The effect of shoulder prosthesis stem length on failure due to torsional loading. A biomechanical study in composite humeri.

Background: Shoulder arthroplasty is becoming increasingly common. With evolving implant designs, multiple humeral stem options exist for the surgeon to choose from. New stemless and short-stem systems are modular, remove less native bone stock, and better adapt to patient anatomy. It has been suggested that shorter stem implants may be protective against periprosthetic fracture; however, this has not been mechanistically evaluated. Therefore, this study aimed to biomechanically test synthetic humeri with long-stem, short-stem, and stemless arthroplasty components in a torsional manner to evaluate their response to loading and characterize failure. Methods: Twenty-four synthetic humeri were implanted with long stem, short stem, or stemless uncemented prosthesis, 8 in each group. Humeri were mounted in a custom testing jig with a morse taper interfacing with a mechanical testing system. After a 20N axial force, specimens were torsionally loaded to failure at 15 degrees/sec, with 50 Hz collection. Torque vs. rotation curves were generated for each specimen, and stiffness, yield, ultimate strength, and failure load were measured. ANOVA and post hoc pairwise comparisons were used to assess effect of stem type on mechanical test variable. The association of the stem type with fracture type was analyzed by a Fisher's Exact test. Statistical significance was set at P < .05. Results: During torsional loading, long-stem implants were significantly stiffer than short or stemless implants. The angle of implant yielding was similar across stem designs; however, stemless implants had a lower yield torque. This correlated with a decreased yield energy in stemless compared to short stems as well. Maximum torque and failure torque was also significantly higher in short-stem and long-stem implants compared to stemless. Discussion: Periprosthetic fractures in shoulder arthroplasty are a concern in low-energy trauma, and stem design likely plays a significant role in early implant-bone failure. Our results suggest stemless implants under torsional load fail at lower stress and are less stiff than stemmed implants. The failure mechanism of stemless implants through metaphyseal cancellous bone emphasizes the effect bone quality has on implant fixation. There is likely a balance of torsional stability to survive physiologic loads while minimizing diaphyseal stress and risk of diaphyseal periprosthetic fracture. This combined with revision and fixation options represent decisions the surgeon is faced with when performing shoulder arthroplasty.

Flight demonstration of a miniature atomic scalar magnetometer based on a microfabricated rubidium vapor cell.

We have developed an atomic magnetometer based on the rubidium isotope 87Rb and a microfabricated silicon/glass vapor cell for the purpose of qualifying the instrument for space flight during a ride-along opportunity on a sounding rocket. The instrument consists of two scalar magnetic field sensors mounted at 45° angle to avoid measurement dead zones, and the electronics consist of a low-voltage power supply, an analog interface, and a digital controller. The instrument was launched into the Earth's northern cusp from Andøya, Norway on December 8, 2018 on the low-flying rocket of the dual-rocket Twin Rockets to Investigate Cusp Electrodynamics 2 mission. The magnetometer was operated without interruption during the science phase of the mission, and the acquired data were compared favorably with those from the science magnetometer and the model of the International Geophysical Reference Field to within an approximate fixed offset of about 550 nT. Residuals with respect to these data sources are plausibly attributed to offsets resulting from rocket contamination fields and electronic phase shifts. These offsets can be readily mitigated and/or calibrated for a future flight experiment so that the demonstration of this absolute-measuring magnetometer was entirely successful from the perspective of increasing the technological readiness for space flight.

The Association of Surgical Timing and Injury Severity With Systemic Complications in Severely Injured Patients With Pelvic Ring Injuries.

