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David R Johnson

Publications and source records attributed to David R Johnson.

13 recordsLinked to original sources
PubMed2026

Soil erosion and landscape elevation as unnoticed determinants of environmental antibiotic resistance distribution.

Climate change is reshaping the global antibiotic resistance gene (ARG) landscape through geomorphological processes that remain largely overlooked in the One Health framework. This critical review synthesises evidence on how soil erosion and landscape elevation gradients redistribute, select for, and disseminate ARGs across terrestrial and aquatic ecosystems. Erosion physically removes and transports ARG-bearing microbes, depletes nutrients, and co-selects for resistance via heavy metal exposure and horizontal gene transfer, creating source-sink dynamics that connect eroding hillslopes to downstream water bodies and food systems. Elevation gradients impose abiotic stressors-declining temperature, elevated UV radiation, and shifting pH-that drive microbial community reassembly through environmental selection and dispersal limitation, with emerging evidence linking bacterial competition at high altitude to enhanced multidrug efflux and resistome complexity. The review identifies critical knowledge gaps, including unquantified ARG mass fluxes across erosion-deposition gradients, unresolved dispersal-versus-selection mechanisms along elevation transects, and the absence of integrated One Health surveillance linking environmental ARG reservoirs to clinical outcomes. A synthesis of global case studies illustrates how these processes converge across diverse landscapes. The review concludes with a mechanistic research agenda-including reciprocal transplant experiments, landscape connectivity modelling, and cross-sectoral surveillance-needed to translate these emerging drivers into actionable climate-AMR mitigation policy.

Drug Resistance, Microbial↗
PubMed2003

Locus-specific constitutive and cytokine-induced HLA class I gene expression.

Cytokine induction of the MHC class I genes increases the nascent molecules available for binding potentially antigenic peptides. The human H chain loci, HLA-A, -B, and -C, encode highly homologous and polymorphic mRNAs. Here, these transcripts were resolved and measured by competitive PCR of cDNA using locus-specific primers. Endothelial cells expressed many HLA-A and -B, but fewer HLA-C, transcripts. In contrast, HeLa cells expressed many HLA-A and -C, but fewer HLA-B, transcripts. The inflammatory cytokines TNF-alpha, IFN-beta, and IFN-gamma induced HLA-B strongly, but HLA-A and -C weakly in both cell types. Combined treatment with IFNs and TNF further increased HLA-A and -B, but not HLA-C transcripts. The constitutive and inducible activities of transfected promoters correlated well with mRNA levels. The weak IFN response of the HLA-A2 promoter was not due to variations in the IFN consensus sequence, the site alpha, or a 3-bp insertion between them. The HLA-Cw6 promoter was less TNF responsive due to a variant kappaB enhancer, which also reduced the IFN responses. The NF-kappaB subunit RelA strongly activated the HLA-A2 and -B7 promoters but only weakly activated the HLA-Cw6 promoter due to the variant kappaB. Cotransfecting NF-kappaB1 with RelA further increased activity of the HLA-A2 and -B7, but not HLA-Cw6, promoters. All three promoters were activated by MHC class II trans-activator, but not CREB-binding protein, whereas IFN regulatory factor-1 and -2 weakly activated the HLA-B7 and -Cw6, but not HLA-A2, promoters. These studies illustrate common and locus-specific mechanisms that may be targeted to modulate immune reactions.

Base Sequence↗
PubMed2003

Testosterone and child and adolescent adjustment: the moderating role of parent-child relationships.

In a sample of established middle- and working-class families with normally developing children and adolescents ranging in age from 6 to 18 years, sons' and daughters' testosterone levels showed little direct connection to risk behavior or symptoms of depression. In contrast, testosterone's positive relation with risk behavior and negative relation with depression were conditional on the quality of parent-child relations. As parent-child relationship quality increased, testosterone-related adjustment problems were less evident. When relationship quality decreased, testosterone-linked risk-taking behavior and symptoms of depression were more in evidence. Few relations were found between parents' testosterone and child behavior. Boys' and girls' ages and stages of pubertal development were important for understanding the expression of hormone-related problem behavior in some cases but not in others.

Adolescent↗
PubMed2002

Expression of rat Multidrug Resistance Protein 2 (Mrp2) in male and female rats during normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny.

