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Kazuko Uno

Publications and source records attributed to Kazuko Uno.

8 recordsLinked to original sources

Clinical utility of 2',5'-oligoadenylate synthetase activity measurement: using whole blood as a highly sensitive method to detect the effects of IFN.

Research progress on the pleiotropic effects of interferons (IFN) has thus far required detecting responses by weak IFN signals. The activity of 2',5'-oligoadenylate synthetase (2-5OAS) is a valuable indicator in the prognosis and IFN treatment of patients with viral diseases such as hepatitis B and C. Although serum samples generally are used to measure enzyme activity, their values depend on the exact conditions under which blood is stored and the degree of haemolysis that occurs during blood drawing or serum separation. This study presents an improved method of evaluating 2-5OAS activity by using whole blood samples containing heparin, which are frozen and then thawed, instead of serum samples. This method is more reliable, convenient, and 50-100 times more sensitive than the conventional methods of measuring serum 2-5OAS activity. The reliability and sensitivity of this improved method enables detection of the effects of low doses of oral IFN administration or changes in the IFN and cytokine system by infection or autoimmune diseases.

2',5'-Oligoadenylate Synthetase↗

Impairment of IFN-alpha production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma.

AIM: To determine the utility of interferon (IFN)-alpha production capacity in patients with hepatitis C virus (HCV) infection for the measurement of immuno-surveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-alpha production capacity of patients with HCV infection. METHODS: HVJ stimulated IFN-alpha production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC). RESULTS: IFN-alpha production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-alpha production capacity was observed. IFN-alpha production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC. CONCLUSION: Measurement of IFN-alpha production in LC patients may be useful for the early detection of HCC.

Adult↗

[Intracellular glutathione (GSH) of monocytes (Mo) directs the development of peritumoral stroma in patients with colon carcinoma].

BACKGROUND: One of the unresolved issues related to immunotherapy for cancers is how to predict the degree of growth of tumor stroma at the periphery of the tumor. We examined the feasibility of predicting stromal growth by measuring the glutathione (GSH) level in monocytes as an indicator of the local redox state of cancer, reflecting anti-tumor immune responses. METHODS: Blood was drawn preoperatively from 21 patients with colorectal cancer. Monocytes were isolated from each blood sample and observed under a fluorescent microscope after fluorescent dye staining. The chromatic responses were rated on a three-grade scale: strongly positive, moderately positive and weakly positive. The monocytes were counted in each grade, and the GSH score was calculated. After surgery, pathology specimens of resected tissue were observed under a microscope to measure the percentage of the surface area of stroma in a given visual field at a magnification of x200. The percentage of stromal surface area was measured for three visual fields (near the deepest area of the tumor) to calculate the stroma score. RESULTS: The mean GSH score was 290.2. The mean stroma score was 60.8. There was a significant correlation between the GSH score and the stroma score (r = 0.421, p < 0.05). CONCLUSION: The monocyte GSH level may serve as a predictor of stromal growth.

Adult↗

Association between IFNA genotype and the risk of sarcoidosis.

Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process ( IFNA17, IFNB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, ETA-1, and NRAMP1) in an association-based study of 102 Japanese patients with sarcoidosis, 114 with tuberculosis, and 110 control subjects. After correction for multiple testing, an IFNA17 polymorphism (551T-->G) was found to be associated with susceptibility to sarcoidosis (odds ratio 3.27 [95% CI: 1.44-7.46], P=0.004, P(c)=0.04), but not to tuberculosis. We observed no significant associations with the other polymorphisms of the Th1-related genes. We further typed another IFNA polymorphism ( IFNA10 60T-->A) and confirmed two major haplotypes of the IFNA gene, viz., allele 1: IFNA10 [60T]- IFNA17 [551T] and allele 2: IFNA10 [60A]- IFNA17 [551G], in the Japanese population. In healthy subjects, IFNA allele 2, which is over-represented in patients with sarcoidosis, was significantly associated with increased IFN-alpha and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN-alpha significantly increases the risk of sarcoidosis.

Adolescent↗

A series of immune responses leading to the induction of T cell IL-12/IL-18 responsiveness in patients with relatively large tumor burdens.

The induction of interleukin-12 (IL-12) responsiveness in T cells depends on T cell receptor (TCR) triggering, and is regarded as a parameter of recently TCR-sensitized T cells. Here, we investigated whether IL-12 responsiveness could be detected in freshly prepared T cells from tumor-bearing patients, and if so whether such patients exhibited additional immunological parameters related to IL-12 responsiveness. CD4(+) and CD8(+) T cell populations from an appreciable proportion of tumor-bearing patients exhibited high levels of IL-12 responsiveness as evaluated by IL-12-stimulated interferon-gamma (IFN-gamma) production. T cell populations with high IL-12 responsiveness were observed in the group of patients with moderate to large tumor mass or tumor metastases rather than in patients with small tumors. The frequency of such a T cell population was also lower in post-surgery tumor-free patients, showing the correlation between IL-12 responsiveness and the presence of a certain extent of tumor burden. More importantly, a higher incidence of IL-12 responsiveness was observed in tumor-bearing patients exhibiting detectable plasma IL-12 levels, and correlated with IL-18 responsiveness. T cell IL-12 and IL-18 responsiveness is induced by TCR triggering and subsequent IL-12 stimulation respectively. Furthermore, TCR-triggered T cells stimulate antigen-presenting cells (APC) to produce IL-12. Therefore, the present observations suggest that an immune response loop from TCR sensitization to the induction of IL-12/IL-18 responsiveness via IL-12 production operates in tumor-bearing patients, particularly in those with relatively large tumor burdens.

Adult↗

Correlation between the severity of clinicopathological parameters and whole blood interferon-alpha production capacity in active phase IgA nephropathy patients.

BACKGROUND/AIMS: Patients with IgA nephropathy (IgA-N) are thought to have immune system disorders that frequently result in high serum IgA levels and a relatively high susceptibility to upper respiratory infections. AIMS: To clarify the influence of the specific immune response of IgA-N patients on the clinicopathological features of the disease, we measured the whole-blood-producing capacity of interferon-alpha (IFNalpha-PC). We then compared these findings with clinical and histopathological parameters, including tissue macrophage infiltration, during both histologically active and latent phases. PATIENTS AND METHODS: Fifty-one inpatients with IgA-N and 70 healthy controls were examined. According to the histological findings, 32 patients had disease in the active phase (AP), and 19 were in the latent phase (LP). RESULTS: In AP patients, IFNalpha-PC showed positive correlations to serum creatinine, blood urea nitrogen, serum beta2-microglobulin (s-beta2MG), urinary total protein (U-TP), and urinary beta2MG, in addition to the number of infiltrated macrophages per area of interstitium. In LP patients, negative correlations were shown between IFNalpha-PC and s-beta2MG, U-TP, and U-N-acetyl-beta-D-glucosaminidase. CONCLUSION: A significant positive relationship exists between IFNalpha-PC and the clinicopathological parameters of deteriorated renal lesions in the AP but not in the LP. Thus, the immune status influencing the functional damage may differ between these two phase.

Adult↗