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Biomedical subjects

J Price

Publications and source records attributed to J Price.

At least 55 records · Page 3Linked to original sources
PubMed2001

Hedgehog signaling is required for pituitary gland development.

Pituitary gland development serves as an excellent model system in which to study the emergence of distinct cell types from a common primordium in mammalian organogenesis. We have investigated the role of the morphogen Sonic hedgehog (SHH) in outgrowth and differentiation of the pituitary gland using loss- and gain-of-function studies in transgenic mice. Shh is expressed throughout the ventral diencephalon and the oral ectoderm, but its expression is subsequently absent from the nascent Rathke's pouch as soon as it becomes morphologically visible, creating a Shh boundary within the oral epithelium. We used oral ectoderm/Rathke's pouch-specific 5' regulatory sequences (Pitx1(HS)) from the bicoid related pituitary homeobox gene (Pitx1) to target overexpression of the Hedgehog inhibitor Hip (Huntingtin interacting protein) to block Hedgehog signaling, finding that SHH is required for proliferation of the pituitary gland. In addition, we provide evidence that Hedgehog signaling, acting at the Shh boundary within the oral ectoderm, may exert a role in differentiation of ventral cell types (gonadotropes and thyrotropes) by inducing Bmp2 expression in Rathke's pouch, which subsequently regulates expression of ventral transcription factors, particularly Gata2. Furthermore, our data suggest that Hedgehog signaling, together with FGF8/10 signaling, synergizes to regulate expression of the LIM homeobox gene Lhx3, which has been proved to be essential for initial pituitary gland formation. Thus, SHH appears to exert effects on both proliferation and cell-type determination in pituitary gland development.

Animals↗
PubMed2001

The levonorgestrel intra-uterine system: therapeutic application in family planning.

OBJECTIVE: To assess the non-contraceptive benefits of the levonorgestrel intra-uterine system 12 months following insertion in a family planning setting. DESIGN: Postal questionnaire survey. SETTING: Family planning clinics at the Ulster and Bangor Hospitals. SUBJECTS: Eighty-six consecutive subjects fitted with the levonorgestrel intra-uterine system. RESULTS: Response rate 87.3%. Outcome measured in terms of compliance, satisfaction and menstrual symptomatology. Reasons for insertion were as follows: 21.7% contraception only; 65.2% menorrhagia, 24.6% dysmenorrhoea and 1.4% premenstrual syndrome. Duration of menses was 8.25 days pre-insertion and 2.41 days at 12 months. Of the subjects, 59.4% experienced at least one hormonal side effect; 10.1% of systems were removed within 12 months. At 12 months 86.9% of women were satisfied and 9.8% of women planned to discontinue. CONCLUSION: The levonorgestrel intra-uterine system was acceptable to almost 80% of women after 12 months, with significant reduction in duration of menses. Family planning clinics are an ideal setting to implement the guidelines for the initial management of menorrhagia.

Adolescent↗
PubMed2001

Developing palliative care services in regional areas. The Ipswich Palliative Care Network model.

BACKGROUND: Although there are over 350 palliative care services present in Australia and New Zealand, the distribution of these is patchy. Patients in some regional and rural areas have little or no access to specialist services, and manage with the enthusiasm and general expertise of local practitioners. OBJECTIVE: This paper discusses the problems encountered in maintaining skills in palliative care in the face of small patient numbers and poor resources, and describes a solution that was developed in Ipswich, Queensland. DISCUSSION: The twin problem of GP skills maintenance and adequate community service provision in palliative care can be overcome by developing a general practice based service in conjunction with local health authorities and the community. Highlighting the benefits to the health authority and the community of maximal general practitioner involvement is the most important lever in securing cooperation.

Australia↗
PubMed2001

Patient monitoring using personal area networks of wireless intelligent sensors.

