Tomohiro Kusaba

High incidence of herpes zoster in patients with systemic lupus erythematosus: an immunological analysis.

The incidence of herpes zoster was determined in patients with systemic lupus erythematosus (SLE) and the cellular and humoral immunity to varicella zoster virus (VZV) investigated in 45 of these 92 patients. The incidence of herpes zoster was high, occurring in 40 patients (43%), though it was benign in all. Patients with SLE who had had zoster showed significantly higher antibody titres than normal subjects. On the other hand, only 13 of 43 (30%) patients with SLE showed positive delayed hypersensitivity skin reactions to VZV antigen, despite a history of infections with VZV, whereas all 15 normal subjects had positive reactions. Skin reactions to VZV correlated directly with the ratio of OKT4+ to OKT8+ T cells and inversely with the dose of corticosteroids. These results suggest that the high incidence of herpes zoster in patients with SLE is probably due to defects in cellular immunity and that normal or higher titres of antibodies to VZV will not act as a preventive against zoster. In addition, reactivation of VZV, whether symptomatic or not, seemed often to occur in patients with SLE.

Characterization of Monoclonal Antibodies against Etiological Agents of Weil's Disease

Monoclonal antibodies against etiological agents of Weils disease were produced by cell fusion technology. Twenty hybridomas were produced through the fusion of P3×63Ag8.653 cells with spleen cells from BALB/c mice immunized against Leptospira interrogans serovar icterohaemorrhagiae RGA strain and serovar copenhageni Shiromizu and M20 strains. Reactivities of the antibodies produced by the hybridomas were determined by the microscopic agglutination test. Among the five hybridoma antibodies to the RGA strain, two reacted specifically to serovar icterohaemorrhagiae, two reacted to serovar icterohaemorrhagiae at a high titer and serovar copenhageni at a low titer, and one reacted to serovars icterohaemorrhagiae, copenhageni, pyrogenes, and canicola. Of the ten hybridoma antibodies to the Shiromizu strain, one reacted specifically to serovar copenhageni, seven reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, and two exhibited intermediate properties. Of the five hybridoma antibodies to the M20 strain, three reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, one reacted to serovar copenhageni at a low titer and serovar icterohaemorrhagiae at a high titer, and one reacted to serovars copenhageni, icterohaemorrhagiae, and pyrogenes. The results revealed that each serovar has its own antigen(s) and their common antigens. In addition, 20 strains of leptospires were recently isolated and tested with three monoclonal antibodies characterized by different reactivities. Twenty strains were clearly identified by their antibodies, i.e., 16 strains were identified as serovar icterohaemorrhagiae and three strains were identified as serovar copenhageni. The remaining strain, which was not agglutinated by three antibodies, was identified as serovar autumnalis by an agglutination test with immune rabbit sera.

Liver abnormalities and liver membrane autoantibodies in systemic lupus erythematosus.

The hepatic involvement of 57 patients with systemic lupus erythematosus (SLE) was studied with special reference to liver membrane autoantibody (LMA). Liver abnormalities were found predominantly in patients with active SLE (27/48 (56%) in active SLE v 3/20 (15%) in inactive SLE). They were, however, rather mild or moderate and tended to disappear as the disease activity of SLE decreased. In this respect the liver abnormalities observed in this study differed from those in patients with lupoid hepatitis. The incidence of LMA in active SLE (8/11 (73%] was significantly greater than that in inactive SLE (4/12 (33%)). The mean LMA index value in active SLE was 8.3, which was also greater than the 2.9 in inactive SLE. Furthermore, in active SLE the mean LMA titre was significantly higher in patients with liver abnormalities than in those without. These results suggest that LMA may be associated with the activity of SLE and may be one of the factors which cause transient liver abnormalities.

Case report: nifedipine-rifampicin interaction attenuates the effect on blood pressure in a patient with essential hypertension.

A 72-year-old woman with 5-year history of essential hypertension developed peritoneal tuberculosis. The patients hypertension, which had been well-controlled by long-acting nifedipine, deteriorated after the administration of rifampicin, an antitubercular agent. During use of nifedipine and rifampicin, both the peak plasma concentration and the area under the curve of nifedipine decreased markedly to about 40% of those without rifampicin. The findings suggest that rifampicin may increase the elimination of nifedipine, presumably by induction of its hepatic metabolism. Nisoldipine, another calcium antagonist, also failed to lower the patients blood pressure, when given in combination with rifampicin. Taken together, these findings indicate that more caution should be urged when calcium antagonist is prescribed along with rifampicin.

