PubMed Health⌕ Search

Biomedical subjects

S Hubbard

Publications and source records attributed to S Hubbard.

At least 19 recordsLinked to original sources
PubMed2005

A fully Bayesian model to cluster gene-expression profiles.

MOTIVATION: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes in a genome can be simultaneously monitored over a time-course or under different experimental conditions. After proper normalization of the data, genes are often classified into co-expressed classes (clusters) to identify subgroups of genes that share common regulatory elements, a common function or a common cellular origin. With most methods, e.g. k-means, the number of clusters needs to be specified in advance; results depend strongly on this choice. Even with likelihood-based methods, estimation of this number is difficult. Furthermore, missing values often cause problems and lead to the loss of data. RESULTS: We propose a fully probabilistic Bayesian model to cluster gene-expression profiles. The number of classes does not need to be specified in advance; instead it is adjusted dynamically using a Reversible Jump Markov Chain Monte Carlo sampler. Imputation of missing values is integrated into the model. With simulations, we determined the speed of convergence of the sampler as well as the accuracy of the inferred variables. Results were compared with the widely used k-means algorithm. With our method, biologically related co-expressed genes could be identified in a yeast transcriptome dataset, even when some values were missing. AVAILABILITY: The code is available at http://genome.tugraz.at/BayesianClustering/

Algorithms↗
PubMed2003

Technology failure analysis: understanding why a diabetes management tool developed for a Personal Digital Assistant (PDA) didn't work in a randomized controlled trial.

Managing Type 1 Diabetes Mellitus is a challenging feat especially for young patients. It is a tedious and demanding disease which requires painful self-monitoring and injections multiple times per day. Many patients are unable to achieve good blood sugar control, in spite of strong evidence that good control leads to better outcomes. Many caregivers believe that more communication between caregivers and patients could lead to better control. This paper describes a tool that was developed to improve communication between caregivers and patients, its testing, how it failed to achieve its outcomes and recommendations for improvement.

Blood Glucose Self-Monitoring↗
PubMed2001

Hyaluronate receptors mediating glioma cell migration and proliferation.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

Antibodies, Monoclonal↗
PubMed2000

Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases.

A series of new 3-substituted indolin-2-ones containing a tetrahydroindole moiety was developed as specific inhibitors of receptor tyrosine kinases associated with VEGF-R, FGF-R, and PDGF-R growth factor receptors. These compounds were evaluated for their inhibitory properties toward VEGF-R2 (Flk-1/KDR), FGF-R1, PDGF-Rbeta, p60(c)()(-)()(Src)(), and EGF-R tyrosine kinases and their ability to inhibit growth factor-dependent cell proliferation. Structure-activity relationships of this new pharmacophore have been determined at the level of kinase inhibition. Compounds containing a propionic acid moiety at the C-3' position of the tetrahydroindole ring represented the most potent indolin-2-ones to inactivate the VEGF, FGF, and PDGF receptor kinases. The inhibitory activities of 9d against VEGF-R2 (Flk-1), 9h against FGF-R1, and 9b against PDGF-Rbeta were 4, 80, and 4 nM, respectively. However, all of these compounds were inactive when tested against the EGF-R tyrosine kinase. Compounds 9a and 9b represented the most potent inhibitors of these classes to inhibit both biochemical kinase and growth factor-dependent cell proliferation for these three targets. In addition, compound 9a was cocrystallized with the catalytic domain of FGF-R1 providing evidence to explain the structure-activity relationship results. This study has provided evidence to support the potential of these new tyrosine kinase inhibitors for the treatment of angiogenesis and other growth factor-related diseases including human cancers.

Animals↗
PubMed1999

Level of education and injecting drug use among African Americans.

