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Parathyroid hormone-related protein in epithelial lining fluid in humans negatively correlates with the severity of lung injury.

OBJECTIVE: To determine the concentration of parathyroid hormone-related protein (PTHrP; an autocrine/paracrine regulator of type-2 alveolar epithelial cells proliferation and apoptosis) in the epithelial lining fluid (ELF) from patients without pulmonary disease and from patients with acute lung injury (ALI), and to evaluate whether PTHrP concentrations correlated with the intensity of lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU in an urban teaching hospital. PATIENTS: A total of 20 patients with ALI receiving mechanical ventilation (patients), and 10 patients without pulmonary disease not receiving mechanical ventilation (control subjects). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PTHrP was detected in all BAL fluids, and ELF PTHrP concentrations (median; 25% to 75% percentiles) tended to be higher in patients (52.2 nmol/mL; 20.8 to 65.6 nmol/mL) than in control subjects (25.4 nmol/mL; 20.5 to 35.4 nmol/mL; p = 0.18). In patients, ELF PTHrP concentration correlated positively with the PaO(2)/fraction of inspired oxygen ratio (r = 0.53; p = 0.005), and negatively with lung injury score (r = - 0.44; p = 0.02), radiologic score (r = - 0.40; p = 0.04), and BAL albumin concentration (r = - 0.42; p = 0.02). CONCLUSION: PTHrP is present in biologically significant concentrations in the alveolar milieu in humans. In patients with ALI, the PTHrP concentration correlates negatively with the degree of lung injury.

Acute Disease↗

Treatment of advanced gastric cancer with etoposide, folinic acid, and fluorouracil in the clinical setting: efficacy of therapy and value of serum tumor markers.

The combination of etoposide, folinic acid, and 5-fluorouracil (5-FU) (ELF regimen) has been proved to be an active chemotherapy in patients with advanced gastric cancer. The aim of this study was to confirm the efficacy in the clinical setting and to correlate response with different parameters like serum tumor markers. We treated 60 patients with advanced gastric cancer with 120 mg/m2 etoposide, 300 mg/m2 folinic acid, and 500 mg/m2 5-FU, on d 1-3. The cycle was repeated on d 21. Objective response was obtained in 23% of all patients with measurable disease. Stable disease was obtained in 37%. The tumor-growth-control rate in patients with proximal carcinoma was significantly higher than in those with distal carcinoma (85% vs 48%, p = 0.04). Median survival for all patients was 8.0 mo (95% confidence interval [CI] 7.0-8.5). In responsive patients, survival was more than two-fold longer than in patients with progressive disease. The administration of ELF could be performed safely on an outpatient basis. Toxicity was rather mild. The most frequently elevated serum tumor marker was CA 72-4 (55% of the patients). An elevated level of carcinoembryonic antigen before treatment was significantly correlated with progressive disease. A more than two-fold elevation of at least one marker under treatment was significantly correlated to progressive disease (p < 0.002). A reduction of at least one marker under treatment was significantly correlated to tumor growth control (p < 0.00015). The results of the present trial confirm the efficacy and low toxicity of the ELF regimen in advanced gastric carcinoma. Serum tumor markers proved suitable parameters for assessing response to treatment.

Adult↗

Exposure to low-frequency electromagnetic fields does not alter HSP70 expression or HSF-HSE binding in HL60 cells.

Environmental exposure to extremely low-frequency electromagnetic fields (ELF EMFs) has been identified as a possible contributor to increased cancer incidence and other diseases. In vitro studies designed to probe for biological mechanisms that might explain such relationships have included several studies of gene expression. While gene expression studies have focused on MYC, effects of ELF EMFs on the expression of beta-actin, histone H2B, beta-tubulin, SRC, FOS and JUN have also been reported. In addition, some investigators have reported both an induction of HSP70 expression and an increase in HSF-HSE binding in HL60 (human promyelocytic leukemia) cells after exposure to a 60 Hz magnetic field. In this study, HL60 cells were exposed to a weak 60 Hz magnetic field (6.3 or 8.0 microT) or to a positive control heat shock (42 or 44 degrees C). While heat shock led to reproducible induction of HSP70 expression and HSF-HSE binding, no significant effect of exposure to ELF EMFs on either of these end points was observed.

Blotting, Northern↗

The fate of exogenous surfactant in neonates with respiratory distress syndrome.

