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Biomedical subjects

C Booth

Publications and source records attributed to C Booth.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of parental separation and divorce on very young children.

Data from the National Institute of Child Health and Human Development Study of Early Child Care were analyzed to explore effects of marital separation on children in the first 3 years of life. The sample included 73 never-married mothers and 97 separated mothers; a comparison group of 170 was conditionally randomly selected from the 2-parent families. Children in 2-parent families performed better than children in 1-parent families on assessments of cognitive and social abilities, problem behavior, attachment security, and behavior with mother. However, controlling for mothers' education and family income reduced these differences, and associations with separated-intact marital status were nonsignificant (the effect size was .01). Thus, children's psychological development was not affected by parental separation per se; it was related to mothers' income, education, ethnicity, child-rearing beliefs, depressive symptoms, and behavior.

Adult↗
PubMed2000

Keratinocyte growth factor increases hair follicle survival following cytotoxic insult.

Hair loss is a distressing side-effect of cancer therapy. Factors that might reduce this loss are therefore likely to improve patient well-being and reduce treatment refusal. Keratinocyte growth factor has been shown to regulate proliferation and differentiation in epithelial tissues and may regulate the clonogenic cells (stem cells) of the hair follicle. Using X-irradiation as a model cytotoxic agent we investigated whether keratinocyte growth factor pretreatment could increase hair follicle survival (by implication clonogen survival) and regeneration of differentiated progeny (a hair). Irradiated telogen follicle survival data were consistent with that published previously. Daily keratinocyte growth factor pretreatment increased hair survival during the first hair growth cycle, the level of protection having a slight radiation dose dependence. Protection was maintained after a second hair cycle, but at a lower level (hairs and follicles). Hairs irradiated in anagen and analyzed during the second cycle exhibited a similar level of protection. No difference in protection levels could be observed between mice treated either once or twice daily with keratinocyte growth factor. Results indicated approximately 10 extra hairs per mm2 (14.5% of unirradiated control) could survive the cytotoxic insult if pretreated with 12.5 microg keratinocyte growth factor. This could be doubled by a 10 x higher keratinocyte growth factor dose. The fact that protection was maintained during two cycles of hair growth indicated that the clonogenic cells had been protected. Keratinocyte growth factor pretreatment had no significant effect on the level of mitosis but increased the number of p21waf1 expressing cells. Intriguingly, the number of apoptotic fragments per follicle were transiently increased in the keratinocyte growth factor pretreated mice, although this effect was most pronounced in the upper half of the follicle bulb, i.e., above (rather than within) the germinal matrix.

Animals↗
PubMed1999

In vivo administration of genistein has no effect on small intestinal epithelial proliferation and apoptosis, but a modest effect on clonogen survival.

The soya metabolite genistein possesses anti-proliferative, pro-apoptotic activities in intestinal epithelial cells in vitro and may reduce epithelial cancer incidence. This could involve cell cycle arrest/apoptosis in the proliferative or clonogenic cells. We investigated the effects of genistein on the small intestinal epithelium in vivo. No effect on the number or distribution of proliferative cells in the crypts was detected. Similarly, no change in spontaneous apoptotic cell incidence or the characteristic stem cell apoptotic response following low dose irradiation was observed. Genistein afforded a modest decrease in clonogen radiosensitivity. Hence, using a range of dosing protocols, sub-cutaneous administration of genistein for periods of up to 1 week did not alter intestinal epithelial homeostasis.

Animals↗
PubMed1999

Maintenance of functional stem cells in isolated and cultured adult intestinal epithelium.

We have previously described a method for the primary culture of adult large intestinal epithelium, suggesting that stem cells had survived both the isolation and the culture procedures. However, as no markers for such cells exist, confirmation of stem cell survival is difficult-only the functional properties can be used to define them. Unfortunately, many of these (e.g., differentiation, crypt regeneration) do not occur in culture, probably due to suboptimal conditions. To address this problem both freshly isolated and cultured small and large intestinal crypts were grown subcutaneously in an immunocompromized mouse. All initially formed cysts lined by a simple epithelium which gradually became multicellular and formed invaginations containing many mitoses and apoptoses. Epithelial differentiation, as assayed by Goblet cell mucin production, was also apparent. Mucin maturation was also typical of the normal intestine. The lumen was frequently filled with mucin and apoptotic bodies. Interestingly, in grafts displaying pronounced crypt-like morphology the regions of proliferation were situated toward the base of the structure and the Goblet cells toward the lumen, i.e., a typical crypt-like morphology. Hence, functional adult stem cells appear to survive isolation and tissue culture, permitting organotypic regeneration, possibly involving homeobox gene expression. This may now allow direct stem cell characterization and experimental manipulation, such as transfection, and may ultimately permit transplantation and therapeutic gene therapy.

