bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of the Different Steps during Neutrophil Migration through Cultured Endothelial Monolayers Treated with Tumour Necrosis Factor-α
Authors: Luu N. Thin , Rainger G. Ed , Nash Gerard B. 
Published: April 2003

To enable a better understanding of the regulation of neutrophil migration, we investigated the kinetics of adhesion and migration over, through and under endothelial monolayers. Neutrophils were perfused over human umbilical vein endothelial cells (HUVEC) which had been treated with tumour necrosis factor-α (TNF; 2–1,000 U/ml) for 4 h. Videomicroscopy showed that transendothelial migration was complete within about 5 min of completion of perfusion of a bolus of neutrophils. Separate populations of adherent cells could then be observed, either rolling, migrating over the surface of the HUVEC or migrating underneath, at different characteristic speeds. Increasing concentration of TNF had little effect on the kinetics of migration, but shifted the balance from rolling adhesion to transendothelial migration. When individual neutrophils were followed from the moment they bound to HUVEC treated with 100 U/ml TNF, we found that ∼40% immobilised essentially immediately on contact, while ∼40% immobilised after rolling for varying periods (average 26 s) and ∼20% rolled continuously. Most of the immobilised cells went on to migrate through the monolayer after spending 20–200 s migrating on top, and took about 60 s to pass through. Overall, the time from first binding to completion of transmigration averaged 152 s (range ∼60–240 s). Interestingly, neutrophils moved relatively slowly on top of the monolayer (about 8 μm/min) but more rapidly underneath (about 16 μm/min). We suggest that the different stages during neutrophil transmigration have characteristic kinetics with separate control mechanisms, which critically influence the efficiency and rate of clearance from the vasculature.
Significance of Nitric Oxide and Peroxynitrite in Permeability Changes of the Retinal Microvascular Endothelial Cell Monolayer Induced by Vascular Endothelial Growth Factor
Authors: Marumo Takeshi , Noll Thomas , Schini-Kerth Valérie B. , Harley Elizabeth A. , Duhault Jacques , Piper Hans M. , Busse Rudi 
Published: April 2003

Reactive oxygen species (ROS) play an important role in signaling pathways stimulated by growth factors in vascular cells. We investigated whether vascular endothelial growth factor (VEGF), which is upregulated in diabetic retinopathy and atherosclerosis, is able to enhance production of ROS, and if so, whether ROS modulate endothelial permeability. ROS levels in bovine retinal microvascular endothelial cells (BMEC) were measured by the oxidation of 2′,7′-dichlorodihydrofluorescein (DCHF), and permeability was examined by monitoring the passage of albumin through BMEC monolayers. VEGF stimulated oxidation of DCHF in BMEC, an effect which was inhibited by superoxide dismutase (SOD) and the nitric oxide (NO) synthase inhibitor, N<sup>G</sup>-nitro-<i>L</i>-arginine methyl ester (<i>L</i>-NAME), but not by <i>D</i>-NAME. Urate, a scavenger of peroxynitrite, attenuated the VEGF-induced oxidation of DCHF. VEGF elicited a significant increase in the macromolecule permeability of BMEC monolayers within 30 min. SOD did not modify the basal or the VEGF-stimulated hyperpermeability, but the combination of SOD and VEGF induced a transient reduction in permeability after 10 min. <i>L</i>-NAME, but not <i>D</i>-NAME, enhanced VEGF-induced hyperpermeability without affecting basal values. Urate did not modify the VEGF-induced changes in permeability. In conclusion, VEGF stimulates oxidation of DCHF, which most likely represents peroxynitrite formation, and induces an increase in permeability of BMEC monolayers. Activation of NO synthase seems to counteract this stimulatory effect of VEGF on endothelial permeability.
Cyclic Nucleotide Hydrolysis in Bovine Aortic Endothelial Cells in Culture: Differential Regulation in Cobblestone and Spindle Phenotypes
Authors: Keravis Thérèse , Komas Narcisse , Lugnier Claire 
Published: April 2003

