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Biomedical subjects

B A Harrison

Publications and source records attributed to B A Harrison.

At least 19 recordsLinked to original sources

Occurrence and relative abundance of mosquitoes in stormwater retention facilities in North Carolina, U.S.A.

Throughout the 2004 mosquito season, 52 stormwater retention facilities were sampled to characterize the seasonal occurrence and relative abundance of mosquito species in relation to the structural complexity and biological diversity of the facilities. The three different types of facilities included standard wet ponds (n=20), innovative ponds (n=14), and wetland ponds (n=18). All retention structures were sampled at the beginning, middle and end of the mosquito season so that seasonal changes in mosquito production could be characterized. Overall samplings, mosquitoes were collected from 34% of the retention structures. Fourteen species representing 7 genera were collected, but only 5 species were commonly collected in all three types of stormwater management facilities. In general, the seasonal prevalence and relative abundance of mosquito species did not vary among three types of retention structures. A significant association (P < 0.01) between the presence of mosquito larvae or pupae and the absence of mosquitofish was found for innovative and wetland stormwater retention facilities but not for standard retention facilities (P > 0.05).

Animals↗

Identification of selective inhibitors of cyclin dependent kinase 4.

A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.

Carbazoles↗

Evaluation of 1-octen-3-ol, carbon dioxide, and light as attractants for mosquitoes associated with two distinct habitats in North Carolina.

Field studies were conducted in North Carolina to determine the responses of mosquitoes found in salt marsh and inland creek flood plain areas to 1-octen-3-ol (octenol), carbon dioxide (CO2), and light in various combinations with Centers for Disease Control (CDC) light traps. Over 56,000 adult mosquito specimens of 12 species in 4 genera were collected in the salt marsh. They exhibited a general response pattern of octenol + CO2 + light > CO2 + light = octenol + CO2 > octenol + light > octenol alone. Significantly, more Aedes sollicitans, Ae. taeniorhynchus, Anopheles bradleyi, and Culex salinarius were attracted to octenol + CO2 + light than to CO2 + light. Over 19,000 specimens of 24 species in 7 genera were collected in the inland creek flood plain. Although the response patterns to the attractants were similar to those in the salt marsh area, there was no significant difference between octenol + CO2 + light and CO2 + light. Aedes vexans, An. crucians, and An. punctipennis were attracted nearly equally to these two attractant combinations. These studies demonstrate that responses to combinations of these attractants are species specific. However, different combinations of attractants can significantly increase the collection of targeted species important in arbovirus transmission. The use of these combinations would be very beneficial in mosquito-borne virus surveillance studies. The use of octenol by itself or in conjunction with light was found the least useful for collecting mosquitoes in both habitats.

Aedes↗

Galectin-3-mediated adherence of Proteus mirabilis to Madin-Darby canine kidney cells.

Proteus mirabilis is an important cause of urinary tract infections (UTIs) and can result in acute pyelonephritis. Proteus mirabilis expresses several, morphologically distinct, fimbrial species, and previous studies have shown that the nonagglutinating fimbriae (NAF) mediate bacterial adherence to a number of cell lines, including Madin-Darby canine kidney (MDCK) cells. Immunoblot overlay analysis of the plasma membrane fraction from MDCK cells with purified NAF revealed a 34-kDa band, which has been analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Database search identified galectin-3 as a potential protein candidate. Immunocytochemical assay of MDCK cells with a galectin-3-specific monoclonal antibody, anti-Mac-2, confirmed its presence on the plasma membrane extracellular surface. Preincubation of P. mirabilis with anti-Mac-2 monoclonal antibodies, specific for galectin-3, resulted in the inhibition of bacterial binding to MDCK cells. These data suggest a role for galectin-3, interacting with appropriately glycosylated surface receptors and P. mirabilis fimbriae, as a mediator of bacterial adherence in vitro.

Animals↗

The binding of Proteus mirabilis nonagglutinating fimbriae to ganglio-series asialoglycolipids and lactosyl ceramide.

Proteus mirabilis is a common opportunistic Gram-negative uropathogen that infects the upper urinary tract. We have examined the role of the nonagglutinating fimbriae (NAF) of P. mirabilis in mediating bacterial adhesion to cell surface receptors. Purified NAF of P. mirabilis were demonstrated to bind to a number of glycolipids, including asialo-GM1, asialo-GM2, and lactosyl ceramide (LacCer) in solid-phase binding assays and in thin layer chromatography (TLC) overlay assays. Furthermore, preincubation of the biotinylated NAF (Bt-NAF) with anti-NAF monoclonal antibodies resulted in inhibition of NAF binding to immobilized asialo-GM1, asialo-GM2, and LacCer. In adherence assays, P. mirabilis binding to Madin-Darby canine kidney (MDCK) cells was inhibited by murine anti-asialo-GM1 monoclonal antibodies H2G10 to about 50% of the binding level in the absence of the antibody, specific for the terminal beta-galactopyranosyl residue of asialo-GM1 (Harrison et al. 1998). The results of this study suggest that NAF of P. mirabilis recognize a GalNAc beta 1-4Gal moiety present in the ganglio-series of asialoglycolipids, and that the terminal beta-galactopyranosyl-containing glycoconjugates play a role in NAF-mediated adherence of P. mirabilis to MDCK cells. Similarly to other bacteria, P. mirabilis NAF was also shown to express the LacCer specificity.

