Corrigendum: Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis.

[This corrects the article DOI: 10.3389/fimmu.2023.1222428.].

Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis.

Introduction: Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. Methods: A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. Results: The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. Conclusion: There is a characteristic cytokine profile at each clinical stage of MAC.

Association between bone mineral density, muscle volume, walking ability, and geriatric nutritional risk index in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Hemodialysis patients are at risk for bone loss and sarcopenia, characterized by reduced muscle mass and limited mobility/function. Osteoporosis and sarcopenia both increase the risk of hospitalization and death in affected individuals. Malnutrition also occurs as a complication of hemodialysis and has been identified as a risk factor for osteoporosis and sarcopenia. In this study, we examined the relationship between osteoporosis, muscle volume, walking ability, and malnutrition in hemodialysis patients. METHODS AND STUDY DESIGN: Forty-five hemodialysis patients were evaluated. Bone mineral density (BMD) and muscle volume were measured by dual-energy X-ray absorptiometry. Muscle volume and strength were evaluated using lean mass index (LMI), handgrip strength, and walking ability. The time required for a patient to walk 10 meters was measured to evaluate walking ability. The geriatric nutritional risk index (GNRI) was used to assess malnutrition. RESULTS: Multiple linear regression analysis showed that older age, female sex, lower LMI, and higher total type I procollagen N-terminal propeptide were correlated with lower BMD of lumbar spine. Higher age and lower LMI were correlated with lower BMD of the femoral neck. Female sex and lower GNRI were correlated with lower LMI. Longer duration of hemodialysis was correlated with lower walking ability. CONCLUSIONS: Our findings suggest that muscle preservation is required to maintain both lumbar spine and femoral neck BMD. Similarly, nutritional management is necessary to maintain BMD via preservation of muscle volume. Complementary nutritional therapies are needed to improve osteoporosis and sarcopenia in high-risk hemodialysis patients.

A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements.

BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied. METHODS: We established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography. RESULTS: Our PEG-column method demonstrated high reproducibility (coefficient of variation <3.52%) and linearity up to 15mg/dl for apoE-rich HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rs=-0.646), LDL size (rs=0.472), adiponectin (rs=0.476), and other lipoprotein components. No significant correlation was obtained with the coronary calcium score. Multiple regression analysis revealed that plasma triglycerides and adiponectin concentrations remained significant independent predictors of apoE-rich (adjusted R2=0.486) but not apoE-poor HDL-C. CONCLUSIONS: The PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis.

Carcinoma Ex Pleomorphic Adenoma of the Tongue: Difficulty in Diagnosis Between Metastasis of Breast Cancer and Salivary Tumor.

Carcinoma ex pleomorphic adenoma (CEPA) is a carcinoma that shows histologic evidence of arising in or from a benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma often occurs in parotid glands, but is extremely rarely in the tongue. A 53-year-old Japanese woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital, because of tumor of the right dorsum tongue. She had a history of surgery of breast cancer (invasive ductal carcinoma) and it was disseminated to the lung and bone. Macroscopic examination revealed an oval tumor with a smooth mucosal surface of 10 mm in diameter in the right dorsum tongue. A clinical diagnosis was metastasis from breast cancer or primary salivary gland tumor. Histologic diagnosis of the biopsy specimen was CEPA. She underwent partial glossectomy under general anesthesia. The final diagnosis of surgical materials was CEPA based on the differential diagnosis from breast carcinoma. She is alive bearing disseminated breast carcinoma without recurrence of CEPA at 6 months after glossectomy.

Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion Injury.

