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Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Weight loss is correlated with an improved lipoprotein profile in obese postmenopausal women.

BACKGROUND: Changes in plasma lipid and lipoprotein distributions that occur after menopause increase the risk of cardiovascular disease in women, especially in those who are overweight. OBJECTIVE: The purpose of this study was to evaluate the impact of a nine-month weight reduction program on plasma lipids, dietary intake and abdominal fat obesity. DESIGN: A partial crossover design was used to study a weight loss treatment consisting of Phentermine hydrochloride (Fastin, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) therapy plus a low energy diet (5040 kJ/d). Forty-seven obese, postmenopausal Caucasian women (BMI of 30-38 kg/m2) were randomized into two groups, both of which received drug and diet treatment over six months. However, Group I started the intervention program three months later than Group II. Plasma total, HDL and LDL cholesterol and triacylglycerol were measured, body composition was assessed by anthropometry and dual energy x-ray absorptiometry, and food frequency records were collected at four timepoints. RESULTS: Over nine months, women in Group II reduced body weight (14.4%), lowered plasma concentrations of LDL cholesterol (14% to 26%) and triacylglycerol (15%) and raised plasma HDL cholesterol concentration (15%). These plasma lipid changes decreased the total cholesterol/HDL cholesterol ratio from 4.3 to 3.2. All subjects decreased abdominal fat measurements and energy and cholesterol intakes, as well as percentage of energy derived from total and saturated fat during the study. Most subjects also increased dietary fiber consumption. CONCLUSION: Both weight loss and diet modifications are associated with an improved plasma lipid profile in obese postmenopausal women.

Adult↗
PubMed2000

Pharmacologic profile of perphenazine's metabolites.

The authors have previously reported that in elderly patients treated with low doses of perphenazine, few extrapyramidal symptoms (EPS) developed in those who were not poor CYP2D6 metabolizers. The authors hypothesized that this atypical side effect profile is due to perphenazine's principal metabolite, n-dealkylperphenazine (DAPZ), which is usually present in vivo at concentrations 1.5 to 2 times that of the parent drug. Perphenazine, DAPZ, and 7-hydroxyperphenazine affinities were examined in vitro by competition-binding analysis to isolated human receptors expressed in transfected cell lines. Perphenazine and metabolite effects were examined in vivo in 54 older patients who were treated with perphenazine, at a target dose of 0.1 mg/kg, for 10 to 17 days. Drug concentrations were determined by high-performance liquid chromatography with electrochemical detection. In in vitro binding studies, DAPZ demonstrated a higher affinity for serotonin-2A receptors than for dopamine-2 receptors to an extent comparable to that of some atypical neuroleptic agents. In contrast, perphenazine and 7-hydroxyperphenazine demonstrated a higher affinity for dopamine-2 receptors than for serotonin-2A receptors. The mean +/- SD concentrations in the 54 subjects were the following: perphenazine, 1.5 +/- 1.4 ng/mL; DAPZ, 2.0 +/-1.6 ng/mL; and 7-hydroxyperphenazine, 0.8 +/- 1.9 ng/mL. The mean +/- SD quotient for the DAPZ/perphenazine concentration was 1.7 +/- 1.1 and for the 7-hydroxyperphenazine/perphenazine was 0.54 +/-1.6. EPS onset was not correlated with the perphenazine concentration, the metabolite concentrations, the DAPZ/perphenazine quotient, or the 7-hydroxyperphenazine/perphenazine quotient. Despite a moderately atypical receptor-binding profile, DAPZ does not seem to moderate perphenazine effects in vivo in older patients. This outcome likely reflects the low potency of DAPZ for dopamine-2 and serotonin-2A receptors relative to the potency of perphenazine for these receptors. Further exploration of atypical properties of DAPZ should include de novo administration of this metabolite in animal models.

Aged↗
PubMed2000

Comparison of Cryptosporidium parvum viability and infectivity assays following ozone treatment of oocysts.