Cyclic nucleotide phosphodiesterases (PDEs) were investigated in cultured bovine aortic endothelial cells having two phenotypes, cobblestone and spindle, representing, respectively, the resting and angiogenic phenotypes in vivo. Spindle cell homogenates displayed higher hydrolytic activities towards cAMP (52%) and cGMP (10-fold). These increases were due to: (1) increased number of spindle PDE isozymes in the cytosolic fraction (for cAMP: PDE1, PDE2, PDE3 and PDE4 compared to PDE2 and PDE4 in cobblestone; for cGMP: PDE2 and PDE5 compared to PDE2 in cobblestone); (2) increased spindle-specific activities of cytosolic and particulate PDE2, cytosolic PDE3 and particulate PDE4. These changes were associated with an increase in spindle transcripts: 7.5 kb PDE3A (6-fold) and 7.0 kb PDE4D (3-fold). Moreover, cAMP hydrolysis in the two phenotypes was differently regulated by 5 μ<i>M</i> cGMP: 60% increase in total cAMP-PDE activity in cobblestone homogenate related to PDE2 stimulation; 30% decrease in spindle homogenate related to PDE3 inhibition. This underlines the roles played by PDE2, PDE3 and PDE5 in the cross-talk involving the two cyclic nucleotides. These changes in PDE isozyme expression along with the cross-talk between cAMP and cGMP may well modulate NO production and consequently might participate in angiogenesis, making PDEs potential targets to modulate angiogenesis.
Characterization of the Secreted Form of Endothelial-Cell-Specific Molecule 1 by Specific Monoclonal Antibodies
Authors: Bechard David , Meignin Véronique , Scherpereel Arnaud , Oudin Severine , Kervoaze Gwenola , Bertheau Philippe , Janin Anne , Tonnel André-Bernard , Lassalle Philippe 
Published: April 2003

Endothelial-cell-specific molecule 1 (ESM-1) is a recently identified endothelial cell molecule. As ESM-1 mRNA is preferentially expressed in human lung and kidney tissues, and as ESM-1 mRNA expression is regulated by inflammatory cytokines, ESM-1 is thought to play a role in the vascular contribution to organ-specific inflammation. In order to define its behavior, mouse anti-ESM-1 monoclonal antibodies were developed, and three distinct epitopes were mapped, which allowed development of a specific ELISA assay, immunohistological staining and immunoblot analysis. Here, we demonstrate that ESM-1 is present in cell lysates of human endothelial cells (human umbilical vein endothelial cells) with an apparent molecular weight of 20 kD. In contrast, the secreted form of ESM-1 is shifted to an apparent molecular weight of 50 kD, indicating that the secreted form of ESM-1 is posttranslationally modified. By ELISA, we show that the secretion of ESM-1 is significantly enhanced in the presence of TNFα. In contrast, the spontaneous as well as TNFα-induced secretion of ESM-1 is strongly inhibited by IFNγ. Moreover, ESM-1 was detected in the serum of healthy subjects at an average concentration of 1.08 ng/ml, and we demonstrated that the serum level of ESM-1 is dramatically increased in patients presenting a septic shock. Analysis of ESM-1 expression in normal human tissues by immunohistochemistry showed that ESM-1 is localized in the vascular network, but also in the bronchial and renal epithelia. Our results demonstrate that ESM-1 is mainly expressed in the vascular endothelium both in vitro and in vivo, but also by different epithelia. ESM-1 may represent a new marker of endothelial cell activation, and may have a functional role in endothelium-dependent pathological disorders.
Role of Fine Needle Aspiration, Intraoperative Imprint Cytology and Frozen Section in the Diagnosis of Breast Lumps and Thyroid Lesions
Authors: Francis Issam M. , Das Dilip K. 
Published: April 2003

<i>Background and Objectives:</i> Lesions of the thyroid and breast represent the two commonest sources of frozen section in Kuwait. This study investigates the value of intraoperative cytology (IC), preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section (FS), in improving the diagnostic accuracy of such lesions. <i>Material:</i> Thirty-one breast masses and 45 thyroid lesions were included. <i>Methods:</i> In each case, diagnosis was established by (1) preoperative FNAC, (2) intraoperative IC and (3) FS. Their accuracy was compared to paraffin section diagnosis. <i>Results:</i> Sensitivity of FNAC, IC and FS for breast malignancy was 82.6, 95.8 and 91.7%, respectively, while for thyroid malignancy sensitivity was 68.4, 85.0 and 65%, respectively. All three had 100% specificity and 0% false-positive rates. A 100% diagnostic accuracy was achieved by combined FNAC and IC in breast, and 93.3% with combined IC and FS in thyroid lesions. <i>Conclusion:</i> Intraoperative IC improves the diagnostic accuracy of FNAC and FS in breast and thyroid lesions.
Risk of Introduction of Drug-Resistant Malaria in a Non-Endemic Country, Kuwait: A Real Threat?
Authors: Iqbal Jamshaid , Sher Ali , Hira P.R. , Al-Anezi Abdul Aziz 
Published: April 2003

