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Biomedical subjects

O Levy

Publications and source records attributed to O Levy.

At least 19 recordsLinked to original sources
PubMed2006

Diel 'tuning' of coral metabolism: physiological responses to light cues.

Hermatypic-zooxanthellate corals track the diel patterns of the main environmental parameters - temperature, UV and visible light - by acclimation processes that include biochemical responses. The diel course of solar radiation is followed by photosynthesis rates and thereby elicits simultaneous changes in tissue oxygen tension due to the shift in photosynthesis/respiration balance. The recurrent patterns of sunlight are reflected in fluorescence yields, photosynthetic pigment content and activity of the two protective enzymes superoxide dismutase (SOD) and catalase (CAT), enzymes that are among the universal defenses against free radical damage in living tissue. All of these were investigated in three scleractinian corals: Favia favus, Plerogyra sinuosa and Goniopora lobata. The activity of SOD and CAT in the animal host followed the course of solar radiation, increased with the rates of photosynthetic oxygen production and was correlated with a decrease in the maximum quantum yield of photochemistry in Photosystem II (PSII) (DeltaF'/F(m)'). SOD and CAT activity in the symbiotic algae also exhibited a light intensity correlated pattern, albeit a less pronounced one. The observed rise of the free-radical-scavenger enzymes, with a time scale of minutes to several hours, is an important protective mechanism for the existence and remarkable success of the unique cnidarian-dinoflagellate associations, in which photosynthetic oxygen production takes place within animal cells. This represents a facet of the precarious act of balancing the photosynthetic production of oxygen by the algal symbionts with their destructive action on all living cells, especially those of the animal host.

Acclimatization↗
PubMed2003

Expression of BPI (bactericidal/permeability-increasing protein) in human mucosal epithelia.

Among the antimicrobial proteins and peptides of humans is the cationic 55 kDa bactericidal/permeability-increasing protein (BPI), which possesses antibacterial, endotoxin-neutralizing and opsonic activity against Gram-negative bacteria. Although identified originally as an abundant constituent of neutrophil granules, we have recently identified functional expression of BPI by human mucosal epithelia. BPI expression was markedly up-regulated by exposure of epithelia to lipoxins, endogenous anti-inflammatory eicosanoids that are generated in vivo in the context of aspirin treatment (aspirin-triggered lipoxins). Epithelial BPI was found to be surface expressed and fully functional, as measured by antibacterial activity against Salmonella typhimurium as well as lipopolysaccharide (LPS; endotoxin)-neutralizing activity. These results suggest a role for BPI as an effector of epithelial antibacterial activity and as a modulator of epithelial responses to LPS. Both BPI and the lipoxins are currently the subject of intensive biopharmaceutical development, raising the possibility that therapeutic use of BPI or modulation of epithelial BPI expression may be a useful adjunctive therapy for conditions in which epithelial inflammation is associated with Gram-negative infections and/or endotoxin.

Antimicrobial Cationic Peptides↗
PubMed2003

Photobehavior of stony corals: responses to light spectra and intensity.

Tentacle expansion and contraction were investigated in four zooxanthellate coral species and one azooxanthellate coral (Cladopsammia gracilis). Favia favus, Plerogyra sinuosa and Cladopsammia gracilis expand their tentacles at night, while tentacles in Goniopora lobata and Stylophora pistillata are expanded continuously. Light at wavelengths in the range 400-520 nm was most effective in eliciting full tentacle contraction in F. favus and in P. sinuosa. Higher light intensities in the range 660-700 nm also caused tentacle contractions in F. favus. Tentacles in C. gracilis did not respond to light. Zooxanthellar densities in tentacles were significantly higher in G. lobata, which has continuously expanded tentacles, than in F. favus and P. sinousa, where tentacles are expanded at night. Photosynthetic efficiency in F. favus and P. sinuosa was lower in specimens with contracted tentacles. However, in the dark, no differences were found in the maximum quantum yield of photochemistry in PSII (Fv/Fm) of the expanded versus the contracted tentacles of any of the four species. This work suggests that species whose tentacles remain continuously expanded have either dense algal populations in their tentacles, as in G. lobata, or minute tentacles, like S. pistillata. Dense algal populations in tentacles allow harvesting of light while small tentacles do not scatter light or shade zooxanthellae in the underlying body of the polyp.

Animals↗
PubMed2002

Subacromial decompression. Treatment for small- and medium-sized tears of the rotator cuff.

