Biomedical subjects

Matthew Brown

Publications and source records attributed to Matthew Brown.

10 recordsLinked to original sources

PubMed2025

Medical guidelines for fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A detailed and updated exploration of the topics outlined in this brief perspective can be found in "The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations" which can be found on the International Clinical Council on FOP (ICC) website (www.iccfop.org).

ACVR1↗

PubMed2006

Further validation of LABORAS using various dopaminergic manipulations in mice including MPTP-induced nigro-striatal degeneration.

The automated behavioural apparatus, LABORAS (Laboratory Animal Behaviour Observation, Registration and Analysis System), has been further validated with respect to the ability of the system to detect behavioural impairments in mice, following various dopaminergic manipulations. Initially data were obtained from mice administered with amphetamine, haloperidol, SCH23390, apomorphine and L-DOPA, with the focus on locomotor and grooming activities. The data recorded by LABORAS on administration of these pharmacological tool compounds, is comparable with published findings using standard LMA systems and conventional observer methods. In addition the home cage behaviour of mice administered with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using an acute dosing regimen was also investigated. In LABORAS, mice subjected to MPTP lesioning showed deficits in spontaneous motor activity at day 6-7 post-MPTP administration, over a 24 h test period, as compared to saline treated controls. The data captured and analysed using LABORAS, suggests that the automated system is able to detect both pharmacologically and lesion-induced changes in behaviour of mice, reliably and efficiently.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2006

Proteomic analysis of reporter genes for molecular imaging of transplanted embryonic stem cells.

Study of stem cells may reveal promising treatment for diseases. The fate and function of transplanted stem cells remain poorly defined. Recent studies demonstrate that reporter genes can monitor real-time survival of transplanted stem cells in living subjects. We examined the effects of a novel and versatile triple fusion (TF) reporter gene construction on embryonic stem (ES) cell function by proteomic analysis. Murine ES cells were stably transduced with a self-inactivating lentiviral vector containing fluorescence (firefly luciferase; Fluc), bioluminescence (monomeric red fluorescence protein; mRFP), and positron emission tomography (herpes simplex virus type 1 truncated thymidine kinase; tTK) reporter genes. Fluorescence-activated cell sorting (FACS) analysis isolated stably transduced populations. TF reporter gene effects on cellular function were evaluated by quantitative proteomic profiling of control ES cells versus ES cells stably expressing the TF construct (ES-TF). Overall, no significant changes in protein quantity were observed. TF reporter gene expression had no effect on ES cell viability, proliferation, and differentiation capability. Molecular imaging studies tracked ES-TF cell survival and proliferation in living animals. In summary, this is the first proteomic study, demonstrating the unique potential of reporter gene imaging for tracking ES cell transplantation non-invasively, repetitively, and quantitatively.

Animals↗

PubMed2006

Dissociative effects of stimulus quality on semantic and morphological contexts in visual word recognition.

Semantic and morphological contexts were manipulated jointly with stimulus quality under conditions where there were few related prime-target pairs (i.e., low relatedness proportion) in a lexical decision experiment. Additive effects of semantic context and stimulus quality on RT were observed, replicating previous work. In contrast, morphological context interacted with stimulus quality. This dissociation is discussed in the context of Besner and colleagues' evolving multistage framework. The essence of the account is that 1) stimulus quality affects feature and letter levels, but not later levels, 2) feedback from semantics to the lexical level is inoperative under low relatedness proportion conditions (hence stimulus quality and semantic context yield additive effects), whereas 3) feedback from the lexical level to the letter level is intact, hence stimulus quality and morphological context produce an interaction by virtue of them affecting a common stage of processing.

Attention↗

PubMed2005

Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy.

Resection alone is rarely curative for advanced tumors, but the outcome generally improves with adjuvant therapy. We have previously shown that a combination of traditional chemotherapy (gemcitabine) and immunotherapy (anti-CD40/FGK-45) without surgery is synergistic and can lead to long-term cure when applied to small tumors. Such cured animals have immunologic memory and are protected from rechallenge. Here we investigate the effectiveness of combination chemotherapy and immunotherapy after partial or complete surgical debulking of large tumors. We found that complete resection followed by combination chemotherapy/immunotherapy led to a high rate of cure (>80%) but failed to induce a long-term, tumor-specific memory. Partial debulking followed by combination therapy elicited the same proportion of cured animals but in contrast to complete resection, a memory response was invoked. We postulate that chemotherapy induced apoptosis of the residual tumor cells following incomplete resection is absolutely required for the induction of long-term immunologic memory.

Animals↗

PubMed2005

Visit frequency and hypertension.

