BACKGROUND: Microdeletion syndromes not detectable by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). Therefore, it is essential to ensure that patients with MR are screened for these microdeletion syndromes. Mental retardation syndrome multiplex ligation-dependent probe amplification (MRS-MLPA) is a new technique for measuring sequence dosages that allows for the detection of copy number changes of several microdeletion syndromes (1p36 deletion syndrome, Williams syndrome, Smith-Magenis syndrome, Miller-Dieker syndrome, DiGeorge syndrome, Prader-Willi/Angelman syndrome, Alagille syndrome, Saethre-Chotzen syndrome, and Sotos syndrome) to be processed simultaneously, thus significantly reducing the amount of laboratory work. METHODS: We assessed the performance of MLPA (MRC-Holland, The Netherlands) for the detection of microdeletion syndromes by comparing the results with those generated using FISH assays. MLPA analysis was carried out on 12 patients with microdeletion confirmed by FISH (three DiGeorge syndrome, four Williams syndrome, four Prader-Willi syndrome, and one Miller-Dieker syndrome). RESULTS: The results of MLPA analysis showed a complete concordance with FISH in 12 patients with microdeletion syndromes. CONCLUSIONS: On the basis of these results, we conclude that MLPA is an accurate, reliable, and cost-effective alternative to FISH in the screening for microdeletion syndromes.
*Chromosome Deletion ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics ; DiGeorge Syndrome/genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Laboratories, Hospital ; Mental Retardation/*diagnosis/genetics ; Nucleic Acid Amplification Techniques/*methods ; Prader-Willi Syndrome/genetics ; Williams Syndrome/genetics

BACKGROUND: The standard PCR with sequence-specific primers (SSP) is a widely used method of HLA-B27 typing in clinical practice. The aim of our study was to evaluate 2 Korean HLA-B27 kits with different real-time PCR chemistries. METHODS: To validate the accuracy of real-time PCR kits, we selected 28 HLA-B27-positive samples and 33 HLA-B27-negative samples with a wide range of different HLA-B specificities typed by standard PCR-SSP. The 2 real-time PCR kits used were the AccuPower(R) HLA-B27 real-time PCR kit (Bioneer, Korea) with TaqMan probes and the Real-Q(TM) HLA-B*27 detection kit (BioSewoom, Korea) with SYBR Green I dye for melting curve analysis. RESULTS: All 61 samples typed by PCR-SSP demonstrated a perfect concordance with the 2 real-time PCR assays. It was possible to clearly discriminate between HLA-B27-positive and -negative samples in both real-time assays. CONCLUSIONS: In summary, both real-time PCR assays for HLA-B27 were fast, reliable, well-adapted for routine laboratory testing, and attractive alternatives to the conventional PCR-SSP method.
HLA-B27 Antigen/*analysis ; Histocompatibility Testing/*methods ; Humans ; Organic Chemicals/chemistry ; Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Transition Temperature

Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- and HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies.
Antiviral Agents/therapeutic use ; Female ; Hepatitis B, Chronic/*complications/drug therapy ; Hepatitis C, Chronic/*complications/drug therapy ; Humans ; Liver Cirrhosis/virology ; Male ; Middle Aged ; Transaminases/blood ; alpha-Fetoproteins/*analysis

BACKGROUND: Leptin, an adipocyte derived hormone, and thyroid hormone have similar effects on energy homeostasis, such that a shortage of both hormones is associated with decreased energy expenditure and increased body weight. Therefore, for the maintenance of energy homeostasis may require a close interaction between leptin and thyroid hormone. This study was performed to investigate the change in plasma leptin levels relating to short-term thyroid manipulation causing no significant change in body weight. METHODS: Hypothyroidism was induced by surgical thyroidectomy and hyperthyroidism by subcutaneous injection of 50 g of L-T3/100 g body weight/day, for 5 days, in 6~8 weeks old male Wistar rats. Body weights and food intakes were monitored daily until sacrifice. Plasma samples were collected, and the thyroid stimulating hormone (TSH), free triiodothyronine (T3) and leptin levels measured. The plasma leptin levels in rats with hypothyroidism and hyperthyroidism were compared with those of body weights at death and food intakes during the study, atched controls. RESULTS: The rats treated with L-T3 consumed equal amount of food as freely fed, rats but their final body weights were significantly lower (L-T3 treated 220.0 +/- 1.8 vs. freely fed 226.0 +/- 2.0 g, p<0.05). There was no difference in food intake during study, and final body weight, between the thyroidectomised rats and their paired controls (thyroidectomised 220.4 +/- 1.7 vs. paired 223.9 +/- 4.7 g, P=NS). Plasma leptin levels in the L-T3 treated rats were significantly lower than those in freely fed rats (L-T3 treated 1.7 +/- 0.1 vs. freely fed 4.8 +/- 0.2 ng/ml, p<0.005). Conversely, the thyroidectomised rats had higher plasma leptin levels, compared to those of their paired controls (thyroidectomised 4.8 +/- 0.3 vs. paired 1.7 +/- 0.1 ng/ml, p<0.005). CONCLUSION: The Plasma leptin levels in the rats were decreased by short term hyperthyroidism, while they were increased by short term hypothyroidism. These findings suggest that thyroid hormones may affect the production or secretion of leptin
Adipocytes ; Animals ; Body Weight ; Eating ; Energy Metabolism ; Homeostasis ; Humans ; Hyperthyroidism ; Hypothyroidism ; Injections, Subcutaneous ; Leptin* ; Male ; Plasma* ; Rats* ; Rats, Wistar ; Thyroid Gland* ; Thyroid Hormones ; Thyroidectomy ; Thyrotropin ; Triiodothyronine

A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1x10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.
Antibodies ; Biopsy ; Codon ; DNA ; Female ; Genotype ; Hepacivirus ; Hepatitis ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis C ; Hepatocytes ; Humans ; Immunoglobulin M ; Interferon-alpha ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Middle Aged ; Ribavirin ; Superinfection ; Viruses

Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

BACKGROUND AND OBJECTIVES: Parkinson’s disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD. METHODS: The soluble RAGE (sRAGE) secreting Umbilical Cord Blood—derived Mesenchymal Stem Cell (UCB-MSC) was generated by gene editing method using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9). These cells were transplanted into Corpus Striatum of rotenone-induced PD animal models then behavioral test, morphological analysis, and immunohistochemical experiments were performed to determine the neuronal cell death and recovery of movement. RESULTS: The neuronal cell death in Corpus Striatum and Substantia Nigra was dramatically reduced and the movement was improved after sRAGE secreting UCB-MSC treatment in PD mice by inhibition of RAGE in neuronal cells. CONCLUSIONS: We suggest that sRAGE secreting UCB-MSC based therapeutic approach could be a potential treatment strategy for neurodegenerative disease including PD.
Animals ; Behavior Rating Scale ; Cell Death ; Corpus Striatum ; Mesenchymal Stromal Cells ; Methods ; Mice ; Microglia ; Models, Animal ; Nervous System ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease ; Rage ; Substantia Nigra ; Umbilical Cord