Drawing upon a nationally representative survey sample of African American (AA) drug injectors and non-injectors, this study tests for a suspected causal association between dropping out of school and the occurrence of injecting drug use (IDU), which remains a major cause of human immunodeficiency virus (HIV) transmission in this population. The data are from public use files of the National Household Surveys on Drug Abuse (NHSDA) conducted between 1991 and 1995. From within the NHSDA's nationally representative sample of adult household residents, a total of 389 AA adults with a history of IDU were matched on neighborhood of residence with 2253 AA adults with no history of IDU. The conditional form of multiple logistic regression was used to estimate the relative risk of having injected a drug for school dropouts relative to a reference category of AA who received the high school diploma but did not go to college. AAs who dropped out of high school were an estimated two times more likely to have injected drugs. With statistical adjustment for age, sex, and Hispanic background, the estimated association was 1.9 (95% confidence interval (C.I.) = 1.3-2.6, P<0.001). Contrary to our advance hypothesis, earning the graduate equivalency certificate (GED) did not seem to affect the magnitude of excess risk for having started IDU (adjusted odds ratio (aOR) = 2.3, 95% C.I. = 1.4-3.8, P<0.001). Hence, school dropout prevention might reduce the risk of IDU per se, in addition to the many other general benefits of educational attainment. The issue of GED-associated reduced risk of IDU remains open for future study.

Adolescent↗
PubMed1996

Expression of stromelysin 1 in human astrocytoma cell lines.

In a wide variety of tumor types, the expression of stromelysin 1 which is one of the matrix metalloproteinases (MMPs) has been shown to correlate with tumor invasion. However, little is known about the distribution of stromelysin in human brain tumors. We have previously shown that a correlation exists between the type IV collagenases, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 transcripts and in vitro invasiveness among 7 human astrocytoma cell lines. In the present study, we analyzed the expression of stromelysin 1 among the same panel of human astrocytoma cell lines and human fibroblasts by northern blot analyses and in situ hybridization. Northern blot analysis demonstrated that SF-126 and U87 MG expressed high level stromelysin 1 transcripts. Following heat shock stimulation, the stromelysin 1 transcript was up-regulated in U87 MG astrocytoma cells. In situ hybridization analysis showed specific intracytoplasmic localization of mRNA for stromelysin in these astrocytoma cell lines. By casein zymography, we have determined that both SF-126 and U87 MG secreted stromelysin 1 protein. We conclude that stromelysin 1 is expressed by certain human astrocytoma cell lines, and this study confirms the importance of continuing to characterize the proteolytic enzyme profile of these tumors to fully understand the molecular mechanisms involved in astrocytoma invasiveness.

Astrocytoma↗
PubMed1996

Inducible expression of glial fibrillary acidic protein in HT-1080 human fibrosarcoma cells.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed almost exclusively by glial cells of the central nervous system. We have previously transfected GFAP-negative human astrocytoma cells with the gene for GFAP and have demonstrated that GFAP transfection decreases astrocytoma proliferation and alters astrocytoma morphology. To determine if the same cellular responses could be elicited upon GFAP transfection of nonglial tumor cells, in the present study we have transfected a GFAP-negative human malignant fibrosarcoma cell line (HT-1080) with a cDNA containing the entire coding sequence of the human GFAP gene under the control of an inducible metallothionein promoter. Stably transfected HT-1080 clones were identified that are GFAP-positive by PCR and immunocytochemistry. GFAP-positive HT-1080 fibrosarcoma cells also demonstrate a decrease in tumor cell proliferation, altered morphological features characterized by cell elongation and cytoplasmic process formation, and reduction of invasive potential when compared to controls. These findings suggest that the inducible expression of the cytoskeletal protein GFAP can also be associated with dramatic cellular effects in nonglial non-central nervous system tumor cells.

Agar↗
PubMed1995

Design and synthesis of 1-heteroaryl-3-(1-benzyl-4-piperidinyl)propan-1-one derivatives as potent, selective acetylcholinesterase inhibitors.

Herein is described the synthesis and structure--activity relationship of a novel series of aromatic and heteroaromatic 3-(1-benzyl-4-piperidinyl)propan-1-one derivatives that display potent and selective inhibition of the enzyme acetylcholinesterase (AChE). 1-(2-Methyl-6-benzothiazolyl)-3-(N-benzyl-4-piperidinyl)propan-1-one hydrochloride, 6d, is one of the most active compounds within this series exhibiting an IC50 for the inhibition of the AChE enzyme equal to 6.8 nM. Compound 6d has shown a dose-dependent elevation of total acetylcholine (ACh) levels in the mouse forebrain with an oral ED50 = 9.8 mg/kg. In addition, in vivo microdialysis experiments in the rat demonstrate that 6d increases extracellular ACh (100% over basal) 1-3 h postdose with an oral ED50 = 4.8 mg/kg.

