The objective of the present study was to investigate the expression of KL ligand and synaptophysin during postnatal development of the cerebellum blocked c-kit function by ACK2 to determine whether the c-kit receptor and KL ligand interacting system could play a role during the migration of cerebellar neuronal cells and during establishment of functional synapses of all cerebellar neurons. In this study, we used in situ hybridization technique in order to examine the expression of KL mRNA in the cerebellar tissue following intraperitoneal injections of ACK2 and to study the localization of synaptophysin and protein products of KL ligand (SCF: Stem Cell Factor) during postnatal development we used immunohistochemical methods. Our findings are that the intensity of immunoreaction to SCF (protein product of KL ligand) antibody is increased while an immunoreactivity to anti-synaptophysin is decreased in the Purkinje cell bodies in the cerebellum of the mouse given ACK2 from the postnatal day 3 (P3) to Pl4. The overexpression of KL mRNA is detected in the Purkinje cell bodies at Pl4 in the cerebellum blocked c-kit function. At postnatal day 21, the period of which establishment of functional connections of all cerebellar neurons is complete, immunoreactivities of SCF and synaptophysin in the ACK2 treated cerebellum is recovered to the same level being observed in the control. With above results, we suggest a role for the c-kit receptor in the synaptogenesis and migration of developing cerebellar neurons with interaction of ckit receptor/KL ligand system. And the overexpression of KL ligand mRNA and protein product in the Purkinje cells is supposed to be one of mechanisms compensate for the lack of c-kit function in the cerebellum induced by ACK2 during postnatal development.
Animals ; Cerebellum ; In Situ Hybridization ; Injections, Intraperitoneal ; Mice ; Nervous System* ; Neurons ; Proto-Oncogene Proteins c-kit* ; Purkinje Cells ; RNA, Messenger ; Stem Cells ; Synapses ; Synaptophysin

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.
Antineoplastic Agents ; Classification ; DNA Repair ; Molecular Docking Simulation

For trauma patients with severe shock, massive fluid resuscitation is necessary. However, shock and a large amount of fluid can cause bowel and retroperitoneal edema, which sometimes leads to abdominal compartment syndrome in patients without abdomino-pelvic injury. If other emergent operations except intraabdomen are needed, a distended abdomen is likely to be recognized late, leading to multiple organ dysfunction. Herein, we report two cases of a 23-year-old woman who was in a car accident and a 53-year old man who was pressed on his leg by a pressing machine; severe brain swelling and popliteal vessel injury were diagnosed, respectively. They were both in severe shock and massive fluid resuscitation was required in the emergency department. Distended abdomen was recognized in both the female and male patients immediately after neurosurgical operation and immediately before orthopaedic operation in the operating room, respectively. Decompressive laparotomy revealed massive ascites with retroperitoneal edema.
Abdomen ; Ascites ; Brain Edema ; Edema ; Emergency Service, Hospital ; Female ; Humans ; Intra-Abdominal Hypertension* ; Laparotomy ; Leg ; Male ; Operating Rooms* ; Resuscitation ; Shock ; Young Adult

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.
Computer Simulation ; DNA, Recombinant ; Humans* ; Insulin ; Molecular Dynamics Simulation* ; Proinsulin ; Protein Sorting Signals ; Trypsin

The effects of kainic acid-induced seizures on GABA and GABA transporter in the rat cerebellum were examined by means of immunohistochemical and Western blot methods. Immunocytochemical analysis showed that kainic acid-induced seizures led to a decreased immunoreactivity for GABA to 3 weeks after seizures with an slight increase in the immunoreactivity of cerebellum 24 h after treatment. Immunoreactivities of GABA transporters, GAT-1 and GAT-3 which are localized neurons and astrocytes, were increased at 24 and 48h and after that weak immunoreactivites for GABA transporters were shown in the cerebellar tissues. Our results indicate that kainic acid-induced seizures exerts specific effects on GABA contents and the GABA transporters in the cerebellum and a decrease of GABA contents might not always associated with the decrease in the number of GABA transporters in the rat cerebellum.
Animals ; Astrocytes ; Blotting, Western ; Cerebellum* ; GABA Plasma Membrane Transport Proteins ; gamma-Aminobutyric Acid* ; Kainic Acid ; Neurons ; Rats* ; Seizures*

