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Summary: We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various‐sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme‐linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1–3 showed negative results. Immunoblotting using the full‐length human Dsg1 recombinant protein showed a positive band. TEM examination showed various‐sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation‐regulated chemokine and interleukin‐5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP. What's already known about this topic? Herpetiform pemphigus (HP) is a rare variant of pemphigus characterized clinically by pruritic annular erythemas with vesicles resembling dermatitis herpetiformis and histopathologically by eosinophilic spongiosis without apparent acantholysis.The targets of IgG autoantibodies in patients with HP are usually desmoglein 1 and 3, which are both components of desmosomes. What does this study add? This study reports the unique case of a patient with HP with IgG autoantibodies reactive to nondesmosomal sites of keratinocytes and characteristic transmission electron microscopic findings of various‐sized vacuoles in keratinocytes, while desmosomal adhesion remained.Regarding pathogenesis, we speculate that the ballooning vacuoles might result in the bullous spongiotic changes without acantholysis seen in this patient.This study also focuses on the relationships between blood eosinophil counts, serum thymus and activation‐regulated chemokine levels and HP disease activity. Linked Comment: Yuan and Pan. Br J Dermatol 2019; 180:22. [ABSTRACT FROM AUTHOR]

In this paper, a numerical description of the ruggedness of punch-through (PT) IGBTs under the unclamped inductive switching (UIS) has been proposed using two-dimensional (2D) simulations with the calibration to experimental results. The UIS capability is an important design factor of device structures for the purpose of screening defects produced during the wafer process. The local hot spot due to the current filament three-dimensionally (3D) distributed over the chip area requires 3D simulations to reproduce the current density of the filament and its behavior leading to the device destruction; however, it is difficult to simulate such a large area with an appropriate mesh size and a boundary condition. To provide a possible solution of this technical issue, 2D simulations using large scale multi-cell structures with the increased current density has been proposed to reproduce experimental results without resorting to 3D simulations. With this approach, not only destructive phenomena including the UIS ruggedness and the latch-up failure mode have been reproduced, but also the device internal state leading to the destruction has been revealed. The spatial distribution of the electric potential and the lateral electric field during the UIS condition is shown to be a key role determining the current filament width and the UIS ruggedness. Besides, the high frequency oscillation of the collector voltage during the UIS observed by experiments has been analyzed and has found to be related with the hopping motion of the current filament from a cell to its neighboring cell of the device. [ABSTRACT FROM AUTHOR]

Investigates a new composition of Bismuth-substituted terbium iron garnet (TB[sub3-x]Bi[subx]Fe[sub5]O[sub12]) for a wideband optical isolator. Magneto-optical properties of (TB[sub3-x]Bi[subx]Fe[sub5]O[sub12]); Development of the wideband optical isolator; Characteristics of the wideband optical isolator.

The single crystal samples of Fe(Br xI1 − x)2 were investigated by the magnetization measurement. Among them, the x = 0.6, 0.8 and 0.9 samples were microscopically studied by the Mössbauer technique. As comparing the results of a magnetic behavior obtained for the x = 0.6, 0.8 and 0.9 samples, we discuss a spin glass-like behavior appeared in the bond random mixture. We propose an x–T magnetic phase diagram of Fe(Br xI1 − x)2. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents characteristics of ionized gas metal arc processing which consists of a torch, a consumable electrode wire, shielding gases and two power sources. One of the power sources ionizes the shielding gases before supplying into the arc region and another stably produces the gas metal arc. The degree of ionization in the shielding gas is well regulated by the primary power source, and then the secondary power source is able to control the arc, including a weld pool formation, a growth of molten droplet at the electrode wire tip and its detachment. It is concluded that the ionized gas metal arc can make a stable processing of welding without spatters and fumes in comparison with the conventional gas metal arc processing. Furthermore, it is suggested that the ionized gas metal arc is very useful for not only welding but also thermal spraying for producing a fine coating of metal surface. [Copyright &y& Elsevier]

