Nitrosylation of b2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice

BACKGROUND@#Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. @*METHODS@#Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. @*RESULTS@#Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. @*CONCLUSION@#This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Serological survey for Getah virus in domestic pigs of South Korea

Several outbreaks of Getah virus (GETV) have been reported in horses and pigs, causing large economic losses. However, there have been no reports describing serological survey for GETV in South Korea pigs. The present study conducted serological survey of GETV in South Korean pigs. A total of 670 whole blood samples were collected from domestic pigs. The overall seropositive rate was 26.4%, higher than the rates observed in racehorses in 2013–2014. Preparations for epidemics of novel diseases caused by climate change should include regular serological survey for these diseases, including GETV, and the development of vaccines against novel pathogens.

Immunogenicity of a new inactivated vaccine against feline panleukopenia virus, calicivirus, and herpesvirus-1 for cats

Feline panleukopenia virus (FPV), feline calicivirus (FCV), and feline herpesvirus type-1 (FHV-1) are major infectious pathogens in cats. We evaluated the immunogenicity of a new vaccine containing inactivated FPV, two FCVs, and FHV-1 in animals. An FPV, two FCVs, and an FHV-1 isolate were continuously passaged 70, 50, 80, and 100 times in CRFK cells. FP70, FC50, FC80, and FH100 were propagated and used as vaccine antigens. Two inactivated feline virus vaccines, Rehydragel-adjuvanted vaccine (FRAV) and Cabopol-adjuvanted vaccine (FCAV) were prepared and inoculated into mice and guinea pigs. Humoral immune responses were measured using hemagglutination inhibition (HI) for FPV and virus-neutralizing antibody (VNA) for two FCVs and FHV-1 tests. Serial passages in CRFK cells resulted in increase in titers of FPV and two FCVs but not FHV-1 The FCAV induced higher mean HI and VNA titers than the FRAV in guinea pigs; therefore, the FCAV was selected. Cats inoculated with FCAV developed a mean HI titer of 259.9 against FPV, and VNA titers of 64, 256, and 3.2 against FCV17D03, FCV17D283, and FHV191071, respectively. Therefore, cats inoculated with the FCAV showed a considerable immune response after receiving a booster vaccination.

Rabies neutralizing antibody titers in Korean dogs and cats intended for overseas travel

Animals imported from abroad are a cause of rabies outbreaks in many countries. Therefore, rabies serology testing for dogs and cats traveling abroad is an important measure to reduce the incidence of rabies. Rabies virus antibodies were measured in sera collected from 2,367 dogs and 894 cats between 2017 and 2021. A serum sample with a value of 0.5 IU/mL or higher was considered a pass. The overall pass rates for rabies virus were 96.4% in dogs and 98.4% in cats. The mean rabies virus neutralization assay titers were higher in cats than in dogs and in female than in male animals. According to age, 6-year-old dogs and 9-year-old cats had the highest virus neutralization assay titers. Of the failure cases, 53.0% (53/100) were dogs or cats less than 1 year old. Although the average failure rates in dogs and cats were low at 3.5% and 1.6%, respectively, the factors influencing failure were age and vaccine manufacturer. Therefore, it is necessary to observe the vaccination interval and timing of blood collection after boosting.

Evaluation of commercial immunochromatography test kits for diagnosing canine parvovirus

Rapid immunochromatography test (RICT) kits are commonly used for the diagnosis of canine parvovirus (CPV) because of their rapid turnaround time, simplicity, and ease of use. However, the potential for cross-reactivity and low sensitivity can yield false-positive or false-negative results. There are 4 genotypes of CPV. Therefore, evaluating the performance and reliability of RICT kits for CPV detection is essential to ensure accurate diagnosis for appropriate treatment. In this study, we evaluated the performance of commercial RICT kits in the diagnosis of all CPV genotypes. The cross-reactivity of 6 commercial RICT kits was evaluated using 8 dog-related viruses and 4 bacterial strains. The limit of detection (LOD) was measured for the 4 genotypes of CPV and feline panleukopenia virus. The tested kits showed no cross-reactivity with the 8 dog-related viruses or 4 bacteria. Most RICT kits showed strong positive results for CPV-2 variants (CPV-2a, CPV-2b, and CPV-2c). However, the 2 kits produced negative results for CPV-2 or CPV-2b at a titer of 105 FAID50/mL, which may result in inaccurate diagnoses. Therefore, some kits need to improve their LOD by increasing their binding efficiency to detect all CPV genotypes.

