[Perioperative management of coagulation in otorhinolaryngologic surgery]. / Perioperatives Gerinnungsmanagement in der HNO-Heilkunde.

Considering the increasing number of patients suffering from drug-induced coagulation disorders caused by antiplatelet or anticoagulant therapy, the right balance between minimizing the risk of bleeding and the risk of a venous thrombosis or embolism during otorhinolaryngologic (ORL) surgery is becoming increasingly important. According to a recent study, the highest risk of intraoperative bleeding in ORL surgery is associated with transoral tumor surgery, tonsillectomy, thyroidectomy, and glomus tumor surgery. The risk of venous thrombosis or embolism during ORL surgery is estimated to be 1%, and increases to 6% among tumor patients. Currently, there is no general recommendation for perioperative hemostatic management because of the limited available data. In the majority of patients who continue antiplatelet therapy with acetylsalicylic acid (ASS) to prevent thromboembolic events, the perioperative bleeding risk is considered to be acceptable. For patients with dual antiplatelet therapy, surgical procedures should be only performed after adaption of the medication.

Decadal Change in Sediment Community Oxygen Consumption in the Abyssal Northeast Pacific.

Long time-series studies are critical to assessing impacts of climate change on the marine carbon cycle. A 27-year time-series study in the abyssal northeast Pacific (Sta. M, 4000 m depth) has provided the first concurrent measurements of sinking particulate organic carbon supply (POC flux) and remineralization by the benthic community. Sediment community oxygen consumption (SCOC), an estimate of organic carbon remineralization, was measured in situ over daily to interannual periods with four different instruments. Daily averages of SCOC ranged from a low of 5.0 mg C m-2 day-1 in February 1991 to a high of 31.0 mg C m-2 day-1 in June 2012. POC flux estimated from sediment trap collections at 600 and 50 m above bottom ranged from 0.3 mg C m-2 day-1 in October 2013 to 32.0 mg C m-2 day-1 in June 2011. Monthly averages of SCOC and POC flux correlated significantly with no time lag. Over the long time series, yearly average POC flux accounted for 63 % of the estimated carbon demand of the benthic community. Long time-series studies of sediment community processes, particularly SCOC, have shown similar fluctuations with the flux of POC reaching the abyssal seafloor. SCOC quickly responds to changes in food supply and tracks POC flux. Yet, SCOC consistently exceeds POC flux as measured by sediment traps alone. The shortfall of ~37 % could be explained by sediment trap sampling artifacts over decadal scales including undersampling of large sinking particles. High-resolution measurements of SCOC are critical to developing a realistic carbon cycle model for the open ocean. Such input is essential to evaluate the impact of climate change on the oceanic carbon cycle, and the long-term influences on the sedimentation record.

Fibrinogen Bonn (p. Arg510Cys) in the Aα-Chain Is Associated with High Risk of Venous Thrombosis.

INTRODUCTION: Inherited dysfibrinogenemia is a qualitative defect of fibrinogen caused by various mutations among three fibrinogen genes. Dysfibrinogenemia can be associated with an increased risk of thrombosis, bleeding, or both. Here, we report a 36-year-old female with dysfibrinogenemia who experienced two successful pregnancies under thromboprophylaxis after cerebral venous sinus thrombosis (CVST). PATIENTS AND METHODS: In addition to plasmatic coagulation tests, fibrinogen genes FGA, FGB, and FGG were screened using direct genomic DNA sequencing. The structural-functional implications of the detected mutation were analyzed in silico. RESULTS: Inherited dysfibrinogenemia was diagnosed in an index patient after CVST in a risk situation. Anticoagulation with warfarin was stopped after 12 months when the first pregnancy was planned. Pregnancy and spontaneous delivery (2020) was uncomplicated. A second pregnancy was interrupted because of acute cytomegalovirus infection and the third pregnancy was successful in 2022. Pregnancies were accompanied by thromboprophylaxis with enoxaparin 40 mg once daily until 6 weeks postpartum. Substitution of fibrinogen has not become necessary in the index patient so far. Genetic analysis revealed a novel missense mutation (p. Arg510Cys) in the FGA gene ("fibrinogen Bonn") in the index patient, as well as an asymptomatic sister, and their father who experienced recurrent pulmonary embolism. Surface exposure of wild-type Arg510 suggested the mutated Cys510 to form nonnative disulfide bonds with surface-exposed reactive cysteines from other plasma proteins like albumin leading to formation of aggregates and impaired fibrinolysis. CONCLUSIONS: Fibrinogen Bonn might be associated with an increased risk of thrombosis, possibly due to impaired polymerization.

