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We report a case of Takayasu arteritis. A woman, 24 years old, was admitted because of fever of unknown etiology. Infection was ruled out. Bruit and asymmetrical pulsation were not found. Ga-scintigram showed abnormal uptake in her upper abdomen. Abdominal echogram revealed neither evidence of abscess nor lymphadenopathy. On abdominal computed tomography, a wall thickening of the abdominal aorta was revealed. In addition, abdominal magnetic resonance imaging(MRI) showed a wall thickening and an enhanced image by gadrinium enhancement. Although we could not carry out conventional aortography because of an allergy to lidocaine, she was diagnosed as having Takayasu arteritis. In response to steroid therapy, the fever promptly dropped and the data indicating inflammation were improved. On the MRI examination after 40 days of steroid therapy, the wall thickening of the abdominal aorta was found to be less prominent. We conclude magnetic resonance imaging is useful for diagnosis and follow-up of early and acute stage of Takayasu arteritis.

The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

Let 0 < α ≤ 1 and let $\boldsymbol{b}_\alpha^{2}$ be a Hilbert space of all square integrable solutions of a parabolic equation (∂t + (−Δ)α)u = 0 on the upper half space. We study the Toeplitz operators on $\boldsymbol{b}_\alpha^{2}$, which we characterize to be of Schatten class whose exponent is smaller than 1. For the proof, we use an atomic decomposition theorem of parabolic Bergman functions. Generalizations to Schatten class operators for Orlicz type and Herz type are also discussed.

Patient age and gender may be associated with response to peginterferon alpha plus ribavirin, the current standard of care (SOC) for chronic hepatitis C genotype 1. We queried whether there was an association between age, gender, and treatment response to SOC in Japanese patients infected with hepatitis C virus (HCV) genotype 1. Between 2006 and 2009, HCV-infected Japanese patients treated with peginterferon alpha-2b plus ribavirin for 48 weeks were enrolled. Patients were allocated into four groups according to age and gender, and epidemiological data and treatment outcomes were retrospectively analyzed. HCV RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0. The overall sustained virological response (SVR) rate was 49.8%: patients aged ≤65 and >65 years, 50.9 and 44.0%, respectively; male and female, 56.5 and 39.0%. SVR rates of SOC against HCV genotype-1 females aged >65 years (19.0%) were inferior to those in males aged >65 years (57.8%) in Japan. Multivariate logistic regression analysis showed that SVR was attained independently of adherence 80/80/80 in all groups. Adherence to medication is also a key factor for the eradication of HCV in patients aged >65 years. As the SVR rate of patients aged ≤65 years was similar to that of patients aged >65 years, SOC could be useful for treating some of the elderly patients.

The current standard treatment for patients infected with hepatitis C virus (HCV) of genotype 2 is the combination of peginterferon (PEG-IFN) plus ribavirin (RBV) for 24 weeks.We assessed the sustained virological response (SVR) rates in HCV genotype 2-infected Japanese patients in relation to the duration of treatment.Between 2006 and 2009, among 147 patients with HCV genotype 2-infection in Chiba Prefecture, 138 consecutive patients were finally enrolled. Twenty-one, 97 and 20 patients were treated with PEG-IFN-alfa 2b plus RBV for 16, 24 and 48 weeks, respectively. Epidemiological data and treatment outcomes were retrospectively evaluated. HCV RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0.The overall SVR rate was 82.6% (114 of 138): treatment-naïve patients, 86.4% (89 of 103); patients with history of previous treatment, 71.4% (25 of 35). Patients treated for 16, 24 and 48 weeks obtained SVR rates of 66.6% (14 of 21), 86.5% (84 of 97) and 80.0 (16 of 20), respectively.The SVR rates of PEG-IFN-alfa 2b plus RBV in Japanese patients were similar to those in previous studies. Combination treatment for 24 weeks for some patients infected with HCV genotype 2 may be superior to that for 16 weeks. More precise patient selection will be needed to shorten the combination treatment.