A wearable device for monitoring multiple physiological signals (polysomnograph) usually includes multiple wires connecting sensors and the monitoring device. In order to integrate information from intelligent sensors, all devices must be connected to a Personal Area Network (PAN). This system organization is unsuitable for longer and continuous monitoring, particularly during the normal activity. For instance, monitoring of athletes and computer assisted rehabilitation commonly involve unwieldy wires to arms and legs that restrain normal activity. We propose a wireless PAN of intelligent sensors as a system architecture of choice, and present a new design of wireless personal area network with physiological sensors for medical applications. Intelligent wireless sensors perform data acquisition and limited processing. Individual sensors monitor specific physiological signals (such as EEG, ECG, GSR, etc.) and communicate with each other and the personal server. Personal server integrates information from different sensors and communicates with the rest of telemedical system as a standard mobile unit. We present our prototype implementation of Wireless Intelligent SEnsor (WISE) based on a very low power consumption microcontroller and a DSP-based personal server. In future we expect all components of WISE integrated in a single chip for use in a variety of new medical applications and sophisticated human computer interfaces. Existing growth of wireless infrastructure will allow a range of new telemedical applications that will significantly improve the quality of health care.

Computer Communication Networks↗
PubMed2001

Atypical glandular cells of undetermined significance. Subtyping as a predictor of outcome.

OBJECTIVE: To determine whether subtyping of atypical glandular cells of undetermined significance (AGUS) cervical smears into reactive process favored (AGUS-RPF) and not otherwise specified (AGUS-NOS) correlates with rates of underlying pathology. STUDY DESIGN: We performed a retrospective chart review of 129,676 routine Pap smears at Kaiser Permanente, San Diego, from June 1998 to November 1999. One hundred fifty of the 129,676 were evaluated as AGUS (0.12%). Subjects with concomitant AGUS/SIL Pap smears, a prior history surgery for dysplasia, prior AGUS, a history of cancer or prior hysterectomy were excluded from the study. The remaining AGUS smears were then subtyped into AGUS-NOS and AGUS-RPF based on the criteria of the 2nd Workshop of the Bethesda System. Sixty-eight subjects with an initial AGUS smear underwent evaluation with colposcopy, endocervical curettage, endometrial biopsy and directed cervical biopsies. Significant pathology was determined to be any tissue diagnosis that required further treatment more than a follow-up Pap smear. AGUS subclassifications and underlying pathology were then compared using the chi 2 test with Fisher's Exact Test. RESULTS: Twenty-seven patients (40%) had AGUS-NOS, and 41 (60%) had AGUS-RPF. There were no significant differences between the groups in regard to age, race, parity, menopause status, HRT use or tobacco use. CONCLUSION: Subtyping AGUS cervical smears correlates with underlying rates of pathology. However, AGUS-RPF smears were still associated with an approximately 10% incidence of significant underlying pathology. Patients with AGUS on cervical smears need thorough evaluation, regardless of subtyping.

Adult↗
PubMed2001

Pediatric emergencies in the office: are family physicians as prepared as pediatricians?

OBJECTIVE: Our objective was to assess the occurrence of pediatric emergencies in the offices of family physicians and pediatricians, the preparedness to respond, and the perceived importance of being prepared. STUDY DESIGN: We performed a cross-sectional random mail survey of physicians. POPULATION: Surveys were sent to 187 family physicians and 129 pediatricians practicing in North Carolina with 75% and 86% response rates, respectively. The 169 total respondents were in community practices regularly treating children and were included for analysis. OUTCOMES MEASURED: We measured the incidence of 8 types of pediatric emergencies, the availability of 11 items for resuscitation and stabilization, whether the physician had Pediatric Advanced Life Support (PALS) training in the previous 2 years, whether the office ever conducted a mock emergency, and beliefs about the importance of preparing for and providing emergency care to children. RESULTS: Six types of pediatric emergencies were seen in one third or more of all practices during the year. The average practice saw 4 or more pediatric emergencies in a year (family physicians = 3.8 vs pediatricians = 4.9, P <.001). Family physicians had fewer resuscitation and stabilization items than pediatricians (5.7 vs 8.6 items, P <.001) and were less prepared in terms of PALS training (19% vs 51%, P <.001). Those with PALS training were more likely to have an intraosseous needle and Broselow tape and to have conducted a mock code. Family physicians considered it is less important than pediatricians to provide such care or to be prepared to do so. CONCLUSIONS: Pediatric emergencies in the office are likely for either specialty. Family physicians may be less prepared, and they discount the importance of the problem and need for preparation.

