In the present experiment, we investigated the mechanism of the suppressed mitogen responses of peripheral blood mononuclear cells (PBMC) from uremic patients. We used phytohemagglutinin (PHA) and concanavalin A (Con A) as T cell mitogens, pokeweed mitogen (PWM) as a T cell-dependent B cell mitogen, and Staphylococcus aureus Cowan I (STA) as a T cell-independent B cell mitogen. PBMC from uremic patients showed significantly suppressed responses to PHA (p < 0.05), Con A (p < 0.05) and STA (p < 0.01) compared with those from healthy controls, but there was no significant difference in PWM response. However, these suppressed responses to PHA and Con A were markedly restored by depletion of phagocytic cells from PBMC. Although STA responses were also restored markedly in uremic patients, some patients still showed lower responsiveness to STA indicating the possibility of functional B cell defects. To further clarify the mechanism of the suppressed responses to mitogens, PBMC or nonphagocytic cells from uremic patients were cocultured with control T cells in the presence of PHA, or the effects of adherent cells from uremic patients on PHA responses of autologous or allogeneic control T cells were studied. From these experiments, it was suggested that the suppressed responses of PBMC to mitogens in uremia were mediated by monocytes.

In order to clarify the prevalence of human T-cell leukemia virus type I (HTLV-I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV-I, antibodies for HTLV-I (anti-HTLV-I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti-HTLV-I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in in females than in males (P less than 0.01). The prevalence of anti-HTLV-I in blood donors was 8.5%. In In hematologic diseases, the prevalence of anti-HTLV-I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti-HTLV-I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti-HTLV-I than healthy residents (P less than 0.01 or 0.05). For autoimmune diseases, the prevalence of anti-HTLV-I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti-HTLV-I increased with the number of blood transfusions. Therefore, HTLV-I transmission via blood transfusion would partially explain these high prevalence of anti-HTLV-I. However, the prevalence of anti-HTLV-I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P less than 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti-HTLV-I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest that possibility that HTLV-I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV-I transmission as soon as possible.

We report 2 cases of adult T cell leukemia (ATL) from hemodialysis (HD) patients with chronic renal failure (CRF) in the Kagoshima district, an endemic area of human T cell leukemia virus type I(HTLV-I) in Japan. The positivity of antibodies to ATL-associated antigen(anti-ATLA) in HD patients, regardless of whether or not blood transfusions were given, has been higher than in healthy persons in the district (p < 0.01). ATL is considered to break out from HTLV-I carriers. Further study should be conducted to clarify the relationship between HTLV-I infection and CRF, and moreover, attention should be directed not only to treatment of HD but accompanying ATL as well, particularly in HTLV-I-endemic areas.

Previously we have established a clonal squamous cell carcinoma cell line OKa‐C‐1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa‐C‐1 cells simultaneously produce granulocyte colony‐stimulating factor (G‐CSF) and parathyroid hormone‐related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G‐CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G‐CSF and PTHrP production in OKa‐C‐1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol‐12‐myristate‐13‐acetate (PMA), tumor necrosis factor‐α (TNF‐α), interleukin‐1 (IL‐1) β and IL‐6] on G‐CSF and PTHrP production, by means of enzyme‐linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TNF‐α or IL‐1β induced both G‐CSF and PTHrP production in the conditioned medium. TNF‐α synergized with IL‐1β to significantly increase G‐CSF production. In addition, TNF‐α and IL‐1β strongly induced G‐CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF‐α PTHrP mRNA expression was more strongly induced by PMA than by TNF‐α. Thus, TNF‐α and IL‐1β could be common factors that individually and synergistically regulate G‐CSF and PTHrP production in OKa‐C‐1 cells. Moreover, G‐CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.

Erythrocyte membrane fluidity was studied by means of electron spin resonance in 15 uremic, hemodialyzed patients and 14 normal subjects. Erythrocyte membrane fluidity determined using a 16-nitroxide stearic acid spin label probe was of a significantly lower level in the uremic patients, when compared with normal control subjects. Alterations in molar ratios of membrane free cholesterol to phospholipid are probably not a principal factor contributing to this change in fluidity. Significant decreases of phosphatidylcholine and molar ratios of phosphatidylcholine to sphingomyelin were noted in the erythrocyte membrane of uremic patients, and these alterations may relate to the fluidity change.