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Therapeutic blockade of FcRn in humans decreases IgG and IgG immune complex levels with the attendant immunologic implications., The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Experimental results on atmospheric-pressure arc plasma convolutes in air around a polytetrafluoroethylene cylindrical shroud containing a magnetic field ( B-field) producing coil are presented. In this paper, the B-field coil is energized by a current separate from that flowing through the arc, and a separate RLC circuit was connected across the arc gap. Thus the magnitude and time duration of the B-field are independent of the arc current and the high-frequency current oscillations produced by the parallel RLC circuit. Experimental results for the time variation of the current through and voltage across the arc plasma for these different conditions are presented, along with high-speed photographs of the oscillating current arc. The effects of varying the B-field upon plasma pulsations formed by the independent B-field and RLC current oscillations are discussed.

This paper introduces the design of a Marx Generator that can generate high attitude pulses up to 25 kV and 2.5 kA. The pulses have a wave shape representative of that used to test High-altitude ElectroMagnetic (HEMP) filters against the pulse current injection (PCI) requirements. The rise time is 20 ns and the pulse width is 230 ns on a 10 Ω resistor. In the design, it was found that parasitic effect of circuit components could significantly affect the performance of the generator. This is mainly because the pulse width is very narrow and its frequency spectrum is very wideband. The high-frequency circuit models of the components used in the generator were obtained by calculation and optimization, and then further verified by experiment. The verified circuit models were then used to design the three-stage generator. The measured performance agrees very well with the simulated one using the proposed circuit models.

Rotary arcs in hollow polymeric cylinders have been monitored using electrical and optical techniques. The arcs burning within hollow cylinders were driven by electromagnetic forces. The arc voltage, current, dielectric strength below the arc gap, the optical emissions from the chamber were measured along with high-speed photography. The diameters of the hollow cylinders and magnitude of the applied magnetic field were varied. The arc voltage, especially the extinction peak prior to current zero, increased for larger bore cylinders and higher magnetic fields. By comparing the arc voltage waveforms and arc photographs, this was shown to be because the arcs were elongated. Luminosity was detected even after current zero, when polytetrafluoroethylene was in the arc chamber. The extensive experimental results obtained have enabled empirical mathematical expressions to be derived which yield approximate indications of current interruption capabilities under different operating conditions.

An optical-fibre probe is described for monitoring the production and build-up of particulate material in high-voltage SF6 circuit breakers, using the wavelength-dependent scattering of polychromatic light in conjunction with a chromatic modulation technique. It has been shown that the probe can be installed and routinely operated in a reliable manner within the tank of a 145 kV/40 kA circuit breaker during live arcing tests. Experimental results show that the severity and duration of arcing as well as the transient evolution of particle production and settling can be determined with the probe. As such, the results provide a means for tracking particulate conditions in a high-voltage circuit breaker with minimal intrusion into the circuit-breaker volume. It is concluded that the particulate mass per unit volume, formed by a single half cycle of arcing at the rated fault current, is only 0.1% of the total mass of SF6 within the circuit breaker. The particulate material may remain in suspension within the circuit-breaker tank for approximately 30 minutes after the arcing event. The formation of a film of particles on the probe following settling may provide a means for determining the fault-current arcing history of an interrupter.

An experimental study has been undertaken into the effects of changes in the spectral content of broadband light used for addressing a photoelastic strain sensor upon the calibration curve of such a transducer. A simple analysis is presented to show how compensation could be provided for random system drifts which produce such spectral variations. This has led to the design of a prototype photoelastic strain sensor with inbuilt compensation means. Some initial results are presented to demonstrate the performance of the transducer.

This paper describes a novel technique for interrupting direct currents (D.C.) with an electromagnetically convoluted arc in air at atmospheric pressure. Investigations are reported on the effects of using a separate current for producing the arc convolving electromagnetic field (B-field) to that being interrupted and using a separate R, L, C circuit in parallel with the arc contacts. Experimental results are presented for the time variation of currents flowing through the arc gap, the B-field coil and the parallel R, L, C circuit, along with the voltage across the arc gap.

Rapid developments in the field of modern optics are already having a major impact upon areas such as communications, sensing, information storage and image processing which have hitherto been the province of the electronic engineer. There is a need for evolving new teaching methods for accelerating the acquisition of relevant optical principles by undergraduate students of electronics from an engineering systems aspect rather than from a conventional physics approach. This contribution describes the development of part of a teaching module for this purpose which involves a combination of computer based methods coupled with practical work to provide experience of optical systems. The module is designed to demonstrate the optical information processing capabilities of a simple optical system through the use of ray optics analysis. It forms part of a unit on optical systems for electronic engineers, the other component of which is a supporting lecture course.

