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Thin-film silicon tandem (MICROMORPH™) module design optimization process for performance maximization is described together with an analysis of some key reliability topics. In the first part, the procedure for module layout optimization to achieve the maximum module power output is described. In monolithic thin-film modules the layout is realized through a laser scribing interconnection process: a well-controlled laser scribing process is therefore essential to ensure optimal module performance and to minimize unwanted losses. The second part of the paper focuses on some of the materials used in the fabrication of a solar cell and module of such technology and the processes used to achieve such module assembly, as well as a description of some of the possible failure modes. Special attention is paid to the zinc oxide transparent conductive oxide (ZnO TCO) layers used for the front and back contacts. The bottom cell (BoCe) and its stability is also analyzed in detail: the influence of process parameters on the BoCe degradation behavior including the differences observed using different thin-film silicon (TF-Si) deposition reactor types, different lamination foils and the impact using different front contact haze is discussed. In the final part of the paper the effect of particle contamination on the module performance is reviewed: specifically contamination by particles generated during deposition and handling processes. Finally relevant countermeasures to prevent additional module performance loss are discussed.

Increased electrical power generated from a thin-film silicon (TF-Si) photovoltaic device can lead to a reduced cost of electricity production that will support the mass adoption of this technology as a renewable energy source. Extracting the highest conversion efficiency from ‘champion’ large area TF-Si modules has been the focus of development at TEL Solar AG, Trubbach. The layer deposition process adjustments and further module technology improvements that led to a significant increase in the absolute stabilized module conversion efficiency of large area (1.43 m 2 ) tandem MICROMORPH™ modules centered first on obtaining high quality amorphous TF-Si deposited materials for the top cell. This was integrated with microcrystalline TF-Si material for the bottom cell that was deposited under conditions close to the transition point between the amorphous and microcrystalline growth regimes. In an optimized solar cell design the TF-Si materials were then combined with effective light management technologies and an improved module layout. The end result of a world record large area (1.43 m 2 ) stabilized module conversion efficiency of 12.34% was certified by the European Solar Test Installation (ESTI). The main technology contributions in the device design for this breakthrough result that generated more than 13.2% stabilized efficiency from each equivalent 1 cm 2 of the active area of the full module are described.

Gas electron multipliers with a liquid crystal polymer insulator (LCP-GEMs) can be employed as X-ray polarimeters in several satellite missions in low-earth orbit. To evaluate their resistance to radiation, LCP-GEMs were exposed to Fe ion and proton beams from the heavy-ion accelerator facility HIMAC, and the gas gain was monitored. The LCP-GEMs survived 14.4-year-equivalent irradiation by fully stripped Fe ions with an energy of 500 MeV nuc-1, which simulated galactic cosmic-ray ions. We also studied the degradation of the insulator layer of the LCP-GEMs by irradiation with 160 MeV protons to simulate geomagnetically trapped protons. After irradiation with protons for 31.6 years equivalent, no significant change in gain was observed.

A centrifugal pellet injector and a guide tube for magnetic high-field side (HFS) injection were developed in JT-60U. The injector can eject trains of up to 40 cubic (1.9 mm) 3 deuterium pellets at frequencies of 1–10 Hz and velocities of 0.2–1.0 km/s. Pellet injection experiments into ohmic heating (OH) plasma were performed. From plasma density measurement, central fueling and enhanced fueling rate compared to gas puffing were observed for magnetic low-field side (LFS) injections. The results of HFS injection through the guide tube connected to the upper port of the vessel showed that the pellet velocity exceeding 220 m/s caused pellet destruction inside the tube.