Respiratory distress syndrome (RDS) in newborn neonates is characterised by deficient secretion of surfactant from type III alveolar cells. Administration of surfactant to airways acutely decreases the degree of respiratory failure and increases the survival rate in neonates with RDS. Clinically available surfactants are lipid extracts derived from animal lung lavage or from whole lung. Synthetic surfactants contain phospholipids or additional spreading agents. An optimal exogenous surfactant would be efficacious, nontoxic and nonimmunogenic, resistant to oxidants and proteolytic agents, widely available at reasonable cost and manufactured with little batch-to-batch variability. Surfactant has been instilled into the airways as a bolus infusion through the endotracheal tube. In addition, surfactant may be given by aerosolisation or continuous infusion into the airways. Suggested dosages range from 50 to 200 mg/kg. Exogenous surfactant is cleared from the epithelial lining fluid (ELF) mainly by alveolar epithelial cells, although alveolar macrophages and the central airways may also contribute to clearance of the drug. Only small quantities of surfactant actually enter the blood stream. A significant fraction of surfactant is taken up, processed, and secreted back into the alveolar space by type II alveolar cells. This process is termed recycling. Phosphatidylglycerol, given to small premature neonates as a component of exogenous human surfactant, has an apparent pulmonary half-life of 31 +/- 3 hours (n = 11). The apparent pulmonary half-life of the main surfactant component dipalmitoyl phosphatidylcholine is 45 hours (n = 3) and that of surfactant protein A is about 9 hours (n = 4). A relationship between the dose of exogenous surfactant and its concentration in the ELF has been demonstrated. Some neonates with RDS respond poorly to surfactant therapy. The reasons for this include insufficient levels of surfactant in the ELF, uneven distribution of exogenous surfactant, inability of exogenous surfactant to enter the metabolic pathways, inhibition of surface activity by plasma-derived proteins, or inactivation of surfactant as a result of proteases, phospholipases, or oxygen free radicals. In addition, surfactant therapy may be ineffective in neonates with respiratory failure caused by factors other than surfactant deficiency. The efficacy of exogenous surfactant can be improved by increasing the dosage of surfactant and by administration of surfactant very early in respiratory failure.

Animals↗

The relationship between oncogene expression and clinical outcome in endometrial carcinoma.

The mechanism of oncogenesis is extremely complicated and controlled by various factors, most of which are based on cell proliferation, tumor invasion, neovascularization, and inhibition of apoptosis. We have investigated the relationship between thirty three oncogenes expression and histopathological prognostic factors of endometrial carcinomas, including clinical stage, histological grade, presence of invasion to greater than one-half the myometrium, clinical outcome, and survival rate. Scoring on the basis of the percentage of positive cells indicated that Plks, EphB4, ephrin-B2, Id1, CaMKIV, c-Ets1, Elf-1, and survivin expression were significantly associated with PCNA-labeling index, clinical stage, histological grade, the presence of invasion to greater than one-half the myometrium, and clinical outcome. Survival data were available for all patients, and univariate Cox regression analysis showed that Plks, CaMKIV, Elf-1, and survivin expression were significantly associated with poor prognosis. Our results demonstrate that some oncogenes expression in endometrial carcinoma correlate with the malignant potential of these tumors. Thus, in addition to being of diagnostic value, modulation of these oncogenes activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value. In this review, we demonstrate the biologic behavior of seven novel molecules (Plks, Eph/ephrin, Id family, CaMK, c-Ets1, Elf-1, and survivin) in the endometrial carcinoma.

Animals↗

Leucine metabolism in IDDM. Role of insulin and substrate availability.

