Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils.
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Amino Acid Sequence↗
Biomedical subjects
W Smith
Publications and source records attributed to W Smith.
Tetanus immunity in an older Australian population.
OBJECTIVE: To evaluate the effectiveness in older Australians of the current tetanus vaccination program. DESIGN: A cross-sectional survey of tetanus immunity (enzyme immunoassay of serum samples) in an older population in New South Wales. Self-reported history of tetanus vaccination was compared with serologically measured immunity. PARTICIPANTS: 430 randomly selected adults, 49 years of age and older, from the Blue Mountains Eye Study population. RESULTS: Fifty-two per cent (95% confidence interval [CI], 47%-57%) of adults 49 years of age and older had protective levels of tetanus antitoxin ( > 0.15 IU/mL). There was a significant decline in the prevalence of immunity with increasing age (chi 2 for linear trend, P = 0.036), and women were less likely to be immune regardless of their age (Mantel-Haenszel weighted odds ratio, 0.65; CI, 0.43-0.92). Thirty-five per cent (95% CI, 31%-40%) of all participants reported that they had been vaccinated in the preceding 10 years. Although self-reported tetanus vaccination history was associated with tetanus immunity, it was neither sensitive nor specific as a test for immunity. CONCLUSIONS: About half the adults 49 years of age and older in the Blue Mountains area of New South Wales do not have protective levels of tetanus antitoxin because of inadequate vaccination coverage in this age group. Vaccination history is not a reliable indicator of tetanus immunity and a system is needed for accurate recording of adult vaccination.
Adult↗
Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus.
The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.
Aged↗
Chronic nonpulsatile blood flow. II. Hemodynamic responses to progressive exercise in calves with chronic nonpulsatile biventricular bypass.
We investigated the effects of stepwise treadmill exercise on animal (calf) hemodynamic variables during chronic nonpulsatile biventricular bypass with ventricular fibrillation. Seven days was allowed for recovery from the effects of anesthesia and surgery; each animal's natural heart was then fibrillated. The pump flows were maintained at nominal rates of 90, 100, and 120 ml.kg-1.min-1 for 1 week each, with the order varying from experiment to experiment. A total of 30 incremental exercise tests were performed on five animals. No significant changes in mean aortic pressure were observed during nonpulsatile perfusion at the three nominal flow rates of nonpulsatile flow either before or during exercise. The systemic vascular resistance decreased significantly during exercise (from 705 +/- 22 to 547 +/- 81 dyne.sec.cm-5, p < 0.01, and from 604 +/- 25 to 510 +/- 15 dyne.sec.cm-5, p < 0.05, at nominal flow rates of 100 and 120 ml.kg-1.min-1, respectively). There were also significant (analysis of variance, Scheffe test, p < 0.05) differences in systemic vascular resistance among three nominal flow rates both before and during exercise. These results suggest that the autonomic nerve reflex control of the cardiovascular system in physical exercise was functioning normally in animals with chronic nonpulsatile blood flow.
Animals↗
Chronic nonpulsatile blood flow. III. Effects of pump flow rate on oxygen transport and utilization in chronic nonpulsatile biventricular bypass.
The relationship between blood flow and oxygen transport was studied in five calves with chronic nonpulsatile biventricular bypass. Seven days was allowed for recovery from the effects of anesthesia and operation; the natural heart was then fibrillated. Pump flows were maintained at nominal rates of 90, 100, or 120 ml.kg-1.min for 1 week each, with the sequence varied from experiment to experiment. Venous and arterial blood samples were taken at rest for blood gas analysis. Serum lactate analysis was done twice a week, on the third and seventh days after each pump flow change. Serum catecholamine levels were assayed on the seventh day of each flow rate. Progressive exercise tests were also conducted during each test segment. Basal oxygen consumption of a 4-month-old calf was 6.3 +/- 0.3 ml.kg-1.min-1. The mixed venous oxygen tension decreased when pump flow rate was reduced (29.6 +/- 1.0, 28.3 +/- 1.2, and 23.8 +/- 0.9 mm Hg at 120, 100, and 90 ml.kg-1.min-1 of pump flow, respectively), and oxygen extraction increased linearly when pump flow rate was reduced. Hemoglobin concentration significantly affected oxygen extraction rate. Serum lactate concentration increased significantly at a 90 ml.kg-1.min-1 perfusion compared with concentrations at other pump flow rates (7.81 +/- 2.42 mEq/L at 90 ml.kg-1.min-1 vs 0.71 +/- 0.19 and 0.73 +/- 0.81 mEq/L at 100 and 120 ml.kg-1.min-1, respectively; p < 0.01, analysis of variance, Scheffe F test). Maximum oxygen extraction during exercise was 78%. These results suggest that a critical flow level between 90 and 100 ml.kg-1.min-1 maintains oxidative metabolism in the calf with chronic nonpulsatile flow. The resulting oxygen delivery was slightly higher than that indicated in the literature. Maximal oxygen extraction was normal.