We describe a patient who presented with flexion contractures of the bilateral fingers due to tenosynovitis of the flexor digitorum tendons as an initial manifestation of systemic lupus erythematosus (SLE). A 17-year-old woman had abrupt onset of diffuse swelling and flexion contractures in the bilateral fingers, accompanied by polyarthritis and cervical lymphadenopathy. Magnetic resonance imaging (MRI) showed flexor tenosynovitis of the hands. A diagnosis of SLE was made by immunological and hematological tests, and treatment with oral corticosteroids resulted in a rapid and complete disappearance of the flexion contractures.

In the setting of α-parabolic Bergman spaces, we consider weighted versions of averaging functions and Berezin transformations. Related norm equivalence relations are shown. They are very useful to study our Bergman spaces. As an application, we characterize the Schatten classes of compact Toeplitz operators.

Effects of dexamethasone, EGF and insulin on the synthesis of rRNA and phosphorylation of nucleolin in primary cultures of adult rat hepatocytes were studied. Hepatocytes were incubated for 8 h with EGF (20 ng/ml) plus insulin (0.1 μM) and/or for 20 h with dexamethasone (1 μM) before the end of incubation. The incorporation of [3H]uridine into acid-insoluble materials and the nuclear activity of RNA polymerase I were stimulated approx. 2-fold with EGF plus insulin and these were further enhanced 2–3-times by dexamethasone, although dexamethasone alone exerted no stimulation. When hepatocytes were incubated with [32P]orthophosphate, similar enhancement by these hormones was also observed in the phosphorylation of a nucleolar protein, nucleolin, which was detected by immunoprecipitation with anti-nucleolin antibodies. The amount of nucleolin was slightly increased by EGF plus insulin in the presence of dexamethasone, but scarcely changed by treatment with EGF plus insulin or dexamethasone alone. Cycloheximide inhibited RNA synthesis to a greater or lesser degree in the case of all hepatocytes which were cultured with or without these hormonal treatments. These results indicate that the in vivo effect of glucocorticoid on rRNA synthesis and nucleolin phosphorylation in liver is primarily a direct action on parenchymal cells and requires other growth factors such as EGF and insulin.

Parabolic Bergman space $\berg[p]$ is a Banach space of all $p$-th integrable solutions of a parabolic equation $(\partial/\partial t + (-\Delta)^{\alpha})u = 0$ on the upper half space, where $0

The key pathological features of chronic pancreatitis are chronic inflammation, acinar atrophy, and pancreatic fibrosis. We have previously shown that ellagic acid, a plant-derived polyphenol found in fruits and nuts, inhibited activation of pancreatic stellate cells, a major profibrogenic cell type in the pancreas, in vitro. Here we examined whether ellagic acid inhibited the development of pancreatic fibrosis in vivo. Ellagic acid was administered orally in the diet to ten-week-old male Wistar Bonn/Kobori rats, an experimental model of spontaneous chronic pancreatitis, for ten weeks. Ellagic acid (100 mg/kg body weight/day) attenuated pancreatic inflammation and fibrosis. The protective effects were confirmed by an increase in pancreatic weight and decreases in myeloperoxidase activity (an index of neutrophil infiltration), collagen content, transforming growth factor-beta1 expression, and the number of alpha-smooth muscle actin-positive cells (activated pancreatic stellate cells) and ED-1-positive cells (macrophages/monocytes). Ellagic acid inhibited the production of reactive oxygen species in pancreatic stellate cells in response to transforming growth factor-beta1 or platelet-derived growth factor. Our results suggest that ellagic acid might be a candidate for treatment of chronic pancreatitis.

Let $\boldsymbol b^p_\alpha$ be the parabolic Bergman space, which is the Banach space of all $L^p$-solutions of the parabolic equation $(\partial/\partial t + (-\Delta)^{\alpha})u = 0$ on the upper half space $\boldsymbol R^{n+1}_+$ with $0 < \alpha \leq 1$. We discuss the relation of Toeplitz operators to Carleson measures.