The best return visit interval to achieve blood pressure control is currently unknown. This study investigates the relationship between return visit interval and percent change in blood pressure. We reviewed a cohort of hypertensive patient charts from two large, urban family practice offices. Four hundred twenty-nine patients with 7910 intervals showed a mean return visit interval of 79.5 days. Blood pressure control occurred during 34.5% of office visits. Pearson's r correlation coefficients between return visit interval and percent change in systolic and diastolic blood pressure demonstrated a small but statistically significant correlation. Shorter return visit intervals were associated with better percent changes in blood pressure. The return visit interval may be a simple and useful tool to improve management of hypertension.

Blood Pressure↗

PubMed2004

Alpha2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse.

Neurite outgrowth is influenced by positive and negative signals that include the semaphorins, an important family of axonal outgrowth inhibitors. Here we report that the Rac GTPase activating protein (GAP)alpha2-chimaerin is involved in Semaphorin 3A (Sema 3A) signaling. In dorsal root ganglion neurons, Sema 3A-induced growth cone collapse was inhibited by alpha2-chimaerin mutated to eliminate GAP activity or interaction with phosphotyrosine. Activation of alpha2-chimaerin by phorbol ester caused growth cone collapse. Active alpha2-chimaerin interacts with collapsin response mediator protein-2 (CRMP-2) and cyclin-dependent kinase (Cdk) 5/p35 kinase through its SH2 and GAP domains, respectively. Cdk5 phosphorylates CRMP-2 at serine 522, possibly facilitating phosphorylation of serine 518 and threonine 514 by glycogen synthase kinase 3beta (GSK3beta), a kinase previously implicated in Sema 3A signaling. Phosphorylation of CRMP-2 serine 522 was essential for Sema 3A-induced growth cone collapse, which is dependent on Cdk5 but not Rho kinase activity. alpha2-chimaerin, like CRMP-2, can associate with the Sema 3A receptor. These results indicate that active alpha2-chimaerin Rac GAP, Cdk5/p35, and its substrate CRMP-2, are implicated in the dynamics of growth cone guidance initiated through Sema 3A signaling.

Animals↗

PubMed2004

In sight but out of mind: do competing views test the limits of perception without awareness?

Over a century's worth of research suggests that "perception" without awareness is a genuine phenomenon. However, relatively little research has explored the question of whether all visually presented information activates representations in long term memory without awareness. Two experiments explored the use of a figure-ground display consisting of competing views in which one view dominates the other such that subjects are (initially) unaware of the non-dominant view. Neither experiment provided evidence that the non-dominant view (an embedded word) activated its representation in long term memory when the subject failed to report being aware of the embedded word in that priming was not seen on a subsequent stem completion task. In contrast, priming was seen when subjects reported being aware of the embedded word. It is suggested that two competing figure-ground relations are not concurrently computed unconsciously.

Awareness↗

PubMed2003

Common hair loss disorders.

Hair loss (alopecia) affects men and women of all ages and often significantly affects social and psychologic well-being. Although alopecia has several causes, a careful history, dose attention to the appearance of the hair loss, and a few simple studies can quickly narrow the potential diagnoses. Androgenetic alopecia, one of the most common forms of hair loss, usually has a specific pattern of temporal-frontal loss in men and central thinning in women. The U.S. Food and Drug Administration has approved topical minoxidil to treat men and women, with the addition of finasteride for men. Telogen effluvium is characterized by the loss of "handfuls" of hair, often following emotional or physical stressors. Alopecia areata, trichotillomania, traction alopecia, and tinea capitis have unique features on examination that aid in diagnosis. Treatment for these disorders and telogen effluvium focuses on resolution of the underlying cause.

Alopecia↗

PubMed2002

Semantic priming: on the role of awareness in visual word recognition in the absence of an expectancy.

By hypothesis, awareness is involved in the modulation of feedback from semantics to the lexical level in the visual word recognition system. When subjects are aware of the fact that there are many related prime-target pairs in a semantic priming experiment, this knowledge is used to configure the system to feed activation back from semantics to the lexical level so as to facilitate processing. When subjects are unaware of this fact, the default set is maintained in which activation is not fed back from semantics to the lexical level so as to conserve limited resources. Qualitative differences in the pattern of data from two lexical decision experiments that employ masked priming are consistent with this hypothesis. Semantic context and stimulus quality interact when the prime is processed with awareness whereas these same two factors produce additive effects on RT when the prime is unlikely to have been processed with awareness. These experiments thus illustrate one way in which awareness (or lack thereof) affects the dynamics of visual word recognition.

Adult↗