Agglutination↗

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension.

Pulmonary artery hypertension in association with liver failure (portopulmonary hypertension [PPHTN]) is a significant barrier to liver transplantation because patients with this condition have a very high mortality when transplantation is undertaken. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, reduces pulmonary artery pressure (PAP) in some patients with primary pulmonary hypertension, but its effect in patients with PPHTN is controversial. We investigated the hemodynamic effects of inhaled NO in 6 patients with PPHTN. Five of 6 patients responded to NO inhalation with decreases in PAP and pulmonary vascular resistance of greater than 10%; these decreases were statistically significant at NO concentrations of 10 and 30 ppm. Cardiac output did not significantly change. We conclude that inhalation of NO reduces PAPs in some patients with PPHTN.

Administration, Inhalation↗

A kinetics approach to the characterization of an IgM specific for the glycolipid asialo-GM1.

The unique features of protein recognition of membrane-anchored glycolipids were investigated by surface plasmon resonance (SPR) monitoring of antibody interactions with glycolipids contained in liposomes. Several positive hybridomas belonging to the IgM and IgG classes were identified when tested for binding to the glycosphingolipid asialo-GM1 (Gal beta1-3GalNAcl beta1-4Gal beta1-4Glc beta1-1-Ceramide). Preliminary screening by enzyme immunoassay and thin layer chromatography (TLC) followed by immunostaining indicated that only those of the IgM type showed specificity for this glycosphingolipid. One of the IgMs, H2G10, was purified and further characterized using a SPR technique that involved antibody binding to liposomal asialo-GM1. This method generated kinetic and affinity constants for the interaction and confirmed the specificity of H2G10 for the terminal galactose of asialo-GM1. Interestingly, inhibition of antibody binding to asialo-GM1 liposomes by the asialo-GM1 tetrasaccharide reduced the total amount of bound antibody but increased the affinity of the antigen-antibody interaction due to an inverse relationship between tetrasaccharide concentration and the H2G10 dissociation rate constant. We believe that this effect is due to the selective inhibition of lower valency binding by the tetrasaccharide which, in turn, promotes higher avidity antibody-carbohydrate interactions. The observation that slower dissociation rate constants were also observed at high antigen to antibody ratios supports this interpretation. These results highlight the insight that kinetic data can provide in efforts to promote and inhibit high avidity interactions such as those involving proteins and carbohydrates.

Antibodies, Monoclonal↗

Preclinical antitumor efficacy of analogs of XK469: sodium-(2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]propionate.

A series of quinoxaline analogs of the herbicide Assure was found to have selective cytotoxicity for solid tumors of mice in a disk-diffusion-soft-agar-colony-formation-assay compared to L1210 leukemia. Four agents without selective cytotoxicity and 14 agents with selective cytotoxicity were evaluated in vivo for activity against a solid tumor. The four agents without selective cytotoxicity in the disk-assay were inactive in vivo (T/C > 42%). Thirteen of the fourteen agents with selectivity in the disk-assay were active in vivo (T/C < 42%). Five of the agents had curative activity. These five agents had a halogen (F, Cl, Br) in the 7-position (whereas Assure had a CI in the 6 position). All agents with curative activity were either a carboxylic acid, or a derivative thereof, whereas Assure is the ethyl ester of the carboxylic acid. All other structural features were identical between Assure and the curative agents. Assure had no selective cytotoxicity for solid tumors in the disk-assay, and was devoid of antitumor activity. The analog XK469 is in clinical development.

Animals↗

North Carolina mosquito records. I. Uncommon Aedes and Anopheles (Diptera: Culicidae).

New distribution records are provided for 10 mosquito species that are rare or uncommon in North Carolina: Aedes aegypti, Ae. cinereus, Ae. dupreei, Ae. fulvus pallens, Ae. hendersoni, Ae. mitchellae, Ae. thibaulti, Ae. tormentor, Ae. trivittatus, and Anopheles atropos. Biological notes are provided for habitats, behavior, and, in some cases, color patterns. Comments are also made about 6 additional species that are rare or uncommon in North Carolina.

Aedes↗

The expression of nonagglutinating fimbriae and its role in Proteus mirabilis adherence to epithelial cells.

