Dae-Kwang Kim

Different frequency of the absence of the palmaris longus according to assessment methods in a Korean population

The palmaris longus (PL) is a slender, spindle-shaped weak flexor of the wrist. Congenital absence of the PL is estimated to occur in 15% among individuals worldwide. However, the frequency of its absence varies considerably among different population groups and with different detection techniques. In the present study, the presence of the PL tendon was examined in a Korean population (n=269) using three clinical tests, namely the Traditional Test, Mishras Test II, and the Gangata Test. We classified subjects into six types based on whether inspection or palpation was required to determine the presence of the PL and flexor carpi radialis. The most reliable test was determined using Kendalls coefficient of concordance. Our results showed that the PL tendon was absent in 4.1% of the subjects in our study, and bilateral and unilateral absences were 2.2% and 1.8%, respectively. Statistical analysis revealed that these tests had similar reliability for assessing the PL tendon, and the Traditional Test showed the highest effectiveness, at 93%. Therefore the Traditional Test was found to be the most effective for revealing the PL in this Korean population.

Glucagon-like peptide-1 protects NSC-34 motor neurons against glucosamine through Epac-mediated glucose uptake enhancement

Bioenergetic deficits are considered a common cause of neurodegenerative diseases. Although creatine supplementation has been shown to be effective in certain neurodegenerative disorders, it is less effective in amyotrophic lateral sclerosis, a disease that primarily affects motor neurons. These neurons are particularly vulnerable to a cellular energy deficit. Using the ATP-depleting drug glucosamine, we evaluated whether the incretin hormone glucagon-like peptide (GLP)-1 protects motor neurons against glucosamine-induced cytotoxicity. Undifferentiated NSC-34 cells were differentiated into glutamate-sensitive motor neurons by a modified serum deprivation technique. Glucosamine inhibited the viability of differentiated NSC-34 cells in a time- and dose-dependent manner. Glucosamine also acutely reduced cellular glucose uptake, glucokinase activity and intracellular ATP levels. As a result, the activity of AMP-activated protein kinase as well as endoplasmic reticulum stress increased. Pretreatment with GLP-1 significantly alleviated glucosamine-mediated neurotoxicity by restoring cellular glucose uptake, glucokinase activity and intracellular ATP levels. The protective effect of GLP-1 was replicated by Exendin-4 but not Exendin-9, and not blocked by inhibitors of phosphoinositide-3 kinase, protein kinase A, cSrc, or epidermal growth factor receptor, but it was blocked by an adenylate cyclase inhibitor. A selective activator for exchange proteins directly activated by cAMP (Epac), but not a selective activator for protein kinase A, mimicked the GLP-1 effect. Therefore GLP-1 may exert its effect mainly through cAMP-dependent, Epac-mediated restoration of glucose uptake that is typically impaired by glucosamine. These findings indicate that GLP-1 could be employed therapeutically to protect motor neurons that are susceptible to bioenergetic deficits.

Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion.

BACKGROUND Genetic instability in gastric cancer represents a key molecular step that occurs early in the carcinogenesis process. To clarify the role of genetic instability in the progression from gastric dysplasia to gastric cancer, mitochondrial microsatellite instability (mtMSI) was studied in gastric cancer and gastric dysplasia. METHODS DNA was isolated from paired normal and tumoral tissues in 24 patients with gastric dysplasia (low grade) and 49 patients with gastric cancer. mtMSI was analyzed using eight microsatellite markers. mtMSI in gastric dysplasia was studied prospectively to elucidate the relation between mtMSI and gastric carcinogenesis. RESULTS mtMSI was found in 5 (10.2%) of 49 gastric cancer patients. The mtMSI phenotype was not associated with age, gender, and Helicobacter pylori infection. However, all of the mtMSI was found in intestinal-type gastric cancer (20.8%, p=0.02). In gastric dysplasia, mtMSI was detected in 3 (12.5%) of 24 patients with gastric dysplasia. mtMSI-positive gastric dysplasia showed a poor prognosis statistically compared to mtMSI negative through progression to high-grade dysplasia or gastric cancer. CONCLUSIONS These data suggest that mtMSI may be an early and important event in the progression of gastric carcinogenesis, especially in intestinal-type gastric cancer.

Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis.

Clinical value of mitochondrial DNA has been described in colorectal cancer (CRC). To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI) and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. DNA was isolated from paired normal and tumoral tissues in 78 tubular adenomas (TAs), 34 serrated polyps (SPs), and 100 CRCs. mtMSI, nucleus microsatellite instability (nMSI), KRAS mutation, and BRAF mutation were investigated in these tumors and their statistical analysis was performed. mtMSI was found in 30% of CRCs and 21.4% of precancerous lesions. Mitochondrial copy number was higher in SPs than TAs and it was associated with mtMSI in low grade TAs. KRAS and BRAF mutations were mutually exclusive in TAs and SPs. CRCs with mtMSI showed shorter overall survival times than the patients without mtMSI. In CRCs without nMSI or BRAF mutation, mtMSI was a more accurate marker for predicting prognosis. The genetic change of mitochondrial DNA is an early and independent event in colorectal precancerous lesions and mtMSI and mitochondrial contents are associated with the tubular adenoma-carcinoma sequence, resulting in poor prognosis. This result suggested that the genetic change in mitochondrial DNA appears to be a possible prognosis marker in CRC.

