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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 289 records · Page 16Linked to original sources

The tammar wallaby: a model to study putative autocrine-induced changes in milk composition.

The marsupial newborn is immature and the mother has the capacity to alter milk composition significantly during lactation, presumably to meet the nutritional requirements of the developing young. Furthermore, macropodid marsupials may practice asynchronous concurrent lactation (ACL)7 whereby the mother provides milk which differs in all the major components from adjacent mammary glands for two young of different ages. This phenomenon suggests that local regulation of mammary function, in addition to endocrine stimuli, is likely to be important for controlling milk composition. This paper explores the possibility that changes in sucking patterns of the young represent the first step in a mechanism to signal the mammary gland for putative autocrine-induced changes in milk composition.

Amino Acid Sequence↗

The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies.

Barth syndrome (BTHS) is an X-linked disorder characterized clinically by the associated features of cardiac and skeletal myopathy, short stature, and neutropenia. The clinical manifestations of the disease are, in general, quite variable, but cardiac failure as a consequence of cardiac dilatation and hypertrophy is a constant finding and is the most common cause of death in the first months of life. X-linked cardiomyopathies with clinical manifestations similar to BTHS have been reported, and it has been proposed that they may be allelic. We have recently identified the gene responsible for BTHS, in one of the Xq28 genes, G4.5. In this paper we report the sequence analysis of 11 additional familial cases: 8 were diagnosed as possibly affected with BTHS, and 3 were affected with X-linked dilated cardiomyopathies. Mutations in the G4.5 gene were found in nine of the patients analyzed. The molecular studies have linked together what were formerly considered different conditions and have shown that the G4.5 gene is responsible for BTHS (OMIM 302060), X-linked endocardial fibroelastosis (OMIM 305300), and severe X-linked cardiomyopathy (OMIM 300069). Our results also suggest that very severe phenotypes may be associated with null mutations in the gene, whereas mutations in alternative portions or missense mutations may give a "less severe" phenotype.

Abnormalities, Multiple↗

Transfusion-transmitted babesiosis in Washington State: first reported case caused by a WA1-type parasite.

Most cases of babesiosis reported in the United States have been tickborne and caused by Babesia microti, the etiologic agent of all previously described transfusion-transmitted cases. A 76-year-old man with the first recognized case of transfusion-transmitted infection with the recently identified WA1-type Babesia parasite is described. The subject received multiple blood transfusions in 1994. Indirect immunofluorescent antibody testing of serum from 57 blood donors implicated a 34-year-old man (WA1 titer, 1:65,536) whose donation had been used for packed red cells. Isolates of the organisms that infected the recipient and the donor, both of whom were spleen-intact residents of Washington State, were obtained by hamster inoculation. The DNA sequence of a 536-bp region of the nuclear small subunit-rRNA gene of both isolates was identical to that of WA1 (isolated in 1991 from the index WA1 case-patient). Effective measures for preventing transmission of babesiosis by blood transfusion are needed.

Adult↗

Killing of methicillin-resistant Staphylococcus aureus in vitro using aluminium disulphonated phthalocyanine, a light-activated antimicrobial agent.

The aim of this study was to determine whether 16 epidemic methicillin-resistant strains of Staphylococcus aureus (EMRSA) could be killed by the light-activated antimicrobial agent aluminium disulphonated phthalocyanine (AIPcS2). EMRSA suspensions were irradiated with light from a laser diode in the presence of AIPcS2 and survivors enumerated. All strains were susceptible to killing, the bactericidal effect being dependent on the AIPcS2 concentration and the light dose. AIPcS2 rendered the bacteria light-sensitive almost immediately and killing was unaffected by the growth phase of the organism. Scavengers of singlet oxygen and free radicals protected the bacteria from killing. These results imply that light-activated antimicrobial agents may be useful in eliminating EMRSA from wounds or carriage sites.

Aluminum↗

Working memory for sign language: a window into the architecture of the working memory system.

Traditionally, working memory has been divided into two major domains: verbal and visuo-spatial. The verbal domain of working memory can be characterized either by its relationship to language or by its grounding in auditory processing. Because of this ambiguity, languages that are not auditory and vocal (i.e., signed languages) pose a challenge to this conception of working memory. We describe several experiments with deaf users of American Sign Language (ASL) that explore the extent to which the architecture of working memory is determined by the constraints of auditory and visual processing and the extent to which it is determined by the characteristics of language. Various working memory effects were investigated: phonological similarity, word length, and articulatory suppression. The pattern of evidence strongly supports the existence of a sign-based 'rehearsal loop' mechanism parallel to the speech-based rehearsal loop. However, we also discuss evidence pointing to differences between the speech loop and the sign loop from forward and backward digit span tasks with deaf and hearing subjects. Despite their similarities based on linguistic properties, the speech loop and the sign loop appear to diverge due to the differing processing demands of audition and vision. Overall, the results suggest that the architecture of working memory is shaped both by the properties of language structure and by the constraints imposed by sensorimotor modality.

