Modulation of gene expression dynamics by co-transcriptional histone methylations

Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation. Despite their important functions in deacetylation, no strong effects on global gene expression have been seen under optimized or laboratory growth conditions. Instead, H3K4me2-Set3 HDAC and Set2-Rpd3S pathways primarily delay the kinetics of messenger RNA (mRNA) and long noncoding RNA (lncRNA) induction upon environmental changes. A majority of mRNA genes regulated by these pathways have an overlapping lncRNA transcription either from an upstream or an antisense promoter. Surprisingly, the distance between mRNA and lncRNA promoters seems to specify the repressive effects of the two pathways. Given that co-transcriptional methylations and acetylation have been linked to many cancers, studying their functions in a dynamic condition or during cancer progression will be much more important and help identify novel genes associated with cancers.

Spontaneous splenic rupture in Plasmodium vivax malaria

Malaria can present with various clinical symptoms and complications. While a tertian malaria form that is especially prevalent in Korea is characterized by mild clinical progression, occasional splenic complications are known to occur. A 26-year-old Korean male soldier without prior medical history visited The Armed Forces Capital Hospital with left upper quadrant abdominal pain one day ago. Hemostasis under laparoscopic approach was attempted. The operation was converted into laparotomy due to friable splenic tissue and consequently poor hemostasis. Splenectomy was performed. The patient was discharged at postoperative day 17 without complication. While numerous diseases can result in splenic complications, such as splenic rupture, malarial infection is known as the most common cause. The incidence of malarial infection in Korea is increasing annually, and there are occasional reports of splenic rupture due to the infection, which requires attention.

Subchronic Inhalation Toxicity Study of n-pentane in Rats

OBJECTIVES: This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. METHODS: This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. RESULTS: During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. CONCLUSION: The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

The Diagnostic Accuracy of Endoscopic Biopsy for Gastric Dysplasia

PURPOSE: There is controversy over the treatment for low grade dysplasia, while resection is recommended for high grade dysplasia. But the concordance of the grade of dysplasia between pre- and post-resection is low because of sampling errors with endoscopic biopsy. We attempted to establish a clearer direction for the treatment of dysplasia by clarifying the discrepancy between the pre- and post-resection diagnoses. MATERIALS AND METHODS: We performed a retrospective review of 126 patients who had undergone resection with the diagnosis of dysplasia on biopsy at Bundang CHA Hospital from 1999 to 2009. RESULTS: Seventy patients were diagnosed with low grade dysplasia and 56 patients were diagnosed with high grade dysplasia. Among the 33 patients who received gastrectomy with lymph node dissection, 30 patients were revealed to have invasive cancers and 4 patients showed lymph node metastasis. Discordance between the diagnoses from biopsy and resection occurred in 55 patients (44%). There was no correlation on the comparative analysis between the size, location or gross type of lesion and the grade of dysplasia. CONCLUSIONS: The rate of discordance between the diagnoses of endoscopic biopsy and the post resection pathologic report was as high as 44%. Endoscopic mucosal resection was not sufficient for some patients who were diagnosed with dysplasia on biopsy due to the presence of lymph node metastasis. It is necessary to be prudent when determining the follow-up and treatment based solely on the result of the biopsy.

The Diagnostic Accuracy of Endoscopic Biopsy for Gastric Dysplasia

PURPOSE: There is controversy over the treatment for low grade dysplasia, while resection is recommended for high grade dysplasia. But the concordance of the grade of dysplasia between pre- and post-resection is low because of sampling errors with endoscopic biopsy. We attempted to establish a clearer direction for the treatment of dysplasia by clarifying the discrepancy between the pre- and post-resection diagnoses. MATERIALS AND METHODS: We performed a retrospective review of 126 patients who had undergone resection with the diagnosis of dysplasia on biopsy at Bundang CHA Hospital from 1999 to 2009. RESULTS: Seventy patients were diagnosed with low grade dysplasia and 56 patients were diagnosed with high grade dysplasia. Among the 33 patients who received gastrectomy with lymph node dissection, 30 patients were revealed to have invasive cancers and 4 patients showed lymph node metastasis. Discordance between the diagnoses from biopsy and resection occurred in 55 patients (44%). There was no correlation on the comparative analysis between the size, location or gross type of lesion and the grade of dysplasia. CONCLUSIONS: The rate of discordance between the diagnoses of endoscopic biopsy and the post resection pathologic report was as high as 44%. Endoscopic mucosal resection was not sufficient for some patients who were diagnosed with dysplasia on biopsy due to the presence of lymph node metastasis. It is necessary to be prudent when determining the follow-up and treatment based solely on the result of the biopsy.

