Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma.

BACKGROUND: Recent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy. METHODS: Data from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils <300/µL [low] vs ≥300/µL [high]) and baseline markers of asthma severity (emergency asthma treatment in prior year, asthma hospitalization in prior year, forced expiratory volume in 1 second [FEV1 ; FEV1 <65% vs ≥65% predicted], inhaled beclomethasone dipropionate dose [<600 vs ≥600 µg/day], and long-acting beta-agonist [LABA] use [yes/no]). RESULTS: Adults/adolescents (N = 1071) were randomized to receive either omalizumab (n = 542) or placebo (n = 529). In the 16-week ICS dose-stable phase, rates of exacerbations requiring ≥3 days of systemic corticosteroid treatment were 0.066 and 0.147 with omalizumab and placebo, respectively, representing a relative rate reduction in omalizumab-treated patients of 55% (95% CI, 32%-70%; P = .002). For patients with eosinophils ≥300/µL or with more severe asthma, this rate reduction was significantly more pronounced. CONCLUSION: In patients with allergic asthma, baseline blood eosinophil levels and/or clinical markers of asthma severity predict response to omalizumab.

Prolonged saltatory fetal heart rate pattern leading to newborn metabolic acidosis.

PURPOSE: The saltatory pattern, characterized by wide and rapid oscillations of the fetal heart rate (FHR), remains a controversial entity. The authors sought to evaluate whether it could be associated with an adverse fetal outcome. MATERIAL AND METHODS: The authors report a case series of four saltatory patterns occurring in the last 30 minutes before birth in association with cord artery metabolic acidosis, obtained from three large databases of internally acquired FHR tracings. The distinctive characteristics of this pattern were evaluated with the aid of a computer system. RESULTS: All cases were recorded in uneventful pregnancies, with normal birthweight singletons, born vaginally at term. The saltatory pattern lasted between 23 and 44 minutes, exhibited a mean oscillatory amplitude of 45.9 to 80.0 beats per minute (bpm) and a frequency between four and eight cycles per minute. CONCLUSIONS: A saltatory pattern exceeding 20 minutes can be associated with the occurrence of fetal metabolic acidosis.

Unraveling the mystery of fever of unknown origin: a remarkable journey towards the diagnosis of peripheral T-cell lymphoma-T follicular helper type: A rare case report.

INTRODUCTION: Fever of unknown origin (FUO) remains one of the most challenging clinical conditions. It demands an exhaustive diagnostic approach, considering its varied etiologies spanning infectious, autoimmune, inflammatory, and malignant causes. PATIENT CONCERNS: This report shows the journey of diagnosing a 28-year-old male who presented with persistent fever and lower-extremity weakness over 9 months. Despite seeking care at multiple hospitals, a definitive diagnosis remained elusive. DIAGNOSIS: The patient underwent a series of evaluations in various specialties, including gastroenterology, infectious diseases, rheumatology, hematology, and cardiology. Multiple tests and treatments were administered, including antiviral therapy for hepatitis B and antibiotics for suspected infections. INTERVENTIONS: After an initial misdiagnosis and unsuccessful treatments, a positron emission tomography-computed tomography scan and lymph node biopsy ultimately led to the diagnosis of peripheral T-cell lymphoma-T follicular helper type (PTCL-TFH) lymphoma. The patient was referred to the hematology clinic and initiated on CHOEP (cyclophosphamide, vincristine, etoposide, and prednisone) chemotherapy. OUTCOMES: The patient showed a positive response to CHOEP therapy, as indicated by a posttreatment positron emission tomography-computed tomography scan. He reported a significant improvement in his quality of life. Additional rounds of the same regimen were planned to further manage the lymphoma. CONCLUSION: This case emphasizes the importance of a comprehensive and persistent diagnostic approach in managing FUO. Initially, the focus on infectious causes led to extensive treatments, but the disease's progression and complications shifted attention to other specialties. The eventual diagnosis of PTCL-TFH lymphoma highlights the significance of advanced imaging techniques and multidisciplinary collaboration in uncovering elusive diagnoses. Thorough surveillance, timely reassessments, and repeated testing can uncover definitive changes critical for diagnosis. PTCL-TFH lymphoma, although rare, should be considered in the differential diagnosis of FUO, especially when initial evaluations are inconclusive.

