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Biomedical subjects

J Foster

Publications and source records attributed to J Foster.

At least 37 records · Page 2Linked to original sources

Vibrio fischeri lux genes play an important role in colonization and development of the host light organ.

The bioluminescent bacterium Vibrio fischeri and juveniles of the squid Euprymna scolopes specifically recognize and respond to one another during the formation of a persistent colonization within the host's nascent light-emitting organ. The resulting fully developed light organ contains brightly luminescing bacteria and has undergone a bacterium-induced program of tissue differentiation, one component of which is a swelling of the epithelial cells that line the symbiont-containing crypts. While the luminescence (lux) genes of symbiotic V. fischeri have been shown to be highly induced within the crypts, the role of these genes in the initiation and persistence of the symbiosis has not been rigorously examined. We have constructed and examined three mutants (luxA, luxI, and luxR), defective in either luciferase enzymatic or regulatory proteins. All three are unable to induce normal luminescence levels in the host and, 2 days after initiating the association, had a three- to fourfold defect in the extent of colonization. Surprisingly, these lux mutants also were unable to induce swelling in the crypt epithelial cells. Complementing, in trans, the defect in light emission restored both normal colonization capability and induction of swelling. We hypothesize that a diminished level of oxygen consumption by a luciferase-deficient symbiotic population is responsible for the reduced fitness of lux mutants in the light organ crypts. This study is the first to show that the capacity for bioluminescence is critical for normal cell-cell interactions between a bacterium and its animal host and presents the first examples of V. fischeri genes that affect normal host tissue development.

Animals↗

Lip-reading ability and patterns of cortical activation studied using fMRI.

Lip-reading is a complex cognitive skill with large individual differences in performance. The basis of these individual differences remains poorly understood. Functional magnetic resonance imaging (fMRI) techniques allows brain activation accompanying complex cognitive activities to be studied noninvasively. In the present paper, fMRI was used to study the patterns of cortical activation that occur during the silent lip-reading of connected speech and to investigate whether there are detectable differences in activation between subjects with widely differing lip-reading abilities. From a cohort of 26 volunteers, nine subjects who fell into three distinct lip-reading ability groups were selected. Brain activation was measured in two conditions: an experimental condition where subjects attempted to lip-read sentences; and a baseline condition where subjects passively viewed a static image of a talker's face. Relative to the baseline condition, lip-reading induced activation in several cortical areas, including the auditory cortices, despite the lack of an auditory component to the task. In comparison to the better two groups of lip-readers, subjects in the poorest group displayed significantly less activation in superior and middle temporal gyrus, but not inferior temporal gyrus. These preliminary results justify more extensive investigations of the cortical basis of individual differences in lip-reading.

Adult↗

Immunolocalization of the prion protein in scrapie affected rodent retinas.

Some mouse and hamster scrapie models are known to replicate infectivity in the retina, and this can be associated with photoreceptor atrophy. We used immuno-labelling to identify the cellular localization of the prion protein (PrP) in the retina and correlated this with infectivity titre. It is only with the 263K scrapie strain in hamsters that disease-associated PrP (PrP(Sc)) staining was always easily detectable. Very little PrP(Sc) immunolabelling was observed in any of the mouse models, even in those demonstrating scrapie-induced retinopathy in which high titres of infective agent are known to occur in the retina.

Animals↗

Genomics and the biology of parasites.

Despite the advances of modern medicine, the threat of chronic illness, disfigurement, or death that can result from parasitic infection still affects the majority of the world population, retarding economic development. For most parasitic diseases, current therapeutics often leave much to be desired in terms of administration regime, toxicity, or effectiveness and potential vaccines are a long way from market. Our best prospects for identifying new targets for drug, vaccine, and diagnostics development and for dissecting the biological basis of drug resistance, antigenic diversity, infectivity and pathology lie in parasite genome analysis, and international mapping and gene discovery initiatives are under way for a variety of protozoan and helminth parasites. These are far from ideal experimental organisms, and the influence of biological and genomic characteristics on experimental approaches is discussed, progress is reviewed and future prospects are examined.

Animals↗

FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4.

We have identified a novel fibroblast growth factor, FGF-19, the most distant member of the FGF family described to date. FGF-19 is a high affinity, heparin dependent ligand for FGFR4 and is the first member of the FGF family to show exclusive binding to FGFR4. Human FGF-19 maps to chromosome 11 q13.1, a region associated with an osteoporosis-pseudoglioma syndrome of skeletal and retinal defects. FGF-19 message is expressed in several tissues including fetal cartilage, skin, and retina, as well as adult gall bladder and is overexpressed in a colon adenocarcinoma cell line.

Adenocarcinoma↗

Factor structure of the CES-D (Center for Epidemiologic Studies Depression Scale) among Filipino-American adolescents.

