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1.
Sci Rep ; 11(1): 22944, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34824322

ABSTRACT

A unique combination of the ultrashort high-energy pulsed laser system with exceptional beam quality and a novel Diffractive Optical Element (DOE) enables simultaneous production of 2601 spots organized in the square-shaped 1 × 1 mm matrix in less than 0.01 ms. By adjusting the laser and processing parameters each spot can contain Laser Induced Periodic Surface Structures (LIPSS, ripples), including high-spatial frequency LIPSS (HFSL) and low-spatial frequency LIPSS (LSFL). DOE placed before galvanometric scanner allows easy integration and stitching of the pattern over larger areas. In addition, the LIPSS formation was monitored for the first time using fast infrared radiometry for verification of real-time quality control possibilities. During the LIPSS fabrication, solidification plateaus were observed after each laser pulse, which enables process control by monitoring heat accumulation or plateau length using a new signal derivation approach. Analysis of solidification plateaus after each laser pulse enabled dynamic calibration of the measurement. Heat accumulation temperatures from 200 to 1000 °C were observed from measurement and compared to the theoretical model. The temperature measurements revealed interesting changes in the physics of the laser ablation process. Moreover, the highest throughput on the area of 40 × 40 mm reached 1910 cm2/min, which is the highest demonstrated throughput of LIPSS nanostructuring, to the best of our knowledge. Thus, showing great potential for the efficient production of LIPSS-based functional surfaces which can be used to improve surface mechanical, biological or optical properties.

2.
Hernia ; 24(2): 387-393, 2020 04.
Article in English | MEDLINE | ID: mdl-32062712

ABSTRACT

PURPOSE: Reconstruction of large abdominal-wall defects (AWD) in patients after massive weight loss (MWL) can be challenging. Patients are left with a sizeable amount of excess skin and subcutaneous tissue which can serve as a natural and readily available source of mesh coverage. In this article, we present our experience in the reconstruction of large AWD in patients after MWL, using autogenous dermal flaps combined with a synthetic mesh. METHOD: All patients with large AWD and MWL, diagnosed between January 2012 and December 2016, were considered to be candidates for the procedure. During the operation, an attempt was made to attain full closure of the defect above the mesh. In those patients for whom such closure was not possible, a dermal flap technique was used. Patients were closely monitored for at least 1 year. Outcome measures included early and late postoperative complications. Data are presented as mean ± standard deviation (SD). RESULTS: Over the study period, a total of 14 patients underwent a surgery involving combined mesh and dermal flap technique. Early post-operative complications included three patients who suffered from minor wound disruption and were treated with local dressings. One patient had an abdominal-wall hematoma that required an evacuation. Two patients suffered from an epidermal cyst and chronic sinuses that required surgical debridement. None of the patients experienced intra-abdominal complication, respiratory failure, or required ICU treatment. No mesh contamination or hernia recurrence was observed during the follow-up period of 22.25 ± 6.4 months. CONCLUSION: Autologous dermal flap combined with mesh technique may serve as an effective surgical alternative in patients after MWL with large AWD for whom full muscular coverage of the underlying prosthesis is not possible.


Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy/methods , Obesity , Plastic Surgery Procedures/methods , Surgical Flaps , Surgical Mesh , Abdominal Wall/surgery , Abdominoplasty/adverse effects , Abdominoplasty/methods , Adult , Bariatrics/methods , Dermis/transplantation , Female , Hernia, Ventral/complications , Herniorrhaphy/adverse effects , Humans , Male , Middle Aged , Obesity/complications , Obesity/therapy , Plastic Surgery Procedures/adverse effects , Retrospective Studies , Surgical Flaps/blood supply , Transplantation, Autologous , Weight Loss
3.
J Appl Physiol (1985) ; 121(3): 606-14, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27311440

ABSTRACT

Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm(2)/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS.