Clinical Competence↗
PubMed2001

Outbreak of Salmonella indiana associated with egg mayonnaise sandwiches at an acute NHS hospital.

An outbreak of Salmonella indiana infection in December 2000 affected 17 staff, relatives and patients at an acute NHS Hospital in Swansea. Epidemiological investigation identified egg mayonnaise sandwiches as the vehicle of infection. It was not possible to definitively determine the source of the infection or how the prepared sandwiches became contaminated. The most likely explanation was a pasteurisation failure of a batch of the egg roll used to make these sandwiches. Sandwiches are the most frequently identified vehicle of infection in foodborne outbreaks of salmonella infection in hospitals in England and Wales. The process of sandwich preparation has inherent risks because it involves considerable handling of food, which is consumed without further cooking. Care is required in all stages of preparation including the sourcing of materials used to produce the sandwiches. NHS Trusts should review their Hazard Analysis Critical Control Point plans for sandwich production.

Case-Control Studies↗
PubMed2000

CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70.

CAIR-1/BAG-3 forms an EGF-regulated ternary complex with Hsp70/Hsc70 and latent phospholipase C-gamma (PLC-gamma). The expression of CAIR-1, CAI stressed-1, was induced in A2058 human melanoma cells by continuous exposure to CAI, an inhibitor of nonvoltage-gated calcium influx. CAIR-1 sequence is identical, save 2 amino acids, to BAG-3 also cloned recently as Bis, a member of the bcl-2-associated athanogene family. We show that CAIR-1/BAG-3 binds to Hsp70/Hsc70 in intact cells and this binding is increased by short term exposure to CAI (P<0.007). CAIR-1/BAG-3 is phosphorylated in vivo in the absence of stimulation. Basal phosphorylation is inhibited by treatment with d-erythrosphingosine (d-ES), a broad inhibitor of the protein kinase C family. CAIR-1/BAG-3 contains several PXXP SH3 binding domains leading to the hypothesis that it is a partner protein of phospholipase C-gamma. PLC-gamma is bound to CAIR-1/BAG-3 in unstimulated cells. It is increased by CAI or d-ES (P=0.05) treatment, and abrogated by EGF (r2=0.99); d-ES treatment blocks the EGF-mediated dissociation. We show that CAIR-1/BAG-3 binds to PLC-gamma and Hsp70/Hsc70 through separate and distinct domains. Hsp70/Hsc70 binds to the BAG domain of BAGs-1 and -3. CAIR-1/BAG-3 from control and EGF-treated cell lysates bound selectively to the SH3 domain of PLC-gamma, but not its N-SH2 or C-SH2 domains. Confirming the SH3 interaction, PLC-gamma was pulled down by CAIR-1/BAG-3 PXXP-GST fusions, but GST-PXXP constructs confronted with lysates from EGF-treated cells did not bind PLC-gamma as was seen in intact cells. Hsp70/Hsc70 was brought down by the PLC-gamma SH3 construct equally from native and EGF-treated cells, but did not bind the PXXP construct under either condition. We propose that CAIR-1/BAG-3 may act as a multifunctional signaling protein linking the Hsp70/Hsc70 pathway with those necessary for activation of the EGF receptor tyrosine kinase signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Central circuits mediating patterned autonomic activity during active vs. passive emotional coping.

