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M Rosenfeld

Publications and source records attributed to M Rosenfeld.

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

A computational fluid dynamic model of antigen-antibody surface adsorption on a piezoelectric immunosensor.

A novel computational fluid dynamic model describing the antigen-antibody binding on an electrode surface is presented. It was assumed that the adsorption rate of the antibody sample is dependent upon the flow field in the vicinity of the electrode. Numerical solution of the steady flow in a two-dimensional triangular cell using the Navier-Stokes equations was carried out for predicting mass adsorption on the surface of the crystal. The relationships between the mass adsorbed over the area surface of the electrode, the kinetics of the binding process, and the flow field were determined. The effect of the inlet conditions (location, velocity magnitude, and direction) on the time constant of the mass adsorption process was investigated. It was found that the time constant was decreased by moving the inlet near the edge of the crystal or increasing the normal to the boundary component of the velocity. These changes may significantly reduce the time needed to conduct the test.

Adsorption↗
PubMed1999

Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo : possible mechanisms for gender differences in atherosclerosis.

The mechanism by which estrogens protect against atherosclerosis is not known. We evaluated in vivo whether there is a gender difference in monocyte adhesion and subendothelial migration in hypercholesterolemic rabbits and whether any gender differences observed are due to estradiol. Monocyte adhesion and subendothelial migration were assessed in a blinded fashion by analyzing a standardized segment of aorta using a scanning electron microscope. We also assessed whether estradiol modulates induction of vascular cell adhesion molecule-1 (VCAM-1) protein using Western blot and flow cytometric analyses. We observed that male rabbits develop more monocyte adhesion and subendothelial migration than do female rabbits during hypercholesterolemia. We also observed that oophorectomized rabbits given physiological estradiol supplementation demonstrate fewer adherent and subendothelial monocytes than do oophorectomized rabbits given placebo. VCAM-1 protein expression was increased in aortae obtained from hypercholesterolemic, oophorectomized animals supplemented with placebo, and this increase was attenuated by estradiol. Finally, in cultured rabbit aortic endothelial cells stimulated with lysophosphatidylcholine, we observed an increase in VCAM-1 protein that was inhibited in a concentration-dependent fashion by estradiol. We have demonstrated in vivo that there is a gender difference in monocyte adhesion to endothelial cells and transendothelial migration after hypercholesterolemia and that this gender difference is due in part to estradiol. Our results also suggest that estradiol inhibits monocyte adhesion by inhibiting expression of VCAM-1.

Animals↗
PubMed1999

Evaluation of impedance technique for detecting breast carcinoma using a 2-D numerical model of the torso.

Previous experimental studies showed that significant changes occur in the electrical properties of breast cancer tissue compared to the surrounding normal tissue. This phenomenon motivated studies on cancer detection using electrical impedance techniques. In the present study, a two-dimensional model of the torso and a numerical method were used to investigate the changes in the potential distribution as a result of a malignant tissue present in the breast. A transverse MRI image of the woman's torso was scanned. Noise reduction and contour-following algorithms were applied to differentiate between eight compartments in the torso. The extracted tissue types were lungs, blood, ribs, bone marrow of the cord, breast fat, skin, skeletal muscle, and heart muscle. Isotropic homogeneous conductivity was assigned to each one of these compartments. The volume conductor problem was solved numerically using the finite volume method to determine the potential distribution developed due to the dipole source. Cases without and with artificially inserted malignant region with realistic sizes were examined to investigate the sensitivity of impedance techniques to detect breast cancer. Significant changes were detected in the potential distribution inside the volume conductor as a result of the realistic size of breast tumors. A linear relation was found between the surface potential in the vicinity of the tumor region and the size of the tumor. For a small malignant area of 0.22 cm2, the surface potential near the tumor region decreased only slightly from a value of 13.81 mV in the normal case to 13.67 mV (0.14 mV change; 1.0%). For a larger malignant area of 5.43 cm2, the potential decrease was more pronounced, 11.29 mV (2.52 mV change; 18.3%), indicating that realistic sizes of breast tumor result in significant changes in the surface potential. Thus, impedance techniques employed in the present study show very good promise in detecting breast cancer.

Algorithms↗
PubMed1999

Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis.

