• 생물정신의학
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• 제7권2호
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• pp.115-122
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• 2000

The development of molecular biology has brought many changes in psychiatry. Molecular biology makes us possible to know the cause of mental disorders that provide the way to prevent the disorders, and to develop various accurate diagnostic and treatment methods for mental disorders. The author discusses the concept, cause, and treatment of mental disorders in the aspect of molecular biology. Importing the methods of molecular biology into psychiatry, we can anticipate to get a number of the goals of psychiatric genetics, including identification of specific susceptibility genes, clarification of the pathophysiological processes whereby these genes lead to symptoms, establishment of epigenetic factors that interact with these genes to produce disease, validation of nosological boundaries that more closely reflect the actions of these genes, and development of effective preventive and therapeutic interventions based on genetic counseling, gene therapy, and modification of permissive or protective environmental influences. In addition to their capacity to accelerate the discovery of new molecules participating in the nervous system's response to disease or to self-administered drugs, molecular biological strategies can also be used to determine how critical a particular gene product may be in mediating a cellular event with behavioral importance. Molecular biology probably enables us discover the environmental factors of mental disorders and allow rational drug design and gene therapies for mental disorders, by isolation of gene products that facilitate a basic understanding of the pathogenesis of these disorders. A specific genetic linkage may suggest a novel class of drugs that has not yet been tried. With respect to gene therapy, the hypothetical method would use a gene delivery system, most likely a modified virus, to insert a functional copy of a mutant gene into those brain cells that require the gene for normal function.

• 생물정신의학
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• 제8권2호
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• pp.226-232
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• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.

• BMB Reports
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• 제55권6호
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• pp.267-274
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• 2022

Molecular imaging is used to improve the disease diagnosis, prognosis, monitoring of treatment in living subjects. Numerous molecular targets have been developed for various cellular and molecular processes in genetic, metabolic, proteomic, and cellular biologic level. Molecular imaging modalities such as Optical Imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) can be used to visualize anatomic, genetic, biochemical, and physiologic changes in vivo. For in vivo cell imaging, certain cells such as cancer cells, immune cells, stem cells could be labeled by direct and indirect labeling methods to monitor cell migration, cell activity, and cell effects in cell-based therapy. In case of cancer, it could be used to investigate biological processes such as cancer metastasis and to analyze the drug treatment process. In addition, transplanted stem cells and immune cells in cell-based therapy could be visualized and tracked to confirm the fate, activity, and function of cells. In conventional molecular imaging, cells can be monitored in vivo in bulk non-invasively with optical imaging, MRI, PET, and SPECT imaging. However, single cell imaging in vivo has been a great challenge due to an extremely high sensitive detection of single cell. Recently, there has been great attention for in vivo single cell imaging due to the development of single cell study. In vivo single imaging could analyze the survival or death, movement direction, and characteristics of a single cell in live subjects. In this article, we reviewed basic principle of in vivo molecular imaging and introduced recent studies for in vivo single cell imaging based on the concept of in vivo molecular imaging.

• Journal of Genetic Medicine
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• 제19권1호
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• pp.32-37
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• 2022

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase B due to mutations in the ARSB gene. Here, we report the case of a Korean female with a novel variant of MPS VI. A Korean female aged 5 years and 8 months, who is the only child of a healthy non-consanguineous Korean couple, presented at our hospital for severe short stature. She had a medical history of umbilical hernia and recurrent otitis media. Her symptoms included snoring and mouth breathing. Subtle dysmorphic features, including mild coarse face, joint contracture, hepatomegaly, and limited range of joint motion, were identified. Radiography revealed deformities, suggesting skeletal dysplasia. Growth hormone (GH) provocation tests revealed complete GH deficiency. Targeted exome sequencing revealed compound heterozygous mutations in the ARSB genes c.512G>A (p.Gly171Asp; a pathogenic variant inherited from her father) and c.1157C>T (p.Ser386Phe; a novel variant inherited from her mother in familial genetic testing). Quantitative tests revealed increased urine glycosaminoglycan (GAG) levels and decreased enzyme activity of arylsulfatase B. While on enzyme replacement therapy and GH therapy, her height increased drastically; her coarse face, joint contracture, snoring, and obstructive sleep apnea improved; urine GAG decreased; and left ventricular mass index was remarkably decreased. We report a novel variant-c.1157C>T (p.Ser386Phe)-of the ARSB gene in a patient with MPS VI; these findings will expand our knowledge of its clinical spectrum and molecular mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3763-3766
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• 2012