A Case of the Primary Small Cell Carcinoma of the Pancreas

A 57-year-old man with severe abdominal pain was admitted to our hospital. Chest PA and simple abdominal X-ray revealed no specific findings, but the abdominal-pelvis CT scan showed a 5cm sized multiloculated cystic tumor originating from the pancreatic head and a 3.2cm sized hepatic lesion that was suspected to be a metastic lesion. A radical operation was not able to be performed because of peritoneal metastasis and gastrocolonal infiltration. Only open lymph node biopsy was done and it revealed metastatic small cell carcinoma. Long-acting octreotide and gemcitabine was administered to the patient, but there was no therapeutic response. The tumor grew very rapidly to 26cm in size and the patient died 2 months later from his first hospital day. Necropsy was performed, and the pathologic finding of the resected mass was confirmed to be small cell carcinoma, the same as the result of the previous lymph node biopsy.

A Case of Surgical Treatment of Nesidioblastosis with Hyperinsulinemic Hypoglycemia in an Adult

Nesidioblastosis is a rare disorder, and it usually considered as a cause of neonatal hyperinsulinemic hypoglycemia. A 35 year-old-woman with hyperinsulinemic hypoglycemia was admitted in an unconscious condition. Abdominal CT, pancreas MRI and celiac angiography with an intra-arterial calcium stimulation test revealed a suspicious insulin-producing tumorous lesion in the head of pancreas. The patient underwent enucleation of the pancreas head tumor under the initial diagnosis of insulinoma. However, the tumor was confirmed histologically as nesidioblastosis that showed ductoendocrine proliferations and numerous small endocrine cell groups. Nesidioblastosis is classified into a focal type and a diffuse type, which are characterized by different clinical outcomes. The patient in our case showed a normal blood glucose level after operation, which is often the case for the focal type. Herein, we report this very rare case of adult nesiodioblastosis that was successfully treated by surgical resection.

A Case of Prenatal diagnosed Chorioangioma of Placenta / 대한산부인과학회잡지

Benigh chorioangioma of the placent is the most common primary tumor of the placenta that similar to hamartoma. Most small sized tumor is not important because it is asymptomatic and not make any clinical problem, but large tumor more than 4 cm in diameter are clinically important, because that can make hydramnios, preterm labor, fetal hydrops, Disseminated intravascular coagulopathy, intrauterine growth retardation, preeclampsia, placenta abruptio, postpartum bleeding. In this respect, the predictional diagnosis and management of chorioangioma and its complication should be done. In this paper, a case of chorioangioma associated with hydramnios, preterm labor, IUGR that diagnosis by antepastun ultrasonography and postpartum histologic study is presented with the brief review of the literature related to this type of tumor.

Inhalation effect of 1,1-dichloro-1-fluoroethane (HCFC-141b) on the respiratory system / 천식및알레르기

BACKGROUND: 1,1-dichloro-1-fluoroethane (HCFC-141b) has been known to be relatively safe except irritation of the skin and upper airway, and pulmonary disease directly associated with HCFC-141b exposure has not been reported yet. OBJECTIVE: We report a highly suspicious case of HCFC-141b-related occupational asthma, which was assessed by workplace challenge, but not confirmed by specific inhalation test. We also performed animal experiment to evaluate whether long-term exposure to HCFC-141b could cause inflammation of the airway and parenchymal lung tissue. METHOD: Forty Sprague-Dawley rats were divided into 4 groups. HCFC-141b exposure for each group was carried out under the condition of 6 hours a day, 5 days a week for 13 weeks by inhalation with different concentration of HCFC-141b; Group A-control: Group B-low concentration, 1500 ppm: Group C-moderate concentration, 3000 ppm: and Group D-high concentration, 6000 ppm. Bronchoalveolar lavage (BAL) and histopathological examination of lung tissue was undertaken after HCFC-141b exposure. RESULTS: HCFC-141b did not induce any abnormal change in the clinical and behavioral signs during and at the termination of the inhalation exposure. Compared with control rat, significantly abnormal findings in the microscopic examination of BAL and tissue preparations was not noted in HCFC-141b exposed rats. CONCLUSION: We report a suspicious case of occupational asthma due to HCFC-141b exposure. Animal experiment, however, revealed that HCFC-141b has no toxic or side effect on the respiratory system regardless of its concentration.

