Interleukin-10-induced CCR5 expression in macrophage like HL-60 cells: involvement of Erk1/2 and STAT-3

As an immunosuppressive and anti-inflammatory cytokine, IL-10 was recently reported to play roles in CCR5 expression in human monocytes. CCR5 promoter regions contain Oct-2, TCF-1alpha, GATA, and STAT binding sites. Here, we studied the signals involved in the CCR5 expression in IL-10-stimulated cells using the HL-60 cell line. HL-60 cells were stimulated with PMA and differentiated to macrophage-like cells, then stimulated with IL-10. IL-10 induced significant expression of CCR5 protein and CCR5 mRNA in these cells. The induction of CCR5 by IL-10 was inhibited by a MEK-1 inhibitor, PD98059. In addition, IL-10 induced tyrosine (Tyr) phosphorylation of Erk, as well as serine (Ser) and Tyr phosphorylation of STAT-3. Tyr phosphorylation of Erk and Ser phosphorylation of STAT-3 were inhibited by PD98059, while Tyr phosphorylation of STAT-3 was not inhibited by PD98059. DNA binding activity of STAT-3 was observed by the stimulation with IL-10, which was inhibited by PD98059. These results first indicate that Erk1/2 and STAT-3 regulate CCR5 expression, and that Erk-mediated phosphorylation of Ser is required for full stimulation of STAT-3 in CCR5 expression.     

Effects of alpha 1-acid glycoprotein on erythrocyte deformability and membrane stabilization

The effects of alpha(1)-acid glycoprotein (AGP) on human erythrocyte membrane were examined in vitro. Bovine and dog AGP, in addition to human AGP or asialo human AGP were used, and the collected data were compared with that for human serum albumin (HSA). A new technique developed by Kikuchi was used to investigate erythrocyte deformability. The addition of AGPs including human AGP facilitated the passage of human erythrocytes with an average diameter of 7.2 microm suspended in phosphate buffered saline (PBS) through a 5 microm wide microchannel; hemolysis was suppressed after the passage. The stabilizing effects of AGPs on membrane were evaluated. Human AGP prevented hemolysis induced by hypotonic phosphate buffer solution. The effects of human AGP on the oxidative changes in erythrocytes exposed to oxygen radicals were investigated. Human AGP protected erythrocytes from H(2)O(2) and prevented the oxidation of dihydrorhodamine 123 to rhodamine 123 from H(2)O(2). We propose that the antioxidant activity of human AGP is due to the binding of free radicals. In all studies, the effects of human AGP on erythrocytes might not be a function of the negative charge associated with sialyl residues, because the presence of N-acetylneuraminic acid had no effect. However, human AGP may promote microcirculation and antioxidant activity compared with HSA. No species differences in the physiological function of AGP were found. These results suggest that an increase in the AGP content of serum above the normal value found under pathological conditions facilitates the passage of erythrocytes through capillaries, stabilizes erythrocyte membranes and protects against oxidative stress, all of which are favorable for microcirculation.     

Inhibitory effect of oolong tea on the oxidative state of low density lipoprotein (LDL)

In the present study, we investigated the anti-oxidant activity of oolong tea in an oxidation model using human low-density lipoprotein (LDL). Oolong tea suppressed the oxidation of LDL induced by 2-2'-azobis 4-methoxy-2,4-dimethyvaleronitrile (V70) in a dose-dependent manner, that is, it prolonged the lag time to 114.3%, 138% and 199.9% as compared with the control group at 0.5 microg/ml, 1.0 microg/ml, and 2.5 microg/ml, respectively. We also determined the scavenging effect of oolong tea on active oxygen radicals using the electron spin resonance (ESR) technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. The intensity of the ESR signals for the DMPO-OOH adduct formed by the hypoxanthine/xanthine oxidase reaction system with DMPO decreased in the presence of oolong tea. The IC(50) of oolong tea was 19.9 microg/ml. These findings suggested that oolong tea has beneficial effects on health related to its anti-oxidative action.     

Nasopharyngeal carcinoma in Indonesia has a low prevalence of the 30-base pair deletion of Epstein-Barr virus latent membrane protein 1

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), one of the highest incidence of tumors in Indonesia. EBV infection is ubiquitous around the world, but NPC occurs with a remarkable geographic distribution. This phenomenon suggests that there are subtypes of EBV, some of which may have greater tumorigenic potential. The latent membrane protein 1 (LMP 1) gene encoded by EBV is tumorigenic due to its ability to transform rodent fibroblast. It was originally shown that the LMP 1 gene from NPC of Chinese patients harbors a deletion of 30-bp in the carboxyl terminal of the gene. However, the deletion is also present in healthy control and in other EBV-positive tumors. We examined the polymorphism of LMP 1 in 56 tumor biopsies of Indonesian patients with NPC and identified low prevalence of the 30-bp deletion of LMP 1. Sequence analysis showed unique mutations of LMP 1 which suggests that strain-specific variations of EBV are found in Indonesia. The low frequency of 30-bp deletion in the country with high prevalence of NPC indicates that the deletion may represent a geographic polymorphism rather than a predisposing factor in the development of NPC.     