Aim Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic fibrosis and inflammation. Endothelin-1 (ET-1), which acts through G-protein coupled ET(A) and ET(B) receptors, has several biological activities. We here examined the ability of ET-1 to affect the cell functions of PSCs and the underlying molecular mechanisms. Methods PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and ET receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain (MLC), extracellular-signal regulated kinase (ERK), and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Results Culture-activated PSCs expressed ET(A) and ET(B) receptors, and ET-1. ET-1 induced phosphorylation of MLC and ERK, but not Akt. ET-1 induced contraction and migration, but did not alter proliferation of PSCs. ET-1-induced contraction was inhibited by an ET(A) receptor antagonist BQ-123 and an ET(B) receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and migration. Conclusion ET-1 induced contraction and migration of PSCs through ET receptors and activation of Rho-Rho kinase. ET(A) and ET(B) receptors play different roles in the regulation of these cellular functions in response to ET-1.

A triple-CPU mobile application processor is developed on an 8.95mm/spl times/8.95mm die in a 0.13/spl mu/m CMOS process. The IC integrates 3/spl times/ARM926 cores, a DSP several accelerators, as well as strong bus and memory interfaces. It consumes 120mW for digital TV, Web browser, and 30 graphics, and 250mW@200MHz for 600MIPS with full processing.

Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic inflammation and fibrosis. Trypsin and tryptase, which are agonists for protease-activated receptor-2 (PAR-2), are involved in the pathogenesis of pancreatitis. Here, we examined whether PSCs expressed PAR-2 and its agonists affect the cell functions of PSCs. PSCs were isolated from rat pancreas tissue. Expression of PAR-2 was examined by Western blotting and reverse transcription-polymerase chain reaction. Trypsin, activating peptide (SLIGRL-NH(2), corresponding to the PAR-2 tethered ligand), and tryptase were tested for their ability to affect proliferation, chemokine production, and collagen synthesis in culture-activated PSCs. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using antiphosphospecific antibodies. The effect of PAR-2 agonists on the activation of freshly isolated PSCs in culture was also examined. PAR-2 expression was observed in culture-activated PSCs, whereas it was undetectable in freshly isolated PSCs. PAR-2 agonists activated activator protein-1 and MAP kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase) but not nuclear factor kappaB. PAR-2 agonists induced proliferation of PSCs through the activation of extracellular signal-regulated kinase. PAR-2 agonists increased collagen synthesis through the activation of c-Jun N-terminal kinase and p38 MAP kinase. PAR-2 agonists did not induce the production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 or initiate the transformation of freshly isolated PSCs in culture. Taken together, our results suggest a role of PAR-2 in the sustenance of pancreatic fibrosis through the increased proliferation and collagen production in PSCs.

In response to pancreatic injury and in cell culture, pancreatic stellate cells (PSCs) are transformed ("activated") into highly proliferative myofibroblast-like cells that express alpha-smooth muscle actin and produce extracellular matrix components. Activated PSCs are implicated in the pathogenesis of pancreatic fibrosis and inflammation. We here evaluated the effects of SP600125 (anthra[1,9-cd]pyrazole-6 (2H)-one), an inhibitor of c-Jun NH(2)-terminal kinase (JNK), on the activation of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. Activation of JNK was determined by Western blotting using anti-phosphospecific JNK and c-Jun antibodies. Activation of transcription factors was determined by electrophoretic mobility shift assay. The effects of SP600125 on the key parameters of activation (chemokine production, collagen production, and proliferation) were examined. The effect of SP600125 on the activation of freshly isolated PSCs in culture also was examined. Interleukin-1beta activated both 46- and 54-kDa JNK, whereas platelet-derived growth factor-BB activated only 46-kDa JNK. SP600125 inhibited interleukin-1beta-induced JNK activity and activator protein-1 activation, but it did not affect the activation of extracellular-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-kappaB. SP600125 inhibited platelet-derived growth factor-induced proliferation, inducible monocyte chemoattractant protein-1 production, and serum-induced type I collagen production. Although SP600125 did not inhibit the transformation, it attenuated the proliferation of freshly isolated PSCs in culture. Collectively, our results suggest a role of JNK in the activation of PSCs, and a potential application of JNK inhibitors for the treatment of pancreatic fibrosis and inflammation.

AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous immortalization. METHODS: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift assay. Activation of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme immunoassay. RESULTS: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution, and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely immortalized. SIPS cells retained morphological characteristics of primary, culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type I collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP kinases. Interleukin-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP kinases. CONCLUSION: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.

Background/Aims: Recent studies have shown an association between the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic pancreatitis (CP). We here examined the prevalence of SPINK1 mutations in Japanese patients with pancreatitis. Methods: Genomic DNA was prepared from 80 Japanese patients with CP, 36 patients with acute pancreatitis (AP), and 165 healthy controls. All exons and the promotor region of the SPINK1 gene were amplified by the polymerase chain reaction, and directly sequenced. Results: We found four types of mutation (N34S, IVS1–37T>C, –215G>A, and IVS3 + 2T>C) and two types of polymorphism (–253T>C and 272C>T). The N34S mutation cosegregated with IVS1–37T>C, and was present in 8 CP and 1 AP patients. The –215G>A mutation was in a complete linkage with IVS3 + 2T>C, and was present in 8 CP and 1 AP patients. The prevalences of [N34S; IVS1–37T>C] and [–215G>A; IVS3 + 2T>C] were significantly higher in patients with familial pancreatitis (38 and 13%, respectively) and with idiopathic CP (13 and 16%) than normal subjects (0.6 and 0%). In addition, the frequency of [N34S; IVS1–37T>C] mutation was higher in patients with autoimmune CP (33%). Conclusion: The SPINK1 gene mutations were associated with pancreatitis also in Japan.

To examine the frequency of depressive symptoms and also to identify factors closely associated with their development in patients with scleroderma (systemic sclerosis, SSc).We evaluated 50 patients with SSc for factors associated with depressive symptoms using the following established scales: the Beck Depression Inventory (BDI); the Rheumatology Attitude Index for measuring helplessness; the Sense of Coherence (SOC) scale (a measure of an individual's resilience in the face of stress and capacity to cope with it); the modified Health Assessment Questionnaire for physical disability, working, and social function; support domains of Arthritis Impact Measurement Scales version 2; and a visual analog pain scale. In addition, disease severity of SSc, including skin thickness and internal organ involvement, was also examined in each patient. Multiple regression analysis was used to determine which factors correlated with depressive symptoms.Depressive symptoms ranging from mild to severe state were seen in 46% of the patients. Total BDI scores were significantly correlated with low working ability, low social activity, low SOC, pain, and helplessness, and not associated with disease severity variables including skin score and internal organ involvement. Multiple regression analysis showed that a high level of helplessness and a low level of SOC might be closely associated with depressive symptoms in SSc.Our results indicate that depressive symptoms are frequent in SSc patients. Medical staffs should pay attention to the possible risk factors for depressive symptoms, such as patient's helplessness and SOC.

We investigated the features and the usefulness of gallium scintigraphy in the diagnosis and the assessment of Adult Still's disease (ASD) by retrospective case review. Gallium scintigraphy have been done for 11 cases of ASD (3 males and 8 females) and 4 females were positive. Among these, 67 Ga-citrate was accumulated to the bone marrow in all 4 cases and to the major joints in 2 cases. Positive cases were rather serious and administered more immunosuppressants than negative cases. In order to characterize gallium scintigraphy findings of ASD, i.e. bone marrow accumulation, we analyzed 130 cases of collagen vascular diseases. Although 101 cases (77.7%) were positive, only 7 cases (5.4%) showed the accumulation of 67Ga-citrate to the bone marrow. These include 3 cases with ASD, and 1 case with systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis and Sjögren's syndrome. We also accumulated 18 patients who exhibited bone marrow accumulation of 67Ga-citrate, and found that 7 patients had collagen vascular and their related diseases. In conclusion, bone marrow accumulation in gallium scintigraphy is a specific feature of collagen vascular diseases, especially ASD, and it is suggested that cases with positive gallium scintigraphy in ASD can be serious and resistant to treatment.

