Pseudohypoparathyroidism is a medical disorder characterized by a complex disorder of renal resistance to parathyroid hormone and the mechanism underlying the disease is still unclear. The authors described two cases of pseudohypoparathyroidism in sibling,who had metabolic anomalies(hypocalcemia and hyperphosphatemia, high circulatin immunoreactive PTH)and basal ganglia calcification. Bilateral basal ganglia calcifications, which was not visible on plain skull film, was detected by CT scan of brain MRI. We report these cases with a review of related literatures.
Basal Ganglia ; Brain ; Humans ; Hyperphosphatemia ; Magnetic Resonance Imaging ; Parathyroid Hormone ; Pseudohypoparathyroidism* ; Siblings* ; Skull ; Tomography, X-Ray Computed

Antidiuretic action of oxytocin is confirmed by in vitro study using with rat IMCD. Vasopressin is elevated in edematous disorders and may play a pathogenetic role in the formation of edema. If oxytocin plays a sirnilar role to vasopressin in water disturbances in human, oxytocin may change as the same way as vasopressin. To verify a role of oxytocin in the regulation of water balance in human, we measured plasma and urine oxytocin with vasopressin by radioimmunoassay in thirteen patients with generalized edema (8 nephrotic syndrome, 3 liver cirrhosis, 2 acute renal failure) before and after control of edema. And they were compared them with those of seven normal controls. Plasma oxytocin level correlated with plasma vasopressin level (r=0.543: P<0.05) and urinary oxytocin level correlated linearly with urinary vaso-pressin (r=0.983, P<0.01). After control of edema, body weight of patients decreased from 65+/- 2 to 58+/-2kg and fractional excretion of sodium decreased from 3.3+/-1.1 to 1.2+/-0.696 (P<0.05). There were no significant changes in serum and urine Na, osmolality, free water clearance, plasma renin activity, aldosterone and norepinephrine. In conclusion, oxytocin was elevated in edematous disorders, and may participate in formation of edema similar to vasopressin.
Aldosterone ; Animals ; Body Weight ; Edema ; Humans ; Liver Cirrhosis ; Nephrotic Syndrome ; Norepinephrine ; Osmolar Concentration ; Oxytocin* ; Plasma ; Radioimmunoassay ; Rats ; Renin ; Sodium ; Vasopressins* ; Water*

STUDY DESIGN: An in-vitro experiment using human ligamentum flavum (LF) and the adnovirus-BMP-2 construct, Ad/BMP-2. OBJECTIVES: To determine the dual roles of LF as an osteoinductive agent and carrier for ex-vivo gene transfer. SUMMARY OF LITERATURE REVIEW: LF is known to have osteogenic potential. Pathologically, ossified LF may cause myelopathy and radiculopathy. BMP-2 is known as an important factor in the differentiation, and maintenance, of osteoblast phenotypes. Ex-vivo gene transfer, using human LF for spinal fusion, has never been attempted before. MATERIALS AND METHODS: The LF cells were cultured from the degenerated LF of spinal stenosis patients. An adenovirus construct, containing BMP-2 cDNA (Ad/BMP-2), was also produced. The LF cell cultures were exposed to the adenoviral construct. The Osteocalcin expression was analysed by Western blot analysis. The osteocalcin and BMP-2 mRNA expressions were analysed by RT-PCR. Bone formation was assessed by alkaline phosphatase and Von Kossa stains. RESULTS: The LF cell cultures, with Ad/BMP-2, showed transgene expression in the Western blot analysis. Also, the cultures exhibited the mRNA expressions of both osteocalcin and BMP-2, in a dose-dependent manner. The LF cultures, with Ad/BMP-2, demonstrated alkaline phosphatase expression and bone nodule formations from the Von Kossa staining. CONCLUSION: The genetically modified LF strongly induced osteogenesis, which can be used during a spinal fusion, as an osteoinductive agent and carrier, for ex-vivo gene transfer.
Adenoviridae ; Alkaline Phosphatase ; Blotting, Western ; Cell Culture Techniques ; Coloring Agents ; DNA, Complementary ; Humans ; Ligamentum Flavum* ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Phenotype ; Radiculopathy ; RNA, Messenger ; Spinal Cord Diseases ; Spinal Fusion* ; Spinal Stenosis ; Transgenes