The normal maturation of biliary organic anion excretion in newborn rats can be enhanced by microsomal enzyme-inducing chemical treatment, yet the mechanism for this phenomenon is not known. Multidrug Resistance Protein 2 (Mrp2) is a biliary efflux transporter that is inducible by select microsomal enzyme-inducing chemicals. Thus, the aims of this study were to compare the normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny of Mrp2 in male and female rats. Mrp2 protein increased in an age-dependent manner in both sexes between 0 and 90 days of age. At birth, Mrp2 protein in both male and female rats was the same, approximately 70% of adult levels. Mrp2 protein in both sexes reached maximal expression levels that were higher than adult levels (male: days 25-40; female: day 45), then decreased to adult levels, at which age Mrp2 protein expression in male and female rats was the same. Second, male and female rats of various ages were treated with PCN (75 mg/kg, ip) or corn oil for 4 days, after which livers were removed and analyzed for Mrp2 protein and mRNA expression. PCN accelerated the expression of Mrp2 protein in male and female rats as early as 10 days of age, whereas, PCN did not affect male and female Mrp2 mRNA ontogeny. These data suggest that PCN increased Mrp2 protein by a sex-independent posttranscriptional mechanism.

Aging↗
PubMed2002

Role of rat multidrug resistance protein 2 in plasma and biliary disposition of dibromosulfophthalein after microsomal enzyme induction.

We have previously demonstrated that microsomal enzyme inducers phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN), but not 3-methylcholanthrene (3-MC) and benzo(a)pyrene (BaP), increase expression and function of rat Multidrug Resistance Protein 2 (Mrp2), a canalicular organic anion transporter. Thus, the purpose of this study was to determine whether Mrp2 protein induction alters the biliary and plasma dispositions of dibromosulfophthalein (DBSP). After four daily ip injections of PB, PCN, 3-MC, BaP, or vehicle, DBSP (100 mg/kg) was injected iv and was measured in blood and bile over a 40-min period. PB and PCN significantly enhanced plasma disappearance and biliary excretion of DBSP, whereas 3-MC and BaP did not. To determine whether the enhanced plasma disappearance and biliary excretion was entirely due an increase in Mrp2, PCN was also administered ip daily for 4 days to Mrp2-null Eisai hyperbilirubinemic (EHBR) rats and then injected iv with DBSP. PCN significantly increased plasma DBSP disappearance in EHBR rats during early time intervals (2-20 min), but not at later time intervals (25-40 min). PCN did not increase DBSP biliary excretion in EHBR rats, but actually decreased it at later time intervals. In summary, the increase in Mrp2 protein after microsomal enzyme induction is responsible for increased biliary DBSP excretion. Furthermore, the increase in Mrp2 protein after microsomal enzyme induction is not responsible for the enhanced plasma DBSP disappearance at early time points, yet may influence plasma DBSP disappearance at later time points. This study also demonstrates the importance of compensatory hepatic transporters in eliminating DBSP by alternative pathways other than Mrp2.

Animals↗
PubMed2002

Increase in bile flow and biliary excretion of glutathione-derived sulfhydryls in rats by drug-metabolizing enzyme inducers is mediated by multidrug resistance protein 2.

Glutathione (GSH) is an important cellular constituent for normal liver homeostasis. Certain drug-metabolizing enzyme inducers (i.e., phenobarbital [PB] and pregnenolone-16alpha-carbonitrile [PCN]) increase biliary excretion of GSH-derived sulfhydryls (SH) as well as bile flow, whereas other drug-metabolizing enzyme inducers (i.e., 3-methylcholanthrene [3MC] and benzo(a)pyrene [BaP]), do not. The purpose of the study was to determine whether rat multidrug resistance protein 2 (Mrp2) is the inducible transporter responsible for increasing biliary SH excretion and bile flow. Sprague-Dawley (SD) rats were injected ip daily for 4 days with PB, PCN, 3MC, BaP, or vehicle; Mrp2-null Eisai hyperbilirubinemic (EHBR) rats were injected ip daily for 4 days with PCN or vehicle. Although no drug-metabolizing enzyme inducer altered hepatic GSH in SD rats, PB and PCN significantly increased the rate of biliary SH excretion and bile flow. Neither 3MC nor BaP affected the biliary SH excretion rate or bile flow. In control EHBR rats, despite elevated hepatic GSH, the rate of biliary SH excretion was almost completely eliminated and bile flow was dramatically reduced compared with SD rats. Furthermore, PCN treatment did not affect bile flow or the biliary SH excretion rate in EHBR rats. PB and PCN also increased Mrp2 protein levels, but 3MC and BaP did not. None of the drug-metabolizing enzyme inducers tested significantly increased Mrp2 mRNA levels. PCN increased Mrp2 protein, but not Mrp2 mRNA, in a time-dependent manner. In conclusion, Mrp2 is the inducible efflux transporter responsible for increased biliary SH excretion and bile flow after administration of some drug-metabolizing enzyme inducers.