The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine. All diabetic subjects were studied while in poor metabolic control (fasting glucose 13.3 +/- 1.1 mM; HbA1c 10.8 +/- 0.2%) and again after 2 mo of intensified insulin therapy (fasting glucose 7.2 +/- 0.5 mM; HbA1c 8.0 +/- 0.2%). Insulin-mediated total-body glucose uptake in poorly controlled diabetic subjects (3.6 +/- 0.5 mg.kg-1.min-1) was significantly reduced compared with control subjects (7.5 +/- 0.2 mg.kg-1.min-1; P less than .001) and improved slightly after insulin therapy (4.8 +/- 0.3 mg.kg-1.min-1; P less than .05), although it still remained significantly lower than in control subjects (P less than .01). During the insulin-clamp study performed in subjects with poorly controlled IDDM, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) all decreased (50.1 +/- 2.0 to 26.4 +/- 0.4; 9.2 +/- 0.4 to 6.0 +/- 0.3; 40.9 +/- 2.0 to 20.4 +/- 2.0 mumol.m-2.min-1, respectively) to the same extent as in control subjects. After 2 mo of intensified insulin therapy, the effect of acute hyperinsulinemia on ELF, LO, and NOLD was comparable to that of control subjects, whereas insulin-stimulated glucose metabolism was still impaired. To examine the effect of substrate availability on leucine turnover, well-regulated IDDM and control subjects underwent a repeat insulin-clamp study combined with a balanced amino acid infusion designed to increase circulating plasma amino acid levels approximately twofold. Under these conditions, NOLD was equally enhanced above baseline in both control and IDDM subjects (P less than .01), whereas ELF was inhibited to a greater extent (P less than .01) than during the insulin clamp performed without amino acid infusion (control vs. diabetic subjects, NS). In conclusion, insulin-mediated glucose metabolism is severely impaired in subjects with both poorly controlled and well-controlled IDDM, whereas the effect of acute insulin infusion on leucine turnover is normal, and combined hyperaminoacidemia/hyperinsulinemia stimulated NOLD to a similar extent in both IDDM and control subjects.

Adult↗

[Software modeling for better understanding of pharmacokinetic-pharmacodynamic relationships: application to azithromycin in the treatment of streptococcal tonsillitis and in acute exacerbation fo chronic bronchitis]].

In order to illustrate the significance of pharmacokinetic/pharmacodynamic (PK/PD) parameters of azithromycin (AZM) in tonsillar and respiratory tract infections, we developed original simulation software. As area under the curve over 24 hours divided by the minimum inhibitory concentration (AUC24/MIC) and time over a 24-hour period that the drug concentration exceeds the MIC (t > MIC) are important predictors of the clinical efficacy of macrolides, our software calculates these indices for plasma, tonsil, epithelial lining fluid (ELF), lung tissue (LT) and alveolar macrophages (AM). For an MIC of 0.5 microgram.mL-1, after administration of AZM 500 mg daily for 3 days (tonsillitis) or AZM 500 mg on day 1 and 250 mg daily for the next 4 days (respiratory tract infections) to a 70 kg subject, PK/PD parameters are as follows: AUC24/MIC (h): 9.5 (plasma); 439 (tonsil); 57.5 (ELF); 439 (LT); 1354 (AM); t > MIC is 24 hours in all tissues. Our simulation model illustrates the following: (i) AUC24/MIC values are above the 25-30-hour threshold in S. pneumoniae infection; and (ii) tissue concentrations exceed the MIC for 6 days after the last dose in ELF and for more than 2 weeks in tonsils, LT and AM.

Anti-Bacterial Agents↗

Clearance of proteins from the air spaces following cardiogenic edema in sheep.

Studies on the clearance of instilled fluid and protein into the lungs of sheep show that fluid initially clears rapidly from the lungs resulting in an increase in an increase in air space protein concentrations. This is followed by a slower monoexponential clearance of proteins during the next few days. To determine whether the clearance of edema fluid follows the same time course as instilled fluid, alveolar edema was induced in 11 sheep by inflating a balloon in the left atrium for 2 h to increase left atrial pressure 35-40 cm H2O. Protein concentrations in the epithelial lining fluid (ELF) were monitored by performing single-cycle lavages immediately after deflation of the left atrial balloon, and again 3, 21, 48, and 96 h later. During the first 3 h of recovery, 44% of the fluid cleared and ELF protein concentrations rose from 7 +/- 2 to 19 +/- 6 mg/mL in the 7 sheep that recovered well. The ELF protein concentration in these sheep remained elevated for 48 h and then cleared at rates similar to that seen following instillation of proteins. We conclude that insights about mechanisms of clearance of edema fluid obtained from studies of clearance of instilled fluid are valid in cardiogenic edema, but the time course of the clearance differs between the two models.

Animals↗

Regulation of human Fc epsilon RI alpha-chain gene expression by multiple transcription factors.