Subject(s)
Airway Resistance/physiology , Electric Stimulation/methods , Hypoglossal Nerve/physiology , Muscle Contraction/physiology , Pharyngeal Muscles/physiology , Pharynx/physiology , Respiration, Artificial/methods , Animals , Male , Muscle Strength/physiology , Pharyngeal Muscles/innervation , Respiratory System Agents , Swine
5.
Neurology ; 75(6): 519-25, 2010 Aug 10.
Article in English | MEDLINE | ID: mdl-20592253

ABSTRACT

OBJECTIVE: To explore efficacy and safety/tolerability of adjunctive brivaracetam (BRV), a novel, high-affinity synaptic vesicle protein 2A ligand, which also inhibits neuronal voltage-dependent sodium channels, in patients with refractory partial-onset seizures (POS). METHODS: This was an exploratory, phase IIb, double-blind, randomized, parallel-group, placebo-controlled, dose-ranging study in patients 16-65 years with epilepsy experiencing > or =4 POS during 4-week baseline despite 1-2 concomitant antiepileptic drugs. Patients were randomized (1:1:1:1) to placebo, BRV 5 mg/day (BRV5), BRV 20 mg/day (BRV20), or BRV 50 mg/day (BRV50), administered BID without uptitration during a 7-week treatment period. Primary efficacy endpoint was POS frequency/week during the treatment period relative to placebo. RESULTS: A total of 208 patients constituted the intention-to-treat population; 197 completed the study. Estimated percentage reductions over placebo in POS frequency/week were 9.8% (BRV5; p = 0.240), 14.9% (BRV20; p = 0.062), and 22.1% (BRV50; p = 0.004). Median percent reductions from baseline in POS frequency/week were 21.7% (placebo), 29.9% (BRV5; p = 0.086), 42.6% (BRV20; p = 0.014), and 53.1% (BRV50; p < 0.001); > or =50% responder rates were 16.7% (placebo), 32.0% (BRV5; p = 0.047), 44.2% (BRV20; p = 0.002), and 55.8% (BRV50; p < 0.001); seizure freedom rates (POS) during the 7-week treatment period were 1.9% (placebo), 8.0% (BRV5; p = 0.193), 7.7% (BRV20; p = 0.193), and 7.7% (BRV50; p = 0.201). BRV was well-tolerated. Most adverse events were mild to moderate and occurred with similar incidence in placebo and BRV groups, and discontinuations due to treatment-emergent adverse events were infrequent (placebo 3.7%; BRV 2.6%). CONCLUSIONS: This interventional study provides preliminary Class I evidence that adjunctive BRV was efficacious and well-tolerated in patients aged 16-65 years with POS.


Subject(s)
Epilepsies, Partial/drug therapy , Epilepsies, Partial/epidemiology , Pyrrolidinones/administration & dosage , Seizures/drug therapy , Seizures/epidemiology , Adolescent , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Humans , Internationality , Male , Middle Aged , Prospective Studies , Young Adult
6.
Eur J Clin Microbiol Infect Dis ; 27(9): 797-803, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18369670

ABSTRACT

Although bactibilia is an important condition of acute cholecystitis, its effect on the course and outcome of the infectious gallbladder disease has rarely been studied, particularly in relation to the laparoscopic procedure. The current study attempts to learn more about the inter-relationship between bactibilia and laparoscopic cholecystectomy during acute cholecystitis. Demographic, preoperative, operative, and postoperative data were prospectively collected in every patient with acute cholecystitis treated in the department of surgery at the Bnai Zion Medical Center, Israel. Intraoperative biliary samples were collected under aseptic conditions at the time of operation for bacteriologic examination and were routinely cultured in aerobic and anaerobic media for 3 days. The study population was divided into culture-positive and culture-negative groups, and the collected parameters were compared between the groups. Age over 60 years, a palpable gallbladder, temperature over 37.5 degrees C, a white blood cell (WBC) count of more than 12,000/cc(3), and serum alkaline phosphatase higher than 100 U/dL were all found to be factors capable of predicting bactibilia. Bactibilia was a significant factor associated with total, as well as infectious, operative complications. Bactibilia is considered to indicate an advanced stage of acute cholecystitis. In cases of laparoscopic cholecystectomy for infectious gallbladder disease, bactibilia is strongly associated with total, as well as local, infectious complications. Preoperative conditions such as older age, elevated temperature, a palpable gallbladder, elevated WBC count, and elevated serum levels of alkaline phosphatase can serve as predictors of bactibilia and its consequent complications. Although the sensitivity and specificity of the predictive factors for bactibilia are limited to 63% and 67%, respectively, in their presence during acute cholecystitis, conservative wide-spectrum antibiotics as the first-line therapy is appropriate, and, upon regimen failure, laparoscopic surgery by an experienced surgeon is indicated as the adjusted therapy.