OBJECTIVES: To evaluate the relationship between timing of definitive fixation, injury severity, and the development of systemic complications in severely injured patients with pelvic ring injuries. DESIGN: Retrospective review. SETTINGS: Level 1 trauma center. PATIENTS: One hundred eighteen severely injured [Injury Severity Score (ISS) ≥ 16] adult patients with pelvic ring injuries undergoing definitive fixation, excluding patients treated with external fixation for hemodynamic instability. INTERVENTION: Early fixation (≤36 hours) in 37 patients and delayed fixation (>36 hours) in 81 patients. MAIN OUTCOME MEASUREMENTS: Systemic complications (acute respiratory distress syndrome, pulmonary embolism, deep venous thrombosis, sepsis, multi-organ failure, and death). RESULTS: The delayed fixation group had a higher ISS and had more patients with chest injuries. There was no detectable difference in the number of patients with systemic complications between early versus delayed fixation groups [8 (22%) vs. 29 (35%), P = 0.1]. The only difference detected in specific complications was a higher incidence of pneumonia with delayed fixation [16 (20%) vs. 0 (0%), P = 0.004] with 11 of the 16 cases being associated with chest injury. Univariate analysis showed an association between complication and time to fixation, ISS, Glasgow Coma Scale, pH, base excess, and injuries to the head, chest, and abdomen. On multivariate analysis, only ISS remained significantly associated with the development of complications [Odds ratio 2.6 per 10 point increase, 95% confidence interval (CI), 1.4-4.4]. CONCLUSIONS: These data suggest that the severity of injury is most highly associated with systemic complications after definitive fixation of pelvic ring injuries. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ultrasound-assisted regeneration of zeolite/water adsorption pair.

The use of ultrasound to enhance the regeneration of zeolite 13X for efficient utilization of thermal energy was investigated as a substitute to conventional heating methods. The effects of ultrasonic power and frequency on the desorption of water from zeolite 13X were analyzed to optimize the desorption efficiency. To determine and justify the effectiveness of incorporating ultrasound from an energy-savings point of view, an approach of constant overall input power of 20 or 25 W was adopted. To measure the extent of the effectiveness of using ultrasound, the ultrasonic-power-to-total power ratios of 0.2, 0.25, 0.4 and 0.5 were investigated and the results compared with those of no-ultrasound (heat only) at the same total power. To analyze the effect of ultrasonic frequency, identical experiments were performed at three nominal ultrasonic frequencies of ~28, 40 and 80 kHz. The experimental results showed that using ultrasound enhances the regeneration of zeolite 13X at all the aforementioned power ratios and frequencies without increasing the total input power. With regard to energy consumption, the highest energy-savings power ratio (0.25) resulted in a 24% reduction in required input energy and with an increase in ultrasonic power, i.e. an increase in acoustic-to-total power ratio, the effectiveness of applying ultrasound decreased drastically. At a power ratio of 0.2, the time required for regeneration was reduced by 23.8% compared to the heat-only process under the same experimental conditions. In terms of ultrasonic frequency, lower frequencies resulted in higher efficiency and energy savings, and it was concluded that the effect of ultrasonic radiation becomes more significant at lower ultrasonic frequencies. The observed inverse proportionality between the frequency and ultrasound-assisted desorption enhancement suggests that acoustic dissipation is not a significant mechanism to enhance mass transfer, but rather other mechanisms must be considered.

Survey of occupational fatigue in anaesthetists in Australia and New Zealand.

Occupational fatigue in anaesthetists is recognised as a patient safety risk. Better understanding of the issues surrounding their fatigue is needed. This study aimed to ascertain the sources and effects of occupational fatigue amongst anaesthetists in Australia and New Zealand. An anonymous online survey was sent to 979 anaesthetists. The response rate was 38.0%. Most participants reported regularly working over 40 hours per week; men reported five more hours per week than women. Stated contributors to fatigue included long work hours, mental strain at work, and personal and family demands. Fatigue-related behaviour was reported more by men (OR [odds ratio]=2.6) and less by respondents reporting eight or more hours of sleep before work (OR=0.6). Reporting at least one instance of less than five hours off between shifts was predictive of falling asleep while administering an anaesthetic (OR=1.6). More data are required to support practices and policies that promote more time off between work periods and increased time for sleep to reduce risk of fatigue.

Population structure within an alpine archipelago: strong signature of past climate change in the New Zealand rock wren (Xenicus gilviventris).

