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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 73 records · Page 4Linked to original sources

Remodeling and suppression of intimal hyperplasia of vascular grafts with a distal arteriovenous fistula in a rat model.

PURPOSE: The purpose of this study was to evaluate the effects of a distal arteriovenous fistula (dAVF) on the morphologic changes occurring in arterial bypass grafts by the use of a novel experimental model. METHODS: Aortofemoral bypass grafts with or without dAVFs were constructed in 36 Sprague-Dawley rats with a microsurgical technique. The bypass graft material consisted of deendothelialized autogenous tail artery (length, 25 mm; inside diameter, 0.5 mm). In 18 rats, dAVFs were constructed at the distal anastomosis. After 6 weeks, flow rates and shear stress were determined, and grafts were then harvested. Luminal, intimal, and medial cross-sectional areas were measured with computer imaging. Desmin, alpha-smooth muscle actin, and von Willebrand factor (vWF) were identified with immunohistochemistry. Endothelialization was evaluated with SEM. RESULTS: All bypass grafts remained patent at the time of graft harvest. Grafts with dAVFs showed increased flow rates (11.5 +/- 0.6 mL/min) compared with grafts without dAVFs (2.1 +/- 0.3 mL/min; P < .01). Shear stress was also increased in the dAVF group (340.9 +/- 23.4 dyne/cm(2) vs 113.7 +/- 12.5 dyne/cm(2); P < .01), with a corresponding suppression of intimal hyperplasia (0.059 +/- 0.011 mm(2) for dAVF grafts vs 0.225 +/- 0.009 mm(2) for non-dAVF grafts; P < .01). Staining for vWF was found in both the reendothelialized flow surface and the neointimal extracellular matrix. Remodeling of the grafts was characterized by a 50% increased luminal area, 70% decreased intimal area, and a 25% decreased medial area when a dAVF was constructed. CONCLUSION: A small animal experimental model of an arterial bypass graft can enable the evaluation of a variety of factors that influence graft patency. Increased blood flow velocity and shear stress induced by a dAVF are associated with a decrease in intimal and medial areas, which may reflect changes in cell proliferation, apoptosis, migration, or matrix deposition. Deposition of vWF was also found both in the endothelium and throughout the hyperplastic intima. These findings suggest that the hemodynamic and morphologic changes associated with dAVF may potentiate graft patency and function.

Actins↗

Population-based active surveillance for neonatal group B streptococcal infections in Alberta, Canada: implications for vaccine formulation.

BACKGROUND: Knowledge of circulating serotypes of group B Streptococcus (GBS) is important for formulation of vaccines. There are no Canadian data on the serotype distribution of neonatal GBS isolates. METHODS: Using a retrospective laboratory and health record survey between 1993 and 1994 (before introduction of Canadian prevention guidelines) and prospective active laboratory-based surveillance from 1995 to 1999 of all laboratories in Alberta, we identified 168 cases of invasive neonatal GBS infections including stillbirths among 262,398 total births; 118 of 123 (96%) isolates from 1995 to 1999 were serotyped, and the corresponding neonatal health records were reviewed. RESULTS: The average annual incidence was 0.64 of 1000 total births/year. Of these 95 (57%) had early onset disease (EOD), 15 (9%) were still births and 58 (34%) had late onset disease (LOD). Eighty-one percent of EOD cases were caused by serotypes Ia, Ia/c, Ia/c/R, III, III/R and V, V/R, whereas 81% of LOD cases were caused by serotypes III and III/R. GBS serotypes containing the C protein along with serotypes III and V as a group constituted 91% (107 of 118) of all GBS cases in our population. The most common clinical presentation was bacteremia without focus (74%) followed by meningitis (14%) and pneumonia (12%). During 1995 to 1999, in addition to 13 stillbirths, there were 6 of 64 (9%) neonatal deaths among EOD cases and 1 of 46 (2%) neonatal death among LOD cases. CONCLUSIONS: In this population-based study stillbirths account for a proportion of cases that are not routinely counted and represent a group for which intrapartum antibiotics would likely not be effective, but potentially preventable by vaccination. Inclusion of serotypes Ia, III and V in a conjugate vaccine or serotypes III and V conjugated with the C protein in a GBS vaccine could theoretically provide protection against the majority of GBS invasive disease in Alberta neonates.

Alberta↗

Pseudomonas aeruginosa exhibits directed twitching motility up phosphatidylethanolamine gradients.