Ultrasound gel causes fine needle aspiration artifact? A clear choice.

OBJECTIVES: Ultrasound-guided fine needle aspiration (FNA) is a commonly employed tool in cytopathologic practice. Artifacts resulting in misinterpretation of specimens have been noted with various ultrasound gel media. Our purpose was to perform a prospective human cadaveric study of this phenomenon to identify a low-cost solution that eliminates the artifact. STUDY DESIGN: Three separate ultrasound-guided FNAs were performed on the thyroid and parotid glands in situ of a fresh human cadaver using three different types of ultrasound gel media. Slides were prepared in standard fashion (Quik-Diff and Papanicolaou stains). Two cytopathologists subsequently analyzed the slides for the presence of any artifact interfering with their ability to visualize and interpret the cellular aspirate material. RESULTS: Two of the three gel media revealed significant artifacts mimicking apoptosis, necrosis or colloid, making it difficult to visualize the cellular components and differentiate the artifact from the thyroid colloid. One gel medium did not show any significant artifact, and there was no discernable difference in its quality with regard to the ultrasound image during FNA procedures. CONCLUSIONS: Ultrasound gels can be associated with a significant artifact in FNA specimens. To eliminate this artifact, which may alter the adequacy, diagnosis or cytologic appearance, we confirm a specific gel type that is useful for ultrasound-guided FNAs.

Renal cell carcinoma presented with a rare case of icteric Stauffer syndrome: A case report.

BACKGROUND: Paraneoplastic syndromes remain poorly understood and manifest as multifaceted clinical symptoms, making their diagnosis difficult. Cholestasis can be observed in various malignancies. In rare cases, it can be a paraneoplastic manifestation, most often associated with renal cell carcinoma and other urogenital tumors, as well as with bronchial carcinoma. The classical form of Stauffer syndrome presents with a reversible anicteric increase of cholestatic liver function tests, thrombocytosis, coagulation impairment, and hepatosplenomegaly, without any proven hepatobiliary obstruction or metastases. CASE SUMMARY: We report a patient who presented with elevated liver enzymes, cholestatic jaundice, weight loss and pruritus, in whom renal cell carcinoma was incidentally found during hospitalization. Clinical, laboratory, and imaging tests excluded primary hepatic cause or metastatic disease. Jaundice and laboratory abnormalities reversed completely a few months after nephrectomy. This case is an example of the many sides of renal cell carcinoma, and it focuses the clinicians' attention on the differential diagnosis of cholestasis, including Stauffer syndrome and its variant. Thus, the correct diagnosis can be straightforward and the associated malignancy can be treated promptly. All cases should be followed up with a multidisciplinary team. Interleukin (IL)-6 is proposed to contribute to the pathophysiology of the condition. The probable mechanism is proinflammatory activity by the IL-6 cytokine, causing elevation of C-reactive protein and haptoglobin and inhibition of hepatobiliary transporter gene expression, impairing biliary outflow. CONCLUSION: Despite being rare, Stauffer syndrome is a potentially reversible paraneoplastic condition, when the primary cause is treatable. This syndrome should be considered by clinicians because of the remediable liver disturbance, after successful treatment of the underlying malignancy.

Response of spring wheat and potato to foliar application of Zn, Mn and EDTA fertilizers on 137Cs uptake.

