Liver, muscle, and adipose tissue are resistant to insulin action in type 2 diabetes. In spite of intensive studies, few diabetic genes have been identified. Recently, mitochondrial impairment has been observed in the muscle and adipose tissues of type 2 diabetes patients, implying that mitochondrial dysfunction could be a pivotal factor in type 2 diabetes. Here, we discuss mitochondrial malfunction leading to type 2 diabetes.
Adipose Tissue ; Humans ; Insulin ; Liver ; Mitochondria*

Liver, muscle, and adipose tissue are resistant to insulin action in type 2 diabetes. In spite of intensive studies, few diabetic genes have been identified. Recently, mitochondrial impairment has been observed in the muscle and adipose tissues of type 2 diabetes patients, implying that mitochondrial dysfunction could be a pivotal factor in type 2 diabetes. Here, we discuss mitochondrial malfunction leading to type 2 diabetes.
Adipose Tissue ; Humans ; Insulin ; Liver ; Mitochondria*

No abstract available.
Dilatation* ; Esophageal Perforation*

Previous reports raised question as to whether 8-chloro-cyclic adenosine 3,5-monophosphate (8-Cl-cAMP) is a prodrug for its metabolite, 8-Cl-adenosine which exerts growth inhibition in a broad spectrum of cancer cells. The present study was carried out to clarify overall cellular affects of 8-Cl-cAMP and 8-Cl-adenosine on SK-N-DZ human neuroblastoma cells by ystematically characterizing gene expression using radioactive human cDNA microarray. Microarray was prepared with PCR-amplified cDNA of 2,304 known genes spotted on nylon membranes, employing (1)P-labeled cDNAs of SK-N-DZ cells as a probe. the expression levels of approximately 100 cDNAs, representing about 8% of the total DNA elements on the array, were altered in 8-Cl-adenosine- or 8-Cl-cAMP-treated cells, respectively. The genome-wide expression of the two samples exhibited partial overlaps; different sets of up-regulated genes but the same set of down-regulated genes. 8-Cl-adenosine treatment up- egulated genes involved in differentiation and development (LIM protein, connexin 26, neogenin, neurofilament triplet L protein and p21( WAF1/CIP1)) and immune response such as natural killer cells protein 4, and down-regulated ones involved in proliferation and transformation (transforming growth factor-beta, DYRK2, urokinase-type plasminogen activator and proteins involved in transcription and translation) which were in close parallel with those by 8-Cl-cAMP. Our results indicated that the two drugs shared common genomic pathways for the down-regulation of certain genes, but used distinct pathways for the up-regulation of different gene clusters. Based on the findings, we suggest that the anti-cancer activity of 8-Cl-cAMP results at least in part through 8-Cl-adenosine. Thus, the systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in anticancer activities of chemotherapeutics.
2-Chloroadenosine/*analogs & derivatives/chemistry/*pharmacology ; 8-Bromo Cyclic Adenosine Monophosphate/*analogs & derivatives/chemistry/*pharmacology ; Antineoplastic Agents/chemistry/*pharmacology ; Blotting, Western ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*drug effects ; Genome, Human ; Human ; Neuroblastoma/*genetics ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Tumor Cells, Cultured ; Up-Regulation/drug effects