<i>Objectives:</i> This study investigates the prevalence of drug-resistant malaria infection in Kuwait in patients with malaria infection to the two most important and primary antimalarial drugs, chloroquine and mefloquine. <i>Study Subjects and Methods:</i> In vitro screening of malarial parasites to chloroquine and mefloquine was done during 1994–1996 in all those cases who presented with malaria-like symptoms and had a parasite density of ≥1,000 asexual pure <i>Plasmodium falciparum</i> parasites per microlitre of blood and had not taken any antimalarial drugs during the last 3 weeks. <i>Results:</i> During 1987–1997 the total number of malaria cases detected ranged between 650 and 1,350 each year. More than 75% of the cases had <i>Plasmodium vivax</i> infection. The majority of these cases (>98%) were detected in individuals coming from various malaria-endemic areas to reside or work in Kuwait. Of the 575 cases tested for drug resistance 42 isolates (7.3%) were resistant to chloroquine (MIC >8 pmol) and 6 isolates (1.04%) were resistant to mefloquine (MIC >64 pmol). The 50% inhibitory concentrations were 2.7 and 4.8 pmol for chloroquine and mefloquine, respectively. All the 6 isolates that were resistant to mefloquine were also resistant to chloroquine. Chloroquine resistance was seen in patients from various malaria-endemic countries. <i>Conclusion:</i> To date no indigenous case of malaria has been detected in Kuwait, however, recent environmental and demographic changes in and around the State of Kuwait may threaten the present status of zero endemicity. In this study we show that 7.3% of the malaria isolates tested were resistant to chloroquine and 1.04% isolates were resistant to mefloquine.
Differentiation of Acute Cortical and Subcortical Ischemic Stroke by Risk Factors and Clinical Examination Findings
Authors: Dulli Douglas , D’Alessio Donn J. , Palta Mari , Levine Ross L. , Schutta Henry S. 
Published: April 2003

<b>Background:</b> Differentiation between acute cortical and subcortical ischemic stroke may be problematic when cortical stroke presents without obvious cortical deficits such as aphasia, neglect or hemianopia. This study explores stroke risk factors and clinical variables that may assist in this differentiation. <b>Methods:</b> Records of consecutive patients with acute ischemic stroke, examined within 72 h of symptom onset, were reviewed. Stroke type was verified by clinical course and follow-up imaging. Stroke risk factors and acute examination findings were compared by odds ratios and positive predictive values for cortical and subcortical stroke. <b>Results:</b> For 355 patients studied, 237 had cortical stroke and 118 had subcortical stroke. Odds ratios for cortical stroke were highest for atrial fibrillation by EKG (OR = 4.77, CI = 2.08–10.94), recent hospitalization (OR = 4.51, CI = 2.39–8.53) and nonalert mental status (OR = 4.50, CI = 2.29–8.87). Possible cardioembolic condition, ischemic heart disease and peripheral vascular disease were also significant, but hypertension, age and diabetes mellitus were not significantly different for the stroke subtypes. Cortical deficits were absent in 19.4% of cortical stroke patients on initial examination. Predictive models were generated based on the presence or absence of cortical deficits and the interaction of significant risk factors with degree of motor deficit. <b>Conclusions:</b> There are clinical features that, in addition to initial examination, may help differentiate cortical from subcortical ischemic stroke. These features may be relevant to both diagnostic and therapeutic approaches to acute stroke.
Effect of Posture and Isoproterenol on Beat-to-Beat Heart Rate and QT Variability
Authors: Yeragani Vikram K. , Pohl Robert , Jampala V.C. , Balon Richard , Kay Jerald , Igel Gina 
Published: April 2003