The impact of foliar fertilization with zinc (ZnSO4) and manganese (MnSO4 on 137Cs uptake by spring wheat and potato was studied. The experiments were conducted during 3 years (2014-2016) in a137Cs-contaminated area, Zhytomyr region of Ukraine. The fertilization was carried out on podzolic loamy sand soil, poor in most of the microelements. Both crops were fertilized at four successive stages of growth. Foliar application of fertilizers caused higher yield of wheat grain/straw and potato tubers yield in 2014-2015 years but had no effect in 2016. Thus, the overall effect of fertilization between 2014 and 2016 was less pronounced and generally insignificant. Application of Zn, Mn and EDTA reduced 137Cs uptake by wheat grain and potato tubers, when fertilized at earlier stages of growth and development in years 2014 and 2015 by factor 1.5-2.0, while in 2016 the effect was generally statistically insignificant. It is suggested, that reduction of 137Cs uptake by spring wheat and potato, at least partly, was caused by an effect of radionuclide dilution due to the higher biomass of the plants. A foliar spray of EDTA at earlier stages of plant growth and development may be considered as a potential countermeasure aiming reducing 137Cs uptake from soil to plants, even if such effect appeared to be conditional.

Deep Learning for Ultrasonic Crack Characterization in NDE.

Machine learning for nondestructive evaluation (NDE) has the potential to bring significant improvements in defect characterization accuracy due to its effectiveness in pattern recognition problems. However, the application of modern machine learning methods to NDE has been obstructed by the scarcity of real defect data to train on. This article demonstrates how an efficient, hybrid finite element (FE) and ray-based simulation can be used to train a convolutional neural network (CNN) to characterize real defects. To demonstrate this methodology, an inline pipe inspection application is considered. This uses four plane wave images from two arrays and is applied to the characterization of cracks of length 1-5 mm and inclined at angles of up to 20° from the vertical. A standard image-based sizing technique, the 6-dB drop method, is used as a comparison point. For the 6-dB drop method, the average absolute error in length and angle prediction is ±1.1 mm and ±8.6°, respectively, while the CNN is almost four times more accurate at ±0.29 mm and ±2.9°. To demonstrate the adaptability of the deep learning approach, an error in sound speed estimation is included in the training and test set. With a maximum error of 10% in shear and longitudinal sound speed, the 6-dB drop method has an average error of ±1.5 mmm and ±12°, while the CNN has ±0.45 mm and ±3.0°. This demonstrates far superior crack characterization accuracy by using deep learning rather than traditional image-based sizing.

A new tool for the validation of umbilical cord acid-base data.

OBJECTIVE: To identify the distribution of carbon dioxide tension (pCO(2) ) relative to pH in validated umbilical cord acid-base data. DESIGN: Observational study. SETTING: European hospital labour wards. POPULATION: Data for 36,432 term newborns were obtained from three sources: two trials of fetal monitoring with electrocardiography (ECG; the Swedish randomised controlled trial and the European Union Fetal ECG trial) and data from Mölndal Hospital. METHODS: From the total study population, cases with missing values or obvious typing errors were excluded. The remaining data were validated based on specified criteria. Percentiles of arterial pCO(2) by pH were calculated using multilevel regression modelling. MAIN OUTCOME MEASURES: Umbilical cord pH, pCO(2) and base deficit. RESULTS: Acid-base values were considered invalid in one out of seven cases. Percentiles for arterial pCO(2) corresponding to specified values of arterial pH were developed from the validated data of 26, 690 cases. CONCLUSIONS: Percentiles for arterial pCO(2) for a specified arterial pH can be used as a tool to identify cases with erroneously low pCO(2) values, and thus avoid an incorrect interpretation of the newborn's acid-base status.

Plane Wave Imaging Techniques for Immersion Testing of Components With Nonplanar Surfaces.