Transcriptional regulation of the gene-encoding human Fc epsilon RI alpha-chain was analyzed in detail. EMSA revealed that either YY1 or PU.1 bound to the region close to that recognized by Elf-1. The alpha-chain promoter activity was up-regulated approximately 2-fold by exogenously expressed YY1 or PU.1 and approximately 7-fold by GATA-1, respectively, in KU812 cells. In contrast, coexpression of GATA-1 with either of PU.1 or YY1 dramatically activated the promoter approximately 41- or approximately 27-fold, respectively. Especially synergic activation by GATA-1 and PU.1 was surprising, because these transcription factors are known to inhibit the respective transactivating activities of each other. These up-regulating effects of PU.1 and YY1 with GATA-1 were inhibited by overexpression of Elf-1, indicating that Elf-1 serves as a repressor for the alpha-chain gene expression. Transcriptional regulation of the alpha-chain gene through four transcriptional factors is discussed.

Antibodies↗

Residential magnetic fields predicted from wiring configurations: I. Exposure model.

A physically based model for residential magnetic fields from electric transmission and distribution wiring was developed to reanalyze the Los Angeles study of childhood leukemia by London et al. For this exposure model, magnetic field measurements were fitted to a function of wire configuration attributes that was derived from a multipole expansion of the Law of Biot and Savart. The model parameters were determined by nonlinear regression techniques, using wiring data, distances, and the geometric mean of the ELF magnetic field magnitude from 24-h bedroom measurements taken at 288 homes during the epidemiologic study. The best fit to the measurement data was obtained with separate models for the two major utilities serving Los Angeles County. This model's predictions produced a correlation of 0.40 with the measured fields, an improvement on the 0.27 correlation obtained with the Wertheimer-Leeper (WL) wire code. For the leukemia risk analysis in a companion paper, the regression model predicts exposures to the 24-h geometric mean of the ELF magnetic fields in Los Angeles homes where only wiring data and distances have been obtained. Since these input parameters for the exposure model usually do not change for many years, the predicted magnetic fields will be stable over long time periods, just like the WL code. If the geometric mean is not the exposure metric associated with cancer, this regression technique could be used to estimate long-term exposures to temporal variability metrics and other characteristics of the ELF magnetic field which may be cancer risk factors.

Algorithms↗

Hazard surveillance for industrial magnetic fields: II. Field characteristics from waveform measurements.

Magnetic field characteristics have been surveyed systematically in six factories with the Multiwave(R) II waveform capture instrument. These six facilities manufactured plastics, pharmaceuticals, cement, liquid air products, aluminum parts, and aluminum-framed filters. The study goals were to survey the physical characteristics of magnetic fields that may be related to biological effects under various interaction mechanisms and to relate those characteristics to the field's sources. From 59 waveform measurements at worker locations near sources, we calculated the extremely low frequency (ELF) and static field magnitudes, their frequency characteristics, and spatial characteristics of the 60Hz component. The RMS vector magnitude of the ELF magnetic field (the usual exposure metric in most studies) had medians ranging from 0.53 to 12.83 microT in the six factories. The static magnetic field magnitudes had medians of 24.2-46.2 microT, which is well below the geomagnetic reference field of 55.0 microT because of shielding from steel structures. The maximum static field was 128.6 microT near a DC motor. The frequency spectra of the most common fields is dominated by 60Hz, and has a median total harmonic distortion equal to 14.8%. The most common higher frequencies are the third, fifth, and second harmonics of 60Hz. However, magnetic fields in these workplaces had many other 60Hz harmonics and non-harmonic frequencies due particularly to electric motors and computer monitors. The 60Hz component magnetic fields have elliptical polarization with median axial ratio of 25.4%. The average proportion of the 60Hz component parallel to the static field vector was 51.5+/-3.0%, which indicates a significant trend towards perpendicular orientation between these two field components. In this survey of only six factories, the Multiwave(R) II measurements documented a wide diversity of complex magnetic field characteristics and non-sinusoidal waveforms. Although these characteristics are important to the various mechanisms postulated to explain biological effects, they are overlooked by the popular exposure assessment methods which only measure the ELF magnitude. Therefore, spot measurements with the Multiwave(R) II or similar waveform capture instruments are necessary for a complete magnetic field exposure assessment.

Electromagnetic Fields↗

Effects of 50 Hz sinusoidal electromagnetic fields on MCP-1 and RANTES generated from activated human macrophages.