The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age. For predicting any growth of Pseudomonas aeruginosa (Pa) from the lower airway in subjects </=18 months of age (mean age, 8 +/- 5 months), OP cultures had a sensitivity of 44% (95% CI 14%, 79%), specificity of 95% (90%, 99%), positive predictive value of 44% (14%, 79%), and negative predictive value of 95% (90%, 99%). Diagnostic accuracy was similar for Haemophilus influenzae (Hi). Specificity was significantly lower for Staphylococcus aureus (Sa). Sensitivity for all organisms improved if a positive lower airway culture was defined as >/=10(3) or >/=10(5) cfu/mL. Specificity for Pa declined significantly with increasing age. In children with CF <5 years of age, the specificity and negative predictive value of OP cultures for Pa are high, while the sensitivity and positive predictive value are poor. Thus, in this age range, a negative throat culture is helpful in "ruling out" lower airway infection with Pa. However, a positive culture does not reliably "rule in" the presence of Pa in the lower respiratory tract. These findings may have implications for study design and interpretation as well as clinical management of young children with CF.

Bacterial Infections↗
PubMed1999

Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease.

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.

Aged↗
PubMed1999

Nutritional effects of long-term gastrostomy feedings in children with cystic fibrosis.

OBJECTIVE: To analyze the long-term nutritional effects of supplemental gastrostomy feedings in undernourished patients with cystic fibrosis. DESIGN: Longitudinal, retrospective assessment of anthropometric measures before and for up to 4 years after gastrostomy. SUBJECTS/SETTING: All patients at a large cystic fibrosis care center who underwent gastrostomy between 1980 and 1993 when they were at least 1 year old and were followed up for a minimum of 1 year after gastrostomy. STATISTICAL ANALYSES PERFORMED: The Mann-Whitney U test was used to compare anthropometric values measured during 4 postgastrostomy time intervals with values measured during the year preceding gastrostomy. RESULTS: The 21 patients ranged in age from 1.1 to 20.8 years (median age = 7.4 years). They had mild to moderate malnutrition at the time of gastrostomy. Patients were followed up for a mean of 39 months after gastrostomy. Supplemental feedings were associated with significant improvements in weight and height percentiles for age, and in weight as a percentage of ideal weight. Improvement in weight occurred earlier than improvement in height. Among subjects followed up for at least 18 months after gastrostomy, median weight percentile for age increased from 2% for the year before gastrostomy to 12% for the period 6 to 18 months after gastrostomy (P < .001) and 19% for the period 30 to 48 months after gastrostomy (P = .002 compared with before gastrostomy). Other nutritional parameters followed similar, although less dramatic patterns. Gastrostomy feedings were well tolerated and associated with only minor complications. CONCLUSIONS: Long-term gastrostomy feedings appear to be a safe and effective means of improving nutrition in malnourished patients with cystic fibrosis. Clinical dietitians should function as care managers for patients with cystic fibrosis who are receiving supplemental gastrostomy feedings.

Adolescent↗
PubMed1998

Neuronal molecular mimicry in immune-mediated neurologic disease.

Molecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody-mediated immune responses to shared viral-host antigens have been associated with the development of disease in these patients. Patients infected with human T-lymphotropic virus type I (HTLV-I) develop HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody-mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV-I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33-kd band in all HAM/TSP patients tested. By contrast, no neuron-specific IgG reactivity could be demonstrated from HTLV-I seronegative controls and, more important, from HTLV-I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV-I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV-I tax (an immunodominant HTLV-I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV-I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV-I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV-I, suggesting viral-specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP.

Autoimmune Diseases↗
PubMed1998

The forced expiratory volume-time curve estimation using the electrocardiogram.

The feasibility of estimating the forced expiratory volume-time curve from the amplitude modulation of the electrocardiogram was studied using a numerical torso model and ECG signal processing. A two dimensional numerical model of the torso was solved for the maximum expiration and inspiration to study the changes in the surface potential as a result of changes in the lung volume. The numerical model showed that significant changes in the surface potential amplitude occur between maximum inspiration and maximum expiration and that this amplitude change in the left-right axis of the torso might be three times as large as in the front-back axis. In the experimental setup, ECG waveforms from the surface of the chest and the mouth air flow were simultaneously recorded from four male subjects during several forced vital capacity (FVC) maneuvers. The amplitude of the QRS complex was measured for different expired lung volumes and an estimation of the forced expiratory volume-time curve was obtained. The FVC and the FEV1 (forced expiratory volume after 1 s) spirometry indices were calculated for the two volume-time curves obtained from the electrocardiogram and from the spirometry measurements. The results differ between 0.1 and 0.8 1. These preliminary results are encouraging and might indicate that a relationship between the volume-time curve during FVC test and the electrocardiogram signals does exist. Further validation in a larger number of subjects and patients is needed before the technique can be applicable for clinical use.

Adult↗
PubMed1998

Home nebulizer use among patients with cystic fibrosis.

