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Vector control of an interior permanent magnet synchronous motor (IPMSM) without the magnetic pole position sensor has been studied. Especially, the extended electromotive force (EMF) based method is one of the famous systems. We proposed a simple method which estimates the magnetic pole position using the output voltage of the d-axis PI current controller without using disturbance observer. In this paper, we develop the early proposed method by introducing a new non-interference control. By the results of simulation and experiment, we have improved the magnetic pole position error in the rotor speed ramp responses.

Long-term effects of Ca antagonist and ACE inhibitor on renal function in hypertensive patients with chronic renal failure of IgA nephropathy were studied. Both Ca antagonists and ACE inhibitors were equally effective in reducing blood pressure.

An rhG-CSF derivative, nartograstim (NTG), at dose levels of 0 (saline), 0.1, 1, 10, and 100 microg/kg, was administered subcutaneously to groups of 3 male and 3 female cynomolgus monkeys once daily for 26 weeks to investigate its toxicity. In Week 4 or later, an increase in leukocyte counts consisting mainly of neutrophils was noted in all NTG dose groups, and was considered to be attributable to the pharmacological action of NTG. The degree of this increase was reduced with repetition of dosing. Increases in granulocytic cells and granulocytic cells/erythrocytic cells (G/E) ratio in the bone marrow, increase in serum ALP activity, and enlarged spleens with increase of neutrophils in the red pulp were observed at 10 microg/kg and higher. Anemia was noted at 10 microg/kg and higher in Week 4 and was accompanied by an increase in reticulocytes and a decrease in total cholesterol level at 100 microg/kg. Anti-NTG antibody was detected in 1 female at 100 microg/kg, but neutralizing antibodies were not detected at any dose levels in Week 4. In Weeks 13 and 26, these antibodies were detected sporadically at all dose levels. However, there were considerable individual variations in antibody titer, and no definite correlation could be found between the dose levels and the antibody titer. Seven NTG-dosed animals including 3 high dose-group animals showed obvious increases in leukocyte counts until Week 26 but no obvious elevation of anti-NTG or neutralizing antibody. In these animals, changes including anemia became slighter but were still observed in Week 26. Under the conditions in this study, 1 microg/kg was concluded to be the no-observed-adverse-effect level (NOAEL) in cynomolgus monkeys.

Anti-angiogenic compound (TNP-470) inhibits mesangial cell proliferation in vitro and in vivo. Growth factors, especially basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) are known to play key roles in the pathogenesis of mesangial proliferative glomerulonephritis. TNP-470 (AGM-1470), a potent anti-angiogenic compound, has anti-growth factor properties and inhibits the activation of cyclin-dependent kinase (cdk) 2 and phosphorylation of RB protein. We investigated whether TNP-470 could suppress growth factor induced mesangial cell proliferation in vitro and experimental model of mesangial proliferative glomerulonephritis in vivo. TNP-470 inhibited potently PDGF- and bFGF-stimulated proliferation of rat mesangial cells in vitro (IC50 = 50 pg/ml). In anti-Thy 1.1 glomerulonephritis, high dose use of TNP-470 (20 mg/kg/day) markedly suppressed mesangial cell proliferation and mesangial matrix expansion on day 6; however, mesangiolysis remained. Low dose use of TNP-470 (10 mg/kg/day) moderately inhibited mesangial cell proliferation and mesangial matrix synthesis, and induced appropriate glomerular healing on day 14 in anti-Thy 1.1 glomerulonephritis. Thus, TNP-470 potently inhibits growth factor-induced proliferation of mesangial cells in vitro, and mesangial cell proliferation and extracellular matrix expansion in anti-Thy 1.1 glomerulonephritis in vivo. These results suggest a novel therapeutic potential of TNP-470 in mesangial proliferative glomerulonephritis.

To elucidate the effects of dietary fatty acid composition on the insulin signaling pathway, we measured the gene expression of the earliest steps in the insulin action pathway in skeletal muscle of rats fed a safflower oil diet or a beef tallow diet. Rats were meal-fed an isoenergetic diet based on either safflower oil or beef tallow for 8 weeks. Both diets provided 45%, 35%, and 20% of energy as fat, carbohydrate, and protein, respectively. Insulin resistance, assessed from the diurnal rhythm of plasma glucose and insulin and the oral glucose tolerance test (OGTT), developed in rats fed a beef tallow diet. Body fat content was greater in rats fed a beef tallow diet versus a safflower oil diet. The level of insulin receptor mRNA, relative expression of the insulin receptor mRNA isoforms, and receptor protein were not affected by the composition of dietary fatty acids. The abundance of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol (PI) 3-kinase mRNA and protein was significantly lower in rats fed a beef tallow diet versus a safflower oil diet. We conclude that long-term feeding of a high-fat diet with saturated fatty acids induces decrease in IRS-1 and PI 3-kinase mRNA and protein levels, causing insulin resistance in skeletal muscle.