Naturally subdivided populations such as those occupying high-altitude habitat patches of the 'alpine archipelago' can provide significant insight into past biogeographical change and serve as useful models for predicting future responses to anthropogenic climate change. Among New Zealand's alpine taxa, phylogenetic studies support two major radiations: the first correlating with geological forces (Pliocene uplift) and the second with climatic processes (Pleistocene glaciations). The rock wren (Xenicus gilviventris) is a threatened alpine passerine belonging to the endemic New Zealand wren family (Acanthisittidae). Rock wren constitute a widespread, naturally fragmented population, occurring in patches of suitable habitat over c. 900 m in altitude throughout the length of the South Island, New Zealand. We investigated the relative role of historical geological versus climatic processes in shaping the genetic structure of rock wren (N = 134) throughout their range. Using microsatellites combined with nuclear and mtDNA sequence data, we identify a deep north-south divergence in rock wren (3.7 ± 0.5% at cytochrome b) consistent with the glacial refugia hypothesis whereby populations were restricted in isolated refugia during the Pleistocene c. 2 Ma. This is the first study of an alpine vertebrate to test and provide strong evidence for the glacial refugia hypothesis as an explanation for the low endemicity central zone known as the biotic 'gap' in the South Island of New Zealand.

Clinical features of endemic community-acquired psittacosis.

Following a large outbreak of community-acquired psittacosis in 2002 in residents of the Blue Mountains, New South Wales, Australia, we reviewed new cases in this area over a 7-year period from 2003 to 2009. Using the 2010 criteria from the Centers for Disease Control National Notifiable Diseases Surveillance System, 85 patients with possible psittacosis were identified, of which 48 were identified as definite or probable infection. Clinical features of these cases are summarized. In addition to Chlamydia-specific serology, specimens, where available, underwent nucleic acid testing for chlamydial DNA using real-time PCR. Chlamydophila psittaci DNA was detected in samples from 23 patients. Four of 18 specimens were culture positive. This is the first description of endemic psittacosis, and is characterized in this location by community-acquired psittacosis resulting from inadvertent exposure to birds. The disease is likely to be under-diagnosed, and may often be mistaken for gastroenteritis or meningitis given the frequency of non-respiratory symptoms, particularly without a history of contact with birds. Clinical characteristics of endemic and outbreak-associated cases were similar. The nature of exposure, risk factors and reasons for the occurrence of outbreaks of psittacosis require further investigation.

Development of a low-cost system for measuring conditional time-averaged gradients of SO2 and NH3.

A conditional time-averaged gradient (COTAG) system has been developed to provide direct long-term (weekly to monthly) average flux gradient measurements for a range of trace gases, between land and atmosphere. Over daily periods, atmospheric conditions can range from high stability, where the vertical gradients of ambient concentration are enhanced due to very small diffusivity, to highly unstable conditions, in which concentration gradients are small due to the intense turbulent activity of the surface layer. The large vertical gradients generated by high stability would bias the estimate of the actual flux: to avoid this, the COTAG system samples conditionally, within a carefully refined range of stability. A comparison with a continuous flux gradient system suggested that the removal of stable conditions from the sampling period does not substantially modify the evaluation of the long-term fluxes.

Sedimentary and water column processes in the Oyster Grounds: a potentially hypoxic region of the North Sea.

The purpose of this research was to investigate the potential causes of low oxygen levels in the bottom water of the Oyster Grounds region of the shallow southern North Sea, an area which provides suitable conditions for low oxygen levels to develop. At the end of the summer stratified period, relevant biogeochemical processes were investigated using a combination of sedimentary and water column rate measurements. Phytoplankton nitrate and ammonium uptake was measured throughout the water column using (15)N labelled isotopes and showed ammonium uptake dominated in the upper and bottom mixed layer with a maximum 294.4 micromol N m(-3)h(-1). In the deep chlorophyll maximum at the thermocline, primary production was dominated by nitrate uptake, with an average of 35.0 micromol N m(-3)h(-1), relative to ammonium uptake, with an average of 24.6 micromol N m(-3)h(-1). This high relative nitrate uptake will in part result in exportable new production to the isolated bottom mixed layer and sediments, as opposed to regenerated ammonium driven uptake. This biomass export was indicated by significant benthic oxygen consumption rates in the stratified region (782-1275 micromol O(2)m(-2)h(-1)micromol N m(-3)h(-1)) long after the end of the spring bloom. The sediments were also an active net source of nitrate, ammonium, phosphate and silicate into the bottom mixed layer of 4.4, 8.4, 2.3 and 68.8 micromol m(-2)h(-1), respectively. The export of new production within the thermocline to the bottom mixed layer and the consequent sediment oxygen consumption in the isolated bottom mixed layer in the Oyster Grounds are expected to have contributed to the low bottom water oxygen concentrations of 2.07 mg l(-1) (64.7 micromol l(-1)) measured. The long stratified period associated with this low oxygen is predicted to occur more regularly in the future and continued monitoring of this ecologically important region is therefore essential if the causes of these potentially damaging low oxygen levels are to be fully understood.