Animals↗
PubMed1999

Dewetting of Thin Block Copolymer Films.

The dewetting of thin films of low molecular weight diblock and triblock copolymers of poly(oxyethylene)/poly(oxybutylene) on silicon has been studied using video microscopy and X-ray reflectivity. Dewetted films were observed to comprise polygonal domains of polymer droplets, with a domain size of several millimeters. The dewetted films were studied using X-ray reflectivity, which showed that a film of polymer <50 Å thick remains on the substrate at the same time as the macroscopic droplets. This suggests that autophobic dewetting occurred in this system; i.e., a microscopically thin film was in equilibrium with macroscopic droplets. The growth velocity of holes in the polymer film was found to be constant at a fixed temperature in the stage of hole growth that could be studied using optical microscopy. The velocity was found to be an exponential function of temperature. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

A DSC study of the miscibility of poly(ethylene oxide)-block-poly(DL-lactide) copolymers with poly(DL-lactide).

The purpose of this study was to examine the miscibility of poly(ethylene oxide)-block-poly(DL-lactide) copolymers with poly (DL-lactide). The copolymers L7E73L7 and L17E78L17 (L = carbonyloxymethylmethylene unit, OCOCH(CH3); E = oxyethylene unit, OCH2CH2) were synthesised by non-catalysed anionic polymerisation and characterised by gel permeation chromatography and 13C NMR. Blends of each of the copolymers with poly(DL-lactide) with compositions over the range from 10 to 90 wt% copolymer were cast as thin films and examined by differential scanning calorimetry (DSC) to determine glass transition temperatures (Tg) and melting temperatures (Tm). The phase diagram showed a region of miscibility above the melting point of the copolymer in the system (approx. 35-40 degrees C). Within this region the system was glassy at low mass fractions of oxyethylene in the copolymer (wE < or = 0.1) and rubbery at higher mass fractions. Below Tm a mechanically compatible glassy blend existed at low wE whilst quenching of systems of higher wE led to phase separation, the biphasic region consisting of crystalline Em-sequences of copolymer separated from non-crystalline poly(DL-lactide). The phase diagram resulting from this study provides the means for the design of drug delivery systems based on blends of poly(DL-lactide) and poly(ethylene oxide)-containing components. The crystal melt boundary can be lowered by the use of block copolymers with short poly(ethylene oxide) blocks permitting the preparation of blends which are miscible at room temperature and rubbery or glassy according to composition.

Biocompatible Materials↗
PubMed1999

Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro.

There have been many reports that high soya-based diets reduce the risk of certain types of cancer. This effect may be due to the presence of high levels of isoflavones derived from the soya bean, particularly genistein which has been shown to be a protein tyrosine kinase (PTK) inhibitor and have both oestrogenic and anti-oestrogenic properties. We have examined the effect of genistein and a number of novel synthetic analogues on both normal (IEC6, IEC18) and transformed (SW620, HT29) intestinal epithelial cell lines. Responses were compared to those elicited by oestradiol, the anti-oestrogen tamoxifen, and the tyrosine kinase inhibitor tyrphostin. Genistein and tamoxifen were potent inhibitors of cell proliferation. Of seven novel isoflavones tested, none were more potent inhibitors than genistein, and all displayed similar relative activities across the different cell lines. In addition to inhibiting cell proliferation, cell death via apoptosis was observed when the cells were exposed to the isoflavones and all but one exhibited PTK inhibitory activity. These data suggest that by reducing proliferation and inducing apoptosis, possibly due in part to PTK inhibition, isoflavones may have a role in protecting normal intestinal epithelium from tumour development (reducing the risk) and may reduce colonic tumour growth.

Animals↗
PubMed1999

Elevated creatinine after ingestion of model aviation fuel: interference with the Jaffe reaction by nitromethane.

A 2 years 9 month-old-boy who ingested model aviation fuel was found to have an elevated serum creatinine concentration of 0.53 mmol/L (normal range 0.02-0.05 mmol/L) by the Jaffe (alkaline picrate) reaction. However, when the creatinine concentration was measured using a specific enzymatic assay, it was within the normal range. It was shown that nitromethane, a constituent of aviation fuel, interferes with the Jaffe reaction, leading to a falsely elevated creatinine reading. This phenomenon has been reported only once previously and, despite its potential clinical importance, nitromethane does not appear in published lists of substances that interfere with the Jaffe reaction.

Aircraft↗
PubMed1998

In vitro release of cytarabine from swellable matrices of CnEmCn triblock copolymers.