OBJECTIVE: To describe current patterns of home nebulizer use among patients with cystic fibrosis. STUDY DESIGN: A population-based survey of home nebulizer practices among 227 patients with cystic fibrosis using nebulizers from 1993 to 1994 (Objective 1), and a prospective study of "typical" home use, including testing of performance and bacterial cultures in nebulizers after use, completed by 36 subjects (Objective 2). RESULTS: Objective 1: 85% of subjects reported using jet and 8% ultrasonic nebulizers (categories not mutually exclusive); 15% used unknown brands. Most jet nebulizers were disposable models, which were used for > 14 days by more than half the subjects. Mixing of medications in a single treatment (other than cromolyn and a bronchodilator) was reported by 28% of patients. Objective 2: no apparent deterioration in aerosol particle size or output rate of returned nebulizers compared with new units was observed. Staphylococcus aureus was cultured from 55% and Pseudomonas aeruginosa from 35% of returned nebulizers. Concordance between nebulizer and sputum cultures was poor. CONCLUSIONS: Although not generally tested for reusability, disposable nebulizers are generally used by patients for long periods. Medication mixing is common, although its effects on aerosol properties are unknown. Cystic fibrosis respiratory pathogens are frequently isolated from used nebulizers. Patient guidelines for home nebulizer use need to be established.

Child↗
PubMed1998

Design, synthesis and biological evaluation of nonpeptide integrin antagonists.

Recent studies demonstrated that peptide and antibody antagonists of integrin alpha v beta 3 block angiogenesis and tumor growth. In this article, the design, synthesis and biological evaluation of a series of nitroaryl ether-based, nonpeptide mimetics are described. The design of these compounds was based on Merck's arylether/alpha-aminoacid/guanidine framework and incorporates a novel nitroaryl system. The synthesized mimetics were tested against a variety of integrins (alpha v beta 3, alpha IIb beta 3, and alpha v beta 5) in order to determine their binding selectivity and ability to inhibit cell adhesion. Selected compounds were also tested for their ability to inhibit angiogenesis in vivo in the CAM (chick chorioallantoic membrane) assay. From the generated compound library, compounds 16 and 19 proved to be potent and selective inhibitors of alpha IIb beta 3 (IC50 = 14 nM) whereas compound 11 showed excellent in vivo inhibition of angiogenesis (at 30 micrograms/embryo).

Allantois↗
PubMed1997

Gender gap in cystic fibrosis mortality.

The authors conducted the largest study to date of survival in cystic fibrosis. The study cohort consisted of all patients with cystic fibrosis seen at Cystic Fibrosis Foundation-accredited care centers in the United States between 1988 and 1992 (n = 21,047), or approximately 85% of all US patients diagnosed with cystic fibrosis. Cox proportional hazards regression analysis was used to compare the age-specific mortality rates of males and females and to identify risk factors serving as potential explanatory variables for the gender-related difference in survival. Among the subjects 1-20 years of age, females were 60% more likely to die than males (relative risk = 1.6, 95% confidence interval 1.4-1.8). Outside this age range, male and female survival rates were not significantly different. The median survival for females was 25.3 years and for males was 28.4 years. Nutritional status, pulmonary function, and airway microbiology at a given age were strong predictors of mortality at subsequent ages. Nonetheless, differences between the genders in these parameters, as well as pancreatic insufficiency, age at diagnosis, mode of presentation, and race, could not account for the poorer survival among females. Even after adjustment for all these potential risk factors, females in the age range 1-20 years remained at greater risk for death (relative risk = 1.6, 95% confidence interval 1.2-2.1). The authors concluded that in 1- to 20-year-old individuals with cystic fibrosis, survival in females was poorer than in males. This "gender gap" was not explained by a wide variety of potential risk factors.

Adolescent↗
PubMed1997

Gene therapy and ovarian cancer: a review.

OBJECTIVE: To provide the obstetrician-gynecologist with the basic concepts of gene therapy, an overview of cancer gene therapy treatment strategies, and a summary of currently approved human gene therapy protocols for ovarian carcinoma. DATA SOURCES: A computerized search of articles published through December 1995 was performed on the MEDLINE data base. Additional sources were identified through cross-referencing. METHODS OF STUDY SELECTION: All identified references were reviewed with particular attention to their relevance to gene therapy for ovarian cancer. TABULATION, INTEGRATION, AND RESULTS: Each reference was reviewed to determine the relevant contribution to the fundamental science of gene therapy. Particular attention was paid to those studies that offered a rational strategy that might contribute to therapy for ovarian malignancy. CONCLUSION: Advances in molecular biology, immunology, and virology have enabled the concept of gene therapy for neoplastic disorders to become a reality. Given the lack of effective conventional therapy, those patients with recurrent or refractory ovarian cancer should be considered for currently approved investigational gene therapy protocols.