A Case of Liver Infarction after a Histoacryl R Injection for Duodenal Ulcer Bleeding / 대한소화기내시경학회지

Injection of the tissue adhesive Histoacryl (N-butyl-2-cyanoacrylate, enbucrilate) has been more effective than conventional sclerosants in the treatment of active upper G-I bleeding. Histoacryl is an effective sclerosant that is polymerized immediately after contact with blood, and has been used for the treatment of bleeding gastric and esophageal varices. We present here a case of infarction of the caudate lobe that developed after an injection of a Histoacryl -Lipiodol mixture for the hemostasis of duodenal ulcer bleeding.

A Case of Transient Hyperkalemia and Hyperaldosteronism secondary to Hydronephrosis / 대한내과학회지

Renal tubular dysfunctions have been observed in hydronephrosis, resulting in metabolic acidosis, hyperkalemia and excessive free water diuresis. These findings are occasionally found in infant and children. Batle et al. first reported distal tubular acidosis associated with low potassium excretion resulting from aldosterone resistance in adults with obstructive uropathy. We have experienced a case of transient hyperkalemia and hyperaldosteronism secondary to hydronephrosis in 63-year-old female patient. The causes of hyperkalemia were examined under the impression of secondary adrenal insufficiency due to corticosteroid abuse or hyporeninemic hypoaldosteronism due to diabetic nephropathy. But it proved to be resulted from hyperaldosteronism due to hydronephrosis. The hyperkalemia resulting from hyperaldosteronism is rare in adults. It may result from aldosterone resistance at distal nephron due to obstructive uropathy or the defect of distal nephron in hydrogen and potassium secretion in the distal nephron rather than from aldosterone deficiency. After she underwent percutaneous nephrostomy, serum potassium was maintained within normal range. She performed total cystectomy with ureterocutaneostomy in purpose for treatment of bladder cancer. So we report this case with a review of literature.

AML1/ETO Fusion Gene Expression and Clinical Characteristics of Adult Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: The (8;21) translocation is one of the most frequent karyotypic abnormalities detected in acute myelogenous leukemia (AML). Up to 92% of cases with this translocation are classified as FAB subtype M2. The chromosomal breakpoints involved in t (8;21) have recently been identified to involve the AML1 gene on chromosome 21 and the ETO gene on chromosome 8. The purpose of this study is to find the frequency of the AML1/ETO gene rearrangement in AML-M2 patients with analysis of clinical and hematologic features of the patients according to the presence or absence of the rearrangement. METHODS: Sixteen patients with AML-M2 were included. RNA were isolated and RT-PCR were done to identify the presence of AML1/ETO rearrangement using Kasumi cell line as positive control. Clinical characteristics were analysed and stastical analysis was done. RESULTS: AML1/ETO gene rearrangement was positive in 12 (75%) of 16 adult patients with AML-M2. In five patient with t (8;21), the AML1/ETO gene rearrangement were positive. In 11 samples without t (8;21), 7 were positive in the RT-PCR. More tests need to be done to identify the overall incidence of AML1/ETO rearrangement in AML-M2 considering the relatively small number of patients included in this study (n=16). Although there was no significant difference in clinical and hematological findings between the two groups, positivity of Auer rods and incidence of splenomegaly were higher in group with the rearrangement, and two cases with extramedullary tumor formation were noted in the group with the rearrangement while no cases without the rearrangement. AML-M2 patients with AML1/ETO rearrangement had a tendency of higher remission rate to chemotherapy and longer duration of survival than AML patient. CONCLUSION: Molecular method using RT-PCR to detect AML1/ETO gene rearrangement is very sensitive and rapid. It will be used in diagnosis and more studies on the leukemogenesis and minimal residual disease are needed.

A Case of Vitamin B12 Deficiency Anemia with Low MCV Combined with Iron Deficiency Anemia / 대한혈액학회지

Vitamin B12 deficiency anemia is a disorder caused by impaired DNA synthesis. Vitamin B12 binds to the intrinsic factor produced by the parietal cells and is absorbed in the distal ileum. After total gastrectomy, megaloblastic anemia is developed due to the absence or deficiency of the intrinsic factor. Concomitant iron deficiency states such as various malabsorption syndromes and alcoholism induce that the bone marrow erythroid megaloblastosis and peripheral blood macroovalocytosis are masked because of countervailing the tendency of iron deficiency to produce microblasts and hypochromic microcytic erythrocytes. We experienced a case of Vitamin B12 deficiency anemia with low RBC mean corpuscular volume (MCV) due to combined with iron deficiency anemia in 42 year-old female patient and report the case with literature review.

