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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 181 records · Page 10Linked to original sources

Antibody-targeted lethal photosensitization of Porphyromonas gingivalis.

We have previously demonstrated that Porphyromonas gingivalis is susceptible to killing by toluidine blue O (TBO) when irradiated with light from a helium-neon (HeNe) laser. The aim of this study was to determine whether a TBO-antibody conjugate (Ab-TBO) could be used to specifically target P. gingivalis to lethal photosensitization in the presence of Streptococcus sanguis or human gingival fibroblasts (HGFs). When a mixture of P. gingivalis and S. sanguis was exposed to 4 microg of TBO/ml and irradiated with HeNe laser light, there were 1.5- and 4.0-log(10)-unit reductions in the viable counts, respectively. In contrast, when TBO was conjugated with a murine monoclonal antibody against P. gingivalis lipopolysaccharide, the reductions in viable counts of P. gingivalis and S. sanguis amounted to 5.0 and 0.1 log(10) units, respectively. Lethal photosensitization of P. gingivalis in the presence of HGFs using unconjugated TBO resulted in a 0.7-log(10)-unit reduction in P. gingivalis viable counts and a 99% reduction in the incorporation of tritiated thymidine ([(3)H]Tdr) by the HGFs. In contrast, when the Ab-TBO conjugate was used, there was a 100% reduction in P. gingivalis viable counts but no significant reduction in the incorporation of [(3)H]Tdr by HGFs. These results demonstrate that specific targeting of P. gingivalis can be achieved using TBO conjugated to a monoclonal antibody raised against a cell surface component of this organism.

Animals↗

An in vitro study of the effect of fluoridated milk on oral bacterial biofilms.

Microcosmic dental plaques were grown in artificial saliva and supplemented with either milk or fluoridated milk. The presence of fluoride in the milk increased the pH of the biofilms and reduced the proportions of streptococci, demonstrating that in this model, fluoridation of milk produces biofilms with reduced cariogenic potential.

Animals↗

Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1.

We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The prototypic gene in this cluster, set1, has been cloned and expressed. Recombinant SET1 stimulated the production of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. aureus but not in the other staphylococcal species examined. Sequence analysis of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency. The distribution of allelic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.

Amino Acid Sequence↗

Brachial vascular reactivity in blacks.

Endothelial function was studied ultrasonographically in a healthy subset of African Americans (blacks) because they have an increased risk of hypertension and vascular disease. Twenty-four healthy black and 28 well-matched white subjects were investigated. Ischemia was induced by inflating a cuff over the forearm to 40 mm Hg higher than systolic pressure for 5 minutes. Brachial artery diameter and blood flow velocity were measured at baseline and at 15, 45, and 60 seconds after deflation by use of an Acuson 128XP10 ultrasonograph with a 7.5 MHz transducer. Mean postischemic dilatation, an index of endothelial function, was 1.76+/-0.56% in blacks and 8.79+/-1.22% in whites (P<0.001). Median postischemic vasodilatation in black men [0% (0% to 2.86%)] was not significantly different to that in black women [0.82% (0% to 3.14%)], whereas white women [11.48% (8.70% to 14.29%)] dilated significantly more than white men [4.20% (2.13% to 5.56%)] (P<0.05). Both groups dilated significantly over baseline diameter to sublingual nitroglycerin administration 18.7+/-2.5% (blacks) and 20.2+/-3.2% (whites; P=NS). Mean hyperemic responses did not differ significantly between the 2 subject groups, nor did they differ between men and women of both ethnic groups. We conclude that endothelium-dependent vasodilatation is significantly impaired in healthy, young blacks compared with whites and that gender differences are not seen in blacks with regard to this phenomenon. An impairment in endothelium-dependent NO generation may be a contributing factor to future hypertension and vascular disease in healthy blacks.

Adult↗

Rapid screening for putative exported proteins from Staphylococcus aureus using alkaline phosphatase as a reporter molecule.

