Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8x10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.
Cytokines ; Granulocyte Colony-Stimulating Factor ; Granulocytes ; Humans ; Length of Stay ; Leukocytes ; Leukocytosis ; Neck ; Prognosis ; Pyelonephritis ; Thyroid Gland ; Thyroid Neoplasms

Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8x10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.
Cytokines ; Granulocyte Colony-Stimulating Factor ; Granulocytes ; Humans ; Length of Stay ; Leukocytes ; Leukocytosis ; Neck ; Prognosis ; Pyelonephritis ; Thyroid Gland ; Thyroid Neoplasms

The use of high throughput screening (HTS) in drug development is principally for the selection new drug candidates or screening of chemical toxicants. This system minimizes the experimental environment and allows for the screening of candidates at the same time. Umbilical cordderived stem cells have some of the characteristics of fetal stem cell and have several advantages such as the ease with which they can be obtained and lack of ethical issues. To establish a HTS system, optimized conditions that mimic typical cell culture conditions in a minimal space such as 96 well plates are needed for stem cell growth. We have thus established a novel HTS system using human umbilical cord derived-mesenchymal stem cells (hUC-MSCs). To determine the optimal cell number, hUC-MSCs were serially diluted and seeded at 750, 500, 200 and 100 cells per well on 96 well plates. The maintenance efficiencies of these dilutions were compared for 3, 7, 9, and 14 days. The fetal bovine serum (FBS) concentration (20, 10, 5 and 1%) and the cell numbers (750, 500 and 200 cells/well) were compared for 3, 5 and 7 days. In addition, we evaluated the optimal conditions for cell cycle block. These four independent optimization experiments were conducted using an MTT assay. In the results, the optimal conditions for a HTS system using hUC-MSCs were determined to be 300 cell/well cultured for 8 days with 1 or 5% FBS. In addition, we demonstrated that the optimal conditions for a cell cycle block in this culture system are 48 hours in the absence of FBS. In addition, we selected four types of novel small molecule candidates using our HTS system which demonstrates the feasibility if using hUC-MSCs for this type of screen. Moreover, the four candidate compounds can be tested for stem cell research application.
Cell Count ; Cell Culture Techniques ; Cell Cycle ; Fetal Stem Cells ; Humans ; Hydrazines ; Mass Screening ; Mesenchymal Stromal Cells ; Seeds ; Stem Cell Research ; Stem Cells ; Umbilical Cord

The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1+ subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.
Animals ; Ataxin-1/*analysis ; Bone Marrow Cells/*cytology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Female ; Hepatocytes/*cytology ; Mice ; Mice, Inbred BALB C

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.
Adult ; Age Distribution ; Aged ; Anti-Bacterial Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Biomarkers/*blood ; Carcinoma, Hepatocellular/blood ; Diagnosis, Differential ; Female ; Humans ; Liver Cirrhosis/blood ; Liver Diseases, Alcoholic/*blood ; Liver Neoplasms/blood ; Male ; Matched-Pair Analysis ; Middle Aged ; Multivariate Analysis ; Protein Precursors/*blood ; Prothrombin/analysis ; Retrospective Studies ; Sex Distribution ; gamma-Glutamyltransferase/blood

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.
Adult ; Age Distribution ; Aged ; Anti-Bacterial Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Biomarkers/*blood ; Carcinoma, Hepatocellular/blood ; Diagnosis, Differential ; Female ; Humans ; Liver Cirrhosis/blood ; Liver Diseases, Alcoholic/*blood ; Liver Neoplasms/blood ; Male ; Matched-Pair Analysis ; Middle Aged ; Multivariate Analysis ; Protein Precursors/*blood ; Prothrombin/analysis ; Retrospective Studies ; Sex Distribution ; gamma-Glutamyltransferase/blood

Opisthorchis viverrini infection was found to be highly prevalent in 3 riverside villages (Ang Svay Chek A, B, and C) of the Prey Kabas District, Takeo Province. This area is located in the southern part of Cambodia, where the recovery of adult O. viverrini worms was recently reported. From May 2006 until May 2010, fecal examinations were performed on a total of 1,799 villagers using the Kato-Katz thick smear technique. In the 3 villages, the overall positive rate for helminth eggs ranged from 51.7 to 59.0% (av. 57.4%), and the percentage positive for O. viverrini was 46.4-50.6% (47.5%). Other helminths detected included hookworms (13.2%), echinostomes (2.9%), Trichuris trichiura (1.3%), Ascaris lumbricoides (0.6%), and Taenia spp. (0.06%). The prevalence of O. viverrini eggs appeared to reflect a lower infection in younger individuals (<20 years) than in the adult population (>20 years). Men (50.4%) revealed a significantly higher (P=0.02) prevalence than women (44.3%). The Ang Svay Chek villages of the Prey Kabas District, Takeo Province, Cambodia have been confirmed to be a highly endemic area for human O. viverrini infection.
Adolescent ; Adult ; Aged, 80 and over ; Animals ; Cambodia/epidemiology ; Child ; Child, Preschool ; Coinfection/epidemiology ; Feces/parasitology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Opisthorchiasis/*epidemiology ; Opisthorchis/*isolation & purification ; Prevalence ; Rural Population ; Young Adult