Intrasphincteric Injection of Botulinum Toxin in Patients with Achalasia / 대한소화기내시경학회지

BACKGROUND/AIMS: Botulinum toxin(Botox) has long been known as one of the most potent paralytic agents of skeletal muscle, and acts by inhibiting the acetylcholine release from nerve terminals. Recently lacally injected Botox has been found to be effective in the reduction of lower esophageal sphincter(LES) tone in patients with achalasia. The aim of this study was to examine the effects of Botox on patients with achalasia in terms of symptomatic relief and improvement of esophageal function. METHODS: Nine patients with achalasia were given endoscopic injections of 100 units of Botox into the LES. One week later, the response to treatment was assessed on the basis of changes in the symptomatic scores, maximal diameters of esophagus clilation on esophagograms, and results of esophageal manometric and scintigraphic studies. Three months later, the symptomatic scores and esophageal manometric results were assessed. Responders to Botox were defined as patients with a decrease in the total symptom score of 50% or more at 1 month of past-treatment without a subsequent treatment.

A Case of intracranial hemorrhage with polyradiculoneuropathy in Hypereosinophilic Syndrome / 대한내과학회지

Clinical criteria have been established for idiopathic hypereosinophilic syndrome (HES): persistent eosinophilia of 1500 eosinophils/mm3 for at least 6 months or death even within 6 months with signs and symptoms of HES; no evidence for parasitic, allergic, or other recognized causes of eosinophilia despite careful evaluation; and signs and symptoms of organ system involvement or dysfunction, such as congestive heart failure, hepatosplenomegaly, central nerveous system disease. Because cerebral hemorrhage in HES has not been reported yet in Korea, we report a case of hypereosinophilic syndrome with peripheral blood eosinophilia, with biopsies of skin and duodenum showing diffuse eosinophilic infiltration, and multiple organ dysfunction in a 49 year old man died of cerebral hemorrhage three months after the occurrence of the disease.

A case of Fulminant Mycoplasma Pneumonia Complicated with ARDS and Hemolytic Anemia / 결핵

The frequency of fulminant peumonia due to Mycoplasma pneumoniae is relatively rare despite the high prevalence of Mycoplasma species infection in the general population We report a case of mycoplasma pneumonia complicated with severe ARDS, overt hemolytic anemia and hepatitis. He had high titers of antimycoplasma antibody and cold agglutinin. Despite erythromycin administration, the pneumonic infiltration on chest radiography was not resolved, and mechanical ventilation was needed for 16 days. During the therapeutic course, his hemoglobin decreased. After the administration of prednisolone, his hemoglobin increased and pneumonic infitration was totally resolved. He had a progressively favorable course and could be discharged in relatively good clinical condition.

Clinical Review of Hepatic Adenoma reported in Korea / 대한내과학회지

OBJECTIVES: Hepatic adenoma is a rare benign tumor, occuring in women of child-bearing age and it is known that hepatic adenoma is associated with history of oral contraceptive use in about 90% of cases, rarely with type I glycogen storage disease or anabolic steroids. There have been five cases of hepatic adenoma reported in Korea and three cases have been confirmed in our hospital. We examined the clinical findings of these eight cases and compare them with those of hepatic adenoma reported in western countries. METHODS: We reviewed five cases published in medical literature of Korea and three cases confirmed in our hospital. The clinical, laboratory, and radiological features of the eight cases were examined and all were pathologically proven cases as hepatic adenoma. RESULTS: Six cases were male and two cases were female. Mean age of them were 37+/-6 years old which ranged from 24 to 45 years old. Two cases of female did not have history of ingestion of oral contraceptives and six cases of male did not have history of having anabolic steroids. The associated diseases were chronic hepatitis B in two cases, glycogen storage disease type I in one case, and ovarian mucinous cystadenoma in one case. The presenting symptoms were upper abdominal discomfort in five cases, chronic fatigue in one case and two cases had no symptom. Hepatic adenomas were single mass in seven cases and only one case suspected of having glycogen storage disease showed six nodules. The mean diameter of the eight hepatic adenoma was 7.7+/-3.7cm which range from 2.0cm to 15cm. Seven of the eight cases were larger than 5cm in diameter. but there was no case of intraperitoneal bleeding. In laboratory studies, AST/ALT was elevated(81/84IU/L, normal range less than 40IU/L) in one case which was suspected of glycogen storage disease. Alkaline phosphatase were elevated in four cases and elevated alpha-FP was not found in any case. Hepatic adenoma was shown as hyperechoic mass with indistinct margin by ultrasonography and hypodense mass with contrast enhancement by computed tomography. Hepatic adenoma showed isodense or low signal intensity in T1WI, and low or high signal intensity in T2WI. Hepatic angiography showed hypervascular mass in six cases but avascular mass in two cases. CONCLUSION: The reported cases of hepatic adenoma were predominant in men, associated with chronic hepatitis B in two cases, and females with hepatic adenoma had no history of having oral contraceptive. Despite the large size of hepatic adenoma, there was no case accompanied by peritoneal bleeding. These findings contrasts with those of hepatic adenoma reported in western countries. Therefore the pathogenesis and clinical course of hepatic adenoma in Korea may be different with those of hepatic adenoma occurring in western countries and further studies are needed.