Animals↗
Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study.
BACKGROUND: The Blue Mountains Eye Study is a population-based study of vision and the causes of visual impairment and blindness in a well-defined urban, Australian population 49 years of age and older. METHODS: The logarithm of the minimum angle of resolution (logMAR) visual acuity was measured before and after refraction in 3647 persons, representing an 88% response rate in two postcode areas in the Blue Mountains area, west of Sydney. RESULTS: Refraction improved visual acuity by one or more lines in 45% of participants and by three or more lines in 13%. Visual impairment (visual acuity 20/40 or worse in the better eye) was found in 170 participants (4.7%). Mild visual impairment (Snellen equivalent 20/40 to 20/60 in the better eye) was found in 3.4% moderate visual impairment (20/80 to 20/160 in the better eye) in 0.6%, and severe visual impairment or blindness (20/200 or worse in the better eye) in 0.7%. Visual impairment increased with age from 0.8% of persons 49 to 54 years of age to 42% of persons 85 years of age or older. Visual impairment was significantly more frequent in females at all ages. Among persons with severe visual impairment, 79% were female. After adjusting for age, females were less likely to achieve 20/20 best-corrected visual acuity than males (odds ratio, 0.57; confidence interval, 0.48-0.66). After adjusting for age and sex, no association was found between visual acuity and socioeconomic status. Age-related macular degeneration was the cause of blindness in 21 of the 24 persons with corrected visual acuity of 20/200 or worse. CONCLUSION: Increasing age and female sex were independent predictors of visual impairment.
Adult↗
Client self-determination and professional intervention: striking a balance.
Social workers find themselves caught in the cross fire between two imperatives: (1) outcome-oriented and competency-based practice requisites and (2) the principle of client self-determination. In this context, the authors hypothesize that social workers use a wide range of gradations along a continuum of practice directiveness. Furthermore, there is ethical justification for this diverse role repertoire. Directiveness modalities are influenced by specific conditional factors that guide practitioner behavior. A study is described that empirically explores and amplifies these hypotheses.
Adult↗
Magnetic resonance imaging of peripartum rupture of the symphysis pubis.
BACKGROUND: Peripartum pubic symphyseal rupture is diagnosed on clinical grounds. Although the diagnosis may be supported by radiography, which shows diastasis of the pubic rami, magnetic resonance imaging (MRI) can visualize the nature of the soft tissue injury. CASE: Two puerperas thought clinically to have pubic symphyseal rupture were imaged with MRI. In addition to diastasis of the pubic rami, clefts were seen within the symphyseal cartilage, extending the entire breadth of the joint. The clefts were filled with fluid or hemorrhage, seen in T1- and T2-weighted images. The fluid was encapsulated within the joint by the surrounding ligaments. Four control normal puerperas, who had vaginal deliveries but were asymptomatic, showed none of the aforementioned findings. CONCLUSION: MRI can visualize the soft tissue injury seen in pubic symphyseal rupture and may be used to confirm the clinical diagnosis.
Adult↗
The use of synthetic Cecropin (D5C) in disinfecting contact lens solutions.
PURPOSE: Microbial keratitis caused by Pseudomonas aeruginosa is the most common contact lens associated corneal infection. Cecropins are microbicidal peptides isolated from the hemolymph of the Cecropia moth. Previous in vitro studies have demonstrated their efficacy against a broad spectrum of ocular pathogens. This study was designed: a) to evaluate the antimicrobial potency of three different contact lens solutions (Renu, Complete, and Opti-Free) against P. aeruginosa, and b) to evaluate the activity of the same contact lens solutions in combination with a synthetic cecropin analog, D5C, against the challenge organism in the presence of a soft contact lens. METHODS: A virulent strain of P.aeruginosa isolated from a case of ulcerative keratitis was used in the study. Three different concentrations of bacteria (10(3), 10(5) and 10(7) CFU/mL) were inoculated into the contact lens solutions and into buffered saline, which was employed as a control. The samples were incubated at 27 degrees C, and at time 0, 30, and 90 minutes, 24, 48, and 72 hours, and aliquots of the test solutions were plated and subcultured on nutrient agar. After 24 hours of incubation at 37 degrees C, colonies observed on the nutrient agar plates were counted. To study the antimicrobial efficacy of D5C (100 micrograms/mL), we used the identical test series and assay, adding a soft contact lens to the solutions and a larger inoculum of bacteria (10(9) CFU/mL). RESULTS: After 72 hours, all of the contact lens solutions tested sterilized 10(3) CFU/mL of P. aeruginosa. At 10(7) CFU/mL, they yielded greater than 2 logs of killing of the bacteria, but the solutions were not sterilized. The addition of D5C (100 micrograms/mL) to the contact lens solutions yielded greater than 3 logs of killing with a larger inoculum of bacteria in the presence of the soft contact lens. CONCLUSION: The contact lens solutions tested were effective against P. aeruginosa at 27 degrees C for up to 72 hours with an inoculum of 10(3) CFU/mL. The addition of D5C augmented their antimicrobial activity in the presence of the contact lens.
