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Biomedical subjects

M Rosenfeld

Publications and source records attributed to M Rosenfeld.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of source location on the scalp potential asymmetry in a numerical model of the head.

The correlation between source asymmetry in the brain and the potential amplitude asymmetry on the scalp was studied by a two-dimensional (2-D) numerical model of the head. The model employed computerized tomography (CT) images to define the different compartments of the head. The source was modeled by a dipole layer in the occiput for an occipital source (visual evoked potential generators) or a dipole layer around the cortex representing spontaneous activity generators. The volume conductor equation for the potential distribution was solved numerically using a finite volume method for two CT images; one had relatively symmetric left-right anatomy while the other had a falx deviation of 6 degrees between the occiput and the nasion-inion line. By examining several arrangements of sources, it has been demonstrated that source asymmetry can cause nonnegligible asymmetry in the potential amplitude at the homotopic points on the scalp. This asymmetry, that is not related to real physiologic or psychological origin, should be taken into consideration in any EEG potential distribution analysis.

Body Fluid Compartments↗
PubMed1995

Correlation between skull thickness asymmetry and scalp potential estimated by a numerical model of the head.

The contribution of asymmetric skull thickness to the scalp potential amplitude was investigated numerically. The model consisted of four conductive layers representing the scalp, the skull, the cerebrospinal fluid, and the cortex with a current dipole in the occipital region. The potential created by the dipole was calculated assuming quasistatic formulation and linear media. The governing equation was discretized by the finite volume method to ensure the conservation of fluxes even in regions with abrupt changes of the conductivity. The large set of the algebraic equations for the electric potential was solved iteratively by the successive overrelaxation method. The model confirmed previous experimental studies suggesting that the potential amplitude is 60% smaller on the side with the thicker bone if the asymmetry of the skull thickness exceeds 40%. The model developed suggests that skull thickness asymmetry can create nonnegligible asymmetries in the potential measured on the scalp above homotopic points of the two hemispheres.

Adult↗
PubMed1995

Polarity of secretion of alpha 1-antitrypsin by human respiratory epithelial cells after adenoviral transfer of a human alpha 1-antitrypsin cDNA.

alpha 1-Antitrypsin (alpha AT) deficiency, a hereditary cause of progressive emphysema, can potentially be treated by transfer of a functional human alpha 1AT gene to the respiratory epithelium. For such an approach to be successful, alpha 1AT must be provided to both the interstitium and the epithelial surface--that is, the alpha 1AT directed by the transferred gene must be secreted to both the apical and basolateral surfaces of the epithelial cells. To evaluate this concept, a recombinant, replication-deficient adenoviral vector (Ad-alpha 1AT) containing a human alpha 1AT cDNA driven by an adenovirus major late promoter was used to infect Bet-1A human respiratory epithelial cells. The infected cells expressed Ad-alpha 1AT-directed mRNA transcripts and synthesized and secreted functional human alpha 1AT as shown by [35S]methionine labeling and immunoprecipitation of a 52-kD glycosylated human alpha 1AT molecule capable of interacting with neutrophil elastase, its natural substrate. Bet-1A cells grown on microporous polycarbonate membranes formed tight junctions (resistance > 150 omega x cm2). After infection with Ad-alpha 1AT, [35S]methionine labeling and enzyme-linked immunoassay demonstrated that alpha 1AT was secreted into both the apical and basolateral compartments, with an average apical to basolateral ratio of 1.9 +/- 0.2. Thus, human respiratory epithelial cells infected with a recombinant adenoviral vector containing a human alpha 1AT cDNA secrete alpha 1AT across both the apical and basolateral cell membranes, suggesting that the respiratory epithelium could serve as a target for in vivo gene therapy of alpha 1AT deficiency.

Adenoviridae↗
PubMed1995

Paraneoplastic encephalomyelitis antigens bind to the AU-rich elements of mRNA.

The Hu antigens are composed of a family of neuronal-specific, RNA-binding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drosophila protein required for neuronal development and maintenance. Although the three proteins are very similar in structure, they are differentiated by alternative splicing of their mRNAs. We report here that the Hu antigens bind avidly to the AU-rich element resident in many mRNAs that regulate cell proliferation. This interaction suggests that the Hu antigens promote neuronal differentiation by suppressing the neuroblast cell cycle. Such a mechanism provides a plausible model for the role of the Hu antigens in tumorigenesis, neuronal differentiation, and paraneoplastic neurologic disorders.

