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Biomedical subjects

E Parrish

Publications and source records attributed to E Parrish.

10 recordsLinked to original sources
PubMed1999

Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant.

The transplantation of satellite cells may constitute a strategy for rebuilding muscle fibres in inherited myopathies. However, its development requires a great understanding of the role of environmental signals in the regenerative process. It is therefore essential to identify the key events triggering and controlling this process in vivo. We investigated whether macrophages play a key role in the course of the regenerative process using skeletal muscle transplants from transgenic pHuDes-nls-LacZ mice. Before grafting, transplants were conditioned with macrophage inflammatory protein 1-beta (MIP 1-beta; stimulating the macrophages infiltration or vascular endothelial growth factor (VEGF) stimulating angiogenesis). Treatment of transplants with MIP 1-beta and VEGF both accelerated and augmented monocyte-macrophage infiltration and satellite cell differentiation and/or proliferation, as compared to controls. In addition, VEGF treatment enhanced the number of newly formed myotubes. When a complete depletion of host monocyte-macrophages was experimentally induced, no regeneration occurred in transplants. Our data suggest that the presence of blood borne macrophages is required for triggering the earliest events of skeletal muscle regeneration. The understanding of macrophage behaviour after muscle injury should allow us to develop future strategies of satellite cell transplantation as a treatment for muscular dystrophies.

Animals↗
PubMed1997

Adenovirus-mediated gene transfer to the brain: methodological assessment.

The purpose of this short review is to analyse major advantages and limitations of the adenovirus (Ad), specifically with relevance to its use as a vector for gene transfer to the brain. The characteristics of Ad transduction include: the relative absence of cell type specificity; the limited spatial spread of the virus; and the long-term expression of the transgene. In the central nervous system, in contrast to that which occurs in other organs, Ad transduction in the adult does not systematically provoke cell death. Nevertheless, a proportion of the transduced cells do die, and this represents a conspicuous problem. Mechanisms leading to cell death in the brain may include immune rejection and inflammation-related toxicity, although this would not explain all of the results, and direct toxicity related to either inappropriate preparation or the transduction itself. Taking into account uncertainties concerning the innocuousness of Ad transduction, it may seem unwise to envisage Ad gene therapy for diseases that are not life-threatening and/or benefit from adequate drug or surgical treatments (e.g. Parkinson's disease or epilepsy). Ad vectors may not be easily used either in diseases displaying major immune dysfunction (e.g. multiple sclerosis). In contrast, malignant brain tumors and numerous neurodegenerative diseases (such as Huntington's, Alzheimer's diseases or amyotrophic lateral sclerosis) are directly life-threatening and deprived of any adequate treatment. They may be appropriate targets for Ad-mediated gene therapy, once both the vector and the gene of interest have been defined and optimized.

Adenoviridae↗
PubMed1996

Involvement of the dihydropyridine receptor and internal Ca2+ stores in myoblast fusion.

The process of myoblast fusion during skeletal myogenesis is calcium regulated. Both dihydropyridine receptor and ryanodine receptor are already present on muscle precursors, at the prefusional stage, before they are required for excitation-contraction coupling. Previous pharmacological studies have shown the need for a special pool of Ca2+ associated with the membrane for the fusion process to occur. We hypothesized that this pool of Ca2+ is mobilized via a machinery similar to that involved in excitation-contraction coupling. The process of fusion in rat L6 muscle precursors was either totally or partially abolished in the presence of the L-type calcium channel inhibitors SR33557 and nifedipine (half inhibition towards 2 microM), respectively. The inhibition was reversible and dose-dependent. Drugs able to deplete internal calcium stores (caffeine, ryanodine, and thapsigargin) were also tested on the fusion. Both caffeine and thapsigargin drastically inhibited fusion whereas ryanodine had no effect. This suggests that fusion may be controlled by internal pools of Ca2+ but that its regulation may be insensitive to ryanodine. We presumed that an early form of the ryanodine receptor may exist, with different pharmacological properties than the adult forms. Indeed, Western blot analysis of pre- and postfusional L6 cells demonstrated the presence, at the prefusional stage, of a transient form of the ryanodine receptor protein with an apparent molecular weight slightly different from those of the classical skeletal and cardiac forms. Taken together, these results support the hypothesis that the fusion process is driven by a mechanism involving both the dihydropyridine receptor (alpha1 subunit of the L-type Ca2+ channel) and the internal stores of Ca2+. The machinery underlying this mechanism might consist of slightly different forms of the classic molecules that in adult muscle ensure excitation-contraction coupling. It remains to be seen, however, whether the mobilization of the internal pool of Ca2+ is triggered by the type of mechanism already described in skeletal muscle.

Animals↗
PubMed1990

B virus (Herpesvirus simiae) infection in humans: epidemiologic investigation of a cluster.

A cluster of four cases of symptomatic B virus infection in humans occurred in Pensacola, Florida, in March 1987. Three cases occurred in persons who worked with monkeys at a research facility, and the fourth resulted from apparent autoinoculation through use of a nonprescription skin cream. Contact tracing identified 159 persons who may have been exposed to B virus (21 had been exposed to monkeys at the facility and 138 had been exposed to one or more of the case-patients), but no further cases were identified. Comparisons of restriction endonuclease patterns from B virus isolates linked two of the three cases in monkey handlers to one clinically ill monkey and the other to a second, healthy monkey. Three risk factors for human infection were identified: nonuse of mechanical or chemical restraints for monkeys before handling, nonuse of available protective gear, and direct viral inoculation through the application of a topical medication.

Acute Disease↗
PubMed1989

Child abduction. Parent and child functioning following return.