Mössbauer spectra of Fe0.05Ni0.95Cl2 were recorded at temperatures between 4.5 and 50 K and fitted by a sum of two sub-spectra as was done previously for Fe x Ni1− x Cl2 with x = 0.034, 0.068 or 0.079. We have found that temperature variations of the hyperfine magnetic field H hf and the quadrupole splitting (1/2) e 2 qQ of one of the sub-spectra are similar for the different compositions while some changes are observed for the other sub-spectrum. A particularly interesting result is found for Fe0.05Ni0.95Cl2 which clearly shows the effect of a spin growth when temperature decreases. [ABSTRACT FROM AUTHOR]

The bond random mixed compound Fe(Br0.9I0.1)2 has been studied by magnetization and Mössbauer measurements. Although the zero-field cooled and field-cooled magnetization variations are not like a typical spin glass one, the Mössbauer spectrum below Néel temperature shows a hyperfine field distribution. It implies that the 10% FeI2 mixed in FeBr2 can be induced by the bond random effect which causes the sample to exhibit a spin glass-like behavior. [ABSTRACT FROM AUTHOR]

Haemodynamic studies were performed by pulmonary artery catheter in 15 patients with severe head injury. To our knowledge, few data are available about the detailed haemodynamic changes after head injury using pulmonary artery catheter. All patients were assessed by the Glasgow Coma Scale, computed tomography and intracranial pressure monitoring. We divided the patients into hypotensive and normotensive groups. All patients showed a high pulmonary vascular resistance and a high pulmonary capillary wedge pressure, probably due to pulmonary vasoconstriction. In the hypotensive group, the two major changes were a marked decrease of the cardiac index and a slight increase of systemic vascular resistance. The low cardiac index was the result of heart failure secondary to myocardial dysfunction. In contrast, the normotensive group was characterized by a high systemic vascular resistance that was induced by generalized vasoconstriction. Increased intracranial pressure is initially associated with an increase of the cardiac index and systemic vascular resistance, so patients with severe head injury also suffer from profound circulatory disturbance. [ABSTRACT FROM AUTHOR]

External decompression can be an effective treatment for acute intracranial hypertension, but the cranial defect must be repaired. The most serious complication of cranioplasty is late infection. Confusing an empyema that occurs after cranioplasty with a fluid collection (haematoma or liquor) can have catastrophic consequences, such as the development of cerebritis. The goal of this study was to assess the ability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to diagnose empyema after cranioplasty. DW MRI and apparent diffusion coefficient (ADC) maps were studied in six patients with surgically verified empyema after cranioplasty. The findings were compared with those in five patients who had surgically verified haematoma or liquorrhoea. In the patients with empyema, the lesion was hyperintense, whereas the fluid collections (haematoma and liquorrhoea) were visualized as hypointense lesions. The ADC maps showed that empyema had a significantly lower intensity than the fluid collections (haematoma or liquorrhoea). DW MRI can be used to identify empyema after cranioplasty and can help to differentiate it from other fluid collections. Hence, this is a useful additional imaging modality for the diagnosis of empyema after cranioplasty. [ABSTRACT FROM AUTHOR]

We report two cases of Kienböck's disease associated with systemic lupus erythematosus (SLE). The characteristics of these cases associated with SLE differed from those previously reported for Kienböck's disease. Corticosteroid may be a cause of Kienböck's disease in SLE. [ABSTRACT FROM AUTHOR]

