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Biomedical subjects

M Levin

Publications and source records attributed to M Levin.

At least 91 records · Page 5Linked to original sources
PubMed1997

Detection of fibronectin expression by human endothelial cells using a enzyme-linked immunosorbent assay (ELISA): enzymatic degradation by activated plasminogen.

An enzyme-linked immunosorbent assay (ELISA) has been developed to measure cellular fibronectin (cFN) in association with human umbilical vein endothelial cells (HUVEC) in culture. The expression of a number of functional domains on the cFN molecule was demonstrated using three specific murine monoclonal antibodies. This system was found to be sensitive, detecting as little as 0.156 microg/ml of cFN, and required only 1.3 x 10(5) cells per well confluent cells per experimental condition. This allowed multiple experiments to be performed on one batch of endothelial cells. cFN was detected on both viable and methanol fixed endothelial cells without significant non-specific antibody binding. The utility of this experimental model was studied by exploring the effect of urokinase activated plasminogen, a potent protease, on the expression of cFN and its functional domains.

Antibodies, Monoclonal↗
PubMed1997

Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos.

Most work on magnetic field effects focuses on AC fields. The present study demonstrates that exposure to medium-strength (10 mT-0.1 T) static magnetic fields can alter the early embryonic development of two species of sea urchin embryos. Batches of fertilized eggs from two species of urchin were exposed to fields produced by permanent magnets. Samples of the continuous cultures were scored for the timing of the first two cell divisions, time of hatching, and incidence of exogastrulation. It was found that static fields delay the onset of mitosis in both species by an amount dependent on the exposure timing relative to fertilization. The exposure time that caused the maximum effect differed between the two species. Thirty millitesla fields, but not 15 mT fields, caused an eightfold increase in the incidence of exogastrulation in Lytechinus pictus, whereas neither of these fields produced exogastrulation in Strongylocentrotus purpuratus.

Abnormalities, Radiation-Induced↗
PubMed1997

Left-right asymmetry in vertebrate embryogenesis.

Embryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero-posterior and dorso-ventral axes, little information has been available regarding the basis for left-right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well-known signaling molecules such as Sonic hedgehog and activin) are asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs.

Abnormalities, Drug-Induced↗
PubMed1997

Induction of human endothelial tissue factor expression by Neisseria meningitidis: the influence of bacterial killing and adherence to the endothelium.

Tissue factor (TF), a small membrane bound high affinity receptor for factor VII, has an important procoagulant role in the haemostatic dysfunction associated with severe sepsis. Using an in vitro model of human endothelial TF expression, defined strains of Neisseria meningitidis were found to upregulate endothelial cell procoagulant activity (PCA) in a dose dependent manner. This TF response was detected with as little as 10(4) cfu/ml and reached similar levels to those seen with high concentrations of purified endotoxin (> 1 ng/ml). Treatment of N. meningitidis with either adult donor immune serum, penicillin or gentamicin failed to enhance this PCA. Limulus amoebocyte lysate assay of lipopolysaccharide in bacterial culture filtrates together with polymyxin B inhibition experiments suggest that endotoxin is largely responsible for endothelial TF induction by N. meningitidis. Incubation of endothelial cells with N. meningitidis B1940 and B1940 siaD- (an eight-fold more adherent unencapsulated isogenic strain), revealed a significantly greater TF response to B1940 siaD- (P < 0.01). In conclusion, bacterial adhesion to the vessel wall and therefore local levels of endotoxin may be important determinants of the endothelial procoagulant response to N. meningitidis and the consequent coagulopathy commonly associated with the disease.

Adult↗
PubMed1997

Two molecular models of initial left-right asymmetry generation.

Left-right (LR) asymmetry is a fascinating problem in embryonic morphogenesis. Recently, a pathway of genes has been identified which is involved in LR patterning in vertebrates. Although this work characterizes the interactions of several asymmetrically-expressed genes, it is still entirely unclear how such asymmetric expression is set up in the first place. There are two promising molecular candidates which may play a role is such a process: the motor protein dynein, and the gap junction protein connexin-43 (Cx43). We present two models, significantly supported by previous findings, which hypothesize that (a) dynein asymmetrically localizes LR determinants in individual cells to establish cell-autonomous LR biasing, and (b) asymmetric activity of Cx43 gap junctions within key cells sets up electric potentials in multicellular fields, thus establishing large-scale LR asymmetry.

