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Seven patients with selective IgM deficiency (SIgMD) were studied for cell surface immunoglobulin (SmIg), T-cell subpopulations, and immunoglobulin (Ig) synthesis in vitro by peripheral blood lymphocytes (PBL). Serum IgM levels were less than 25 mg/dl, while IgA, IgG, and IgD were within normal levels. The patients had respiratory or urinary tract infections and two were diagnosed as having systemic lupus erythematosus (SLE). T/B-cell ratios in PBL were within normal ranges. Percentage ratios of B cells bearing SmIg were normal in five patients and decreased in two; however, normal values were seen after 7 days of culture in the presence of PWM. OKT4/OKT8 ratios decreased in five of seven patients, in whom two were due to a decrease in OKT4 and two to an increase in OKT8 cells. One showed a decrease in OKT4 and an increase in OKT8. Analysis of lymphocyte function for Ig synthesis in vitro, using a coculture of counterpart T and B cells from healthy individuals and patients with SIgMD, revealed that the increased function of IgM isospecific suppressor T cells (Ts) was responsible for the IgM deficiency in all seven patients.

De novo synthesis of alpha1-antitrypsin (α1AT) by human peripheral lymphocytes has been demonstrated in the present study. Treatment of the mononuclear cells with concanavalin A(Con A) resulted in a triple increase in the amount of α1AT synthesized by the untreated cells. A small amount of α1AT, equivalent to that synthesized by the unstimulated mononuclear cells, was observed in cultures of monocyte-depleted lymphocytes, with or without Con A stimulation. Monocytes treated with or without Con A scarcely synthesized α1AT. Conditioned media derived from monocyte enriched mononuclear cells treated with Con A enhanced about threefold α1AT synthesis by the Con A-stimulated lymphocytes. α1AT is suggested to be synthesized by lymphocytes assisted by monocytes.

Systemic lupus erythematosus (SLE)の患者に,静脈血栓が合併しやすいことは,古くからよく知られているが,今回,我々は, SLEの経過中に,肝静脈主幹および下大静脈に広範に血栓を形成し,典型的なBudd-Chiari症候群の病像を呈し, 2年後,肝性脳症に至つた症例を経験した.症例は, 17才,女性. 12才でSLEを発症し,以後ステロイド療法を受けていたが, 15才時急速に腹水,下腿浮腫が出現し,下大静脈の閉塞を伴うBudd-Chiari症候群と診断された.約2年後,急速に肝性脳症に到り死亡した. SLEの凝固亢進状態については,種々の要因が考えられているが,本症例における血栓形成にcirculating anticoagulantの存在が強く疑われた.

Rat alpha 2-macroglobulin (alpha 2M) is a typical acute phase protein, the concentration of which in serum increases more than 100-fold after inflammation. It is also known that the protein increases during pregnant (and neonatal) stages. Using a specific cDNA probe, expression of the alpha 2M gene during pregnancy was studied at the mRNA level. During inflammation, the liver is almost the only organ producing alpha 2M, but during pregnancy the placenta and uterus were found to be major organs producing a large amount (70-80% of that of inflamed liver) of alpha 2M mRNA at days 12-15. The yolk sac, maternal liver and fetal (or neonatal) liver also produced a small but significant amount (5-20% of that of inflamed liver) of the mRNA. Southern blotting analysis showed that only one copy of the alpha 2M gene was present in a haploid rat genome. These results indicated that a single alpha 2M gene has the ability to respond to two completely-different physiological states.