Several in vitro surrogates have been developed as convenient, user-friendly alternatives to mouse infectivity assays for determining the viability of Cryptosporidium parvum oocysts. Such viability assays have been used increasingly to determine oocyst inactivation following treatment with chemical, physical, or environmental stresses. Defining the relationship between in vitro viability assays and oocyst infectivity in susceptible hosts is critical for determining the significance of existing oocyst inactivation data for these in vitro assays and their suitability in future studies. In this study, four viability assays were compared with mouse infectivity assays, using neonatal CD-1 mice. Studies were conducted in the United States and United Kingdom using fresh (<1 month) or environmentally aged (3 months at 4 degrees C) oocysts, which were partially inactivated by ozonation before viability and/or infectivity analyses. High levels of variability were noted within and between the viability and infectivity assays in the U.S. and United Kingdom studies despite rigorous control over oocyst conditions and disinfection experiments. Based on the viability analysis of oocyst subsamples from each ozonation experiment, SYTO-59 assays demonstrated minimal change in oocyst viability, whereas 4',6'-diamidino-2-phenylindole-propidium iodide assays, in vitro excystation, and SYTO-9 assays showed a marginal reduction in oocyst viability. In contrast, the neonatal mouse infectivity assay demonstrated significantly higher levels of oocyst inactivation in the U.S. and United Kingdom experiments. These comparisons illustrate that four in vitro viability assays cannot be used to reliably predict oocyst inactivation following treatment with low levels of ozone. Neonatal mouse infectivity assays should continue to be regarded as a "gold standard" until suitable alternative viability surrogates are identified for disinfection studies.

Animals↗
PubMed2000

Impulsivity.

Disorders characterized by impulsivity include disorders of impulse control (intermittent explosive disorder, pyromania, kleptomania, pathological gambling and trichotillomania), paraphilias, sexual impulsions and sexual addictions and impulsive aggression personality disorders (borderline, antisocial, histrionic and narcissistic personality disorders). Impulsivity has a substantial impact on both individuals and society. Impulse control disorders may be conceptualized as a subset of the obsessive-compulsive spectrum. In this article, we examine the genetic and neurobiological aetiology of these disorders and possible treatment options. The link between serotonergic dysfunction and the pathophysiology of impulsivity is discussed, and studies that examine the efficacy of various selective serotonin reuptake inhibitors and other alternatives in the treatment of impulsive disorders such as pathological gambling, sexual addictions and borderline personality disorder are presented.

Disruptive, Impulse Control, and Conduct Disorders↗
PubMed2000

Hidden Markov models of minimally invasive surgery.

A crucial process in surgical education is to evaluate the level of surgical skills. For laparoscopic surgery, skill evaluation is traditionally preformed subjectively by experts grading a video of a procedure performed by a student. By its nature, this process is preformed using fuzzy criteria. The objective of the current study was to develop and assess a skill scale using Discrete Hidden Markov Models (DHMM). Ten surgeons (5 Novice Surgeons--NS; 5 Expert Surgeons--ES) performed a cholecystectomy and Nissen fundoplication in a porcine model. An instrumented laparoscopic grasper equipped with a three-axis force/torque sensor was used to measure the forces/torques at the hand/tool interface synchronized with a video of the tool operative maneuvers. A synthesis of frame-by-frame video analysis and a vector quantization algorithm, defined force/torque signatures for 14 types of tool/tissue interactions. From each step of the surgical procedures, two DHMM were developed representing the performance of 3 surgeons randomly selected from the 5 in the ES and NS groups. The data obtained by the remaining 2 surgeons in each group were used for evaluating the performance scale. The final result was a surgical performance index which represented a ratio of statistical similarity between the examined surgeon's DHMM and the DHMM of NS and ES. The difference between the performance index value, for a surgeon under study, and the NS/ES boundary, was considered to indicate the level of expertise in the surgeon's own group. Using this index, 87.5% of the surgical procedures were correctly classified into the NS and ES groups. The 12.5% of the procedures that were misclassified were preformed by the ES and classified as NS. However, in these cases the performance index values were very close to the NS/ES boundary. Preliminary data suggest that a performance index based on DHMM and force/torque signatures provides an objective means of distinguishing NS from ES. In addition this methodology can be further applied to evaluate haptic virtual reality surgical simulators for improving realism in surgical education.

Animals↗
PubMed1999

Performances of hill-type and neural network muscle models-toward a myosignal-based exoskeleton.