The present study used factor analytic procedures to examine the factor structure of the CES-D among Filipino-American adolescents residing in rural and small town Hawaii. A total of 243 Filipino-American high school students completed the 20-item scale, and maximum likelihood analyses were employed to obtain a final solution. The results indicated that two factors provide a reasonably good fit: factor I combined depressed affect, somatic-retardation and interpersonal items, and factor II consisted of the remaining four positive affect items. The overlap of depressed affect and somatic symptoms support previous findings found among Asian American adults and other ethnic minority adolescents. The loading of the interpersonal items on the first factor is more unusual and suggests that interpersonal factors are not distinguished from depressed affect for the Filipino-American adolescent group. The usefulness of the CES-D as a tool to gain an understanding of the concept of depression across cultures is discussed.

Adolescent↗

Magnetic resonance imaging techniques demonstrate soft tissue damage in the diabetic foot.

AIMS: Our objective was to assess the qualitative soft tissue changes which occur in the diabetic neuropathic foot, which may predispose to ulceration, using a specific magnetic resonance imaging (MRI) contrast sequence, magnetization transfer (MT) which produces contrast based on exchange between water bound to macromolecules (e.g. collagen) and free water (e.g. extracellular fluid). METHODS: The first metatarsal head of 19 diabetic neuropathic subjects and 11 diabetic non-neuropathic controls was studied using a 'targeted' radiofrequency coil. Neuropathy was classified using vibration perception threshold (VPT) (< or > 25 V), cold threshold (< 1 degree C or > 4 degrees C) and Michigan neuropathy score (< 5 or > 15). Peripheral vascular disease was excluded. Results were expressed as percentage of tissue MT activity in a cross-sectional area. At autopsy full thickness biopsies were taken from the plantar fat pad of 10 unrelated subjects with diabetic neuropathy. RESULTS: Healthy muscle displays high MT activity, whereas adipose tissue induces little activity. Muscle MT activity was considerably reduced (75+/-20%, 30+/-24%, P<0.001) and fat pad MT activity was considerably increased in subjects with neuropathy (37+/-17% 68+/-21%, P<0.001). Muscle fibre atrophy decreases MT activity, whereas fibrous infiltration of the fat pad increases MT activity, fibro-atrophic post-mortem histological changes were found in the plantar fat pads of all neuropathic subjects examined (n = 10). CONCLUSIONS: Changes in MT activity reflect qualitative structural changes which this study reveals are extensive in the diabetic neuropathic foot. Fibrotic atrophy of the plantar fat pad may affect its ability to dissipate the increased weight-bearing forces associated with diabetic neuropathy.

Adipose Tissue↗

Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging.

UNLABELLED: Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging. BACKGROUND: Left ventricular hypertrophy (LVH) is a common finding and a strong adverse prognostic factor in patients with chronic renal failure. An accurate method of measuring left ventricular mass (LV mass) is therefore a prerequisite in the management of these patients. Recent evidence has suggested that echocardiography overestimates LV mass in patients with essential hypertension, and this error increases with increasing LV mass. METHODS: We studied 35 patients on maintenance hemodialysis within 24 hours of their last dialysis. LV mass was measured by both echocardiography and magnetic resonance imaging (MRI) performed less than three hours apart. Clinic and ambulatory blood pressure (ABPM), resting echocardiogram, and blood sampling were performed at the same visit. RESULTS: Thirty-two patients had results from both methods. Clinic blood pressure, ABPM, and QT dispersion all correlated with LV mass, with a stronger correlation observed for MRI values. Intraobserver and interobserver variability were significantly greater for echocardiography (although similar to other published data). Comparing the two methods, the difference in LV mass values (echo minus magnetic resonance) increased in a linear fashion with an increasing mean mass and chamber diameter. CONCLUSIONS: Echocardiography significantly overestimates LV mass relative to MRI in the presence of LVH and dilation. This overestimation is the result of assumptions made in the calculation of mass from echocardiography M-mode images, which are invalid when LV geometry is abnormal. This error is therefore amplified in dialysis patients, the majority of whom have LVH and in whom intravascular volume is constantly changing.

Adult↗

Experimentally induced bovine spongiform encephalopathy did not transmit via goat embryos.

Goats are susceptible to experimental challenge with bovine spongiform encephalopathy (BSE). This study set out to investigate whether the transmission of BSE could occur in goats following the transfer of embryos from experimentally infected donor females into uninfected recipient females. The results showed no evidence of transmissible spongiform encephalopathy disease in any of the offspring which developed from embryos from infected donors, nor indeed in any of the recipient females used as surrogate dams. In addition, there was no indication of experimental BSE spreading as either a venereal infection to males used in mating or by maternal transmission to offspring born naturally to experimentally infected donors, although numbers were small.

Animals↗

Induction of hyperplasia and increased DNA content in the uterus of immature rats exposed to coumestrol.