Mitochondrial biogenesis is known to accompany adipogenesis to complement ATP and acetyl-CoA required for lipogenesis. Here, we demonstrated that mitochondrial proteins such as ATP synthase alpha and beta, and cytochrome c were highly expressed during the 3T3-L1 differentiation into adipocytes. Fully-differentiated adipocytes showed a significant increase of mitochondria under electron microscopy. Analysis by immunofluorescence, cellular fractionation, and surface biotinylation demonstrated the elevated levels of ATP synthase complex found not only in the mitochondria but also on the cell surface (particularly lipid rafts) of adipocytes. High rate of ATP (more than 30 micrometer) synthesis from the added ADP and Pi in the adipocyte media suggests the involvement of the surface ATP synthase complex for the exracellular ATP synthesis. In addition, this ATP synthesis was significantly inhibited in the presence of oligomycin, an ATP synthase inhibitor, and carbonyl cyanide m-chlorophenylhydrazone (CCCP), an ATP synthase uncoupler. Decrease of extracellular ATP synthesis in acidic but not in basic media further indicates that the surface ATP synthase may also be regulated by proton gradient through the plasma membrane.
Adenosine Triphosphate/analysis/*biosynthesis ; Adipocytes/*enzymology/ultrastructure ; Animals ; Cell Differentiation/physiology ; Cell Membrane/chemistry ; Cells, Cultured ; Humans ; Membrane Microdomains/chemistry/*enzymology ; Mice ; Mitochondria/metabolism/ultrastructure ; Mitochondrial Proton-Translocating ATPases/analysis/*physiology ; Research Support, Non-U.S. Gov't

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to significant global casualties. This study examines the postoperative impact of COVID-19 on patients who underwent gastrointestinal surgery, considering their heightened vulnerability to infections and increased morbidity and mortality risk. Methods: This retrospective observational study was conducted at a tertiary center and patients who underwent gastrointestinal surgery between January 2022 and February 2023 were included. Postoperative COVID-19 infection was defined as the detection of severe acute respiratory syndrome coronavirus 2 RNA by RT-PCR within 14 days after surgery. Propensity score matching was performed including age, sex, American Society of Anesthesiology physical status classification, and emergency operation between the COVID-19-negative (–) and -positive (+) groups. Results: Following 1:2 propensity score matching, 21 COVID-19(+) and 42 COVID-19(–) patients were included in the study. In the COVID-19(+) group, the postoperative complication rate was significantly higher (52.4% vs. 23.8%, P = 0.023).Mechanical ventilator requirement, intensive care unit (ICU) admission, and readmission rate did not significantly differ between the 2 groups. The median length of ICU (19 days vs. 4 days, P < 0.001) and hospital stay (18 vs. 8 days, P = 0.015) were significantly longer in the COVID-19(+) group. Patients with COVID-19 had a 2.4 times higher relative risk (RR) of major complications than patients without COVID-19 (RR, 2.37; 95% confidence interval, 1.254–4.467; P = 0.015). Conclusion COVID-19 infection during the postoperative period in gastrointestinal surgery may have adverse outcomes which may increase the risk of major complications. Preoperative COVID-19 screening and protocols for COVID-19 prevention in surgical patients should be maintained.