Amino Acid Sequence↗
PubMed1994

Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels.

A single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of integrin alpha v beta 3 disrupts ongoing angiogenesis on the chick chorioallantoic membrane (CAM). This leads to the rapid regression of histologically distinct human tumors transplanted onto the CAM. Induction of angiogenesis by a tumor or cytokine promotes vascular cell entry into the cell cycle and expression of integrin alpha v beta 3. After angiogenesis is initiated, antagonists of this integrin induce apoptosis of the proliferative angiogenic vascular cells, leaving preexisting quiescent blood vessels unaffected. We demonstrate therefore that ligation of integrin alpha v beta 3 is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors.

Allantois↗
PubMed1994

Numerical calculation of the potential distribution due to dipole sources in a spherical model of the head.

A three-dimensional spherical model of the head was investigated numerically. The model consists of four conductive layers representing the scalp, the skull, the cerebrospinal fluid, and the cortex with a dipole current source. The potential created by the dipole was calculated using quasistatic formulation and a linear medium. The volume conduction equation was discretized by the finite volume method to ensure the conservation of fluxes and efficient solution method. The large set of algebraic equations for the electric potential was solved iteratively by the successive over relaxation method. The new formulation of the volume conduction problem was validated by comparing the numerical results with two analytical solutions. The first test-case considers a homogeneous spherical model with a dipole in the center. The potential on the outer surface, as well as within the volume conductor, was calculated and very good agreement was obtained with the analytical solution. In the second test-case, the scalp potential due to a radially oriented eccentric dipole in a four concentric spheres model was compared with an analytic solution. It was found that a grid of 90 x 90 x 90 volume elements yielded accurate results on the scalp surface with errors on the order of 1%. The present numerical model can be extended to general cases with any volume conductor shape or with any distribution or orientation of the current dipoles. Compared to other numerical methods, this approach offers enhanced accuracy for given computational resources (both in CPU time and memory). The gain might be more than one order of magnitude, allowing simulation with considerably larger meshes.

Body Surface Area↗
PubMed1994

Persistence of the SV40 early region without expression in permissive simian cells.

SV40 containing recombinant vectors were introduced into permissive simian, non-permissive rodent and semi-permissive human cell lines, and assayed for transformation. All mouse and human cell clones expressed T-antigen (T-Ag) and were morphologically transformed when they contained only the wt T-Ag gene (E-SV40) or the entire wt viral genome with an interrupted late region. However, of 63 simian clones with these recombinant vectors, none became morphologically transformed and T-Ag containing cells were rare or absent. Nearly all simian cell lines made either no detectable early SV40 RNA or only small amounts of viral RNA but contained viral DNA restriction fragments similar to those in the original recombinant vectors. Functional T-Ag genes were recoverable from several cell clones and used to regenerate infectious virus. Hence, T-Ag gene expression had been suppressed. We found two conditions where T-Ag expression was activated. In a BSC-1 cell line containing E-SV40 DNA, subsequent introduction of a vector with a functional viral late coding region (L-SV40) resulted in the appearance of T-Ag and transformation. These findings suggest that L-SV40 sequences activate or enhance T-Ag expression and that this activation requires a functional Vpl gene. We found also, that vectors with E-SV40 DNA from the bipartite variant EL-SV40 consistently transformed simian CV-1 cells. Transformation was shown to be effected by the multiple alterations present in the regulatory region of this variant.

Animals↗
PubMed1994

Mathematical and computer modeling of acute normovolemic hemodilution.