Age-dependent changes in electroencephalographic responses to alcohol consumption in subjects with aldehyde dehydrogenase-2 genetic variations

BACKGROUND: We have recently reported that alcohol consumption resulted in a significant increase in alpha power of the EEGs in aldehyde dehydrogenase-2 (ALDH2)-normal (NN) subjects but not in ALDH2-deficient heterozygote (ND) subjects. The purpose of the present study was to investigate interactive effects of individual factors such as age and ALDH2 genotype on alcohol-induced EEG changes. METHODS: We examined EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion in 53 NN and 21 ND subjects of two different age groups: younger and older groups. Blood ethanol and acetaldehyde levels were also determined in 17 NN and 13 ND subjects in separate studies. RESULTS: Alcohol consumption markedly increased EEG power in the NN subjects of the older group, especially in theta and slow alpha power, whereas only slight increases were noted in fast alpha and beta power in the NN subjects of the younger group. However, no such differences between the two age groups were observed in the ND subjects. It should be noted that there were no differences in blood ethanol and acetaldehyde level at 30 min after alcohol ingestion between the different age groups in both genotypes. However, there was a significant increase in frequency of alcohol intake in the older group of both genotype groups. The multiple regression analysis indicated that both alcohol use habits and genotype, as well as aging, significantly modulated EEG changes after alcohol ingestion. CONCLUSIONS: The results suggest that both ALDH2 genotype and age as well as alcohol use habits modify alcohol sensitivity in the central nervous system, resulting in greater increases in EEG energy in response to alcohol intake in the older group of the NN subjects.     

Insulin allergy; desensitization with crystalline zinc-insulin and steroid tapering

The insulin analogues, aspart and lispro, have been considered safe alternatives for patients with insulin allergy, because of their decreased immunogenicity. However, recent several reports showed that neither of them was completely free from allergic reactions. We also experienced a patient with insulin allergy not only to human regular insulin but also to both of the insulin analogues. Interestingly, the insulin analogues, which readily dissociate from polymer to monomer, induced the most severe allergic reaction among several types of human insulin reagents in the present case. Allergy to crystalline zinc-insulin, the three-dimensional structure of which results in delayed dissociation and absorption, was negative on intradermal tests. However, its large subcutaneous injection caused local allergic reaction. These results suggested that the allergic reaction might depend on the rapidity of insulin monomerization and absorption, and thus that the immunogenic residue of insulin is concealed when insulin is polymerized. Based on the intradermal tests, we speculated that the antigenic epitope might be B30-Thr in the present case. We also report here the modified method of insulin desensitization using crystalline zinc-insulin with prednisolone tapering. This might be a simple and useful treatment for insulin allergy.     

Tuberculosis in elderly

We compared patients with active tuberculosis treated at Kurume University Hospital between cases 65 years and above and below 65. The comparison included immunologic and clinical features. Anergy to tuberculin skin tests with purified protein derivative (PPD) was evident in 7% of patients under 65 and in 14% of those over 65. Older patients had fewer lymphocytes in peripheral blood and lower serum concentrations of interferon (IFN)-gamma than younger patients. Complications were more frequently seen in patients above 65, but the time required for negative conversion of sputum cultures did not differ by age. Adequacy of the regimen of chemotherapy and the sensitivity to anti-mycobacterial drugs were the most important determinants of the time for negative conversion of sputum culture. Major clinical problems of old tuberculosis patients were concurrent diseases, bed ridden states, necessity of nursing care, and poor performance status of patients.     

Factors affecting progression of renal failure in patients with type 2 diabetes

OBJECTIVE: Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients. RESEARCH DESIGN AND METHODS: We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr >1.5 and <3.7 mg/dl, 61 +/- 11 years old, 51 men and 34 women, mean s-Cr 2.3 +/- 0.6 mg/dl). RESULTS: The survey period (mean +/- SD) was 14.2 +/- 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252-0.750, P = 0.0027), serum albumin (0.484, 284-0.823, P = 0.0074), mean blood pressure (1.023, 1.004-1.043, P = 0.017), and hemoglobin (0.841, 0.728-0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA(1c) or serum cholesterol were not. CONCLUSION: In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA(1c) does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.     

A case study of shifting a patient with percutaneous endoscopic gastrostomy (PEG) to home care

We studied the primary factor preventing a patient with PEG from being transferred to home care focusing on the dietetic situation. The study has revealed differences in not the age of the patient, the days of hospitalization or hematological and biochemical test data but in the condition of use of home care services or family makeup. In other words, insufficient use of social resources is considered to prevent shifting to home care or continuation of home care of patients with PEG. It is necessary to understand not only dietetic situation but social backgrounds of patients and supply information.