PURPOSE: After the first umbilical cord blood transplantation was reported in 1988, the use of cord blood as a source of hematopoietic stem cell instead of allogeneic bone marrow increased surprisingly and currently in the worldwide, more than 1,000 cases of cord blood transplantation were reported. We, herein, report the nine cases of cord blood transplants in Korea (Jul. 1996 - Jan. 1999). METHODS: The study of childhood cord blood transplantation from July 1996 to January 1999 were analyzed. 1. Patient population 1) Diseases on patients receiving umbilical cord blood transplantation included 3 aplastic anemia (1 Fanconi's anemia), 3 acute myelogenous leukemia, 1 acute lymphoblastic leukemia, 1 chronic myelogenous leukemia and 1 Gaucher disease. 2) Patients included 5 males and 4 females and were aged a range of 1~15 years (median 5 years), and a range of body weight at transplantation was 10 kg~50 kg (median 20 kg). 3) Four cases were used related cord blood as a source of stem cells for the transplant and 5 cases were used unrelated cord blood. In unrelated cord blood transplantation, cord blood was provided by Catholic Cord Blood Bank in 4 cases and by Samsung Medical Center in 1 case. 4) Only one case had a HLA-compatible cord blood graft. Two cases had 1 HLA antigen disparate grafts, 4 cases had 2 HLA antigen disparate grafts and 2 cases had 3 HLA antigen disparate grafts. 2. Transplantation Procedures 1) The total number of nucleated cells infused was 0.2+/-13x107/kg (median number 4.4x107/kg) and the number of CD34+ cells was 0.4+/-9.4x105/kg (median number 3.3x105/kg). 2) Patients received a variety of preparative regimens that varied with the disease and disease state at time of transplantation. All patients received ATG as a part of preparation. 3) While several regimens were used for prophylaxis of GVHD, 3 patients received cyclosporine A and methylprednisolone, 3 patients received cyclosporine and methotrexate, 2 patients received cyclosporine A alone and 1 patients received cyclosporine A, methtrexate and prednisolone. RESULTS: 1. The 6 cases of total 9 cases have successed to engraft persistently and the rate of engraftment was 67%. Two of 3 cases in severe aplastic anemia failed to engraft, 1 case failed to transplant due to rejection of grafts. All 5 cases in leukemia have successed to engraft. 2. On 6 cases of engraftment, the time to achieve an absolute neutrophil count (ANC)> or =0.5x109/L, > or = 1.0x109 /L was 10~37 days (median 13 days) and 11~40 days (median 14 days), respectively, and platelet count > or = 30x109/ L was 15~114 days (19.5 days). 3. Two of evaluable 7 cases had grade II acute GVHD and cured by steroid. 4. Seven of 9 cases (77.8%) survive (2~32 months; median 11 months) after transplantation. Five of 7 surviving cases (55.6%) live with disease-free (2~11 months; median 5 months). Four of 5 patients with leukemia (80%) live without relapse (2~11 months (median 5months). 5. The complications associated with cord blood transplantation were 2 sepsis, 2 CMV infections, 1 hemorrhagic cystitis and venoocclusive disease. 6. Two of 9 patients died of 1 graft failure and 1 venoocclusive disease. CONCLUSION: Cord blood transplantation is curative strategy for the treatment of children with malignant disease and inborn error of metabolism. For aplastic anemia and myelodysplastic syndrome, the role of cord blood transplantation would be investigated.
Anemia, Aplastic ; Body Weight ; Bone Marrow ; Child ; Cord Blood Stem Cell Transplantation* ; Cyclosporine ; Cystitis ; Female ; Fetal Blood* ; Gaucher Disease ; Hematopoietic Stem Cells ; Humans ; Korea ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Male ; Metabolism ; Methotrexate ; Methylprednisolone ; Myelodysplastic Syndromes ; Neutrophils ; Platelet Count ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prednisolone ; Recurrence ; Sepsis ; Stem Cells ; Transplantation ; Transplants ; Umbilical Cord*

Extracellular ATP (exATP) has been known to be a critical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly increased with the high level of adenylate kinase 1 (AK1) and ATP synthase beta during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase beta in C2C12 myotubes, suggesting that AK1 is required for exATP synthesis in myotubes. However, membrane-bound AK1beta was not involved in exATP synthesis because its expression level was decreased during myogenesis in spite of its localization in the lipid rafts that contain various kinds of receptors and mediate cell signal transduction, cell migration, and differentiation. Interestingly, cytoplasmic AK1 was secreted from C2C12 myotubes but not from C2C12 myoblasts. Taken together all these data, we can conclude that AK1 secretion is required for the exATP generation in myotubes.
Adenosine Triphosphate/*biosynthesis ; Adenylate Kinase/*metabolism ; Animals ; Cell Line ; Extracellular Space/metabolism ; Isoenzymes/*metabolism ; Mice ; Muscles/cytology/*metabolism