Local clustering of hepatitis C virus (HCV) infection has been demonstrated in various regions in Japan. HCV genotypes have now been compared between infected individuals from districts of Saga prefecture with either a high (H district) or low (L district) prevalence of HCV-seropositivity. The prevalence of HCV genotype 1b was significantly higher (P< 0.001) in the H district (45/50 ; 90%) than in the L district (19/36 ; 52.8%). A phylogenetic tree was constructed based on the genomic sequences of viral isolates from 20 patients infected with genotype 1b in the H district. Almost all these HCV strains clustered in the same regions of the tree. With regard to risk factors for HCV transmission, the percentage of patients with a history of surgery was significantly higher in the H district than in the L district (58 versus 33.3% ; P< 0.05). Of 20 patients infected with similar strains of HCV in the H district, 16 (80%) had at least one parenteral risk factor associated with medical care. These results indicate an increased transmission of similar strains of HCV in the H district as a result of nosocomial infection.

Alternative splicing of insulin receptor mRNA and gene expression of insulin receptor, IRS-1 and MAP kinase isoforms were examined in skeletal muscle of trained and sedentary rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill: 30 m/min at 6 degrees incline, 90 min/day, 5 days/week. Endurance training increased insulin receptor mRNA level without change in alternative splicing of insulin receptor mRNA in skeletal muscle. The levels of IRS-1 and MAP kinase (ERKI) mRNA were significantly higher in trained rats than sedentary rats. Our findings provide the first evidence that gene expression of insulin receptor and postreceptor signal transduction pathway is enhanced by endurance training, without affecting alternative splicing of insulin receptor isoforms.

To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

To examine the role of cAMP in the regulation of intracellular free magnesium concentration ([Mg2+]i), we measured [Mg2+]i in human erythrocytes by 31P-NMR spectroscopy. (-)-Isoproterenol, forskolin, Bt2cAMP and 8-bromo-cAMP decreased [Mg2+]i in human erythrocytes. Bt2cAMP did not increase the efflux rate of Mg2+ from erythrocytes. HA1004, a potent inhibitor of cAMP-dependent kinases, markedly increased the [Mg2+]i in a Mg(2+)-free buffer solution. Addition of 8-bromo-cGMP or 12-O-tetradecanoylphorbol 13-acetate (TPA) did not affect the [Mg2+]i. These results suggest that beta-adrenergic stimulation and cAMP play an important role in the regulation of [Mg2+]i in human erythrocytes.

We previously found that transferrin (Tf) differentially stimulated the growth of highly metastatic variant lines of murine melanoma and that these highly metastatic cells also had greater numbers of Tf receptors on their cell surfaces. In the present study we found that highly metastatic rat mammary adenocarcinoma cell lines also responded differentially to Tf in proliferation assays, and cell monolayers bound Tf in relation to their metastatic potential (MTPaB10 > MTPaB5 > MTLn3 > MTLn2 > MTC > MTF7 > MTPa). The brain-colonizing lines PaB10 and PaB5 were the most responsive to Tf and had the highest numbers of Tf receptors. Different human breast cancer cell lines also responded differentially to Tf in proliferation assays and bound different amounts of Tf to their cell surface Tf receptors. Transferrin binding, but not growth response, correlated with metastatic and invasive properties of lines selected from the human MCF-7 series (MCF7/LCC2 > MCF7/LCC1 > MCF7). In examining the transferrin binding and growth response of lines from the human MDA series, the Tf binding and growth response was MDA231 > MDA435 > MDA468. The lines MDA435 and MDA231 were metastatic in nude mouse assays, whereas the line MDA468 was not. Scatchard analysis indicated the presence of a single class of receptor for Tf on the rat and human mammary cell lines. The results suggest that neoplastic cells displaying various metastatic properties may express differing numbers of Tf receptors and respond differently to growth factors such as Tf. © 1993 Wiley-Liss, Inc.