Inventories of fallout 210Pb and 137Cs radionuclides in moorland and woodland soils around Edinburgh urban area (UK).

Inventories of fallout (210)Pb and (137)Cs have been measured in moorland and woodland soils around the Edinburgh urban area, using a high purity germanium detector. The (210)Pb inventories in moorland soils were relatively uniform, with a mean value of 2520+/-270Bqm(-2). The mean (137)Cs inventory in moorland soils varied greatly from 1310 to 2100Bqm(-2), with a mean value of 1580+/-310Bqm(-2). The variability was ascribed mainly to the non-uniform distribution of fallout Chernobyl (137)Cs. The mean (210)Pb and (137)Cs inventories in woodland canopy soils were found to be 3630+/-380Bqm(-2) and 2510+/-510Bqm(-2), respectively. At sites for which both moorland and woodland data were available, the mean inventories provided fairly similar average enhancements of (47+/-7)% and (46+/-18)% of (210)Pb and (137)Cs under woodland canopy soils relative to open grassland soils, respectively. The enhancement factors are broadly in line with other independent findings in literature. Enhancement of both (210)Pb and (137)Cs in woodland soils relative to moorland soils is, in part, due to deposition by impaction during air turbulence, wash-off, gravitational settling and deposition during leaf senescence. Results of this study suggest that these processes affect both (210)Pb and (137)Cs carrier aerosols in a similar way.

MEAD: an interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat.

This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions.

Mapping of genetic determinants of the sympathoneural response to stress.

Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NE responses in the F(2) rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.

Ammonia emission and deposition in Scotland and its potential environmental impacts.

The main source of atmospheric ammonia (NH3) in Scotland is livestock agriculture, which accounts for 85% of emissions. The local magnitude of emissions therefore depends on livestock density, type, and management, with major differences occurring in various parts of Scotland. Local differences in agricultural activities therefore result in a wide range of NH3 emissions, ranging from less than 0.2 kg N ha(-1) year(-1) in remote areas of the Scottish Highlands to over 100 kg N ha(-1) year-1 in areas with intensive poultry farming. Scotland can be divided loosely into upland and lowland areas, with NH3 emission being less than and more than 5 kg N ha(-1) year(-1), respectively. Many semi-natural ecosystems in Scotland are vulnerable to nitrogen deposition, including bogs, moorlands, and the woodland ground flora. Because NH3 emissions occur in the rural environment, the local deposition to sensitive ecosystems may be large, making it essential to assess the spatial distribution of NH3 emissions and deposition. A spatial model is applied here to map NH3 emissions and these estimates are applied in atmospheric dispersion and deposition models to estimate atmospheric concentrations of NH3 and NH4+, dry deposition of NH3, and wet deposition of NHx. Although there is a high level of local variability, modelled NH3 concentrations show good agreement with the National Ammonia Monitoring Network, while wet deposition is largest at high altitude sites in the south and west of Scotland. Comparison of the modelled NHx deposition fields with estimated thresholds for environmental effects ("critical loads") shows that thresholds are exceeded across most of lowland Scotland and the Southern Uplands. Only in the cleanest parts of the north and west is nitrogen deposition not a cause for concern. Given that the most intense effects occur within a few kilometres of sources, it is suggested that local spatial abatement policies would be a useful complement to traditional policies that mitigate environmental effects based on emission reduction technologies.