The functioning of 17 children who had been abducted by one parent but subsequently returned was examined. The parent to whom the child was returned completed a behavior rating scale on the child for each of three time periods: pre-abduction, immediately post-abduction, and follow-up (the present time). The parents also completed a measure regarding the coping strategy they utilized while the child was missing and a measure of their own functioning at each of three times: pre-abduction, during the abduction, and follow-up. The results indicated that the child was rated as functioning worse immediately post-abduction than at pre-abduction and at follow-up was functioning between that reported at pre-abduction and post-abduction. However, the level of maladjustment was not in the severe range at any of the assessments. Parents reported using a problem-focused or action style of coping. Parents also reported that their psychological functioning decreased during abduction and then improved at follow-up. Again, functioning was not in the severe range at any assessment. Variables such as age at the time of abduction and length of abduction were only minimumally related to parent or child functioning.

Adaptation, Psychological↗
PubMed1987

Recognition, calcium and the control of desmosome formation.

Since desmosome formation requires the participation of two adjacent cells, a crucial initiating event must be recognition between desmosomal adhesion molecules. Studies of mutual desmosome formation between different cell types suggest that the recognition mechanisms are highly conserved between different tissues and different species of animals. A further requirement for desmosome formation is an adequate extracellular concentration of Ca2+ (greater than 0.1 mM). Keratinocytes, MDCK cells and MDBK cells all show Ca2+-induced desmosome formation. The desmosomes of these cells also show variable stability to reduction in [Ca2+] and Ca2+ chelation. Desmosome formation at low [Ca2+] is triggered by tunicamycin in keratinocytes, suggesting that the carbohydrate moieties of desmosomal glycoproteins may be involved in the Ca2+ control mechanism. The desmosomal glycoproteins appear to bind Ca2+, while the desmosomal adhesion molecules known as desmocollins, like other Ca2+-dependent adhesion molecules, yield a soluble fragment on trypsinization in the presence of Ca2+. For desmocollins the soluble fragment has a relative molecular mass of 42,000.

Animals↗
PubMed1980

Studies of blood pressure in schoolchildren (ages 6--19) and their parents in an integrated suburban school district.

Systolic blood pressure (SBP) and diastolic blood pressure (DBP), along with demographic and anthropometric variables were assessed in a biracial group of schoolchildren and parents in an integrated suburban school district: 682 schoolchildren, ages 6--19, including 268 white males, 236 white females, 85 black males and 93 black females; 362 adults, ages 20--64, including 142 white males, 159 white females, 20 black males and 41 black females. There were no significant black-white SBP or DBP differences in children, while SBP and DBP were higher in adult blacks than whites. Using multiple regression analysis, with BP as the dependent variable, SBP in children was significantly associated with pulse, weight, skinfold thickness, age and height; DBP was significantly associated with age, pulse, weight, and skinfold thickness. Race, sex, and education of the head of household did not significantly enter the multiple regression matrix for children's BP. Respectively, 29% and 22% of the variance of the children's SBP and DBP was accounted for by the measured variables. In adults, SBP was significantly related to weight, race, pulse, and age; DBP was significantly related to weight, race, age, and skinfold thickness. Respectively, 27% and 24% of the variance of the adults' SBP and DBP was accounted for by the measured variables. Covariance adjusted mean SBP and DBP were higher in hypertriglyceridemic than in hypotriglyceridemic children (p = 0.001), and were lower in hyperalpha-lipoproteinemic than hypoalpha-lipoproteinemic children (p less than or equal to 0.03). Children in an integrated school district may have shared behaviors, goals, and environments contributing to shared BP, while differing environmental factors may become amplified with age and life experience and contribute to higher BP in black adults.

Adolescent↗
PubMed1979

HLA-B17 and the HLA-A1, B17 haplotype in acute myelogenous leukemia.

Seventy-nine Caucasians with acute myelogenous leukemia (AML) were genotyped to determine whether AML, the induction of remission or patient survival were associated with particular HLA phenotypes or haplotypes. HLA-B17 and B27 were increased in AML patients over 40 years of age. Combined analysis of four independent studies indicates that HLA-B17 is significantly but weakly associated with AML, relative risk = 1.48 (.01 less than P less than .025). The A1, B17 and Aw24, Bw35 haplotypes occurred more frequently in the AML group as compared to racial and geographic controls (uncorrected P = 0.0068 and 0.0098, respectively Fisher's Exact Test). Induction of remission occurred less frequently in patients with the B17 phenotype as compared to patients lacking this antigen (P = 0.047). Patient survival was associated with remission status (P = 0.002) but was not significantly associated with particular HLA phenotypes or haplotypes. These results indicate that a gene or genes in the HLA-B region of the major histocompatibility complex can influence susceptibility to AML and also the response to chemotherapy.

Adolescent↗
PubMedDate not supplied

Computerised dystrophic muscle simulator: prospecting potential therapeutic strategies for muscle dystrophies using a virtual experimental model.

Inherited muscle diseases are often characterised by widespread muscle damage in the body, limiting the clinical relevance of cell or gene therapy based upon direct injections into muscles. Recent studies have shown, however, that cells originating from the bone marrow are able to target necrosis-regeneration sites as they occur and, in addition, may also participate in the muscle regeneration after undergoing myogenic differentiation. Here, we present a computerised dystrophic muscle simulator that allows the prospecting of different scenarios of both disease evolution and appropriate employment of blood-borne cells as therapeutic shuttles. It provides the option of examining their use either to transfer a healthy gene into the tissue or to impart substances designed to boost its regeneration. One of the major advantages of this tool is that it offers the opportunity of visualising and composing therapeutic strategies in virtual paradigms in which severe clinical situations, not necessarily available in animal models, can be created. The dystrophic muscle simulator is freely accessible via the Genethon web site (www.genethon.fr), and in the online version via http:@www.wiley.co.uk/genmed.

Algorithms↗