A helium-burning white dwarf binary as a supersoft X-ray source.

Type Ia supernovae are cosmic distance indicators1,2, and the main source of iron in the Universe3,4, but their formation paths are still debated. Several dozen supersoft X-ray sources, in which a white dwarf accretes hydrogen-rich matter from a non-degenerate donor star, have been observed5 and suggested as Type Ia supernovae progenitors6-9. However, observational evidence for hydrogen, which is expected to be stripped off the donor star during the supernova explosion10, is lacking. Helium-accreting white dwarfs, which would circumvent this problem, have been predicted for more than 30 years (refs. 7,11,12), including their appearance as supersoft X-ray sources, but have so far escaped detection. Here we report a supersoft X-ray source with an accretion disk whose optical spectrum is completely dominated by helium, suggesting that the donor star is hydrogen-free. We interpret the luminous and supersoft X-rays as resulting from helium burning near the surface of the accreting white dwarf. The properties of our system provide evidence for extended pathways towards Chandrasekhar-mass explosions based on helium accretion, in particular for stable burning in white dwarfs at lower accretion rates than expected so far. This may allow us to recover the population of the sub-energetic so-called Type Iax supernovae, up to 30% of all Type Ia supernovae13, within this scenario.

Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography.

Detailed knowledge of the ultrastructure of intracellular compartments is a prerequisite for our understanding of how cells function. In cardiac muscle cells, close apposition of transverse (t)-tubule (TT) and sarcoplasmic reticulum (SR) membranes supports stable high-gain excitation-contraction coupling. Here, the fine structure of this key intracellular element is examined in rabbit and mouse ventricular cardiomyocytes, using ultra-rapid high-pressure freezing (HPF, omitting aldehyde fixation) and electron microscopy. 3D electron tomograms were used to quantify the dimensions of TT, terminal cisternae of the SR, and the space between SR and TT membranes (dyadic cleft). In comparison to conventional aldehyde-based chemical sample fixation, HPF-preserved samples of both species show considerably more voluminous SR terminal cisternae, both in absolute dimensions and in terms of junctional SR to TT volume ratio. In rabbit cardiomyocytes, the average dyadic cleft surface area of HPF and chemically fixed myocytes did not differ, but cleft volume was significantly smaller in HPF samples than in conventionally fixed tissue; in murine cardiomyocytes, the dyadic cleft surface area was higher in HPF samples with no difference in cleft volume. In both species, the apposition of the TT and SR membranes in the dyad was more likely to be closer than 10 nm in HPF samples compared to CFD, presumably resulting from avoidance of sample shrinkage associated with conventional fixation techniques. Overall, we provide a note of caution regarding quantitative interpretation of chemically-fixed ultrastructures, and offer novel insight into cardiac TT and SR ultrastructure with relevance for our understanding of cardiac physiology.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

[Quality indicators for rescue operations in terrorist attacks or other threats : A pilot study after the Würzburg terrorist attack of July 2016]. / Qualitätsindikatoren für rettungsdienstliche Einsätze bei Terroranschlägen oder anderen Bedrohungslagen : Eine Pilotstudie nach dem Würzburger Terroranschlag vom Juli 2016.

BACKGROUND: Terrorist attacks have become reality in Germany. The aim of this work was, after the Würzburg terrorist attack, to define quality indicators and application characteristics for rescue missions in life-threatening situations. The results can be used to record data from future missions using this template in order to make them comparable with each other. METHODS: After approval of the local ethic committee, the first step was to designate a group of experts in order to define the template in a consensus process. The next step was to perform the consensus process by defining the template. An independent expert for emergency medicine and disaster management reviewed and approved the results afterwards. RESULTS: The expert group defined 13 categories and 158 parameters that will further serve the systematic evaluation of the rescue mission of the Würzburg terror attack. Preliminary results of this evaluation process are given in this paper; the full evaluation has not yet been completed. DISCUSSION: In this study we first describe quality indicators and parameters suitable for the German rescue system in order to evaluate rescue operations for violence caused mass casualties. There is similar international documentation, but it does not specifically focus on life-threatening operations and are not adapted to the German context. CONCLUSION: There is an important need to systematically evaluate rescue missions after mass killing incidents. In this study we report a template of parameters and quality indicators in order to systematically evaluate mass violence events. The presented template is the result of an expert consensus process and may serve as a basis for further development and research.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Very fast optical flaring from a possible new Galactic magnetar.