Evaluation of porcine intestinal organoids as an in vitro model for mammalian orthoreovirus 3 infection

Background@#Mammalian orthoreovirus type 3 (MRV3), which is responsible for gastroenteritis in many mammalian species including pigs, has been isolated from piglets with severe diarrhea. However, the use of pig-derived cells as an infection model for swineMRV3 has rarely been studied. @*Objectives@#This study aims to establish porcine intestinal organoids (PIOs) and examine their susceptibility as an in vitro model for intestinal MRV3 infection. @*Methods@#PIOs were isolated and established from the jejunum of a miniature pig.Established PIOs were characterized using polymerase chain reaction (PCR) and immunofluorescence assays (IFAs) to confirm the expression of small intestine-specific genes and proteins, such as Lgr5, LYZI, Mucin-2, ChgA, and Villin. The monolayered PIOs and threedimensional (3D) PIOs, obtained through their distribution to expose the apical surface, were infected with MRV3 for 2 h, washed with Dulbecco’s phosphate-buffered saline, and observed. Viral infection was confirmed using PCR and IFA. We performed quantitative realtime reverse transcription-PCR to assess changes in viral copy numbers and gene expressions linked to intestinal epithelial genes and antiviral activity. @*Results@#The established PIOs have molecular characteristics of intestinal organoids. Infected PIOs showed delayed proliferation with disruption of structures. In addition, infection with MRV3 altered the gene expression linked to intestinal epithelial cells and antiviral activity, and these effects were observed in both 2D and 3D models. Furthermore, viral copy numbers in the supernatant of both models increased in a time-dependent manner. @*Conclusions@#We suggest that PIOs can be an in vitro model to study the infection mechanism of MRV3 in detail, facilitating pharmaceutical development.

Basaloid Squamous Cell Carcinoma of the Lung: Two Case Reports with CT Imaging Findings

Basaloid squamous cell carcinoma of the lung is now considered a subtype of squamous cell carcinoma as per the 2015 WHO classification and remains a relatively unknown type of lung cancer due to its rarity. Here we report two cases of basaloid squamous cell carcinoma of the lung and their CT findings to clarify some of the radiologic features of this type of cancer. Two patients aged 85 and 68 years with lung basaloid squamous cell carcinoma visited our institution and underwent surgical resection. On CT, the lesions were 3.1 and 2.8 cm in size, respectively, well-defined, round in shape with lobulated margins and prominent intratumoral necrosis. The latter case was followed after operation for 20 months, and there was no recurrence of the disease on CT. Although very rare, basaloid squamous cell carcinoma should be considered a subtype of lung cancer in tumors sharing these CT findings.

A Case of Management for Advanced Hepatocellular Carcinoma with Extrahepatic Metastasis by Autologous Natural Killer Cells Combined with Immune Checkpoint Inhibitor

Hepatocellular carcinoma (HCC) has extremely poor prognosis. Immunotherapy has emerged as a new treatment for a number of cancers. Adoptive immunotherapy is one of the important cancer immunotherapy, which relies on the various lymphocytes including cytotoxic T lymphocytes, natural killer (NK) and cytokine induced killer cells. Also, there has been advance in techniques of NK cell activation to more effectively kill the cancer cells. Of note, recently the blocking antibodies targeting programmed cell death protein 1 (PD-1) have shown promising results in diverse cancers including HCC. We report our recent experience of a patient accompanying advanced HCC with extrahepatic metastases. Disease progression had occurred after sorafenib administration, while the patient showed local tumor control and tumor marker decrease by NK cell immunotherapy combined with PD-1 inhibitor therapy. Though, there was no definite survival advantage due to impaired liver function, which might be caused by treatment related toxicities as well as cancer progression.