BACKGROUND: Hepatitis B Virus (HBV) is a major risk factor for hepatocellular carcinoma, and about five to six percents of people are infected with HBV in Korea. Lamivudine is a first-line drug having good control against HBV replication, but long-term treatment by lamivudine induces drug resistance. We analyzed the rate of HBV resistance mutation for lamivudine by direct sequencing and CLIP sequencing. METHODS: HBV DNA was isolated from 371 patients who were in treatment, or were planning to be treated with lamivudine. The direct sequencing for lamivudine resistance mutation was performed in 371 patients and CLIP sequencing in 138 patients. We analyzed the mutation rate and the type of mutations for lamivudine resistance. RESULTS: The mutation was detected in 203 patients (54.7%) and (CTG) L180M (ATG) was most common (36.1%) followed by (ATG) M204I (ATT) (29.9%) and (ATG) M204V (GTG) (18.6%). According to the duration of treatment, mutation rates were as follows: 45.3% for less than one year, 71.7% for one to two years, 66.7% for two to three years, and 87.9% for more than three years. The results of the direct sequencing and CLIP sequencing agreed in 134 out of 138 patients, in whom both tests were performed. CONCLUSIONS: We confirmed that HBV mutation rates for lamivudine resistance increased as the lamivudine treatment period increased. The lamivudine resistance mutations detected were similar to the previous studies. CLIP sequencing showed good correlation with the direct sequencing and gave additional mutation information. CLIP sequencing is a promising tool for the detection of lamivudine resistance mutation in HBV that can assist treatment plans.
Carcinoma, Hepatocellular ; DNA ; Drug Resistance ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Korea ; Lamivudine ; Mutation Rate ; Risk Factors

STUDY DESIGN: In-vitro experiments using human mesenchymal stem cells (MSCs), intervertebral disc (IVD) cells and type 5 adenovirus/transforming growth factor-beta1 construct (Ad/TGF-beta1). OBJECTIVES: To determine the effect of MSC-based gene therapy for matrix regeneration of IVD cells. SUMMARY OF LITERATURE REVIEW: MSCs are known to be multipotent in tissue regeneration. In degeneration of IVD, cellular replacement with genetic modification other than that of IVD cells may prove an enhanced mechanism for the regeneration of MATERIALS AND METHODS: MSCs and IVD cells were cultured and an adenovirus construct containing TGF-beta1 cDNA (Ad/TGF-beta1) was also produced. In the first step, the MSCs were transduced with Ad/TGF-beta1, then mixed with IVD cells in various proportions and three dimensionally cultured. [methyl-(3)H]Thymidine and [(35)S]Sulfur incorporation for DNA and proteoglycan synthesis, respectively, were measured. RT-PCR was performed to assess the aggrecan and collagen types I and II mRNA RESULTS: Mixed cultures of MSC and IVD cells showed relatively similar amounts of newly synthesized proteoglycan compared with cultures of IVD cells only. In mixed cultures transduced with Ad/TGF-beta1, there were significant decreases in newly synthesized proteoglycan with increasing the proportions of MSCs, which was also found with the aggrecan and collagen type II mRNA expressions. However, the collagen type I mRNA expression increased with increased proportions of MSCs transduced with Ad/TGF-beta1. CONCLUSION: Cell therapy with MSCs and IVD cells provided a mechanism for cellular augmentation. However, MSC-based gene therapy coupled with IVD cells did not maintain a chondrogenic phenotype.
Adenoviridae ; Aggrecans ; Cell- and Tissue-Based Therapy ; Collagen ; Collagen Type I ; Collagen Type II ; DNA ; DNA, Complementary ; Genetic Therapy* ; Humans ; Intervertebral Disc ; Mesenchymal Stromal Cells ; Phenotype ; Proteoglycans ; Regeneration ; RNA, Messenger ; Stem Cells* ; Transforming Growth Factor beta1

