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Biomedical subjects

M C Fisher

Publications and source records attributed to M C Fisher.

At least 19 recordsLinked to original sources
PubMed2026

Addressing the dual-use of antifungals and fungal antimicrobial resistance (fAMR) through a One Health approach.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

Journal Article↗
PubMed2001

Biogeographic range expansion into South America by Coccidioides immitis mirrors New World patterns of human migration.

Long-distance population dispersal leaves its characteristic signature in genomes, namely, reduced diversity and increased linkage between genetic markers. This signature enables historical patterns of range expansion to be traced. Herein, we use microsatellite loci from the human pathogen Coccidioides immitis to show that genetic diversity in this fungus is geographically partitioned throughout North America. In contrast, analyses of South American C. immitis show that this population is genetically depauperate and was founded from a single North American population centered in Texas. Variances of allele distributions show that South American C. immitis have undergone rapid population growth, consistent with an epidemic increase in postcolonization population size. Herein, we estimate the introduction into South America to have occurred within the last 9,000-140,000 years. This range increase parallels that of Homo sapiens. Because of known associations between Amerindians and this fungus, we suggest that the colonization of South America by C. immitis represents a relatively recent and rapid codispersal of a host and its pathogen.

Base Sequence↗
PubMed2001

Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos.

BACKGROUND: Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency. METHODS: To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology. RESULTS: Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos. CONCLUSIONS: Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face.

Abnormalities, Drug-Induced↗
PubMed2001

Nosocomial infections in the neonatal intensive care unit.

Nosocomial infections are significant causes of morbidity and mortality in patients who require newborn intensive care. The most common bacterial pathogens are Gram-positive bacteria, including Staphylococcus epidermidis, Staphylococcus aureus, and Enterococcus species. Gram-negative enteric bacilli and Gram-negative environmental bacteria are involved in outbreaks and occasional cases of nosocomial infection. The incidence of fungal infection has increased over the past 10 years; fungemia is the most commonly recognized infection. Surveillance for nosocomial infection is essential to identify outbreaks and detect unsuspected reservoirs of pathogens. A variety of molecular techniques can be used to determine the genetic relatedness of pathogens. Prevention of infection requires the identification of contaminated equipment, education regarding infection control methods including hand washing, and the judicious use of antimicrobial agents.

Cross Infection↗
PubMed2000

Phylogenetic species recognition and species concepts in fungi.

The operational species concept, i.e., the one used to recognize species, is contrasted to the theoretical species concept. A phylogenetic approach to recognize fungal species based on concordance of multiple gene genealogies is compared to those based on morphology and reproductive behavior. Examples where Phylogenetic Species Recognition has been applied to fungi are reviewed and concerns regarding Phylogenetic Species Recognition are discussed.

Evolution, Molecular↗
PubMed2000

Inferring infection processes of a parasitic nematode using population genetics.

The distribution of genetic differentiation in a population of the parasitic nematode Strongyloides ratti divided between rat hosts was determined. We applied population genetic theory to these data to determine the source of new infections. We estimate the rate at which a rat acquires a new infection from (a) the existing subpopulation of parasites within that rat ('self-reinfection') versus (b) the wider environment ('immigration'). We find that the observed levels of genetic diversity and differentiation in the study population are consistent with low to moderate rates of self-reinfection and inconsistent with high rates of self-reinfection.

Animals↗
PubMed2000

A test for concordance between the multilocus genealogies of genes and microsatellites in the pathogenic fungus Coccidioides immitis.

Uncovering the correct phylogeny of closely related species requires analysis of multiple gene genealogies or, alternatively, genealogies inferred from the multiple alleles found at highly polymorphic loci, such as microsatellites. However, a concern in using microsatellites is that constraints on allele sizes may occur, resulting in homoplasious distributions of alleles, leading to incorrect phylogenies. Seven microsatellites from the pathogenic fungus Coccidioides immitis were sequenced for 20 clinical isolates chosen to represent the known genetic diversity of the pathogen. An organismal phylogeny for C. immitis was inferred from microsatellite-flanking sequence polymorphisms and other restriction fragment length polymorphism-containing loci. Two microsatellite genetic distances were then used to determine phylogenies for C. immitis, and the trees found by these three methods were compared. Congruence between the organismal and microsatellite phylogenies occurred when microsatellite distances were based on simple allele frequency data. However, complex mutation events at some loci made distances based on stepwise mutation models unreliable. Estimates of times of divergence for the two species of C. immitis based on microsatellites were significantly lower than those calculated from flanking sequence, most likely due to constraints on microsatellite allele sizes. Flanking-sequence insertions/deletions significantly decreased the accuracy of genealogical information inferred from microsatellite loci and caused interspecific length homoplasies at one of the seven loci. Our analysis shows that microsatellites are useful phylogenetic markers, although care should be taken to choose loci with appropriate flanking sequences when they are intended for use in evolutionary studies.