Measurements were described as current, voltage, and local dielectric strength for a current interrupter which utilized a novel form of electromagnetically convolved electric arc in air. Experiments have been performed with various interrupter structures and operational conditions. Precurrent zero-voltage extinction peaks and post-arc local breakdown voltages have been measured and are compared with values for nonconvoluted arcs in nitrogen and SF6. An empirical relationship between the extinction peak voltage and various design and operational parameters is presented. Signatures for the various interrupter structures under different operational conditions have been obtained by using a chromatic methodology and embodying the extinction peak and a local breakdown voltage.

From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia.

This contribution explores the role of PTFE ablation in enhancing current interruption for various background gases in high voltage circuit breakers. An assessment of the current interruption capability has been made in terms of the arcing duration and the contact gap length at which critical arc extinction is achieved. These observations are supported by measurements of the magnitude of extinction and re-ignition voltage peaks. Most previous and other current experimental work on gas filled circuit breaker design follows conventional wisdom in investigating arcing behaviours at elevated gas pressures (usually up to 6 bar). But in this work we concentrate on the effects of using low gas pressures (less than 1 bar) in the presence of a close-fitting shield of ablatant polymer material (PTFE) that surrounds the electrode assembly of an experimental high power circuit breaker. We demonstrate that for several different gases, arc extinction capability compares well under these conditions with SF6, suggesting that SF6 could be replaced entirely in this novel system by more environmentally friendly gases. Moreover, the critical contact gap lengths at extinction are only slightly greater than when using SF6 at 6 bar. Weight loss measurements from the ablatant shield suggest that a chemical puffer action is the most likely mechanism for achieving the observed arc extinctions in this system.

Interruption of currents flowing in a high-voltage power network is a complex process involving intricate interactions between the mechanics, electromagnetics and electrical discharging in a circuit breaker. Consequently, ensuring correct operation, and more ambitiously attempting to predict incipient failure to operate, is a difficult proposition. To deal with such a complex situation, there is a need to evolve an intelligent monitoring methodology which will enable such objectives to be achieved in a generic manner. In this contribution, the use of the chromatic approach to optical fibre sensing and subsequent fusion of multisensors output is described as a basis for such intelligent monitoring of HV circuit breakers. The parameters measured with the chromatic fibre sensors are listed, taking advantage of the inherent electrical insulated nature and electromagnetic immunity of such sensors. These measurements are supplemented by voltage and radiofrequency emission measurements during circuit breaker operation. The time varying outputs from this array of different sensors have been further chromatically processed in the time domain enabling the complex information contained in the outputs to be compressed in chromatic space. This has enabled changes in the operational trends of the circuit breaker to be conveniently tracked in a simple manner, so forming an advantageous monitoring strategy.

In this paper, the authors attempt to demonstrate: how optical fibre sensors can provide valuable information about circuit breaker operation, free from the uncertainties and malfunction from which electronic sensors suffer during live testing; and how the sensor information can be used to validate fundamental physical modelling of the arc-aerodynamic interaction on the one hand and from the basis of condition monitoring via chromatic processing on the other. The example chosen shows clearly the conflicting needs of the modelling and monitoring applications.

Approximately 25% of hemophilia A patients infused with factor VIII (fVIII) mount an immune response, which leads to its inactivation. Anti-fVIII autoantibodies are also seen rarely in individuals with normal fVIII. We have previously demonstrated that some anti-A2 and anti-C2 domain antibodies are fVIII inhibitors and that many patients have additional inhibitors with a fVIII light chain (LCh) epitope outside C2. Because the contribution of the different antibodies to the plasma inhibitor titer had been examined in a limited number of patients (14), we report in this study a more extensive analysis of 55 plasmas. The dominant inhibitors in 62% (13 of 21) of autoantibody plasmas were directed only against C2 or A2, but not both, whereas this pattern was found in only 15% (5 of 34) of hemophilic plasmas. In addition, anti-A2 inhibitors were present in 71% (24 of 34) of hemophilic plasmas, but only 33% (7 of 21) of autoantibody plasmas. These results demonstrated that the inhibitor response in hemophiliacs was more complex and the epitope specificity was somewhat different. A comparison of hemophiliacs treated only with plasma fVIII or recombinant fVIII showed no significant differences in the complexity of the inhibitor response, asor = 2 different inhibitor antibodies were present in 78% (18 of 23) of the former and 82% (9 of 11) of the latter. In contrast, the major inhibitors in 35% (8 of 23) of hemophiliacs treated with plasma fVIII were directed against C2 and another LCh epitope within residues 1649-2137, but not A2, while none (0 of 11) treated with recombinant fVIII had this pattern.