Fusion performance of reversed shear discharges with an {ital L}-mode edge has been significantly improved in a thermonuclear dominant regime with up to 2.8 MA of plasma current in the JT-60U tokamak. The core plasma energy is efficiently confined due to the existence of persistent internal transport barriers formed for both ions and electrons at a large minor radius of r/a{approximately}0.7 near the boundary of the reversed shear region. In an assumed deuterium-tritium fuel, the peak fusion amplification factor defined for transient conditions involving the dW/dt term would be in excess of unity. {copyright} {ital 1997} {ital The American Physical Society}

The scientific objective of the X-ray Advanced Concepts Testbed (XACT) is to measure the X-ray polarization properties of the Crab Nebula, the Crab pulsar, and the accreting binary Her X-1. Polarimetry is a powerful tool for astrophysical investigation that has yet to be exploited in the X-ray band, where it promises unique insights into neutron stars, black holes, and other extreme-physics environments. With powerful new enabling technologies, XACT will demonstrate X-ray polarimetry as a practical and flight-ready astronomical technique. Additional technologies that XACT will bring to flight readiness will also provide new X-ray optics and calibration capabilities for NASA missions that pursue space-based X-ray spectroscopy, timing, and photometry.

The aim of this paper was to investigate the growth rate of abdominal aortic aneurysms (AAA) in Japanese patients.We retrospectively studied patients conservatively followed with infrarenal AAA in terms of AAA diameter measured using computed tomography (CT) in our hospital between 1999 and 2009. The AAA surgery criterion in our institute was a diameter ≥ 5.0 cm or a growth rate ≥5 mm/year. We estimated operation-free ratios by initial AAA diameter and changes in AAA growth rates. Patients with an initial AAA diameter5.0 cm were divided into 2 groups. Patients with AAA that met the criteria for surgery were classified into the expansion group, and those remaining into the non-expansion group. Their AAA growth rates were compared.The group consisted of 124 patients (average age, 73.7±8.6 years (range 54-92)) who had at least 2 recorded AAA measurements. The average follow-up period was 3.0±2.2 years (range 0.3-10.2). There were no cases of rupture during follow-up. Twenty-six patients (21.0%) underwent surgery (open replacement [N.=20]; endovascular abdominal aneurysm repair [N.=6]). The growth rate determined from the initially measured diameter was significantly faster in AAAs measuring 5.0-5.4 cm than in AAAs measuring 4.5-4.9 cm (P=0.01). More than 90% of patients with an initial AAA diameter5.0 cm were observed conservatively for 2 years or more. However, more than half of the patients with an initial AAA diameter ≥4.0 cm needed surgery within 5 years. The growth rates of AAAs for each size during growth were significantly faster when the AAA diameter was 4.5-4.9 cm than when it was 4.0-4.4 cm (P=0.006), and when the AAA diameter was 5.0-5.4 cm than when it was 4.5-4.9 cm (P = 0.009). The expansion and non-expansion groups consisted of 38 (34.2%) and 73 (75.8%) patients, respectively. The AAA growth rate in the expansion group was significantly faster than that in the non-expansion group (3.4±2.2 mm/year vs. 1.4±1.3 mm/year, P=0.0001).It may be considered that the appropriate indication for AAA repair is defined by a diameter of 5.0 cm for Japanese patients. Patients with AAA that is growing continuously by ≥3 mm/year and who have low operative risk may undergo surgery even if their AAA is5.0 cm.

We successfully produced Resistive-Electrode GEM (RE-GEM) that was applied Resistive-Kapton to electrodes. We measured the gain curve of RE-GEM using an 55Fe radioactive source in the gas mixture of Ar 70 % and CO 2 30 %. We obtained the maximum gain of about 300 at an applied voltage of 740 V.

The Gravity and Extreme Magnetism Small Explorer (GEMS) is an astrophysical observatory dedicated to X-ray polarimetry (2-10 keV) and is being developed for launch in 2014. To maximize the polarization sensitivity of the observatory, GEMS uses polarimeters based on the photoelectric effect with a gas micropattern time projection chamber (TPC). We describe the TPC polarimeter concept and the details of the GEMS implementation, including factors that affect the ultimate polarization sensitivity, including quantum efficiency, modulation factor, systematic errors, and background.

The Gas Electron Multiplier (GEM) is a new device that amplifies an input electron cloud, while keeping its shape unchanged [1]. We have developed various type GEMs using a laser etching technique. Those GEMs had different geometry (pitch, hole diameter and thickness) and materials (polyimide; PI or liquid crystal polymer; LCP). We have applied the GEMs to a photoelectric polarimeter that measures polarization of X-rays emitted from stellar objects. To obtain the polarization accurately, it is necessary for GEMs to have good uniformity in two-dimension. As a result of gain mapping, the standard deviation of gain variation of our standard GEM was ∼ 5%. Our GEMs showed enough uniformity to detect X-ray polarization. Comparing hole diameter and gain maps of the same region, there was no correlation between these two maps. Comparing maps of different type GEMs, there was no difference among them and PI GEMs were more uniform than LCP ones.