Laser acceleration of quasi-monoenergetic MeV ion beams.

Acceleration of particles by intense laser-plasma interactions represents a rapidly evolving field of interest, as highlighted by the recent demonstration of laser-driven relativistic beams of monoenergetic electrons. Ultrahigh-intensity lasers can produce accelerating fields of 10 TV m(-1) (1 TV = 10(12) V), surpassing those in conventional accelerators by six orders of magnitude. Laser-driven ions with energies of several MeV per nucleon have also been produced. Such ion beams exhibit unprecedented characteristics--short pulse lengths, high currents and low transverse emittance--but their exponential energy spectra have almost 100% energy spread. This large energy spread, which is a consequence of the experimental conditions used to date, remains the biggest impediment to the wider use of this technology. Here we report the production of quasi-monoenergetic laser-driven C5+ ions with a vastly reduced energy spread of 17%. The ions have a mean energy of 3 MeV per nucleon (full-width at half-maximum approximately 0.5 MeV per nucleon) and a longitudinal emittance of less than 2 x 10(-6) eV s for pulse durations shorter than 1 ps. Such laser-driven, high-current, quasi-monoenergetic ion sources may enable significant advances in the development of compact MeV ion accelerators, new diagnostics, medical physics, inertial confinement fusion and fast ignition.

Climate, carbon cycling, and deep-ocean ecosystems.

Climate variation affects surface ocean processes and the production of organic carbon, which ultimately comprises the primary food supply to the deep-sea ecosystems that occupy approximately 60% of the Earth's surface. Warming trends in atmospheric and upper ocean temperatures, attributed to anthropogenic influence, have occurred over the past four decades. Changes in upper ocean temperature influence stratification and can affect the availability of nutrients for phytoplankton production. Global warming has been predicted to intensify stratification and reduce vertical mixing. Research also suggests that such reduced mixing will enhance variability in primary production and carbon export flux to the deep sea. The dependence of deep-sea communities on surface water production has raised important questions about how climate change will affect carbon cycling and deep-ocean ecosystem function. Recently, unprecedented time-series studies conducted over the past two decades in the North Pacific and the North Atlantic at >4,000-m depth have revealed unexpectedly large changes in deep-ocean ecosystems significantly correlated to climate-driven changes in the surface ocean that can impact the global carbon cycle. Climate-driven variation affects oceanic communities from surface waters to the much-overlooked deep sea and will have impacts on the global carbon cycle. Data from these two widely separated areas of the deep ocean provide compelling evidence that changes in climate can readily influence deep-sea processes. However, the limited geographic coverage of these existing time-series studies stresses the importance of developing a more global effort to monitor deep-sea ecosystems under modern conditions of rapidly changing climate.

Laser field absorption in self-generated electron-positron pair plasma.

Recently, much attention has been attracted to the problem of limitations on the attainable intensity of high power lasers [A. M. Fedotov et al., Phys. Rev. Lett. 105, 080402 (2010)]. The laser energy can be absorbed by electron-positron pair plasma produced from a seed by a strong laser field via the development of the electromagnetic cascades. The numerical model for a self-consistent study of electron-positron pair plasma dynamics is developed. Strong absorption of the laser energy in self-generated overdense electron-positron pair plasma is demonstrated. It is shown that the absorption becomes important for a not extremely high laser intensity I ∼ 10(24) W/cm(2) achievable in the near future.

Temporal change in deep-sea benthic ecosystems: a review of the evidence from recent time-series studies.