On the decrease in polyclonal Ig levels in patients with multiple myeloma (MM), several hypotheses have been proposed. By measuring in vitro Ig synthesis by mononuclear cells from peripheral blood (PMC) and from bone marrow aspirates (BMC) in a patient with IgG K myeloma, interesting results were obtained.The patient's WBC and lymphocytes are normal in number. Serum Ig levels were IgA 27, IgG 993 and IgM 58mg/dl. Urinary excretion of Bence-Jones protein was 7_??_10g/day. The amounts of IgG synthesized by PMC were markedly reduced, while those of IgA and IgM were almost equal to normal values. Hyperactivity of IgG specific suppressor T cells was responsible for the impairment of IgG synthesis. The amounts of Ig synthesis by BMC were markedly impaired for IgA and IgM and some what low for IgG. BMC could synthesize IgG without PWM-stimulation and moreover, B cells in BMC could synthesize IgG in the absence of T cells. Therefore, IgG synthesized by BMC was probably myeloma protein, not polyclonal IgG.Considering these results, we proposed a hypothesis that low levels of polyclonal IgA and IgM in this case were certainly caused by decreased synthesis of them in the bone marrow. Low level of IgG was caused by impaired synthesis of polyclonal IgG in PMC and also reduced synthesis of myeloma protein in the bone marrow. As myeloma protein synthesis by BMC was reduced, this case seems to belong to so called “oligo-M-component type” in multiple myeloma.

Rat Kupffer cells stimulated with bacterial lipopolysaccharide (LPS) produced high levels of interleukin 1 (IL-1), as determined by thymocyte proliferation assay. Indomethacin revealed a dose-dependent augmentation in IL-1 production, in parallel with a dose-dependent reduction in prostaglandin E2 production by Kupffer cells. The addition of exogenous prostaglandin E2, dibutyryl cAMP, or isoproterenol led to a dose-dependent suppression of IL-1 production. The supernatant from LPS-stimulated Kupffer cells also contained factors that inhibited IL-1-induced thymocyte proliferation. Upon gel filtration, two inhibitory peaks, at apparent MW of 27,000 and 6000, were obtained. The latter but not the former fraction also affected interleukin 2 (IL-2)-induced thymocyte proliferation. Increasing amounts of IL-1 overcame the inhibitory activity derived from the 27,000 MW fractions. These results suggest to us that prostaglandin E2 and IL-1 inhibitor released by Kupffer cells may be involved in negative self-control in regulating IL-1 production and its action.

We treated a Japanese woman who presented symptoms of subacute necrotizing lymphadenitis (SNL), which occurred following an EB virus infection, i.e., infectious mononucleosis (IM). No such cases have been reported and the possibility that SNL may be induced by an EB virus infection has to be given attention.The patient was a 26 year-old Japanese woman who admitted to Kyushu University Hospital because of persistent fever and sore throat. Systemic lymphadenopathy, hepatomegaly, leukocytosis, an increased number of atypical lymphocytes and the elevation of serum EB VCA-IgM titer were evident and the diagnosis of IM was made. Two months after the onset of IM, she again had a high fever and marked swelling of the left submandibular lymph nodes accompanied by marked tenderness. Serum markers of EB virus showed evidence of the convalescent stage of IM. Leukocytopenia was present and she recovered 40 days later with no specific treatment. Though SNL was not histologically proven, the diagnosis of SNL was made. Immunological investigations showed that the ratio of OKT 4+ to OKT 8+ lymphocytes was decreased and the natural killer cell activity had deteriorated.

細小細胞癌では,経過中高エコーから低エコーに変化する可能性が報告されている.また肝細胞の脂肪化は小肝細胞癌の特徴であり,前癌病変としての可能性が報告されている.われわれはこれらの可能性を支持する症例を経験したので報告する.症例は59歳男性.腹部超音波検査で肝右葉に径8mmの高エコー結節像を指摘され,細径針による生検で,脂肪沈着を伴う大型の細胞群が認められた.1年6ヵ月後結節像は径12mmに増大し,低エコーに変化した.さらに4ヵ月後,結節像は19mmに増大した.血管造影では腫瘍濃染像は認められなかったが,リピオドールCTにてリピオドールの沈着が認められたため,切除術を施行した.切除標本では高分化(Edmondson I型)の肝細胞癌であり,脂肪化は腫瘍の辺縁に認められた.