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Methods: A literature search was performed using Pubmed and CNKI databases for published studies through May 2012. We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41). However, no significant association was found in Caucasians. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association.

• 대한통합의학회지
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• 제9권2호
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• pp.105-108
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• 2021

Background : Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare, autosomal recessive metabolic disorder which is caused by genetic mutations that disrupt the urea cycle. It is characterized by variable clinical presentation and the age of onset. Patients may present with gait disturbance and progressive paraplegia and muscle tightness in the lower extremities. The use of botulinum toxin in metabolic disease has rarely been discussed. We describe a case of a 14-year-old-boy with HHH syndrome, who presented with a several - month history of gait disturbance and lower extremity weakness. Case presentation : A 14-year old male had a history of recurrent upper respiratory tract infections, occasional vomiting, loss of appetite, and general weakness, all of which started since he was 10 months old. He was diagnosed with HHH syndrome at one year of age. At the age of 14, he was referred for the assessment and treatment of his gait disturbance and aggravated weakness of the lower extremities. Brain MRI, electrodiagnostic study and blood test were performed to exclude any lesions related to neurologic dysfunction. Botulinum toxin type A were injected into muscles of adductor longus, adductor magnus, lateral and medial hamstring, and lateral and medial gastrocnemius muscle heads under needle electromyography guidance to reduce lower limb spasticity. Intensive physical therapy including gait training and stretching exercise of adductor and calf muscles were also provided. After intensive physical therapy and botulinum toxin injection to reduce lower limb spasticity, he was able to ambulate for 20 meters independently without any walking aids. There were no adverse events after the injection. Conclusion : Botulinum toxin injection is a safe and effective therapy for patients with HHH syndrome who suffer from gait disturbance.

• Journal of Ginseng Research
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• 제43권4호
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• pp.684-691
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• 2019

Background: We have reported that defective nef and gag genes are induced in HIV-1-infected patients treated with Korean Red Ginseng (KRG). Methods: To investigate whether KRG treatment and highly active antiretroviral therapy (HAART) affect genetic defects in the pol gene, we amplified and sequenced a partial pol gene (p-pol) containing the integrase portion (1.2 kb) by nested PCR with sequential peripheral blood mononuclear cells over 20 years and compared it with those patients at baseline, in control patients, those taking ginseng-based combination therapy (GCT; KRG plus combinational antiretroviral therapy) and HAART alone. We also compared our findings to look for the full-length pol gene (pol) (3.0-kb) Results: Twenty-patients infected with subtype B were treated with KRG for $116{\pm}58months$ in the absence of HAART. Internal deletion in the pol gene (${\Delta}pol$) was significantly higher in the KRG group (11.9%) than in the control group and at baseline; its detection was significantly inhibited during GCT as much as during HAART. In addition, the ${\Delta}pol$ in p-pol significantly depended on the duration of KRG treatment. In pol, the proportion of ${\Delta}pol$ was significantly higher in the KRG group (38.7%) than in the control group, and it was significantly inhibited during GCT and HAART. In contrast, the proportion of stop codon appeared not to be affected by KRG treatment. The PCR success rate was significantly decreased with longer GCT. Conclusion: The proportion of ${\Delta}pol$ depends on template size as well as KRG treatment. HAART decreases the detection of ${\Delta}pol$.