Societal concerns over the potential impacts of recent global change have prompted renewed interest in the long-term ecological monitoring of large ecosystems. The deep sea is the largest ecosystem on the planet, the least accessible, and perhaps the least understood. Nevertheless, deep-sea data collected over the last few decades are now being synthesised with a view to both measuring global change and predicting the future impacts of further rises in atmospheric carbon dioxide concentrations. For many years, it was assumed by many that the deep sea is a stable habitat, buffered from short-term changes in the atmosphere or upper ocean. However, recent studies suggest that deep-seafloor ecosystems may respond relatively quickly to seasonal, inter-annual and decadal-scale shifts in upper-ocean variables. In this review, we assess the evidence for these long-term (i.e. inter-annual to decadal-scale) changes both in biologically driven, sedimented, deep-sea ecosystems (e.g. abyssal plains) and in chemosynthetic ecosystems that are partially geologically driven, such as hydrothermal vents and cold seeps. We have identified 11 deep-sea sedimented ecosystems for which published analyses of long-term biological data exist. At three of these, we have found evidence for a progressive trend that could be potentially linked to recent climate change, although the evidence is not conclusive. At the other sites, we have concluded that the changes were either not significant, or were stochastically variable without being clearly linked to climate change or climate variability indices. For chemosynthetic ecosystems, we have identified 14 sites for which there are some published long-term data. Data for temporal changes at chemosynthetic ecosystems are scarce, with few sites being subjected to repeated visits. However, the limited evidence from hydrothermal vents suggests that at fast-spreading centres such as the East Pacific Rise, vent communities are impacted on decadal scales by stochastic events such as volcanic eruptions, with associated fauna showing complex patterns of community succession. For the slow-spreading centres such as the Mid-Atlantic Ridge, vent sites appear to be stable over the time periods measured, with no discernable long-term trend. At cold seeps, inferences based on spatial studies in the Gulf of Mexico, and data on organism longevity, suggest that these sites are stable over many hundreds of years. However, at the Haakon Mosby mud volcano, a large, well-studied seep in the Barents Sea, periodic mud slides associated with gas and fluid venting may disrupt benthic communities, leading to successional sequences over time. For chemosynthetic ecosystems of biogenic origin (e.g. whale-falls), it is likely that the longevity of the habitat depends mainly on the size of the carcass and the ecological setting, with large remains persisting as a distinct seafloor habitat for up to 100 years. Studies of shallow-water analogs of deep-sea ecosystems such as marine caves may also yield insights into temporal processes. Although it is obvious from the geological record that past climate change has impacted deep-sea faunas, the evidence that recent climate change or climate variability has altered deep-sea benthic communities is extremely limited. This mainly reflects the lack of remote sensing of this vast seafloor habitat. Current and future advances in deep-ocean benthic science involve new remote observing technologies that combine a high temporal resolution (e.g. cabled observatories) with spatial capabilities (e.g. autonomous vehicles undertaking image surveys of the seabed).

Transcriptome-wide analysis of filarial extract-primed human monocytes reveal changes in LPS-induced PTX3 expression levels.

Filarial nematodes modulate immune responses in their host to enable their survival and mediate protective effects against autoimmunity and allergies. In this study, we examined the immunomodulatory capacity of extracts from the human pathogenic filaria Brugia malayi (BmA) on human monocyte responses in a transcriptome-wide manner to identify associated pathways and diseases. As previous transcriptome studies often observed quiescent responses of innate cells to filariae, the potential of BmA to alter LPS driven responses was investigated by analyzing >47.000 transcripts of monocytes from healthy male volunteers stimulated with BmA, Escherichia coli LPS or a sequential stimulation of both. In comparison to ~2200 differentially expressed genes in LPS-only stimulated monocytes, only a limited number of differentially expressed genes were identified upon BmA priming before LPS re-stimulation with only PTX3↓ reaching statistical significance after correcting for multiple testing. Nominal significant differences were reached for metallothioneins↑, MMP9↑, CXCL5/ENA-78↑, CXCL6/GCP-2↑, TNFRSF21↓, and CCL20/MIP3α↓ and were confirmed by qPCR or ELISA. Flow cytometric analysis of activation markers revealed a reduced LPS-induced expression of HLA-DR and CD86 on BmA-primed monocytes as well as a reduced apoptosis of BmA-stimulated monocytes. While our experimental design does not allow a stringent extrapolation of our results to the development of filarial pathology, several genes that were identified in BmA-primed monocytes had previously been associated with filarial pathology, supporting the need for further research.

Simulating pathways of subsurface oil in the Faroe-Shetland Channel using an ocean general circulation model.