D-dimer fragments can be measured easily in plasma and whole blood, and the presence or absence of D-dimer could be useful in the diagnostic evaluation of venous thromboembolism. We systematically reviewed the English literature for articles that compared D-dimer results with those of other tests for deep venous thrombosis or pulmonary embolism. Twenty-nine studies were selected for detailed review, and we noted wide variability in assay performance, heterogeneity among subjects, and failure to define absence or presence of venous thromboembolism by a comprehensive criterion standard for diagnosis. These methodologic problems limit the generalizability of the published estimates of D-dimer accuracy for deep venous thrombosis or pulmonary embolism, and the clinical utility of this potentially important test remains unproved.

This contribution describes an optical fibre whitelight interferometric technique for monitoring temperature. Modulated wide-band interference signals are detected by photodiodes and electronically processed into a single value. The device is suitable for industrial applications.

Portable instruments that measure the prothrombin time and automatically calculate the international normalized ratio (INR) with the use of a drop of whole blood have simplified the treatment of patients who are receiving warfarin therapy. The accuracy of these portable monitors has never been determined by comparing INR results with a criterion (gold) standard INR determination.Duplicate whole-blood INR determinations were made with two commercially available portable INR monitors. Duplicate frozen-plasma samples were measured with four different thromboplastin reagents, each with a different international sensitivity index. The criterion standard INR was determined by using an international reference thromboplastin and the manual tilt-tube technique. Agreement was evaluated by determining how accurately laboratory and monitor INR determinations matched criterion standard values in designating a sample to be within or outside of currently recommended INR target ranges.Two of the laboratory methods, which used relatively sensitive thromboplastins, showed close agreement with the criterion standard, whereas two laboratory methods that used less sensitive thromboplastin reagents showed poor agreement. Both of the portable monitors fell between these extremes. The two best laboratory methods ere significantly better (P.003) than both monitors, which in turn were better (P.003) than the remaining two laboratories.There is large interlaboratory variation in the accuracy of INR determinations. Laboratory methods that used insensitive (high international sensitivity index) thromboplastins performed poorly. Accuracy of monitor measurements appears satisfactory.

This contribution describes an optical fibre temperature sensor which is robust enough for encapsulation into concrete used as a backfill in a landfill site. The sensing element is a Fabry-Perot cavity specifically designed to operate from 20 to 110°C with long lengths of optical fibre cable (up to 600 m). The sensor has been tested in a pressure chamber up to 10 bars and subjected to vibration in a 145 kV circuit breaker, it showed no degradation in performance. The sensor also demonstrated good stability during extended temperature cycling tests and during prolonged drift tests. The accuracy of the sensor is 2% with a resolution 0.5%. The optical support system for the sensor was a stabilised white light source and an optoelectronic detection system which optically compresses the modulated polychromatic signal representing it as a single number. This number is calibrated against temperature. The sensing system can support up to eight different or similar sensors simultaneously providing cost benefits for industrial applications. (4 pages)

Acquired coagulopathies, such as are observed in patients with liver disease, uremia, and acute disseminated intravascular coagulation, are complex disorders usually involving a combination of deficiency of multiple coagulation factors, platelet dysfunction, and thrombocytopenia. Transfusion of specific blood products, such as fresh-frozen plasma, platelets, and cryoprecipitate, may be effective in the treatment and prevention of hemorrhage in patients with these disorders; however, the optimal regimens continue to be defined. Because the risks of virus transmission along with hemolytic and allergic reactions continue to accompany blood product transfusions, nontransfusional forms of treatment of acquired coagulopathies, such as desmopressin acetate, antifibrinolytic agents, and aprotinin, have assumed greater roles in the treatment of these hemostatic disorders. Much work remains to define better the most effective and safest approach to the treatment of the acquired coagulopathies.