The effect of Arteriovenous Fistula Cannulation Direction and Puncture Distance on the Recirculation Rate of Hemodialysis Patients / 중환자간호학회지

PURPOSE: The purpose of this study was to compare the effect of recirculation rate according to cannulation direction and interval among hemodialysis patients with arteriovenous fistula (AVF).METHOD: The research used repeated measures design. This study was conducted among thirty patients who received hemodialysis three times a week for longer than a year through AVF at the I University hospital. Three different types of interventions were administered to the participants each week for three weeks. Needles were placed at a different distance and in a different direction each week: 7 cm apart from each other in antegrade direction during the first week, 5 cm apart in retrograde direction in the following week, and 7 cm apart in retrograde direction in the third week.RESULTS: No significant differences in the recirculation rate were found due to any of the three tested methods (p = 1.00).CONCLUSION: This finding suggests that, if the patients have well-functioned AVF, we can choose an appropriate intervention from among the three methods in consideration of the patient's diverse needs.

Factors Affecting Cognitive Function in Patients with Stomach Cancer

PURPOSE: This study aimed to identify factors affecting cognitive function in stomach cancer patients. METHODS: This was a cross-sectional study designed to obtain data from stomach cancer patients. The Global Assessment of Recent Stress, Hospital Anxiety-Depression Scale, Distress Thermometer, Korean version of the Montreal Cognitive Assessment, and electronic medical records were used to assess stress, anxiety, depression, psychological distress, and cognitive function, respectively. RESULTS: Among 182 total participants, there were statistically significant differences in sex between the group of patients who received chemotherapy and those who did not (χ2=5.32, p=.029). There were statistically significant differences in stress and cognitive function between the two groups. The factors affecting cognitive function in stomach cancer patients included distress, stress, anxiety, and depression. CONCLUSION: Cognitive function should be examined with consideration of the psychological distress, stress, anxiety, and depression in patients with stomach cancer. Moreover, an improved program to manage cognitive function is needed, which includes mediation between psychological and physiological factors including stress, anxiety, and cognitive level.

Relationship between Expectations of Clinical Ladder System, Career Commitment and Turnover Intention of Nurses in Small and MediumSized Hospitals / 임상간호연구

PURPOSE: This study was done to explore the relationship between expectations of the clinical ladder system (CLS), career commitment and turnover intention in nurses employed in small-medium sized hospitals. METHODS: Participants were 154 nurses from 3 small-medium sized hospitals in Gyeonggi Province and Gwangju City. From February, 8 to April, 14, 2017, self-report questionnaires were collected and analyzed using frequency, t-test, ANOVA, Scheffé test, and Person correlation coefficients. RESULTS: Of the participant nurses, 61% perceived the CLS as needed. The mean score for expectation of CLS, career commitment, and turnover intention on 5-point scale were 3.38, 3.17, 3.21, respectively. There were no significant differences in expectation of CLS according to general characteristics, but career commitment and turnover intention did show significant differences depending on age, position, type of work shift. Expectation of CLS correlated positively with career commitment (r=.23, p=.005), and career commitment correlated negatively with turnover intention (r=−.49, p < .001). CONCLUSION: The results of this study show that there is a need to adopt the clinical ladder system to improve career commitment.

A Case of Soft Tissue Metastasis in Contralateral Submandibular Space by Regional Recurrence of Lower Lip Cancer / 대한이비인후과학회지

The most common cause of treatment failure in oral cavity cancer is when it is found to have local recurrence, usually occurring in the ipsilateral cervical lymph node. On the contrary, it is extremely rare to find local recurrence in soft tissue metastasis (STM) in the contralateral neck. Furthermore, lung cancer and malignant lymphoma are most commonly confined to their primary sites. The poor general condition increases the likelihood of STM, which indicates bad prognosis. A 72-year-old man with a hard and fixed mass on the right submandibular space visited our clinic. He had received a wide excision with local flapreconstruction for squamous cell carcinoma in the left corner of lower lip 18 months ago. We performed the wide excision with bilateral selective neck dissection (I–III), and he was finally diagnosed as STM from contralateral lip cancer. We report this unique and rare disease entity with a literature review.