A mechanism of the decrease in polyclonal immunoglobulin (Ig) levels in a patient with multiple myeloma of Bence-Jones type was investigated by measuring Ig synthesis in vitro by mononuclear cells from peripheral blood and bone marrow aspirates. The levels of IgG, A and M in the serum were 579, 37 and 9 mg/dl, respectively. The lymphocytes in the peripheral blood were normal in number and no myeloma cells were found in the Giemsa stained preparation. Ig synthesis by peripheral mononuclear cells was slightly decreased because of the increase in suppressor activity in T cell fraction. Ig synthesis by mononuclear cells from the bone marrow specimen was decreased, approximately to one tenth of the normal controls. Co-culture of the patient's T and B cells with counterpart lymphocytes from a normal donor revealed increase in suppressor activity in T cells in peripheral blood and decrease in bone marrow B cell function in response to T cell stimulation. Considering these results, low levels of Ig in the serum in this patient were considered to be caused mainly by impaired synthesis of Ig in the bone marrow.

When stimulated with lipopolysaccharide (LPS), primary cultures of Kupffer cells from the rat secreted a hepatocyte-stimulating factor (Kupffer factor) which induced the synthesis of alpha 2-macroglobulin (a2M) by hepatocytes. The effect of this Kupffer factor was found only when dexamethasone was present in the hepatocyte culture medium. Dexamethasone alone stimulated the a2M synthesis, to some extent, in a dose-dependent manner. When both Dex and the Kupffer factor were added to the medium, cultured hepatocytes synthesized 100-fold a2M, quantitative evidence that explains the in vivo phenomenon in which the serum a2M concentration increases more than 100-fold in the acute phase. A co-culture study with hepatocytes and Kupffer cells indicated that the latter cells have a major function in the induction of a2M synthesis in vivo. A hybridization study with rat a2M cDNA showed that the concentration of mRNA increased in cultured hepatocytes in the presence of the Kupffer factor, but only when dexamethasone was present. From these results we concluded that Kupffer cells secrete a hepatocyte-stimulating factor when stimulated by LPS and that glucocorticoid is essential for the induction of a2M in rat hepatocytes. The effect of the Kupffer factor and glucocorticoid appears to be regulated in the pretranslational, probably the transcriptional, phase.

10例の選択的IgM欠損症について,リンパ球表面の免疫グロブリン, Eロゼット形成細胞数,モノクローナル抗体による表面マーカーの検索と合わせて, in vitroにおける免疫グロブリン産生能を検索した,血清IgM濃度は全例25mg/dl以下であり,他の免疫グロブリン濃度は正常範囲であった.基礎疾患としては,これらの患者は呼吸器または尿路感染症を発症しており, 3例に全身性エリテマトーデス(SLE), 1例に慢性関節リウマチ(RA)がみられた.リンパ球表面免疫グロブリンのうち, IgA, IgD, IgG, IgMは2例を除いて正常範囲にあり,この2例はすべてのリンパ球表面免疫グロブリンが減少していた. Eロゼット形成率はすべて正常であった,モノクローナル抗体による表面マーカーの検索では, OKT4が2例に低く, OKT8が3例に高く,全体としてOKT4/OKT8比が低値であった. in vitroでの免疫グロブリン合成は,全例IgA, IgG産生は正常でIgM産生のみ著明に低下していた.患者と健常者のT, B細胞を組み合わせて免疫グロブリン産生を検討した成績では,患者のB細胞およびhelper T細胞異常はなく, IgM特異的suppressor T細胞の活性上昇が証明された.これら10例のIgM欠損は, IgM特異的サプレッサーT細胞の機能亢進によることが示唆される.

We treated a Japanese man with Rendu-Osler-Weber disease and a recurrent encephalopathy with hyperammonemia concomitant with recurrent epistaxis, G-I bleeding, congestive heart failure with aortic and mitral regurgitation, and chronic renal failure. At peritoneoscopy, several telangiectasia were noted on the surface of the liver. Angiographical studies revealed widened and tortuous hepatic arteries with early filling of hepatic veins and small pools of contrast medium scattered throughout the parenchyma. The recurrent encephalopathy was attributed to the porto-systemic shunt formed in the liver.