Animals↗
PubMed1995

Proximal femoral focal deficiency: results of rotationplasty and Syme amputation.

We reviewed the results of treatment of sixteen patients who had had an isolated unilateral proximal femoral focal deficiency; nine were managed with a rotationplasty and seven, with a Syme amputation combined with an arthrodesis of the knee. We evaluated the perceived physical appearance, gross motor function, and metabolic energy expended in walking. The mean duration of follow-up was 9.9 years (range, four to fourteen years). The mean age of the patients at the time of the study was 13.9 years (range, eight to 18.4 years) in the rotationplasty group and 14.8 years (range, 9.5 to 19.9 years) in the Syme-amputation group. There were three female patients in each group. Roentgenograms showed that the femoral head was in the acetabulum (Aitken class A or B) in four of the seven patients in the Syme-amputation group and in five of the nine patients in the rotationplasty group; the remaining patients did not have this finding (Aitken class C or D). There was no difference in gross motor function or perceived physical appearance between the groups. Rotationplasty was associated with a more energy-efficient gait (mean, 0.153 milliliter of oxygen per kilogram-meter [range, 0.128 to 0.173 milliliter of oxygen per kilogram-meter] than was Syme amputation (mean, 0.169 milliliter of oxygen per kilogram-meter [range, 0.151 to 0.182 milliliter of oxygen per kilogram-meter]). Both types of treatment resulted in a net oxygen utilization per distance (efficiency) that was less than the values reported after amputations performed for non-congenital disorders.

Activities of Daily Living↗
PubMed1993

Drug analysis in fly larvae.

We reared larvae of Calliphora vicina on human skeletal muscle obtained from cases of suicidal overdose with co-proxamol (propoxyphene and acetaminophen) and amitriptyline. After 4 days, third-instar larvae were either transferred to drug-free muscle or continued to feed on drug-laden muscle for a further 2 days prior to harvesting. Amitriptyline and nortriptyline were detected in both groups of larvae, but propoxyphene was only in those fed continuously on drug-laden muscle, and acetaminophen was in neither. Drug concentrations in muscle food source were amitriptyline 0.48 microgram/g, nortriptyline 0.38 microgram/g, propoxyphene 0.99 microgram/g, and acetaminophen 14.13 micrograms/g. For triplicate rearings, the mean ratios of drug concentrations in larvae to food source were amitriptyline, 0.56; nortriptyline, 0.5; and propoxyphene, 0.06. In triplicate rearings, no drug or metabolite was detected in puparia, puparial cases, or imagos. We conclude that the absence of a drug in maggots is not necessarily an indication that the drug was not present in significant concentrations in the food source. The malpighian tubules and the "nephrocytes" of fly larvae appear capable of eliminating different drugs with varying efficiency.

Acetaminophen↗
PubMed1992

Double gloving. Protecting surgeons from blood contamination in the operating room.

Health care workers, particularly surgeons, understand the importance of preventing contamination from blood of patients infected with deadly viruses. One of the most common areas of contamination is the hands and fingers due to the failure of glove protection. There are varying opinions regarding the frequency of glove failure, the necessity of wearing two gloves for added protection, and the ability to operate when wearing two gloves. We performed a prospective, randomized, trial of 143 procedures involving 284 persons to answer these questions for surgeons and first assistants. Overall, the glove failure rate (blood contamination of the fingers) was 51% when one glove was worn and 7% when two gloves were worn. Acceptability was 88% in the group who agreed to wear two gloves, and 88% of these did not perceive that tactile sense was significantly impaired. We believe that double gloving should be, and can be, used routinely during major surgical procedures to protect surgeons from blood contamination.

Blood↗
PubMed1992

In-use evaluation of surgical gowns.