Animals, including humans, react with distinct emotional coping strategies to different sets of environmental demands. These strategies include the capacity to affect appropriate responses to "escapable" or "inescapable" stressors. Active emotional coping strategies--fight or flight--are particularly adaptive if the stress is escapable. On the other hand, passive emotional coping strategies-quiescence, immobility, decreased responsiveness to the environment-are useful when the stress is inescapable. Passive strategies contribute also to facilitating recovery and healing once the stressful event is over. Active vs. passive emotional coping strategies are characterised further by distinct patterns of autonomic change. Active strategies are associated with sympathoexcitation (hypertension, tachycardia), whereas passive strategies are associated with sympathoinhibitory patterns (hypotension, bradycardia). Distinct neural substrates mediating active vs. passive emotional coping have been identified within the longitudinal neuronal columns of the midbrain periaqueductal gray region (PAG). The PAG offers then a potentially useful point of entry for delineating neural circuits mediating the different forms of emotional coping and their associated patterns of autonomic activity. As one example, recent studies of the connections of orbital and medial prefrontal cortical (PFC) fields with specific PAG longitudinal neuronal columns are reviewed. Findings of discrete orbital and medial PFC projections to different PAG columns, and related PFC and PAG columnar connections with specific subregions of the hypothalamus, suggest that distinct but parallel circuits mediate the behavioural strategies and patterns of autonomic activity characteristic of emotional "engagement with" or "disengagement from" the external environment.

Adaptation, Psychological↗
PubMed2000

Asymptomatic maternal myasthenia as a cause of the Pena-Shokeir phenotype.

We report six sibs with arthrogryposis multiplex congenita and a Pena-Shokeir phenotype, born to a healthy woman who was discovered to have asymptomatic myasthenia gravis (MG). This is the first report of anti-acetylcholine receptor (AChR) antibodies causing fetal akinesia/hypokinesia sequence in the offspring of an asymptomatic mother.

Abnormalities, Multiple↗
PubMed2000

Neurotransplantation in neurodegenerative disease: a survey of relevant issues in developmental neurobiology.

Neural development and transplantation therapies in neurodegenerative disease share a particular feature. In both cases, undifferentiated neural precursor cells are required to differentiate into a range of neural cell types in a tissue-specific fashion. This similarity opens the possibility that the mechanisms that drive neural development play a similar role in CNS repair. In this chapter, two aspects of neural development are considered in terms of their relevance to CNS repair: the diversity of neural precursor cells and positional specification. We present evidence to suggest that neural stem cells have a degree of diversity that is beyond what might have been expected a priori. We also show that neural stem cells express genes that might encode a positional specification for these cells, and consider a number of hypotheses about the role of positional specification in CNS repair.

Animals↗
PubMed2000

Differential display of genes expressed at the midbrain - hindbrain junction identifies sprouty2: an FGF8-inducible member of a family of intracellular FGF antagonists.

Specification and polarization of the midbrain and anterior hindbrain involve planar signals originating from the isthmus. Current evidence suggests that FGF8, expressed at the isthmus, provides this patterning influence. In this study, we have sought to identify novel genes which are involved in the process by which regional identity is imparted to midbrain and anterior hindbrain (rhombomere 1). An enhanced differential display reverse transcription method was used to clone cDNAs derived from transcripts expressed specifically in either rhombomere 1 or midbrain during the period of isthmic patterning activity. This gene expression screen identified 28 differentially expressed cDNAs. A clone upregulated in cDNA derived from rhombomere 1 tissue showed a 91% identity at the nucleotide level to the putative human receptor tyrosine kinase antagonist: sprouty2. In situ hybridization on whole chick embryos showed chick sprouty2 to be expressed initially within the isthmus and rhombomere 1, spatially and temporally coincident with Fgf8 expression. However, at later stages this domain was more extensive than that of Fgf8. Introduction of ligand-coated beads into either midbrain or hindbrain region revealed that sprouty2 could be rapidly induced by FGF8. These data suggest that sprouty2 participates in a negative feedback regulatory loop to modulate the patterning activity of FGF8 at the isthmus.

Amino Acid Sequence↗
PubMed2000

TR3 death receptor expression in the normal and ischaemic brain.

Members of the death receptor family may play a prominent role in developmental and pathological neuronal cell death. We report the expression of the TR3 and TR7 death receptors in the adult human and rat central nervous system. Whereas expression of TR3 appears to be high in the human cerebellum, with lower levels in other brain regions, robust expression is observed in many regions of the rat brain. We also analyzed modulation of death receptor expression in an in vivo rat model of acute stroke. In contrast to tumor necrosis factor receptor 1, Fas and p75(NGFR), which all show up-regulation specifically in lesioned cortex of the permanent middle cerebral artery occlusion model of stroke. TR3 shows a rapid global increase in both lesioned and unlesioned brain. In comparison, the recently described death receptor TR7 shows no change in this model. These data indicate that the death receptors show clear differences in patterns of expression in response to ischemic injury. ¿ 2000 IBRO. Published by Elsevier Science Ltd.