Little is known about the fate of subsurface hydrocarbon plumes from deep-sea oil well blowouts and their effects on processes and communities. As deepwater drilling expands in the Faroe-Shetland Channel (FSC), oil well blowouts are a possibility, and the unusual ocean circulation of this region presents challenges to understanding possible subsurface oil pathways in the event of a spill. Here, an ocean general circulation model was used with a particle tracking algorithm to assess temporal variability of the oil-plume distribution from a deep-sea oil well blowout in the FSC. The drift of particles was first tracked for one year following release. Then, ambient model temperatures were used to simulate temperature-mediated biodegradation, truncating the trajectories of particles accordingly. Release depth of the modeled subsurface plumes affected both their direction of transport and distance travelled from their release location, and there was considerable interannual variability in transport.

An approach for the identification of exemplar sites for scaling up targeted field observations of benthic biogeochemistry in heterogeneous environments.

Continental shelf sediments are globally important for biogeochemical activity. Quantification of shelf-scale stocks and fluxes of carbon and nutrients requires the extrapolation of observations made at limited points in space and time. The procedure for selecting exemplar sites to form the basis of this up-scaling is discussed in relation to a UK-funded research programme investigating biogeochemistry in shelf seas. A three-step selection process is proposed in which (1) a target area representative of UK shelf sediment heterogeneity is selected, (2) the target area is assessed for spatial heterogeneity in sediment and habitat type, bed and water column structure and hydrodynamic forcing, and (3) study sites are selected within this target area encompassing the range of spatial heterogeneity required to address key scientific questions regarding shelf scale biogeochemistry, and minimise confounding variables. This led to the selection of four sites within the Celtic Sea that are significantly different in terms of their sediment, bed structure, and macrofaunal, meiofaunal and microbial community structures and diversity, but have minimal variations in water depth, tidal and wave magnitudes and directions, temperature and salinity. They form the basis of a research cruise programme of observation, sampling and experimentation encompassing the spring bloom cycle. Typical variation in key biogeochemical, sediment, biological and hydrodynamic parameters over a pre to post bloom period are presented, with a discussion of anthropogenic influences in the region. This methodology ensures the best likelihood of site-specific work being useful for up-scaling activities, increasing our understanding of benthic biogeochemistry at the UK-shelf scale.

Long-term change in benthopelagic fish abundance in the abyssal northeast Pacific Ocean.

Food web structure, particularly the relative importance of bottom-up and top-down control of animal abundances, is poorly known for the Earth's largest habitats: the abyssal plains. A unique 15-yr time series of climate, productivity, particulate flux, and abundance of primary consumers (primarily echinoderms) and secondary consumers (fish) was examined to elucidate the response of trophic levels to temporal variation in one another. Towed camera sled deployments in the abyssal northeast Pacific (4100 m water depth) showed that annual mean numbers of the dominant fish genus (Coryphaenoides spp.) more than doubled over the period 1989-2004. Coryphaenoides spp. abundance was significantly correlated with total abundance of mobile epibenthic megafauna (echinoderms), with changes in fish abundance lagging behind changes in the echinoderms. Direct correlations between surface climate and fish abundances, and particulate organic carbon (POC) flux and fish abundances, were insignificant, which may be related to the varied response of the potential prey taxa to climate and POC flux. This study provides a rare opportunity to study the long-term dynamics of an unexploited marine fish population and suggests a dominant role for bottom-up control in this system.

A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia. Predicted structure and function consequences.

Afibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function. PATIENTS AND METHODS: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico. RESULTS: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta-chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain. CONCLUSIONS: The novel missense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.

High resolution study of the spatial distributions of abyssal fishes by autonomous underwater vehicle.

On abyssal plains, demersal fish are believed to play an important role in transferring energy across the seafloor and between the pelagic and benthic realms. However, little is known about their spatial distributions, making it difficult to quantify their ecological significance. To address this, we employed an autonomous underwater vehicle to conduct an exceptionally large photographic survey of fish distributions on the Porcupine Abyssal Plain (NE Atlantic, 4850 m water depth) encompassing two spatial scales (1-10 km(2)) on and adjacent to a small abyssal hill (240 m elevation). The spatial distributions of the total fish fauna and that of the two dominant morphotypes (Coryphaenoides sp. 1 and C. profundicolus) appeared to be random, a result contrary to common expectation but consistent with previous predictions for these fishes. We estimated total fish density on the abyssal plain to be 723 individuals km(-2) (95% CI: 601-844). This estimate is higher, and likely more precise, than prior estimates from trawl catch and baited camera techniques (152 and 188 individuals km(-2) respectively). We detected no significant difference in fish density between abyssal hill and plain, nor did we detect any evidence for the existence of fish aggregations at any spatial scale assessed.