Early digging of nursery stocks will profit nurserymen through early dealing in failing nursery stocks. However, digging too early is desirable as it affects the growth after planting.The effects of digging time on the growth after planting were investigated in 1 year-old nursery stocks of Japanese pear‘Kosui’, Japanese chestnut‘Tsukuba’ and Japanese persimmon‘Fuyu’from 1980 to 1983.The nursery stocks were dug and planted temporarily at intervals of about 15 days from September 15 to December 15, then replanted in a field during the winter. The growth was recorded in the following October or December.Sugar and starch levels in the shoot and root of the pear were also determined for each digging time.1. Death and dieback were observed in the early-digging nursery stocks, but not in the nursery stocks of pear and chestnut dug after November or in persimmon dug after October 15.2. The earlier the digging time, the shorter the total shoot length in all fruit studied.3. There was more new root production in the nursery stocks of the pear and chestnut dug on November 1 and 15 than in those dug before October 17.4. Sugar levels in the shoot and root of the pear nursery stocks did not change greatly from October 2 to November 15.Starch levels in the above increased to November 2 and decreased slowly since then.5. A digging time later than November 1 is recommended for nursery stocks of pear, chestnut and persimmon.

症例は34歳女性.妊娠32週で性器出血し,部分前置胎盤早期剥離の診断で帝王切開を受けた.術後急速に大量の腹水貯留を来し,利尿剤に抵抗性であった.腹水の性状は滲出性であり,腹腔鏡肝生検で肝うつ血の所見が認められた.下大静脈造影で下大静脈の総腸骨静脈からの入口部より肝静脈流入部までの閉塞が証明され,下大静脈閉塞を伴う,Budd-Chiari症候群と診断された.妊産婦は,凝固因子の増加,線溶能の低下,血小板粘着能の上昇など血栓を形成しやすい状態にある.本例は,部分前置胎盤早期剥離と帝王切開に伴い,組織トロンボプラスチンが血中へ大量流入し,急速に血栓が形成されたものと推定された.妊娠を契機に発症したBudd-Chiari症候群は1980年までに約30例が報告されているが,本邦では,初めての報告である.

A case with typical lupoid hepatitis whose hepatic histology could be obtained prior to development of the disease, is described. The case was 46 years old female. Since her 32 year old age, she suffered from polyarthralgia. Hypergammaglobulinemia and antinuclear antibody were detected since her 40 year of age. At her 45 year old age, Hashimoto's disease developed. At the same time abnormalities in the liver function test were pointed out. Since then she had repeated acute exacerbation of the liver injury for these 5 years. Thereafter serum IgG concentration was raised, and liver cell membrane antibody and LE cell phenomena became positive. Number of peripheral OKT 4 positive lymphocyte was gradually increased while that of OKT 8 positive lymphocyte fell. By biopsy of the liver, the histological feature changed from chronic hepatitis inactive type to the active one, and finally typical lupoid hepatitis developed during this observation period.As shown in the present case, immunological abnormalities may be observe preceding the development of lupoid hepatitis.

The effects of alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AGP), and haptoglobin (Hp), the main constituents of alpha-globulin and which belong to acute-phase proteins, on NK activity were examined using K562 cells as the NK target cells. Among the three proteins, alpha 1-AT and alpha 1-AGP had inhibitory effects on NK activity for "fast target" K562 cells. The alpha 1-AT preparations having the same protein concentration and a different trypsin inhibitory capacity (TIC) had an equal effect. Although alpha 1-AT and alpha 1-AGP equally reduced the NK activity, the mechanism involved in the reduction differed, in that the effect of alpha 1-AT directed toward NK cells reduced their binding capacity with the target cells. alpha 1-AGP probably interacts with a cytotoxic factor secreted from NK cells following effector-target interaction. These studies suggest that each of the acute-phase proteins, which increase following inflammation, inhibits NK cell function by two distinct mechanisms.

Summary We show a northern transfer experiment revealed two mRNA of Iaassociated invariant chain (In) gene in chronic lymphocytic leukemia (CLL) cells which are apporoximately 1580 and 1440 nucleotides in length. Primer extension experiment shows that less prominent transcript was found to initiate 140 nucleotides upsteam from the major cap site. The newly identified cap site was preceded by CG rich sequence but no typical promotor sequence. Southern hybridization analysis with In cDNA probe indicates no recombination or amplification of In gene in the CLL cells. This is the first documented example of such a mode of expression in malignant cells in vivo.