PURPOSE: Traumatic diaphragmatic rupture resulting from blunt trauma is usually severe. However, it is often overlooked during initial evaluation because there are no characteristic signs and symptoms. Thus, this study aimed to determine the clinical characteristics of diaphragmatic rupture caused by blunt trauma and investigate the diagnostic usefulness of diaphragmatic height index (DHI) measured using chest radiographs. METHODS: The cohort comprised patients who were admitted due to diaphragmatic rupture from blunt trauma. Patients were divided into 2 groups; the control group comprised patients with blunt trauma who were matched for age, sex, and Injury Severity Score, while the DHI group comprised patients with diaphragmatic rupture from blunt trauma. Receiver operating characteristic curve was used to determine the cutoff value of DHI for diaphragmatic injury. The sensitivity, specificity, predictability, accuracy, and likelihood ratio of the cutoff were then determined. RESULTS: A total of 60 patients were confirmed to have diaphragmatic rupture. The mean DHI in patients with diaphragmatic rupture on the right and left side were both significantly different compared to that in the control group. A DHI cutoff value of >1.31 showed 71% sensitivity and 87% specificity for diagnosing right diaphragmatic rupture, while a cutoff value of <0.43 showed 87% sensitivity and 76% specificity for diagnosing left diaphragmatic rupture. CONCLUSION: DHI can be useful in the diagnosis of diaphragmatic rupture. DHI as determined using chest radiographs in patients with blunt abdominal trauma, particularly in those ineligible for diagnostic work-up, may help in the diagnosis of diaphragmatic rupture.
Abdominal Injuries ; Cohort Studies ; Diagnosis ; Diaphragm ; Humans ; Injury Severity Score ; Multiple Trauma ; Radiography, Thoracic ; ROC Curve ; Rupture ; Sensitivity and Specificity

Objective: This study aimed to determine the clinical factors associated with positive brain magnetic resonance imaging (MRI) findings in patients presenting to the emergency department (ED) with acute altered mental status (AMS). Methods: Patients with acute AMS who presented to the ED were retrospectively analyzed from September 2019 to March 2020. Non-traumatic patients with abnormal alert, verbal, pain, unresponsive (AVPU) scale scores and exhibiting acute change in mental status were included in the study. We evaluated the clinical characteristics of patients with acute AMS according to the results of their brain MRI. A multivariable logistic regression model was used to determine the clinical factors associated with positive brain MRI findings. Results: During the study period, 138 patients underwent brain MRI in the ED, with 36 (26.1%) positive results. A majority of patients with positive brain MRI findings had underlying malignancies, cerebrovascular disease, higher serum total bicarbonate (TCO2) levels, TCO2≥22 mmol/L, lower blood urea nitrogen levels, abnormal findings on brain computed tomography and abnormal findings on neurologic examination. In the multivariable analysis, serum TCO2≥22 mmol/L (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.09-4.12) and the presence of cranial nerve abnormalities (OR, 3.88; 95% CI, 1.55-9.68) and extremity abnormalities (OR, 2.76; 95% CI, 1.11-6.88) were significantly associated with positive brain MRI results. Conclusion Serum TCO2 level and the presence of cranial nerve and extremity abnormalities in the neurologic examinations were significantly associated with positive brain MRI results in patients with acute AMS.

