We observed three patients with CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia) syndrome and 2 with primary biliary cirrhosis (PBC)-incomplete CREST syndrome. In 85 patients with CREST syndrome reported in Japan, 21 (including our 5 cases) were immunogenetically investigated for HLA.
In the 85 patients with CREST syndrome, PBC, Sjögren's syndrome, pulmonary fibrosis, other liver diseases, chronic thyroiditis and pulmonary hypertension were overlapped in 29, 18, 7, 7, 5 and 3, respectively. PBC was clinically asymptomatic in 21 (72.4%) and symptomatic in 8 (27.6%) of 29 cases with PBC-CREST overlap syndrome.
Anticentromere antibody (ACA) were positive in 22 of 27 patients (81.4%) with CREST syndrome. In contrast, antimitochondrial antibody (AMA), which often coexists with ACA, were observed in 19 of 21 patients (90.4%) with PBC-CREST overlap syndrome.
HLA-B 7 and DR 1 were found more frequently in Japanese patients with CREST syndrome than in controls, but either DR 9 or DR 3 was found more frequently in the patients with PBC-CREST overlap syndrome. These results suggest genetic differences between CREST syndrome and PBC-CREST overlap syndrome.

View full abstract

The tumor growth inhibitory effect of supernatants from peripheral blood mononuclear cells (PBMC) primed with either rIL-2 alone or rIL-2 plus anti-CD 3 Ab was evaluated. PBMC isolated from fourteen healthy donors were cultured with 1, 000 U/ml of rIL-2 to induce LAK cells. LAK cells were stimulated with 10 ng/ml of OKT-3 for first 48 hours of incubation (CD 3 (+) LAK). The inhibitory effect of these cells on tumor growth was evaluated by MTT assay using HT 29 and LS 174 T as target cells. The supernatants from CD 3 (+) LAK inhibited both target cells in a dose dependent fashion, but did not those from ordinaly LAK (CD 3 (-) LAK). The inhibitory effect of the supernatants was not reversed by anti-TNF-alpha and anti-IFN-gamma. This fact indicated that the inhibitory factor in the supernatants from CD 3 (+) LAK was not TNF-alpha nor IFN-gamma. The factor was a molecular weight of 67Kd by the SDS-PAGE analysis and was inactivated at pH3.5 or pH9.5, and also ten minutes heating.
The inhibitory factor was thought to be the same factor as LAK inhibitory factor which was identified, we reported previously, in the supernatants from CD 3 (+) LAK.

View full abstract

We have demonstrated that exogenous/endogenous TNF therapy (EET therapy) is efficient for advanced colorectal cancers. This therapy is based on the idea that endogenous TNF is induced in the serum of most cancer patients when treated firstly with recombinant TNF-S_AM2 (TNF-S) followed by administration of OK-432. We evaluated the changes in the counts of peripheral blood lymphocytes (PBL) and its subsets especially CD 8⁺DAF^- lymphocytes, of ten colorectal cancers patients who had received EET therapy. We examined them 2 hours after infusion of TNF-S as the primer, and then 4 and 24 hours after injection of OK-432 as the trigger. Band-form neutrophil counts increased remarkably after TNF-S infusion and even more after OK-432 injection. WBC, PBL, monocytes, CD 16⁺ cells, CD 8⁺CD 11 b^- lymphocytes and CD 8⁺DAF^- lymphocytes, however, tended to decrease after TNF-S infusion and recover within several days after OK-432 injection. CD 4/CD 8 ratio kept a higher level for 24 hours due to the decrease of CD 8⁺ lymphocytes. CD 8⁺DAF^- lymphocytes, to which we paid special attention as activated T cells, decreased rapidly to below 3% in 60 minutes after TNF-S infusion. CD 16⁺ cells and CD 14⁺ cells showed the same pattern as CD 8⁺DAF^- cells.
However CD 8⁺DAF^- lymphocytes did not decrease in vitro when treated with TNF-S or with serum obtained from a patient treated with TNF-S. Therefore, the decrease of CD 8⁺ DAF^- lymphocytes in peripheral blood might not be due to the down regulation of DAF expression by TNF itself or some TNF-induced cytokines. The temporary decrease of cells related to immunological activities, such as CD 8⁺DAF^- lymphocytes by TNF-S, could be due to them becoming trapped in cancer lesions, lymphoid organs or capillaly walls. The reason for the latter is, as yet, unknown.

View full abstract

In 1988, we reported on the presence of anti-Is antibody in sera from patients with either primary biliary cirrhosis (PBC) or autoimmune hepatitis. In the present study, we characterize such a patient who has been followed for the past 14 years. Medical examination revealed liver dysfunction at the age of 69. He was sent to the liver outpatient section at hospital B at age 75 because of serum hyperalkaline phosphatase and hyper γ GTP. The result of ERCP showed no evidence of extrahepatic and biliary involvement, and AMA determination was positive, suggesting the presence of PBC. He was hospitalized in order to undergo liver needle biopsy. However the biopsied specimen showed no evidence of PBC, but instead, revealed the presence of chronic persistent hepatitis. Immunopreciptation using ³⁵S methionine labelled HeLa cell extract found the corresponding antigen of anti-Is antibody to be 95 kDa in size and found mainly in the cytosolic fraction. Thus, we have decided to call this antibody the anti-p 95 C antibody. Further immunological examination of this patient showed the presence of anti-centromere antibody and anti-p 95 C antibody instead of AMA positive. Furthermore the patient continued to show obstructive hepatic dysfunction upon blood chemistry examination. However, the patient has denied general malaise, iching, and jaundice, and is thought to be a case with a good prognosis. Finally, we present 15 further cases with anti-p 95 C antibody, and discuss the clinical significance of this antibody.

View full abstract

In March 1990, a 19-year-old woman developed facial erythema. In May, when she came to the Kawasaki Municipal Hospital, she was found to have leukopenia (2, 800/mm³), high titer of anti-nuclear antibodies (2, 560×) and anti-SSA and SSB antibodies. In September, anti-U 1 RNP antibody and in December, anti-Sm antibody appeared for the first time respectively. In January 1991, she developed depression and she was admitted in February. She had akinesis, convulsion, involuntary movement of tongue. She was diagnosed as systemic lupus erythematosus complicated with central nervous system involvement (CNS lupus). She was treated with steroid pulse therapy and monthly intravenous cyclophosphamide injection and left the hospital in May. In June, anti-Sm antibody was negative but in August, it appeared again. In September 1991, she was readmitted because of mania. She had no convulsion at this time. Interferon-α(INFα) and interleukin-6 (IL-6) in cerebro-spinal fluid (CSF) were measured on admittion and after steroid pulse therapy. The levels of these cytokines were elevated (INFα346IU/ml, IL-6 680 pg/ml) and decreased before improvement of psychic symptoms. Measurement of CSF INFα and IL-6 seemed to be useful in diagnosing the CNS lupus and predicting the response to the treatment.

View full abstract