Proteus mirabilis is a common causative agent of human urinary tract infections, especially in catheterized patients and in those patients with structural abnormalities of the urinary tract. In addition to the production of hemolysin and urease, fimbriae-mediated adherence to uroepithelial cells and kidney epithelium may be essential for virulence of P. mirabilis. A single P. mirabilis strain is capable of expressing several morphologically distinct fimbrial species, which can each be favoured by specific in vitro growth conditions. The fimbrial species reported to date include mannose-resistant/Proteus-like fimbriae, ambient temperature fimbriae, P. mirabilis fimbriae, and nonagglutinating fimbriae (NAF). Here, using intact bacteria or purified NAF as immunogens, we have generated the first reported NAF-specific monoclonal antibodies (mAbs). Bacteria expressing NAF as their only fimbrial species adhered strongly to a number of cell lines in vitro, including uroepithelial cell lines. Binding of P. mirabilis was markedly reduced following preincubation with NAF-specific mAbs and Fab fragments. The presence of NAF with highly conserved N-terminal sequences on all P. mirabilis strains so far examined, combined with the ability of both anti-NAF mAbs and purified NAF molecules to inhibit P. mirabilis adherence in vitro, suggests that NAF may contribute to the pathogenesis of P. mirabilis.

Antibodies, Bacterial↗

Ticks (Acari: Ixodida) uncommonly found biting humans in North Carolina.

Collection records are presented that document human-biting by Otobius megnini, Amblyomma maculatum, Haemaphysalis leporispalustris, Ixodes cookei, Ixodes dentatus, and Rhipicephalus sanguineus in North Carolina. These species are either extremely rare in North Carolina or they are normally considered non-human feeders. The record of Otobius megnini represents the first collection of this species in North Carolina in over 50 years. It is proposed that immature Rhipicephalus sanguineus feed on humans much more than previously suspected and that they represent a threat for the transmission of pathogens to humans.

Animals↗

The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55).

Enterovirus 70 (EV70) is a recently emerged human pathogen belonging to the family Picornaviridae. The ability of EV70 to infect a wide variety of nonprimate cell lines in vitro is unique among human enteroviruses. The importance of virus receptors as determinants of viral host range and tropism led us to study the host cell receptor for this unusual picornavirus. We produced a monoclonal antibody (MAb), EVR1, which bound to the surface of HeLa cells and protected them against infection by EV70 but not by poliovirus or by coxsackievirus B3. This antibody also inhibited the binding of [35S]EV70 to HeLa cells. MAb EVR1 did not bind to monkey kidney (LLC-MK2) cells, nor did it protect these cells against virus infection. In Western immunoassays and in immunoprecipitations, MAb EVR1 identified a HeLa cell glycoprotein of approximately 75 kDa that is attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. Decay-accelerating factor (DAF, CD55) is a 70- to 75-kDa GPI-anchored membrane protein that is involved in the regulation of complement and has also been shown to function as a receptor for several enteroviruses. MAb EVR1 bound to Chinese hamster ovary (CHO) cells constitutively expressing human DAF. Anti-DAF MAbs inhibited EV70 binding to HeLa cells and protected them against EV70 infection. Transient expression of human DAF in murine NIH 3T3 cells resulted in binding of labelled EV70 and stably, transformed NIH 3T3 cells expressing DAF were able to support virus replication. These data indicate that the HeLa cell receptor for EV70 is DAF.

3T3 Cells↗

Identifying Psorophora horrida females in North Carolina (Diptera:Culicidae).

Morphological characters to separate Psorophora horrida (Dyar and Knab) and Psorophora ferox (Von Humboldt) females are identified and defined. In addition to the 3 characters used to separate these 2 species in published keys, an additional 6 characters were found. Of the total of 9 characters identified, 6 are reliable at the 100% level, based on North Carolina specimens. These additional characters will assist greatly in identifying Ps, horrida specimens. Variation or hindtarsomere 4 of Ps. horrida, consisting of dark-scaled patterns, were also noted. Characters for separating Psorophora cyanescens (Coq.) and Psorophora mathesoni Belkin and Heinemann from Ps. ferox and Ps. horrida are discussed.

Animals↗

Isolation of potosi virus from Aedes albopictus in North Carolina.

A total of 4,169 adult mosquitoes were aspirated from 3 tire disposal sites in North Carolina for virus assays. Aedes albopictus was the dominant species, with a relative abundance of approximately 99%. Potosi virus was isolated from one pool of 68 female Ae. albopictus. Priorities for future Potosi virus research and the implications of the North Carolina isolate are discussed.

Aedes↗

Opioids and benzodiazepines.

Most patients in the intensive care unit experience pain and anxiety, which are treated most commonly with an opioid or a benzodiazepine. These compounds are effective and have a well-established safety record. With the exception of associated respiratory depression, they have a relatively wide therapeutic window. New approaches and formulations for opioids and benzodiazepines are being used with continued success in the clinical setting.

Analgesia, Patient-Controlled↗