In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-kappaB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-kappaB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.

To investigate the role of lipopolysaccharide (LPS) in hepatocyte activation, we examined the expression of Toll-like receptor 4 (TLR4), the putative receptor for LPS in human hepatocytes. TLR4 mRNA and protein expression was confirmed in human hepatocytes. Stimulation of human hepatocytes with LPS results in rapid degradation of IkappaB-α and mitogen activated protein kinase activation. Human hepatocytes stimulated by LPS produced serum amyloid A protein. Our data suggest that human hepatocytes utilize components of TLR4 signal transduction pathways in response to LPS and these direct LPS-mediated effects on hepatocytes may contribute to liver inflammation and injury.

クローン病の治療経過中に続発性のアミロイドーシスを合併した症例を報告する.症例は23才男性, 6年前より腹痛を伴う下痢が出現し1年後回腸・結腸型のクローン病と診断され,その後約5年間症状の寛解と増悪をくり返していた.入院5日前より水様下痢,腹痛および体重減少等が急速に進行した.入院後の検査において,回腸および結腸のクローン病の病変の増悪は認められなかったのに対して,新たに空腸を中心にびまん性に内視鏡上粗造かつ易出血性粘膜と顆粒状隆起を認め,同部の生検よリアミロイド(AA蛋白)の沈着を証明した. 5年前の大腸の病変の組織学的検索ではアミロイドの沈着を認めなかった.治療として中心静脈栄養とdimethylsulfoxideの併用療法を行い症状の改善を認めた.

A 38-year-old Japanese man had cholangiocarcinoma in association with typical features of Werner's syndrome. The replicative capacity of fibroblasts in culture was characteristically reduced, and the in vitro natural killer cell activity was deficient. He died of massive G-I tract bleeding 8 months after admission.

Isolated rat Kupffer cells produced a factor which stimulated the synthesis of alpha 2-macroglobulin (alpha 2M) in primary cultured rat hepatocytes. Although Kupffer cells placed in culture produced the factor without stimulation by lipopolysaccharide (LPS), the LPS-stimulated cells produced larger amounts of the factor. On the other hand, the production of the factor was inhibited by addition of actinomycin D. The induction of alpha 2M synthesis by cultured hepatocytes was enhanced in the presence of dexamethasone (Dex), in that hepatic synthesis of alpha 2M increased by addition of the factor alone and with Dex 1.5 and three- to four-fold, respectively. The factor was nondialyzable and stable at 60 degrees C for 30 min. When the factor was fractionated using the molecular sieve method, the activity recovered in the fraction had a molecular weight of over 30,000.

Spleen size in patients with infectious mononucleosis (IM) was measured using ultrasound, and the findings were compared with data obtained in cases of acute viral hepatitis (AVH). The size was expressed as the spleen index (SI) or the product of the longitudinal and transverse diameters, expressed in cm2, of the maximum cross-sectional area of the spleen. A normal value obtained from 28 healthy individuals was 15 +/- 7 cm2. The SI (mean +/- SD) of patients with AVH and IM were 38 +/- 7 cm2 and 88 +/- 26 cm2, respectively. When the SIs were divided into five groups--grade 0 (0-25), grade I (26-50), grade II (51-75), grade III (76-100), and grade IV (100+), 83.3% of the patients with AVH were graded as Grade 0 or I, whereas 88.9% patients with IM belonged to higher grades. Splenomegaly with a SI value over 75, grade III or IV, strongly suggests IM when IM and AVH are being considered in the absence of other potential causes of splenomegaly. Because the clinical features of IM sometimes resemble those of AVH, it is often difficult to differentiate the two entities. The measurement of spleen size could be a significant supplemental aid in the diagnosis of IM in primary medicine, before clinical data can be obtained.

