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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 163 records · Page 9Linked to original sources
PubMed1999

Subharmonic imaging with microbubble contrast agents: initial results.

The subharmonic emission from insonified contrast microbubbles was used to create a new imaging modality called Subharmonic Imaging. The subharmonic response of contrast microbubbles to ultrasound pulses was first investigated for determining adequate acoustic transmit parameters. Subharmonic A-lines and gray scale images were then obtained using a laboratory pulse-echo system in vitro and a modified ultrasound scanner in vivo. Excellent suppression of all backscattered signals other than from contrast microbubbles was achieved for subharmonic A-lines in vitro while further optimization is required for in vivo gray scale subharmonic images.

Animals↗
PubMed1999

Hearing from children who have diabetes.

Previous research provided children with few opportunities to say what they feel about 'being diabetic'. A phenomenological approach is helpful in undertaking research with children. Children are able to express their feelings about being diabetic. The experiences of children aged 7-12 years who have diabetes can be clustered into six themes--finding out, daily discipline, being normal, good things, bad things and support. Findings of the study are discussed, identifying some implications for practice.

Activities of Daily Living↗
PubMed1999

Comparison of the efficacy and safety of a new aluminium-free paediatric alginate preparation and placebo in infants with recurrent gastro-oesophageal reflux.

The aim of the present study was to compare the efficacy and safety of a new aluminium-free formulation of alginate with placebo in infants with recurrent gastro-oesophageal reflux. This was a double-blind, randomised, parallel-group study conducted at 25 centres in the UK. Of the 90 paediatric patients recruited in a general practice setting, 42 were randomised to receive alginate and 48 to receive placebo. Infants were assessed before treatment and again after seven and 14 days of treatment. Analyses were based on the last, valid, non-missing observation for each variable for the intent-to-treat (ITT) population of 42 alginate and 46 placebo patients. For the primary efficacy measure (number of vomitting/regurgitation episodes), alginate was significantly superior to placebo (p = 0.009). For the secondary efficacy measure (severity of vomiting), a trend in favour of alginate was observed (p = 0.061). Patients receiving alginate achieved superior assessments of treatment outcome by both investigators (p = 0.008) and parent/guardians (p = 0.002) alike. In addition, alginate achieved a significantly greater reduction in the mean severity of vomiting episodes recorded in a daily diary compared with placebo (p = 0.027) and resulted in more patients having at least 10% symptom-free days (p = 0.027). For none of the variables measured did placebo have a superior effect. More than one-half of all patients experienced some adverse event, although no statistically significant differences were observed between the two treatment groups (p > 0.1), and adverse events accounted for withdrawal in only 12.5% of the patients (alginate, n = 4; placebo, n = 7). Aluminium-free alginate demonstrated superior efficacy over placebo in treating recurrent gastro-oesophageal reflux in paediatric patients. The safety profile of alginate was similar to that of placebo.

Age of Onset↗
PubMed1999

Expression and signal transduction of calcium-sensing receptors in cartilage and bone.

We previously showed that Ca2+-sensing receptors (CaRs) are expressed in chondrogenic RCJ3.1C5.18 (C5.18) cells and that changes in extracellular [Ca2+]([Ca2+]o) modulate nodule formation and chondrogenic gene expression. In the present study, we detected expression of CaRs in mouse, rat, and bovine cartilage and bone by in situ hybridization, immunocytochemistry, immunoblotting, and RT-PCR; and we tested the effects of CaR agonists on signal transduction in chondrogenic and osteogenic cell lines. In situ hybridization detected CaR transcripts in most articular chondrocytes and in the hypertrophic chondrocytes of the epiphyseal growth plate. Expression of CaR transcripts was weak or absent, however, in proliferating and maturing chondrocytes in the growth plate. In bone, CaR transcripts were present in osteoblasts, osteocytes, and bone marrow cells, but rarely in osteoclasts. A complementary DNA was amplified from mouse growth plate cartilage, which was highly homologous to the human parathyroid CaR sequence. Immunocytochemistry of cartilage and bone with CaR antisera confirmed these findings. Western blotting revealed specific bands (approximately 140-190 kDa) in membrane fractions isolated from growth plate cartilage, primary cultures of rat chondrocytes, and several osteogenic cell lines (SaOS-2, UMR-106, ROS 17/2.8, and MC3T3-E1). InsP responses to high [Ca2+]o were evident in C5.18 cells and all osteogenic cell lines tested except for SaOS-2 cells. In the latter, high [Ca2+]o reduced PTH-induced cAMP formation. Raising [Ca2+]o also increased intracellular free [Ca2+] in SaOS-2 and C5.18 cells. These studies confirm expression of CaRs in cartilage and bone and support the concept that changes in [Ca2+]o may couple to signaling pathways important in skeletal metabolism.