Although granulation tissue formation is an important step for second-intention wound healing, the molecular events underlying this process are still poorly understood. To investigate the role of telomerase in the formation of granulation tissue, we measured the activity of this enzyme and determined the expression and localization of human telomerase reverse transcriptase mRNA using human skin samples. Telomerase activity in the tip of the granulation tissue where fibroblasts actively proliferate was detected at a level 5.6 +/- 1.5 times higher than that at the edge of the tissue when using a polymerase chain reaction-based telomeric repeat amplification protocol assay coupled with enzyme-linked immunosorbent assay. This, together with the findings from semiquantitative reverse transcriptase-polymerase chain reaction and in situ hybridization of human telomerase reverse transcriptase, revealed that proliferating cell nuclear antigen-positive fibroblasts and endothelial cells in the progressing granulation tissue showed de novo activation of telomerase with high human telomerase reverse transcriptase mRNA expression. This condition may be a prolongation of cellular replicative capacity taking advantage of the positive regulatory dynamics of cell growth. We conclude that the regulation of telomerase activity may play an important role in granulation tissue formation in wound healing. [ABSTRACT FROM AUTHOR]

Neoplastic B cells from two patients with hyperleucocytic hairy cell leukaemia (HCL) and 19 patients with chronic lymphocytic leukaemia of B cell Type (B-CLL) were investigated to examine the mitogenic responses to the F(ab')2 fraction of anti-human immunoglobulins (anti-Igs) and Staphylococcus aureus Cowan I (STA). Neoplastic cells from both HCL patients lacked surface Tac antigen. Mononuclear cells from the two HCL patients strongly responded to both anti-Igs and STA as measured by 3H-thymidine incorporation in vitro. Although the mononuclear cells from two patients with B-CLL showed high response to STA. cells from none of the patients with B-CLL responded to anti-Igs. Mononuclear cells as well as T-cell-depleted fractions from the two HCL patients showed a strong proliferative response by anti γ chain antibody (anti-γ) and the mononuclear cells from one of the patients were also induced to proliferate by anti-δ, whereas those from normal subjects responded only to a high concentration of anti-μ. Based on the difference in reactivity to anti-Ig, it is suggested that the HCL cells in this study originate from a subset equivalent to 'memory' B cells, whereas the B-CLL cells originate from a subset equivalent to 'virgin' B cells. [ABSTRACT FROM AUTHOR]

The random bound mixed compound Fe(Br0.8I0.2)2has been investigated by magnetization and Mössbauer spectroscopy. The experimental results for Fe(Br0.8I0.2)2were compared with those of Fe(Br0.6I0.4)2studied previously. A magnetic structure below the magnetic transition temperature observed by Mössbauer spectroscopy has been suggested which shows a large distribution ofthe hyperfinefields. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study 'Magneto-Optical Properties of (TbBi)[sub3]Fe[sub5]O[sub12] and Its Application to a 1.5 μm Wide-Band Optical Isolator,' by T. Tamaki, H. Kaneda and N. Kawamura.

When a femtosecond laser pulse is focused at the interface of two transparent substrates, localised melting and quenching of the two substrates occur around the focal volume, bridging them due to nonlinear absorption. The substrates can then be joined by resolidification of the materials. We investigate the optimum irradiation conditions needed to join borosilicate glass substrates and fused silica substrates using a 1 kHz 800 nm Ti:sapphire amplifier. We characterised the joint strength and the transmittance through joint volumes as a function of laser energy and translation velocity. We found that a joining strength as large as 14.9 MPa could be obtained in both fused silica and borosilicate glass. Annealing the joint samples led to an increase in the joint strength. [ABSTRACT FROM AUTHOR]

Single-walled carbon nanotubes (SWNTs) were prepared with double laser vaporization of a graphite target and a metal/alloy target inside an electric furnace at 1200 °C ambient temperature with 500 torr Ar gas atmosphere. Each target was vaporized simultaneously with a different Nd:YAG laser. Several kinds of metal/alloy target (Ni, Co, Fe, and permalloy) were tested in order to see the difference in the resulting SWNT yield and the diameter distribution of them. The Raman spectra of SWNT-containing soot prepared by use of this technique with permalloy/carbon system indicated that permalloy gives almost the same yield as compared with Ni/Co carbon composite rod with single laser vaporization technique, though the diameter distribution of them is slightly different. Also, time-resolved images of the plume by carbon and permalloy nanoparticles after laser vaporization were collected using a high-speed video camera. These images suggest that the hot plumes due to carbon and permalloy nanoparticles do not mix together so extensively, at least in a few hundred microseconds after laser vaporization. The effect of time delay between two laser pulses on the yield and the diameter distribution of SWNTs was also presented and discussed. [ABSTRACT FROM AUTHOR]