Separation and quantitation of crystallin subunits in embryonic and post-hatched chicken lens were carried out by two-dimensional gel electrophoresis and an image analysing system in order to elucidate detail in the accumulation process of each crystallin subunit in lens differentiation. Complete separation of the subunits was possible when 7 M urea was included in the second dimension gel of the electrophoresis. In particular, beta-crystallin could be separated into more than 24 spots on the gel. These experiments showed that delta-crystallin accumulated rapidly during early development up to more than 80% of total crystallins, while beta-crystallin accumulated quickly only after hatching. In contrast with the contents of beta- and delta-crystallins, alpha-crystallin content in total crystallins was kept at approximately 18% throughout lens development. Therefore, it was concluded that crystallins accumulated in several different ways. This suggests that different regulation mechanisms work on the accumulation of each crystallin subunit and that the subunit composition of lens proteins is specific to each state of lens development.

1. Na+ influx into cultured vascular smooth muscle cells (VSMC) obtained from spontaneously hypertensive rats (SHR) and from Wistar-Kyoto rats (WKY) was measured. Na+ influx via the Na+/H+ exchange system was measured as the rate of 22Na+ influx into cultured VSMC sensitive to ethylisopropylamiloride (EIPA), a specific inhibitor of the exchange system. 2. The total 22Na+ influx rate in SHR was significantly higher than in WKY (6.08 +/- 0.16 vs 4.13 +/- 0.09 nmol/min per mg protein; P less than 0.001; n = 14). The EIPA (1 X 10(-4) mol/L)-sensitive 22Na+ influx rate in SHR was significantly higher than that in WKY (4.32 +/- 0.27 vs 2.17 +/- 0.14 nmol/min per mg protein; P less than 0.001; n = 14). There was no difference in EIPA-insensitive 22Na+ influx between SHR and WKY. The EIPA-sensitive 22Na+ influx rate into VSMC was significantly decreased in SHR but not in WKY by the addition of 1 X 10(-4) mol/L 1-(5-isoquinoline-sulfonyl)-methylpiperazine (H-7), an inhibitor of protein kinase C (PK-C). 3. These results suggest that the increase in Na+ influx in SHR may be due to elevation of the Na+/H+ exchange activity, and possible involvement of PK-C in the increased Na+/H+ exchange activity in VSMC from SHR.

アガロースゲルを一次元目に用いた二次元電気泳動法を紹介し, この方法が種々の試料にも応用できるか否かについて考察した. この方法を, 筋肉, 肝臓, 腎臓, レンズにおける全タンパク質の分離分析に用いたところ, 一次元目のゲルトップに引っ掛かることなく, ほとんどすべての成分が分析でき, 分析できる等電点, 分子量の範囲は広いものであった. 植物材料, 細胞核試料以外のほとんどすべての材料で理想的な分離が可能であった. このパターンに画像解析法を適用することにより, 骨格筋タンパク質トロポニンTやトロポミオシンの多くのアイソフォームを検出し, トロポニンTとトロポニンCの間やレンズクリスタリンサブユニットの間での蓄積の相互関係を調べ, さらにはトロポミオシンアイソフォームの組織特異的分布を調べた.

The acute effects of endothelin, a potent vasoconstrictor peptide, were investigated on renal hemodynamics, blood pressure and heart rate in conscious and unrestrained DOCA-salt hypertensive rats to compare with those in normotensive, sham-operated rats. The plasma concentration of immunoreactive endothelin was measured following the administration of endothelin, 0.4 nmole IV. After a dose of 1 nmole/kg IV, the blood pressure fell transiently and then rose gradually, while the renal blood flow remained decreased throughout the observation period. Both the blood pressure elevation and the renal blood flow decline in DOCA-salt hypertensive rats exceeded that in controls. In both experimental groups the arterial plasma endothelin concentration decreased rapidly after the peak was achieved. The disappearance of endothelin from plasma was significantly delayed in the DOCA-salt hypertensive rats. These findings suggest that the marked increase in blood pressure and the altered renal hemodynamics induced by endothelin in DOCA-salt hypertensive rats are due in part to a decrease in endothelin clearance.

A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.