Subject(s)
Bile/microbiology , Cholecystectomy, Laparoscopic , Cholecystitis, Acute/microbiology , Cholecystitis, Acute/surgery , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Child , Cholecystitis, Acute/complications , Cholecystitis, Acute/diagnosis , Female , Humans , Male , Middle Aged , Prognosis , Young Adult
7.
Radiat Prot Dosimetry ; 101(1-4): 601-6, 2002.
Article in English | MEDLINE | ID: mdl-12382821

ABSTRACT

The title of this banquet talk was selected to entertain conferees with recollections of major advances in dosimetry that have stimulated appetites for scientific progress. Recalling over fifty years of use of dosimetric instruments and concepts in the 1950-2000 era leads to an appreciation of many advances in solid state dosimetry, which others here know well and pursue vigorously. This author has been mainly a user, admirer, and interpreter of the fundamental methods of dose measurement. These advances have allowed ease of application in radiation protection and medical physics, for determining current routine and accidental exposures to workers, and for precise radiotherapeutic dose delivery. In more recent years, advances in identifying means of locating selective depositions of energy in various materials are providing ways of retrospectively assessing doses to tissue that were deposited many years ago. These methods also will allow development of quantitative theories of radiation damage once the lesions of interest are identified through further advances in molecular genetics. Yet, reflections on the past fifty years lead to increasing appreciation of the enormous achievements of our predecessors in the 1900-1950 period. Therefore, this presentation emphasises methods used by the author and some of his data interpretations during his 52 year career, with somc examination of the earlier origin of some of these methods.


Subject(s)
Radiometry/standards , Radiometry/trends , Film Dosimetry/trends , Government Agencies , Nuclear Energy , United States
8.
Am J Public Health ; 91(12): 1987-94, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11726381

ABSTRACT

OBJECTIVES: This study examined differences between the visibility of drugs and drug use in more than 2100 neighborhoods, challenging an assumption about drug use in poor, minority, and urban communities. METHODS: A telephone survey assessed substance use and attitudes across 41 communities in an evaluation of a national community-based demand reduction program. Three waves of data were collected from more than 42 000 respondents. RESULTS: Measures of neighborhood disadvantage, population density, and proportion of minority residents explained more than 57% of the variance between census tracts in visibility of drug sales but less than 10% of tract-to-tract variance in drug use. Visible drug sales were 6.3 times more likely to be reported in the most disadvantaged neighborhoods than in the least disadvantaged, while illicit drug use was only 1.3 times more likely. CONCLUSIONS: The most disadvantaged neighborhoods have the most visible drug problems, but drug use is nearly equally distributed across all communities. Thus, efforts to address drug-related problems in poorer areas need to take into account the broader drug market served by these neighborhoods.


Subject(s)
Community Health Services , Illicit Drugs/supply & distribution , Residence Characteristics/statistics & numerical data , Substance-Related Disorders/epidemiology , Substance-Related Disorders/prevention & control , Adolescent , Adult , Community Health Services/methods , Female , Health Policy , Humans , Illicit Drugs/legislation & jurisprudence , Male , Surveys and Questionnaires , United States/epidemiology
9.
Am J Community Psychol ; 29(5): 679-99, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11594695

ABSTRACT

Neighborhood norms are an important determinant of beliefs and attitudes about parenting, and measuring changes in community norms is an important component of evaluating community-based programs for improving child outcomes. The purpose of this study was to determine whether or not a survey of community residents' perceptions of parenting could be used to measure community parenting norms and whether these perceptions differed by individual or community characteristics. Two community surveys with 870 and 914 respondents, respectively, were conducted in 3 low-income neighborhoods. Results indicated that perceptions of parenting could be measured reliably at the community level although it is important to consider the presence of multiple norms when using such measures. Furthermore, differences in perceptions of parenting associated with individual characteristics were markedly decreased when neighborhood characteristics were considered, suggesting that the association of individual characteristics with perceptions of parenting is confounded by neighborhood characteristics.