Objective We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105-negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. Methods RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6). For the assay of autoantibodies, RP105-positive and RP105-negative B cells were cultured separately for 10 days with anti-CD3 antibody–stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme-linked immunosorbent assay. Results We demonstrated that RP105-negative B cells, but not RP105-positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL-10, produced IgG, although the amount was very small compared with that produced by RP105-negative B cells. Most important, under these conditions, anti–double-stranded DNA antibodies were produced only by the RP105-negative B cells obtained from SLE patients. Conclusion These data indicate that RP105-negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.

A case is reported of a 56-year-old male who presented with bilateral pleural effusion as an initial manifestation of idiopathic fibrosing mediastinitis. The patient showed shortness of breath with severe loss of vital capacity and weight loss. A mediastinal mass surrounding the thoracic aorta and bilateral pleuritis was identified by the chest CT scan. The mass extended, along the abdominal aorta, to the upper portion of retroperitoneum. Laboratory data showed elevated levels of C-reactive protein (CRP), erythrocyte sedimentation ratio (ESR), and IgG. Biopsy of the mediastinal and the pleural mass showed adipose tissue and fibrosis with mild perivascular inflammatory infiltration. A diagnosis of idiopathic fibrosing mediastinitis was made, and 40 mg/day of prednisolone was administered. Although CRP and ESR was normalized, the mass size and vital capacity were almost unchanged.

Let D D be a domain in R n {{\mathbf {R}}^n} and let S + ( D ) {S^ + }(D) be the set of all nonnegative superharmonic functions on D D . It is shown that if S + ( D ) ⊂ L p ( D ) {S^ + }(D) \subset {L^p}(D) with some p > 0 p > 0 , then for each x 0 ∈ D {x_0} \in D there is a constant C = C ( D , p , x 0 ) > 0 C = C(D,p,{x_0}) > 0 such that the inequality \[ ∫ D u ( x ) p d x ⩽ C u ( x 0 ) p \int _D {u{{(x)}^p}dx \leqslant Cu{{({x_0})}^p}} \] holds for all u ∈ S + ( D ) u \in {S^ + }(D) .

A case is reported of a 29 year old female who had autoimmune hepatitis associated with mixed connective tissue disease (MCTD). The patient developed MCTD at the age of 19, and was treated with prednisolone. Liver dysfunction developed 7 years later, which exacerbated shortly after the patient suffered intrauterine fetal death during the second trimester of pregnancy. Laboratory data showed negative anti-hepatitis C antibody and hepatitis B antigen, but positive anti-smooth muscle antibody. A liver biopsy showed chronic active hepatitis. Referring to the criteria we diagnosed her as having autoimmune hepatitis. Although hepatomegaly is sometimes observed in MCTD patients, only 5 cases of autoimmune hepatitis associated with MCTD have been reported in the past. In our case, it is of note that autoimmune hepatitis developed while symptoms of MCTD were in remission, and that autoimmune hepatitis exacerbated with the emergence of anti-smooth muscle antibody following the termination of pregnancy.