Animals↗
PubMed1997

Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia.

Digital gangrene was observed in a patient who had angiographic findings of digital arterial occlusion. The patient's blood showed a marked red blood cell aggregation with rouleaux formation in long chains, which could not be dispersed at shear rates up to 200 sec-1. Studies of the patient's blood revealed the presence of an abnormal fibrinogen capable of aggregating normal red blood cells. This fibrinogen was found by Raman spectroscopy to have an increased alpha-helical content, whereas the beta-sheet content was decreased. Defibrinogenation therapy with ancrod resulted in a dramatic symptomatic relief. The disappearance of the abnormal fibrinogen 6 months later and an absence of a family history indicate that this dysfibrinogenemia was acquired.

Arterial Occlusive Diseases↗
PubMed1997

Feeding density influences acquisition of Borrelia burgdorferi in larval Ixodes scapularis (Acari: Ixodidae).

The intensity of Borrelia burgdorferi transmission in nature is dependent upon the efficiency of acquisition of spirochetes by larval Ixodes scapularis Say (= I. dammini Spielman, Clifford, Piesman & Corwin). White-footed mice infected with B. burgdorferi were infested weekly for 5 consecutive weeks with 25 or 250 larval I. scapularis. Prevalence of infection in nymphs derived from larvae fed at high density (25.0-38.9%) was consistently higher than in nymphs derived from larvae fed at low density (6.7-23.5%). Spirochete prevalence in nymphal I. scapularis populations in nature may be influenced by larval population density.

Animals↗
PubMed1997

Effect of aerosolization on culturability and viability of gram-negative bacteria.

Estimations of the bacterial content of air can be more easily made now than a decade ago, with colony formation the method of choice for enumeration of airborne bacteria. However, plate counts are subject to error because bacteria exposed to the air may remain viable yet lose the ability to form colonies, i.e., they become viable but nonculturable. If airborne bacteria exhibit this phenomenon, colony formation data will significantly underestimate the bacterial populations in air samples. The objective of the study reported here was to determine the effect of aerosolization on viability and colony-forming ability of Serratia marcescens, Klebsiella planticola, and Cytophaga allerginae. A collision nebulizer was used to spray bacterial suspensions into an aerosol chamber, after which duplicate samples were collected in all-glass impingers over a 4-h period. Humidity was maintained at ca. 20 to 25%, and temperature was maintained at 20 to 22 degrees C for each of two replicate trials per microorganism. Viability was determined by using a modified direct viable count method, employing nalidixic acid or aztreonam and p-iodonitrotetrazolium violet (INT). Cells were stained with acridine orange and observed by epifluorescence microscopy to enumerate total and viable cells. Viable cells were defined as those elongating in the presence of antibiotic and/or reducing INT. CFU were determined by plating on tryptic soy agar and R2A agar. It was found that culture techniques did not provide an adequate description of the bacterial burdens of indoor air (i.e., less than 10% of the aerosolized bacteria were capable of forming visible colonies). It is concluded that total cell count procedures provide a better approximation of the number of bacterial cells in air and that procedures other than plate counting are needed to enumerate bacteria in aerosol samples, especially if the public health quality of indoor air is to be estimated.

Aerosols↗
PubMed1997

Effect of ingested sodium bicarbonate on muscle force, fatigue, and recovery.

The influence of acute ingestion of NaHCO3 on fatigue and recovery of teh quadriceps femoris muscle after exercise was studied in six healthy male subjects. A bicycle ergometer was used for exercising under three loading conditions: test A, load corresponding to maximal oxygen consumption; test B, load in test A + 17%; test C, load in test B but performed 1 h after acute ingestion of NaHCO3. Functional electrical stimulation (FES) was applied to provoke isometric contraction of the quadriceps femoris. The resulting knee torque was monitored during fatigue (2-min chronic FES) and recovery (10-s FES every 10 min, for 40 min). Quadriceps torques were higher in the presence of NaHCO3 (P < 0.05): with NaHCO3 the peak, residual, and recovery (after 40 min) normalized torques were, respectively, 0.68 +/- 0.05 (SD), 0.58 +/- 0.05, and 0.73 +/- 0.05; without NaHCO3 the values were 0.45 +/- 0.04, 0.30 +/- 0.06, and 0.63 +/- 0.06. The increased torques obtained after acute ingestion of NaHCO3 indicate the possible existence of improved nonoxidative glycolysis in isometric contraction, resulting in reduced fatigue and enhanced recovery.