We present the association of a lupus anticoagulant with hypoprothrombinemia in a 5-year-old girl, who presented with ecchymoses and a hematoma. This coagulopathy should be included in the differential of bleeding in the previously healthy children.Coagulation and immunology laboratory evaluation was performed at the time of presentation with bleeding and 2 months later, after complete clinical recovery.A 5-year-old girl presented with ecchymoses and a hematoma after after an upper respiratory illness. Laboratory evaluation showed prolongation of both the prothrombin time (PT) and activated partial thromboplastin time (aPTT) due to the presence of a strong lupus anticoagulant associated with a decreased level of prothrombin (15 U/dl). Hypocomplementemia was also detected. Bruising resolved spontaneously, and the PT and aPTT gradually normalized. Reevaluation 2 months later showed that the lupus anticoagulant had disappeared and the prothrombin deficiency was markedly improved.This case demonstrates that transient lupus anticoagulants must be included in the differential for bleeding in young children. Also, in children with lupus anticoagulants, neither the association of hypoprothrombinemia nor the presence of evidence of activation of the immune system appears to predict whether a patient will have or develop systemic lupus erythematosus.

Recently, indications for anticoagulation with warfarin have increased, prothrombin time (PT) monitoring at offices and homes has become available, and the international sensitivity index (ISI) has been recognized as a means of adjusting for differences in thromboplastins to standardize warfarin sodium dosing. However, different coagulation instruments may yield differences in PTs even after correcting for the ISI by means of the international normalized ratio (INR) (INR = [PT measured ISI/PT normal]). Because the PTs and INRs from our Anticoagulation Clinic (portable PT monitor, ISI = 2.04, normal PT = 12.0 seconds) differed from the hospital reference laboratory (ISI = 2.01, normal PT = 12.0 seconds) despite nearly identical ISIs and equivalent control or normal PTs, we systematically compared the two systems. During a 3-month period, we studied two groups of 50 consecutive patients who had been receiving a stable dose of warfarin. After a single venipuncture, PTs and INRs were measured independently, and regression lines were calculated. Within each group, the results from the different instruments were not identical, but they were highly correlated. In comparing INRs, the regression lines for the separate and combined groups were as follows: group 1 monitor INR = 0.49 reference INR + 0.81, r = .94; group 2 monitor INR = 0.57 reference INR + 0.86, r = .88; and combined monitor INR = 0.49 reference INR + 0.95, r = .89. Only 82% of the differences for all samples were within 1.0 INR units. We concluded that the instrumentation effect may be clinically meaningful, and coagulation instruments as well as thromboplastins should be calibrated to standardize warfarin therapy.

The Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) is an autosomal dominant disorder of blood vessels associated with mucocutaneous telangiectasis and arteriovenous malformations of internal organs.A 23-year-old woman was found on routine gynecologic examination to have asymptomatic vaginal telangiectasias, a previously unreported initial site of involvement in this syndrome.The finding of asymptomatic vaginal telangiectasias on routine pelvic examination should alert the clinician to the possibility of the Osler-Weber-Rendu syndrome.

A 64-year-old man with both Factor XI deficiency and a lupus anticoagulant who suffered two myocardial infarctions within a 3-month period is described. Although thromboembolic disorders, including myocardial infarction, have been associated with the antiphospholipid syndrome, myocardial infarction in patients with Factor XI deficiency is rare. The potential role of Factor XIa in fibrinolysis is discussed.

The purpose of this investigation was to characterize the reaction of alpha 2-antiplasmin (alpha 2AP) and alpha 2-macroglobulin (alpha 2M) with human plasmin bound to rat C6 glioma cells and human umbilical vein endothelial cells (HUVECs). Binding of plasmin (0.1 microM) to C6 cells at 4 degrees C did not cause cell detachment, decrease viability or change cell morphology. The KD and Bmax for the binding of diisopropyl phosphoryl plasmin (DIP-plasmin) to C6 cells were 0.9 microM and 2.6 x 10(6) sites/cell. The dissociation rate constants (koff) for 125I-plasmin were 9.7 x 10(-4) and 4.0 x 10(-4) s-1 at 4 degrees C in the presence and absence of 0.3 microM DIP-plasmin, respectively. Similar constants were determined for 125I-plasminogen and 125I-DIP-plasmin. Neither alpha 2AP nor alpha 2M affected the dissociation of DIP-plasmin. C6 cell-associated 125I-plasmin reacted slowly with alpha 2AP; however, the inhibition rate constants exceeded the koff. alpha 2AP-plasmin complex formed after the plasmin dissociated into solution (reaction pathway 1) and by direct reaction of alpha 2AP with cell-associated enzyme (reaction pathway 2). High concentrations of alpha 2AP favored pathway 2. C6 cell-associated plasmin was also protected from inhibition by alpha 2M. While the same pathways were probably involved in this reaction, alpha 2M was less effective than alpha 2AP as an inhibitor of nondissociated plasmin (pathway 2). When C6 cell-bound plasmin reacted with alpha 2AP, alpha 2AP-plasmin complex was recovered primarily in the medium, suggesting dissociation of complexes formed on the cell surface. Plasmin-receptor dissociation and inhibition experiments were performed at 22 degrees and 37 degrees C, confirming the conclusions of the 4 degrees C studies. Comparable results were also obtained using HUVEC cultures. These studies demonstrate that cell-associated plasmin is protected from inhibition by alpha 2M as well as alpha 2AP. At least two reaction pathways may be demonstrated for the inhibition of plasmin that is initially receptor-bound; however, neither pathway is highly effective, accounting for the "plasmin-protective" activity of the cell surface.