A newly-designed bifurcated graft with the distal end larger than the conventional type has been developed. The purpose of this study was to evaluate the early results of graft replacement using this new graft, and to compare whether the new graft is more advantageous than the conventional graft in terms of peripheral blood flow and arterial stiffness.Records of 36 patients who underwent bifurcated graft replacement for infrarenal abdominal aortic aneurysm (AAA), from May 2003 to September 2006 were reviewed after excluding peripheral arterial disease (ABI0.9). Subjects were divided into two groups: group C (N.=20), with implantation of the conventional type and group N (N.=16), with implantation of the new type. We investigated changes in brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI), measurements being performed preoperatively and postoperatively.baPWV in the postoperative group as a whole was significantly higher than in the preoperative group (P0.05), while ABI in the postoperative group was lower than in the preoperative group (P0.05). In group C, baPWV increased (P0.05) and ABI decreased (P0.05) after bifurcated graft replacement, whereas in group N, there were no significant differences in changes of baPWV and ABI.This study shows that the new graft reduces the development of arterial stiffness postoperatively compared with the conventional type. These results may predict the new type graft decrease in the risk of morbidity and mortality caused by atherosclerotic disease.

We have produced thick-foil and fine-pitch gas electron multipliers (GEMs) using a laser etching technique. To improve production yield we have employed a new material, Liquid Crystal Polymer, instead of polyimide as an insulator layer. The effective gain of the thick-foil GEM with a hole pitch of 140 um, a hole diameter of 70 um, and a thickness of 100 um reached a value of 10^4 at an applied voltage of 720 V. The measured effective gain of the thick-foil and fine-pitch GEM (80 um pitch, 40 um diameter, and 100 um thick) was similar to that of the thick-foil GEM. The gain stability was measured for the thick-foil and fine-pitch GEM, showing no significant increase or decrease as a function of elapsed time from applying the high voltage. The gain stability over 3 h of operation was about 0.5%. Gain mapping across the GEM showed a good uniformity with a standard deviation of about 4%. The distribution of hole diameters across the GEM was homogeneous with a standard deviation of about 3%. There was no clear correlation between the gain and hole diameter maps., Comment: 21 pages, 9 figures

A gas electron multiplier (GEM) is a key device for the photoelectric X-ray polarimeters, which will be launched in the near future. Our GEMs have spatial resolution enough for tracking of photoelectrons and low risk of discharge. GEMs need to perform well in all sorts of tolerance tests for space missions before launch. As a result of gain stability test after switching ON/OFF 6500 times repeatedly, our GEM gain variation is within ±2%. This repetition time scale corresponds to 2-year space mission in the Low Earth Orbit. As a result of charged particle (Fe) irradiation to GEM, our GEM survived more than 500 seconds of Fe ion irradiation (flux is 130 cts/cm2/s). This corresponds to 40-year irradiation in space. Thus, we conclude that our GEMs are stable enough for space missions and tolerance against discharge which is caused by charged particles.

Total aortic arch replacement using the 'elephant trunk (ET)' procedure has commonly been applied to acute aortic dissection, but enlargement of a residual false lumen of the descending thoracic aorta sometimes occurs. We performed endovascular stent-grafting to close the entry as the second operation and obtained successful outcomes. From April 1997 to January 2004, we performed the modified ET procedure for acute aortic dissection in 29 patients and evaluated postoperative changes of the false lumen. In many cases of the residual false lumen, kinks and wrinkles were observed at the site of the ET grafts in the descending aorta. An adequate length of ET would be about 8 cm long to prevent kinking, and a diameter about 20 mm to prevent wrinkles.