Journal Article↗

Modality of language shapes working memory: evidence from digit span and spatial span in ASL signers.

Deaf children who are native users of American Sign Language (ASL) and hearing children who are native English speakers performed three working memory tasks. Results indicate that language modality shapes the architecture of working memory. Digit span with forward and backward report, performed by each group in their native language, suggests that the language rehearsal mechanisms for spoken language and for sign language differ in their processing constraints. Unlike hearing children, deaf children who are native signers of ASL were as good at backward recall of digits as at forward recall, suggesting that serial order information for ASL is stored in a form that does not have a preferred directionality. Data from a group of deaf children who were not native signers of ASL rule out explanations in terms of a floor effect or a nonlinguistic visual strategy. Further, deaf children who were native signers outperformed hearing children on a nonlinguistic spatial memory task, suggesting that language expertise in a particular modality exerts an influence on nonlinguistic working memory within that modality. Thus, language modality has consequences for the structure of working memory, both within and outside the linguistic domain.

Journal Article↗

Clinical isolates of Staphylococcus aureus have osteolytic surface proteins and a proportion of the population have antibodies that block this activity: is this of prognostic significance?

Staphylococcus aureus is directly implicated in the bone destruction associated with infected orthopaedic implants and bacterial arthritis. The Oxford (laboratory) strain of this organism has surface-associated proteins (SAPs) which have potent osteolytic activity. In this study, we have examined the osteolytic activity of SAPs from clinical isolates and also investigated the role of the humoral immune response to such proteins. Nine patients with infected orthopaedic prostheses or infective arthritis, and six volunteers not suffering from overt S. aureus infection, were examined. The sera from 5/9 patients and 4/6 volunteers were able to neutralize the osteolytic activity of the SAPs. The SAPs were extracted from four clinical isolates and were found to have osteolytic activity, but with a wide range of efficacies and potencies. All four patients from whom the clinical isolates were obtained had serum IgG antibodies to the surface proteins from their autologous isolates as determined by ELISA. In conclusion, clinical isolates of S. aureus contain osteolytic SAPs which may be responsible for bone destruction. Apparently disease-free individuals and patients have antibodies able to block this activity. However, since the capacity of patients' sera to neutralize the activity of the SAPs derived from their own S. aureus isolate was not investigated, it is unclear whether these findings are of prognostic value.

Antibodies, Bacterial↗

Staphylococcus epidermidis produces a cell-associated proteinaceous fraction which causes bone resorption by a prostanoid-independent mechanism: relevance to the treatment of infected orthopaedic implants.

Staphylococcus epidermidis is the most commonly isolated coagulase-negative staphylococcus from the skin, gut and upper respiratory tract. Although it is less virulent than Staphylococcus aureus, it has emerged in recent years as an important causative agent of infections associated with metal implants, prosthetic devices and i.v. lines. We have previously demonstrated that a saline wash of S. aureus contained proteins which had potent bone-resorbing activity in vitro. The purpose of this study was to determine whether gently washing S. epidermidis in saline also released osteolytically active proteins. The so-called surface-associated material (SAM) eluted from S. epidermidis in saline was able to induce osteolysis, and activity was heat and trypsin sensitive, suggesting that the active component was proteinaceous. Fractionation studies have suggested that activity is due to a small number of cationic proteins. This SAM-induced bone resorption was not inhibited by the cyclo-oxygenase inhibitor, indomethacin, or the 5-lipoxygenase inhibitors BWA70C and MK886. However, it was partially inhibited by high concentrations of interleukin-1 receptor antagonist and was completely blocked by a neutralizing antibody to tumour necrosis factor-alpha. Thus, the SAM from this organism is a potent osteolytic agent which differs from that of S. aureus SAM in not being inhibited by cyclo-oxygenase inhibitors. As adjunctive therapy is becoming necessary in infectious diseases, either as a result of the side-effects of antibiotics or their lack of efficacy, consideration should be given to the future treatment of bone infections with staphylococci in the light of the different mechanisms of action of the surface proteins produced by these bacteria.

Animals↗

Merger motorway. Giving staff the tools to reengineer.

Mergers and health care agencies' response to mergers dominate current conversations in this evolving managed care environment. Hospitals are rapidly learning to adjust to declining occupancy rates and deceased utilization of resources. A business model to guide mergers was adapted to assist staff with the people, structural, cultural and political issues of organizational change. Creating successful new work environments, moving from a "We-they" mentality to unity and decreasing use of resources are outcomes described in this article.

Adaptation, Psychological↗

Susceptibilities of Actinobacillus actinomycetemcomitans biofilms to oral antiseptics.