INTRODUCTION: The reduction of endogenous nitric oxide (NO) production during hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO synthase activity, leads to liver injury. We hypothesized that administration of an exogenous NO donor into the portal vein may ameliorate hepatic blood flow reduction after a period of ischemia. MATERIAL AND METHODS: A total of 90 min of ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs, using the Pringle method under sevoflurane anesthesia. All animals were administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after ischemia. The portal venous blood flow and hepatic artery blood flow were measured continuously using transonic flow probes attached to each vessel. Endogenous NO (NOx = NO2- + NO3-) production was measured every 10 min using a microdialysis probe placed in the left lobe of the liver. RESULTS: In the SNP group, portal venous flow remained unchanged and hepatic artery flow significantly increased compared to baseline. Although the production of liver tissue NOx transiently decreased to 60% after ischemia, its level in the SNP group remained higher than the control saline group. CONCLUSION: Regional administration of SNP into the portal vein increases hepatic arterial flow during ischemia reperfusion periods without altering mean systemic arterial pressure. We speculate that administration of an exogenous NO donor may be effective in preventing liver injury via preservation of total hepatic blood flow.

Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22µg sarin (GB), 100µg soman (GD), 210µg tabun (GA), 55µg cyclohexylsarin (GF), 4.8µg sulfur mustard, 390µg nitrogen mustard 1, 140µg of nitrogen mustard 2, 130µg nitrogen mustard 3, 120µg of 2-chloroacetophenone and 990µg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation.

Effect of vegf gene knockdown on growth of the murine sarcoma cell line MS-K.

The murine sarcoma cell line MS-K was previously established as a Ki-ras-positive cell line. Inoculation of this cell line under the flank of C3H/HeN mice results in the growth of large tumors with well-developed blood vessels within day 30 of transplantation without any metastasis because MS-K cells produce vascular endothelial growth factor (VEGF). To elucidate the role of VEGF in tumor formation in vivo, stable vegf-knockdown-MS-K clones were obtained using plasmid-based knockdown vectors. Interestingly, tumorigenesis was completely suppressed in a vegf-A-knockdown-MS-K clone [designated MS-K (A-KD)]. Proliferation and colony formation capacity of the MS-K (A-KD) cells in a semi-solid medium under low serum conditions was significantly lower than that of control MS-K (SCR) cells; however, the expression of vegf-receptor 1 (vegf-r-1) was not changed. Addition of the recombinant VEGF-A(165) partially restored the colony formation capacity of MS-K (A-KD) cells and caused the phosphorylation of VEGF-r-1 (Flt-1) in MS-K (Normal) cells. Furthermore, tumorigenicity of the vegf-r-1-knockdown-MS-K clone [designated MS-K (R1-KD)] had obviously delayed or strongly suppressed compared with the MS-K (Normal). These results indicate that Vascular endothelial growth factor-A, produced from MS-K, acts as a growth factor for MS-K cells itself and supports tumor formation in vivo by inducing the blood vessel formation.

Implications of measuring soluble receptor activators of nuclear factor-kappaB ligand and osteoprotegerin in bone metabolism of elderly women.

BACKGROUND/AIM: The discovery of a signaling system consisting of a soluble receptor activator of the NF-kappaB ligand (sRANKL) and its decoy receptor osteoprotegerin (OPG) has provided a valuable key to understanding the pathophysiology of the bone microenvironment. We conducted a cross-sectional study of the role of sRANKL and OPG levels as they relate to bone metabolism in elderly postmenopausal women with and without osteoporosis. SUBJECTS AND METHODS: Fifty-one elderly women with or without osteoporosis were enrolled in the study. Bone alkaline phosphatase, osteocalcin, urinary deoxypyridinoline and urinary type I collagen N-terminal telopeptide (NTx) were measured as bone metabolic markers. Serum levels of OPG and sRANKL were measured by sandwich enzyme-linked immunosorbent assay and the lumbar spine bone mineral density (LSBMD) with dual-energy X-ray absorptiometry. Furthermore, we compared the sRANKL and OPG levels in elderly women with and without vertebral fractures (VFs). RESULTS: In elderly postmenopausal women, there was a significant positive association between OPG levels and the T score and Z score of LSBMD (r = 0.345 and p = 0.014 for T score; r = 0.438 and p = 0.001 for Z score). sRANKL levels were not significantly correlated with T score, Z score of LSBMD, or any of the four bone metabolic markers. There were no significant differences in the sRANKL levels among the three groups (normal bone mineral density, osteopenia, and osteoporosis), but a trend toward a higher value in the osteoporosis group. The sRANKL/OPG ratio was negatively correlated with the T score and Z score of LSBMD (r = -0.336, p = 0.017; r = -0.384, p = 0.006, respectively), but not with any of the four bone metabolic markers. OPG levels in elderly women with VFs were lower than in those without VFs (p = 0.05). Multiple regression analysis showed that OPG and NTx are contributing factors to bone loss in elderly women (p = 0.014 and 0.012, respectively). CONCLUSION: The OPG level provides a good predictor of osteoporosis as well as NTx in elderly women; additionally, the findings suggest that OPG might protect elderly women from bone loss or fractures.