Matrices loaded with cytarabine were prepared by compression of the tailor made triblock copolymers C17E227C17 and C17E454C17 (where C=methylene and E=oxyethylene). Observations of the swelling characteristics of copolymer matrices on immersion in distilled water indicated an increase in the thickness of the gel layer around the matrices following ingress of water into the matrices. The in vitro release of cytarabine was characterised from matrices of different molar mass and with different known drug loadings. The release of cytarabine from the copolymer matrices was predominantly by a Fickian diffusion mechanism; the release rate was dependent on drug loading and independent of copolymer molar mass.

Antimetabolites, Antineoplastic↗
PubMed1998

Measurement of impact force, simulation of fall and hip fracture.

It has been shown that the incidence of hip fracture in the elderly may be influenced by the type of floor covering commonly used in homes for the elderly. This study describes the development of a method for modelling a fall during a hip fracture event, to examine the influence of different floors on impact force. An impact transducer is dropped in free fall through a smooth plastic tube. The impactor nose of the transducer models the curvature of the greater trochanter, and a steel spring is used to simulate the compliance of the skeletal structure. A weight, which corresponds to one-sixteenth of average body mass, compresses the spring and applies force to the impactor nose on striking the floor. The temporal variation in the force of impact with the floor is measured by the transducer to within 0.41 percent (SD = 0.63%, n = 10). Five common floor coverings were tested over a concrete floor slab (vinyl, loop carpet and pile carpet--both with and without underpad). ANOVA analysis showed that the differences between mean forces for each floor covering were highly significant (p > 0.001), with the thicker coverings producing 7 percent lower forces. The transducer may be used to examine the correlation between impact force and fracture incidence for a variety of different floors in homes for the elderly.

Accidental Falls↗
PubMed1998

Dissociation of early glucocorticoid inhibition of ACTH secretion and glucose uptake in mouse AtT20 D16:16 corticotrophs.

Adrenal glucocorticoid hormones rapidly exert powerful effects on neurons, immune and neuroendocrine cells through induction of de novo protein synthesis. In this study, we investigated, using mouse clonal anterior pituitary AtT20 D16:16 corticotrophs, whether (i) glucocorticoids rapidly inhibit glucose transport and (ii) whether this inhibition of glucose transport is directly correlated with early inhibition of ACTH secretion. Glucose uptake in AtT20 D16:16 cells was Na+-independent because the Na+-independent glucose transport inhibitor phloretin (100 microM) completely inhibited specific 14C-deoxygluose (DoG) uptake and replacement of extracellular Na+ with N-methyl D-glucamine+ had no effect. Furthermore, the Na+-independent glucose transporters, GLUTs 1 and 3 were expressed in AtT20 D16:16 cells. The synthetic type II glucocorticoid receptor agonist dexamethasone, rapidly, within 2 h, inhibited DoG uptake into AtT20 D16:16 cells through a mechanism that was dependent on de novo mRNA synthesis. Glucocorticoid inhibition of glucose transport was not correlated with early inhibition of ACTH secretion because removal of glucose from the external medium had no effect on CRF-stimulated ACTH secretion or the efficacy of early glucocorticoid inhibition of ACTH release. Although the Na+-independent glucose transport inhibitor phloretin significantly inhibited CRF-stimulated ACTH release, this effect of phloretin was a result of its potent activation of large conductance calcium-activated potassium (BK) channels. These data suggest that different molecular pathways and/or glucocorticoid induced proteins underlie the mechanism(s) of early glucocorticoid inhibition of glucose uptake and ACTH release, respectively.

Adrenocorticotropic Hormone↗
PubMed1997

Regulation and significance of apoptosis in the stem cells of the gastrointestinal epithelium.

In rapidly proliferating tissues the stringent control of cell proliferation and cell death by apoptosis is central to the maintenance of tissue homeostasis. In the gastrointestinal tract most work studying the control of tissue cell number has traditionally focused on the growth factor control of proliferation, and the changes that occur during carcinogenesis. However, in recent years it has become increasingly apparent that the control of apoptosis is also crucial. Apoptosis is an important mechanism for eliminating both excess normal cells and those cells which have sustained damage; therefore maintaining a tissue, i.e., stem cells with preserved DNA integrity. In this review the incidence of apoptosis in the stem cells of both the small and large intestine will be discussed in relation to the expression of a number of apoptosis regulating genes (e.g. p53, Bcl-2, bax) within these cells. The importance of apoptosis as a means of controlling stem cell number (and therefore cellular output) will be addressed, as will the mechanisms by which any alterations to this process may contribute to malignancy.

Animals↗