Pseudomonas aeruginosa translocates over solid surfaces by a type IV pilus-dependent form of multicellular motility known as twitching. We wondered whether cells utilize endogenous factors to organize twitching, and we purified from wild-type cells a lipid that caused directed movement. Wild-type P. aeruginosa, but not a pilJ pilus-deficient mutant, showed biased movement up gradients of phosphatidylethanolamine (PE) established in agar. Activity was related to the fatty acid composition of the lipid, as two synthetic PE species, dilauroyl and dioleoyl PE, were capable of directing P. aeruginosa motility while many other species were inactive. P. aeruginosa PE did not contain either laurate or oleate, implying that the native attractant species contains different fatty acids. Uniform concentrations of PE increased cell velocity, suggesting that chemokinesis may be at least partly responsible for directed movement. We speculate that PE-directed twitching motility may be involved in biofilm formation and pathogenesis.

Chemotactic Factors↗

EEG effects of smoking: Is there tachyphylaxis?

Smoking generally affects the human EEG by reducing low-frequency activity and increasing higher-frequency activity. Using a double-blind design, we sought to determine if acute tolerance (tachyphylaxis) to this effect can be observed. EEG was recorded in overnight-abstaining participants before and after smoking three cigarettes at 40-min intervals in two separate sessions. In one session ('short interval'), all three cigarettes had 'typical' nicotine yields (1.1 mg, FTC method). In the other session ('long interval'), the second cigarette had a very low nicotine yield (0.05 mg; thus making the interval between 1.1-mg cigarettes 80 min). Eyes-closed alpha power decreased and eyes-open beta-2 power increased following smoking each of the 'typical-yield' cigarettes but not the low-yield cigarettes. The decrease in alpha power after smoking the 'typical-yield' cigarette at the 40- and 80-min intervals was less than that following the first cigarette of the day, indicating tachyphylaxis. In contrast, the increase in eyes-open beta-2 power did not differ among cigarettes regardless of the order or interval between 'typical-yield' cigarettes. EEG changes in other frequency bands produced by smoking the first cigarette of the day were not consistent across sessions, making interpretation in terms of tachyphylaxis somewhat problematic. Overall, lower-frequency alpha activity displayed patterns consistent with tachyphylaxis while beta-2 did not.

Adult↗

Rare detection of Neospora caninum in placentas from seropositive dams giving birth to full-term calves.

Neospora caninum is thought to be transmitted to cattle by dogs, the only known definitive host. Although aborted fetuses seem the most likely source of infective material for dogs, placentas from seropositive dams appear also as a potential source of infective material. The objective of the study was to evaluate the presence of N. caninum organisms in placentas of full-term calves born to seropositive cows. Sixteen placentas, 11 from Neospora-seropositive cows, were examined histologically and by immunohistochemistry and polymerase chain reaction (PCR) assay for the presence of N. caninum. Mild placentitis was observed in all placentas. Neospora caninum was not identified by immunohistochemistry, but placentas from 2 seropositive dams were positive for N. caninum by PCR. These results suggest that placentas of full-term calves from seropositive cows may be a potential source of N. caninum for dogs, but the incidence of this mode of transmission is likely to be low.

Animals↗

The use of a new continuous wireless cardiorespiratory telemonitoring system by elderly patients at home.

The diagnosis and management of increasing numbers of patients with chronic diseases in the community require new technologies and strategies of care. We have used a new wireless cardiorespiratory telemonitoring system to monitor 14 elderly patients with a variety of chronic diseases at home. The electrocardiogram (ECG), heart rate and variability, and breathing were recorded on two separate occasions for 24 h. There was no difference in the data recorded when a research nurse applied the monitoring system and when the patients applied it themselves. The ECG and heart rate were recorded for 98% of the monitored time, and the frequency and periodicities of breathing were recorded for 74% and 61% of sleep and rest time by visual and automatic analysis, respectively. The results show that 24 h activity and cardiorespiratory telemonitoring can be performed by elderly patients at home. Significant unsuspected abnormalities of breathing and heart rhythm, amenable to treatment, were also detected.

Aged↗

The effects of a multi-modal intervention trial of light, exercise, and vitamins on women's mood.