Highly luminous rapid flares are characteristic of processes around compact objects like white dwarfs, neutron stars and black holes. In the high-energy regime of X-rays and gamma-rays, outbursts with variabilities on timescales of seconds or less are routinely observed, for example in gamma-ray bursts or soft gamma-ray repeaters. At optical wavelengths, flaring activity on such timescales has not been observed, other than from the prompt phase of one exceptional gamma-ray burst. This is mostly due to the fact that outbursts with strong, fast flaring are usually discovered in the high-energy regime; most optical follow-up observations of such transients use instruments with integration times exceeding tens of seconds, which are therefore unable to resolve fast variability. Here we show the observation of extremely bright and rapid optical flaring in the Galactic transient SWIFT J195509.6+261406. Our optical light curves are phenomenologically similar to high-energy light curves of soft gamma-ray repeaters and anomalous X-ray pulsars, which are thought to be neutron stars with extremely high magnetic fields (magnetars). This suggests that similar processes are in operation, but with strong emission in the optical, unlike in the case of other known magnetars.

LINC01013 Is a Determinant of Fibroblast Activation and Encodes a Novel Fibroblast-Activating Micropeptide.

Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFß1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFß1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFß1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFß1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation. TGFß1 stimulation of atrial fibroblasts induces expression of LINC01013, whose knockdown reduces fibroblast activation. Overexpression of a smORF contained within LINC01013 localises to mitochondria and activates fibroblasts.

An optical supernova associated with the X-ray flash XRF 060218.

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes--analogues of GRBs, but with lower luminosities and fewer gamma-rays--can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.

Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics.

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

Endothelial progenitor cell number and colony-forming capacity in overweight and obese adults.

OBJECTIVE: To investigate whether adiposity influences endothelial progenitor cell (EPC) number and colony-forming capacity. DESIGN: Cross-sectional study of normal weight, overweight and obese adult humans. PARTICIPANTS: Sixty-seven sedentary adults (aged 45-65 years): 25 normal weight (body mass index (BMI) or=30 kg/m(2); 18 males/6 females). All participants were non-smokers and free of overt cardiometabolic disease. MEASUREMENTS: Peripheral blood samples were collected and circulating EPC number was assessed by flow cytometry. Putative EPCs were defined as CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells. EPC colony-forming capacity was measured in vitro using a colony-forming unit (CFU) assay. RESULTS: Number of circulating putative EPCs (either CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells) was lower (P<0.05) in obese (0.0007+/-0.0001%; 0.050+/-0.006%) compared with overweight (0.0016+/-0.0004%; 0.089+/-0.019%) and normal weight (0.0015+/-0.0003%; 0.082+/-0.008%) adults. There were no differences in EPC number between the overweight and normal weight groups. EPC colony formation was significantly less in the obese (6+/-1) and overweight (4+/-1) compared with normal weight (9+/-2) adults. CONCLUSION: These results indicate that: (1) the number of circulating EPCs is lower in obese compared with overweight and normal weight adults; and (2) EPC colony-forming capacity is blunted in overweight and obese adults compared with normal weight adults. Impairments in EPC number and function may contribute to adiposity-related cardiovascular risk.

Interspecies variations in mammalian lens metabolites as detected by phosphorus-31 nuclear magnetic resonance.

Multiple interspecies differences were detected between humans and seven other mammals in 15 of the 24 metabolites measured in the intact crystalline lens and lens perchloric acid extracts. Generally, the number of statistically significant metabolite differences among the various species, relative to the human, increase in the following order: cat or approximately dog greater than pig greater than rat greater than sheep greater than rabbit greater than cow.

Recombinant interferon enhances monoclonal antibody-targeting of carcinoma lesions in vivo.

