Evaluation of the antigenic stability of influenza virus like particles after exposure to acidic or basic pH

Purpose@#Virus-like particles (VLPs) are being developed as a promising vaccine platform and therapeutic delivery. Various strategies for effectively constructing VLPs have been studied, but relatively few studies have been done on various factors affecting storage. In this study, we investigated the antigenic changes of VLPs in an acidic or basic pH environment using influenza VLPs as an experimental model. @*Materials and Methods@#Influenza VLPs containing hemagglutination and M1 proteins were generated and their antigenicity and protective immunity in vitro and in vivo were evaluated after exposure to acidic (pH 4 and 5) or basic (pH 9 and 10) pH buffers. @*Results@#VLP exposed to basic pH showed similar levels of antigenicity to those stored in neutral pH, while antigenicity of VLP exposed to acidic pH was found to be significantly reduced compared to those expose neutral or basic pH. All groups of mice responded effectively to low concentrations of virus infections; however, VLP vaccine groups exposed to acid pH were found not to induce sufficient protective immune responses when a high concentration of influenza virus infection. @*Conclusion@#In order for VLP to be used as a more powerful vaccine platform, it should be developed in a strategic way to respond well to external changes such as acidic pH conditions.

Influence of temperature on the antigenic changes of virus-like particles

Purpose@#In this study, we investigated whether the antigenic changes of the virus-like particles (VLPs) are affected by the temperature during storage. @*Materials and Methods@#After exposing the recombinant influenza VLPs to various temperatures for a period, antigenic changes were examined through in vitro hemagglutination receptor binding assay and in vivo mouse experiments. @*Results@#Influenza VLPs were exposed at three different temperatures of low, middle, and high on a thermo-hygrostat. High temperature exposed influenza VLPs were showed significantly reduced HA activity and immunogenicity after mouse single immunization over time compared low and middle. When the VLPs exposed to the high temperature were inoculated once in the mice, it was found that the immunogenicity was significantly reduced compared to the VLPs exposed to the low temperature. However, these differences were almost neglected when mice were inoculated twice even with VLPs exposed to high temperatures. @*Conclusion@#This study suggests that similar protective effects can be expected by controlling the number of vaccination and storage conditions, although the antigenic change in the VLP vaccines occurred when exposed to high temperature.

Influence of temperature on the antigenic changes of virus-like particles

Purpose@#In this study, we investigated whether the antigenic changes of the virus-like particles (VLPs) are affected by the temperature during storage. @*Materials and Methods@#After exposing the recombinant influenza VLPs to various temperatures for a period, antigenic changes were examined through in vitro hemagglutination receptor binding assay and in vivo mouse experiments. @*Results@#Influenza VLPs were exposed at three different temperatures of low, middle, and high on a thermo-hygrostat. High temperature exposed influenza VLPs were showed significantly reduced HA activity and immunogenicity after mouse single immunization over time compared low and middle. When the VLPs exposed to the high temperature were inoculated once in the mice, it was found that the immunogenicity was significantly reduced compared to the VLPs exposed to the low temperature. However, these differences were almost neglected when mice were inoculated twice even with VLPs exposed to high temperatures. @*Conclusion@#This study suggests that similar protective effects can be expected by controlling the number of vaccination and storage conditions, although the antigenic change in the VLP vaccines occurred when exposed to high temperature.

Relationship between Bronchodilator Response, Airway Hyperresponsiveness, and Exhaled Nitric Oxide Levels in Patients with Suspected Bronchial Asthma / 대한내과학회지

BACKGROUND/AIMS: Exhaled nitric oxide (NO) has been extensively investigated as a marker of airway inflammation in asthma, and fractional exhaled nitric oxide (FeNO) is recognized as a useful tool for its evaluation. The aim of this study was to investigate the relationships between FeNO levels and bronchodilator response (BDR), and between FeNO and mannitol-induced airway hyperresponsiveness (AHR), in patients with suspected asthma. METHODS: Clinical variables were collected from patients aged ≥ 13 years with suspected bronchial asthma and measured levels of FeNO. These levels were compared with patient values for forced expiratory volume in the first second (FEV1) and forced expiratory flow at 25 and 75% of the pulmonary volume (FEF(25-75%)) in bronchodilator response tests under control conditions, and during bronchial provocation with mannitol. Correlations and receiver operating characteristic (ROC) curves between FeNO levels and each test were assessed. RESULTS: A total of 259 patients were included in the analysis. The mean ages of the two test groups were 41.1 and 47.8 years, respectively. FeNO levels were strongly correlated with bronchodilator response (%) and with the mannitol dose producing a 15% fall in FEV1 (PD15). On the other hand, FeNO levels were only weakly correlated with FEF(25-75%). The optimal cut-off values for FeNO to predict a positive BDR and AHR were 38.5 and 29.5 parts per billion, respectively. CONCLUSIONS: This study suggests that FEV1 and FEF(25-75%) airway responses correlate with FeNO levels in patients with suspected bronchial asthma. FeNO levels may help to predict positive responses to BDR and AHR.