PURPOSE: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. MATERIALS AND METHODS: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Omega, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). RESULTS: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05). CONCLUSION: EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
Adult ; Aspirin/pharmacology ; Cell Proliferation/*radiation effects ; Collagen/metabolism ; Dinoprostone/metabolism ; *Electromagnetic Fields ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Intervertebral Disk/*pathology/radiation effects ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Tetrazolium Salts/pharmacology ; Thiazoles/pharmacology ; omega-N-Methylarginine/pharmacology

Ael is a rare blood type which has the least amount of A antigen among A subgroups. It can be detected by special tests performed to resolve the discrepancy between red cell and serum typing in routine serological typing. The presence of A antigen on Ael red cell is demonstrable only by adsorption and elution tests. An Ael individual does not secret A substance in the saliva and may have anti-A antibody in the serum which is usually less reactive with the reagent red cells than anti-B antibody. In Korea, Ael02 has been reported more frequently than other Ael alleles. We report a case of Ael02/O04 who presented as typical phenotype O with strong anti-A and anti-B antibodies and no A antigen detected even by adsorption and elution tests. The case has been proved to be Ael02/O04 by direct sequencing analysis. In individuals with history of discrepancies in the results of ABO phenotyping, ABO genotyping is needed for an accurate evaluation of their blood type.
ABO Blood-Group System/classification/*genetics ; Alleles ; Child ; Genotype ; Heterozygote ; Humans ; Male ; Pedigree ; Phenotype ; Sequence Analysis, DNA

Alcohol can cause rhabdomyolysis by either direct toxicity or associated metabolic abnormality such as hypophosphatemia and hypokalemia. It can also predispose to or cause trauma, seizures, or coma- induced ischemic pressure necrosis. In order to investigate the clinical features of acute renal failure caused by alcohol induced rhabdomyolysis, we reviewed the medical records of the 12 patients. All patients had been drinking much amounts of alcohol for several years. All patients showed elevation of muscle enzyme such as creatine phosphokinase, lactic dehydrogenase, aspartate transaminase and blood urea nitrogen and serum creatinine. Predisposing factors of rhabdomyolysis were ischemic compression due to unconsciousness and dehydration(2 cases), and hypophosphatemia and dehydration(1 case), seizure and dehydration(1 case), and only severe dehydration(3 cases). Initial symptoms were painful swelling at lesion site(5 cases), abdominal pain(2 cases), general ache(2 cases), leg pain without swelling(1 case), dyspnea(1case), and lethargy(1 case). Seven patients developed delirium tremens during recovery stage. Eight patients showed oliguric acute renal failure and 8 patients were treated with hemodialysis. Complications were disseminated intravascular coagulation(DIC)(3 cases), compartment syndrome(2 cases), capillary leak syndrome and DIC(1 case). One of 12 patients died of disseminated intravascular coagulation and other patients showed complete recovery of renal function.
Acidosis* ; Acute Kidney Injury ; Alcohol Withdrawal Delirium ; Aspartate Aminotransferases ; Blood Urea Nitrogen ; Capillary Leak Syndrome ; Causality ; Creatine Kinase ; Creatinine ; Disseminated Intravascular Coagulation ; Drinking ; Humans ; Hypokalemia ; Hypophosphatemia ; Leg ; Medical Records ; Necrosis ; Oxidoreductases ; Renal Dialysis ; Rhabdomyolysis ; Seizures ; Unconsciousness