Anti-reflection coating (ARC) is well known as an important technique to enhance solar cell performance. Typical ARC has been applied on the glass surface to reduce light reflection loss at the air/glass interface. However, reflection loss occurs not only at glass surface but also at other interfaces such as glass/transparent conductive oxide (TCO) interface. The refractive index of SiNx is tunable from 1.6 to 2.7, and the range from 1.7 to 2.0 is suitable for ARC at glass/TCO interface. In this study, we examined the AR effect of silicon nitride (SiNx) deposited by plasma enhanced chemical vapor deposition at the glass/TCO interface with thin film silicon solar cell and module. Reflectivity reduction of 1.6% for glass/ZnO substrate has been obtained with optimal SiNx layer, which contribute 2.0% gain in cell efficiency. Besides, we also confirmed the relative efficiency gain of around 2% for large-sized solar module, leading to a world-record large area stabilized module conversion efficiency of 12.34%.

Cm-level high accuracy real-time GPS positioning system is realized nation wide in Japan based on networked Real Time Kinematics GPS (RTK-GPS), and has been commercially operated by Mitsubishi Electric Co. named PAStrade, Positioning Augmentation Services, since September 2003. Also we have recently devised more convenient method at submeter or decimeter accuracy using low cost and compact code-ranging GPS receiver utilizing correction data fed from PAS system. Both of these methods will reduce time and cost significantly to produce precise satellite imagery based on Ground Control Point (GCP), as well as to update maps in geo-centric coordinate, which is necessary to use satellite imagery operationally with GPS

The premises cordless telephone (PCT) system provides a full function access to PSTN (public switched telephone network) subscriber lines via an existing PBX (private branch exchange) and/or a single controller or a network of controllers. The system enhances corporate communications by giving callers direct dial-through access to executives on the move and engineers and technicians working out of reach of wired telephones. The system offers similar benefits for offices, hotels, hospitals, building maintenance services, department stores, shopping malls, trade fairs, etc. Base stations configure the microcell structures with location registration and handoff features which will enable system planners to tailor the system economically to the diverse needs of traffic density and to eliminate the shadowing effects of building structures, walls, etc. The system features are described, including uses of the dynamic frequency assignment and flexible base station arrangement (irregularly located) within a microcell (or picocell) structure to ensure user-friendly operations, full extension of system flexibility, and significant increase in the traffic capacity within a highly dense traffic area. >

Objective. The purpose of this study was to examine how gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF ) is involved in the molecular mechanism of cartilage degradation in rheumatoid arthritis (RA) with special reference to the GLS-induced gene expression and protein synthesis of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysin-1). Methods. Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS. Changes in the expression levels of GLS, MMP-1 and MMP-3 were assessed by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) for GLS, and by RT-PCR and enzyme-linked immunosorbent assay for MMPs and tissue inhibitor of metalloproteinase 1. Results. GLS demonstrated a self-induction of mRNA in cultured RA FLSs. GLS evoked a dose-dependent induction of MMP-1 and MMP-3 mRNAs, and subsequently their extracellular secretion. Conclusion. These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs.

We reported valuable MRI findings of the brachial plexus seen in two cases with chronic inflammatory demyelinating polyneuropathy (CIDP). Case 1 was a 44-year-old man who developed slowly progressive weakness and atrophy of the extremities with no sensory disturbances. Studies of CSF showed a normal level of protein and no increase of cell counts but nerve conduction studies demonstrated a significant conduction block between the axilla and the elbow in the right ulnar nerve. Case 2 was a 34-year-old male who had been suffering from distal limb weakness and sensory disturbance. Protein content in CSF was markedly elevated without pleocytosis, and nerve conduction studies revealed a conduction block between the elbow and the wrist in the right ulnar nerve. He received corticosteroid therapy, resulting in a good recovery. Brachial plexus in both cases showed enlargement with marked high signal on short TI inversion recovery (STIR) of MRI. STIR is a fat suppressed T2 weighted image and this technique is known to be useful to identify the morphology of peripheral nerve tissues. CIDP is one form of hypertrophic neuritis and the MRI findings seen in these two cases strongly support the diagnosis of CIDP.