Amino Acid Sequence↗
PubMed2000

PC3 overexpression affects the pattern of cell division of rat cortical precursors.

The PC3 gene is transiently expressed during neurogenesis in precursor cells of the telencephalic ventricular/subventricular zone, and is rapidly downregulated before cell migration and differentiation. It is thought to have a role in controlling cell proliferation, but its precise function is not known. Here we present evidence that PC3, when overexpressed in vitro by retroviral-mediated gene transfer, acts by interfering with the normal pattern of cell division. Firstly, we report evidence that PC3 overexpression reduces the rate of cell proliferation in both NIH 3T3 cells and embryonic precursor cells from the rat cerebral cortex. Secondly, when studying the pattern of BrdU dilution in clones of cortical precursors, we observe that clones transduced with PC3 show an asymmetric pattern of BrdU dilution more frequently than clones transduced with a control vector. We discuss the hypothesis that the higher number of PC3 transduced clones showing an asymmetric pattern of BrdU dilution may be due to an increase in asymmetric cell divisions.

3T3 Cells↗
PubMed2000

Efficacy of nebulized fluticasone propionate compared with oral prednisolone in children with an acute exacerbation of asthma.

The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma.

Acute Disease↗
PubMed2000

A high oat-bran intake does not impair zinc absorption in humans when added to a low-fiber animal protein-based diet.

Oat bran has a high phytate content and a low or inactivated phytase activity. A high intake of oat bran could therefore result in an impaired absorption of trace elements. The effect of a mean daily intake of 142 g of oat bran (102 g/10 MJ) on absorption of zinc was evaluated by the use of stable isotopes and fecal monitoring in 12 healthy subjects (6 males and 6 females). Each subject participated in two separate diet periods each of 21 d with identical low-fiber diets and with oat bran added in one of the periods. The oat bran was incorporated into bread and served at three daily main meals. The intake of zinc and phytate per 10 MJ was 138 micromol (9.0 mg) and 0.5 mmol, respectively, in the low-fiber period and 225 micromol (14.7 mg) and 4.0 mmol, respectively, in the oat bran period. Stable isotopes of zinc ((70)Zn) were added to the diets at d 7 of each period. The fractional absorptions (means +/- SD) of zinc from the low-fiber and oat bran diets were 0.48 +/- 0.11 and 0.40 +/- 0.15 (P = 0.07), respectively. The higher zinc content in the oat bran period resulted in a greater amount of zinc absorbed (64 +/- 19 micromol and 99 +/- 51 micromol, respectively, P = 0.009). Balance data suggest that the higher absorbed amount of zinc resulted in correspondingly higher intestinal endogenous excretion of zinc. In conclusion, the absorption of zinc was high and not affected by addition of oat bran.

Adult↗
PubMed2000

The role of inhaled corticosteroids in children with asthma.

Inhaled corticosteroids offer a wide range of anti-inflammatory activity and have consistently proved to be the most effective medication for the control of childhood asthma. The high efficacy of inhaled corticosteroids has led to their use in milder disease and younger children in the hope that permanent changes in lung function and airway remodelling may be prevented. However, evidence has emerged over the past six years that the first of the inhaled corticosteroids to become available, beclomethasone dipropionate, may cause growth deceleration at a dose of 400 microg per day. This is especially apparent in children with mild symptoms. The newest of the inhaled corticosteroids to be developed, fluticasone propionate, is equipotent to older compounds at half the dose and in low doses is superior in efficacy to sodium cromoglycate. Two recent studies have shown that fluticasone propionate 100-200 microg per day does not cause growth suppression in children with mild asthma. The long term outcome for children who wheeze in early life is difficult to predict. For this reason the use of inhaled corticosteroids in very young children is best reserved for those with severe symptoms or a strong family history of asthma, and evidence, from measurement of inflammatory markers, of airway inflammation.

Administration, Inhalation↗