Preparation and immunogenicity of influenza virus-like particles using nitrocellulose membrane filtration

PURPOSE: Nitrocellulose membrane–based filtration system (NCFS) is widely used for protein concentration. In this study, we applied NCFS for production of virus-like particle (VLP) as a vaccine candidate and evaluated yield property and immunogenicity. MATERIALS AND METHODS: Influenza VLPs were generated by baculovirus-insect cell protein expression system. NCFS and sucrose gradient ultracentrifugation were used for purification of VLP. Immunogenicity of VLP was evaluated by animal experiment. RESULTS: Influenza VLPs expressing hemagglutinin (HA) and neuraminidase proteins derived from highly pathogenic influenza virus (H5N8) were effectively produced and purified by NCFS. HA activity of VLP which correlated with antigenicity was well conserved during multiple purification steps. This NCFS based purified VLPs induced influenza virus–specific antibody responses. CONCLUSION: Our results indicate that the influenza VLP vaccine could be prepared by NCFS without loss of immunogenicity and elicit antigen-specific immune responses.

Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice

Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.

A case of hypervascular hyperplastic nodules mimicking hepatocellular carcinoma in alcoholic liver cirrhosis / 대한간학회지

Benign hypervascular hyperplastic nodules (HHN) in liver cirrhosis are very rare. It is important to distinguish between regenerative nodules (hyperplastic nodules) and tumorous nodules (dysplastic or neoplastic nodules) in hepatocellular nodular lesions. The differential diagnosis between HHN and hepatocellular carcinoma on the basis of radiologic imaging is often difficult, and is clinically important when determining the therapeutic plan. Therefore, histological confirmation by needle biopsy sampling of the liver is necessary for a correct diagnosis of HHN. We report herein a case of benign HHN mimicking hepatocellular carcinoma in a 32-year-old male alcoholic liver cirrhosis patient without viral hepatitis infection.

A Case of Endogenous Klebsiella Endophthalmitis Associated with Acute Pyelonephritis in a Patient with Chronic Renal Failure / 대한신장학회지

Endogenous endophthalmitis is any inflammation of the internal ocular space that usually has a poor prognosis for visual recovery, and is a rare complication of Klebsiella pneumoniae septicemia. We report here a case of endogenous endophthalmitis due to K. pneumoniae in a patient with acute pyelonephritis and chronic renal failure who did not have any history of diabetes mellitus. A 75-year-old woman was admitted to our hospital, complaining of severe pain and decreased vision in the right eye, accompanied by fever and nausea, of 48 hours' duration. Ophthalmologic evaluation and intervention were performed. Blood, urine and vitreous cultures were all positive for K. pneumoniae. She was treated with intravenous antibiotics, intravitreal antibiotics injection and pars plana vitrectomy. However, her right eye showed progressive worsening to enucleation, and she has been on maintenance hemodialysis ever since.

Skeletal Muscle Metastasis from a Cecal Mucinous Adenocarcinoma: A Case Report

Skeletal muscle metastasis is a relatively rare finding in the setting of mucinous adenocarcinoma of the colon, and it typically exhibits nonspecific imaging findings. We report a case of a skeletal muscle metastasis originating from mucinous adenocarcinoma of the cecum. The skeletal lesion closely resembled intramuscular myxoma with regard to imaging findings, due to abundant mucin and internal calcification.

Uptake of 18F-FDG in the Angioleiomyoma of the Leg / 핵의학분자영상

Angioleiomyoma is a rare benign tumor arising from the vascular smooth muscle (tunica media) and characterized by either a painful or painless, solitary subcutaneous nodule occurring most often in the lower extremity. We report a case of intense FDG uptake in the angioleiomyoma of right lower leg on 18F-FDG PET/CT.