Plane wave imaging (PWI) is an ultrasonic array imaging technique used in nondestructive testing, which has been shown to yield high resolution with few transmissions. Only a few published examples are available of PWI of components with nonplanar surfaces in immersion. In these cases, inspections were performed by adapting the transmission delays in order to produce a plane wave inside the component. This adaptation requires prior knowledge of the component geometry and position relative to the array. This article proposes a new implementation, termed PWI adapted in postprocessing (PWAPP), which has no such requirement. In PWAPP, the array emits a plane wave as in conventional PWI. The captured data are input into two postprocessing stages. The first reconstructs the surface of the component; the latter images inside of it by adapting the delays to the distortion of the plane waves upon refraction at the reconstructed surface. Simulation and experimental data are produced from an immersed sample with a concave front surface and artificial defects. These are processed with conventional and surface corrected PWI. Both algorithms involving surface adaptation produced nearly equivalent results from the simulated data, and both outperform the nonadapted one. Experimentally, all defects are imaged with a signal-to-noise ratio (SNR) of at least 31.8 and 33.5 dB for, respectively, PWAPP and PWI adapted in transmission but only 20.5 dB for conventional PWI. In the cases considered, reducing the number of transmissions below the number of array elements shows that PWAPP maintains its high SNR performance down to the number of firings equivalent to a quarter of the array elements. Finally, experimental data from a more complex surface specimen are processed with PWAPP resulting in detection of all scatterers and producing SNR comparable to that of the total focusing method.

Activated Ras prevents downregulation of Bcl-X(L) triggered by detachment from the extracellular matrix. A mechanism of Ras-induced resistance to anoikis in intestinal epithelial cells.

Detachment of epithelial cells from the extracellular matrix (ECM) results in a form of apoptosis often referred to as anoikis. Transformation of intestinal epithelial cells by oncogenic ras leads to resistance to anoikis, and this resistance is required for the full manifestation of the malignant phenotype. Previously, we demonstrated that ras-induced inhibition of anoikis in intestinal epithelial cells results, in part, from the ras-induced constitutive downregulation of Bak, a pro-apoptotic member of the Bcl-2 family. Since exogenous Bak could only partially restore susceptibility to anoikis in the ras-transformed cells, the existence of at least another component of the apoptotic machinery mediating the effect of activated ras on anoikis was suggested. Indeed, here we show that, in nonmalignant rat and human intestinal epithelial cells, detachment from the ECM or disruption of the cytoskeleton results in a significant downregulation of the antiapoptotic effector Bcl-X(L), and that activated H- or K-ras oncogenes completely abrogate this downregulation. In addition, we found that enforced downregulation of Bcl-X(L) in the ras-transformed cells promotes anoikis and significantly inhibits tumorigenicity, indicating that disruption of the adhesion-dependent regulation of Bcl-X(L) is an essential part of the molecular changes associated with transformation by ras. While the ras-induced downregulation of Bak could be reversed by pharmacological inhibition of phosphatidylinositol 3 kinase (PI 3-kinase), the effect of ras on Bcl-X(L) was PI 3-kinase- and mitogen-activated protein kinase (MAP kinase)-independent. We conclude that ras-induced resistance to anoikis in intestinal epithelial cells is mediated by at least two distinct mechanisms: one that triggers downregulation of Bak and another that stabilizes Bcl-X(L) expression in the absence of the ECM.

Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo.

ARIA (for acetylcholine receptor-inducing activity), a protein purified on the basis of its ability to stimulate acetylcholine receptor (AChR) synthesis in cultured myotubes, is a member of the neuregulin family and is present at motor endplates. This suggests an important role for neuregulins in mediating the nerve-dependent accumulation of AChRs in the postsynaptic membrane. Nerve-muscle synapses have now been analyzed in neuregulin-deficient animals. Mice that are heterozygous for the deletion of neuregulin isoforms containing an immunoglobulin-like domain are myasthenic. Postsynaptic AChR density is significantly reduced, as judged by the decrease in the mean amplitude of spontaneous miniature endplate potentials and bungarotoxin binding. On the other hand, the mean amplitude of evoked endplate potentials was not decreased, due to an increase in the number of quanta released per impulse, a compensation that has been observed in other myasthenic states. Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal.

Variations of sex development: The first German interdisciplinary consensus paper.

