Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Serum from Mycobacterium bovis BCG-infected mice that had been challenged with lipopolysaccharide (LPS) exhibited a marked ability to induce gamma interferon (IFN-y) in cultures of spleen cells of normal mice in the presence of interleukin-2 (IL-2). The inducing activity became detectable in the circulatory system about 90 min after LPS challenge, disappeared at around 5 h, and was observable upon 640x dilution of the serum. Addition of monoclonal anti-IL-2 receptor antibody to the culture inhibited the induction by the serum. The activity induced high levels of IFN-y even in nylon wool-nonadherent cells, while concanavalin A failed to do so. Serum from uninfected mice challenged with LPS contained no such activity. The molecular weight of the active substance, estimated by gel filtration, was about 70,000. There were pronounced differences among mouse strains in the activities of the sera prepared, which paralleled the amounts of IFN-y produced in vivo. However, the levels of IFN-y produced in whole spleen cells and in nylon wool-nonadherent cells from mice of various strains were the same when stimulated with competent serum. These results indicate the existence of an unidentified factor that induces IFN-y in cooperation with IL-2 in macrophage-depleted splenocytes. They also suggest that IFN-,y production in vivo is not genetically controlled at the lymphocyte level but, rather, at the level of synthesis of the unknown factor.

Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms (IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia (P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A (P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis.

No abstract

The serum autoantibodies, antinuclear antibody, anti-DNA antibody, anti-smooth muscle antibody, antithyroglobulin antibody, antimicrosomal antibody, antimitochondrial antibody, rheumatoid factor and antibody to deoxyribonucleoprotein were measured at the baseline and on completion of interferon-a2a (IFN-oc2a) treatment in chronic hepatitis C (CHC) patients who did not present with any autoimmune disease prior to treatment. Of the 57 patients examined, 27 spontaneously manifested at least one autoantibody. Only the prevalence of rheumatoid factor (26%) was significantly higher in the CHCpatients than in the control subjects. There were no differences in the prevalence of the 8 autoantibodies examined between hepatitis C virus (HCV) genotypes, lb and 2a/2b. Twenty-six patients responded to IFN-oc2a. Subclinical hypothyroidism developed in two patients with elevated antithyroid antibody titers during treatment. Norelation-ship was observed betweenchanges in the status of autoantibodies and either response to IFN-a2a or HCVgenotype. Irrespective of the HCVgenotype, autoantibodies might be present in CHC patients before and during the IFN-oc2a treatment. The presence of such antibodies does not represent a contraindication to the use of IFN-a2a in CHCpatients not complicated by auto-immune diseases. Careful observations are necessary for CHCpatients positive for antithyroid antibodies during the IFN-oc2a treatment. Preexisting or newly developed autoantibodies do not necessarily predict a poor response to IFN-oc2a.

This study aimed to clarify the effects of the interruption of cardiac rehabilitation (CR) and refraining from going outside due to the COVID-19 pandemic on hemodynamic response and rating of perceived exertion (RPE) during exercise including differences by age in phase 2 CR outpatients. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the < 75 years group and ≥ 75 years group. Fiftythree patients were enrolled in the final analysis. Post-CR interruption, peak heart rate increased significantly (p = 0.009) in the < 75 years group, whereas in the ≥ 75 years group, weight and body mass index decreased significantly (p = 0.009, 0.011, respectively) and Borg scale scores for both dyspnea and lower extremities fatigue worsened significantly (both, p < 0.001). CR interruption and refraining from going outside due to the COVID-19 pandemic affected the hemodynamic response, RPE during exercise and body weight in phase 2 CR outpatients. In particular, patients aged ≥ 75 years appeared to be placed at an increased risk of frailty.

Sjogren's syndrome occurs as an occasional complication of autoimmune hepatitis, and purpura or thrombocytopenia develops in some patients with this syndrome. This report describes a 62-year-old womanwith a 6-year history of autoimmune hepatitis who concurrently had hypergammaglobulinemic purpura, immune thrombocytopenia and Sjogren's syndrome. Treatment with prednisolone resulted in marked improvement of biochemical, hematological and dermatological abnormalities. This case emphasizes the manifestation of purpura or thrombocytopenia as an associated disorder during the course of autoimmunehepatitis concomitant with Sjogren's syndrome. (Internal Medicine 40: 308-311, 2001)

Infection of mice with Mycobacterium bovis BCG sensitizes them for immune induction of interferon (IFN)-gamma by specific antigen. These mice were found also to respond to lipopolysaccharide (LPS) and concanavalin A (Con A) with high level production of IFN-gamma in the circulation, which was not observed in control mice. In this study, we compared the IFN-gamma response to LPS with that to Con A in an attempt to clarify the cellular mechanisms responsible for in vivo LPS-induced IFN-gamma production. Consequently, (i) the responses to LPS and Con A differed in the kinetics, that to LPS having a longer lag period. (ii) Spleen cells taken from infected mice produced little IFN-gamma in response to LPS, but they showed a higher IFN-gamma response to Con A than those from control mice. (iii) By treating infected mice with immunosuppressive drugs or antibodies to T and natural killer cells before challenge with the inducers, it was indicated that different cellular systems are involved in the IFN-gamma responses to LPS and to Con A.