Angiolipoma on the Lumbar Spine

Angiolipomas are composed of mature adipose tissue and blood vessels. Spinal angiolipomas are rare benign tumors with a good prognosis, and most symptoms are due to progressive compression of the spinal cord and root. The treatment of choice is total resection without any additional therapy. We report a case of an epidural angiolipoma on the lumbar spine in a 69-year-old man with weakness of the lower extremities. Lumbar magnetic resonance images revealed a well-enhanced epidural mass. He underwent laminectomy, and the tumor was completely removed. Pathologic examination confirmed the tumor was an angiolipoma. The patient’s symptoms gradually improved postoperatively.

A serological study of severe fever with thrombocytopenia syndrome using a virus neutralization test and competitive enzyme-linked immunosorbent assay

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV). The SFTSV appears to have a wide host range, as SFTSV-positive ticks have been isolated from both farm animals and wild rodents. Therefore, it is important to monitor SFTSV-positive animals to prevent the transmission of SFTSV from animals to humans. Previously, we developed a competitive enzyme-linked immunosorbent assay (cELISA) to detect SFTSV-specific antibodies from field animals and compared the cELISA results to those from an indirect immunofluorescence assay (IFA). In this study, cELISA results were compared to and evaluated against the results from both an IFA and a virus neutralization (VN) test of 193 bovine serum samples (including two bovine positive control sera) and 70 horse serum samples. The consistency (98.9%) between cELISA and VN results was higher than that (97.4%) between cELISA and IFA for the bovine serum samples. Similarly, for the horse serum samples, the consistency (88.6%) between cELISA and VN results was higher than that (84.3%) between the cELISA and IFA. These findings indicate that our newly developed cELISA can be used for surveillance or epidemiological studies of SFTSV in animals.

A Case of Co-Existence Squamous Cell Carcinoma with Granuloma in Posterior Glottis / 대한이비인후과학회지

The laryngeal granuloma (LG) is non-neoplastic lesion that mainly develops in the posterior vocal folds. It is welknown that mis- or overuse of voice, habitual coughing, and endotracheal intubation can become the cause of LG. The laryngopharyngeal reflux also comes into the spotlight as an etiologic factor. Although LG has a tendency to recur easily, it is not a premalignant lesion. The co-existence with granuloma and laryngeal cancer has not been reported earlier. Recently, we encountered a 72-year-old man with a posterior glottic mass, which was diagnosed as squamous cell carcinoma coexisting with granuloma. To our knowledge, this is a first report on two coexisting carcinomas in the glottis.

Two Cases of Immunoglobulin G4-Related Sclerosing Disease in Submandibular Triangle / 대한이비인후과학회지

Immunoglobulin G4-related sclerosing disease (IgG4-RD) is histologically a chronic inflammatory disorder characterized by infiltration of lymphoplasmacytes, sclerosis, and an elevated serum level of IgG4 and IgG4 positive plasmocytes. IgG4-RD is associated with autoimmune pancreatitis, sclerosing cholangitis, sialalithiasis, retroperitoneal diseases, inflammatory arotitis and Mikulicz's disease, typically including the lacrimal glands, salivary glands, pancreas, thyroid gland, lungs and kidneys. It is important to distinguish IgG4-RD from neoplastic disease as it responses well to steroid. Because consensus for nomenclature of IgG4-RD is recently made, reports of IgG4-RD in the Head and Neck area are still rare. In the first case, a 68-year-old man presented with a recurring submandibular gland mass from 7 years ago; he underwent submandibular gland resection and was diagnosed as IgG4-RD. In the second case, a 69-year-old mass presented with a relapsing right neck mass on level Ib. He underwent an exsional biopsy and was diagnosed with the same disease entity. We experienced two cases of IgG4-RD, and so report them with a brief literature review.