BACKGROUND: Although effective antifungal agents for the treatment of candidemia have recently been introduced, the mortality rate attributed to candidemia remains high (19~49%). OBJECTIVE: This study aimed at evaluating the risk factors for mortality in patients with candidemia and at assessing the usefulness of a Candida Score in these patients. METHODS: A cohort of patients with positive blood cultures for Candida species was retrospectively analyzed at Soonchunhyang University Hospital, a 750-bed teaching hospital, from May 2003 to February 2012. The Candida Score was calculated by assigning 1 point to any of total parenteral nutrition (TPN), surgery, or multifocal Candida species colonization, and 2 points to severe sepsis. RESULTS: Sixty patients (68.3% men; mean age (standard deviation [SD]), 61.8 [18.9] years) with blood cultures positive for Candida species were identified. Most patients had been admitted to an intensive care unit (48 [80%]), were receiving broad-spectrum antibiotics (37 [61.7%]), had TPN (29 [48.3%]), had diabetes mellitus (23 [38.3%]), and were receiving hemodialysis (10 [16.7%]). The mean (SD) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19.60 (8.8). Twenty-three patients (38.3%) had a Candida Score >2.5. The Candida species causing infection included C. albicans (41 [68.3%]), C. tropicalis (7 [11.7%]), C. parapsilosis (4 [6.7%]), C. krusei (3 [5%]), C. glabrata (3 [5%]), C. guilliermondii (1 [1.7%]), and C. catenulata (1 [1.7%]). Only 32 patients (53.3%) received adequate antifungal treatment. The candidemia-related mortality rate was 61.7% (n = 37 patients). Multivariate logistic regression analysis demonstrated that a high APACHE II score (adjusted odds ratio [aOR], 1.2; 95% confidence interval [95% CI], 1.0~1.3; p = 0.01), presence of a malignancy (aOR, 14.8; 95% CI, 2.5~88.0; p = 0.003), and treatment with an antifungal agent (aOR, 0.2; 95% CI, 0.0~1.0; p = 0.048) were associated with disease-related mortality. CONCLUSION: The risk factors for mortality in patients with candidemia are a high APACHE II scores and presence of a malignancy. However, the sensitivity of the Candida Score was not high (38.3%). New methods to rapidly identify candidemia and avoid delays in treatment with appropriate antifungal therapy are needed.
Anti-Bacterial Agents ; Antifungal Agents ; APACHE ; Blood ; Candida* ; Candidemia* ; Cohort Studies ; Colon ; Diabetes Mellitus ; General Surgery ; Hospitals, Teaching ; Humans ; Intensive Care Units ; Logistic Models ; Male ; Methods ; Mortality* ; Odds Ratio ; Parenteral Nutrition, Total ; Renal Dialysis ; Retrospective Studies ; Risk Factors*

OBJECTIVE: The aim of this study was to determine the efficacy of the use of an ultrasound-guided fine-needle aspiration biopsy (US-FNAB) to diagnose thyroid nodules smaller than 5 mm in the maximum diameter and to evaluate pathological findings of small thyroid malignancies. MATERIALS AND METHODS: From May 2007 to April 2008, we evaluated the findings of US-FNABs of small thyroid nodules less than 5 mm in the maximum diameter. The cytopathological findings were retrospectively reviewed and the diagnostic performance of the use of an US-FNAB was examined in all patients. RESULTS: Of 201 small thyroid nodules in 180 patients, there were 162 adequate specimens (81%). Among 180 patients, 75 patients underwent thyroid surgery and 50 malignant and 33 benign nodules were identified based on a pathological examination. All small malignant thyroid nodules were identified as papillary thyroid microcarcinomas (PTMCs). There were 34 (55%) true positive, 0 (0%) false positive, 23 (37%) true negative and five (8%) false negative results for malignancy after performing a first US-FNAB in 62 surgically confirmed nodules. The sensitivity (87%), specificity (100%), positive predictive value (100%), negative predictive value (82%), accuracy (92%), false positive rate (0%) and false negative rate (8%) for an US-FNAB were determined. In 23 patients with a primary PTMC, capsular invasion (9%, 2 of 23), a perithyroidal lymph node metastasis (30%, 7 of 23), the rate of multifocality (9%, 2 of 23) and bilaterality (4%, 1 of 23) were also determined. CONCLUSION: An US-FNAB of thyroid nodules smaller than 5 mm in the maximum diameter is an effective diagnostic procedure.
Adolescent ; Adult ; Aged ; *Biopsy, Fine-Needle ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Neoplasms/*pathology/ultrasonography ; Thyroid Nodule/*pathology/ultrasonography ; *Ultrasonography, Interventional