Surgical gowns must protect patients from the bacteria of operating room personnel and also protect staff members from the lethal viruses in the blood of patients. The current study was done to evaluate the barrier function of several surgical types of gowns during use in surgical procedures and identify the frequency of failure of the gowns and some causes for this failure. We performed direct observation of 234 operations during which the surgeon and the first assistant wore 535 gowns. Blood strikethrough occurred most often when contamination on the outside of the gown was heavy (20 per cent), but still occurred after medium (7 per cent) and small (1 per cent) contamination. We found significant differences between gowns based on the material used and the design of the gowns. Gowns reinforced with a second layer of material or a layer of plastic material were more effective at preventing strikethrough than a single layer of material. One gown was identified that was unacceptable for any use in the operating room. Gowns of different designs and degrees of protection should be chosen based on the body area likely to be exposed to blood and the amount of predicted blood contamination. Further improvement in gown materials and design are required, since surgeons cannot consider any of these gowns protective during strenuous use.

Blood↗
PubMed1991

History of clinical trials.

Advances in medical treatments have occurred because of the application of new knowledge gained from clinical experiments conducted over the last 250 years. New sources of compounds with anti-tumor activity in human cancer are constantly under investigation. The development of a new drug is a complex process: screening, formulation, production, toxicology studies, FDA approval, and evaluation in phase I, II, and III clinical trials.

Antineoplastic Agents↗
PubMed1991

Risk of blood contamination and injury to operating room personnel.

The potential for transmission of deadly viral diseases to health care workers exists when contaminated blood is inoculated through injury or when blood comes in contact with nonintact skin. Operating room personnel are at particularly high risk for injury and blood contamination, but data on the specifics of which personnel are at greater risk and which practices change risk in this environment are almost nonexistent. To define these risk factors, experienced operating room nurses were employed solely to observe and record the injuries and blood contaminations that occurred during 234 operations involving 1763 personnel. Overall 118 of the operations (50%) resulted in at least one person becoming contaminated with blood. Cuts or needlestick injuries occurred in 15% of the operations. Several factors were found to significantly alter the risk of blood contamination or injury: surgical specialty, role of each person, duration of the procedure, amount of blood loss, number of needles used, and volume of irrigation fluid used. Risk calculations that use average values to include all personnel in the operating room or all operations performed substantially underestimate risk for surgeons and first assistants, who accounted for 81% of all body contamination and 65% of the injuries. The area of the body contaminated also changed with the surgical specialty. These data should help define more appropriate protection for individuals in the operating room and should allow refinements of practices and techniques to decrease injury.

Blood↗
PubMed1991

Standards of care: integrating nursing care plans and quality assurance activities.

Traditionally, standards are used to define the level of care that a patient can expect to receive in a given institution or on a given nursing unit. These standards are the foundation of quality assurance programs. Unfortunately, with the increased emphasis on monitoring care, many standards are being written after the quality assurance activities have been developed and are in place. Often, standards are placed neatly in a book that is dusted off and brought out when the Joint Commission for Accreditation of Healthcare Organizations representative (JCAHO) visits. The nursing staff at the unit level has no real knowledge or understanding of the standards. This may result in a nonfunctioning quality assurance program.

Humans↗
PubMed1990

Hepatic ultrasonic tissue characterization of video image data.

A study measuring in vivo three quantitative parameters of human liver was performed to assess the feasibility of measuring these parameters using standard ultrasound equipment and technique and to evaluate their potential for diagnosing diffuse liver disease. The parameters measured were: (1) d-bar, the average scatter spacing between semiperiodic scatterer; (2) r, a measure of the relative scattering strength; and (3) sigma, a measure of the variability in the relative scattering strength. Using linear discriminant and multivariate analysis, the above parameters are able to significantly separate normal livers from those with cirrhosis. This technique shows promise in the clinical identification of diffuse liver disease.

Humans↗
PubMed1990

Modified Van Nes rotationplasty for osteosarcoma of the proximal tibia in children.

Above-knee amputation has been the traditional treatment for osteosarcoma of the proximal tibia. Recent advances in chemotherapy have encouraged the development of limb-salvage techniques. Van Nes rotationplasty for malignant lesions of the distal femur has increased in popularity as a reconstructive technique, but no similar procedure has been described for lesions of the proximal tibia. We have developed a modified rotationplasty for this lesion and have performed it in four children. The surgical technique, postoperative management and results of the procedure are described. Two patients had delayed wound healing. No other complications have developed and our patients were disease-free at follow-up, while the appearance of the leg was well accepted by the patients and their parents. This procedure is a useful addition to the armamentarium of the tumour surgeon for the treatment of malignant lesions of the proximal tibia.

Amputation, Surgical↗