The effect of Kupffer cells on natural killer (NK) cell-mediated cytotoxicity was examined. Kupffer cells prepared from rat liver suppressed NK activity against K562 cells and other tumor cell lines through a soluble factor secreted into the culture supernatant. When human peripheral blood mononuclear cells were incubated with the Kupffer cell-culture supernatant, a significant reduction of the cytotoxic activity was observed in the 6-hr chromium-release assay. This activity was dose dependent and was evident at various effector/target cell ratios. Lipopolysaccharide stimulated generation of the suppressive factor released from Kupffer cells in a dose-dependent manner. Suppression of the NK activity was observed when the Kupffer cell-culture supernatant was present in the assay system, whereas pretreatment of effector/target cells with the supernatant had minimal inhibitory effects. Autologous monocytes in human peripheral mononuclear cells were not related to this suppression. The suppressive factor in the fraction had a molecular weight below 10,000. Indomethacin, an inhibitor of prostaglandin synthesis, ameliorated the suppressive effects. These results suggest that Kupffer cells may modulate NK activity by producing PGs (E 1 , E 2 , and F 2α ).

Rat α 2 -macroglobulin was isolated and purified from the pooled sera of turpentine-injected rats by sequential use of dextran sulphate, DEAE-cellulose, and gel filtration chromatography. The final protein product obtained by this procedure proved to be α 2 -macroglobulin of a high degree of purity based on electrophoretic, immunologic and centrifugal analysis. The α 2 -macroglobulin preparation also binds stoichiometrically to trypsin preventing subsequent inhibition by protein trypsin inhibitors. SDS-polyacrylamide gel electrophoresis of rat α 2 -macroglobulin after incubation with trypsin suggested that there are at least two susceptible peptide bonds in the 170 000-dalton α 2 -macroglobulin subunit. The concentration of α 2 -macroglobulin in the sera of rats was measured by electroimmuno assay using a monospecific antiserum against α 2 -macroglobulin. Purified α 2 -macroglobulin was used as a standard. Sera from normal male rats contained 32 ± 4 μ g of α 2 -macroglobulin per ml. To determine the time course of response of α 2 -macroglobulin to inflammation, rats were subjected to either laparotomy or subcutaneous injection of turpentine. After either type of injury, the concentration of α 2 -macroglobulin increased rapidly, reaching a maximum value of 110–140 times that of the control value by 24 h. Little difference was noted in responsiveness between the two sexes.

Changes in hepatic hexosamine metabolism and serum seromucoid concentrations during postnatal development were investigated in the rat. A relatively low activity of hepatic L-glutamine: D-fructose-6-phosphate aminotransferase (AT) was observed within 24 hr of birth. This rapidly increased to a maximum at about 2 weeks of age, followed by a decline to adult levels after another 2 weeks. The developmental pattern of hepatic UDP-N-acetylglucosamine 2'-epimerase (EP) closely resembled that of AT. It was relatively low in the newborn, increased to a maximum at about 2 weeks and then declined to adult values after another 2 weeks. The serum seromucoid concentration was low in the new born rats and then increased gradually with development to adult levels at about 50 days. The hepatic concentrations of UDP-GlcNAC and CMP-NANA both were relatively high at 24 hr after birth compared to values observed at 50 days. The developmental pattern observed for both over this time period was quite similar and was almost the reciprocal to that for the seromucoid fraction. After 50 days the concentration of UDP-GlcNAc remained constant at adult levels as did that of the seromucoid fraction, but the concentration of CMP-NANA showed a marked increase. It is suggested that the hepatic concentrations of these amino-sugar nucleotides during development primarily reflect the demand for the hepatic synthesis and secretion of plasma glycoproteins as reflected in the seromucoid fraction.

The addition of glucagon (10−6 M) to an incubation mixture containing 32Pi and hepatocytes isolated from livers of rats fed ad libitum results in both a 3-fold increased incorporation of 32P into L-type pyruvate kinase and a decreased catalytic activity. The 32P incorporated into pyruvate kinase was covalently bound to the enzyme as evidenced by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. In addition, exogenous cyclic AMP (10−3 M) stimulated the phosphorylation and the suppression of catalytic activity to a similar extent. On the other hand, insulin (10−7 M) had essentially no effect on the incorporation of 32P into pyruvate kinase or on its catalytic activity under the conditions used in this study. These results suggest that phosphorylation of pyruvate kinase invivo is stimulated by glucagon via cyclic AMP and cyclic AMP-dependent protein kinase and that the activity of the enzyme is, at least in part, regulated by a phosphorylation-dephosphorylation mechanism.