Colony-Forming Units Assay↗
The expression of neuronal voltage-dependent calcium channels in human cerebellum.
Little is known about the comparative distribution of voltage-dependent calcium channel subtypes in normal human brain. Previous studies in experimental animals have predominantly focused on the regional expression of single alpha 1 genes. We describe the preparation of riboprobes and antisera specific for human alpha 1A, alpha 1B and alpha 1E subunits and their application in comprehensive mapping studies of the human cerebellum. Within the cerebellar cortex, these pore forming proteins were found to have differential localisations when examined in adjacent sections. The alpha 1A and alpha 1B subunits broadly colocalised and were both present, though at apparently different levels, in the molecular, Purkinje and granule cell layers whilst alpha 1E was predominantly expressed in Purkinje cells. In the dentate nucleus, an area which has received little attention in previous studies, alpha 1A was highly expressed in regions in which Purkinje cell nerve terminals form synapses with deep cerebellar neurones.
Aged↗
Affinity purification of rat cortical and chicken forebrain synaptosomes using a biotinylated derivative of omega-CgTx GVIA.
We describe a magnetophoretic method for the affinity purification of synaptosomes expressing omega-CgTx GVIA-sensitive, N-type voltage-sensitive calcium channels (VSCCs). The method utilizes a biotinylated derivative of omega-CgTx GVIA which retains its ability to displace [125I] omega-CgTx GVIA from its binding sites on rat synaptic membranes. When coupled to streptavidin coated magnetizable beads, the hexanoyl spacer between omega-CgTx GVIA and the biotin:streptavidin bead complex is sufficiently long to allow flexibility of the toxin to bind to its receptor on synaptosomes. We have used this ligand successfully to isolate deaggregated synaptosomes from the parent fractions of chicken forebrain and rat cortex. In the chicken synaptosome parent fraction, omega-CgTx GVIA (1 nM-1 microM) produced a concentration-dependent block of the KCl-induced intracellular free Ca2+, [Ca2+]i, elevation with an IC50 of 28 nM. After affinity magnetophoresis no increase in [Ca2+]i elevation was observed in either the bound or unbound fractions. In the rat synaptosome parent fraction, the KCl-induced increase in free intracellular Ca2+ ([Ca2+]i) elevation was partially blocked by omega-CgTx GVIA (17 +/- 2% / 1 microM) and to a greater extent by omega-Aga IVA (55 +/- / 1 microM): a combination of the two toxins was additive (72 +/- 4% / 1 microM). The block obtained by omega-CgTx GVIA (1 microM) in the unbound fraction was reduced to 3 +/- 2%, whereas that by omega-Aga IVA (1 microM) increased to 82 +/- 3%. The block obtained by a combination of both toxins (83 +/- 2%) was the same as that with omega-Aga IVA alone (82 +/- 3%). No increase in free [Ca2+]i elevation was observed in the bound fraction although single synaptosome-like structures, displaying synaptophysin immunoreactivity, were detected on the beads. We conclude that omega-CgTx GVIA-sensitive N-type calcium channels are present on all chicken forebrain synaptosomes but only a subset of rat cortical synaptosomes.
Animals↗
Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.
OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.
Aged↗
Effect of a leukotriene B4 receptor antagonist SC-53228 on ozone-induced airway hyperresponsiveness and inflammation in dogs.
The importance of the potent neutrophil chemoattractant leukotriene (LT)B4 in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs was studied using the LTB4-receptor antagonist SC-53228. Seven dogs from random sources were studied three times, at least 2 wk apart. On each occasion, acetylcholine (Ach) airway responsiveness was measured before and 1 h after ozone (3 ppm, 30 min) or dry air inhalation, followed by a bronchoalveolar lavage (BAL). On the first day, dogs were treated with SC-53228 (0.4 mg/kg intravenously) followed by a continuous intravenous infusion of 1.2 mg/kg/h before ozone inhalation. On the other two days, diluent was infused followed by ozone or dry air inhalation. Cell counts were measured in BAL and cell activation was measured by spontaneous and by phorbol myristate acetate-stimulated (PMA) (2.4 mumol/L) oxygen radical release, measured from washed BAL cells (4 x 10(6) cells) by lucigenin-enhanced chemiluminescence. Ozone inhalation caused bronchoconstriction and airway hyperresponsiveness. SC-53228 inhibited the ozone-induced airway hyperresponsiveness (p = 0.006), but not the bronchoconstriction. Spontaneous (p = 0.004) and PMA-stimulated (p = 0.04) lucigenin-enhanced chemiluminescence were increased after ozone inhalation. The ozone-induced increases in PMA-stimulated chemiluminescence were significantly attenuated by treatment with SC-53228 (p = 0.04). These results suggest that LTB4 is involved in the pathogenesis of ozone-induced airway hyperresponsiveness, possibly through activation of airway inflammatory cell.