Objective—To investigate the incidence of retinopathy in systemic lupus erythematosus (SLE) and to clarify its significance in relation to other clinical manifestations. Methods—A cross sectional study on lupus retinopathy was made in 69 patients with SLE. One expert ophthalmologist examined the ocular fundi of the lupus patients without any information of their disease state. Clinical and laboratory findings in the patients with retinopathy and those without were compared. Results—Retinopathy was found in 7/69 (10%) patients. The findings included haemorrhages, vasculitis, cotton wool spots,and hard exudates,all of which were considered to reflect vascular damage. Retinopathy was found to be associated with the presence of anticardiolipin antibody (p

We describe a case of a Japanese patient initially presenting with Sjogren's syndrome who later developed polymyositis and sarcoidosis. A 67-year-old woman with a 4 month history of myalgia was admitted in April 1998 for examination. The patient had a 10 year history of symptoms consistent with Sjogren's syndrome. A diagnosis of polymyositis was made based on a biopsy of the muscle and an electromyogram. Positive Shirmer and Rose Bengal tests and results of a minor salivary gland biopsy were all consistent with Sjogren's syndrome. Chest computed tomography detected a bilateral hilar lymphadenopathy. Microscopic examination of a mediastinal lymph node demonstrated multiple noncaseating granulomas with multiple epithelioid cells and Langhans-like giant cells. A diagnosis of sarcoidosis was made based on these findings. Hepatitis C infection was also detected by elevated antibody levels. The patient was given 40 mg/day of oral prednisolone and a remission of her myositis and lymphadenopathy was obtained. The patient exhibited HLA-B7 and HLA-DR 8. HLA-DR 8 is commonly associated with these three disorders, and HLA-B7 is also associated with overlap syndrome in Japanese patients. The present case suggested the possibility of a common etiological background for these three disorders. Furthermore, the importance of genetic background, including HLA phenotype, in determining susceptibility to these disorders was demonstrated.

Objective. RP105 is a leucine-rich repeat (LRR) protein found on all mature mouse B cells. Its function is poorly defined, although it has been suggested that RP105 activates B cells to make them resistant to apoptosis. The human homolog of RP105 has been reported, but knowledge of its function is limited. We explored the expression and the function of the human homolog of murine RP105 on B cells in patients with systemic lupus erythematosus (SLE). Methods. The expression of RP105 and various markers on B cells in patients with SLE was analyzed using monoclonal antibodies and flow cytometry. Susceptibility to corticosteroid-induced apoptosis was examined by annexin V binding, and the production of immunoglobulin by RP105-negative B cells was examined by intracellular staining of IgG. Results. As in mice, virtually all B cells in the peripheral blood of normal humans expressed the RP105 molecule. However, a significant proportion of circulating B cells (15.9%) in SLE patients were RP105 negative. Serial analyses of B cells in 7 SLE patients revealed that RP105-negative B cells markedly decreased in parallel with a reduction in disease activity (from 35.2% to 3.3%; P 5 0.000003). The SLE Disease Activity Index and serum levels of IgG also correlated with the percentage of RP105-negative B cells. The phenotype of RP105-negative B cells was defined as CD95-positive, CD86-positive, CD38-bright, IgDnegative, IgM-dull, indicating that the cells were highly activated, as further suggested by the detection of intracellular IgG. RP105-negative B cells were clearly distinct from CD5-positive B1 cells. In vitro experiments indicated that RP105-negative B cells were susceptible to corticosteroid-induced apoptosis. Conclusion. These findings suggest that loss of RP105 is associated with B cell activation and increased disease activity in SLE patients.

In this article we prove the following: If u u is a nonzero superharmonic function on a proper subdomain D D in R n {R^n} , then \[ ∫ D | u ( x ) | p δ D ( x ) n p − n − 2 p d x = ∞ , {\int _D {\left | {u(x)} \right |} ^p}{\delta _D}{(x)^{np - n - 2p}}dx = \infty , \] where 0 > p ≤ 1 0 > p \leq 1 and δ D ( x ) {\delta _D}(x) denotes the distance between x x and the boundary of D D .