Pseudohypertrophy of the Calf Muscles in a Patient with Diabetic Neuropathy: A Case Report

Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers.

Intestinal Arteriovenous Malformation Involving the Descending Colon: A Case Report

Arteriovenous malformations (AVMs) comprising a feeding artery, nidus, and draining vein rarely develop in the gastrointestinal tract. Although almost all AVMs are asymptomatic, they cause massive painless rectal bleeding and subsequent chronic anemia. The definitive diagnosis of AVM is achieved by selective mesenteric angiography, and surgical resection is the treatment of choice. We detected an intestinal AVM involving the descending colon in a patient with severe hematochezia. The diagnosis was made by CT angiography performed using a 64-channel MDCT and the obtained 3D reconstruction images. The AVM showed an extensive vascular network on CT images, and it was treated by surgical resection. Here, we report this case of an intestinal AVM along with its imaging findings.

Mesenteric Lymphadenopathy in Childhood Epidemic Aseptic Meningitis: Sonographic Features and Clinical Significance

PURPOSE: To evaluate the sonographic features of mesenteric lymphadenopathy in childhood epidemic aseptic meningitis and to assess their clinical significance. MATERIALS AND METHODS: Thirty-three patients (25 male, 8 female; mean age, 8.6 years) with a diagnosis of aseptic meningitis were prospectively evaluated with abdominal ultrasonography for the presence of enlarged mesen-teric nodes. The size and number of enlarged mesenteric lymph nodes were analyzed in relationship with the pa-tient's age, between the patients with abdominal pain or diarrhea (16 cases, 48%) and asymptomatic patients(17 cases, 52%). RESULTS: Mesenteric lymphadenopathy was seen in 31 patients (94%), all 16 symptomatic and 15 of the 17 asymp-tomatic patients. The number of enlarged nodes was most prevalent between 6 -10, seen in 16 patients (52%) and the largest node ranged in size from 4 to 8 mm. Among the 31 patients with mesenteric lymphadenopathy, the mean size of the largest node was statistically different between the symptomatic (6.0 mm) and asympto-matic (5.0 mm) groups (p = 0.021). The number of enlarged nodes and the patient's age were not statistically d-ifferent between the two groups. CONCLUSION: Mesenteric lymphadenopathy was seen in almost all cases of childhood epidemic aseptic meningitis, and may be related to the mesenteric lymphadenitis caused by enterovirus.

Radiologic Findings of Cervical Varix Developed in Late Pregnancy: Case Report

Cervical varix is a rare cause of obstetric hemorrhage which needs accurate diagnosis and prompt management because the lesion may be associated with preterm delivery and maternal complications. Our patient was diagnosed with cervical varix and vaginal bleeding at 32 weeks' gestation, using transvaginal ultrasound and MRI. Persistent vaginal bleeding and preterm labor led to an emergency cesarean section at 33 weeks'gestation. After delivery, cervical varix was spontaneously resolved in the follow-up transvaginal ultrasound and CT. We report various radiologic features of cervical varix combined with vaginal bleeding in late pregnancy.

The Lengths of the Left and Right Mainstem Bronchi Measured by Computed Tomography with Minimum Intensity Projection in Korean Adults / 대한마취과학회지

the height of the patients and the length of the left and right mainstem bronchi. CONCLUSIONS: These results provide reference data to help determine the precise margin of safety using a double lumen endobronchial tube for thoracic surgery.

Early Detection of Intrathecal Migration of Epidural Catheter for Postoperative Pain Control: A case report / 대한마취과학회지

A 68 years old male patient was scheduled for open cholecystectomy and common bile duct exploration for gallstone and common bile duct stones with cholecystitis. With the patient in lateral decubitus position, a 17 G Tuohy needle was inserted into the epidural space via midline approach at the T10-11 interspace by using the loss of resistance technique. Then, an 18 G epidural catheter was inserted into the epidural space upward 5 cm for postoperative pain control without complications such as bleeding, paresthesia or CSF leakage. After the epidural catheterization, general anesthesia was induced. During the surgery, the aspiration test via the epidural catheter was done once more before connection of PCA device to the epidural catheter, and some clear fluid was found to be aspirated. Intrathecal migration of the epidural catheter was doubted and confirmed by a measurement of glucose level and the thiopental precipitation test. After the end of surgery, the epidural catheter was removed and the patient was discharged from the PACU 1 hour later without any complication or sequelae. We report a case of early detection of intrathecal migration of an epidural catheter by a measurement of glucose level and the thiopental precipitation test of the aspirated fluid.