Staphylococcus aureus causes a wide range of infections in humans, ranging from superficial skin infections to the more serious toxin-mediated diseases such as toxic shock syndrome. Owing to the increasing resistance of this bacterium to a wide range of antibiotics, the need to determine the virulence factors involved in infection is becoming more important as these molecules are potential therapeutic targets. In this study, we have screened for putative exported proteins from S. aureus on the basis that these proteins are likely to be the first point of contact between the bacterium and host during infection. We have constructed gene fusions between S. aureus DNA and a truncated version of the Escherichia coli phoA gene, and we report on the characterization of the recombinants exhibiting alkaline phosphatase activity. As well as known S. aureus proteins, we have identified a number of putative open reading frames that encode proteins similar to those from nonstaphylococcal species and also unique proteins that do not have any homologues on the current databases.

Alkaline Phosphatase↗

The effect of photodynamic action on two virulence factors of gram-negative bacteria.

Photodynamic therapy could provide an alternative to antibiotics for the treatment of local infections since a wide range of microorganisms have been shown to be susceptible to killing by photodynamic action (PDA) in vitro. The purpose of this study was to determine whether PDA was also able to affect the potency of two key bacterial virulence factors--lipopolysaccharide (LPS) and proteases. Suspensions of LPS from Escherichia coli and culture supernatants containing proteases of Pseudomonas aeruginosa were exposed to red light in the presence of toluidine blue O (TBO). The activity of each virulence factor was determined before and after irradiation. The limulus amoebocyte lysate (LAL) assay and the induction of proinflammatory cytokine (interleukin-8 and -6) release from human peripheral blood mononuclear cells (PBMC) were used for assessing the biological activity of LPS. Protease activity was quantified by azocasein hydrolysis. The biological activities of the LPS (both the LAL activity and its ability to induce cytokine release from PBMC) and the proteases were reduced significantly by irradiation with red light in the presence of TBO in a dose-dependent manner with respect to both the light energy dose and the TBO concentration. The ability of TBO-mediated PDA to reduce the activities of key virulence factors may be an additional benefit of using light-activated antimicrobial agents in the treatment of infectious diseases.

Endopeptidases↗

Biological control agents for white grubs (Coleoptera: Scarabaeidae) in anticipation of the establishment of the Japanese beetle in California.

We tested biological control agents for the control of 3rd-instar scarab turfgrass pests, both for the masked chafer Cyclocephala hirta LeConte and the Japanese beetle, Popillia japonica Newman. The former species is endemic in California whereas the latter, although not yet established, constitutes a permanent serious threat to agriculture and horticulture in California. We conducted experiments using C. hirta in California and P. japonica in New Jersey. A field trial conducted in 2 different California turfgrass sites compared the field persistence in the absence of hosts of Bacillus thuringiensis Berliner subspecies japonensis Buibui strain, the milky disease bacterium, Paenibacillus (=Bacillus) popilliae (Dutky), and the entomopathogenic nematodes Steinernema kushidai Mamiya and Heterorhabditis bacteriophora Poinar to that of the organophosphate diazinon. Soil samples taken 0-70 d after applications were bio-assayed with P. japonica. Only diazinon and the entomopathogenic nematode S. kushidai caused substantial mortality and S. kushidai activity persisted significantly longer than diazinon activity. In greenhouse experiments, combinations of entomopathogenic nematode species usually resulted in additive mortality of scarab larvae. Combinations of S. kushidai and diazinon also resulted in additive mortality. In field trials, the efficacy of H. bacteriophora and especially S. kushidai and S. glaseri, was comparable to that of diazinon over 14-18 d. However, it is likely that at least S. kushidai would have outperformed diazinon over an extended period because of its longer persistence and potential for recycling in the hosts. S. kushidai, should it become commercially available, deserves further examination as an alternative to chemical white grub control especially as a highly compatible component of sustainable turfgrass management.

Animals↗

Failure to identify alveolar echinococcosis in trappers from South Dakota in spite of high prevalence of Echinococcus multilocularis in wild canids.