Background/Aims: The mature form of collagen cross-linking increases the resistance of collagen to degradative enzymes, and thus renders the protein in the fibrotic lesions extremely stable and the fibrosis virtually irreversible. It is crucial to elucidate the extent of cross-linking in fibrotic and cirrhotic livers if we are to control the subsequent removal of the excessive deposited collagen, whether by natural enzymes or induced by therapy. We aimed to quantitative pyridinoline, a mature form of the cross-linking, in normal control livers, viral fibrotic livers with various degrees of fibrosis and viral cirrhotic livers. Methods: Needle liver biopsy samples from 75 patients with chronic viral hepatitis and 13 patients with viral liver cirrhosis, and six normal control livers were analyzed. Collagen and pyridinoline contents were determined by high-performance liquid chromatography. Results: Significantly higher levels of pyridinoline cross-links per collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43] pmol/pmol of collagen, p =0.03491). But no differences were found in levels between cirrhosis and chronic hepatits with various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrhosis and in chronic viral hepatitis. Conclusion: The extent of the pyridinoline cross-linking of hepatic collagen does not seem to be responsible for the irreversibility of viral liver fibrosis.

A woman of 79 years was admitted to our hospital because of headache and high erythrocyte sedimentation rate (ESR). Temporal artery biopsy demonstrated giant cell arteritis and nonsteroidal antiinflammatory drugs were effective. Another woman of 69 years was admitted because of headache, high ESR, and polymyalgia. Temporal arteritis (TA) with polymyalgia rheumatica (PMR) was established in biopsy of the temporal artery, and steroid therapy was effective. In our hospital, a third patient of 81 years was also suffering from TA with PMR, but temporal artery biopsy was not performed. Those three cases were followed for several years after the diagnosis of TA. Two years later, cancer in cervix of uterus was diagnosed in first case, and acute myelogenous leukemia in second case. However, such symptoms were not observed in third case. These findings and recently described reports suggest that the patients with biopsy-proven TA may have an increased risk of developing malignancy.

BACKGROUND: IPMN is a precursor lesion to pancreatic ductal adenocarcinoma consisting of 4 epithelial subtypes with varying grades of dysplasia. Intestinal type (IPMN-I) often involves the main duct and has a higher risk of developing invasive carcinoma in comparison to gastric type (IPMN-G). Differentiation of high-risk/malignant IPMN from low-risk IPMN and other benign/low-grade cystic pancreatic lesions remains a challenge, especially in the preoperative setting. mAb Das-1 reacts specifically to a colonic epithelial phenotype. It is both sensitive and specific in identifying various pre-malignant and malignant lesions of the upper GI tract including Barrett's esophagus and incomplete gastrointestinal metaplasia associated with gastric cancer. We have previously demonstrated that it specifically detects high risk IPMN tissue histologically. AIM: To assess the ability of mAb Das-1 to identify cyst fluid of IPMN with a high risk of malignant transformation. METHODS: Cyst fluid was aspirated during surgical resection of IPMN (n=10), serous cystadenoma (n=1), and cystic low-grade neuroendocrine tumor (n=1). Cyst fluid was also aspirated during EUS-FNA of pancreatic pseudocysts (n=4). Sandwich ELISA was performed on each sample (utilizing mAb Das-1 IgM & IgG isotypes) and results were confirmed by Western Blot analysis. Statistical significance was calculated by T-test. RESULTS: Pancreatic cyst fluid from all benign/low-grade lesions (n=8) demonstrated very little reactivity with mAb Das-1 (OD 0.137±0.181). Specifically, reactivity was low among cyst fluid collected from low-grade IPMN-G (OD 0.088±0.003, n=2), pseudocyst (n=4) (OD 0.088±0.041), and non-pseudocyst, benign/low-grade lesions (n=4) (OD 0.187±0.251). In comparison, high-risk and malignant IPMN lesions (intermediate-grade IPMN-I & all high-grade/invasive IPMNs n=8) expressed a significantly higher amount of reactivity (OD 0.866±0.151) when compared to low-grade IPMN-G (p

An audio player apparatus includes a first speaker disposed to output a sound from a front face of a flat panel television apparatus to the outside, a second speaker disposed to output a sound from a backside of the flat panel television apparatus to the outside, a microphone disposed on the backside of the flat panel television apparatus to receive the sound output from the second speaker and to convert the received sound into an electric signal, an analysis unit configured to detect a reflected sound and reflection time of the sound output from the second speaker based on a second audio signal supplied to the second speaker and the electric signal output from the microphone, and a phase correction unit configured to correct a phase of at least one of a first audio signal supplied to the first speaker and the second audio signal based on the reflection time.

