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Biomedical subjects

J W Stevens

Publications and source records attributed to J W Stevens.

At least 19 recordsLinked to original sources
PubMed2002

Dynamic modelling of a challenge-escalation cross-over study of treatment of capsaicin-induced coughing.

In a complex seven-period cross-over trial to study the effects of a drug in attenuating capsaicin-induced coughing, counts of numbers of coughs were recorded 32 times in each period. Subjects were subjected to four escalating levels of capsaicin at each of one and five hours after treatment, with counts of coughs being recorded in four one-minute intervals at each level. Such longitudinal count studies often show considerable individual variability about any regression curve that might be fitted. We develop a non-linear autoregressive model for such count data that also allows for overdispersion.

Adrenergic beta-Agonists↗
PubMed2002

Bayesian methods for design and analysis of cost-effectiveness trials in the evaluation of health care technologies.

We review the development of Bayesian statistical methods for the design and analysis of randomized controlled trials in the assessment of the cost-effectiveness of health care technologies. We place particular emphasis on the benefits of the Bayesian approach; the implications of skew cost data; the need to model the data appropriately to generate efficient and robust inferences instead of relying on distribution-free methods; the importance of making full use of quantitative and structural prior information to produce realistic inferences; and issues in the determination of sample size. Several new examples are presented to illustrate the methods. We conclude with a discussion of the key areas for future research.

Arthritis↗
PubMed2001

Bayesian cost-effectiveness analysis from clinical trial data.

A key tool for assessing the relative cost-effectiveness of two treatments in health economics is the incremental C/E acceptability curve. We present Bayesian computations for this curve in the case where data on both costs and efficacy are available from a clinical trial. Analysis is given under various formulations of prior information. A case study is analysed in which reasonable prior information is shown to strengthen substantially the posterior inference, leading to a more conclusive assessment of cost-effectiveness. Calculations can be performed using readily available Bayesian software.

Anti-Asthmatic Agents↗
PubMed2001

A framework for cost-effectiveness analysis from clinical trial data.

We present a general Bayesian framework for cost-effectiveness analysis (CEA) from clinical trial data. This framework allows for very flexible modelling of both cost and efficacy related trial data. A common CEA technique is established for this wide class of models through linking mean efficacy and mean cost to the parameters of any given model. Examples are given in which efficacy may be measured as a continuous, binary, ordinal or time-to-event outcome, and in which costs are modelled as distributed normally, log-normally, as a mixture or non-parametrically. A case study is presented, illustrating the methodology and illuminating the role of prior information.

Bayes Theorem↗
PubMed2001

The social ecology of the co-occurrence of substance use and early coitus among poor, urban black female adolescents.

Currently, the profession of social work has proclaimed the need for an empirical research agenda to broaden its knowledge base. The profession's positivists rightly argue that a sound knowledge base is derived from rigorous scientific empirical methods. Unquestionably, the profession's unique contribution to the study of human development has been its emphasis on environmental effects and individual adaptation. Presently, social scientists embrace an ecological perspective when studying how social environmental effects are mediated. As researchers shift to a social ecological perspective, an empirical contextual model will allow the study of racial/ethnic differences in the incidence of adolescent problem behaviors (Stevens, 1998). An examination of the social ecology of poor, urban black female adolescents was undertaken to examine claims of the co-occurrence of early coitus and substance use, behaviors evident in black adolescents. An ecological framework operationalized by the constructs structural strain, kinscriptions, and community bridging is used to explicate how coital behavior among black females may not co-occur with drug use. The article's exegesis is directed by four postulates that help clarify the relationship of social ecology to the linkage of early coital behavior and substance use. The article concludes with adolescent narratives that illumine the cogency of the ecological analysis.

Adolescent↗
PubMed2000

CD44 expression in the developing and growing rat intervertebral disc.

CD44 has been identified at the time of extracellular matrix formation and expansion in several sites of the developing embryo (Wheatley et al. [1993] Development 119:295-306). The nucleus pulposus, consisting of a hydrated extracellular matrix tissue at birth, not previously closely analyzed, was examined for expression of CD44 in the developing and aging rat intervertebral disc. CD44 was identified solely on notochordal cells from the first onset of intervertebral disc formation (day 15 embryo) through the loss of notochordal cells from the nucleus pulposus (12-24 months of age). No CD44 expression was found in the notochordal cells prior to disc formation or in any cells other than the notochordal cells in the annulus fibrosus or nucleus pulposus of the intervertebral disc. Using reverse transcriptase-polymerase chain reaction methodology, the single 365 amino acid CD44 standard, CD44s, open reading frame was amplified from notochordal cells isolated from the nucleus pulposus. Western blot analysis of a cultured nucleus pulposus notochordal cells total protein extract identified a single CD44 species devoid of chondroitin sulfate with a mass of approximately 85 kDa, characteristic of CD44s. Cell surface detection for CD44 was co-localized with hyaluronan and proteoglycans at first appearance of disc formation in the nucleus pulposus.