Echinococcus multilocularis causes a rare but potentially lethal zoonotic disease in humans. This tapeworm has been known to be endemic in foxes (Vulpes vulpes) and coyotes (Canis latrans) within the northern United States since the 1960s. One purpose of this study was to provide recent data on the prevalence of E. multilocularis in foxes and coyotes from eastern South Dakota. In a survey conducted from 1987 to 1991 and involving 137 foxes and 9 coyotes from this area, 74.5% of the foxes and 4 of the coyotes were infected. To assess the possible prevalence of alveolar echinococcosis in a group at presumptive high risk, we also conducted a serological survey of members of the South Dakota Trappers Association in 1990 and 1991. Serum samples from 115 trappers were evaluated for the presence of E. multilocularis antibodies using enzyme-linked immunosorbent assay tests involving a purified antigen called Em2, a crude E. multilocularis antigen, and a recombinant E. multilocularis antigen called II/3-10. None of the trappers showed antibody evidence for the presence of E. multilocularis. Roughly half of the surveyed individuals had trapped more than 50 foxes during their life, and almost one-fourth had trapped more than 1,000 foxes.

Adolescent↗

Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.

Adolescent↗

Measurement of tissue factor activity in whole blood.

High circulating levels of the procoagulant molecule tissue factor (TF) are associated with thrombosis in a variety of diseases including unstable angina, cancer, and sepsis. Currently, there are no clinical assays to measure the level of TF activity in whole blood. We present an assay called Tissue Factor Clotting Time ("TiFaCT") that detects fibrin formation in human blood. The mean baseline clotting time in a healthy population was 472 +/- 94 s (mean +/- SD, n = 150). Bacterial lipopolysaccharide (LPS or endotoxin) shortened the clotting time in a time-dependent manner. Inhibitory anti-TF antibodies prolonged the clotting time of LPS-stimulated blood, indicating that the shortened clotting time was due to induction of TF expression. Patients with unstable angina had shortened mean baseline clotting time (284 +/- 86, n = 13) compared with healthy volunteers (474 +/- 98, n = 30), suggesting that these patients had elevated levels of circulating TF. The TiFaCT assay should prove clinically useful in quantifying the levels of circulating TF in patients at risk of thrombosis.

Adult↗

Self-measurement of blood pressure in clinical trials and therapeutic applications.

Self-measurement of blood pressure (SMBP) is increasingly used to assess blood pressure outside the medical setting. A prerequisite for the wide use of SMBP is the availability of validated devices providing reliable readings when they are handled by patients. This is the case today with a number of fully automated oscillometric apparatuses. A major advantage of SMBP is the great number of readings, which is linked with high reproducibility. Given these advantages, one of the major indications for SMBP is the need for evaluation of antihypertensive treatment, either for individual patients in everyday practice or in clinical trials intended to characterize the effects of blood-pressure-lowering medications. In fact, SMBP is particularly helpful for evaluating resistant hypertension and detecting white-coat effect in patients exhibiting high office blood pressure under antihypertensive therapy. SMBP might also motivate the patient and improve his or her adherence to long-term treatment. Moreover, SMBP can be used as a sensitive technique for evaluating the effect of antihypertensive drugs in clinical trials; it increases the power of comparative trials, allowing one to study fewer patients or to detect smaller differences in blood pressure than would be possible with the office measurement. Therefore, SMBP can be regarded as a valuable technique for the follow-up of treated patients as well as for the assessment of antihypertensive drugs in clinical trials.

Antihypertensive Agents↗

Involving families in an urban HIV preventive intervention: how community collaboration addresses barriers to participation.

This article addresses the increasing need within urban communities for effective, culturally relevant HIV prevention programs. The recruitment efforts of a family-based prevention program aimed at promoting health and preventing HIV risk exposure in urban, African American fourth and fifth grade children living in a community with high rates of HIV infection is detailed. The program, referred to as the CHAMP (Chicago HIV Prevention and Adolescent Mental Health Project) Family Program, is overseen by a collaborative partnership of community parents, school staff, and university-based researchers (Paikoff & McKay, 1995). The recruitment strategies developed as a result of this community-research collaboration are described. Preliminary results of the project's efforts to reach out to families within the targeted, inner-city community are presented.

Black or African American↗