BACKGROUND: Advocates of acute normovolemic hemodilution (ANH) frequently neglect to consider the decreasing hematocrit of the patient during both hemodilution and the subsequent operative procedure and the need to begin transfusion at some minimal hematocrit. STUDY DESIGN AND METHODS: For more accurate prediction of the efficacy of ANH, equations were derived and a computer model developed that allowed accounting for the decreasing hematocrit due to blood loss in an isovolemic patient and calculating the red cell volume on a minute-by-minute basis; the model also began the transfusion of ANH blood on a mL-for-mL basis when the minimal hematocrit was reached and transfused any remaining blood following completion of the case. The red cell volume saved by performing ANH for a given estimated blood volume (EBV) was expressed as either the fraction of the red cell volume of a routinely banked unit of blood (red cells stored in additive solution: volume 350 mL, hematocrit 0.65) or the number of units saved. RESULTS: The number of units saved in a typical example--EBV, 5000 mL; pre-ANH hematocrit, 0.40; minimal hematocrit at which transfusion was begun, 0.25 over a range of estimated blood losses (500-2500 mL); and 1 to 5 ANH units drawn--never exceeded 0.6. Even with extensive hemodilution, as in a child (EBV, 1500 mL; pre-ANH hematocrit, 0.40; minimal hematocrit at which transfusion was begun, 0.15; 5 units drawn; and estimated blood losses, 2500, 1500, and 1000 mL) with a postdilution hematocrit of 0.16, the savings would have been only 0.29, 0.44, and 0.49 units, respectively. CONCLUSION: Because of the decreasing hematocrit in a bleeding isovolemic patient and the need to begin transfusion at some minimal hematocrit, the theoretic savings in red cell volume attributable to ANH is less than had previously been appreciated, and additional ANH does not necessarily result in additional patient benefit.

Blood Transfusion↗
PubMed1994

Mechanism of enhancement of DNA expression consequent to cointernalization of a replication-deficient adenovirus and unmodified plasmid DNA.

Given the knowledge that replication-deficient adenoviruses can mediate the delivery of unlinked plasmid DNA into eukaryotic cells (K. Yoshimura, M. A. Rosenfeld, P. Seth, and R. G. Crystal, J. Biol. Chem. 268:2300-2303, 1993), this study focuses on the role of receptor-mediated endocytosis in this process. AdCFTR (an E1- E3- adenovirus type 5-based replication-deficient adenovirus containing the 4.5-kb human cystic fibrosis transmembrane conductance regulator cDNA) was added to Cos-7 cells together with plasmid pRSVL (containing the Rous sarcoma virus long terminal repeat promoter followed by the luciferase cDNA), and luciferase activity was quantified as a measure of the expression of the plasmid DNA. When AdCFTR was bound to Cos-7 cells at 4 degrees C and the cells were subsequently incubated at 37 degrees C in the presence of pRSVL, the expression of luciferase activity was increased in proportion to the amount of AdCFTR added, reaching > 10(4)-fold at 3,000 PFU per cell. AdCFTR-mediated increase in pRSVL was inhibited by addition of purified adenovirus fiber but not hexon, suggesting cell surface adenovirus receptors were involved in the cointernalization process. Cell lines with a high number of adenovirus receptors (Cos-7 and HeLa) showed significant AdCFTR-dependent pRSVL expression, while cell lines with low numbers of adenovirus receptors (NIH 3T3 and U-937) showed little. AdCFTR-mediated increase in the expression of pRSVL was prevented when AdCFTR was heat treated and exposed to antibody against adenovirus or when the cointernalization process was evaluated in the presence of chloroquine, conditions all known to prevent adenovirus-mediated disruption of endocytic vesicles. In contrast, the uptake of AdCFTR into Cos-7 cells was not affected by any of these conditions. When AdCFTR was exposed to UV light, its ability to grow in 293 cells was obviated, but AdCFTR-dependent increase in pRSVL expression was minimally reduced. Finally, empty capsids of AdCFTR were able to enhance the delivery and expression of plasmid pRSVL into Cos-7 cells, suggesting that the adenovirus genome is not required for AdCFTR-mediated plasmid cointernalization. Together, these observations suggest that the ability of a replication-deficient recombinantly adenovirus to mediate the cointernalization and expression of plasmids is mediated by the receptor-mediated endocytosis pathway.

Adenoviruses, Human↗
PubMed1993

Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms.

Human umbilical vein endothelial cell attachment, spreading and migration on collagen and vitronectin are mediated by integrins alpha 2 beta 1 and alpha v beta 3, respectively, and these events take place in the absence of cytokines, growth factors, or chemoattractants. Cell attachment and spreading on these ligands occur in the absence of extracellular calcium, as does migration on collagen. In contrast, vitronectin-mediated migration is absolutely dependent on the presence of extracellular calcium. Cell contact with immobilized vitronectin or anti-alpha v beta 3 mAbs promotes a measurable rise in [Ca2+]i which requires an extracellular calcium source, whereas collagen, or anti-alpha 2 beta 1 mAbs fail to promote this signaling event. In fact, vitronectin-mediated migration and the rise in intracellular calcium showed the same dose dependence on extracellular calcium. While vitronectin and collagen differ in their ability to induce a calcium influx both ligands or antibodies to their respective integrins promote an equivalent increase in intracellular pH consistent with activation of the Na/H antiporter an event independent of extracellular calcium. These results support two salient conclusions. Firstly, collagen and vitronectin, through their respective integrins, promote distinct intracellular signaling events. Secondly, the alpha v beta 3 specific influx of calcium is not required for cell spreading yet appears to facilitate cellular migration on vitronectin.