A Case of Fetus in Fetu / 대한주산의학회잡지

Fetus in fetu is an extremely uncommon cause of abdominal mass in the neonate with an incidence of 1 in 500,000 births. This is thought to occur when a monozygotic, diamniotic twin is incorporated into the body of its sibling early in embryonic development. A case of retroperitoneal fetus in fetu in a 3 day old male infant is reported, the excised round mass contained the vertebral column, 2 feet, 2 arms, small penis and testis. The presence of vertebral axis and organogenesis differentiates it from a teratoma. More than 100 cases of fetus in fetu have been reported, most of which have been in the abdomen. We report a case of a well developed fetus in the retroperitoneal area of a neonate delivered at term.

Analysis of factors to affect on MR assessment of myometrial invasion and cervical involvement in endometrial cancer / 대한산부인과학회지

OBJECTIVE: The aim of this study was to assess the depth of myometrial invasion and cervical involvement by endometrial cancer using magnetic resonance imaging (MRI). METHODS: Forty three patients with histological diagnosis of endometrial cancer were studied with the results of MRI at 1.5T and subsequently underwent staging operation. The MRI results were compared with pathologic results. Presence of large polypoid tumors, leiomyoma, adenomyosis, distension of uterine cavity by large tumor, atrophy of uteri, utetrine anomalies and tumor protruding into the cervical canal were analyzed. RESULTS: On review, the sensitivity for the detection of myometrial invasion was 93.5%, specificity 58.3%, positive predictive value (PPV) 85.3% and negative predictive value (NPV) 77.8%. For the detection of deep myometrial invasion, sensitivity was 87.5%, specificity 85.7%, PPV 58.3% and NPV 96.8%. For the detection of cervical involvement, sensitivity was 100%, specificity 92.9%, PPV 25%, NPV 100%. Distension of uterine cavity by large tumor (p=0.009) and adenomyosis (p=0.041) were associated with incorrect MRI assessment of myometrial invasion. For cervical involvement, tumor protruding into the cervical canal was associated but did not reach statistical significance (p=0.062). CONCLUSION: MRI scans as reported offered some clinical benefit in preoperative assessment of endometrial cancer, but for assessment of cervical involvement, showed low PPV. When present, distension of uterine cavity by large tumor and adenomyosis may make it difficult to assess myometrial invasion at MR imaging.

Sonographic Findings of Calcific Tendinitis around the Hip

PURPOSE: To evaluate the sonographic findings of calcific tendinitis around the hip. MATERIALS and METHODS: Ten patients (7 women and 3 men; mean age, 42 years; age range, 34-52 years) with a diagnosis of calcific tendinitis around the hip were evaluated. All the patients underwent radiography and sonography (color Doppler sonography in 6 patients). The sonographic findings were analyzed to determine the level of tendon thickening compared with the contralateral side as well as the shape and posterior acoustic shadowing of the calcification, and vascularity on color Doppler sonography. RESULTS: In all cases, sonography showed a thickening of the tendon compared with the contralateral normal tendon as well as hyperechoic calcific shadows within the thickened tendon. Intratendinous calcifications were mainly observed as a homogeneous ovoid hyperechoic shadow with or without acoustic shadowing. Color Doppler sonography showed increased vascularity within or around the thickened tendon in four of the six patients. CONCLUSION: Sonography is effective in detecting a thickening of the tendon as well as intratendinous calcification, and can be used to diagnose calcific tendinitis around the hip.

Epinephrine-induced Metabolic Acidosis during Orthognatic Surgery: A case report / 대한마취과학회지

Epinephrine has a variety of clinical uses one is its use as a topical hemostatic agent on bleeding surfaces, such as in the mouth. We report a temporal association between the administration of topical epinephrine and the development of metabolic acidosis during general anesthesia. A 21 year-old patient, with facial asymmetry, had undergone orthognatic surgery. During the operation, serial blood gas analysis revealed the onset of a metabolic acidosis following the local infiltration (0.036 mg) and topical application of a high dose of epinephrine-Bosmin(R) (1:1,000 epinephrine). The metabolic acidosis resolved within 5 hours.