We report the results of arthroscopic subacromial decompression and debridement of the rotator cuff for chronic small- and medium-sized tears in 114 patients (118 shoulders) between two and five years after surgery. The mean Constant score was improved to 69.8, and 88 shoulders (74.6%) had a satisfactory outcome. Of patients under the age of 60 years the outcome was satisfactory in 59.3%, and in those over 60 years, in 87.5% (p < 0.001). An unsatisfactory outcome was related to manual work (p < 0.001) and a duration of symptoms of more than 12 months (p < 0.05). The outcome was not related to the size of the tear, the muscles involved or biceps pathology. Further surgery was required in 25 patients after a mean of 13.7 months (3 to 35); ten tears had progressed in size, but none became irreparable. There was no relationship between the increase in the size of the tear and its initial size, the muscles involved or the presence of biceps pathology. No tear became smaller with time.

Activities of Daily Living↗
PubMed2001

A new class of antiarrhythmic-defibrillatory agents.

Novel dibenzoazepine and 11-oxo-dibenzodiazepine derivatives are shown to be effective ventricular defibrillating drug candidates. They exhibit significant in vivo defibrillatory activity with no observed changes in ECG either before or after the VF event. These compounds also exhibit antifibrillatory activity by elevating the fibrillation threshold potential, all suggesting that such drugs could be used to treat VF either by themselves or together with electrical defibrillators.

Animals↗
PubMed2001

Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin.

The Na(+)/I(-) symporter (NIS) is a key plasma membrane glycoprotein that mediates active I(-) transport in the thyroid gland (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460), the first step in thyroid hormone biogenesis. Whereas relatively little is known about the mechanisms by which thyrotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS activity, post-transcriptional events have been suggested to play a role (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 3789-3793). Here we show that TSH induces de novo NIS biosynthesis and modulates the long NIS half-life ( approximately 5 days). In addition, we demonstrate that TSH is required for NIS targeting to or retention in the plasma membrane. We further show that NIS is a phosphoprotein and that TSH modulates its phosphorylation pattern. These results provide strong evidence of the major role played by post-transcriptional events in the regulation of NIS by TSH. Beyond their inherent interest, it is also of medical significance that these TSH-dependent regulatory mechanisms may be altered in the large proportion of thyroid cancers in which NIS is predominantly expressed in intracellular compartments, instead of being properly targeted to the plasma membrane.

Animals↗
PubMed2001

Fréedericksz transition in confined liquid crystals: concentration and microgeometry effects.

The Fréedericksz transition in dispersions of liquid-crystal droplets is studied analytically by balancing the electrostatic energy of the droplets with a strong anchoring elastic energy. Explicit dependence of the transition threshold field on the liquid-crystal volume fraction and the spatial arrangement of the droplets is obtained for the first time. As a result of the confined geometry, this threshold field does not depend on the thickness of the sample and splitting of the transition occurs in some situations.

Journal Article↗
PubMed2001

Cementless surface replacement arthroplasty of the shoulder. 5- to 10-year results with the Copeland mark-2 prosthesis.

Cementless surface replacement arthroplasty of the shoulder is designed to replace the damaged joint surfaces and restore normal anatomy with minimal resection of bone. We have used the Copeland shoulder arthroplasty for 14 years. Between 1986 and 2000, 285 surface replacement arthroplasties were implanted in our unit. The prosthesis has evolved during this time, but the principle of minimal bone resection has remained the same. Between 1990 and 1994, 103 Mark-2 prostheses were inserted into 94 patients (9 bilateral). The operations were carried out for the treatment of osteoarthritis, rheumatoid arthritis, avascular necrosis, instability arthropathy, post-traumatic arthropathy and cuff arthropathy. The mean follow-up was for 6.8 years (5 to 10). The best results were achieved in primary osteoarthritis, with Constant scores of 93.7% for total shoulder replacement and 73.5% for hemiarthroplasty. The poorest results were seen in patients with cuff arthropathy and post-traumatic arthropathy with adjusted Constant scores of 61.3% and 62.7%, respectively. Most patients (93.9%) considered their shoulder to be much better or better than before the operation. Of the 88 humeral implants available for radiological review, 61 (69.3%) showed no evidence of radiolucency, nor did 21 (35.6%) of the 59 glenoid prostheses. Three were definitely loose, and eight shoulders required revision (7.7%), two (1.9%) for primary loosening. The results of this series are comparable with those for stemmed prostheses with a similar follow-up and case mix. The cementless surface replacement arthroplasty diminishes the risk of complications involving the humeral shaft and periprosthetic fractures. Revision or arthrodesis can be undertaken easily since the bone stock has been maintained with no loss of length.