Animals↗
PubMed2000

Teenage parents and welfare reform: findings from a survey of teenagers affected by living requirements.

An important component of welfare reform aimed at minor teenage parents is a requirement that the teenager live in an appropriate living situation, typically with a parent or guardian. The State of Massachusetts developed Teen Living Programs as an alternate living arrangement for minor teenage parents receiving welfare who are unable to live with family members. This article reports on a survey of 199 teenage parents who lived in the Teen Living Programs. Three research questions were asked: Who are the teenagers served by these programs? What services were provided? To what extent have teenagers attained key outcomes? Outcomes measured included educational attainment, employment, welfare status, homelessness, and subsequent pregnancy. Implications for social policy, further program development, and clinical intervention are discussed.

Adolescent↗
PubMed2000

Inference for the cost-effectiveness acceptability curve and cost-effectiveness ratio.

The aim of this article is to consider Bayesian and frequentist inference methods for measures of incremental cost effectiveness in data obtained via a clinical trial. The most useful measure is the cost-effectiveness (C/E) acceptability curve. Recent publications on Bayesian estimation have assumed a normal posterior distribution, which ignores uncertainty in estimated variances, and suggest unnecessarily complicated methods of computation. We present a simple Bayesian computation for the C/E acceptability curve and a simple frequentist analogue. Our approach takes account of errors in estimated variances, resulting in calculations that are based on distributions rather than normal distributions. If inference is required about the C/E ratio, we argue that the standard frequentist procedures give unreliable or misleading inferences, and present instead a Bayesian interval.

Antirheumatic Agents↗
PubMed1999

A 14-year experience with 6 cm as a criterion for surgical treatment of abdominal aortic aneurysm.

BACKGROUND: It remains unclear when to recommend operation for an asymptomatic abdominal aortic aneurysm (AAA). This study examined a prospective series of patients for whom standard criteria were applied. METHODS: Some 584 consecutive patients with an AAA of diameter 3 cm or greater detected by ultrasonographic screening have been observed for up to 14 years. Repeat ultrasonographic examinations have been performed at intervals. Surgery was not considered unless the aneurysm measured 6 cm in diameter, expanded at a rate equivalent to at least 1 cm per year, caused the patient symptoms, or an iliac aneurysm was present that required treatment. RESULTS: Operation was performed on 127 patients; the majority (80; 63 per cent) had an aneurysm that reached 6 cm in diameter. Use of the above criteria prevented rupture in all but 24 (4 per cent) of the 584 patients over the 14-year interval. Of these 24 patients, 11 were unfit for planned surgery and eight declined operation or follow-up. Rupture in the five remaining patients (1 per cent) who were available for treatment compared favourably with the reported 30-day mortality rate for elective surgical treatment of 1.4-12 per cent. CONCLUSION: Repeated observation is preferable to surgical intervention until an aortic aneurysm measures 6 cm in diameter, expands by 1 cm per annum or causes symptoms. Presented as a poster to the 52nd Annual Meeting of the Society for Vascular Surgery, San Diego, California, USA, June 1998

Aged↗
PubMed1999

Pseudoachondroplastic dysplasia: an Iowa review from human to mouse.