<i>Rationale:</i> Recent literature emphasizes the utility of QT variability to study ventricular electrophysiologic function. In this investigation, we sought to test the hypothesis that beat-to-beat fluctuations in QT intervals are mediated by sympathetic activity in normal subjects using postural challenge and isoproterenol infusions. <i>Subjects and Methods:</i> We obtained ECG in the supine and standing postures during spontaneous breathing, at 12, 15 and 20 per minute controlled breathing (n = 19), and before and after infusions of isoproterenol, a β-adrenergic agent, in the supine posture during spontaneous breathing (n = 11) using lead II configuration in healthy human adult subjects. Heart rate (HR) and QT time series data were analyzed by spectral analysis of 256 s of real-time data. Beat-to-beat QT intervals were measured by automated analysis of ECG. A QT variability index (QT<sub>vi</sub>) was calculated for each subject as the logarithm of the ratio of normalized QT variance to normalized HR variance. We also calculated fractal dimensions of QT time series during spontaneous breathing. <i>Results:</i> QT<sub>vi</sub> was significantly higher in the standing than in the supine posture (–1.93 ± 0.27 vs. –1.47 ± 0.41; p = 0.0001), and also during isoproterenol infusions in the supine posture (–1.83 ± 0.39 vs. –1.27 ± 0.43; p = 0.0001). Fractal dimensions of QT time series were also significantly higher during standing (p = 0.00001) and isoproterenol infusions (p = 0.0002). Respiratory rate or tidal volume did not account for the increased QT variability seen in the standing posture. <i>Conclusions:</i> A change from the supine to the standing posture as well as infusion of isoproterenol significantly increased the absolute as well as normalized QT variability, which appears to be due to an increase in sympathetic activity associated with these conditions.
Ocular Changes in Mucopolysaccharidosis IV A (Morquio A Syndrome) and Long-Term Results of Perforating Keratoplasty
Authors: Käsmann-Kellner Barbara , Weindler Josef , Pfau Britta , Ruprecht KlausW. 
Published: April 2003

<i>Background:</i> The mucopolysaccharidoses (MPS) are an inhomogeneous group of disorders of errors in the carbohydrate metabolism with severe ocular involvement (corneal opacification, retinal degeneration, optic atrophy). <i>Patient Presentation:</i> We report on a boy aged 12 years, with Morquio A (MPS IV A) syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits, increasing corneal stromal clouding, intermittent dissociated manifest nystagmus of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05. Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration and optic atrophy. <i>Treatment and Course of Disease:</i> OS: perforating keratoplasty. Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by progressive reopacification of the corneal graft. Both eyes: progressive signs of tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD 0.05, OS 0.1. <i>Conclusions:</i> Success of a keratoplasty is limited by (1) reopacification of the cornea, (2) visual impairment due to (a) retinal degeneration and (b) optic atrophy. The indication for perforating keratoplasty has to be thought about very carefully in these multimorbid patients. In our patient, beside progressive visual impairment there is a progressive deafness which dominates his social and school life. Attending school is severely complicated by the double handicap. Perforating keratoplasty enabled the boy to attend a school for physically handicapped without a special low-vision care for another year. Progressive visual loss without further treatment options now renders optical and electronic low-vision aids necessary. Although the time of improved visual acuity lasted less than a year, we think patients with a life expectancy of less than 20 years should have every possible improvement of their situation – even if it does not last permanently. We therefore propose perforating keratoplasty in spite of insufficient long-term results.
Effect of Beta-Blocker Eyedrops on Corneal Epithelial Barrier Function
Authors: Niiya Akiko , Yokoi Norihiko , Matsumoto Yasuhiro , Komuro Aoi , Ishibashi Takeshi , Tomii Satoshi , He Jiucheng , Kinoshita Shigeru 
Published: April 2003

To investigate the long-term effect of a topically applied β-blocker on human corneal epithelium, the corneal epithelial barrier function and the superficial cell area of the corneal epithelium were evaluated. Seventeen normal healthy volunteers (without medication), 7 cataract patients (treated with pyrenoxine eyedrops) and 7 glaucoma or ocular hypertension patients (treated with 0.5% timolol maleate) were assigned to this study. The eyedrops had been used on a daily basis for at least 3 months. In the evaluation of corneal epithelial barrier function, fluorescein uptake was measured using a slitlamp fluorophotometer after application of 3 μl of 0.5% fluorescein for 10 min. In the evaluation of the superficial cell area, the central corneal epithelium was measured by tandem scanning confocal microscopy (TSCM). The healthy control and timolol groups were compared. Corneal fluorescein uptake in the healthy control, pyrenoxine and timolol groups was 20.3 ± 3.2, 21.5 ± 4.0 and 76.2 ± 30.0 ng/ml (mean ± standard error), respectively. There was a significantly higher fluorescein uptake in the timolol group compared to the pyrenoxine group (p = 0.0088) and the healthy control group (p = 0.0055). TSCM showed no significant difference in the superficial cell areas of the corneal epithelium between the healthy control and timolol groups. β-Blocker eyedrops decreased the corneal epithelial barrier function. Their application was not accompanied by any biomicroscopic change in the superficial cell area.
Myringosclerosis Develops within 9 h of Myringotomy
Authors: Mattsson Cecilia , Johansson Cathrine , Hellström Sten 
Published: April 2003