Administration of the phytoestrogen coumestrol to ovariectomized rats leads to increases in both wet and dry uterine weights in the absence of an increase in uterine DNA content, as reported by Markaverich et al. [Effects of Coumestrol on Estrogen Receptor Function and Uterine Growth in Ovariectomized Rats. Environ Health Perspect 103:574-581 (1995)]. It was not possible to know if the observed atypical uterotrophic response of coumestrol was associated uniquely with the ovariectomized uterotrophic assay protocol. This question is answered in the present paper. Two experiments are described in which three daily oral gavage administrations of 60 mg/kg/day coumestrol to immature AP rats were followed by assessment of the reproductive tract on the fourth day. In both experiments coumestrol increased uterine fluid content and increased the weights of the uterus, cervix, and vagina. In addition, bromodeoxyuridine staining of uterine sections enabled confirmation of uterine hyperplasia for the coumestrol-treated animals. In the second experiment, total uterine DNA was determined; it doubled in the coumestrol-treated animals. Estradiol benzoate acted as the positive control agent for both of these experiments, and in each case it gave similar responses to those seen for coumestrol. We conclude that the uterotrophic activity of the phytoestrogen coumestrol in the immature intact rat is typical of the activity of the natural estrogen estradiol.

Animals↗

Concerns and confidence of general practitioners in providing telephone consultations.

BACKGROUND: In recent years the number of telephone consultations provided out of hours has increased. However, most general practitioners (GPs) have received little training in this area despite the specific skills needed to compensate for lack of visual information. Moreover, there has been no research exploring GPs' concerns and training needs in telephone consulting. AIM: To assess GPs' concerns and levels of confidence in providing telephone consultations in order to inform the development of a new training course. METHOD: Prior to attending the course, GPs were surveyed by interview or self-completion questionnaire to explore their confidence in providing telephone consultations. RESULTS: Thirty-eight GPs participated, and the sample was highly skewed towards females. The average age of participants was 42 years, 5 years less than the mean for GPs in the area. Low levels of confidence were reported by GPs in providing telephone consultations out of hours. A number of characteristics were common to telephone consultations described as difficult. The most important were lack of visual clues and lack of information about the patient, both of these were heightened in the out-of-hours period. Organizational factors leading to reduced confidence levels were also identified. CONCLUSIONS: This study demonstrates low levels of confidence among GPs conducting telephone consultations, and highlights contributing factors. Although it is not clear how far these results can be generalized, they demonstrate the need to consider telephone consulting skills training in the context of new out-of-hours arrangements. The results have been used to develop a two-day course.

Adult↗

Autocrine transforming growth factor alpha provides a growth advantage to malignant cells by facilitating re-entry into the cell cycle from suboptimal growth states.

CBS human colon carcinoma cells are poorly tumorigenic in athymic nude mice, whereas FET colon carcinoma cells are non-tumorigenic. Both cell lines have well differentiated properties in tissue culture. Transforming growth factor alpha (TGF-alpha) was ectopically expressed by stable transfection of a TGF-alpha cDNA under repressible tetracycline control. The TGF-alpha-transfected cells showed enhanced clonal initiation and shortened lag phase growth in tissue culture without an alteration in doubling time in exponential phase relative to untransfected cells. Furthermore, the TGF-alpha transfectants showed increased independence from exogenous growth factors in clonal growth assays and induction of DNA synthesis after release from quiescence. Growth factor independence was associated with sustained epidermal growth factor receptor activation in quiescent TGF-alpha-transfected cells and the requirement of exogenous insulin for stimulation of quiescent cells to re-enter the cell cycle. Higher cloning, reduced lag time in tissue, and the acquisition of growth factor independence for DNA synthesis without a change in doubling time of TGF-alpha-transfected cells indicate that autocrine TGF-alpha functions by facilitating re-entry into the cell cycle from sub-optimal growth states rather than promoting or controlling the proliferation of actively cycling cells. The modulation of growth regulation by autocrine TGF-alpha was associated with increased malignant properties as TGF-alpha transfectants showed increased tumorigenicity in athymic nude mice. The administration of tetracycline reversed the effects of TGF-alpha expression in these cells both in vivo and in vitro, indicating that the alterations of the biological properties were due to the expression of TGF-alpha. Since these cells are continuously grown in a completely chemically defined medium without serum supplementation, it was possible to assign the mechanism underlying the generation of growth factor independence to the replacement of a requirement for exogenous insulin in parental cells by autocrine TGF-alpha.

Adaptor Proteins, Signal Transducing↗

Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells.

We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.

Amino Acid Sequence↗

Transmissible spongiform encephalopathies: transmission, mechanism of disease, and persistence.

Prion protein is central to the control of development of all transmissible spongiform encephalopathies. Controversy exists as to whether the protein itself is responsible for disease manifestation, in one of perhaps several isoforms, or whether an additional informational molecule must be involved in conjunction with the protein. Recent studies have been trying to resolve these issues.

Animals↗

Expanded superficial temporalis fascial flap for orbital reconstruction in a postirradiated orbit: a patient report.

The temporalis musculofascial flap can be pre-expanded to increase its area prior to transfer. The large size of the preexpanded flap enabled orbital reconstruction to be carried out in a postirradiated orbit in a three-year-old girl. The flap was split, transferred in two parts, and covered with a buccal mucosal graft. A prosthetic shell was satisfactorily fitted postoperatively.

Child, Preschool↗