Animals↗
PubMed1999

Calcium sensing in cultured chondrogenic RCJ3.1C5.18 cells.

The availability of Ca2+ in the extracellular fluid plays an important role in regulating cartilage and bone formation. We hypothesized that chondrocytes detect changes in the extracellular [Ca2+] ([Ca2+]o) and modify their function. The effects of changing [Ca2+]o on the expression of matrix proteins were quantified by staining of cartilage nodules with alcian green and assessing RNA levels of cartilage-specific genes in chondrogenic RCJ3.1C5.18 (C5.18) cells. Alcian green staining in these cells decreased with increasing [Ca2+]o in a dose-dependent and reversible manner (ID50, approximately 2 mM Ca2+). RNA levels for aggrecan and type II collagen decreased with increasing [Ca2+]o (ID50, approximately 2.0 and 4.1 mM Ca2+, respectively). RNA levels for type X collagen and alkaline phosphatase were also reduced by high [Ca2+]o with ID50 values of approximately 2.9 and 1.6 mM Ca2+, respectively. These responses were rapid, in that increasing [Ca2+]o from 1.0 to more than 6 mM suppressed aggrecan RNA levels by about 50%, and lowering [Ca2+]o from 2.9 to 1.0 mM increased aggrecan RNA levels by about 300% within 4 h. As Ca2+ receptors (CaRs) mediate extracellular Ca2+ sensing in parathyroid and kidney, we assessed the expression of CaRs in these cells. C5.18 cells stained positively for CaR protein with an anti-CaR antiserum and for CaR RNA by in situ hybridization. An approximately 150-kDa protein was detected by immunoblotting with anti-CaR antiserum. CaR antisense oligonucleotides suppressed the expression of CaR protein and enhanced RNA levels of aggrecan in C5.18 cells. These data support the idea that CaRs are expressed in this cell system and may be involved in regulating chondrogenic gene expression.

Aggrecans↗
PubMed1999

MR angiography and flow quantification of the internal mammary artery graft after minimally invasive direct coronary artery bypass.

OBJECTIVE: Six patients who had undergone minimally invasive direct coronary artery bypass surgery were examined to evaluate an MR imaging protocol that provided information about cardiac function, bypass graft patency, and flow characteristics with a single examination. CONCLUSION: Preliminary results suggest that our imaging protocol allows accurate follow-up of patients after minimally invasive direct coronary artery bypass surgery. Bypass graft patency was correctly determined in all patients. In four patients, anastomoses were visualized by MR angiography, and flow measurements revealed a volume range of 28-84 ml/min (native and grafted internal mammary arteries) and a trend for the flow values of bypass grafts to be lower than those of native vessels. Interobserver reproducibility was good (r = .99; slope, .98).

Contrast Media↗
PubMed1999

Renal MR angiography at 1.0 T: three-dimensional (3D) phase-contrast techniques versus gadolinium-enhanced 3D fast low-angle shot breath-hold imaging.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic usefulness of three different MR angiographic techniques at 1.0 T. SUBJECTS AND METHODS: In 22 patients with renal artery stenosis confirmed at intraarterial catheter angiography, we also performed unenhanced and gadolinium-enhanced three-dimensional phase-contrast MR angiography and gadolinium-enhanced single breath-hold three-dimensional fast low-angle shot MR angiography. We determined circulation time to optimize signal acquisition in gadolinium-enhanced breath-hold MR angiography after bolus injection of contrast material. RESULTS: Sensitivity, defined as the detection of a hemodynamically significant stenosis (>50% luminal narrowing), was 85% for enhanced phase-contrast MR angiography, 91% for gadolinium-enhanced MR angiography, and 95% for unenhanced phase-contrast MR angiography. The combination of unenhanced phase-contrast MR angiography and gadolinium-enhanced MR angiography yielded 100% sensitivity for hilar artery stenoses. There were 13 false-positive findings with unenhanced phase-contrast MR angiography, 10 with enhanced phase-contrast MR angiography, and four with gadolinium-enhanced MR angiography (specificity: 38%, 52%, and 79%, respectively). Accessory renal arteries were not seen on unenhanced or enhanced phase-contrast MR angiography (0/8 patients) but were detected with gadolinium-enhanced MR angiography in five of the eight patients. Interobserver agreement (kappa = .62) was best with gadolinium-enhanced MR angiography. The quality of the images was unsatisfactory for adequate evaluation of segmental renal arteries with all three MR angiographic techniques. CONCLUSION: A combination of unenhanced phase-contrast MR angiography and gadolinium-enhanced MR angiography at 1.0 T proved useful as a screening protocol for renal artery stenosis.