• BMB Reports
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• 제56권8호
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• pp.463-468
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• 2023

Screening for genetic defects in the cells should be examined for clinical application. The Pearson syndrome (PS) patient harbored nuclear mutations in the POLG and SSBP1 genes, which could induce systemic large-scale mitochondrial genome (mtDNA) deletion. We investigated iPSCs with mtDNA deletions in PS patient and whether deletion levels could be maintained during differentiation. The iPSC clones derived from skin fibroblasts (9% deletion) and blood mononuclear cells (24% deletion) were measured for mtDNA deletion levels. Of the 13 skin-derived iPSC clones, only 3 were found to be free of mtDNA deletions, whereas all blood-derived iPSC clones were found to be free of deletions. The iPSC clones with (27%) and without mtDNA deletion (0%) were selected and performed in vitro and in vivo differentiation, such as embryonic body (EB) and teratoma formation. After differentiation, the level of deletion was retained or increased in EBs (24%) or teratoma (45%) from deletion iPSC clone, while, the absence of deletions showed in all EBs and teratomas from deletion-free iPSC clones. These results demonstrated that non-deletion in iPSCs was maintained during in vitro and in vivo differentiation, even in the presence of nuclear mutations, suggesting that deletion-free iPSC clones could be candidates for autologous cell therapy in patients.

• Journal of Microbiology and Biotechnology
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• 제22권9호
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• pp.1301-1306
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• 2012

We combined real-time RT-PCR and real-time PCR (R/P) assays using a hydrolysis probe to detect Mycobacterium tuberculosis complex (MTBC)-specific 16S rRNA and its rRNA gene (rDNA). The assay was applied to 28 non-respiratory and 207 respiratory specimens from 218 patients. Total nucleic acids (including RNA and DNA) were extracted from samples, and results were considered positive if the repeat RT-PCR threshold cycle was ${\leq}35$ and the ratio of real-time RT-PCR and real-time PCR load was ${\geq}1.51$. The results were compared with those from existing methods, including smear, culture, and real-time PCR. Following resolution of the discrepant results between R/P assay and culture, the overall sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of all samples (including non-respiratory and respiratory specimens) were 98.2%, 97.2%, 91.7%, and 99.4%, respectively, for R/P assay, and 83.9%, 89.9%, 72.3%, and 94.7%, respectively, for real-time PCR. Furthermore, the R/P assay of four patient samples showed a higher ratio before treatment than after several days of treatment. We conclude that the R/P assay is a rapid and accurate method for direct detection of MTBC, which can distinguish viable and nonviable MTBC, and thus may guide patient therapy and public health decisions.

• 식물병연구
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• 제22권4호
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• pp.236-242
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• 2016

Bacterial wilt caused by Ralstonia solanacearum is one of the most devastating diseases in major Solanaceae crops. The pathogen is easily disseminated and survives for many years in plant farming system. Although chemicals are applied to control the disease, they are of limited efficacy and cause several problems. Therefore, the use of phage therapy has been suggested to control the disease as a biological agent. In this study, we discovered bacteriophages lysing diverse Ralstonia isolates from plant and soil samples obtained from the potato cultivated field in Jeju. Three times repeated pickings of plaques resulted in obtaining 173 single phages showing diverse spectrum of host-specificity. With the results, 12 core phages were selected and dendrogram was generated. Genetic diversity of the selected phages was also confirmed by AFLP (Amplified Fragment of Length Polymorphism) fingerprinting. The stability of the phages was investigated in various temperatures and various conditions of pH in vitro. The phages were stable at $16^{\circ}C-44^{\circ}C$ and pH 6-10. Morphological characterization of the phages revealed they were all classified into the Podoviridae, but had diverse head sizes. The results of this research will contribute to control the disease and further researches regarding genetic and molecular aspects will facilitate understanding phage and bacteria interaction.