As a part of our ongoing search for a safe and efficient anti-tumor vaccine, we attempted to determine whether the molecular nature of certain tumor antigens would influence immune responses against tumor cells. As compared with freeze-thawed or formaldehyde-fixed tumor antigens, heat-denatured tumor antigens elicited profound anti-tumor immune responses and greatly inhibited the growth of live tumor cells. The heat-denatured tumor antigens induced a substantial increase in the anti-tumor CTL response in the absence of any adjuvant material. This response appears to be initiated by strong activation of the antigen-presenting cells, which may recognize heat-denatured protein antigens. Upon recognition of the heat-denatured tumor antigens, macrophages and dendritic cells were found to acutely upregulate the expression of co-stimulatory molecules such as B7.2, as well as the secretion of inflammatory cytokines such as IL-12 and TNF-alpha. The results of this study indicate that heat-denatured tumor extracts might elicit protective anti-tumor adaptive immune responses and also raise the possibility that a safe and efficient adjuvant-free tumor vaccine might be developed in conjunction with a dendritic cell-based tumor vaccine.
Adjuvants, Immunologic ; Animals ; Antibodies, Neoplasm/immunology ; Antibody Specificity/immunology ; Antigens, Neoplasm/immunology ; Cancer Vaccines/*immunology ; Cell Line, Tumor ; Cell Proliferation ; Cytokines/biosynthesis ; Cytotoxicity, Immunologic/immunology ; Dendritic Cells/immunology ; *Hot Temperature ; Immunity, Cellular/immunology ; Immunization ; Immunologic Memory/immunology ; Macrophages, Peritoneal/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms/*immunology/*pathology ; Survival Analysis ; T-Lymphocytes, Cytotoxic/immunology

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Acute Kidney Injury/diagnosis/etiology/*metabolism/physiopathology/therapy ; Adolescent ; Adult ; Biomarkers/analysis ; Biopsy ; Down-Regulation ; Female ; Glucuronidase/*analysis ; Humans ; Immunohistochemistry ; Kidney/*chemistry/pathology/physiopathology ; Kidney Tubular Necrosis, Acute/diagnosis/etiology/*metabolism/physiopathology/therapy ; Male ; Middle Aged ; Necrosis ; Predictive Value of Tests ; Recovery of Function ; Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; Young Adult

A 59-year-old man visited our hospital for facial edema and muscle weakness in both lower extremities. He was diagnosed with dermatomyositis (DM) about 1 year previously, and sudden development of proteinuria was noted. Renal biopsy revealed focal global and segmental glomerulosclerosis with slight mesangial expansion. Glomerulonephritis is rare in DM. According to our review of related literature, membranous nephropathy is the main type of DM, while mesangial proliferative glomerulonephritis is the most common type in polymyositis. The mechanism underlying the association between DM and glomerulonephritis remains to be elucidated. We herein report a case of DM associated with focal segmental glomerulosclerosis, which has not been reported previously.
Biopsy ; Dermatomyositis ; Edema ; Glomerulonephritis ; Glomerulonephritis, Membranous ; Glomerulosclerosis, Focal Segmental ; Humans ; Lower Extremity ; Middle Aged ; Muscle Weakness ; Polymyositis ; Proteinuria

Lactococcus lactis (L. lactis) is an important gram-positive bacterium in dairy products. It is a rare cause of opportunistic infections with only four cases of Lactococcus peritoneal dialysis (PD) peritonitis reported in the literature. In Korea, L. lactis infection was first reported in a liver abscess patient in 2010; however, PD peritonitis with Lactococcus has not been reported in Korea. Recently, we experienced a case of Lactococcus-associated polymicrobial PD peritonitis. The patient was initially managed with broad-coverage antibiotics; however, owing to a poor response, the PD catheter was removed and the patient was switched to hemodialysis. We discuss this case and review the literature.
Anti-Bacterial Agents ; Catheters ; Dairy Products ; Humans ; Korea ; Lactococcus ; Lactococcus lactis ; Liver Abscess ; Opportunistic Infections ; Peritoneal Dialysis ; Peritonitis ; Renal Dialysis