The susceptibilities of Actinobacillus actinomycetemcomitans cultures, grown as 1- or 3-day-old biofilms or as planktonic suspensions, to concentrations of chlorhexidine digluconate, cetylpyridinium chloride or triclosan used in commercial mouthwashes were compared. Three-day biofilms were the most resistant form of the organism and chlorhexidine was the most active antiseptic. Comparison of solutions of the pure antibacterial agent with commercial products containing the same concentration of antiseptic showed little difference in in-vitro activities. The results emphasise that the testing of antimicrobial mouthwashes should be performed on bacteria grown as biofilms.

Aggregatibacter actinomycetemcomitans↗

The bactericidal effects of dental ultrasound on Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. An in vitro investigation.

This study investigated the possible bactericidal acoustic effects of the dental ultrasonic scaler. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis suspensions, were subjected to the vibrations of a Cavitron P1 insert for 2.5 and 5.0 min in an acoustically-simulated pocket model and the survivors enumerated. The extent of any cavitation occurring within the pocket model to which the statistically significant bactericidal activity observed might be attributed, was determined by 'sonoluminescence', which was then investigated by photomultiplication techniques. However, these failed to detect any sonoluminescence within the pocket space and, moreover, the necessary deflection of the water coolant away from the insert tip, to avoid flooding of the experimental pocket, proved to result in temperatures of 47.6 degrees C and 52.3 degrees C at the respective time intervals, and thereby constituted an alternative possible bactericidal mechanism. Examination of the effects of such temperature changes on the target bacteria then revealed statistically significant differences in the viable counts of both microorganisms after 5.0-min periods, and as such were comparable to those previously detected in relation to the pocket model. Whilst it must be presumed that the bacteriolytic effect observed in the main investigation was due to the incidental temperature changes, in the absence of acoustic cavitation the influence of any associated acoustic microstreaming cannot be discounted. Further investigations to assess the bactericidal potential of acoustic phenomena using a modified experimental to exclude any hyperthermic effects are therefore necessary.

Acoustics↗

Absence of Helicobacter pylori DNA in salivary lymphoepithelial lesions.

Helicobacter pylori is a common cause of chronic gastritis and has been implicated as the main agent responsible for the development of lymphomas of mucosa associated lymphoid tissue (MALT) in the stomach. An uncommon cause of salivary gland swelling is salivary lymphoepithelial lesion (SLEL), which shows histological features of acquired MALT and is associated with the development of MALT-type lymphomas. Since H. pylori has been identified in the oral cavity, we hypothesised that this organism might act as a potential antigen for the development of MALT in salivary glands. Routinely processed biopsies of 20 SLEL were screened for H. pylori DNA using a sensitive two-stage PCR technique to amplify the 16S ribosomal RNA gene. Immunoglobulin heavy chain gene monoclonality was determined by amplifying the VDJ gene using a nested PCR technique. All SLEL had histological features of organised MALT and 14 cases showed Ig heavy chain gene monoclonality consistent with MALT lymphoma. None of the SLEL contained H. pylori DNA. In contrast to the putative role of H. pylori as an antigenic stimulus in gastric MALT lymphomas, it appears not to play a role locally in the development of MALT or MALT lymphomas of the salivary gland.

Adult↗

Interactions between periodontopathogenic bacteria and cytokines.

Cytokines produced in response to plaque bacteria clearly play a key role in the periodontal diseases. However, we know very little about the interactions between cytokines and periodontopathogenic bacteria. The aims of this study were to determine whether the key pro-inflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 could affect the growth of Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis and to determine whether these organisms could hydrolyse IL-1 beta, IL-6 or the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Culture medium containing up to 100 ng/ml of IL-1 beta or IL-6 was inoculated with A. actinomycetemcomitans (serotypes a, b and c) or P. gingivalis and growth was monitored by measuring changes in electrical conductivity every 3 min for up to 48 h. IL-1 beta, IL-6 or IL-1ra were added to culture supernatants and incubated for up to 24 h. Samples were taken at various times, analysed by SDS-PAGE and the separated proteins transferred by Western blotting to PVDF membranes and probed with anti-cytokine antibodies. None of the cytokines tested had any effect on the rate of growth or yield of A. actinomycetemcomitans or P. gingivalis. Supernatants from P. gingivalis cultures, but not those from A. actinomycetemcomitans, hydrolysed IL-1 beta, IL-6 and IL-1ra. The hydrolysate from the P. gingivalis supernatant-treated IL-1 beta was unable to stimulate the release of IL-6 from human gingival fibroblasts showing that it had lost biological activity. These results suggest that P. gingivalis can perturb the cytokine network, not only by stimulating the release of cytokines from host cells, but also by removing them from its local environment.