Autosomal dominant nocturnal frontal lobe epilepsy and mild memory impairment associated with CHRNB2 mutation I312M in the neuronal nicotinic acetylcholine receptor

Certain paroxysmal nocturnal behaviors have been established as features of nocturnal frontal lobe epilepsy (NFLE). Despite insight into its genetics, the majority of patients with NFLE are not linked to a known mutation and clinical diagnosis remains a challenge. We describe a family presenting with stereotyped nocturnal arousals from non-rapid eye movement sleep, bilateral hand posturing, and pelvic thrusting in the mother, but subtle motor activity in the daughter, and minimal or no epileptiform EEG discharges. Despite normal IQ, there were moderate and severe verbal memory deficits in the mother and daughter, respectively. Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. Phenotypic similarities in unrelated families suggest the determining role of this mutation in NFLE, whereas different inter- and intrafamilial cognitive profiles point to other factors. The absence of clear motor features of NFLE in the daughter emphasizes the shortcomings of current clinical criteria and the potential for genetic testing to further guide clinical diagnostic criteria.

The double retro-aortic left renal vein

The renal veins drain the kidney into the inferior vena cava and unite in a variable fashion to form the renal vein. The left renal vein is normally located in front of the aorta. However, the retro-aortic renal vein may course posterior to the aorta due to embryological developmental anomalies. During educational dissection, a rare variation of the left renal vein was found in a 66-year old male cadaver. The double retro-aortic renal veins coursed behind the aorta to drain into the inferior vena cava. The superior retro-aortic renal vein drained into the inferior vena cava at the lower border of the L2 vertebra, and the inferior retro-aortic renal vein drained into the inferior vena cava at the upper border of the L4 vertebra. Such a variant is rare, and is a clinically important observation which should be noted by vascular surgeons, oncologists, and traumatologists.

Genetic instability in the human lymphocyte exposed to hypoxia

Hypoxia, one of the key tumor microenviromental factors, promotes genetic instability, which is the hallmark of human cancers. Many recent studies have demonstrated that hypoxia by itself can lead to conditions that elevate mutagenesis and inhibit the DNA repair process in cancer. The aim of this study was to investigate the cytogenetic damage and DNA repair functions in human peripheral lymphocytes exposed to hypoxia by means of sister chromatid exchange and nuclear and mitochondrial microsatellite instability (nMSI and mtMSI), respectively. Primary lymphocyte cultures obtained from blood samples of 40 healthy donors were exposed to hypoxia for 12 and 24 hours. Genomic DNA was then isolated from the fixed lymphocytes to analyze the DNA repair process by nMSI and mtMSI. The present results revealed gradual increases in SCE for both exposure times, compared to the controls, but there was no significant correlation between hypoxia and MSI. The SCE assay showed that hypoxia by itself may induce mutagenesis by causing DNA damage in normal cells. However, the DNA repair function through MSI analysis was intact.

Different characteristics of mitochondrial microsatellite instability between uterine leiomyomas and leiomyosarcomas.

Uterine leiomyomas are benign tumors of the uterus that arise clonally from smooth muscle cells of the myometrium and are the most common reason for hysterectomies. The aim of this study was to evaluate mitochondrial microsatellite instability (mtMSI) in uterine leiomyomas and leiomyosarcomas to clarify the molecular pathogenetic distinction between these tumors. DNA was isolated from paired normal and tumoral tissues in 50 patients with uterine leiomyomas and 14 patients with leiomyosarcomas. mtMSI was analyzed by using eight microsatellite markers. Our result showed that mitochondrial microsatellite instability was not found in all uterine leiomyomas. However, 3 (21.4%) of 14 patients with leiomyosarcomas had mtMSI and the frequencies of mtMSI in these tumors were significantly different (p < 0.01). Distinctive characteristics of mitochondrial genetic instability in uterine leiomyomas and leiomyosarcomas suggested the potential of mtMSI as a marker for differential diagnosis between them.

Haddad Syndrome with PHOX2B Gene Mutation in a Korean Infant

Congenital central hypoventilation syndrome with Hirschsprungs disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprungs disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.

A specific chromosome aberration in a keratoacanthoma

Specific cytogenetic changes observed in various tumors indicate that a chromosomal event may play a key role in malignant transformation. We present a patient with keratoacanthoma with a sole chromosome abnormality. The karyotype found in short-term culture was 46,XY,t(2;8)(p13;p23); a normal male chromosome complement was also found. The finding of t(2;8) as a sole anomaly suggests that this aberration is a primary change in keratoacanthoma and might be important in the pathobiology of this tumor.