The effect of light on magnetic initial permeability (the so-called photomagnetic effect) and photoinduced disaccommodation were studied in samples of yttrium iron garnet over the temperature range 77-300 K. The samples studied were bulk crystalline, produced by the floating zone method and the flux method, polycrystalline, produced by the usual sintering method, and single-crystalline films, produced by in situ liquid-phase epitaxis. One or both of the studied phenomena were observed in our experimental samples. To explain the experimental results, we suggest there is photoinduced structural distortion around oxygen vacancies due to a photoinduced change of charge imbalance. [ABSTRACT FROM AUTHOR]

As the prevalence of anorexia nervosa (AN) increased, surgery in severe AN patients also increased in the 2000s. We experienced a surgical case of a patient with severe AN, showing an extremely low BMI of 8.6 kg m−2. We investigated the problems associated with this case and propose criteria to manage severe AN. We endeavour to report on the perioperative management of rare and severe symptoms and surgical indications of severely malnourished patients.All published reports were identified through comprehensive searches using PubMed, BioMedLib, and the Japan Medical Abstracts Society with the following terms and keywords: ‘anorexia nervosa’, ‘eating disorder’, ‘hypoglycaemia’, ‘leucocytopaenia’, ‘gelatinous bone marrow’, ‘surgery’, and ‘operation’. In cases of AN with a BMI under 13 kg m−2, marked hypoglycaemia, leucocytopaenia <3.0×109 litre−1, or both, potentially fatal complications frequently occur. Accordingly, patients need strict nutritional support to avoid re-feeding syndrome until surgery. During the course of anaesthesia, careless loading of glucose or catecholamine may lead to disturbance of electrolytes or fatal arrhythmia. Intensive care and early feeding as soon as possible after surgery are important to prevent surgical site infection. Although not many perioperative cases of AN have been reported, clinicians must be aware of the danger and the causes of mortality in critical cases. Thus, the decision to undertake surgery must be taken carefully and close perioperative coordination among physicians, surgeons, psychiatrists, anaesthesiologists, and intensivists is essential. [ABSTRACT FROM AUTHOR]

Background Patients with human immunodeficiency virus (HIV) infection exhibit various skin diseases. HIV-associated eosinophilic folliculitis (EF) and pruritic papular eruption (PPE) are frequently seen. Objective To understand the mechanisms underlying HIV-associated EF and PPE. Methods In order to know frequencies of EF and PPE among patients with HIV infection, we first collected HIV+ patients who visited dermatology clinic in National Center for Global Health and Medicine during February 2007. We next collected 25 serum samples from HIV+ patients with skin diseases from May 2008 to May 2010. Eight of 25 patients had EF (EF group), four had PPE (PPE group) and others had non-itchy skin problems such as condyloma acuminatum (no itch group). Results We first confirmed high frequencies of EF (10.7%) and PPE (5.3%) among 75 HIV+ patients who visited our clinic during one month. We then measured serum levels of CCL11, CCL17, CCL26 and CCL27. Serum CCL17 levels in EF were significantly higher than those of PPE and no itch group. Serum CCL26 and CCL27 levels in EF were higher than those of no itch group. The number of CD4+ cells in EF was significantly lower than that in no itch group. Conclusion High serum levels of CCL17, CCL26 and CCL27, and low CD4+ cell counts may account for the development of HIV-associated EF. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical effectiveness of pretreatment [18F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials: Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results: The patients with a nodal SUV≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p=.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p=.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p=.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p=.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p=.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). Conclusion: Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection. [ABSTRACT FROM AUTHOR]