Adult↗
PubMed1999

Prostate cancer risk assessment program. A model for the early detection of prostate cancer.

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.

Humans↗
PubMed1999

Exploring family relationships in cancer risk counseling using the genogram.

OBJECTIVES: The genogram is a tool that has facilitated counseling in family therapy and social work for many years. It is hypothesized that genograms may also be useful in genetic counseling, because they help the counselor to acquire more objective and consistent information from the client, as well as to incorporate family dynamics and psychosocial issues into the counseling approach. MATERIALS AND METHODS: A pilot study of genograms used as an adjunct to genetic counseling was performed at Fox Chase Cancer Center's Family Risk Assessment Program. A questionnaire was developed to elicit genograms from 38 women at risk for familial breast and/or ovarian cancer. After standard pedigree expansion, a series of questions was asked about the consultand's relationship with other family members, communication patterns within the family, attitudes toward genetic testing, family reactions to cancer, roles individuals play in the family, and significant historical or anniversary events. Relationships were defined by the consultand as close, very close, conflictual, fused and conflictual, distant, or estranged. RESULTS: The majority of relationship types reported by 38 individuals was "very close" or "close." Eighty-one % reported having close/very close relationships with their spouses, 83% reported close/very close relationships with their mothers, and 70% reported close/very close relationships with their fathers. The degree of familial cohesion as depicted by the genogram correlates positively with scores obtained on the standardized Social Adjustment Scale Self-Report (P = 0.01). CONCLUSIONS: Given the family-wide implications of genetic testing, the genogram may offer important guidance in family-targeted interventions.

Adult↗
PubMed1999

[The efficacy on natural extrinsic stain of Colgate whitening dentifrice--eight-week study].

OBJECTIVE: To assess the effect on natural extrinsic dental stain by use of a dentifrice containing 1% tetrasodium polyphosphate (TSPP), 7% sodium tripolyphosphate (STPP), 0.243% sodium fluoride and 10% high cleaning silica (HCS) over an eight-week period was compared to a sodium fluoride/silica placebo dentifrice without stain removal ingredients. METHODS: Ninety one subjects were selected and stratified into two balanced groups randomly assigned to use the test dentifrice or the placebo dentifrice. The two groups were well balanced with regard to their mean baseline stain index scores, gender and tobacco habits. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice and a commercially available soft bristled toothbrush. Extrinsic dental stain examinations, which included mean stain area and mean stain intensity, were conducted at baseline, four and eight weeks. The same dental examiner conducted examinations on the subjects at each examination. RESULTS: After eight-week use of their assigned products, those subjects in the TSPP/STPP/HCS dentifrice group demonstrated a statistically significant (P = 0.0001) stain reduction of 37.1%, as compared to the fluoride placebo dentifrice group without stain removal ingredients. CONCLUSION: The use of a dentifrice containing 1% tetrasodium polyphosphate, 7% sodium tripolyphosphate, 0.243% sodium fluoride and 10% high cleaning silica is effective in reducing natural extrinsic dental stain, when compared to a placebo fluoride dentifrice.

Adolescent↗
PubMed1998

Postexposure prophylaxis after nonoccupational HIV exposure: clinical, ethical, and policy considerations.