INTRODUCTION: The term variations of sex development subsumes a large number of congenital conditions including chromosomal mosaics and variations of chromosomal, gonadal, and phenotypic sex. A situation of this nature may cause severe distress to both, parents and affected persons. One of the reasons for this is the binary form of gender classification in the society. In the past, because of a fear of possible stigmatization and an inability to cope with complex situations, it has been medical policy and practice for newborns to undergo early, mostly 'feminizing' elective surgery with the aim of achieving an outer genital appearance that is unambiguously male or female. Protests by advocacy groups for the most part as well as the results of outcome studies have shown that the development of affected persons may be very different to what has been expected and often does not result in the intended clear female or male gender identity as had been intended. It, therefore, seemed a matter of urgency to implement this new awareness as well as the ethical and personal human rights perspectives in the recommendations for the medical and psychosocial management of diverse sex development (DSD) in the future. STUDY DESIGN: In 2012, an interdisciplinary group of German academics engaged in the field of DSD decided to work on a consensus paper for this topic. It involved the participation of all faculties and non-scientific groups dealing with DSD, in particular advocacy and service-user groups. In a structured consensus, process recommendations were developed based on scientific literature as well as personal experiences of clinicians and affected individuals. RESULTS: Finally, 37 recommendations were agreed on. The strength of consensus is reflected in the degree of agreement as expressed in percentages. CONCLUSION: The introduction of the consensus paper reflects on the emerging paradigm shift and the necessity for a more open view of gender within society. The paper is intended to aid the performance of appropriate diagnostics in DSD-affected newborns and especially to help parents and affected persons cope with the biological and social consequences of DSD. With regard to medical or surgical therapy, it gives information about the most recent treatment trends.

Differential expression of ARIA isoforms in the rat brain.

ARIA, heregulin, neu differentiation factor, and glial growth factor are members of a new family of growth and differentiation factors whose effects have been assayed on Schwann cells, skeletal muscle cells, and mammary tumor cell lines. To gain insight into their roles in the CNS, we studied the expression of ARIA in the rat brain. We found ARIA mRNA in all cholinergic neurons throughout the CNS, including motor neurons and cells of the medial septal nucleus and the nucleus basalis of Meynert. We also found that ARIA induces tyrosine phosphorylation of a 185 kDa protein in central and peripheral targets of these cholinergic neurons. ARIA mRNA, however, is not restricted to cholinergic neurons, suggesting that it may also play a role at other types of synapses. Its distribution in germinal layers of the telencephalon and cerebellum suggests that it may also play a role in the proliferation and/or migration of neuronal and glial precursor cells.

Activity-dependent modulation of synaptic AMPA receptor accumulation.

Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.

Transfer of radionuclides and dose assessment to ants and anthills in a Swedish forest ecosystem.

In forest ecosystems soil organisms are important for immobilization, translocation and recycling of radionuclides. Still, there is a lack of studies on the role of insects such as ants in the turnover of radionuclides and how radioactivity affects an ant community. In this study seven anthills were sampled in an area that was heavily contaminated after the fallout from the Chernobyl accident. Samples of ant and anthill materials were taken from different depths of the anthills as well as from the surrounding soil and the activity concentrations of 137Cs were determined. In addition, a radiation dose assessment was performed for ants and anthills using the ERICA tool. The deposition of 137Cs in 1986 in the study area was calculated back to be on average 110,500 Bq m-2. The averaged data for all the seven locations investigated indicate that the level of 137Cs activity concentrations in the anthill's material increased with depth of the anthill being highest at the depth 50-65 cm. The concentration in the upper layers (0-2 cm) and of the ants showed significant correlations with the deposition upon multivariate analysis. The concentration ratio (CR) defined as the ratio between the mass activity for 137Cs density in ants (Bq kg-1 d.w.) and mass activity density in soil (Bq kg-1 d.w.) was determined to be in the range of 0.04-0.14. Also, the transfer factor (TF) defined as the ratio between the mass activity for 137Cs density in ant (Bq kg-1 d.w.) and to the unit area activity density (in Bq m-2 d.w.) was determined for 137Cs to be 0.0015 m2 kg-1 d.w. The assessed radiation doses were found to be a 4.9 µGy h-1 which is below international reference levels for non-human biota.

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells.