The kinetics of the disposition of MRK16, an anti-P-glycoprotein monoclonal antibody, was studied in two human colorectal tumor cell lines, HCT-15 and COLO205, whose P-glycoprotein expression is extensive and poor, respectively. In a series of in vitro binding studies, the amount of MRK16 associated with HCT-15 cells at steady state was approximately 40 times greater than that associated with COLO205 cells. In in vivo studies, the disposition of MRK16 was determined in tumor-bearing mice after intravenous administration. The difference in the tumor-to-plasma concentration ratio between the two cell lines was only 2.3-fold at 72 hr after injection. To explain the large difference observed between the in vitro and in vivo results, a series of kinetic simulation studies were performed. By considering the physiological parameters specific for MRK16 (such as permeability-surface area product and the kinetic parameters determined in vitro), the time profiles for the tumor concentration were predicted. The predicted difference in the tumor-to-plasma concentration ratio at 72 hr was calculated to be 2.6-fold, although the permeability-surface area product across the tumor capillary and other physiological parameters were comparable between the two tumor cell lines. The discrepancy between the in vitro and in vivo results was accounted for by the fact that the tumor extracellular fluid concentration at this time point was 13-fold lower in HCT-15 tumors than in COLO205 tumors because of the restricted penetration of MRK16 through the tumor capillaries. This finding suggests that this factor accounts for the in vitro and in vivo difference in the tumor disposition of MRK16.

Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Since P-glycoprotein (P-gp) encoded by the MDR-1 gene plays a key role in MDR, many P-gp-specific monoclonal antibodies (MAbs) have been generated for characterization and analysis of P-gp. Among those antibodies, MRK16 has been widely used not only for elucidation of the mechanisms of P-gp-mediated MDR but also for diagnostic and therapeutic studies. Two types of magnetic cell sorting assays, termed MRK16-MACS and MRK16-MACS-FACS, have been established by us and may offer a useful tool to quantitate low levels of P-gp expression. This article describes the characteristics of the antibodies against P-gp and discuss the diagnostic implications of the antibodies.

We present broadband X-ray analyses of the magnetar 1E 1547.0 5408 observed with Suzaku on 2010 August 7, nearly one and a half years after an intense outburst in 2009 January. The 2–10 keV flux decreased to (1.06 0.01) 10 11 erg cm 2 s , while the hard X-ray detection was 3.5 (18–40 keV) and 2.4 (18–35 keV) significance levels, where the former includes only the 2% systematic error of the non X-ray background, and the latter further takes into account possible near-by contaminating sources, respectively. Our confirmation of both soft and hard X-ray components during the late phase of the outburst strengthened the possibility that most magnetars are composed of the two spectral components, both in burst-active and less-active states. Together with a similar decay speed between the soft and hard components, their radiation mechanisms are suggested to be tightly related to each other. The 1–40 keV broadband spectrum was successfully fitted with the same model as used in the fit just after the onset of the outburst in 2009: a surface blackbody radiation with photoelectric absorption and a hard power-law. The blackbody flux decreased to be 30% of that in 2009 while keeping its temperature at kT = 0.65 keV, suggesting a shrinking hotspot on the magnetar surface by a factor of 0.3. The hard power-law extended up to at least 35 keV with a photon index of Γ = 1.1 0.4, which was consistent with the 2009 value. The flux ratio, , of the 1–60 keV power-law to 1–60 keV thermal component was calculated to be = 1.2 0.7 at the late phase of the outburst for the first time. The obtained value follows the previously known negative correlation with the characteristic age, implying that the correlation holds for most of the magnetar states: no burst, onset and late phase of outbursts.

We here report a case of Miller Fisher syndrome (MFS) in which serum anti-cerebellar antibody was detected by Western blot analysis. The 32-year-old male studied suffered from diplopia, gait ataxia and sensory disturbance in the distal portion of the upper limbs preceded by cold-like symptoms. Neurological examination on admission revealed that he had external ophthalmoplegia with bilateral ptosis, cerebellar ataxia and areflexia. A cerebrospinal fluid examination showed albuminocytologic dissociation with a protein concentration of 60 mg/dl. Brain CT and MRI showed no significant abnormalities. The patient was diagnosed as MFS, and treated it with two sessions of immunoadsorption plasmapheresis (IAPP). After receiving IAPP therapy, the patient's neurological symptoms and signs were improved. Western blot analysis showed the existence of antibody directed against mouse cerebellum but not against mouse cerebrum, brain stem, and spinal cord in his serum, the level of which was decreased after the IAPP therapy. Serum anti-GQ1b antibody was also elevated. As far as we are aware, there have been no reports showing the existence of anti-cerebellar antibodies detected by Western blot analysis. Though the pathogenesis of MFS remains unclear, our findings suggest that anti-cerebellar antibody detected by Western blot analysis may be caused by cerebellar ataxia in MFS.