In the wake of recent breakthroughs in antiviral therapies and Centers for Disease Control and Prevention (CDC) recommendations advocating occupational postexposure prophylaxis (PEP), health care workers are increasingly receiving inquiries about PEP following exposures to the human immunodeficiency virus (HIV) through sex and injection drug use. The probability of HIV transmission by certain sexual or injection drug exposures is of the same order of magnitude as percutaneous occupational exposures for which the CDC recommends PEP. In such cases, if the exposure is sporadic, it seems appropriate to extrapolate from the data on occupational PEP and recommend prophylaxis. However, for individuals with continuing or low-risk exposures, we instead recommend referrals to state-of-the-art risk reduction programs. Clinicians, using local HIV seroprevalence data and their knowledge of transmission probabilities, can help exposed patients make an informed decision regarding PEP. Because of the large number of risky encounters that will not be treated prophylactically, even after significant outreach efforts, public health interventions that emphasize PEP as part of a comprehensive HIV prevention program should be confined to cities with highest HIV prevalences.

Anti-HIV Agents↗
PubMed1998

Retraction.

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

A reversibly unfolding fragment of P22 tailspike protein with native structure: the isolated beta-helix domain.

The homotrimeric tailspike endorhamnosidase of phage P22 has been used to compare in vivo and in vitro folding pathways and the influence of single amino acid substitutions thereon. Its main structural motif, which contains the known folding mutation sites, consists of three large right-handed parallel beta-helices. A thermodynamic analysis of the stability of tailspike is prevented by the irreversibility of unfolding at high temperatures or high concentrations of denaturant, probably due to interdigitation of the domains neighboring the beta-helix. We therefore expressed and isolated a tailspike fragment comprising only its central beta-helix domain (residues 109-544). As shown by equilibrium ultracentrifugation, the isolated beta-helix is a monomer at concentrations below 1 microM and trimerizes reversibly at higher protein concentrations. Both the similarity of fluorescence and CD spectra, compared to the complete protein, and the specific binding and hydrolysis of substrate suggest a nativelike structure. Moreover, urea denaturation transitions of the beta-helix domain are freely reversible, providing the basis for a future quantitative analysis of the effects of the folding mutations on the thermodynamic stability of the domain and of structural features responsible for folding and stability of the parallel beta-helix motif in general.

Bacteriophage P22↗
PubMed1998

The G protein-coupled receptor kinase 2 is a microtubule-associated protein kinase that phosphorylates tubulin.

The G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase that phosphorylates and desensitizes agonist-occupied G protein-coupled receptors (GPCRs). Here we demonstrate that GRK2 is a microtubule-associated protein and identify tubulin as a novel GRK2 substrate. GRK2 is associated with microtubules purified from bovine brain, forms a complex with tubulin in cell extracts, and colocalizes with tubulin in living cells. Furthermore, an endogenous tubulin kinase activity that copurifies with microtubules has properties similar to GRK2 and is inhibited by anti-GRK2 monoclonal antibodies. Indeed, GRK2 phosphorylates tubulin in vitro with kinetic parameters very similar to those for phosphorylation of the agonist-occupied beta2-adrenergic receptor, suggesting a functionally relevant role for this phosphorylation event. In a cellular environment, agonist occupancy of GPCRs, which leads to recruitment of GRK2 to the plasma membrane and its subsequent activation, promotes GRK2-tubulin complex formation and tubulin phosphorylation. These findings suggest a novel role for GRK2 as a GPCR signal transducer mediating the effects of GPCR activation on the cytoskeleton.

Animals↗
PubMed1998

Receptor-coupled phospholipase C and adenylyl cyclase function with different calcium pools in astrocytes.

Astrocytes express phospholipase C (PLC)-coupled metabotropic glutamate receptors (only mGluR5 is detectable) and adenylyl cyclase (AC)-linked beta-adrenergic receptors. Calcium-sensitive effector enzymes are associated with these signal transduction pathways, but the relevant calcium compartments involved were found to be different. mGluR5-linked PLC responded primarily to extracellular Ca2+, suggesting a close spatial relation between the enzyme and Ca2+ entry channels. On the other hand, the calcium-inhibited AC associated with beta-adrenergic receptors was sensitive to intracellular Ca2+ selectively accessible to intracellular Ca2+ chelation. Furthermore, cAMP formation induced by direct activation of AC by forskolin was less responsive to intracellular Ca2+ chelation than that evoked by the receptor-activated AC, raising the possibility of selective access of the receptor to a pool of calcium-inhibited AC and/or the calcium modulation of some components of the coupling pathway.

Adenylyl Cyclases↗