Subject(s)
Health Knowledge, Attitudes, Practice , Parenting/psychology , Psychology, Social , Residence Characteristics , Adult , Baltimore , Child , Child, Preschool , Community Health Planning , Female , Humans , Infant , Male , Middle Aged , Outcome Assessment, Health Care , Poverty , Program Evaluation , Reproducibility of Results , Surveys and Questionnaires , United States
11.
Ultrasonics ; 39(2): 97-100, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11270635

ABSTRACT

Theoretical and experimental evidence is presented in support of quantum collective effects in sonoluminescence.


Subject(s)
Luminescence , Ultrasonics , Sodium
12.
Int J Pediatr Otorhinolaryngol ; 57(1): 1-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11165635

ABSTRACT

OBJECTIVES: To evaluate the clinical course and identify the causative organisms of acute mastoiditis in a community where most of the patients who develop acute otitis media are treated with antibiotics. METHODS: A multicenter retrospective review of a series of 223 consecutive cases of acute mastoiditis. SETTING: Nine secondary or tertiary academic or non-academic referral centers. RESULTS: Prior to the diagnosis of acute mastoiditis, 121 of the patients (54.3%) had been receiving oral antibiotic treatment for acute otitis media for periods ranging from 1 to 21 days (mean 5.3 days). Samples for bacterial culture were obtained from 152 patients. Cultures were negative in 60 patients. The organisms isolated in the 92 positive cultures were: Streptococcus pneumoniae (15 patients), Streptococcus pyogenes (14 patients), Staphylococcus aureus (13 patients), Staphylococcus coagulase negative (three patients), Pseudomonas aeruginosa (eight patients), Haemophilus influenzae (four patients), Proteus mirabilis (two patients), Escherichia coli (two patients), Klebsiella pneumoniae (one patient), Enterobacter (one patient), Acinetobacter (one patient), anaerobic gram-negative bacilli (one patient), and fungi (two patients). Ten patients had mixed flora. Sixteen patients presented with complications (cerebellar abscess, perisinus empyema, subdural abscess or empyema, extradural abscess, cavernous sinus thrombosis, lateral sinus thrombosis, bacterial meningitis, labyrinthitis, petrositis, or facial nerve palsy). CONCLUSIONS: Antibiotic treatment cannot be considered an absolute safeguard against the development of acute mastoiditis. Early myringotomy for acute otitis media seems to decrease the incidence of complications. The distribution of causative organisms in acute mastoiditis differs from that in acute otitis media. Intracranial complications in acute mastoiditis are not rare. Because of the diversity of causative organisms in acute mastoiditis and the growing resistance of bacteria to the various antibiotics, all means to obtain a sample for culture prior to antibiotic treatment, including general anesthesia.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Mastoiditis/drug therapy , Acute Disease , Bacterial Infections/diagnosis , Bacterial Infections/epidemiology , Child, Preschool , Female , Humans , Israel/epidemiology , Male , Mastoiditis/complications , Mastoiditis/epidemiology , Mastoiditis/microbiology , Otitis Media/drug therapy , Otitis Media/microbiology , Retrospective Studies
13.
Curr Protoc Nucleic Acid Chem ; Chapter 7: Unit 7.7, 2001 May.
Article in English | MEDLINE | ID: mdl-18428875

ABSTRACT

Despite recent advances in the solution of NMR structures of RNA and RNA-ligand complexes, the rate limiting step remains the gathering of a large number of NOE and torsion restraints. Additional sources of information for structure determination of larger RNA molecules have recently become available, and it is possible to supplement NOE and J-coupling data with the measurement of dipolar couplings and cross-correlated relaxation rates in high-resolution NMR spectroscopy.


Subject(s)
Nuclear Magnetic Resonance, Biomolecular/methods , Nucleic Acid Conformation , RNA/chemistry , Base Sequence , Hydrogen Bonding , Isotope Labeling , Molecular Sequence Data , RNA/genetics
14.
J Opt Soc Am A Opt Image Sci Vis ; 17(11): 2024-33, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11059598

ABSTRACT

We present a new nonperturbative theoretical method for the analytical description of light propagation in random multiscattering media. The method is illustrated through the calculation of an expression that describes optical backscattering from a semi-infinite disordered medium. A companion paper [J. Opt. Soc. Am. A 17, 2034 (2000)] compares the theoretical expression with experimental data.