Detachment of normal epithelial cells from the extracellular matrix triggers apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be relatively more anoikis-resistant than their normal counterparts, and this increased resistance represents a critical feature of the malignant phenotype. Mechanisms that control susceptibility and resistance to anoikis are not fully understood. It is now known that detachment of non-malignant epithelial cells triggers both pro- and antiapoptotic signals, and it is the balance between these signals and the duration of detachment that determine further fate of the cells. Detachment-induced antiapoptotic events delay anoikis and if cells reattach relatively soon after detachment they survive. Direct regulators of apoptosis responsible for this delay of anoikis are unknown. We found that detachment of non-malignant intestinal epithelial cells triggers upregulation of inhibitors of apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated that this upregulation requires detachment-dependent activation of the transcription factor nuclear factor-kappaB. We further observed that various IAP antagonists accelerate anoikis, indicating that upregulation of the IAPs delays detachment-triggered apoptosis. We conclude that the IAPs are important regulators of the balance between detachment-triggered life and death signals. Perhaps, not by coincidence, these proteins are often upregulated in carcinomas, tumors composed of cells that tend to be anoikis-resistant.

Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells.

Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix [1] [2] [3]. In epithelial cells of the intestine and other organs, activated rasinduces resistance to anoikis [3] [4], but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours [5]. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells [6] [7]. Here, we show that activated rasinduces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis [8]. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of rasto downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.

The electrophysiological effects of ouabain on sinus node and atrium in man.

Electrophysiological studies were performed in 16 patients before and 30 min after intravenous administration of ouabain (0.1 mg/kg). P-A interval (mean+/-SEM) was 40+/-2.1 ms before and 44+/- 1.5 ms after ouabain (P less than 0.001). Atrial effective and functional refractory periods (ERP and FRP) were measured in all patients during sinus rhythm and during driving at equivalent paced rates in 12 patients. The mean atrial ERP and FRP during sinus rhythm were, respectively, 244+/-10.5 and 307+/-11.0 ms before and 253+/-9.7 and 318+/-11.4 ms after infusion of ouabain (NS). Mean atrial ERP and FRP during driving were, respectively, 231+/-15.3 and 264+/-14.9 ms before and 266+/-18.6 and 296+/-19.7 ms after ouabain (P less than 0.01 and P less than 0.01). Mean sinus cycle length and sinus recovery times were, respectively, 887+/-31.2 and 1,113+/-38.7 ms before and 905+/-38.2 and 1,008+/-30.7 ms after infusion of ouabain (NS and P less than 0.005). Calculated sinoatrial conduction times before and after ouabain were 90+/-6.8 and 110+/-8.5 ms, respectively (P less than 0.005). In summary, ouabain produced depression of intraatrial conduction as manifested by increase in P-A interval and atrial effective and functional refractory periods. Ouabain significantly increased calculated sinoatrial conduction time without significant effect on spontaneous sinus cycle length.

Interleukin 6 gene expression in normal and neoplastic B cells.

In the present report we demonstrate that the IL-6 gene is expressed in anti-Ig-activated and neoplastic B cells. After activation with anti-Ig, splenic B cells rapidly expressed IL-6 mRNA with peak expression occurring at 4 h and declining rapidly thereafter. In an attempt to exclude that the IL-6 mRNA expression was in non-B cells, T cells and monocytes were extensively depleted. In this highly purified B cell population, IL-6 mRNA was retained, whereas the expression of the T cell- and monocyte-restricted CD2 and CD14 genes was nearly undetectable. These results are consistent with the conclusion that activated B cells express IL-6 mRNA. Because we found IL-6 mRNA expression in normal activated B lymphocytes, we examined the expression of IL-6 mRNA in B cell neoplasms. 11 of 25 non-Hodgkins B cell lymphomas and 4 of 4 myelomas and plasma cell leukemias expressed IL-6 mRNA, whereas only 1 of 19 B cell leukemias was positive. To exclude that IL-6 mRNA expression in neoplastic B cells was the result of contaminating non-B cells, T cells and monocytes were extensively depleted from the tumor specimens. In the three IL-6-positive tumor samples depleted of T cells and monocytes, IL-6 mRNA expression was retained in all cases. These observations provide support for the idea that the IL-6 gene is expressed in normal activated and neoplastic B cells.