The purpose of this study was to test the efficacy of a tri-modal intervention (LEVITY) to improve women's mood. This eight-week randomized experiment with a placebo-control group targeted women with symptoms of mild to moderate depression. Women in the intervention group were instructed to take a brisk 20-minute outdoor walk at target heart rate of 60% of maximum heart rate, to increase light exposure throughout the day and to take a specific vitamin regimen. Women in the control group took a daily placebo vitamin. The sample consisted of 112 women ages 19-78 who reported mild to moderate depressive symptoms. They were in otherwise good health and were not currently taking any mood-altering medication. Pre- and post-intervention assessment utilized live measures of mood: Center for Epidemiology Studies Depression Scale, Profile of Mood States, Depression-Happiness Scale, Rosenberg Self-Esteem Scale, and the General Well-Being Schedule. Analysis of covariance indicated that the intervention was effective in improving women's overall mood, self-esteem, and general sense of well-being and in decreasing symptoms on two measures of depression. Of particular note, the data from all five outcome measures supported the efficacy of the intervention. In addition, a high level of adherence to the intervention protocol was observed with two-thirds of the women reporting 100% adherence. Study implications suggest that this type of intervention may provide an effective, clinically manageable therapy for mild-to-moderately depressed women who prefer a self-directed approach or who have difficulties with the cost or side-effects of medication or psychotherapy.

Adult↗

Detection of Aeromonas hydrophila in a drinking-water distribution system: a field and pilot study.

A 16-month study was conducted on the presence of Aeromonas hydrophila in drinking water in Indiana, U.S.A. Enumeration was conducted in source water, in various sites within a water treatment plant, and in the distribution system in both bulk water and biofilm, as well as in a simulated (annular reactors) drinking-water distribution system. Presumptive Aeromonas spp. counts on source waters regularly approached 10(3)-10(4) CFU/100 mL, during summer months and granular activated carbon - filtered water counts ranged from <1 to 490 CFU/100 mL. In source water, presumptive Aeromonas levels were related to water temperature. Aeromonas hydrophila was never detected in the treatment plant effluent or distributed bulk water, showing disinfectant efficiency on suspended bacteria; however, isolates of A. hydrophila were identified in 7.7% of the biofilm samples, indicating a potential for regrowth and contamination of drinking-water distribution systems.

Aeromonas hydrophila↗

Examination of the structured withdrawal program to prevent relapse of nocturnal enuresis.

PURPOSE: A variety of treatment options are available for children with nocturnal enuresis. The success of any intervention depends on if the child remains dry once the treatment is withdrawn. All interventions for children with nocturnal enuresis are vulnerable to some degree of relapse. Pharmacological interventions, involving either desmopressin or imipramine, seem particularly susceptible to relapse occurring rapidly once medication is withdrawn. The usual practice is to taper the dose gradually although this is time-consuming and of questionable effectiveness. An alternative approach is to use a time-limited structured withdrawal program, the success of which has been recently documented. We investigated the effectiveness of the structured withdrawal program to understand the variables related to success. MATERIALS AND METHODS: A total of 51 patients 7 to 16 years old were included in the 8-week structured withdrawal program. Patients were 90% dry with medication taken for 4 to 24 months before the program and had experienced 2 unsuccessful withdrawal attempts. Patients were offered the choice of using an enuresis alarm on medication-free nights. Progress was monitored at 2, 5 and 8 weeks, and long-term success was defined as no relapse 6 months after cessation of treatment. RESULTS: At weeks 9 and 10 with complete cessation of medication 74.5% of children remained dry, and success was not related to use of an enuresis alarm. CONCLUSIONS: The structured withdrawal program significantly reduces relapse rates, and offers an alternative and rapid means of successfully withdrawing medication. It is argued that the influential variable concerns the ability of the child to shift attribution for success from an external source (that is medication) to an internal focus (that is changes in themselves).

Adolescent↗

Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates.

BACKGROUND: The gp120 exterior envelope glycoprotein of HIV-1 binds sequentially to CD4 and chemokine receptors on cells to initiate virus entry. During natural infection, gp120 is a primary target of the humoral immune response, and it has evolved to resist antibody-mediated neutralization. We previously reported the structure at 2.5 A of a gp120 core from the HXBc2 laboratory-adapted isolate in complex with a 2 domain fragment of CD4 and the antigen binding fragment of a human antibody. This revealed atomic details of gp120-receptor interactions and suggested multiple mechanisms of immune evasion. RESULTS: We have now extended the HXBc2 structure in P222, crystals to 2.2 A. The enhanced resolution enabled a more accurate modeling of less-well-ordered regions and provided conclusive identification of the density in the central cavity at the crux of the gp120-CD4 interaction as isopropanol from the crystallization medium. We have also determined the structure of a gp120 core from the primary clinical HIV-1 isolate, YU2, in the same ternary complex but in a C2 crystal lattice. Comparisons of HXBc2 and YU2 showed that while CD4 binding was rigid, portions of the gp120 core were conformationally flexible; overall differences were minor, with sequence changes concentrated on a surface expected to be exposed on the envelope oligomer. CONCLUSIONS: Despite dramatic antigenic differences between primary and laboratory-adapted HIV-1, the gp120 cores from these isolates are remarkably similar. Taken together with chimeric substitution and sequence analysis, this indicates that neutralization resistance is specified by quaternary interactions involving the major variable loops and thus affords a mechanism for viral adaptation. Conservation of the central cavity suggests the possibility of therapeutic inhibitors. The structures reported here extend in detail and generality our understanding of the biology of the gp120 envelope glycoprotein.