腹部超音波検査にて偶然発見され,外科的に切除・確認した副腎骨髓脂肪腫の1例を報告する.症例は47才男性,腹部超音波検査にて高エコーを呈する右副腎腫瘍を指摘された. CTにてfat densityを示し,やや不均-な内部構造を有していた.内分泌学的には無機能であった.組織学的には脂肪組織に骨髄類似の造血組織が混在する特徴ある所見が得られた.

We studied on the prognosis-related factors on 17 cases of Japanese encephalitis experienced during the last ten years and compared the clinical features with those in previous reports, especially when the disease was prevalent. The patients, ranging from 33 to 91 years old, consisted of 7 men and 10 women. All of them showed an encephalitis type. 47.1% of the patients were completely cured, 35.3% cured with sequelae and 17.6% died. The mortality rate was decreased compared to that of previous reports. All of the death cases were women. There was no relationship between the mortality rate and the patients' age. As previously reported, the more severe the disturbance of consciousness, the higher the mortality was. However the rate of death was lower than that of previous reports. We conclude from this study that clinical features of the disease have changed when compared with that of the older days.

There have been several recent advances in our understanding of primary biliary cirrhosis. Foremost amongst these has been the cloning and identification of the mitochondrial autoantigens as members of the 2-oxo-dehydrogenase complex. These include the E2 components of PBC, BCKD and OGDC. The immunodominant autoepitopes of the autoantigens have been mapped and, in all cases, correspond to the inner lipoyl domain. Limited progress has also been made on T cells, particularly the CD4 response. However, the fundamental mechanisms and the role, if any, of CD8 cells are unknown. Finally, at least 2 groups have identified a molecule that cross-reacts with PDC-E2, i.e., a mimic, on the luminal surface of biliary epithelium in PBC but not controls. The identification of this molecule will be critical in further understanding the immune response of this disease.

Mitochondrial autoantigens and their B and T cell autoepitopes have been well defined in primary biliary cirrhosis (PBC). However, the relationships of the antimitochondrial antibodies and the mechanisms of bile duct destruction in PBC remain an enigma. The serological hallmark of PBC remains the presence of antibodies to mitochondria, particularly to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). However, several mechanisms may now be proposed which may explain the immune-mediated bile duct damage in PBC. These include the possible role of T cell-mediated cytotoxicity as well as the interaction between the IgA class of antimitochondrial antibodies and the mitochondrial autoantigens. A prominent feature in this discussion is the highly directed and specific immune response to the mitochondrial antigens, including PDC-E2 as well as other members of the 2-oxo-acid dehydrogenase complexes. Ultimately, the mechanisms that lead to this immune reaction should provide data on other questions in PBC, including the reasons for female predominance, the absence of PBC in children and the relative ineffectiveness of immunosuppressive agents.

Background The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4+ T cells. Results CD4+ T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4+ T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70. Conclusions Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.

Introduction Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis. Methods Fibroblast-like synoviocytes (FLS) were isolated from RA patients and stimulated with recombinant oncostatin M (OSM). The cellular supernatants were analyzed using cytokine protein chips. IL-6 mRNA and protein expression were analyzed by real-time PCR method and ELISA, respectively. Protein phosphorylation of rheumatoid synoviocytes was assessed by Western blot using phospho-specific antibodies. Results OSM was found to be a potent inducer of IL-6 in FLS. OSM stimulation elicited rapid phosphorylation of STATs suggesting activation of the JAK/STAT pathway in FLS. CP690,550 pretreatment completely abrogated the OSM-induced production of IL-6, as well as OSM-induced JAK/STAT, and activation of mitogen-activated kinases (MAPKs) in FLS. Conclusions These findings suggest that IL-6-type cytokines contribute to rheumatoid synovitis through activation of the JAK/STAT pathway in rheumatoid synoviocytes. Inhibition of these pro-inflammatory signaling pathways by CP690,550 could be important in the treatment of RA.