Muscle models are the essential components of any musculoskeletal simulation. In addition, muscle models which are incorporated in neural-based prosthetic and orthotic devices may significantly improve their performance. The aim of the study was to compare the performances of two types of muscle models in terms of predicting the moments developed at the human elbow joint complex based on joint kinematics and neuromuscular activity. The performance evaluation of the muscle models was required to implement them in a powered myosignal-driven exoskeleton (orthotic device). The experimental setup included a passive exoskeleton capable of measuring the joint kinematics and dynamics in addition to the muscle myosignal activity (EMG). Two types of models were developed and analyzed: (i) a Hill-based model and (ii) a neural network. The task, which was selected for evaluating the muscle models performance, was the flexion-extension movement of the forearm with a hand-held weight. For this task the muscle model inputs were the normalized neural activation levels of the four main flexor-extensor muscles of the elbow joint, and the elbow joint angle and angular velocity. Using this inputs, the muscle model predicted the moment applied on the elbow joint during the movement. Results indicated a good performance of the Hill model, although the neural network predictions appeared to be superior. Relative advantages and shortcomings of both approaches were presented and discussed.

Arm↗
PubMed1999

Research potential of a unique xenograft model of human proliferative breast disease.

A workshop on the 'Research potential of a unique xenograft model of human proliferative breast disease' was held at the Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, in November of 1998. The accumulated information and current experimental findings on the MCF10AT model of preneoplastic, proliferative breast disease were reviewed. Discussions focused on the relevance of the model to clinical breast cancer and on the most profitable lines of further research to strengthen its utility.

Animals↗
PubMed1999

Force controlled and teleoperated endoscopic grasper for minimally invasive surgery--experimental performance evaluation.

Minimally invasive surgery generates new user interfaces which create visual and haptic distortion when compared to traditional surgery. In order to regain the tactile and kinesthetic information that is lost, a computerized force feedback endoscopic surgical grasper (FREG) was developed with computer control and a haptic user interface. The system uses standard unmodified grasper shafts and tips. The FREG can control grasping forces either by surgeon teleoperation control, or under software control. The FREG performance was evaluated using an automated palpation function (programmed series of compressions) in which the grasper measures mechanical properties of the grasped materials. The material parameters obtained from measurements showed the ability of the FREG to discriminate between different types of normal soft tissues (small bowel, lung, spleen, liver, colon, and stomach) and different kinds of artificial soft tissue replication materials (latex/silicone) for simulation purposes. In addition, subjective tests of ranking stiffness of silicone materials using the FREG teleoperation mode showed significant improvement in the performance compared to the standard endoscopic grasper. Moreover, the FREG performance was closer to the performance of the human hand than the standard endoscopic grasper. The FREG as a tool incorporating the force feedback teleoperation technology may provide the basis for application in telesurgery, clinical endoscopic surgery, surgical training, and research.

Algorithms↗
PubMed1999

Design of conditionally active STATs: insights into STAT activation and gene regulatory function.

The STAT (signal transducer and activator of transcription) signaling pathway is activated by a large number of cytokines and growth factors. We sought to design a conditionally active STAT that could not only provide insight into basic questions about STAT function but also serve as a powerful tool to determine the precise biological role of STATs. To this end, we have developed a conditionally active STAT by fusing STATs with the ligand-binding domain of the estrogen receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are estrogen-inducible transcription factors that retain the functional and biochemical characteristics of the cognate wild-type STATs. In addition, these tools have allowed us to evaluate separately the contribution of tyrosine phosphorylation and dimerization to STAT function. We have for the first time provided experimental data supporting the model that the only apparent role of STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is sufficient to unmask a latent STAT nuclear localization sequence and induce nuclear translocation, sequence-specific DNA binding, and transcriptional activity.

Binding Sites↗
PubMed1999

Surgeon-tool force/torque signatures--evaluation of surgical skills in minimally invasive surgery.

The best method of training for laparoscopic surgical skills is controversial. Some advocate observation in the operating room, while others promote animal and simulated models or a combination of surgical related tasks. The mode of proficiency evaluation common to all of these methods has been subjective evaluation by a skilled surgeon. In order to define an objective means of evaluating performance, an instrumented laparoscopic grasper was developed measuring the force/torque at the surgeon hand/tool interface. The measured database demonstrated substantial differences between experienced and novice surgeon groups. Analyzing forces and torques combined with the state transition during surgical procedures allows an objective measurement of skill in MIS. Teaching the novice surgeon to limit excessive loads and improve movement efficiency during surgical procedures can potentially result in less injury to soft tissues and less wasted time during laparoscopic surgery. Moreover the force/torque database measured in this study may be used for developing realistic virtual reality simulators and optimization of medical robots performance.