Lamellar inclusions of the rough endoplasmic reticulum in growth plate chondrocytes, first identified (1972) in the Department of Orthopaedic Surgery, University of Iowa, has become the cytochemical hallmark for the pseudoachondroplastic dysplasia (PSACH) phenotype, linking an endoplasmic reticulum storage disorder with the osteochondrodysplasia. Since this original observation, great advances have been made, leading to the molecular understanding of this altered longitudinal bone growth anomaly. A PSACH canine model suggested that abatement of cumulative vertical growth of growth plate chondrocytes seen in PSACH results from (1) altered extracellular matrix constraints for horizontal growth and (2) uncoupling of endochondral and perichondral growth that causes metaphyseal flaring. PSACH, an autosomal dominant disease, is linked to mutation of the cartilage oligomeric matrix protein (COMP) gene. Amino acid substitutions, deletions, or additions is proposed to alter COMP structure that cause its retention in the rough endoplasmic reticulum of growth plate chondrocytes, leading to (1) compositional and structural change of the extracellular matrix, and (2) altered cellular proliferation and volume expansion. Normal growth and development occurs in COMP gene knockout mice that do not synthesis COMP, demonstrating that a mutant COMP, not absence of COMP, is required for the PSACH phenotype. The mechanism by which mutant COMP induces a PSACH phenotype remains to be elucidated. At the University of Iowa a cell culture system has been developed whereby mutant COMP transgenes are introduced into chondrocytes and the expressed product COMP is retained in the endoplasmic reticulum. This readily manipulated system makes it possible to decipher systematically the system's cellular secretory processing pathway, in order to clarify the mechanism(s) by which the mutant COMP is retained within the endoplasmic reticulum. Concurrent with this is the development of transgenic mice expressing the mutant COMP used in the cell culture system. This will make it possible to establish that expression of a human PSACH-linked mutant COMP will produce a PSACH phenotype. A PSACH animal model will provide a means to characterize the mechanism of altered longitudinal bone growth and to test gene therapy approaches for correcting the anomaly.

Animals↗
PubMed1998

Spatial and temporal expression of CD44 isoforms in the developing and growing joints of the rat limb.

Hyaluronan is an integral component of proteoglycan-rich extracellular matrices such as hyaline cartilage. Hyaluronan is commonly found in embryonic tissue and is important in the formation of hydrated matrices that allow cellular expansion and migration. Cell surface hyaluronan-binding proteins such as CD44 are presumed to be important in the cellular interactions with hyaluronan in both of these processes. The primary aim of this study was to document the spatial and temporal expressions of CD44 isoforms during the development and growth of the diarthrodial joints of rat limbs. With use of in situ hybridization and immunohistochemistry, the CD44s isoform is selectively identified as localized to a single cell layer on opposing sides of the joint at the first appearance of joint cavitation (on the 18th day of gestation). After joint formation in the neonate, the expression of the CD44s isoform in the cells at the joint surface is lost. These findings suggest that the CD44s isoform has a role in the development of the diarthrodial joint, presumably through interaction with hyaluronan.

Animals↗
PubMed1996

Expression of CD44 isoforms in human prostate tumor cell lines.

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.

Animals↗
PubMed1996

Spatial distribution of CD44 and hyaluronan in the proximal tibia of the growing rat.

CD44 has been described as a cell surface hyaluronan receptor present on a variety of different cells, and it is generally assumed to be prevalent in most connective tissues that contain hyaluronan. A major aim of this study was to test that presumption by localizing CD44 and hyaluronan within several tissues of the proximal tibia of the growing rat. Comparison of these profiles would reveal whether CD44 and hyaluronan co-localize with high fidelity, as would be expected if CD44 were a major hyaluronan binding protein. Using in situ hybridization and immunohistochemistry, CD44 was identified on osteoclasts, chondroclasts, osteocytes, hematopoietic marrow cells, synovial cells, and connective tissue fibroblasts (ligaments, tendons, and fascia). Although the majority of osteocytes expressed CD44, reduced expression was observed for osteoblasts and ostcoprogenitor cells. Additionally. CD44 was not detected on chondrocytes from epiphyseal and metaphyseal growth cartilages or in meniscal fibrocartilage. Using biotinylated G1 domain from aggrecan and link protein, hyaluronan was observed in the maturational and hypertrophic zones of all growth cartilages, the synovium and other fibroblastic connective tissues, regional areas of the periosteum and endosteum (around osteoblasts, osteoprogenitor cells, and osteoclasts), osteocyte lacunae, and surrounding blood vessels. In regions of co-localization for CD44 and hyaluronan, it seems that CD44 is a likely hyaluronan binding protein in several tissues of the proximal tibia. However, it does not appear to be the predominant hyaluronan binding protein in growing cartilages of the weanling rat.

Aggrecans↗
PubMed1995

Cellular deformation reversibly depresses RT-PCR detectable levels of bone-related mRNA.

