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ABSTRACT: To track changes in interferon (IFN) production in healthy individuals to shed light on the effect these changes have on the course of healthy ageing.
Study is based on data that were collected over 24 years from a cohort of individuals whose IFN-α production was quantified as a part of their annual routine health check-up.
All individuals in this study underwent regular health check-ups at Louis Pasteur Center for Medical Research.
295 healthy individuals (159 males and 136 females) without a history of cancer, autoimmune diseases and hepatitis C virus (HCV) whose IFN-α production was quantified more than five times within 24 years were selected. Finally, 29 males and 4 females whose IFN-α production was quantified more than 25 times were selected and their data were analysed using a mixed model.
HVJ stimulated IFN-α production was quantified. Healthy individual's periodical log transformed IFN-α values (y) were plotted versus age (x) and fitted to linear (y=mx+n) and quadratic formula (y=ax(2)+bx+c) expressions to reveal changes in the IFN-α production in these healthy individuals.
The linear expression showed that log (IFN-α) had a slight tendency to decline (3% over 10 years). However, the quadratic formula analysis showed the quadratic expression to be more positive than negative (a concave U-shaped pattern) which means that individuals' once declining IFN production recovered as they aged.
Although we observed a marginal decline in IFN-α production, we also observed that IFN production recovered even in individuals in their mid50s to early 60s. These results combined with our previous cross-sectional studies of patients with various diseases suggest that in healthy individuals, the impairment of IFN production is triggered more by the onset of disease (notwithstanding the cause) rather than by ageing.
BMJ open. 01/2013; 3(1).
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ABSTRACT: The ability to predict anti-tumor immune responses at local tumor growing sites using only peripheral blood specimens would be helpful in determining therapeutic options for patients with solid tumors. Here, we show that the glutathione intracellular content (icGSH) of peripheral monocytes (Mo) correlates positively with T cell infiltration within tumor islets and overall survival in patients with colorectal carcinoma. IcGSH redox status was determined in CD14(+) Mo prior to surgery by staining with monochlorobimane. The tumor-infiltrating T cells (TIL) were quantified as CD45RO(+) T cells in resected tumors using paraffin sections. A positive association was found between the GSH index and TIL in tumor islets (P < 0.001). The 50% cut-off value for the GSH index, that is the determinant between TIL presence or absence in tumor islets, was calculated to be almost 0.7 through logistic regression analysis. Mo with a GSH index of > or =0.7 were termed reductive (R)-Mo, and those with <0.7 were designated as oxidative (O)-Mo. Cox's proportional hazards regression analysis of patients with R-Mo or O-Mo prior to surgery, and the presence or absence of TIL, was found to correlate significantly with the overall survival rate of stage II and III patients. Kaplan-Meier analysis also showed a significant correlation. These results indicate that the Mo icGSH index is a useful biomarker parameter for better understanding the host/tumor relationship prior to surgery, thereby enabling the development of an individual patient-oriented therapeutic strategy.
Cancer Immunology and Immunotherapy 10/2010; 59(10):1457-65. · 3.70 Impact Factor
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ABSTRACT: A prompt and regulated interferon (IFN) system is critical for host defense against infectious pathogens. Although increased susceptibility to infection has been observed in subjects with diabetes or obesity, little is known about the relationship between metabolic disorders and increased susceptibility to infection. In order to evaluate the association between immune function and metabolic parameters, we examined the relationship between capacity of IFN-alpha production and metabolic parameters including fasting plasma glucose (FPG), lipids, uric acid, body mass index (BMI), and blood pressure in 575 healthy subjects. Linear regression analysis showed that log(IFN-alpha production) was positively correlated with log(triglyceride) (r = 0.088, P = 0.03) and uric acid (r = 0.091, P = 0.03), and negatively correlated with age (r = -0.158, P = 0.0001) and FPG (r = -0.088, P = 0.03). Multiple regression analysis showed that log(IFN-alpha production) was independently determined by age (beta = -0.148, P < 0.0001), sex (beta = -0.240, P = 0.0003), and FPG (beta = -0.096, P = 0.0209), suggesting that lesser degrees of hyperglycemia also affect IFN-alpha production. We conclude that hyperglycemia but not BMI, hypertension, or hyperlipidemia may be associated with decreased capacity of IFN-alpha production and glycemic control is critical even for both subjects without any medication for diabetes and subjects under the diagnosis of diabetes on infectious diseases.
Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 03/2010; 30(6):451-4. · 1.63 Impact Factor
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ABSTRACT: To relate clinical severity of idiopathic carpal tunnel syndrome (CTS) to current perception threshold (CPT).
Subjects were 51 patients with CTS (involving 51 hands), and 50 healthy control subjects (50 hands). Involved hands were grouped into three clinical grades (mild, moderate, severe). Using a neurometer (Neurotron, Baltimore, MD), we investigated the relationship between clinical grade and CPT abnormalities.
In the mild CTS group, most hands showed CPT abnormalities only at 2000 Hz stimulation. The moderate group included a higher percentage of hands showing abnormalities at both 2000 and 250 Hz stimulation increased. The severe group included the highest percentage of hands with abnormal values at all frequencies tested.
CPT showed abnormalities appear progressively from 'higher to lower' frequency stimulations relative to the increasing severity of CTS.
Sensory nerve fiber dysfunction apparently begins in larger fibers, extending stepwise to smaller fibers as the clinical grade of CTS progresses.
Clinical Neurophysiology 09/2004; 115(8):1921-4. · 3.41 Impact Factor
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ABSTRACT: The purpose of this study was to determine the sensitivity and specificity for the current perception threshold (CPT) test during clinical examination of idiopathic carpal tunnel syndrome (CTS). We studied 71 patients (102 hands) with CTS; 50 healthy individuals (100 hands) served as a control group. Using a neurometer, we investigated standard CPT values to obtain the sensitivity and specificity of the CPT test in the clinical examination of CTS. In the CTS group, cases that had abnormal values in the range analysis, the ratio analysis, or both were called "true-positive CPTs"; in the control group cases that had normal values in the range and ratio analyses were called "true-negative CPTs." We defined the sensitivity as the percentage of true-positive CPTs in the CTS group and the specificity as the percentage of true-negative CPTs in the control group. The sensitivity of the CPT test using both range and ratio analyses was 73%, and its specificity was 74%. Based on these results we concluded that the CPT test is a reliable quantitative sensory function test.
Journal of Orthopaedic Science 02/2003; 8(5):625-8. · 0.84 Impact Factor
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ABSTRACT: The recovery level for sensory function after carpal tunnel release for the treatment of idiopathic carpal tunnel syndrome (CTS) was assessed with the current perception threshold (CPT) test. Seventeen CTS patients (21 hands) were followed, and the CPTs at the index finger of each patient was measured preoperatively and at 1, 3, and 6 months postoperatively. After carpal tunnel release, there was significant recovery of CPT at all stimulation frequencies, indicating improvement of all sensory functions including sensations of temperature, pain, touch, and vibration.
Journal of Orthopaedic Science 02/2003; 8(4):500-4. · 0.84 Impact Factor