Base Sequence↗
PubMed2000

Predictors of infectious complications after burn injuries in children.

BACKGROUND: Infections are the major life-threatening complication of burn injury and occur with the greatest frequency in children. Knowledge of their occurrence and management, however, is extrapolated from studies in adults. We performed a prospective study of infectious complications in burned children. OBJECTIVE: To delineate epidemiology, risk factors and microbiology of infections in burned children where burn care and surgical interventions are optimal. METHODS: Children hospitalized for burns were entered into prospective study. Characteristics of the burn injury were assessed, and active surveillance for infections was performed. RESULTS: Seventy patients were entered [mean age, 42 months; mean total body surface area (TBSA), burn 15%]. Twenty-seven percent of patients developed 39 infections: 13 involved the burn wound (burn wound sepsis, 6; graft loss, 5; and cellulitis, 2); 13 were catheter-associated septicemia; 13 involved other sites (i.e. pneumonia, 4; urinary tract infection, 3; bacteremia, 2; endocarditis, 1; myocardial abscess, 1; toxin-mediated syndrome, 1; and otitis media, 1). Twenty-three infections were caused by a single organism, 9 infections by more than 1 organism and in 7 infections defined by CDC criteria no organism was recovered. Organisms causing infection were: Staphylococcus aureus, 19; Candida albicans, 4; Pseudomonas aeruginosa, 4; coagulase-negative Staphylococcus, 4; Enterococcus sp., 3; Escherichia coli, 1; Klebsiella oxytoca, 1; Serratia marcescens, 1; Streptococcus pneumoniae, 1; Streptococcus pyogenes, 1; Aspergillus fumigatus, 1; and Candida parapsilosis, 1. Burn mechanism (flame and inhalation), extent (TBSA >30%) and depth (full thickness) were risk factors for infection; young age and site of burn were not. CONCLUSION: The most common infections occurring in burn children are burn wound infections and catheter-associated septicemia. Characteristics of burn injury predict risk of infection. Children with flame and inhalation injury, TBSA burned >30% and full thickness burns are at high risk of infectious complications.

Burns↗
PubMed2000

Pathogenic clones versus environmentally driven population increase: analysis of an epidemic of the human fungal pathogen Coccidioides immitis.

For many pathogenic microbes that utilize mainly asexual modes of reproduction, it is unknown whether epidemics are due to either the emergence of pathogenic clones or environmentally determined increases in the population size of the organism. Descriptions of the genetic structures of epidemic populations, in conjunction with analyses of key environmental variables, are able to distinguish between these competing hypotheses. A major epidemic of coccidioidomycosis (etiologic agent, Coccidioides immitis) occurred between 1991 and 1994 in central California, representing an 11-fold increase above the mean number of cases reported from 1955 to 1990. Molecular analyses showed extensive genetic diversity, a lack of linkage disequilibria, and little phylogenetic structure, demonstrating that a newly pathogenic strain was not responsible for the observed epidemic. Epidemiological analyses showed that morbidity caused by C. immitis was best explained by the interaction between two variables, the lengths of droughts preceding epidemics and the amounts of rainfall. This shows that the principal factors governing this epidemic of C. immitis are environmental and not genetic. An important implication of this result is that the periodicity of cyclical environmental factors regulates the population size of C. immitis and is instrumental in determining the size of epidemics. This knowledge provides an important tool for predicting outbreaks of this pathogen, as well as a general framework that may be applied to determine the causes of epidemics of other fungal diseases.

Coccidioides↗
PubMed1998

The population genetic structure of the facultatively sexual parasitic nematode Strongyloides ratti in wild rats.

We have investigated the population genetic structure of the parasitic nematode Strongyloides ratti in wild rats. In the UK, S. ratti reproduces predominantly by mitotic parthenogenesis, with sexual forms present at a rate of less than 1%. S. ratti was found to be a prevalent parasite and substantial genetic diversity was detected. Most rats were infected with a genotypic mixture of parasites. A hierarchical analysis of the genetic variation found in S. ratti sampled across Britain and Germany showed that 73.3% was explained by variation between parasites within individual hosts and 25.3% by variation between rats within sample sites. Only a small proportion (1.4%) of the total genetic variation was attributable to genetic subdivision between sample sites, suggesting that there is substantial gene flow between these sites. Most parasites sampled were found to exist in Hardy-Weinberg equilibrium and this population genetic structure is discussed in view of the virtual absence of sexual reproduction.

Animals↗