Acetylcholine↗
N omega-nitro-L-arginine methyl ester reduces the incidence of IDDM in BB/E rats.
Evidence that nitric oxide (NO) is involved in cytokine-mediated islet beta-cell dysfunction and destruction in vitro has led to the hypothesis that increased production of NO may contribute to the pathogenesis of insulin-dependent diabetes mellitus (IDDM). This study demonstrates that oral administration of N omega-nitro-L-arginine methyl ester (an inhibitor of NO synthase) from 30 to 150 days of age significantly reduced (P < 0.05) the incidence of IDDM in diabetes-prone BB/E rats. This supports the idea that NO plays a significant role in the pathogenesis of IDDM in this animal model.
Administration, Oral↗
Investigation and management of cervical intraepithelial neoplasia in Canadian Inuit: enhancing access to care.
Cervical intraepithelial neoplasia (CIN) is a major cause of morbidity among Circumpolar women. Cervical cancer comprised 15% of all cancers in Canadian Inuit women from 1969-1988. The age standardized incidence for invasive cervical cancer in Canadian Inuit women is 3.1 times the rate in the general Canadian population. Management of CIN in women of remote Arctic regions has traditionally required multiple visits to specialized medical centres for diagnosis, therapy and follow-up. Such centralized care requires separation of women from their families, resulting in significant medical, emotional and economic costs for the patient, her family and community. In the Canadian Central Arctic, a program for the diagnosis and therapy of CIN has been established using colposcopy with loop electrosurgery, performed by a trained local family practitioner and visiting gynecologist. Early program evaluation has indicated reduction in medical expenditures due to travel costs, minimal procedure-related morbidity and discomfort, and improved patient satisfaction associated with reduced separation from family and community. It is hoped that the program design, which harnesses technology in order to provide improved care closer to home, will be applicable to other Circumpolar regions.
Arctic Regions↗
Increasing response rates in telephone surveys: a randomized trial.
BACKGROUND: Sampling frames and mode of contact and administration of questionnaires are important factors contributing to response rates and selection bias in population-based research. The purpose of this paper is to evaluate whether contact by mail before contact by telephone increases response rate, and to assess the concurrent validity of telephone surveys for collecting health research and service data. METHODS: Two thousand households were randomly selected from electronic white pages. Half were randomly allocated to receive or not to receive an explanatory letter before telephone contact. Interviewers were blinded to whether a household received a letter. Respondents aged 18 years or over were randomly selected from within each household using a Kish grid and interviewed by telephone. RESULTS: The overall response rate was 68 per cent [confidence interval (CI) 66-70]. The response rate of those who received the letter was 76 per cent (CI 73-79), and of those who did not receive the letter was 60 per cent (CI 56-63). Use of the Kish grid to select randomly a respondent decreased the response rate by less than 10 per cent. The internal validity of the data was as follows: in a 10 per cent sub-sample, the Kish grid had been correctly applied in 93 per cent of households, and in 99 per cent of households the exclusion criteria had been correctly adhered to. The external validity was as follows: comparisons with data obtained from the same reference population using similar instruments administered face-to-face revealed no meaningful or significant differences in population estimates. CONCLUSIONS: Mail-out before telephone contact greatly increases response rates at low cost. Telephone surveys can yield valid, useful data for health research and service evaluation.
Adult↗
An outbreak of gentamicin-resistant Klebsiella pneumoniae in a neonatal ward.
Gentamicin-resistant Klebsiella pneumoniae (GRKP) was isolated from nineteen patients in the neonatal ward of Sultan Qaboos University Hospital (SQUH) in Oman. Thirteen cases were infected and six were colonized. Two infected patients died due to septicaemia, eight cases occurred within SQUH and eleven cases were imported from other hospitals. Sixteen isolates were of the same serotype (K25), three were non typeable. Referred patients from peripheral hospitals were the source of the organism and hand carriage the probable vehicle of transmission. The first strain of gentamicin-sensitive Kleb. pneumoniae was isolated five months after combating the outbreak.
Anti-Bacterial Agents↗