PURPOSE: Homeless patients usually live outside and are therefore frequently exposed to injury and tetanus infection. Thus, after visits to an emergency department (ED) due to injury, homeless patients need to be vaccinated for the prevention of tetanus infection with tetanus immunoglobulin regardless of tetanus antibody titer or previous vaccination history. Because the exact history of previous tetanus vaccination in homeless patients is unclear, the tetanus antibody titer between homeless patients and general patients was assessed. METHODS: Subjects who visited the ED after injury from October 2008 to February 2010 were enrolled. All participants answered questions on age, gender, previous vaccination or prophylaxis history, and military service. The Tetanus Immunoglobulin G ELISA (Enzyme-linked immunosorbent assay) method was used for the analysis of serum samples. Propensity score-matched analysis was used to control for age, gender, previous vaccination or prophylaxis history, and military service. RESULTS: A total of 1325 samples were analyzed. There was 83 samples from homeless patients and 1242 samples from general patients. After matched analysis using the propensity score, 56 subjects were matched. The geometric mean titer of tetanus antibody was 0.204+/-0.392 IU/mL in homeless patients and 0.105+/-0.143 IU/mL in general patients (p=0.078). The proportion of patients with a safe tetanus antibody titer was 66.1 percent of homeless patients and 23.2 percent of general patients (p<0.001). CONCLUSION: Homeless patients had a higher mean titer and a statistically higher proportion had a safe titer compared to general patients.
Emergencies ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Immunoglobulins ; Methods ; Military Personnel ; Propensity Score ; Tetanus* ; Vaccination

PURPOSE: Homeless patients usually live outside and are therefore frequently exposed to injury and tetanus infection. Thus, after visits to an emergency department (ED) due to injury, homeless patients need to be vaccinated for the prevention of tetanus infection with tetanus immunoglobulin regardless of tetanus antibody titer or previous vaccination history. Because the exact history of previous tetanus vaccination in homeless patients is unclear, the tetanus antibody titer between homeless patients and general patients was assessed. METHODS: Subjects who visited the ED after injury from October 2008 to February 2010 were enrolled. All participants answered questions on age, gender, previous vaccination or prophylaxis history, and military service. The Tetanus Immunoglobulin G ELISA (Enzyme-linked immunosorbent assay) method was used for the analysis of serum samples. Propensity score-matched analysis was used to control for age, gender, previous vaccination or prophylaxis history, and military service. RESULTS: A total of 1325 samples were analyzed. There was 83 samples from homeless patients and 1242 samples from general patients. After matched analysis using the propensity score, 56 subjects were matched. The geometric mean titer of tetanus antibody was 0.204+/-0.392 IU/mL in homeless patients and 0.105+/-0.143 IU/mL in general patients (p=0.078). The proportion of patients with a safe tetanus antibody titer was 66.1 percent of homeless patients and 23.2 percent of general patients (p<0.001). CONCLUSION: Homeless patients had a higher mean titer and a statistically higher proportion had a safe titer compared to general patients.
Emergencies ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Immunoglobulins ; Methods ; Military Personnel ; Propensity Score ; Tetanus* ; Vaccination

Objective: Practice guidelines for diverticulitis have been developed in countries where left-colon diverticulitis is dominant,but there is limited information on right-colon diverticulitis. This study examined the clinical characteristics and riskfactors of clinically severe right-colon diverticulitis. Methods: A retrospective chart review of patients diagnosed with diverticulitis in an emergency department in Koreabetween 2013 and 2017 was performed. Clinically severe diverticulitis was defined as any cause of death, intensive careunit admission, surgery, or invasive intervention due to diverticulitis, and admission for seven or more hospital days.Multivariable logistic regression was used to identify the risk factors for clinically severe diverticulitis. Results: This study analyzed 302 patients. Patients with older age (odds ratio [OR], 1.044; 95% confidence interval [CI],1.009-1.080; P=0.013), complications observed on computed tomography (CT) (OR, 6.906; 95% CI, 2.514-18.968;P<0.001), rebound tenderness on a physical examination (OR, 2.542; 95% CI, 1.041-6.218; P=0.041), high alkalinephosphatase (ALP) levels (OR, 1.014; 95% CI, 1.002-1.026; P=0.026), and high C-reactive protein (CRP) levels (OR,1.095; 95% CI, 1.017-1.178; P=0.013) were at higher risk of clinically severe diverticulitis. Conclusion Among patients diagnosed with right-colon diverticulitis in the emergency department, those of older age,distinct complications on CT, rebound tenderness on physical examination, high ALP, and high CRP levels are related toclinically severe disease.