The Response to Therapy and Outcome in Adult Focal Segmental Glomerulosclerosis / 대한내과학회지

BACKGROUND: The response to therapy in adult patients with nephrotic syndrome caused by rimary focal segmental glomerulosclerosis (FSGS) was discouraging, but recent reports have shown high remission rate. Of these patients in remission, few progressed to end stage renal disease. METHODS: we analyzed author's experiences in 42 Korean adults with primary FSGS between January 1986 and December 1995 in attempt to know the response to therapy and outcome. RESULTS: 1) Twenty-six of 42 patients(62%) had nephrotic range proteinuria, and renal insufficiency (serum creatinine>1.4 mg/dL) was present in 14 patients(34%). Nephrotic patients had higher serum level of creatinine than that of nonnephrotic patients, and there was no difference between the two groups in blood pressure, age, and hematuria. 2) Twenty-six patients with nephrotic range proteinuria received combined treatment with prednisolone and cyclophosphamide. Complete remission (proteinuria300 mg/d) was observed in 10 cases(39%), and partial remission(2.50g/d) in 11 cases(42%), with mean remission time of 4.12.2 months after initiation of treatment. They had remission within 6 months of therapy except one. Relapse was noticed in 11 cases (52%) during follow-up. 3) None of responder group progressed to ESRD, while two of 5 non-responders progressed to ESRD, but there was no significant difference in slope of inverse creatinine between two groups. 4) The degree of proteinuria, initial serum creatinine, age, and sex did not affect the patient's response to therapy 5) The risk factors related to progression of renal failure were the initial serum creatinine level and degree of proteinuria. CONCLUSION: Nephrotic adult patients with primary FSGS may benefit from a more prolonged course of therapy with prednisolone and cyclophosphamide.

A Case of traumatic Pancreatic Pseudoaneurysm / 대한소화기내시경학회지

In spite of advances in the management of the victim of trauma, the reported incidence of mortality and significant morbidity after pancreatic and/or duodenal injuries is still remained high. The key to treatment is thought to be early, accurate evaluation and proper management according to the degree of injury. We experienced a case of 26-year-old man who had melena after surgery for gun-shot wound of abdomen. In operation, it was noted that duodenum, superior mesenteric artery, and inferior vena cava were lacerated. He was treated by primary suture and drainage. But, 9 months later, hematochezia was developed. Duodenoscopic findings showed buldging mass with blood oozing at the medial side of duodenum second portion. Abdominal CT and angiography revealed pseudoaneurysm of superior mesenteric artery in the pancreas head. The surgery was postponed because severe adhesion between adjacent structures and pseudoaneurysm was suspected. So we decided medical treatment for him and melena was stopped spontaneously. We report this case with a review of literatures.

A Case of Multifocal Cerebral Infarction Associated with Idiopathic Hypereosinophilic Syndrome / 대한내과학회지

The idiopathic hypereosinophilic syndrome represent a heterogenous group of disorders with common features of prolonged eosinophilia of an undetectable cause and organ system dysfunction. Recently, we experienced a case of idiopathic hypereosinophilic syndrome with multifocal cerebral infarction. The patient was 33-year-old male and visited our hospital with right upper extremity weakness and headache. The blood eosinophil counts were 8,316/mma and the marrow showed eosinophils were predominant and in mature forms The two-dimensional echocardiogram showed hyperechoic density at left ventricular apical wall without thrombus formation. Multifocal infarctions were seen at left cerebellar hemisphere, left thalamus, right frontal lobe and left periventricular white matter on brain MRI scan. No cause for hypereosinophilia was found. He was treated with prednisone and hydroxyurea.