Proton acceleration by irradiation of isolated spheres with an intense laser pulse.

We report on experiments irradiating isolated plastic spheres with a peak laser intensity of 2-3×10^{20}Wcm^{-2}. With a laser focal spot size of 10 µm full width half maximum (FWHM) the sphere diameter was varied between 520 nm and 19.3 µm. Maximum proton energies of ∼25 MeV are achieved for targets matching the focal spot size of 10 µm in diameter or being slightly smaller. For smaller spheres the kinetic energy distributions of protons become nonmonotonic, indicating a change in the accelerating mechanism from ambipolar expansion towards a regime dominated by effects caused by Coulomb repulsion of ions. The energy conversion efficiency from laser energy to proton kinetic energy is optimized when the target diameter matches the laser focal spot size with efficiencies reaching the percent level. The change of proton acceleration efficiency with target size can be attributed to the reduced cross-sectional overlap of subfocus targets with the laser. Reported experimental observations are in line with 3D3V particle in cell simulations. They make use of well-defined targets and point out pathways for future applications and experiments.

Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group.

In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.

Germ-line transcripts of the immunoglobulin lambda J-C clusters in the mouse: characterization of the initiation sites and regulatory elements.

Transcription of unrearranged immunoglobulin gene segments strongly correlates with their accessibility to the V(D)J recombination machinery. The regulatory mechanisms governing this germ-line transcription are still poorly defined. In order to identify new regulatory elements, we first carried out a detailed characterization of the transcription initiation sites for the J-C germ-line transcripts, using rapid amplification of 5' cDNA ends, assisted by a template switching mechanism at the 5'-end of the RNA. Transcripts were observed that initiated heterogeneously, starting up to 293 (lambda1), 116 bp (lambda2) and 79 bp (lambda3) upstream from the respective Jlambda gene segment. Additional RT-PCR analysis revealed the existence of germ-line transcripts of lambda and also of kappa that initiate even more upstream of these transcription initiation sites, although their frequencies were low. Promoter activity was detected in vitro 5' of Jlambda2, with the minimal promoter activity mapping to the region between positions -35 and -120. In addition, computer analysis allowed the prediction of a nuclear scaffold/matrix attachment (S/MAR) region between the two J-C gene clusters at each hemi-locus. This region between the lambda1/lambda3 clusters binds to the nuclear matrix in vitro, and J-C lambda1 germ-line transcription initiates a short distance downstream from this S/MAR element.

Spatial and temporal variation in sponge spicule patches at Station M, northeast Pacific.

Changes in habitat-forming organisms can have complex consequences for associated species. Sessile epibenthic glass "plate" sponges (Porifera: Hexactinellida) are conspicuous inhabitants of soft-sediment abyssal areas and their siliceous spicules create persistent spicule patches on the seafloor. Sponge spicule patch density, spatial dispersion, and percent cover were examined over a seven-year period (2006-2013) using remotely operated vehicle videos from Station M in the abyssal northeast Pacific (50˚00N, 123˚00W, ~4,000 m depth). There was an apparent large increase in newly dead plate sponges in February 2007 compared with December 2006, with this trend continuing through June 2007 (mean 0.03 % cover increasing to 0.33 %). A second increase in mean percent cover of dead plate sponges occurred from May 2011 (0.24 %) through June 2012 (0.60 %). Among the 28 megafaunal taxa occurring in association with the patches, the distributions of three taxa [two sponge taxa (Porifera) and brittle stars (Ophiuroidea)] suggested selectivity for the sponge spicule patches. The community structure of visible megafauna within sponge spicule patches was different when compared with that outside the patches suggesting that the sponges, after death, provide preferred habitat patches for certain benthic megafauna. These findings indicate that sponge spicule patches contribute to habitat heterogeneity in space and time.

Neoplasm-induced bleeding in inherited, heterozygous FXIII-A deficiency.