Apolipoprotein E regulates primary cultured human mesangial cell proliferation.

BACKGROUND: The role of apolipoprotein (apo) E in kidney disease is still unclear. Animal studies have been performed, but it is doubtful if the conclusions are applicable to human beings. The objective of this study was to determine how apo E acts on human kidneys using primary cultured normal human mesangial cells (NHMCs) rather than animals used in previous studies. METHODS: apo E and its isoforms E2, E3 and E4, or combinations with apo B were cocultured with primary NHMCs in serum-free medium. Premix WST-1 Cell Proliferation Assay System and DNA-Prep Reagent System were used to measure the proliferation and apoptosis of NHMCs, respectively. RESULTS: (1) apo E itself increased NHMC proliferation at 24 h of culture, while it inhibited this proliferation after 48 h. (2) At 72 h of culture, apo E alone inhibited NHMC proliferation at concentrations higher than 0.78 microg/ml in concentration-dependent manner. (3) When co-cultured with both apo E and apo B, NHMC proliferation was higher than that with apo E alone and lower than that with apo B alone. (4) At 72 h of culture, apo E2, E3 and E4 inhibited NHMC proliferation at different intensities, with no proliferative effect observed. (5) Neither apo E nor apo B caused NHMC apoptosis. CONCLUSION: apo E regulates primary NHMC proliferation by (1) inhibiting NHMC proliferation or reducing NHMC proliferation induced by apo B, which implies that apo E has a protective effect on the kidney, and (2) increasing the proliferation under certain conditions.

Reproductive characteristics of the feral raccoon (Procyon lotor) in Hokkaido, Japan.

Reproduction of feral raccoons (Procyon lotor) in Hokkaido, Japan, was examined during a 2-year period by analysis of placental scars or fetuses in the uterus. Of 242 collected females, 69 (29%) were juveniles, 71 (29%) yearlings, and 102 (42%) adults. The pregnancy rate averaged 66% in yearlings and was significantly lower than the 96% average observed in adults (p<0.01). Litter size ranged from 1 to 7 offspring per female, and averaged 3.6 in yearlings and 3.9 in adults. There was no significant difference in mean litter size between yearlings and adults. In Hokkaido, the raccoon mating season peaked in February and the majority of litters were born between March and May, similar to patterns described in North America, but some females mated in summer. The reproductive potential of feral raccoons in Hokkaido was similar to that reported in North America. The recent increase in raccoon numbers can be explained by their high productivity. Harvest data suggest that hunting pressure on juveniles is lower than that for older age classes when using box traps in summer. In order to reduce the feral raccoon population, alternative hunting methods that increase juvenile mortality rates are needed.

Growth pattern and seasonal weight changes of the feral raccoon (Procyon lotor) in Hokkaido, Japan.

The growth pattern and seasonal weight fluctuations of feral raccoons in Hokkaido were evaluated between 1999 and 2001. The growth rates inbody length and body weight were described for juveniles (young of the year) and yearlings (animals born in the previous season) using the Gompertz growth model. The asymptotic body sizes for males were greater than those for females. Young raccoons born during spring in the study area could potentially grow up to their asymptotic size at the beginning of their first winter, but they would not reach their full adult sizes until at least their second fall. Adult raccoons (animals > or = 2 -year-old) had seasonal weight fluctuations with annual weight loss of 25% to 28% of mean maximum weights in west-central Hokkaido, but these result would be an underestimate of the degree of annual weight fluctuations. Juvenile raccoons can be distinguished from the older animals by measuring body length or body weight during fall in Hokkaido.