ATP-Binding Cassette Transporters↗
PubMed2002

Regulation of rat multidrug resistance protein 2 by classes of prototypical microsomal enzyme inducers that activate distinct transcription pathways.

Microsomal enzyme inducers are capable of modulating biliary excretion of organic anions and bile flow, but the mechanism for modulation is unknown. Therefore, this study was designed (1) to determine the effects of microsomal enzyme inducers on protein and mRNA expression of rat multidrug resistance protein 2 (Mrp2), a canalicular organic anion transporter; and (2) to determine whether classes of microsomal enzyme inducers affect Mrp2 expression in similar manners, thus implying specific nuclear receptor-activated transcription pathways. Male Sprague-Dawley rats were treated with aryl hydrocarbon (Ah) receptor (AhR) ligands/cytochrome P450 (CYP) 1A inducers, constitutive androstane receptor (CAR) ligands/CYP2B inducers, pregnane-X receptor (PXR) ligands/CYP3A inducers, peroxisomal proliferator-activating receptor-alpha (PPARalpha) ligands/CYP4A inducers, antioxidant/electrophile response element (ARE/EpRE) ligands, CYP2E1 inducers, or control vehicle. Mrp2 protein levels were significantly increased by all 3 PXR ligands/CYP3A inducers (pregnenolone-16alpha-carbonitrile [PCN], spironolactone [SP], and dexamethasone [DEX]) and by both ARE/EpRE ligands (ethoxyquin [EQ] and oltipraz [OPZ]). In contrast, PPARalpha ligands/CYP4A inducers (clofibric acid [CLOF], di-(2-ethylhexyl)phthalate [DEHP], and perfluorodecanoic acid [PFDA]) tended to decrease Mrp2 protein levels. Mrp2 mRNA expression was not significantly affected by any microsomal enzyme inducer, though ARE/EpRE ligands tended to upregulate Mrp2 mRNA. In summary, this study demonstrates that Mrp2 protein levels are significantly increased by PXR ligands/CYP3A inducers and ARE/EpRE ligands, and appear to be decreased by PPARalpha ligands/CYP4A inducers by posttranscriptional mechanisms. Furthermore, these data suggest that measuring Mrp2 mRNA is not a good indicator for Mrp2 protein expression in vivo.

Animals↗
PubMed2002

Daily charting of posttraumatic stress symptoms: a pilot study.

This pilot study describes a prospective life-charting method for posttraumatic stress (PTS) symptoms. This method summarizes daily symptoms, functional impairment, life events, substance use, and treatment. Findings include experience with 17 cases over periods lasting from 3 to 25 months, with a description of 4 case examples that are characteristic of the pilot sample. People with posttraumatic stress disorder (PTSD) can complete day charting of their symptoms over an extended period of time. Some people reported that day charting distressed them mildly as they analyzed daily thoughts or feelings that they ordinarily avoided or pushed from awareness. Nonetheless, most people reported that they learned and benefited from daily symptom charting. In addition to enhancing patient self-understanding (or "insight"), the method may prove useful in assessing treatments for PTSD. Finally, these preliminary findings have suggested hypotheses regarding the clinical phenomenology and course of PTSD. For example, PTS symptom cluster exacerbation, severity, and duration appear to be highly consistent within any given patient, but highly variable across patients. Daily charting of PTS symptoms over prolonged periods is feasible. This prospective PTSD symptom charting method may have therapeutic, clinical, and research potential for understanding individual and group patterns in PTSD over time.

Acute Disease↗
PubMed2002

Postnatal expression and induction by pregnenolone-16alpha-carbonitrile of the organic anion-transporting polypeptide 2 in rat liver.