Osteoblastic cells respond to mechanical stimuli with alterations in proliferation and/or phenotypic expression. In some cases, these responses occur within only a few applications of stimuli (i.e. 'cycle-dependent trigger response') rather than in a dose-dependent manner. To explore potential mechanisms of the cycle dependent trigger response, we raised the following questions: (1) Does strain of bone cells alter gene expression; if so, how quickly does it occur and how long does it last? (2) Are alterations in message level strain magnitude dependent? (3) Are alterations in steady-state message levels cycle dependent? Cultures were evaluated for osteocalcin mRNA one week following a daily stretch application at four stretch magnitudes and four cycle numbers and compared to nonstretched controls. Steady state mRNA message was ascertained prior to and at 10, 20, 30, 60, 120, 180, and 240 min following initiation of stretch. Following mRNA isolation, first strand cDNA synthesis was performed and fluorometrically quantitated. A reverse transcriptase based PCR (RT-PCR) approach allowed assessment of osteocalcin mRNA levels from microcultures (50,000 cells per 10 microliters culture or 5000 cells mm2) of rat calvarial osteoblasts. Optimized PCR was performed using primers to the bone specific protein, osteocalcin (OC) and two 'housekeeping' genes, beta-actin and GAP-DH. PCR products were separated on 4% agarose gels and band intensities digitized with relative quantitation based on internal standards in each gel. The lowest magnitude of stretch (- 1 KPa) at 1800 cycles per day reproducibly depressed message for osteocalcin, but not beta-actin when assayed immediately following the cessation of strain application. By three hours following the initiation of stretch, message levels returned to control values. At the time of stretch cessation, the 1800 cycle stretch regimen diminished (p < 0.0001) steady-state osteocalcin message independently of the four stretch magnitudes. Stretch for 300 cycles failed to depress (p = 0.05) osteocalcin message cultures at any time, but 600 cycles depressed message by 30 min. By one and two hours, cultures stretch 600, 900, and 1800 cycles showed similar levels of message depression. Four hours following the initiation of stretch, message levels returning to nonstrained levels in all groups. We conclude that alterations in cell response to strain are in part mediated by gene expression, that alterations last 3-4 h in this system, and that the message mechanism itself exhibits a trigger-response dependency to cycle number.

Actins↗
PubMed1994

Recombinant and native zymogen forms of human complement factor D.

We have expressed a full-length cDNA clone encoding human factor D by using a baculovirus expression system. The purified recombinant protein reacted with Ab against native factor D, but was hemolytically inactive and slightly larger than factor D. These results suggested that the recombinant protein was the elusive zymogen of factor D. Amino acid sequencing demonstrated that the recombinant factor D consisted of two proenzyme forms with respective activation peptides, AAPPRGR and APPRGR. Catalytic amounts of trypsin converted recombinant profactor D to its enzymatically active form, exhibiting SDS-PAGE mobility and specific hemolytic activity similar to those of native factor D. About 90% of trypsin-activated recombinant profactor D had the same NH2-terminus as factor D. Human thrombin, kallikrein, and plasmin could also activate recombinant profactor D, but relatively high concentrations of these enzymes were required and the specific hemolytic activity of the "activated" profactor D was about one-third that of native factor D. Trypsin-activatable profactor D was also purified from the urine of a patient with Fanconi's syndrome. This native profactor D represented less than 1.0% of the total antigenic factor D in the patient's urine and had a Gly-Arg dipeptide as the activation peptide. Apparently, urine profactor D was produced by cleavage of pre-profactor D at Arg-(-3) by a serine protease with trypsin-like specificity, which probably is different from the putative leader peptidase that produces the recombinant profactor D. Urine profactor D was inhibited by diisopropyl fluorophosphate although the recombinant proenzyme was resistant to this inhibitor.

Amino Acid Sequence↗
PubMed1992

Isolation and characterization of bovine gingival proteoglycans versican and decorin.

1. We have isolated, chemically and immunologically characterized versican and decorin from bovine gingiva. 2. Versican was of large molecular weight and the molecular size of the core protein was estimated to be greater than 200 kDa. 3. The glycosaminoglycan chains were susceptible to chondroitinase ABC and N-linked oligosaccharides were present on the protein core of the molecule. 4. Immunological studies provided evidence that a hyaluronic acid binding region was present in the core protein of versican. 5. The overall structure was similar to that of versican isolated from bovine sclera. 6. Decorin had a molecular weight of 102 kDa and its glycosaminoglycan chain was completely digested by specific glycosidases. 7. The partially deglycosylated core protein had a molecular weight of 55 kDa and N-linked oligosaccharides were present on the molecule.

Amino Acids↗