Heterogeneity in the expression of tumor-associated antigens, as defined by the binding of monoclonal antibodies, is a characteristic common to most, if not all, human carcinoma cell populations. Antigen-negative cells within the population can escape detection and therapy by their failure to bind the appropriate antibody. Therefore, the extent of antigenic heterogeneity is an important consideration when designing protocols for the management of cancer by administration of monoclonal antibodies. One approach to counteracting the effect of antigenic heterogeneity is the use of clone A of recombinant human leukocyte interferon (Hu-IFN-alpha A). Administration of Hu-IFN-alpha A in vivo effectively increased the amount of tumor antigen expressed by a human colon xenograft in situ and augmented the localization of a radiolabeled monoclonal antibody to the tumor site. Concomitant administration of Hu-IFN-alpha A and monoclonal antibody may thus be effective in overcoming the antigenic heterogeneity of carcinoma cell populations and in enhancing the efficacy of monoclonal antibodies in the detection and treatment of carcinoma lesions.

Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators.

BACKGROUND: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. METHODS: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. RESULTS: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. CONCLUSION: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.

Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia.

Antigen targeted immunotherapies might represent a novel treatment for B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor-associated antigens (TAAs) from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, syntaxin, hTERT, WT-1) and TAAs defined previously by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55-90%, and mRNA of HSJ2, MAZ and OFAiLRP was expressed in 90-100% of the patients. No expression of WT-1, hTERT, BAGE, G250, MAGE1 or survivin was observed. Low (2-20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in CLL patients, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T-cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T-cells were detected. RHAMM/CD168 might be a possible target for future immunotherapies in both ZAP-70(+) and ZAP-70(-) B-CLL patients.

Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia.

Recently, immunotherapies with allogeneic dendritic cells (DCs) pulsed with tumor antigens to generate specific T-cell responses have been tested in clinical trials for patients with solid tumors. This is the first report on a clinical vaccination study with DCs for patients with B-cell chronic lymphocytic leukemia (B-CLL). The potential of allogeneic DCs pulsed ex vivo with tumor cell lysates or apoptotic bodies to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Monocyte-derived DCs were obtained from unrelated healthy donors. Nine patients (clinical stage 0 and 1 according to Rai) were vaccinated five times with a mean number of 32 x 10(6) stimulated DCs administered intradermally once every 2-3 weeks. No signs of autoimmunity were detected, and only mild local skin reactions were noted. During the treatment period, we observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells. In one patient, a significant increase of specific cytotoxic T lymphocytes against RHAMM/CD168, a recently characterized leukemia-associated antigen, could be detected after DC vaccination. Taken together, the study demonstrated that DC vaccination in CLL patients is feasible and safe. Immunological and to some extent hematological responses could be noted, justifying further investigation on this immuno-therapeutical approach.

Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells.

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.

mRNA expression of transforming growth factor alpha in human breast carcinomas and its activity in effusions of breast cancer patients.

Transforming growth factor alpha (TGF alpha) mRNA expression was measured by Northern blot analysis in 18 human, primary, infiltrating, ductal breast carcinomas. Expression of a 4.8-kilobase TGF alpha mRNA transcript was detected in nine of 18 tumors. No evidence was observed of any gross amplifications or major rearrangements of the TGF alpha gene in the breast carcinoma specimens. Biologically active and immunoreactive TGF alpha was measured in the pleural effusions or in the ascitic fluids from 37 noncancer and 63 cancer patients. The TGF alpha activity detected ranged from 0.2 to 26 ng/mL in most effusions from both groups. However, 29 of 63 (46%) of the effusions from cancer patients exhibited TGF alpha levels that were 6 ng/mL or higher, whereas only seven of 37 (19%) of those from noncancer patients exceeded this level (P less than .03). In particular, effusions obtained from breast cancer patients showed a significantly higher level of TGF alpha, compared with those from noncancer patients (P less than .001). Effusions from 14 cancer patients also contained elevated levels of two tumor-associated antigens, CEA and/or TAG-72, and within this group, nine also had elevated levels of TGF alpha.

Temporal dynamics of cortisol and dexamethasone prevention of benzo(a)pyrene-induced morphological transformation of Syrian hamster cells.