Algorithms↗
PubMed1999

Utility of intracardiac echocardiography (ICE) in electrophysiology: ICEing the CAKE (catheter ablation knowledge enhancement).

PURPOSE: Previous studies have demonstrated the utility of intracardiac echocardiography (ICE) during electrophysiologic procedures including radiofrequency catheter ablation. The purpose of this study was to analyze the initial learning experience with ICE during invasive electrophysiologic procedures. METHODS: During a 1-month ICE trial, patients scheduled for radiofrequency catheter ablation underwent concurrent imaging using a 9 French, 9 MHz catheter in the right atrium proximal to important endocardial structures and diagnostic/ablation catheters. The procedure length, fluoroscopy and ICE times were systematically recorded during each procedure. In addition, the images were analyzed and recorded and their utility was evaluated after each case. A case control analysis was also performed. RESULTS: Seven patients underwent ICE (as part of an ICE trial period) during their electrophysiology study between July 21 and August 13, 1998. This study demonstrated the utility of ICE in identifying radiofrequency catheter tip stability and intracardiac and endocardial structures, including the crista terminalis, coronary sinus, and foramen ovale. CONCLUSION: ICE contributes to the electrophysiology arsenal for both diagnostic and therapeutic procedures. In particular, this technique demonstrated a decrease in fluoroscopy time as compared to a case control population. This technique limits radiation to the patient and operator. In addition, endocardial structures, which may be pivotal in diagnosing and treating cardiac arrhythmias, were easily identified. Radiofrequency catheter stability can also be assessed with this technique.

Adult↗
PubMed1998

Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A.

Postsynaptic density-93 (PSD-93)/Chapsyn-110 is a member of the membrane-associated guanylate kinase (MAGUK) family of PDZ domain-containing proteins. MAGUKs are widely expressed in the brain and are critical elements of the cytoskeleton and of certain synapses. In the ultrastructural studies that are described here, PSD-93 localizes to both postsynaptic densities and dendritic microtubules of cerebellar Purkinje neurons. The microtubule localization is paralleled by a high-affinity in vivo interaction of PSD-93 via its guanylate kinase (GK) domain with microtubule-associated protein 1A (MAP1A). GK domain truncations that mimic genetically identified mutations of a Drosophila MAGUK, discs-large, disrupt the GK/MAP-1A interaction. Additional biochemical experiments demonstrate that intact MAGUKs do not bind to MAP1A as effectively as do isolated GK domains. This appears to be attributable to an intramolecular inhibition of the GK domain by the PDZs, because GK binding activity of full-length MAGUKs is partially restored by a variety of PDZ ligands, including the C termini of NMDA receptor 2B, adenomatous polyposis coli (APC), and CRIPT. Beyond demonstrating a novel cytoskeletal link for PSD-93, these experiments support a model in which intramolecular interactions between the multiple domains of MAGUKs regulate intermolecular associations and thereby may play a role in the proper targeting and function of MAGUK proteins.

Animals↗
PubMed1998

A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see commetns].

A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.

Animals↗
PubMed1998

Cognitive and motor slowing in Alzheimer's disease and geriatric depression.

While response slowing on psychological tasks is a symptom of both depression and Alzheimer's disease (AD), the underlying mechanisms may be quite different: a slowing of cognitive processing in AD and a motor retardation in depression. This hypothesis was tested by examining the rate at which participants performed a simple cognitive operation: subvocal pronunciation. Participants were shown words of between one and three syllables and were asked to decide whether each word ended in a particular sound. This task required participants to transform the written word into its phonological representation, an operation thought to involve subvocal pronunciation. Decision time rose linearly with the number of syllables in all three subject groups. The linear function of the AD patients had a significantly greater slope, indicating a slower rate of subvocal pronunciation, whereas the slope was the same for the normal old and depressed. Both the depressed and AD patients had a higher intercept than the normal old, suggesting a sensorimotor slowing. After treatment, the intercept of the linear function for depressed patients fell, but there was no change in the slope. Thus, this study suggests that AD produces a slowing in both cognitive and motor processes, whereas depression results solely in a motor retardation.

Aged↗