Background: Vibrio parahaemolyticus causes acute gastroenteritis and inflammations in humans. A variety of pathogenic bacteria can stimulate mitogen-activated protein kinases (MAPKs) in host cells. Phosphorylation of MAPKs leads to production of interleukin (IL)- 8 and subsequently causes inflammations. Thus, MAPK cascades were strong candidates for the main signaling pathway of V. parahaemolyticus-induced acute inflammation.Methods: To determine whether the signaling pathway on V. parahaemolyticus infection induces inflammation, we analyzed the secretion level of IL-8 and phosphorylation of MAPKs by use of intestinal epithelial Caco-2 cells.Results: V. parahaemolyticus infection of Caco-2 cells activated extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK signal pathways, leading to IL-8 secretion, whereas MAPK inhibitors, UO126 or SB203580, suppressed IL-8 secretion. A strain carrying a deletion of VP1680, a type three secretion system 1 (T3SS1) effector protein, failed to activate phosphorylation of ERK1/2 and p38 MAPK and secretion of IL-8. ERK1/2 pathway inhibitor, UO126, failed IL-8 promoter activity, whereas p38 MAPK inhibitor, SB203580, decreased the stabilization of IL-8 messenger RNA following V. parahaemolyticus infection.Conclusions: We showed that V. parahaemolyticus infection of Caco-2 cells results in the secretion of IL-8, and that VP1680 plays a pivotal role in manipulating host cell signaling and is responsible for triggering IL-8 secretion. [ABSTRACT FROM AUTHOR]

Background: Nodal status has been reported to be one of the most important factors affecting survival in patients with lung cancer. For determining treatment strategy, accurate evaluation of nodal status is expected. Purpose: To evaluate the accuracy of 18F-2-deoxy-fluoro-D-glucose (FDG) positron emission tomography (PET) for diagnosing nodal status in lung cancer patients with pathologically proven N1 (pN1) lymph node metastases, in comparison with that of computed tomography (CT). Material and Methods: Nineteen pN1 patients with primary lung cancer undergoing preoperative CT and FDG-PET were investigated. The diagnosis was confirmed by surgery in all patients. Lymph nodes were considered to be positive when uptake higher than the surrounding mediastinum level was visually observed. Radiological and pathological correlation was investigated, and the association between FDG uptake and the size of metastatic nodes was evaluated. Results: Of the 19 pN1 patients, nodal stage determined by FDG-PET was cN0 in eight, cN1 in four, cN2 in six, and cN3 in one. Thus, FDG-PET provided correct N-staging in 21%, under-staging in 42%, and over-staging in 37%. FDG-PET could not depict pN1 lymph node in six (32%) of 19 patients. In two patients (11%), mild symmetrical hilar and mediastinal accumulation was found and considered as benign physiological uptake. In six patients (32%), the ipsilateral mediastinal uptake was depicted and diagnosed as cN2. One patient was diagnosed as cN3 because of FDG accumulation at the supraclavicular fossa. On CT, nodal staging was cN0 in nine, cN1 in six, and cN2 in four. CT staging was therefore correct in 32%, underestimated in 47%, and overestimated in 21%. Conclusion: The diagnostic accuracy of FDG-PET (21%) was low and similar to that of CT (32%); under- and over-diagnosis were found in similar proportions. The limitation of FDG-PET should be recognized when nodal staging might alter the therapeutic strategy in patients with primary lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Ultra-fine patterning of several ten nanometer pitch for semiconductor devices is required for higher integrations of circuit elements and, therefore, extremely high preciseness and quality are also required for patterning of microstructures on photo masks. A serious problem that causes the deterioration of pattern preciseness of photo mask is the deposition of micron or sub-micron particles, such as oil dusts, that generate from mechanical bearings of the spin processors in the grooves of the micro patterns. In this work, application of magnetic levitation utilizing high temperature superconducting (HTS) bulks to the spin processors for the photo mask production is proposed. To address this issue, a small size test spinner utilizing the magnetic levitation with the HTS bulks is developed to investigate its applicability to the spin processors for the photo mask production. The structure of the test spinner is presented and the results of levitation and rotation tests are reported in this paper. The test results show the basic compatibility of the magnetic levitation with the HTS bulks to the spin processor. [Copyright &y& Elsevier]