15.
J Opt Soc Am A Opt Image Sci Vis ; 17(11): 2034-9, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11059599

ABSTRACT

We present experimental results of measurements of light backscattering from semi-infinite disordered media by low-coherence interferometry (LCI). These results are compared with the theory developed in part I [J. Opt. Soc. Am. A 17, 2024 (2000)]. A comparison of the experimental data with the theoretical formulas based on the coherent phase approximation allows us to extract substantial information about the structure of the studied media. Our results demonstrate that LCI is an effective optical technique for studying nonuniform media even in the case in which the dimensions of nonuniformities are much less than the wavelength of the scattered light.

16.
Drug Alcohol Depend ; 60(3): 221-47, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11053757

ABSTRACT

The aim of this paper is to identify positive psychological concomitants of moderate alcohol consumption. Current research and public-health perspectives on alcohol emphasize harms disproportionately relative to benefits. The major exception is research establishing beneficial effects of moderate drinking on cardiovascular health and overall mortality. In addition, much observational and experiential data suggest the widespread prevalence of positive drinking experiences. This paper is one of the first attempts since 1985 to codify such benefits in epidemiological terms. Methodological difficulties in accomplishing this include defining moderate drinking, controlling for confounding variables, and establishing causality. Nonetheless, evidence of psychological benefits has been found in experimental, observational, interview, self-report, correlational, and some prospective research. These positive findings are in the areas of subjective health, mood enhancement, stress reduction, sociability, social integration, mental health, long-term cognitive functioning, and work income/disability. Problem drinkers and alcoholics also seek mood and other benefits from alcohol, but are more likely to drink to counteract negative feelings and to support their egos than are social drinkers. It is as yet impossible to determine to what extent moderate alcohol consumption causes positive psychological outcomes and to what extent it is part of a complex pattern of mutually reinforcing variables.


Subject(s)
Alcohol Drinking/psychology , Adolescent , Adult , Affect/drug effects , Aged , Cardiovascular Diseases/prevention & control , Cognition/drug effects , Ethanol/pharmacology , Female , Heart/drug effects , Humans , Male , Mental Health , Middle Aged
17.
Surg Endosc ; 14(8): 755-60, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10954824

ABSTRACT

BACKGROUND: Laparoscopic cholecystectomy (LC) in acute cholecystitis is associated with a relatively high rate of conversion to an open procedure as well as a high rate of complications. The aim of this study was to analyze prospectively whether the need to convert and the probability of complications is predictable. METHODS: A total of 215 patients undergoing LC for acute cholecystitis were studied prospectively by analyzing the data accumulated in the process of investigation and treatment. Factors associated with conversion and complications were assessed to determine their predictive power. RESULTS: Conversion was indicated in 44 patients (20.5%), and complications occurred in 36 patients (17%). Male gender and age >60 years were associated with conversion, but these factors had no sensitivity and no positive predictive value. The same factors, together with a disease duration of >96 h, a nonpalpable gallbladder, a white blood count (WBC) of >18,000/cc(3), and advanced cholecystitis, predicted conversion with a sensitivity of 74%, a specificity of 86%, a positive predictive value of approximately 40%, and a negative predictive value of 96%. However, these data became available only when LC was underway. Male gender and a temperature of >38 degrees C were associated with complications, but these factors had no sensitivity and no positive predictive value. Progression along the stages of admission and therapy did not add predictive factors or improve the predictive characteristics. Male gender, abdominal scar, bilirubin >1 mg%, advanced cholecystitis, and conversion to open cholecystectomy were associated with infectious complications. Their sensitivity and positive predictive value remained 0 despite progression along the stages of admission and therapy. CONCLUSION: Although certain preoperative factors are associated with the need to convert a LC for acute cholecystitis, they have limited predictive power. Factors with higher predictive power are obtained only during LC. The need to convert can only be established during an attempt at LC. Preoperative and operative factors associated with total and infectious complications have no predictive power.


