomodulatory effects which occur following opioid administration. In general, the sympathetic nervous system has been shown to play a role in regulating lymphocyte proliferation and natural killer cell activity as well as several other parameters of immune function. Here, we will focus primarily on the role of the sympathetic nervous system in modulating opioid induced immunosuppression. The role of the hypothalamic-pituitary adrenal axis is reviewed elsewhere in this issue.

Animals↗