Spherical multicellular aggregates of adult rat hepatocytes (spheroid) which have tissue like structure, were formed and immobilized in the pores of polyurethane foam (PUF) which was used as a culture substratum. These hepatocyte/spheroids, about 100 µm in diameter, have maintained higher differentiated functions (the albumin secretion activity and the urea synthesis activity) than those of hepatocyte/monolayer for about 3 weeks. Then, we designed a prototype module of an artificial liver support system using a PUF/spheroid packed-bed, in which hepatocyte/spheroids were immobilized at high density (0.5~1.0x107 cells/cm3-PUF). We also developed the rat extracorporeal circulation system and examined the performance of hybrid artificial liver in an ex vivo extracorporeal experiment with a D-galactosamine induced acute hepatic failure rat. The blood ammonia concentration, which was one of the toxic causal substances for hepatic coma, decreased at normal level after the extracorporeal circulation for 3 hours and the hepatic failure rat was recovered by this hybrid artificial liver.

We successfully produced Resistive-Electrode Gas Electron Multiplier (RE-GEM) which has resistive electrodes instead of the metal ones which are employed for the standard GEM foils. RE-GEM has a resistive electrode of 25 micron-thick and an insulator layer of 100 micron-thick. The hole structure of RE-GEM is a single conical with the wider and narrower hole diameters of 80 micron and 60 micron, respectively. A hole pitch of RE-GEM is 140 micron. We obtained the maximum gain of about 600 and the typical energy resolution of about 20% (FWHM) at an applied voltage between the resistive electrodes of 620 V, using a collimated 8 keV X-rays from a generator in a gas mixture of 70% Ar and 30% CO2 by volume at the atmospheric pressure. We measured the effective gain as a function of the electric field of the drift region and obtained the maximum gain at an drift field of 0.5 kV/cm.

We have performed a systematic investigation of the gain properties of the GEM foil made from copper-clad liquid crystal polymer insulator (LCP-GEM), which will be used for a satellite mission. We have measured the gain curve of LCP-GEM in pure DME at 190 Torr, and achieved a gain of 3 × 104 at an applied high voltage of 605 V between the LCP-GEM electrodes with a thickness of 100 μm. The charge sharing between the GEM electrodes and readout pad were measured as a function of drift (Ed) or induction (Ei) field. We found that the parallel plate multiplication occurred between the bottom electrode of LCP-GEM and the readout pad above Ei = 6 kV, and the amount of charge collected in each electrode was almost constant with Ed. We investigated the signal shape obtained in each electrode and found that the rise time of signals was explained as induced charge by moving ions and electrons.

Mononuclear cells (MNCs) infiltrating in spinal cords (SCs) of Lewis rats with EAE were isolated in order to permit flow cytometric (FCM) analysis of these cell populations, using monoclonal antibody to T cell, CD4, CD8. MHC class II antigen (Ia), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1). The number of MNCs isolated from SC varied from 5 to 620 x 10(4). They were increased and reached a peak on day 2 post clinical onset, and subsequently declined through the clinical course. The increase of infiltrating cells in SC paralleled the severity of the disease development. The surface phenotypes of MNCs from rats on the day of clinical onset were determined by flow cytometry. The phenotypes found in these rats were as follows: T cells (70.3%); CD4 + (58.3%); CD8 + (40.3%); Ia (51.9%); ICAM-1 (62.6%); LFA-1 (75.8%). These findings suggest that high proportion of ICMA-1 and LFA-1 expression may be important in antigen presentation in the inflammatory lesions of SC and in promoting lymphocyte extravasation across the blood-brain barrier during the disease. The approach we employed offered more sophisticated and quantitative analysis of CNS inflammatory cells, which is unobtainable by tissue section staining.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is thought to be an inflammatory autoimmune disease against peripheral myelin. Recently several animal models have suggested that preferential activation of Th1 cell response is central to the pathogenesis of this disease. We studied the function of CD4 positive T cell subsets, Th1 cells and Th2 cells by analyzing their representative secreting cytokines. Th1 cells secrete Interferon gamma (IFH gamma) and Th2 cells secrete Interleukin 4 (IL4). Using enzyme linked immunospot (ELISPOT) assay, a very sensitive single cell analysis system, we enumerated IFN gamma and IL4 secreting peripheral blood lymphocytes in patients with CIDP. Also we examined these cytokines in supernatants of cultured peripheral blood lymphocytes by a very sensitive enzyme linked immunosorbent assay (ELISA), Immunodot assay and westernblot assay. In culture supernatants of CIDP patients' peripheral blood lymphocytes, the levels of both IFN gamma and IL4 were higher during the exacerbation stage than the remission stage. In the remission period, though the levels of IFN gamma and IL4 were low in the supernatants, the ELISPOT assay revealed that the number of IL4 secreting cells was elevated compared with that of IFN gamma secreting cells. Our results suggest that the switch from Th1 to Th2 might play an important role in inducing the remission stage in patients with CIDP.