Newborn rats are more sensitive to the toxic effects of cardiac glycosides than are adult rats. This is associated with a decreased ability to remove cardiac glycosides from blood into the liver. Pregnenolone-16alpha-carbonitrile (PCN), a prototypical rodent CYP3A inducer and pregnane-X-receptor (PXR) ligand, stimulates the hepatic clearance of cardiac glycosides in newborn rats, which results in decreased toxicity of the cardiac glycosides. The mechanism responsible for this phenomenon is not clear; however, if elucidated, it would help in understanding and preventing potential drug-drug interactions. The recently cloned rat organic anion-transporting polypeptide 2 (oatp2) (Slc21a5) is a sinusoidal hepatic uptake transporter, with very high affinities for cardiac glycosides, and thus it was hypothesized that rat oatp2 increases during postnatal development and is inducible by PCN. In the present study, livers were removed from Sprague-Dawley rats from postnatal days (pnd) 0 to 45, in 5-day increments; as well as from pnd 10 to 90, in 10-day increments, after PCN (75 mg/kg i.p., for 4 days) or corn oil (vehicle for PCN) treatment. The protein and mRNA levels of rat oatp2 were determined by Western blot analysis and branched DNA signal amplification technique, respectively. Expression of rat oatp2 protein and mRNA increased gradually during postnatal development. PCN treatment increased liver to body weight ratio in both genders, and dramatically accelerated the maturation of hepatic oatp2 protein and mRNA levels. In summary, rat oatp2 undergoes age-dependent and chemical regulation during postnatal development, and is a potential target for drug-drug and age-drug interactions.

Age Factors↗
PubMed2002

Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats.

Many phase I and II microsomal enzyme inducers share common mechanisms of transcriptional activation and thus share a similar battery of genes that are coordinately regulated. Many phase II metabolites are thought to be transported out of cells by multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3). The purpose of this study was to determine the organ distribution of these three transporters in rat, and whether they are coordinately regulated with phase I and II drug-metabolizing enzymes. Therefore, Mrp1, 2, and 3 mRNAs were quantified using branched DNA signal amplification in multiple tissues and in tissues from rats that were treated with 18 chemicals thought to induce drug-metabolizing enzymes by six different transcription activation mechanisms [aryl-hydrocarbon receptor ligands, constitutive androstane receptor (CAR) activators, pregnane-X-receptor ligands, peroxisome proliferator activator receptor ligands, electrophile response element (EpRE) activators, and CYP2E1 inducers]. It was found that Mrp1 was expressed at a high level in kidney, lung, intestine, and brain, with low expression in liver. Mrp2 was highly expressed in liver and duodenum, and Mrp3 was highly expressed throughout the intestine but very low in liver. Microsomal enzyme inducers did not markedly increase the expression of Mrp1 or Mrp2. However, Mrp3 expression was significantly increased by each of the CAR activators and an EpRE activator in liver. Mrp3 was not similarly induced in kidney and large intestine, demonstrating that the coordinate inducibility of Mrp3 is specific to the liver. We conclude that rat hepatic Mrp3 is induced by CAR activators, thus enhancing the vectoral excretion of some phase II metabolites from the liver to the blood.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2002

Development of the spray drift task force database for aerial applications.

This article is part of a series describing the development of the Spray Drift Task Force (SDTF) database and its application to agricultural chemical exposure risk assessment modeling. The series describes the development of a large generic database (assuming that active ingredient rate is not a factor affecting physical drift) and its use in estimating spray movement immediately following application by aerial methods. The components of the database are described. In agreement with field trials in the open literature, the database shows that the major variables affecting off-target spray deposition are droplet size, spray release position (boom height and length), and wind speed and direction. In addition, secondary parameters that can affect these variables and drift are also discussed.

Aerosols↗
PubMed2002

Unrecognized torture affects the health of refugees.

Recognizing the symptoms and signs of torture and documenting their cause may be key to providing effective health care for refugees from countries where torture is known to have occurred. Generalist or primary care physicians are in a unique position to establish a trust relationship with patients, to identify potential signs and symptoms of torture, and encourage patients to talk about their experiences. With knowledge about, understanding of, and sensitivity toward torture survivors, physicians can help these patients regain their health and a sense of well-being.

Adult↗