STUDY DESIGN: An in vitro experiment. OBJECTIVES: To evaluate the mRNA expressions of matrix components, and analyze the cellular proliferation and proteoglycan synthesis of human intervertebral disc cells in response to dexamethasone and TGF-beta1 SUMMARY OF LITERATURE REVIEW: Corticosteroids are responsible for the regulation of a diverse range of biological processes through modulation of the expression of target genes. The direct injection of methylprednisolone to the intervertebral disc (IVD) has been shown to cause degeneration and calcification of the disc in rabbits. Systemic administration of hydrocortisone induced degeneration of notochordal cells, which accelerated the aging process of the disc in mice. Transforming growth factor beta-1 (TGF-beta1) is known as a potent agent for the proliferation, differentiation and matrix synthesis of IVD. MATERIALS AND METHODS: IVD cells were isolated from ten patients, and subsequently cultured. Various doses of dexamethasone (DEX) and/or TGF-beta1 were administered to the IVD cultures. DNA and proteoglycan syntheses were measured by the incorporation of [3H]-thymidine and [35S]-sulfate, respectively. RT-PCRs were performed for the expressions of aggrecan, collagen types I and II, and osteocalcin mRNA. RESULTS: Cultures with DEX showed increased cellular proliferation and decreased proteoglycan synthesis (p<0.05). TGF-beta1 potentiated the proliferative effect of DEX, but failed to stimulate proteoglycan synthesis in the cultures containing DEX. There were no recognizable changes in the mRNA expressions of aggrecan, collagen types I and II, and osteocalcin in response to DEX and TGF-beta1. CONCLUSIONS: DEX demonstrated a proliferative effect on human IVD cells, with the combination of DEX and TGF-beta1 showing potentiation of the proliferative effect, while at high doses(100 and 1000nM, the DEX was shown to down-regulate the proteoglycan synthesis. Caution should be exercised in the use of corticosteroid in the therapeutic approaches for the treatment of disc disease or in the regenerative matrix of the IVD.
Adrenal Cortex Hormones ; Aggrecans ; Aging ; Animals ; Biological Processes ; Cell Proliferation ; Collagen ; Dexamethasone* ; DNA ; Humans* ; Hydrocortisone ; Intervertebral Disc* ; Methylprednisolone ; Mice ; Notochord ; Osteocalcin ; Proteoglycans ; Rabbits ; RNA, Messenger ; Transforming Growth Factor beta1 ; Transforming Growth Factors

STUDY DESIGN: An in vitro experiment. OBJECTIVES: To assess the effect of pulsed sinusoidal EMF on human intervertebral disc (IVD) cells. LITERATURE REVIEW SUMMARY: Electromagnetic field (EMF) is known to modify some relevant physiological parameters of cells cultured in vitro, such as proliferation, synthesis, secretion of growth factors and transcription. EMF induces bone formation in delayed, non union and spinal fusion models. Also, the exposure of EMF has been shown to protect against the hazardous effect of smoking in the rabbit IVD. MATERIALS AND METHODS: Human IVD cells were three-dimensionally cultured in alginate beads and exposed to a 650 omega, 1.8millitesla magnetic flux density, 60Hz sinusoidal wave of EMF. The cultures were divided into the control and EMF groups, with various exposure times. The cytotoxicity, and DNA and proteoglycan syntheses were measured by the MTT assay, and [3H]-thymidine and [35S]-sulfate incorporation, respectively. RT-PCRs were performed for aggrecan, and collagen types I and II mRNA expressions. RESULTS: There was no recognizable cytotoxicity in the EMF group, but cellular proliferation was stimulated (p<0.05). Newly synthesized proteoglycan, normalized by DNA synthesis, was decreased in the EMF group (p<0.05) as were the expressions of aggrecan (48hour exposure) and type II collagen (72 hours exposure) mRNA compared to the control group. CONCLUSIONS: EMF seems to be hazardous in the synthesis of the chondrogenic matrix, while marginally beneficial in the cellular proliferation of human IVD cells.
Aggrecans ; Cell Proliferation ; Collagen ; Collagen Type II ; DNA ; Electromagnetic Fields* ; Humans* ; Intercellular Signaling Peptides and Proteins ; Intervertebral Disc* ; Magnets* ; Osteogenesis ; Proteoglycans ; RNA, Messenger ; Smoke ; Smoking ; Spinal Fusion