To elucidate the molecular mechanism underlying insulin sensitivity, we have thought to investigate gene expression of insulin signaling pathway intermediates in skeletal muscle from sedentary and endurance-trained rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill; 30 m/min at a 6 degrees incline, 90 min/day, 5 days/week. The levels of PI 3-kinase, GLUT4, p70 S6 kinase and Ras mRNA were significantly increased by 89, 40, 38, and 47%, respectively, with running training; however, the Nck mRNA level was decreased by 24%. mRNA levels of SHP-2, Grb2, Sos, Shc, GAP, p62 and p90 S6 kinase were unaltered by running training. We have previously reported that endurance training increases mRNA levels of insulin receptor, IRS-1 and ERK1 in skeletal muscle of rats. Taken together, our data suggest that gene expression of the insulin signal pathway intermediates is modulated by endurance training that may be associated with alteration of insulin sensitivity.

We examined the gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats using reverse transcribed polymerase chain reaction method. The gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats showed a two-fold increase when compared with that in normotensive control rats. These results raise a possibility that the up-regulation of endothelial angiotensin AT1A receptors participates in the pathogenesis of cyclosporine induced hypertension.

The correlation between renal histology and class specific (IgG and IgM) antibodies to double stranded DNA (dsDNA) and single stranded DNA (ssDNA) was studied by enzyme linked immunosorbent assay (ELISA) in 40 untreated patients with systemic lupus erythematosus (SLE). The levels of IgG antibodies to dsDNA were significantly higher in patients with World Health Organisation class IV nephritis than in those with class I, class II, or class III nephritis. IgG antibodies to ssDNA were higher in patients with class IV than in those with class II nephritis. IgG antibodies to dsDNA showed a close correlation with the histological activity score and the amount of electron dense deposit. IgG antibodies to ssDNA showed only a weak correlation with the renal histological activity score. IgM antibodies to dsDNA and IgM antibodies to ssDNA were not correlated with renal histological features. Patients with moderate to severe nephritis had a lower ratio of IgM antibodies to dsDNA to IgG antibodies to dsDNA than those with mild nephritis. These results indicate that the measurement of IgG antibodies to dsDNA is predictive in evaluating renal histological activity in patients with SLE.

We examined angiotensin II induced changes of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using a specific protein binding assay system. We observed a rapid biphasic Ins(1,4,5)P3 response, which peaked at 5 s and at 30 s after angiotensin II stimulation. At every period of time the Ins(1,4,5)P3 level of SHR was 2- to 5-fold higher than that of WKY. Thus, the Ins(1,4,5)P3 specific assay revealed a complex Ins(1,4,5)P3 response after angiotensin II stimulation and suggested the need for further investigation of the Ins(1,4,5)P3 metabolism following agonist stimulation in vascular smooth muscle cells.

This study was designed to investigate the effect of propranolol on endothelin (ET)-1-induced increase in cytosolic Ca2+ [( CA2+]i) in cultured vascular smooth muscle cells (VSMCs) obtained from rat aorta. Propranolol (0.01 to 1 mmol/L) reduced the changes in the initial transient and the later sustained phase of [Ca2+]i induced by 100 nmol/L ET-1 as well as 10 mmol/L procaine. The inhibitory action of propranolol on the change in [Ca2+]i induced by ET-1 may be involved in one of the mechanisms of propranolol-induced reduction of vasospasms.

The present study was designed to examine the effect of thrombin on endothelin production by cultured human umbilical vein endothelial cells (HUVEC) by radioimmunoassay. Cultured HUVEC released immunoreactive endothelin-1 (ir-endothelin-1) into the medium in a time-dependent manner. This release was inhibited completely by 10 micrograms/mL cycloheximide and is, therefore, directly related to de novo protein synthesis. Further endothelin release was stimulated by the addition of thrombin to the culture medium. Thrombin-induced ir-endothelin-1 release also was inhibited completely by 10 micrograms/mL cycloheximide. These results suggest that HUVEC in culture produce ir-endothelin-1 slowly, but continuously, and that this production is stimulated by thrombin.

There is evidence that protein kinase C activity in platelets from adult SHR is significantly higher than this activity in age-matched WKY. In the present study, protein kinase C activity in the SHR was measured following antihypertensive drug treatment. Chronic administration of enalapril to SHR for 2 weeks decreased both systolic blood pressure and protein kinase C activity to the levels seen in the WKY. Similar results were obtained in case of chronic treatment of SHR with hydralazine or nifedipine. These results suggest that enhanced protein kinase C activity of SHR can be suppressed by lowering blood pressure by antihypertensive drugs.