Subject(s)
Cholecystectomy, Laparoscopic , Cholecystitis/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Cholecystectomy, Laparoscopic/adverse effects , Cholecystectomy, Laparoscopic/economics , Cholecystectomy, Laparoscopic/methods , Cholecystitis/classification , Female , Humans , Male , Middle Aged , Multivariate Analysis , Postoperative Complications , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Sex Factors , Treatment Failure
19.
Hematología (B. Aires) ; 4(2): 57-76, mayo-ago. 2000. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-341326

ABSTRACT

Con el objeto de explorar su potencial empleo en terapéutica no citotóxicas, se estudió, en células leucémicas humanas, la vía de señalización y probable rol regulatorio del receptor a histamina H2. Mediante ensayos de binding, se detectaron sitios de unión específica de tipo H2, en casi todas las muestras de M.O.y S.P. de pacientes con L.A., con diferentes grados de infiltración. esto sugiere la presencia del receptor H2, en células hemopoyéticas normales y transformadas. La líneas U-937, modelo de célula monoblástica, presenta receptores H2, acoplados a AMPc. Su estímulo no produjo cambios proliferativos, ni deferenciación celular, pero sí un aumento transitorio, vía proteín kinasa A (PKA), en la expresión de Fos y Hun, sin reducción de Myc. Se hipotizó que el fracaso del estímulo H2, para diferenciar las células U-937 podría deberse a que su activación de la PKA es breve. Concordante con lo anterior, los receptores H2, mostraron una veloz de desensibilización homóloga (T. 1/2 = 20ï). En cambio la forskolina, un activador directo de la adenil ciclasa, no desensibilizó su estímulo ni aún después de 24 horas de incubación. La forskolina también inhibió la proliferación U-937 a las mismas concentraciones en que estimuló la síntesisde AMPc e indujo su diferenciación fagocitaria, con reducción del NBT y respuesta quimiotáctica al C5a. Conclusiones: 1) La desensibilización veloz de un receptor que transduce una señal diferenciadora, como el H2, en las células U-937, podría ser un mecanismo fisiopatogénico de la malignificación, al bloquear la recepción de estímulos madurativos por la célula neoplásica. 2) Dados estos resultados, y los efectos diferenciadores del dibutril AMPc (DBAMPc) en líneas celulares mieloides, los agentes que elevan el AMPc merecen ser valorados en la terapia de las LMA


Subject(s)
Humans , Burkitt Lymphoma , Receptors, Histamine H2
20.
Hematología [B. Aires] ; 4(2): 57-76, mayo-ago. 2000. ilus, tab, graf
Article in Spanish | BINACIS | ID: bin-5985

ABSTRACT

Con el objeto de explorar su potencial empleo en terapéutica no citotóxicas, se estudió, en células leucémicas humanas, la vía de señalización y probable rol regulatorio del receptor a histamina H2. Mediante ensayos de binding, se detectaron sitios de unión específica de tipo H2, en casi todas las muestras de M.O.y S.P. de pacientes con L.A., con diferentes grados de infiltración. esto sugiere la presencia del receptor H2, en células hemopoyéticas normales y transformadas. La líneas U-937, modelo de célula monoblástica, presenta receptores H2, acoplados a AMPc. Su estímulo no produjo cambios proliferativos, ni deferenciación celular, pero sí un aumento transitorio, vía proteín kinasa A (PKA), en la expresión de Fos y Hun, sin reducción de Myc. Se hipotizó que el fracaso del estímulo H2, para diferenciar las células U-937 podría deberse a que su activación de la PKA es breve. Concordante con lo anterior, los receptores H2, mostraron una veloz de desensibilización homóloga (T. 1/2 = 20´). En cambio la forskolina, un activador directo de la adenil ciclasa, no desensibilizó su estímulo ni aún después de 24 horas de incubación. La forskolina también inhibió la proliferación U-937 a las mismas concentraciones en que estimuló la síntesisde AMPc e indujo su diferenciación fagocitaria, con reducción del NBT y respuesta quimiotáctica al C5a. Conclusiones: 1) La desensibilización veloz de un receptor que transduce una señal diferenciadora, como el H2, en las células U-937, podría ser un mecanismo fisiopatogénico de la malignificación, al bloquear la recepción de estímulos madurativos por la célula neoplásica. 2) Dados estos resultados, y los efectos diferenciadores del dibutril AMPc (DBAMPc) en líneas celulares mieloides, los agentes que elevan el AMPc merecen ser valorados en la terapia de las LMA (AU)


Subject(s)
Humans , Receptors, Histamine H2
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