Summary:We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12–10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08–20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090–0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.Bone Marrow Transplantation (2005) 36, 205–213. doi:10.1038/sj.bmt.1705027; published online 6 June 2005 [ABSTRACT FROM AUTHOR]

Abstract: Tb–Fe–Co/Co–Cr–Pt–B hybrid media with various Tb–Fe–Co thicknesses were prepared in order to investigate high-density recording characteristics and thermal decay. As a result, the magnetic cluster size of hybrid media increased in proportion to the Tb–Fe–Co thickness. The hybrid media with 7.5nm thickness of Tb–Fe–Co showed the highest signal-to-noise ratio and low thermal decay. [Copyright &y& Elsevier]

Abstract: The dependence of magnetic properties on thermal fluctuation and relationship between magnetic cluster size and thermal decay are investigated. It is shown that the use of the thermal stability factor explains the thermal decay of a perpendicular magnetic recording medium well when the magnetic cluster volume in AC erased magnetization is regarded as the effective volume. [Copyright &y& Elsevier]

There are few reports describing the mechanism of HDL-elevating action of HMG-CoA reductase inhibitors (statins). As it is considered that the key step of HDL production is the secretion of apolipoprotein A-I (apoA-I), we investigated the effect of statins on apoA-I synthesis and secretion by HepG2 cell to elucidate the mechanism of the action. Each statin induced apoA-I expression (mRNA and protein) dose-dependently: the rank order of the apoA-I induction pitavastatin (3μM)>simvastatin (10μM)>atorvastatin (30μM). The induction of apoA-I by statins disappeared with addition of mevalonate, which indicates that the effect is HMG-CoA reductase inhibition-dependent. Based on HMG-CoA reductase inhibition, pitavastatin-induced apoA-I more efficiently than simvastatin and atorvastatin. Further study revealed that pitavastatin increased ABCA1 mRNA in HMG-CoA reductase-dependent manner and that Rho and Rho kinase inhibitor (C3T and Y27632) increased apoA-I production in the HepG2 cells. These results suggest that pitavastatin efficiently increases apoA-I in the culture medium of HepG2 cells by promoting apoA-I production through inhibition of HMG-CoA reductase and suppression of Rho activity and by protecting apoA-I from catabolism through ABCA1 induction and lipidation of apoA-I. [Copyright &y& Elsevier]

The effects of glucose and insulin on J-ST-segment elevation were evaluated in seven men (mean age 45 +/- 10 years) with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intavenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of 51 +/- 40 minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were 111 +/- 158 mg/dL and -0.30 +/- 0.48 mEq/L, respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J-ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET) is known to stimulate mesangial cell (MC) proliferation, extracellular matrix (ECM) synthesis, and thereby contribute to the progression of glomerulonephritis (GN). To clarify the molecular and cellular mechanisms of how ET is involved in the development of glomerular sclerosis, we investigated the influence of ET on the MC-α1β1 integrin-mediated collagen matrix reorganization using a collagen gel contraction assay. ET enhanced MC-α1β1 integrin-mediated gel contraction in a dose-dependent manner. Addition of the endothelin A (ETA) receptor antagonist, BQ123, into collagen gels abolished ET-induced gel contraction by MC. Cell behavior involved in ET-induced gel contraction was investigated in combination with function-blocking anti-α1-integrin antibody. Migration and adhesion assays revealed that ET stimulated α1β1 integrin-mediated MC migration but did not influence cell adhesion to type I collagen (collagen I). Integrin-function blocking studies using anti-α1 integrin antibody indicated that MC-α1β1 integrin is required not only for collagen-dependent migration, but also for gel contraction. Zymography showed that ET increased MC matrix metalloproteinase-2 (MMP-2) activity in a dose-dependent manner during MC-induced gel contraction process. Finally, flow cytometry analysis indicated that ET did not affect the cell surface expression of the MC-α1β1 integrin within the collagen gel. These data suggested that ET promotes collagen matrix reorganization through the enhancement of MC-α1β1 integrin-dependent migration and MMP-2 activity. We therefore conclude that ET is a potential molecule inducing pathological collagen matrix remodeling observed in progressive GN. [Copyright &y& Elsevier]