UNLABELLED: Inherited mild factor XIII deficiency belongs to one of the most underdiagnosed bleeding disorders so far. This is, because most patients do not develop bleeding complications in daily life. Patient, methods: A man (age: 64 years) without a history of bleeding presented with painful swelling of neck, weight loss, anemia and episodic bleeding from the right tonsil necessitating tonsillectomy. Histologic and immunohistochemical evaluation revealed cytokeratin-positive epitheloid angiosarcoma. Blood coagulation status showed significantly elevated D-dimer and decreased FXIII levels (FXIII-activity 35%, FXIIIA-Ag 16-26%). Plasma mixing studies excluded neutralizing antibodies against FXIII. RESULTS: A novel heterozygous F13A1 gene nonsense mutation (p.Glu103Ter, c.307G>T) was found confirming heterozygous FXIII-A deficiency. The same mutation was detected in two further asymptomatic relatives. For further clinical management the patient was transfused with FXIII-concentrate and showed an adequate increase of FXIII ruling out FXIII deficiency to be induced by increased turnover. Despite this haemostatic management and antifibrinolytic treatment the patient had to undergo several revisions due to delayed, Hb relevant bleeding after cervical lymph nodes extirpation and resection of tonsil. Two chemotherapy cycles with paclitaxel and palliative radiotherapy of the neck area were performed, but the patient died unfortunately two months after diagnosis. CONCLUSIONS: It is a unique case showing the combination of a highly aggressive angiosarcoma and presence of inherited FXIII deficiency. It is also a rare example demonstrating the benefit of FXIII genotyping besides the expected acquired FXIII deficiency possibly due to neoplasm induced increased consumption by elevated crosslinking of fibrin fibers.

Impaired B lymphocyte reactivity in patients after radiotherapy.

The effect of therapeutic irradiation upon B lymphocyte function was investigated in patients with various malignancies. The test system used was a reverse hemolytic plaque assay, which made it possible to study the activation and differentiation of B lymphocytes into immunoglobulin-secreting cells (ISC). Peripheral blood lymphocytes from normal individuals and patients before and after radiotherapy were stimulated in vitro with the polyclonal B cell activator pokeweed mitogen, and the number of ISC was estimated. B cell reactivity was markedly reduced in those patients who had received irradiation within the last six months. In patients in whom radiotherapy had been terminated more than 12 months before the lymphocytes were tested, B cell reactivity was comparable to that of patients prior to radiotherapy. By means of marker analyses, there was a reduction of B lymphocytes and T lymphocytes in the peripheral blood with a preponderance of T helper cells. Several mechanisms--e.g., reduced or defective B cell differentiation, altered regulatory T-helper or suppressor cell function or activation of suppressive monocytes--could be responsible for impaired B cell reactivity after radiotherapy.

Expanded T gamma cell populations with the morphology of large granular lymphocytes -- I. Immunological, clinical and morphological characterization.

Lymphocytes from two patients with T gamma cell proliferations displaying the morphology of large granular lymphocytes (LGL) were characterized in terms of cell marker phenotyping and immunologic functions. In both patients, the lymphocytes were positive for E-R, HuTLA, OKT5, OKT8, OKT11, OKM1, VEP13, Leu1, Leu2a, Lyt2 and Lyt3 and were negative for Tmu, Tar, SIg, BA1, BA2, EM-R, C3d-R, C3b-R, OKT6, OKT9, Leu3a, OKIa1 and TdT. In addition, investigations for T411, T811 and M522 in patient 1 yielded positive results. There were differences in the phenotype of the two patients with regard to the reactions with OKT3, OKT10 and VEP10. While, in patient 1, OKT3 was very pronounced and OKT10 and VEP10 were completely negative, OKT10 and VEP10 were very pronounced in patient 2, whereas OKT3 was positive only in a very small percentage of cells. Though the lymphocytes in both patients were potent effectors of NK and K functions (patient 2 more strongly than patient 1) and a noticeably reduced mitogen response was shown to PHA, Con A and zinc, patient 1 showed a distinct suppression of allogenic and autologous B cell response to transformation into ISC, coinciding with the clinical observation of a hypogammaglobulinemia; neither B cell suppression nor dysgammaglobulinemia was seen in patient 2. The results are discussed with regard to other comparable T gamma proliferations reported in the literature.