Thyroid peroxidase (TPO) was purified from each thyroid of 10 patients (experiment 1) and 4 patients (experiment 2) with toxic diffuse goiter by a simplified method with monoclonal anti-TPO antibody-assisted immunoaffinity column chromatography. The final preparations were used to measure the heme concentration based on the cyanide difference spectrum, and to determine the Km and kcat values from double reciprocal plots in the assay employing guaiacol and iodide as the second substrates. The heme-based specific activities of TPO purified from thyroids in experiment 1 were higher than those in experiment 2, which were probably impaired by freezing-thawing, and those of porcine TPO previously reported. There were some differences in the kinetic properties between experiment 1 and experiment 2, but the individual differences within each group were relatively small, the values for CV (= SD/mean) being 0.16-0.48.

Ribosomal RNA (rRNA) synthesis in murine P 1798 lymphosarcoma cells is reversibly inhibited by glucocorticoids. The effects of dexamethasone upon nucleolin phosphorylation and upon the amount and activity of casein kinase II have been examined. P 1798 cells were exposed to 0.1 μM dexamethasone for 36 h. Cells were labeled in vivo with [ 32 P]orthophosphate followed by immunoprecipitation with anti-nucleolin antibody. Nucleolin phosphorylation was reduced by 60% in dexamethasone-treated cells. Nucleoli were isolated and labeled with [γ- 32 P]ATP in vitro . Nucleolin protein was reduced to 40% of control in nuclei from dexamethasone-treated cells. Nucleolin phosphorylation was reduced to 20% of control. Nucleolar casein kinase II activity and protein were also reduced (30–55% and 35–50% of control, respectively) by treatment with dexamethasone. Cycloheximide (10 μg/ml for 3 h) reduced the amount and activity of casein kinase II, but did not cause a decrease in nucleolin protein. These observations are discussed relative to the hypothesis that glucocorticoids regulate the amount or activity of proteins of short biological half-life that are involved in the regulation of rRNA synthesis.

The in vivo effect of thyrotropin (TSH) on the intracellular localization of thyroid peroxidase (TPO) in rat thyroid epithelial cells was examined by an indirect immunofluorescence method. The staining for TPO in the epithelial cells of normal rats appeared all over the cytoplasm, especially in the apical region. The injection of propylthiouracil for 3-10 days increased the staining in the apical region. The administration of L-thyroxine for 7-10 days to normal rats abolished the relatively high localization of TPO in the apical region, and resulted in TPO staining all over the cytoplasm. Six hours after TSH was injected into the thyroxine-treated rats, localization of TPO staining in the apical region was observed. These results suggest that TSH may play a role in the translocation of preexisting TPO to the apical region before TSH-induced biosynthesis becomes evident.

AIM: To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of pancreatic stellate cells (PSCs). METHODS: PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2’-deoxyuridine. Cell migration was assessed using modified Boyden chambers. Cyclin D1, p21Waf1, and p27Kip1 expression and phosphorylation of PDGF β-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phospha-tidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide. RESULTS: EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyond the G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF β-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways. CONCLUSION: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibition of PDGF-mediated signaling pathways.

Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis, where oxidative stress is thought to play a key role. 4-hydroxy-2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs.PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 micromol/L) of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type I collagen and monocyte chemoattractant protein-1 was determined by enzyme-linked immunosorbent assay. The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed.HNE activated activator protein-1, but not nuclear factor kappaB. In addition, HNE activated three classes of MAP kinases: extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase. HNE increased type I collagen production through the activation of p38 MAP kinase and c-Jun N-terminal kinase. HNE did not alter the proliferation, or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype.Specific activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic disorders.