Administration, Oral↗
PubMed1997

A volumetric approach to virtual simulation of functional endoscopic sinus surgery.

Advanced display technologies have made the virtual exploration of relatively complex models feasible in many applications. Unfortunately, only a few human interfaces allow natural interaction with the environment. Moreover, in surgical applications, such realistic interaction requires real-time rendering of volumetric data-placing an overwhelming performance burden on the system. We report on a collaboration of an interdisciplinary group developing a virtual reality system that provides intuitive interaction with volume data by employing real-time volume rendering and force feedback (haptic) sensations. We describe our rendering methods and the haptic devices and explain its utility of this system in the real-world application of Endoscopic Sinus Surgery (ESS) simulation.

Computer Simulation↗
PubMed1997

ENT endoscopic surgical training simulator.

This paper describes work in progress on the design and development of a prototype simulator for minimally invasive otolaryngology surgical training. The anatomy of the paranasal sinuses is geometrically complex and dangerously close to the brain and orbits, making this procedure challenging to practice and difficult to learn. We discuss the potential role of computer simulation to enhance and accelerate acquisition of surgical skills. The design goals of the prototype include high-fidelity simulation of the endoscopic imagery and haptic cues of surgical palpation. The prototype enables endoscopic navigation and limited interactive tissue manipulation and dissection tasks on a virtual patient using realistic replicas of surgical tools. We present an overview of the system architecture with a discussion of the technological challenges, design issues and current status of the efforts.

Computer Simulation↗
PubMed1997

Immunopathogenesis of HTLV-I associated neurologic disease: massive latent HTLV-I infection in bone marrow of HAM/TSP patients.

The localization of mammalian retroviruses to specified immune organs has significant implications on the pathophysiology of retroviral associated diseases. Human T-cell Lymphotropic Virus Type I (HTLV-I) is considered a CD4+ lymphotropic virus although the virus has been shown to infect a large variety of cells in vitro. Similarly, the human immunodeficiency virus (HIV), once thought to be harbored only in CD4+ peripheral blood lymphocytes (PBL) has been shown to be present in latent form in lymph nodes of HIV infected patients. HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a chronic progressive neurologic disorder of the central nervous system and is believed to result from infection of HTLV-I in association with an immunopathogenic or autoimmune mechanism. Here we describe experiments which utilize the in situ hybridization/polymerase chain reaction technology to demonstrate extensive HTLV-I infection of bone marrow in HAM/TSP patients. We discuss these results in the context of HTLV-I associated neurologic disease and extend these observations to other disorders of potential retroviral etiology and autoimmune involvement.

Bone Marrow↗
PubMed1996

A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection.

BACKGROUND: Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor. METHODS: We used microsatellite analysis, immunofluorescence studies, and sequence analysis to study the affected patients, unaffected family members, and normal controls. RESULTS: A genome search using microsatellite markers identified a region on chromosome 6q in which the affected children were all homozygous for eight markers. The gene for interferon-gamma receptor 1 maps to this region. Immunofluorescence studies showed that the receptor was absent on leukocytes from the affected children. Sequence analysis of complementary DNA for the gene for interferon-gamma receptor 1 revealed a point mutation at nucleotide 395 that introduces a stop codon and results in a truncated protein that lacks the transmembrane and cytoplasmic domains. CONCLUSIONS: Four children with severe mycobacterial infections had a mutation in the gene for interferon-gamma receptor 1 that leads to the absence of receptors on cell surfaces and a functional defect in the up-regulation of tumor necrosis factor alpha by macrophages in response to interferon-gamma. The interferon-gamma pathway is important in the response to intracellular pathogens such as mycobacteria.

Antigens, CD↗