Phorbol Ester Receptors and the Induction of Differentiation in the Human T Lymphoblastic Cell Line MOLT-3

To examine the mechanism of induction of differentiation in the human malignant T-lymphoblastic cell line, MOLT-3, by 12-O-tetradecanoylphorbol-13-acetate (TPA), the role of receptors for phorbol esters was investigated. Binding of [20-3H]-phorbol-12,13-dibutyrate to TPA-resistant subclones derived from MOLT-3 was less than 50% of that of the parental MOLT-3. Scatchard analysis showed that the concentration of phorbol ester receptors in a TPA-resistant subclone was about 50% of that in the parental MOLT-3, but affinities of binding were similar, indicating that more than a certain number of phorbol ester receptors is required to induce differentiation by TPA in this human T cell line.

A pedigree of deficiency of the ninth component of complement (C9)

SummaryFindings in a large family with a hereditary deficiency of the ninth component of complement (C9) were reported. The proposita was a 64-year-old Japanese woman with gastric cancer. C9 was undetectable by both rocket immunoelectrophoresis and hemolytic assays. Despite the C9 deficiency her serum showed half the normal level of hemolytic complement activity (16 CH50 U/ml). C9 was not detectable in her two sisters who had no underlying disease. Other complement components were of normal levels in these two sisters. In 8 males and 7 females from three generations of the family, levels of C9 protein were reduced and ranged from 22 to 46% of the normal. Such corresponds to heterozygote for the mutant gene, and this defect may be due to autosomal incompletely dominant gene.The C9 deficient individuals were not liable to specific diseases.

Behçet's disease associated with complement component 9 (C9) deficiency.

Abstract Behçets disease is a multisystem inflammatory disorder with unknown etiology. It has been shown that the titer of plasma complement component 9 (C9) is a good indicator of the disease activity. Therefore, the involvement of C9 in the pathogenesis of Behçets disease has been suggested. We report a case of Behçets disease associated with complete C9 deficiency (C9D) carrying the homozygous nonsense mutation at Arg-95 of C9 (R95X). The patient presented the typical characteristics of Behçets disease, such as uveitis, recurrent oral aphthae and genital ulcers, and arthritis, suggesting that C9 does not play an essential role in the pathogenesis of Behçets disease.

A case with primary biliary cirrhosis associated with renal tubular acidosis and Sjoegren's syndrome.

遠位及び近位尿細管性アシドーシス(dRTA & pRTA)とSjogren症候群(SjS)を合併した原発性胆汁性肝硬変症(PBC)の症例を報告する.症例は51歳女性,下肢脱力発作,躯幹筋肉痛などのRTAに基づく自覚症状が前景に現われ,SjSとPBCの症状は隠されていた.検査成績では,d & pRTAの所見,抗ミトコンドリア抗体(AMA)陽性,IgM著増(3300mg/dl)などがみられた.SjS, PBCの生検病理所見はともに初期像であった.PBCやSjSにRTAが合併した症例はみられるが,これら3者合併の報告は稀である.本症例においては,門脈域の胆管周囲,唾液腺周囲および腎の間質に単核細胞浸潤がみられたことから,これら3つの組織に共通な抗原を標的としてリンパ球が作用し,障害が生じた可能性が考えられた.RTAの発症は,小血管基底膜並びにその周辺へのIgMの沈着が関与しているものと考えられた.

Phagocytosis-Connected Oxygen Consumption by Peripheral Leukocytes from Patients with Systemic Lupus erythematosus

The phagocytic activity of peripheral blood leukocytes was assayed by means of oxygen consumption in 28 patients with systemic lupus erythematosus (SLE) and 22 normal individuals. The method in which zymosan was added to a small volume of whole blood enabled us to assay quantitatively and rapidly both the phagocytosis-connected oxygen consumption and the opsonizing time. The degree of oxygen consumption by phagocytes from SLE patients was not significantly different from that in normals. Opsonizing time of zymosan by autologous serum in SLE patients did not differ from that in normals either. It should be emphasized, however, that the opsonizing time of zymosan in SLE patients was inversely correlated with serum complement level, especially C3 level (coefficient of correlation = -0.76, p less than 0.001). This raises the possibility that the phagocytosis may be delayed in SLE patients with low titers of C3.