We immunologically examined the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy in a patient with HB hepatitis. A 41-year-old male clerk has been suffered from muscle weakness, tingling and numbness in the distal portion of all limbs. All symptoms were compatible with the typical patterns of chronic inflammatory demyelinating polyradiculoneuropathy. We examined the patient's serum and biopsied sural nerve, using histochemical and immunological techniques. We detected the band that reacted with anti-HBs antibody in the sural nerve in western blotting. The result indicated that HBs antigen was expressed on the peripheral nerves in the patient. There were no anti-peripheral nerve antibodies neither in the sural nerve or serum. There was no increase of immune complex in the serum. No deposition of immunoglobulins and complements were detected in the sural nerve. Immunoadsorption therapy had no effect on this patient, but administration of prednisolone improved his symptoms drastically. These findings suggest that a cytotoxic T cell may had played a more important role than humoral factors in this patient's nerve injury. Though the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy remains unclear, our findings seem to be very interesting in that they go some way toward clarifying the pathogenesis of this disease.

Anti-P-glycoprotein (P-gp) monoclonal antibody, MRK16, and its F(ab')2 fragment were evaluated for its therapeutic efficacy to P-gp-mediated multidrug resistant human colorectal carcinoma cell lines in a nude mouse model. In a blood clearance experiment, 125I-labeled MRK16 had a half-life (16 h) 7 times longer than its F(ab')2 fragment (half-life of 1.8 h) in circulation in nude mice, and approximately 16 and 5% of MRK16 were retained on days 10 and 20 after injection, respectively. In biodistribution experiments using nude mice bearing HCT-15, an intrinsically resistant cell line, 125I-labeled MRK16 accumulated at the tumor site significantly higher than its F(ab')2 fragment as revealed by the percentage of injected dose/g of tissue values (7.4 versus 0.6%) on day 3 after injection. In contrast, the tissue to blood ratio at the tumor site of the MRK16 was significantly lower than that of its F(ab')2 fragment (1.2 versus 10.5). Specific targeting of the MRK16 F(ab')2 fragment to the P-gp-positive tumor (HCT-15) but not to the P-gp-negative tumor (COLO 205) was observed in the nude mice bearing both tumors. In the therapeutic efficacy tests, when administered i.v. 3 times on days 1, 4, and 7 after tumor s.c. inoculation, MRK16 alone showed the significant inhibition of tumor growth of P-gp-positive cell lines, HCT-15, DLD-1, SW480, and SW1417 in contrast to cases of P-gp-negative cell lines, COLO 205 and KM20L2. This inhibitory effect of MRK16 was enhanced in combination with Adriamycin, which alone hardly inhibited the tumor growth. However, MRK16 F(ab')2 fragment alone, even at 1 mg/mouse, had little inhibitory effect on the growth of HCT-15 in the same treatment schedule. When administered at early palpable stage, the degree of HCT-15 tumor growth suppression depended on the number of MRK16 injections. At more progressed stages, treatment with MRK16 alone showed little antitumor activity but when combined with Adriamycin resulted in significant suppression of tumor growth. The present results suggest that MRK16 may be useful for in vivo immunoscintigraphy and immunotherapy of multidrug-resistant colorectal carcinoma.