The temporal aspects of the anticarcinogenic action of cortisol were investigated by measurement of the frequency of carcinogen-induced morphological transformation of Syrian hamster embryo cells relative to treatment regimen. Treatment of hamster cells with 10(-5) to 10(-11) M cortisol, dexamethasone, corticosterone, 17 beta-estradiol, progesterone, or testosterone did not result in morphological transformation. However, cortisol or dexamethasone treatment beginning 48 hr before the carcinogen caused a dose-dependent reduction in the transformation frequency associated with benzo(a)pyrene [B(a)P] or ultraviolet irradiation treatment. The frequency of B(a)P transformation was reduced 54, 66, and 84% by 10(-11), 10(-10), and 10(-9) M cortisol, respectively, without altering colony formation efficiency. Dexamethasone was equipotent as cortisol as an inhibitor of B(s)P, N-methyl-N'-nitro-N-nitrosoguanidine, or ultraviolet irradiation-induced transformation. Sex steroids, non-steroid antiinflammatory compounds, and steroids without antiinflammatory activity also reduced the transformation frequency but only at concentrations that reduced colony formation. Cortisol inhibition of transformation increased as steroid exposure occurred closer (48, 24, and 8 hr) yet prior to B(a)P treatment. In contrast, if cortisol was added simultaneously with or up to 72 hr after B(a)P, the frequency of transformation was unaffected. Dexamethasone addition after B(a)P, however, reduced the transformation frequency. Thus, physiological concentrations of cortisol when present prior to carcinogen exposure can prevent carcinogen-induced morphological transformation. The ability of cortisol to inhibit ultraviolet irradiation-induced transformation indicates that the anticarcinogenic activity may be mediated by steroid-induced cellular changes which are independent to metabolic activation of the carcinogen.

Identification of a novel tumor-associated Mr 110,000 gene product in human gastric carcinoma cells that is immunologically related to carcinoembryonic antigen.

A novel gene product which is immunologically related to carcinoembryonic antigen (CEA) and constitutively expressed by six of eight human gastric carcinoma cell lines is described. The antigen was initially identified by the differential binding patterns of four monoclonal antibodies (MAbs) which recognize the putative Mr 180,000 CEA and/or the Mr 90,000 CEA-related gene product, NCA (normal cross-reacting antigen). Western blot analyses of partially purified membrane fractions prepared from Hs 746T gastric carcinoma cells identified an Mr 110,000 antigen. Northern blot analyses using CEA- and NCA-specific complementary DNA probes did not identify any specific CEA or NCA transcripts in polyadenylate-selected mRNA isolated from the Hs 746T cells. Likewise, a probe designed to hybridize with different CEA-related family members failed to identify a CEA-related message in the Hs 746T cells. Subsequent studies revealed that interferon-gamma (IFN-gamma) treatment substantially increased the level of expression of the Mr 110,000 antigen on the Hs 746T and five other gastric cell types that constitutively expressed the antigen. IFN-gamma treatment also de novo induced the expression of the Mr 110,000 antigen on the surface of GaCa gastric carcinoma cells. A high percentage of Hs 746T (i.e., greater than 85%) and GaCa (approximately 75%) gastric carcinoma cells expressed the Mr 110,000 antigen after IFN-gamma treatment; yet, neither cell type expressed CEA or NCA as measured by the binding of the anti-CEA MAb, COL-1, or B6.2, an anti-NCA MAb. In contrast to CEA and NCA, phosphatidylinositol phospholipase C treatment failed to release the Mr 110,000 antigen from the surface of the Hs 746T or IFN-gamma-treated GaCa cells, suggesting that membrane attachment of this novel antigen is not via a glycosyl-phosphatidylinositol anchor. Finally, primers that amplify the 420 base pairs of the immunoglobulin-like domain of CEA and NCA detected an appropriately sized product in untreated as well as IFN-gamma-treated GaCa cells using the polymerase chain reaction method. Thus, a potentially novel gene product coding for an Mr 110,000 antigen that is strongly upregulated by IFN-gamma has been identified in human gastric carcinoma cells. Immunologically, the antigen shares reactive epitopes with CEA and its related NCA gene product; however, Northern blot analyses, polymerase chain reaction, and phosphatidylinositol phospholipase C results suggest that the antigen may be, at best, a distant relative of the CEA gene family.