A corticosteroid- and furosemide-induced excessive increase in proteinuria developed in a 34-year-old nephrotic patient with focal glomerulosclerosis. The concentration of urinary protein increased almost in parallel with that of urinary glucose. This finding indicates that corticosteroids and/or furosemide can promote the disturbance of the tubular reabsorption mechanism together with increases in glomerular permeability and glomerular filtration rate.

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.

Common variable hypogammaglobulinemia (CVH) probably includes a variety of disorders, in that, B cell or helper T cell deficiency and suppressor T cell hyperfunction.A 24-year-old male had had recurrent eczema since his tender age. He had suffered from idiopathic thrombocytopenic purpura(ITP) at 11-year-old, peptic ulcer and colitis at 17-year-old, pyelonephritis at 18-year-old. He suffered from liver damage and ITP at 21-year-old and was given glucocorticoid and thrombocyte infusion. Since Dec' 1980, he was taken pneumonia and low immunoglobulin level was found. The quantitative immunoglobulin levels were IgG 126, IgA, 3, IgM 29, IgD 1 (mg/dl), IgE 14 IU/ml. Peripheral lymphocyte counts were normal and T: B ratio was 72: 26 (control 68: 32). The patient had delayed hypersensitivity skin reactions for PHA and SK-SD. His lymphocytes responded to in vitro stimulation by PHA or Con A.Ig production in vitro by PWM-stimulated lymphocytes from the patient was examined. Co-culture of B cells from the patient and T cells from normal resulted in reduced synthesis of all classes of Ig. Combination of the patient T cells and normal B cells also gave low Ig synthesis and X-ray treatment of the patient T cells did not enhance Ig synthesis. Moreover, coculture of normal lymphocytes and patient T cells resulted in reduced synthesis of Ig. Thus it was demonstrated that poor immunoglobulin synthesis was due to B cell insufficiency, and hypofunction of helper T cells, as well as hyperfunction of suppressor T cells.

To examine the relationship between the urinary levels of alanine aminopeptidase (AAP) or N-acetyl-beta-D-glucosaminidase (NAG) and the advance of essential hypertension, we measured the urinary levels of these enzymes in 20 normotensive controls, 8 subjects with borderline hypertension and 40 subjects with WHO stage I and stage II essential hypertension. The urinary level of NAG in stage II hypertensives was higher than that in the normotensives, and borderline or stage I hypertensives (p less than 0.01). Systolic blood pressure and the urinary level of NAG was positively correlated in hypertensives (rs = 0.43, p less than 0.01). The urinary level of NAG was correlated inversely with renal blood flow (rs = -0.61, p less than 0.01). The urinary level of AAP in stage II hypertensives was also higher than that in the normotensives (p less than 0.01) or stage I hypertension (p less than 0.01), but the urinary AAP level was not significantly correlated with systolic blood pressure or renal blood flow in hypertension.

The cellular basis of the pathogenesis of selective IgA deficiency (SIgAD) was investigated by examining surface immunoglobulin (SmIg) and in vitro pokeweed mitogen (PWM)-stimulated immunoglobulin (Ig) synthesis and by assaying in combination the counterpart lymphocytes from individuals with SIgAD and healthy donors. Peripheral blood lymphocytes (PBL) from 14 individuals with SIgAD synthesized normal amounts of IgG and IgM but did not synthesize normal amounts of IgA. Functional defects of lymphocytes for IgA synthesis were classified into four types: (i) B-lymphocyte dysfunction, (ii) increased function of suppressor T lymphocytes (Ts), (iii) decreased function of helper T lymphocytes (Th), and (iv) B-lymphocyte dysfunction and increased Ts function. The cells bearing SmIgG, SmIgM, and SmIgD were demonstrated at normal percentage ratios in all cases by immunofluorescent staining. The cells bearing SmIgA were at normal percentage ratios in the cases of T-lymphocyte dysfunction, while in the cases of B-lymphocyte defect SmIgA-bearing cells were reduced.

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.