Amino Acid Sequence↗

Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia.

BACKGROUND: NO has been advocated as an adjunct to cardioplegia solutions. However, NO undergoes a rapid biradical reaction with superoxide anions to produce peroxynitrite (ONOO(-)). ONOO(-) in crystalloid cardioplegia solution induces injury to coronary endothelium and to systolic function after cardioplegia and reperfusion. However, ONOO(-) may be degraded to less lethal or cardioprotective intermediates with glutathione (GSH) in reactions separate from its well known antioxidant effects. We hypothesized that GSH detoxifies ONOO(-) and reverses defects in endothelial function and systolic function when present in crystalloid cardioplegia. METHODS AND RESULTS: In anesthetized dogs on cardiopulmonary bypass, a 45-minute period of global normothermic ischemia was followed by 60 minutes of intermittent cold crystalloid cardioplegia (Plegisol) and 2 hours of reperfusion. The cardioplegia solution contained 5 micromol/L authentic ONOO(-); catalase was included to attenuate the potential antioxidant effects of GSH and to unmask the effects on ONOO(-). In 1 group (CP+GSH, n=5), the cardioplegia contained 500 micromol/L GSH, whereas 1 group received crystalloid cardioplegia without GSH (CCP, n=6). There were no group differences in postcardioplegia left ventricular systolic function (end-systolic pressure-volume relation, impedance catheter: CCP 10.0+/-2.4 versus CP+GSH 10.6+/-1.3 mm Hg/mL) or diastolic chamber stiffness (ss-coefficient: CCP 0.35+/-0.2 versus CP+GSH 0.31+/-0.18). Myocardial neutrophil accumulation (myeloperoxidase activity) was attenuated in CP+GSH versus CCP (2.2+/-0.7 versus 5.4+/-1.2, P:<0.05). In postexperimental coronary arteries, maximal endothelium-dependent relaxation was greater in CP+GSH than in CCP (118+/-6% versus 92+/-5%, P:<0.05), with a smaller EC(50) value (-7. 10+/-0.05 versus -6.98+/-0.03, respectively, P:<0.05). Smooth muscle relaxation was complete in both groups. The adherence of neutrophils to postexperimental coronary arteries as a measure of endothelial function was less in CP+GSH than in CCP (98+/-18 versus 234+/-36 neutrophils/mm(2), P:<0.05). Nitrosoglutathione, a byproduct of the reaction between ONOO(-) and GSH, was greater in CP+GSH than in CCP (4.1+/-2.3 versus 0.4+/-0.2 microg/mL, P:<0.05). CONCLUSIONS: GSH in crystalloid cardioplegia detoxifies ONOO(-) and forms cardioprotective nitrosoglutathione, resulting in attenuated neutrophil adherence and selective endothelial protection through the inhibition of neutrophil-mediated damage.

Animals↗

A tyrosine-sulfated peptide based on the N terminus of CCR5 interacts with a CD4-enhanced epitope of the HIV-1 gp120 envelope glycoprotein and inhibits HIV-1 entry.

The sequential association of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 with CD4 and a seven-transmembrane segment coreceptor such as CCR5 or CXCR4 initiates entry of the virus into its target cell. The N terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in the CD4-dependent association of gp120 with CCR5 and in viral entry. Here we demonstrate that a tyrosine-sulfated peptide based on the N terminus of CCR5, but not its unsulfated analogue, inhibits infection of macrophages and peripheral blood mononuclear cells by CCR5-dependent, but not CXCR4-dependent, HIV-1 isolates. The sulfated peptide also inhibited the association of CCR5-expressing cells with gp120-soluble CD4 complexes and, less efficiently, with MIP-1alpha. Moreover, this peptide inhibited the precipitation of gp120 by 48d and 23e antibodies, which recognize CD4-inducible gp120 epitopes, but not by several other antibodies that recognize proximal epitopes. The ability of the sulfated peptide to block 48d association with gp120 was dependent in part on seven tropism-determining residues in the third variable (V3) and fourth conserved (C4) domains of gp120. These data underscore the important role of the N-terminal sulfate moieties of CCR5 in the entry of R5 HIV-1 isolates and localize a critical contact between gp120 and CCR5.

Amino Acid Sequence↗