Adjuvants, Immunologic↗
PubMed1997

Defective adenoassociated viral-mediated transfection of insulin gene by direct injection into liver parenchyma decreases blood glucose of diabetic mice.

The present study assessed the feasibility of transferring the insulin gene into liver cells of diabetic individuals using a defective adenoassociated viral (AAV) vehicle. AAV offers several advantages over other viral vectors, since this vehicle can facilitate transfection in vivo without cell division and without any viral coding sequences (thus minimizing inflammation). The rat insulin gene and lacZ were each packed into a defective AAV vehicle (AAV-INS and AAV-lacZ, respectively). Successful AAV-mediated transfection and expression of lacZ into hepatocytes in primary cell culture were demonstrated by chemiluminescent assay of beta-galactosidase. Similarly, AAV-mediated transfection and expression of the insulin gene into hepatocytes was demonstrated by immunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). After AAV-mediated transfection of the insulin gene into hepatocytes, glucose in the medium was significantly reduced for up to 5 days. After direct injection of AAV-INS into liver parenchyma of diabetic mice, successful transfection was demonstrated by RT-PCR, and blood glucose was significantly decreased for at least 6 days. These studies suggest that the AAV vector may be used to transfer the insulin gene into liver cells in vitro and in vivo.

Animals↗
PubMed1996

In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase.

Rab8 is a small GTP-binding protein that plays a role in vesicular transport from the trans-Golgi network to the basolateral plasma membrane in polarized epithelial cells (MDCK), and to the dendritic surface in hippocampal neurons. As is the case for most other rab proteins, the precise molecular interactions by which rab8 carries out its function remain to be elucidated. Here we report the identification and the complete cDNA-derived amino acid sequence of a murine rab8-interacting protein (rab8ip) that specifically interacts with rab8 in a GTP-dependent manner. Rab8ip displays 93% identity with the GC kinase, a serine/threonine protein kinase recently identified in human lymphoid tissue that is activated in the stress response. Like the GC kinase, rab8ip has protein kinase activity manifested by autophosphorylation and phosphorylation of the classical serine/threonine protein kinase substrates, myelin basic protein and casein. When coexpressed in transfected 293T cells, rab8 and the rab8ip/GC kinase formed a complex that could be recovered by immunoprecipitation with antibodies to rab8. Cell fractionation and immunofluorescence analyses indicate that in MDCK cells endogenous rab8ip is present both in the cytosol and as a peripheral membrane protein concentrated in the Golgi region and basolateral plasma membrane domains, sites where rab8 itself is also located. In light of recent evidence that rab proteins may act by promoting the stabilization of SNARE complexes, the specific GTP-dependent association of rab8 with the rab8ip/GC kinase raises the possibility that rab-regulated protein phosphorylation is important for vesicle targeting or fusion. Moreover, the rab8ip/GC kinase may serve to modulate secretion in response to stress stimuli.

Amino Acid Sequence↗
PubMed1996

Alpha interferon-2b, leucovorin, and 5-fluorouracil (ALF) in non-small cell lung cancer.

Eighteen patients with non-small cell lung cancer (NSCLC) who had previously received no systemic chemotherapy, were treated on this phase II study with interferon-alfa-2b 8 MU tiw, leucovorin 500 mg/m2 IVPB over 2 hours and 5-Fluorouracil 500 mg/m2 i.v. for 6 weeks followed by a 2-week rest. There were was no rest period for interferon. Median age of patients on this study was 63 years. Fatigue, nausea, and diarrhea were the most common toxicities. There were no grade IV toxicities and no treatment-related deaths. Seven partial responses (39%) with median duration of 4.5 months were seen. An additional patient has had stable disease/minor response for 12+ months. Median survival is 10 months. ALF has activity in NSCLC.

Adult↗
PubMed1996

Numerical solution of the potential due to dipole sources in volume conductors with arbitrary geometry and conductivity.

The integral conservation equation for biological volume conductors with general geometry and arbitrary distribution of electrical conductivity is solved using a finite volume method. An effective conductivity was defined for the boundaries between regions with abrupt change of the conductivity to allow the simultaneous solution of the entire domain although the derivatives are not continuous. The geometrical singularities arising from the spherical topology of the coordinate system are removed using the conservation law. The resulting finite volume solution method is efficient both in central processing unit (CPU) time and memory requirements, allowing the solution of the volume conductor equation using a large number of mesh points (of the order of 10(5)) even on small workstations (like SGI Indigo). It results in very accurate solutions, as several comparisons with analytical solutions of head models reveal. The proposed finite volume method is an attractive alternative to the finite element and boundary element methods that are more common in bioelectric applications.

Anisotropy↗