Echocardiographic studies were performed to evaluate myocardial function in active patients with systemic lupus erythematosus (SLE). Fourteen patients were studied in the active stage before corticosteroid therapy (active SLE); 10 of them were reexamined after therapy (inactive SLE). Computer-assisted analysis of digitized echoes of the left ventricular dimension was performed. The peak rate of change in dimension during systole (-dD/dt) was reduced in active SLE compared with normal control subjects (2.57 +/- 0.15 cm/sec vs 3.37 +/- 0.14 cm/sec, p less than 0.01). The peak rate of change in dimension during diastole (+dD/dt) was also reduced in active SLE compared with normal control subjects (3.16 +/- 0.19 cm/sec vs 4.41 +/- 0.20 cm/sec, p less than 0.01). After therapy, -dD/dt in inactive SLE was improved compared with active SLE (from 2.56 +/- 0.20 cm/sec to 3.13 +/- 0.19 cm/sec, p less than 0.001). Positive dD/dt in inactive SLE was also improved compared with active SLE (from 3.29 +/- 0.22 cm/sec to 4.23 +/- 0.23 cm/sec, p less than 0.01). No significant differences were found between inactive SLE and normal control subjects as to -dD/dt and +dD/dt. Significant correlations were found between anti-DNA antibody titers and both -dD/dt and +dD/dt (r = -0.97 p less than 0.0001, and r = -0.71 p less than 0.05, respectively). These results suggest that active SLE patients have left ventricular dysfunction that may be caused by an immunopathologic mechanism in SLE.

An immunoperoxidase technique was applied to the study of chromosomal structure. Using the immunoperoxidase technique with the anti-native DNA antibody, fibrous structure of human chromosomes and interchromosomal connections could be revealed by light microscopy in acid-alcohol fixed and air-dried chromosomal preparations.

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.

We performed immunopathologic studies of the pericarditis present in a patient with mixed connective tissue disease. A large number of nuclear RNP (nRNP) immune complexes (ICs) were found in the pericardial fluid, but not in the serum. The pericardial small vessels had no deposits of IgG. These results suggest that locally formed nRNP ICs were closely associated with the pathogenesis of pericarditis in this patient.

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.

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.

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 novel and potent vasoconstrictive peptide, endothelin, has recently been purified from the culture supernatant of porcine aortic endothelium. In this study we examined the acute effects of synthetic endothelin on renal hemodynamics and blood pressure in anesthetized rats. Blood pressure and renal blood flow were measured before and 1, 2, 5, and 10 minutes after endothelin administration (1.0, 0.5, or 0.1 nM/kg body weight). After a transient fall, the blood pressure gradually increased. At five and ten minutes after administration of each of the three doses, the blood pressure was significantly elevated compared with baseline values. Renal blood flow decreased immediately after infusion of 1 nM/kg endothelin, and this decrease lasted throughout the observation periods, while 0.1 nM/kg endothelin did not affect renal blood flow. At 2, 5, and 10 minutes after infusion of 1.0 or 0.5 nM/kg endothelin, renal vascular resistance was significantly elevated. These hemodynamic alterations were dose-dependent. The results show that endothelin has potent hypertensive and renal vasoconstrictive effects in rats.

We studied the expression of c-myc proto-oncogene in hearts and cultured aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), in order to investigate the association of the c-myc gene with cardiac hypertrophy and atherosclerosis in SHR. Transcription of the c-myc gene in hearts of SHR was higher than that of WKY at 10 weeks of age, when cardiac hypertrophy had developed in SHR. The c-myc gene expression in cultured aortic smooth muscle cells of SHR, after the addition of serum to the serum-deprived cultures, was higher than that of WKY. These results suggest that the enhanced expression of the c-myc gene in the hearts and cultured aortic smooth muscle cells of SHR may be associated with the growth control of these cells, and may play a role in the development of cardiac hypertrophy and atherosclerotic lesions in SHR.

A 36-year-old woman with systemic lupus erythematosus (SLE) developed septicaemia and subsequently suppurative coxitis due to Salmonella typhimurium. Although systemic treatment with antibiotics eradicated salmonella from the arterial blood, cup arthroplasty and irrigation of the operative wounds with effective antibiotics were needed for eradication of the organism from the affected joints.

An 18-yr-old male developed Mycoplasma pneumoniae pneumonia associated with IgA nephropathy. In the biopsied renal tissue, immunofluorescence showed striking deposits of IgA, C3 and C3 activator in the mesangium, and electron microscopic examination showed electron-dense deposits in the mesangial region. When the patient's serum was preincubated with rabbit antiserum to human IgA, the passive hemagglutination titer for M. pneumoniae was much decreased. We suggest that in some cases, IgA nephropathy may follow infection by an organism which stimulates in IgA antibody response, leading to the formation of IgA antigen antibody immune complex deposits in the glomerular mesangium.