Calcium↗
PubMed1992

Evolution of airway microbiology in the infant with cystic fibrosis: role of nonpseudomonal and pseudomonal pathogens.

Bacterial colonization of the airways of the infant with cystic fibrosis is usually established early in life, and, once established, is difficult to eradicate and is associated with progressive lung disease. Thus, understanding of early airway microbiology is critical to the development of appropriate early interventions such as prophylactic antibiotics, immunotherapy, and, potentially, gene therapy. The barriers to the study of infant airway microbiology are discussed, and the properties of infant lung anatomy, physiology, and immunity, which predispose the young patient to serious infection, are reviewed. We examine the natural history of lung infection in young patients, reviewing the roles of each of the main bacterial pathogens. Recent research on risk factors for early Pseudomonas aeruginosa colonization, including the potential role of respiratory viral infections, is discussed. We conclude with a discussion of the role of prophylactic antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1992

Evolving a blueprint for certification: the responsibilities and knowledge comprising American professional oncology nursing practice.

Ensuring adequate content validity of a certification examination is a major concern in the development and administration of a test. To establish content validity of the Oncology Nursing Certification Corporation (ONCC) certification exam, a job analysis study was conducted to provide empirical data about the responsibilities and knowledge areas required for practice at the level of the newly certified oncology nurse. The study involved The Profession of Oncology Nursing: An Inventory of Responsibilities and Knowledge (IRKPON), a questionnaire that was developed based on a review of the literature, professional practice information, interviews with oncology nurses, the original ONCC certification exam table of specifications, and evaluations undertaken by two advisory committees. The IRKPON consisted of three parts: 56 responsibilities clustered into eight job dimensions, 217 knowledge areas grouped into seven knowledge dimensions, and demographic information. The IRKPON was sent to a stratified random sample of 3,000 oncology nurses in the United States, who were asked to rate both the responsibilities and knowledge areas by level of importance. The 1,297 (43%) responding nurses rated 45 of 56 responsibilities (80.4%) as "very important" and 8 of 56 responsibilities (14.3%) as "extremely important"; they also rated 163 of 217 knowledge areas (75.1%) as "very important" and 41 of 217 knowledge areas (18.9%) as "extremely important." These findings identified the specific responsibilities most important to the oncology nurse role at the level of the newly certified nurse, as well as the knowledge areas necessary for competent performance. Subsequent ONCC certification examinations were modified; the test blueprint that guides the construction of the examination was revised, and the passing score was adjusted.

Adult↗
PubMed1991

HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal.

A neuronal antigen (HuD) recognized by the sera of patients with antibody-associated paraneoplastic encephalomyelitis has been isolated by screening a lambda cerebellar expression library. The recombinant antigen provides an unambiguous assay for this rare condition associated with small cell lung cancer. The recombinant antigen has been used to identify specific infiltrating lymphocytes in tumors and affected brain tissues of patients with antibody-associated paraneoplastic encephalomyelitis and sensory neuronopathy. HuD mRNA is uniquely expressed in brain tissue. The HuD protein shows a remarkable homology to the Drosophila proteins Elav and Sex-lethal and is likely to play a role in neuron-specific RNA processing.

Amino Acid Sequence↗
PubMed1991

Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine.

The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1991

A report of familial carotid body tumors and multiple extra-adrenal pheochromocytomas.

A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and 131iodine-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1990

In vitro and in vivo experiments with the new inhibitor of mycobacterium leprae brodimoprim alone and in combination with dapsone.

The antibacterial effect of brodimoprim alone and in combination with dapsone has been studied in vitro in cell-free systems and in whole mycobacterial cells as well as in vivo in mice and humans. The obtained inhibitory effects in vitro and in vivo against model mycobacterial strains and M. leprae, the pharmacokinetic properties in human and its synergistic effect with the most used drug in the chemotherapy of leprosy, dapsone, make brodimoprim a promising candidate in the therapy of leprosy.

Adenosine Triphosphate↗