A 39 year old man with Marfan syndrome presented with multiple pulmonary emboli and renal, hepatic, and splenic infarcts of unknown aetiology. The combination of thromboemboli and physical features initially suggested homocystinuria; however, laboratory examination showed no evidence for this disorder. Laboratory evaluation identified no coagulation abnormalities. This patient represents the unusual occurrence of hypercoagulability in a patient with Marfan syndrome.

Fluoxetine (Prozac) is a nontricyclic serotonin (5-hydroxytryptamine) reuptake inhibitor commonly prescribed for the treatment of depression. Fluoxetine also blocks 5-hydroxytryptamine reuptake in platelets and could potentially lead to clinically significant platelet dysfunction. We describe a patient who developed petechiae and prolongation of the bleeding time while receiving fluoxetine therapy.

Experimental results have been obtained about conditions within SF/sub 6/ puffer circuit breakers during and after the interruption of fault currents up to 45 kA peak using optical-fibre sensors based on chromatic modulation. The particular parameters measured with the optical-fibre sensors were the contact travel, the gas pressure in both the puffer piston chamber and the circuit-breaker tank, the radiative emission from the electric arc and the concentration of micron-sized particles produced by the arcing. The experimental results are compared where possible with theoretical calculations from a computational-fluid-dynamics computer package. The possible role of the particulate material in the longer-timescale conditions within the circuit-breaker tank is considered and the need for a better understanding of the particulate-material properties and formation is highlighted.

Intelligent monitoring encompasses the extraction of information from data sets, which are only partially complete because of practical constraints on the deployment of measurement techniques. An experimental technique is described for monitoring a number of conditions within oil-filled circuit breakers from a single measurement method and using an optimised number of optical fibre sensing channels. The technique is based upon detecting changes in the optical intensity of light transmitted through the circuit breaker medium, using optical fibre delivery and capture at a number of different axial and radial locations within the circuit breaker chamber. It has been used during development testing at a short circuit test station for two oils with very similar physical characteristics but different kinematic viscosity as the arc extinguishing media. Results are presented which examine the dependence of the contact travel time upon arc duration and oil type. Quantitative information is given concerning the optical recovery time of the oil as a function of arc duration and axial location within the circuit breaker. The technique also detects the occurrence of fresh oil injection into the contact gap and enables the duration of its occurrence to be determined.

Shessel et al. (Invest. Urol., 17: 529-533, 1980) have reported previously that the serially transplantable Dunning R-3327-G rat prostatic, adenocarcinoma grows faster in intact versus castrated male rats. The present study has demonstrated that this is because the G tumor is composed of androgen-independent but -sensitive prostatic cancer cells. The inclusion that G tumor cells are androgen independent is based upon the observations that these cells are capable of growing following inoculation into castrated male rats and that castration of intact male rats bearing established G tumors induces neither regression of tumor volume nor cessation of the continuous growth of the tumor. The G tumor cells, while being androgen independent, are, however, highly sensitive to androgen for their maximal rate of tumor growth. This androgen sensitivity is demonstrated by the fact that the G tumor cells can be reversibly shifted to a faster or slower growth rate simply by manipulation of the host androgen status. The androgen sensitivity of G tumor growth rate is unusual in that it is not due to androgenic stimulation of cell division but to androgen-induced inhibition of G tumor cell loss (i.e., the rate of G tumor cell loss is reduced by over 50% when androgen is present). The androgen sensitivity of G tumor cell loss is also unusual in that, due to the low level of 5 alpha-reductase activity of the G tumor, the predominant intracellular androgen responsible for this inhibition in untreated intact hosts appears to be testosterone and not dihydrotestosterone (DHT). In castrated rats, however, exogenous treatment with DHT is equally as effective as exogenous testosterone in inhibiting G tumor cell loss. These results suggest that G tumor cells are sensitive to either testosterone or DHT but that in untreated intact hosts little DHT is formed by the tumor cells.