Abstract A growing body of evidence suggests that prostate-specific antigen (PSA) is a novel prognostic factor for breast cancer. The molecular mechanism of variant PSA expression in breast cancer has remained poorly understood in spite of intensive research. Previous studies have shown that the coding region of the ISA gene is not a target for mutations in prostate cancer and breast cancer. The purpose of this study was to analyze genetic variations in the promoter region of the PSA gene, and to detect whether such variations are correlated with PSA mRNA expression in breast tumors. We identified two polymorphisms in the proximal promoter region of the PSA gene. These polymorphisms are located at positions -252 (G or A) and -205 (A or AA), and generate three genotypes. The genotypes were associated with PSA mRNA expression. Our findings suggest that these polymorphisms identified in the proximal promoter region may affect the transcriptional activity of PSA. [ABSTRACT FROM AUTHOR]

Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1 influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we carried out an experimental and a clinical study. PGE1 was continuously administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of 0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in eight patients PGE1 was administered through the hepatic artery at a rate of 0.01 micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic hemodynamics and oxygen metabolism did not change during the administration of PGE1 into the portal vein. During administration of PGE1 into the hepatic artery, hepatic arterial flow increased 1.5-fold after administration compared to the rate before administration (P < 0.01). Hepatic arterial pressure, hepatic arterial resistance, and post-sinusoidal resistance significantly decreased after administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen supply increased significantly (P < 0.01). In the patients, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels remained low after surgery, and the recovery of protein synthesis was improved compared with that in eight hepatectomized patients without PGE1 administration (controls). The intrahepatic arterial infusion of PGE1 was considered useful for the recovery of liver function. [ABSTRACT FROM AUTHOR]

Sera from patients with localized scleroderma frequently produce cytoplasmic staining by indirect immunofluorescence, although the antigen remains to be determined. We studied the prevalence, antigen specificity and associated clinical characteristics of anti-cytoplasmic antibodies in localized scleroderma. Serum samples from 60 patients with localized scleroderma were examined by indirect Immunofluorescence analysis and immunoblotting. By immunofluorescence analysis on HEp-2 cell substrate, seven of 60 (12%) patients were shown to be positive for anti-cytoplasmic antibodies. Among these, six patients with generalized morphea had anti-mitochondrial antibodies as shown by immunoblotting: they showed reactivity with the E2 component of pyruvate dehydrogenase complex (PDC), with protein X, and with the E2 component of α-oxo-glutarate dehydrogenase complex, while two of them showed reactivity with PDC-E1α. One of these patients who was positive for anti-PDC-E1α antibody showed laboratory abnormalities, suggesting the presence of primary biliary cirrhosis. The age of disease onset was significantly higher in these six patients than in those without anti-mitochondrial antibodies. Furthermore, five of them were classified into generalized morphea with multiple plaque lesions but without linear lesions (multiple plaque type). These observations suggest that major antigens for anti-cytoplasmic antibodies in patients with localized scleroderma are mitochondrial enzymes, 2-oxo-acid dehydrogenase complexes. Patients with anti-mitochondrial antibodies may comprise a unique subset of localized scleroderma designated multiple plaque type of generalized morphea of older onset. [ABSTRACT FROM AUTHOR]