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is an important risk factor for coronary heart disease, especially in the context of the insulin resistance syndrome where it often occurs with hypertension. The two phenotypes are also associated in the hereditary hypertriglyceridaemic (hHTg) rat. The aim of this study was to map quantitative trait loci that affect plasma triglyceride concentration in the hHTg rat and determine whether they co-localize with loci for blood pressure. METHODS: Second filial generation progeny (n=189) from a cross of the hHTg rat with the Brown Norway rat were phenotyped for fasting plasma triglyceride, glucose and insulin concentrations, and direct unrestrained resting blood pressure. A partial genome-scan was conducted using 153 microsatellite markers that were polymorphic between the two strains. RESULTS: A major locus (lod score 6.5) influencing plasma triglyceride concentration in a co-dominant fashion was mapped to chromosome 4 between D1Mit 5 and D1Mit17. Chromosome 8 contained multiple peaks with a lod score greater than 4.0 influencing triglyceride concentration. Importantly, none of the triglyceride loci had an effect on blood pressure. The triglyceride locus on chromosome 4 co-localized with a locus for fasting plasma insulin (lod score 4.1), although the effect on insulin concentration was in the opposite direction to that on triglyceride. CONCLUSION/INTERPRETATION: We have mapped the major loci that affect plasma triglyceride concentration in the hHTg rat. These loci do not influence blood pressure suggesting that these commonly associated phenotypes of the insulin resistance syndrome are not be due to pleiotropic effects of the same gene(s).

Long-range effects of retroviral insertion on c-myb: overexpression may be obscured by silencing during tumor growth in vitro.

The c-myb oncogene is a frequent target for retroviral activation in hemopoietic tumors of avian and mammalian species. While insertions can target the gene directly, numerous clusters of retroviral insertion sites have been identified which map close to c-myb and outside the transcription unit in T-lymphomas (Ahi-1, fit-1, and Mis-2) and monocytic and myeloid leukemias (Mml1, Mml2, Mml3, and Epi-1). Previous analyses showed no consistent effect of these insertions on c-myb expression, raising the possibility that other nearby genes were the true targets. In contrast, our analysis of four cell lines established from lymphomas bearing insertions at fit-1 (fti-1) (feline leukemia virus) and Ahi-1 (Moloney murine leukemia virus) shows that these display higher expression levels of c-myb RNA and protein compared to a panel of phenotypically similar cell lines lacking such insertions. An interesting feature of the cell lines with long-range c-myb insertions was that each also carried an activated Myc allele. The potential for oncogenic synergy between Myb and Myc in T-cell lymphoma was confirmed in transgenic mice overexpressing alleles of both genes in the T-cell compartment, lending further credence to the case for c-myb as the major target for long-range activation. In contrast, mapping and analysis of c-myb neighboring genes (HBS1 and FLJ20069) showed that the expression of these genes did not correlate well with the presence of proviral insertions. A possible explanation for the paradoxical behavior of c-myb was provided by one of the murine T-lymphoma lines bearing an insertion at Ahi-1 (p/m16i) that reproducibly down-regulated c-myb RNA and protein to very low levels or undetectable levels on prolonged culture. Our observations implicate c-myb as a key target of upstream and downstream retroviral insertions. However, overexpression may become dispensable during outgrowth in vitro, and perhaps during tumor progression in vivo, providing a potential rationale for the previously observed discordance between retroviral insertion and c-myb expression levels.

Partner notification in the management of sexually transmitted infections in Nairobi, Kenya.

OBJECTIVE: To assess utilization of partner notification as a tool in prevention and control of Sexually transmitted infections in Nairobi City Council clinics. DESIGN: A cross-sectional study carried out between April and September 2000. SETTING: Nairobi City Council health clinics were stratified into eight administrative divisions and a total of 16 out of 54 primary health clinics with at least four STIs patients per day were selected. A standard questionnaire was administered to every fourth patient with clinical diagnosis of STIs who gave consent on exist. Sexual partners referred by index cases during the five day period from each clinic were also enrolled into the study. An additional questionnaire was administered to HCP who were managing STIs patients and their sex partners. RESULTS: Of 407 STIs patients recruited between April and September 2000, 20.6% were primary and 2% were secondary referrals giving an average referral rate of 23%. Respondents with multiple sex partners were less likely to refer their partners compared to those who had one partner (17.9% vs 82.1%, p < 0.005). Counseling of STI patients on the importance of partner referral was more effective than issuing referral cards alone (72.8% vs 56.8% % p = < 0.006). Barriers to partner notification included partners being out of town (44.6%) fear of quarrels and violence from partners (32.5%) and casual partners (15.1%) whose sex partners were unknown. CONCLUSION: Counseling and understanding of STIs patients on the need to treat all sexual partners is pivotal to the success of partner referral.