Extremely low frequency electromagnetic fields (ELF-EMF) induce cellular changes and modulate signal transduction pathways, and may be beneficial in the treatment of inflammatory diseases. In this paper we studied two inflammatory chemokines, MCP-1 and RANTES produced by human cultured isolated monocytes from peripheral blood, with or without PHA and in the absence or presence of 50 Hz magnetic field of 1.0 mT for 24 h. The production of MCP-1 and RANTES was determined by ELISA method. Here, we found that ELF-EMF strongly inhibited the production of these chemokines stimulated by PHA, while the control was not affected. Since MCP-1 and RANTES exert chemoattraction for several populations inflammatory leukocytes, the inhibitory effect of these chemokines could be one of the mechanisms by which ELF-EMF is therapeutic in inflammatory diseases.

Journal Article↗

[Levels of occupational exposure to extremely low frequency magnetic fields among workers in different jobs].

Using personal dosimeters, occupational exposure to ELF-MF was measured in 150 workers employed in 28 different occupations. The main results are presented. The overall arithmetical mean in the whole sample was 0.36 microT, the overall geometric mean 0.21 microT. A high variability among workers engaged in the same occupation, and among different days in the same worker, was observed. The results suggest a relatively low exposure to ELF-MF in the large part of workers. Nevertheless, the higher levels measured in some workers, and the high variability, show the need of adequate measurements of ELF-MF exposure in workers.

Electromagnetic Fields↗

Efficacy and safety of a musically modulated electromagnetic field (TAMMEF) in patients affected by knee osteoarthritis.

OBJECTIVE: Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in clinical practice. Moreover, the effects of these fields seems to depend on their respective codes (frequency, intensity, waveform). In our study we want to value the effects of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, which field is piloted by a musical signal. METHODS: Ninety subjects, affected by primary osteoarthritis of the knee, were enrolled in the study and randomly divided into three groups of 30 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrolment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later: RESULTS: All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF system is efficacious in the control of pain symptoms and in the reduction of functional limitation in patients with knee osteoarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.

Aged↗

[Occupational exposure to 50 Hz magnetic fields in workers employed in various jobs].

BACKGROUND: Information on occupational exposure to ELF magnetic fields (MF) in workers is largely insufficient, and is mostly based on results obtained in Scandinavian countries and North America. Accordingly, the collection of further data is needed, especially in workers exposed in other countries, including in Italy. METHODS: One hundred and fifty workers (84 males and 66 females) employed in 28 different jobs in the Emilia-Romagna Region of Italy were examined. Individual exposure was measured using personal monitors worn on the hip in a belted pouch during three whole work-shifts (8 hours each) of a normal working week. A sampling interval of 10 seconds was adopted, resulting in the collection of more than 8600 measurements for each worker. The individual Time-Weighted Average (TWA) occupational exposure of workers was calculated as the arithmetic mean of all measurements during each work-shift. Environmental non-occupational exposure was also measured. RESULTS: The 50 degrees percentile of individual TWA in the whole group was 0.15 microT, and the 5 degrees - 95 degrees percentile was respectively 0.02-1.45 microT. Job-related exposure (expressed as the mean of the TWA measured in all workers engaged in that job) was highest in substation electric power plant workers (1.12 microT) and in sewing machine workers (0.84 microT), but was lower than 0.2 microT in more than the 70% of the examined jobs. Considering the geometric mean of individual TWA are 27 out of 28 the jobs inducing an exposure lower than 0.2 microT. The lowest exposure was observed in infant school teachers. A high variability was observed among different workers engaged in the same occupation, mainly in substation electric power plant workers, machine testers and grinders in the engineering industry and in sewing machine workers and quality control in garment production. A marked variability of the pattern of exposure during the work-shift was also observed The overall environmental (non-occupational) exposure was 0.044 microT, and individual exposure was lower than 0.2 microT in about 97% of the examined subjects. Occupational exposure was usually higher and was not correlated with environmental exposure. CONCLUSIONS: The results show that the occupational component of overall exposure must be considered in studies on the biological effects of ELF-MF in populations. The high variability observed among workers engaged in the same occupation and the variability of the pattern of exposure certainly constitute major problems and could be a cause of the scarce coherence of the results of epidemiological studies on biological effects of ELF-MF to date. An improvement in protocols for the evaluation of exposure in workers, including the use of personal monitoring, is certainly needed.