Adult↗
PubMed2001

Thermal capsular shrinkage for shoulder instability. Mid-term longitudinal outcome study.

We present the short- and medium-term clinical results of thermal shrinkage in selected groups of patients with multidirectional or capsular stretch-type instability. We treated 56 patients (61 shoulders) by laser-assisted capsular shrinkage (LACS) and 34 patients (38 shoulders) by radiofrequency (RF) capsular shrinkage. The two groups were followed for mean periods of 40 months and 23 months, respectively. In the LACS group the mean Walch-Duplay score improved to 90 points 18 months after the operation, but then declined to a plateau of about 80 points; 59% of patients considered their shoulders to be 'much better' or 'better' but there was a failure rate of 36.1%. For the RF group the mean Walch-Duplay and Constant scores were 80 points at the various follow-up times; 76.3% of patients considered their shoulder to be 'much better' or 'better'. RF failed in nine shoulders (23.7%). These results match some clinical series of patients with multidirectional instability, undergoing open inferior capsular shift, with a similar rate of failure. We believe that the minimal morbidity involved makes thermal shrinkage a viable alternative to open capsular shift in this difficult group of patients.

Adolescent↗
PubMed2001

Factors controlling the expansion behavior of favia favus (Cnidaria: Scleractinia): effects of light, flow, and planktonic prey.

Colonies of the massive stony coral Faviafavus were exposed to different flow speeds and levels of light, and to the addition of zooplankton prey. The relative importance of each factor in controlling polyp expansion behavior was tested. The coral polyps fully expanded when they were exposed to low light intensity (0-40 micromol m(-2) s(-1)) and high flow speed (15 cm s(-1)), regardless of prey presence. They also partially expanded under low and medium light (40-80 micromol m(-2) s(-1)) at medium flow speed (10 cm s(-1)). The corals expanded their polyps only when they were exposed to light levels below compensation irradiance (Icom: light level at which photosynthesis = respiration), which was determined to be about 107 +/- 24 micromol m(-2) s. The results presented here indicate that high flow, low light, and the presence of planktonic prey induce coral expansion. There is a hierarchy of response to these stimuli, in which light level and flow speed are dominant over prey presence. Coral response to these three factors is probably due to the relative importance of gas exchange and zooplankton prey.

Animals↗
PubMed2000

Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site.

During the maturation of rotaviral particles, non-structural protein 4 (NSP4) plays a critical role in the translocation of the immature capsid into the lumen of the endoplasmic reticulum. Full-length NSP4 and a 22 amino acid peptide (NSP4(114-135)) derived from this protein have been shown to induce diarrhea in young mice in an age-dependent manner, and may therefore be the agent responsible for rotavirally-induced symptoms. We have determined the crystal structure of the oligomerization domain of NSP4 which spans residues 95 to 137 (NSP4(95-137)). NSP4(95-137) self-associates into a parallel, tetrameric coiled-coil, with the hydrophobic core interrupted by three polar layers occupying a and d-heptad positions. Side-chains from two consecutive polar layers, consisting of four Gln123 and two of the four Glu120 residues, coordinate a divalent cation. Two independent structures built from MAD-phased data indicated the presence of a strontium and calcium ion bound at this site, respectively. This metal-binding site appears to play an important role in stabilizing the homo-tetramer, which has implications for the engagement of NSP4 as an enterotoxin.

Amino Acid Sequence↗
PubMed2000

Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents.

The innate immune system provides rapid and effective host defense against microbial invasion in a manner that is independent of prior exposure to a given pathogen. It has long been appreciated that the blood contains important elements that mediate rapid responses to infection. Thus, anatomic compartments with ample blood supply are less frequently infected and recover more readily once infected, whereas regions with poor perfusion are prone to severe infection and may require surgical debridement. Blood-borne innate immune mediators are either carried in circulating blood cells (ie, leukocytes and platelets) or in plasma after release from blood cells or on secretion by the liver. (Blood. 2000;96:2664-2672)

Administration, Topical↗
PubMed2000

The mammary gland iodide transporter is expressed during lactation and in breast cancer.