Parallelisation and application of a multi-layer atmospheric transport model to quantify dispersion and deposition of ammonia over the British Isles.

An atmospheric transport model, FRAME (Fine Resolution AMmonia Exchange), has been used to model the spatial pattern of ammonia concentrations and deposition over the British Isles for the first time. The model uses a multi-layer approach with diffusion through 33 layers to describe vertical concentration profiles in the atmosphere explicitly. Together with the necessary description of atmospheric reactions with sulphur and oxidised nitrogen, this imposes a major computational requirement, with the model having a run-time of 8.5 days on a mid-range workstation. Improvement in the model run-time was sought by developing a parallel implementation coded in a data-parallel approach using High Performance Fortran. Running the code on a Cray T3E with 128 processors provided a speedup by a factor of 69. The code's portability, its validation with measurements and new maps of its application to the British Isles, are presented. Good agreement is found with measured NH3 concentrations, while wet de-position is underestimated. In addition to model uncertainties, this may be due to an underestimation of the NH3 emissions input data.

Possible role of high-dose corticosteroids in the treatment of cat-scratch disease encephalopathy.

Approximately 2% of the estimated 24,000 patients in the United States who contract cat-scratch disease annually develop neurologic complications. Between 1989 and 1999, 36 patients were admitted to our hospital with cat-scratch disease; 25% had neurologic complications, and the majority experienced lengthy hospital stays. We describe a case of cat-scratch disease encephalopathy in a 4-year-old girl who responded to high-dose corticosteroid therapy. Further studies are warranted to determine if corticosteroid therapy shortens the duration of symptoms, lessens the severity of disease, and ultimately improves the outcome for patients with cat-scratch disease encephalopathy.

IgM expressed by leukemic CD5(+) B cells binds mouse immunoglobulin light chain.

Mouse immunoglobulin (Ig) molecules have previously been shown to bind to the surface of CD5(+) B cells from patients with B-cell chronic lymphocytic leukemia (B-CLL). The results indicated that surface IgM was involved in the interaction and suggested the phenomenon was an example of the polyreactive binding capacity of the surface Ig (sIg) expressed by these malignant cells. This article describes the further characterization of the interaction between human IgM and mouse Ig molecules and subunits. Mouse Ig molecules of both kappa and lambda light chain classes bound to the B-CLL cell surface. The dissociation constant for the interaction of mouse IgG1 (K121) with the B-CLL cell surface was 3.6 x 10(-7) M. To confirm the involvement of the human IgM expressed by the B-CLL cells in the interaction, the malignant cells were stimulated in vitro to induce secretion of human IgM. Enzyme immunoassay was used to show that secreted human IgM bound to intact mouse Ig, as occurred with the cell surface analysis. The mouse Ig epitope recognized by the purified secreted human IgM was shown by Western blot analysis to be located on the light chain of the mouse Ig molecule and to be conformationally dependent. K121 light chain was cloned and expressed in E. coli and the recombinant light chain bound to the surface of CLL B cells. The results confirm that human IgM is the reactive ligand in the interaction with mouse Ig and indicate that the interaction of polyreactive IgM with mouse IgG occurs via the light chain component of IgG.

c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of Tcells and is required for PKB-mediated protection from apoptosis.

During T-cell activation, c-Myb is induced upon interleukin 2 (IL-2) stimulation and is required for correct proliferation of cells. In this paper, we provide evidence that IL-2-mediated induction of the c-myb gene occurs via the phosphoinositide 3-kinase (PI3K) signaling pathway, that protein kinase B (PKB) is the principal transducer of this signal, and that activation of the c-myb promoter can be abolished by deletion of conserved E2F and NF-kappaB binding sites. We show that Myb is required to protect activated peripheral T cells from bcl-2-independent apoptosis and that overexpression of oncogenic v-Myb is antiapoptotic. Overexpression of a Myb dominant-negative transgene abrogates PKB-mediated protection from apoptosis. Taken together, these results suggest that induction of c-myb transcription is an important downstream event for PKB-mediated protection of T cells from programmed cell death.