Peripheral blood T cells from 40 patients with idiopathic thrombocytopenic purpura (ITP) were analysed for the presence of surface la antigens using monoclonal antibodies by indirect immunofluorescence. The percentage of la-positive (Ia &plus;) T cells was significantly increased in patients with ITP (6.8±2.9%. P<0.005) as compared with normal controls (2.3 ± 0.9%), There was an inverse correlation between the percentages of Ia+ T cells and platelet counts (r = 0.58, P<0.005)and a positive correlation between the percentage of these cells and platelet-associated IgG (PAIgG) values (r = 0.55, P<0.01), The percentage of la+ T cells was found to decrease within two weeks during therapy with high dose γ - globulin or corticosteroid. We have previously reported the presence of T cells bearing both helper/inducer (H/I) and suppressor/cytotoxic (S/C) phenotypes (double labelled cells. DI.C) in patients with ITP and an inverse correlation between the percentages of DLC and their platelet counts. In the present study, we showed that a major part of Ia+ T cells had both H/I and S/C phenotypes. We also examined the correlation between Ia+ T cells and autologous mixed lyniphocyle reaction (AMLR). A defective AMLR was demonstrated in patients with ITP. Furthermore, an inverse correlation was found between the percentages of la+ T cells and the proliferative responses to AMLR (r= --0.49, P< 0.01). These results suggest that increased circulating Ia+ T cells play a role in the abnormalities of the immunoregulatory system of ITP. especially in the regulation of autoantibody production. [ABSTRACT FROM AUTHOR]

T cell subsets of peripheral lymphocytes were studied using monoclonal antibodies (OKT3. OKT4, OKT8) and immunoglobulin (IgG, IgM, IgA) synthesis in vitro by peripheral mononuclear cells stimulated with pokeweed mitogen was studied in adult patients with idiopathic thrombocytopenic purpura before and after high-dose intra-venous intact gamma(γ-)globulin therapy, at a daily dose of 0.4g/kg body weight for 5 consecutive days. A transient increase in platelet count which reached a peak on the 1st to 2nd day after the end of the therapy was observed in four of five patients. Immunoglobulin synthesis in vitro was suppressed remarkably following therapy in all cases: the mean reduction of IgG, IgM and IgA was 78, 66 and 48% respectively. Titres of various autoantibodies, TGHA, MCHA, ANF and anti-DNA antibody, also decreased following therapy. In correspondence to this, phenotypic analysis in T cell subsets showed a decrease of OKT4+ : OKT8+ ratio following therapy, without a change in the proportion of OKT3+ cells. These data indicate that the intravenous γ-globulin preparations suppressed synthesis of antibodies non-specificially and caused a relative increase of OKT8+ suppressor T cells. [ABSTRACT FROM AUTHOR]

The effect of amiloride, a potent inhibitor of Na+/H+ exchange, on ischaemic reperfused rat hearts was studied in order to investigate whether Na+/H+ exchange or Na+/Ca2+ exchange is involved in ischaemia-reperfusion injury, When hearts were pre-ischaemically loaded with 100 microM amiloride, recovery of left ventricular developed pressure was significantly better than in control hearts, whereas recovery of heart rate at 30-min reperfusion was unaffected. Amiloride pretreatment also decreased creatine phosphokinase activity in the coronary effluent and completely abolished occurrence of ventricular arrhythmias during reperfusion. It also inhibited intracellular Na+ accumulation early in reperfusion (within 5 min), whereas in the late stage (from 5 to 30 min), Ca2+ overload was inhibited. The findings suggest that Na+/H+ exchange participates mainly in the early stage of reperfusion injury and the Na+/Ca2+ exchange system, secondary to Na+/H+ exchange, in the late stage. The reduction in post-ischaemic cardiac dysfunction induced by amiloride pretreatment may be attributable to inhibition of the resultant Ca2+ accumulation during reperfusion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Episodic angioedema associated with eosinophilia.