Aggregatibacter actinomycetemcomitans↗

Effect of dosimetric and physiological factors on the lethal photosensitization of Porphyromonas gingivalis in vitro.

The aims of this study were to (1) determine the effect of dosimetric and physiological factors on the lethal photosensitization of Porphyromonas gingivalis using toluidine blue O (TBO) and light from a helium/neon (HeNe) laser; (2) determine the influence of sensitizer concentration, preirradiation time, serum and growth phase on sensitizer uptake by P. gingivalis. The dosimetric factors studied were concentration of TBO, light dose and preirradiation time. The physiological factors were presence of serum, pH and bacterial growth phase. Sensitizer uptake by P. gingivalis under various conditions was determined using tritiated TBO (3H-TBO). In the presence of TBO, a light dose-dependent increase in kill was attained (100% kill at 4.4 J). There was no significant effect on the numbers killed when TBO was increased from 12.5 to 50 micrograms/mL. An increase in preirradiation time gave slightly increased kills. High kills were achieved at all three pH (6.8-8.0). Although kills were substantial in the presence of serum, they were significantly less than those obtained in the presence of saline. Cells in all three growth phases were susceptible to lethal photosensitization, although stationary phase cells were slightly less susceptible. Maximum uptake of TBO occurred within 60 s and uptake in serum was less than in saline. The uptake by the log phase cells was greater at lower concentrations of sensitizer (50 micrograms/mL), compared to the other two phases.

Dose-Response Relationship, Radiation↗

Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers.

In a double-blind and randomized manner, 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate (Cr) or a maltodextrin placebo (P) for 9 days during training. Prior to and following supplementation, subjects performed three 100-m freestyle sprint swims (long course) with 60 s rest/recovery between heats. In addition, subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests. Significant differences were observed among swim times, with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint. There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group. Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance.

Adolescent↗

Evaluation of six commercial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii. The FDA Toxoplasmosis Ad Hoc Working Group.

As a result of reports received by the Food and Drug Administration (FDA) of false-positive results obtained with FDA-cleared in vitro diagnostic kits for the detection of Toxoplasma-specific human immunoglobulin M (IgM) antibodies, an FDA-sponsored evaluation of six kits was performed. A battery of 258 serum specimens, including 30 specimens drawn 1 to 5 months after initial Toxoplasma infection and 228 specimens from Toxoplasma IgG-positive individuals, Toxoplasma IgG-negative individuals, rheumatoid factor-positive persons, and persons determined to be Toxoplasma IgM positive by commercially available assays, was assembled, randomly assorted, and coded. The battery was tested at the FDA with six commercially available kits, at the Palo Alto Medical Foundation (PAMF) by the PAMF double-sandwich IgM enzyme-linked immunosorbent assay (PAMF IgM ELISA), and at the Centers for Disease Control and Prevention (CDC) by the CDC EIA IgM. The results of the PAMF IgM ELISA that were obtained with the battery were considered to be the "gold standard" for this study; specificity rates were computed by considering the PAMF results to be 100% specific. Sensitivity and specificity rates were found to be as follows: CDC EIA IgM, 100 and 99.1%, respectively; Abbott IMx Toxo IgM, version 1, 100 and 77.5%, respectively; Abbott IMx Toxo IgM, version 2, 93.3 and 97.3%, respectively; Abbott Toxo-M EIA, 100 and 84.2%, respectively; BioMérieux Vitek VIDAS Toxo IgM, 100 and 98.6%, respectively; BioWhittaker Toxocap-M, 100 and 95.9%, respectively; Gull Toxo IgM, 97 and 85.6%, respectively; and Sanofi Diagnostics Pasteur Platelia Toxo IgM, 100 and 96.8%, respectively. Although the extent of false-positive reactions with these kits cannot be calculated because the study was retrospective and sample choices were biased, the results may be useful as an indicator of the relative specificities of these kits.

Animals↗

Are some minis multiquantal?

The amplitude distribution of miniature postsynaptic currents (minis) in many central neurons has a large variance and positive skew, but the sources of this variance and skew are unresolved. Recently it has been proposed that spontaneous Ca2+ influx into a presynaptic bouton with multiple release sites could cause spontaneous multiquantal minis by synchronizing release at all sites in the bouton, accounting for both the large variance and skew of the mini distribution. We tested this hypothesis by evoking minis with internally perfused, buffered Ca2+ and the secretagogue alpha-latrotoxin, both in the absence of external Ca2+. With these manipulations, the synchronized release model predicts that the mini distribution should collapse to a Gaussian distribution with a reduced coefficient of variation. Contrary to this expectation, we find that mini amplitude distributions under these conditions retain a large variance and positive skew and are indistinguishable from amplitude distributions of depolarization-evoked minis, strongly suggesting that minis are uniquantal.

Animals↗