Development and evaluation of an immunochromatographic assay using a gp51 monoclonal antibody for the detection of antibodies against the bovine leukemia virus

Infection of cattle with bovine leukemia virus (BLV) has been observed and reported worldwide, including in Korea. The onsite identification of infected cattle would help decreasing and eradicating BLV infections on farms. Here, we present a new immunochromatographic assay that employs monoclonal antibodies (MAbs) for the detection of antibodies against BLV in the field. BLV envelope glycoprotein (gp)51 was expressed in E. coli, and MAbs against recombinant BLV gp51 were generated for the development of an immunochromatographic assay to detect BLV antibodies in cattle. The sensitivity and specificity of the assay were determined by comparing these results with those obtained from a standard enzyme linked immunosorbent assay (ELISA). A total of 160 bovine sera were used to evaluate the new immunochromatographic assay. Using ELISA as a reference standard, the relative specificity and sensitivity of this assay were determined to be 94.7% and 98%, respectively. Because of its high sensitivity and specificity, this BLV antibody detection assay would be suitable for the onsite identification of BLV infection in the field.

Triple Arterial Phase MR Imaging with Gadoxetic Acid Using a Combination of Contrast Enhanced Time Robust Angiography, Keyhole, and Viewsharing Techniques and Two-Dimensional Parallel Imaging in Comparison with Conventional Single Arterial Phase

OBJECTIVE: To determine whether triple arterial phase acquisition via a combination of Contrast Enhanced Time Robust Angiography, keyhole, temporal viewsharing and parallel imaging can improve arterial phase acquisition with higher spatial resolution than single arterial phase gadoxetic-acid enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Informed consent was waived for this retrospective study by our Institutional Review Board. In 752 consecutive patients who underwent gadoxetic acid-enhanced liver MRI, either single (n = 587) or triple (n = 165) arterial phases was obtained in a single breath-hold under MR fluoroscopy guidance. Arterial phase timing was assessed, and the degree of motion was rated on a four-point scale. The percentage of patients achieving the late arterial phase without significant motion was compared between the two methods using the χ2 test. RESULTS: The late arterial phase was captured at least once in 96.4% (159/165) of the triple arterial phase group and in 84.2% (494/587) of the single arterial phase group (p < 0.001). Significant motion artifacts (score ≤ 2) were observed in 13.3% (22/165), 1.2% (2/165), 4.8% (8/165) on 1st, 2nd, and 3rd scans of triple arterial phase acquisitions and 6.0% (35/587) of single phase acquisitions. Thus, the late arterial phase without significant motion artifacts was captured in 96.4% (159/165) of the triple arterial phase group and in 79.9% (469/587) of the single arterial phase group (p < 0.001). CONCLUSION: Triple arterial phase imaging may reliably provide adequate arterial phase imaging for gadoxetic acid-enhanced liver MRI.

Development and evaluation of a competitive enzyme-linked immunosorbent assay using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia syndrome virus in bovine sera

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne infectious disease that impacts humans. This disease manifests as a decreased blood cell count and multi-organ failure, with a case-fatality rate of more than 12% in China. Because vaccines or antiviral drugs for the treatment of this disease are not available, monitoring the SFTS circulation in animals and controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal antibodies against the recombinant nucleoprotein of SFTSV were generated to develop a competitive enzyme-linked immunosorbent assay (cELISA) for the detection of antibodies against SFTSV infection in cattle. The specificity and sensitivity of cELISA was assessed by comparing the results of this assay to those of an immunofluorescence assay (IFA). The results of the cELISA using 416 field bovine serum samples and laboratory-immunized positive sera showed 98.1% consistency with those of the IFA. The cELISA used in this study did not show cross-reactivity with antisera against other viral cattle diseases. The cELISA presented in this study can be applied to detect antibodies against SFTSV in cattle.

A Case of Anisakiasis Invading the Oropharynx / 대한이비인후과학회지

Anisakiasis is one of the fish-transmitted infections that result from the accidental ingestion of third-stage larva belonging to the family Anisakidae. A large number of cases of gastric anisakiasis have been reported in countries where the eating of raw fish is customary; however, there have been very few reports of anisakiasis involving the oral cavity and oropharynx. A 46-year-old woman complained of sore throat shortly after eating raw flatfishes. The oropharyngeal examination revealed two living tubular spinning objects in the submucosal layer of left posterior pillar. It was removed with biopsy forceps. We report a very rare and unique case of anisakiasis in oropharynx confirmed by pathologic findings. To best of our knowledge, this is the first case report involving oropharyngeal anisakiasis in Korea.