The sodium/iodide symporter mediates active iodide transport in both healthy and cancerous thyroid tissue. By exploiting this activity, radioiodide has been used for decades with considerable success in the detection and treatment of thyroid cancer. Here we show that a specialized form of the sodium/iodide symporter in the mammary gland mediates active iodide transport in healthy lactating (but not in nonlactating) mammary gland and in mammary tumors. In addition to characterizing the hormonal regulation of the mammary gland sodium/iodide symporter, we demonstrate by scintigraphy that mammary adenocarcinomas in transgenic mice bearing Ras or Neu oncogenes actively accumulate iodide by this symporter in vivo. Moreover, more than 80% of the human breast cancer samples we analyzed by immunohistochemistry expressed the symporter, compared with none of the normal (nonlactating) samples from reductive mammoplasties. These results indicate that the mammary gland sodium/iodide symporter may be an essential breast cancer marker and that radioiodide should be studied as a possible option in the diagnosis and treatment of breast cancer.

Amino Acid Sequence↗
PubMed2000

Local field effects and the field-dependent dielectric response of polymer dispersed liquid crystals

An anisotropic version of the Maxwell Garnett approximation is applied for studying the dielectric properties of polymer dispersed liquid crystals containing bipolar liquid crystal droplets. This approach provides an explicit link between the droplet orientation distribution and the macroscopic response of the material. The electrostatic energy of the droplets is balanced with a strong anchoring elastic energy term for different initial orientation distributions. For aligned droplets we find a switching process whose sharpness depends on the initial orientation and a concentration dependent threshold field. For a planar distribution we find sharp transitions with a hysteresis loop whose width depends on the droplet concentration. For a random distribution the droplet reorientation is more gradual. The theory is also applied to the negligible elastic energy limit, recently observed at temperatures near the nematic-isotropic phase transition, where the droplets consist of bipolar nematic cores coated by isotropic liquid shells. This structural change within the droplets causes a considerable modification of the electro-optical properties. The Maxwell Garnett approach is used to calculate the dielectric response of this structure and reproduces all the main features of the experimental results.

Journal Article↗
PubMed2000

Enhancement of neonatal innate defense: effects of adding an N-terminal recombinant fragment of bactericidal/permeability-increasing protein on growth and tumor necrosis factor-inducing activity of gram-negative bacteria tested in neonatal cord blood ex vivo.

Innate defense against microbial infection requires the action of neutrophils, which have cytoplasmic granules replete with antibiotic proteins and peptides. Bactericidal/permeability-increasing protein (BPI) is found in the primary granules of adult neutrophils, has a high affinity for lipopolysaccharides (or "endotoxins"), and exerts selective cytotoxic, antiendotoxic, and opsonic activity against gram-negative bacteria. We have previously reported that neutrophils derived from newborn cord blood are deficient in BPI (O. Levy et al., Pediatrics 104:1327-1333, 1999). The relative deficiency in BPI of newborns raised the possibility that supplementing the levels of BPI in plasma might enhance newborn antibacterial defense. Here we determined the effects of addition of recombinant 21-kDa N-terminal BPI fragment (rBPI(21)) on the growth and tumor necrosis factor (TNF)-inducing activity of representative gram-negative clinical isolates. Bacteria were tested in citrated newborn cord blood or adult peripheral blood. Bacterial viability was assessed by plating assay, and TNF-alpha release was measured by enzyme-linked immunosorbent assay. Whereas adult blood limited the growth of all isolates except Klebsiella pneumoniae, cord blood also allowed logarithmic growth of Escherichia coli K1/r and Citrobacter koseri. Bacteria varied in their susceptibility to rBPI(21)'s bactericidal action: E. coli K1/r was relatively susceptible (50% inhibitory concentration [IC(50)], approximately 10 nM), C. koseri was intermediate (IC(50), approximately 1,000 nM), Klebsiella pneumoniae was resistant (IC(50), approximately 10,000 nM), and Enterobacter cloacae and Serratia marcescens were highly resistant (IC(50), >10,000 nM). All isolates were potent inducers of TNF-alpha activity in both adult and newborn cord blood. In contrast to its variable antibacterial activity, rBPI(21) consistently inhibited the TNF-inducing activity of all strains tested (IC(50), 1 to 1,000 nM). The antibacterial effects of rBPI(21) were additive with those of a combination of conventional antibiotics typically used to treat bacteremic newborns (ampicillin and gentamicin). Whereas ampicillin and gentamicin demonstrated little inhibition of bacterially induced TNF release, addition of rBPI(21) either alone or together with ampicillin and gentamicin profoundly inhibited release of this cytokine. Thus, supplementing newborn cord blood with rBPI(21) potently inhibited the TNF-inducing activity of a variety of gram-negative bacterial clinical pathogens and, in some cases, enhanced bactericidal activity. These results suggest that administration of rBPI(21) may be of clinical benefit to neonates suffering from gram-negative bacterial infection and/or endotoxemia.

Adult↗