Hemodynamic situation immediately after cardiopulmonary bypass was studied in cases of CABG using bilateral ITAs and right GEA. Though cardiac output was kept greater than 4.0 l/min, the blood pressure soon after weaning from cardiopulmonary bypass was low in patients who necessitated further circulatory assist, intraaortic balloon pumping (IABP) and/or additional surgical bypass procedure. In cases of CABG using arterial grafts and no vein graft, the perfusion pressure is most important to stabilize the hemodynamic status because low pressure may provoke peripheral vasoconstriction resulting in spastic reaction of the ITA and GEA. These arterial grafts seemed to keep the characteristics as the peripheral artery. Some papers pointed out less flow capacity of arterial grafts compared with that of saphenous vein graft, but CABG with arterial grafts alone was safe clinically if care is taken for keeping the perfusion pressure as high as preoperatively.

A case of B cell lymphoma with clinical and histological features of malignant histiocytosis was described. A 57-year-old male was admitted to Shinshu University Hospital because of transverse myelopathy. Five months before admission, he noticed urinary disturbance, which progressed to urinary obstruction. The following month, bilateral muscular weakness appeared in his legs. A few days later he could not stand up, and was admitted to a local hospital. Neurological examination revealed sensory disturbances below the level of Th12 in all modalities, and marked weakness and hyperreflexia in the lower limbs. A spinal tumor was suspected. However, myelography showed no abnormality. The patient's condition worsened and he became bed-ridden in February 1990. He was transferred to Shinshu University Hospital for further evaluation. On admission he was poorly nourished with fever, anemia, hepatomegaly, and bilateral pretibial pitting edema. No lymphadenopathy was observed. Neurological examination showed total sensory loss below the level of Th12, spastic paraplegia, hyperreflexia in the legs, and urinary obstruction. Laboratory findings revealed an elevated erythrocyte sedimentation rate, increased CRP, pancytopenia, and hypoalbuminemia. Serum level of IgG, IgA, IgM, LDH, ALP, GPT and total bilirubin were increased. CSF and MRI imaging of the spinal cord were normal. Proliferation of atypical histiocytes with marked erythrophagocytosis, which is a characteristic pathological feature of malignant histiocytosis, was observed in peripheral blood and aspirated bone marrow. Immunoenzyme staining of bone marrow using monoclonal antibody L-26, which is a B-cell marker, revealed B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

A series of MDR cell lines with various levels of P-glycoprotein have been established from a human colorectal carcinoma cell line, HCT-15, by stepwise exposure to adriamycin. The relative drug resistance of these cell lines correlated directly with both MDR1 mRNA levels and P-glycoprotein expression levels. Intracellular accumulation of adriamycin decreased inversely to their resistance. Drug sensitivities of these lines were reversed using verapamil. Since these cell lines are transplantable to nude mice, they may provide a useful animal model of MDR solid tumors for therapeutic experiments.

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This paper describes two rat monoclonal antibodies (MAbs) (1A6 and 2H7, both IgG2a) directed against a human adenocarcinoma of the lung (A549). Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry (Avidin-Biotin-complex method) as the screening of the hybridoma cells revealed that 1A6 and 2H7 MAb mainly reacted with adenocarcinoma of the lung, breast and pancreas, and 2H7 MAb also recognized large cell carcinoma, epithelia of the lung, trachea, tongue or small cell carcinoma of the lung. The antigen molecules recognized by 1A6 MAb was not detected by immunoprecipitation but the molecular size of the antigen by 2H7 was ca. 40Kd. The antibody-producing heterohybridoma cells could be transplanted into peritoneal cavities of nude mice to form ascites. We found these monoclonals useful for immunohistodiagnosis of surgical specimens from patients with lung cancer. Furthermore, we utilized 125I-labeled 2H7 MAb, aiming at localizing A549 tumor mass transplanted into nude mice subcutaneously. This antibody clearly localized the tumor mass. It is suggested that they may be useful as both diagnostic and therapeutic agents.