Electromagnetic Fields↗

Evaluation of two media and different plating techniques for enumeration of thermotolerant coliforms in river water.

Testing for evidence of faecal contamination in river water has been traditionally accomplished by enumeration of thermotolerant coliform bacteria. In this work, deoxycholate lactose and m-Endo Agar LES media were evaluated using different techniques. The colony count methods were pour plate technique on Deoxycholate Agar (DCL pour plate), spread plating on m-Endo Agar LES (ELS spread), and membrane filtration on m-Endo Agar LES (ELF filtration). Typical thermotolerant coliform colonies were analysed by conventional biochemical tests. The three matched pairs showed statistically significant differences (P < 0.05) by the Wilcoxon signed rank test. One hundred and twenty three isolates obtained on m-Endo Agar LES (65%) were confirmed as E. coli. Likewise, one hundred and twenty isolates obtained on Deoxycholate Agar (71%) were confirmed as E. coli. The results of this study showed that the matched DCL-ELF presented the smaller statistically significant difference (P = 0.042) so, DCL could be used as alternative to ELF.

Agar↗

Respiratory tract gene transfer. Transplantation of genetically modified T-lymphocytes directly to the respiratory epithelial surface.

To evaluate the strategy for potentially treating respiratory disorders with genetically modified T-lymphocytes, the interleukin-2 (IL-2)-dependent murine T-cell line, CTLL2, was genetically altered with the Escherichia coli beta-galactosidase (beta-gal) gene (lacZ) in vitro with a retroviral vector and the modified T-cells were transplanted directly to the respiratory epithelial surface of syngeneic C57Bl/6 mice. Southern and Northern analyses confirmed that the neomycin-selected modified T-cells contained and expressed the lacZ gene. The fate of the modified T-cells (CTLL2/lacZ) was followed by flow cytometry with T-cell surface marker Thy1.2 and fluorescent beta-gal analysis. One day after transplantation (7.5 x 10(5) CTLL2/lacZ T-cells/g of body weight), 95 +/- 3% of the Thy1.2+ T-cells recovered from respiratory epithelial lining fluid (ELF) were beta-gal+. Importantly, the modified T-cells remained in the lung for some time; at 3 days, Thy1.2+ beta-gal+ T-cells represented 63 +/- 12% of ELF Thy1.2+ T-cells and 59 +/- 6% of Thy1.2+ T-cells recovered from the whole lung. At 7 days, 33 +/- 8% of the Thy 1.2+ cells in ELF and 75 +/- 6% of the Thy1.2+ cells in whole lung were Thy1.2+ beta-gal+. In contrast, the proportion of the Thy1.2+ beta-gal+ T-cells in the spleen, the major extrapulmonary lymphatic organ, never rose above 3 +/- 1% of the total Thy1.2+ cells. The number of Thy1.2+ beta-gal+ T-cells in the lung could be modified by the systemic administration of IL-2, with whole lung Thy1.2+ beta-gal+ T-cells increasing 4.6-fold 3 days after transplantation, compared with non-IL-2-treated animals. These studies suggest that direct transplantation of genetically modified T-cells into the lung is feasible and represents a viable strategy for lung-specific gene transfer.

Animals↗

No effect of 60 Hz electromagnetic fields on MYC or beta-actin expression in human leukemic cells.

Epidemiological studies have shown weak correlations between exposure to extremely low-frequency electromagnetic fields (ELF EMFs) and the incidence of several cancers, particularly childhood leukemias, although negative studies have also been reported. These observations have prompted a broad range of in vitro cellular studies in which effects of ELF EMFs have been observed. However, no reported response has been replicated widely in independent laboratories. One potentially important response is the rapid activation of proto-oncogenes and other genes in human leukemic (HL60) cells and a wide variety of other eukaryotic cells, because of the role of these genes in cell proliferation. We describe quantitative Northern analysis of MYC and beta-actin mRNAs from HL60 cells exposed to fields under conditions very similar to those reported previously to activate these genes, namely 60 Hz sinusoidal magnetic fields of 0.57, 5.7 or 57 microT for 20 min. In addition we have used a new design of field-exposure system and introduced a number of other modifications to the protocol to optimize any response. We have also developed a novel method providing enhanced accuracy for the quantitative measurement of mRNA. No significant effect of ELF EMFs on gene expression was observed using any of these systems and analytical methods.

Actins↗