The aim of the present experimental study was to elucidate the temporal development of myringosclerosis. Twenty-four Sprague-Dawley rats were myringotomized bilaterally. At 3, 6, 9, 12, 18, 24, 30, 36, 48, 60, 72 and 84 h after the myringotomy, 2 animals at each time were examined otomicroscopically and thereafter sacrificed. The pars flaccida and pars tensa were excised and prepared for light- and electron-microscopic studies. Otomicroscopically, myringosclerosis was visible in the pars tensa 24 h after myringotomy, whereas no sclerotic lesions were noted in the pars flaccida. Histologically, sclerotic lesions were present in the pars tensa and pars flaccida 9 and 12 h, respectively, after myringotomy. The pars flaccida responds promptly with an inflammatory reaction characterized by abundant macrophages. Myringosclerosis develops promptly after myringotomy and its establishment is related to an inflammatory reaction.
Hyalinizing Clear Cell Carcinoma of the Oral Cavity and of the Parotid Gland
Authors: Rinaldo Alessandra , McLaren Kathryn M. , Boccato Paolo , Maran ArnoldG.D. 
Published: April 2003

Hyalinizing clear cell carcinoma (HCCC) is a rare, recently described tumor of salivary gland origin. Differential diagnosis includes benign lesions as clear cell change in a pleomorphic adenoma or in oncocytoma and malignant tumors – i.e. epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, mucoepidermoid carcinoma, clear cell acinic carcinoma, clear cell squamous carcinoma, clear cell malignant melanoma, clear cell odontogenic carcinoma, clear cell rhabdomyosarcoma, sebaceous carcinoma and metastasis of renal carcinoma. A favorable prognosis after wide local excision has been evidenced. Three new cases of HCCC (2 in the oral cavity and 1 in the parotid gland) are presented.
Transcranial Cortical Magnetic Stimulation of Lower-Lip Mimetic Muscles: Effect of Coil Position on Motor Evoked Potentials
Authors: Rödel R. , Laskawi R. , Markus H. 
Published: April 2003

The effect of the coil position along the interaural line on motor evoked potentials of lower-lip muscles to cortical transcranial magnetic stimulation was investigated in 17 healthy subjects. Using a figure-8-shaped coil, we observed ipsi- and contralateral middle-latency motor evoked potentials in all subjects, when the coil was centered within an area between 4 and 13 cm lateral to the vertex. Maximal responses (mean amplitude 1.4 ± 0.8 mV contralateral, 0.7 ± 0.5 mV ipsilateral) with shortest mean onset latencies (11.3 ± 1.6 ms contralateral, 12.1 ± 2.8 ms ipsilateral) were obtained at a stimulus position of 10 cm lateral to the vertex. Cortical maps of mean amplitude and mean response duration showed inverse U-shaped configuration. Furthermore, we observed an additional polyphasic and mostly bilateral response in 16 of the 17 subjects.
Long-Term Telomere Dynamics: Modest Increase of Cell Turnover in HIV-Infected Individuals Followed for up to 14 Years
Authors: Feng Yan-Ru , Biggar Robert J. , Gee Dennis , Norwood David , Zeichner Steven L. , Dimitrov Dimiter S. 
Published: April 2003

To quantify the long-term dynamics of telomere lengths and the effect of HIV infection on lymphocyte turnover rates, we measured in a blinded study longitudinal samples from 6 individuals using a highly accurate method based on two-dimensional calibration of DNA sizes. For two uninfected controls followed 8 and 10 years the average telomeric terminal restriction fragment (TRF) shortening rate in peripheral blood mononuclear cells (PBMCs) was 50 and 60 bp/year, respectively, in agreement with previous measurements of cross-sectional samples. The TRF lengths of PBMCs from two slow progressors followed for 14 years declined by a rate of 120 ±10 bp/year, i.e. 2-fold higher than the rate of TRF shortening for uninfected individuals. The rate of TRF shortening was higher in CD8 (140 ±10 bp/year) than in CD4 (100 ±10 bp/year) cells. The CD8 cell TRFs of the two fast progressors shortened faster (240 ±10 bp/year) and the rate of CD4 cell TRF shortening in one of the fast progressors was 160 bp/year. These data suggest that HIV infection causes only a modest increase in the lymphocyte turnover which we speculate could be due to chronic activation of the immune system, and may not result in the exhaustion of its regenerative capacity and immunopathogenesis.