A case of multiple organ injury resuscitated by collaboration of damage control surgery and interventional radiology in hybrid emergency room.

Background: Hybrid emergency room systems, namely hybrid ER (HER), enable us to perform computed tomography (CT), surgery, and interventional radiology (IVR) without patient transfer. HER significantly shortened the time to CT after arrival and allowed us to achieve early intervention, resulting in reduced mortality from exsanguination in patients with severe blunt trauma. Case Presentation: We encountered a patient diagnosed with left common iliac artery occlusion and dissection caused by blunt traumatic compressive abdominal injury with transection of the small intestine, kidney, and adrenal and pelvic ring fractures. Although the patient experienced cardiopulmonary arrest (CPA) immediately after CT, we performed damage control surgery (DCS) and IVR after temporary aortic occlusion in the HER and resuscitated the patient. Conclusion: The present case, in which rapid diagnosis and intervention were performed and the patient was successfully resuscitated, supports the efficacy of the HER system for managing severe blunt trauma.

Why Do Cochlear Implant Candidates Defer Surgery? A Retrospective Case-Control Study.

OBJECTIVE(S): Despite undergoing thorough cochlear implant (CI) candidacy evaluation and counseling, some patients ultimately elect against implantation. This study sought to identify patient-related and socioeconomic factors predicting CI deferral. METHODS: A retrospective study of adult (≥18 years old) CI candidates presenting between 2007 and 2021 at a tertiary academic CI center was performed. The primary outcome was device implantation. Data collected included age, gender, hearing status, race, zip code of residence, median family income (MFI), distance traveled from the CI center, marital status, employment status, and insurance status. Multivariable binary logistic regression was performed to identify predictors of implantation. RESULTS: A total of 200 patients qualifying for CI were included, encompassing 77 adults deferring surgery (CI-deferred) and 123 consecutive adults electing for surgery (CI-pursued). Age, gender, hearing status, insurance type, employment status, distance from the implant center, and MFI were comparable between the groups (p > 0.05). Compared to CI-pursued patients, CI-deferred patients were more likely to be non-Caucasian (24.7% vs. 9.8%, p = 0.015) and unmarried (55.8% vs. 38.2%, p = 0.015). On multivariable logistic regression, older age (OR 0.981, 0.964-0.998, p = 0.027), African American race (OR 0.227, 0.071-0.726, p = 0.012), and unmarried status (OR 0.505, 0.273-0.935, p = 0.030) were independent predictors of implant deferral. CONCLUSION: This study demonstrates that increasing age at evaluation, African American race, and unmarried status are predictors for deferring CI surgery despite being implant candidates. These patients may benefit from increased outreach in the form of counseling, education, and social support prior to undergoing CI surgery. LEVEL OF EVIDENCE: 3 - retrospective study with internal control group Laryngoscope, 134:2857-2863, 2024.

Update on oral and oropharyngeal cancer staging - International perspectives.

Squamous cell carcinoma of the oral cavity and oropharynx have been used synonymously and interchangeably in the world literature in the context of head and neck cancers. As the 21st century progresses, divergence between the two have become more evident, particularly due to evidence related to human papillomavirus-associated oropharyngeal squamous cell carcinoma. As such, the American Joint Committee on Cancer recently published the 8th edition Cancer Staging Manual, serving as a continued global resource to clinicians and researchers. Through changes in staging related to T and N clinical and pathologic classifications, the new system is expected to influence current management guidelines of these cancers that have distinct anatomic and etiopathogenic characteristics. This article aims to review such impactful changes in a time of critical transition of the staging of head and neck cancer and how these changes may affect clinicians and researchers worldwide.

Comparison of psychosocial factors over time among HPV+ oropharyngeal cancer and tobacco-related oral cavity cancer patients.

INTRODUCTION: The role of human papilloma virus (HPV) in the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC) is well documented, as is the excellent prognosis of patients with HPV-associated disease; in contrast, oral cavity squamous cell carcinoma (OCSCC) is associated with tobacco and alcohol use and has a worse prognosis. While causative factors, staging, and treatment guidelines differ between these cancer subsets, few studies have compared psychosocial factors in these groups. OBJECTIVE: To explore differences in psychosocial factors between HPV+ OPSCC patients versus OCSCC smokers. METHODS: A prospective cohort study at a single multidisciplinary, tertiary care HNC center was completed with recruitment from 2010 to 2013 using self-administered questionnaires before treatment and at 12 months. Patients were included with a diagnosis of HPV+ OPSCC or OCSCC with a smoking history. 38 (21 HPV+ OPSCC/17 OCSCC) met criteria. The main outcomes included self-efficacy, symptom severity, cancer worry, and depression. RESULTS: A total of 38 (21 HPV+ OPSCC/17 OCSCC) patients (mean age: 57 [32-76], 73.7% male, 78.9% Caucasian, 71% stage IV) met inclusion criteria. OPSCC patients tended to be of male sex, Caucasian race, and single. Furthermore, OPSCC patients were more likely than OCSCC patients to have private insurance, be employed, and use alcohol and tobacco less frequently. Regarding psychosocial factors, HPV+ OPSCC patients reported lower symptom severity (2.7 versus 3.3), depression (12.0 versus 14.0) and cancer worry (2.8 versus 3.2) at baseline compared to OCSCC patients. Depression decreased significantly over time in OPSCC patients (12.0 to 9.9; effect size: -3.2 (95% CI: -5.9 to -0.4)). Although not statistically significant, cancer worry decreased in both groups (2.8 to 2.4 and 3.2 to 2.7, respectively, effect sizes: -0.3 (95% CI: -0.7-0.08) and -0.6 (95% CI: -1.2-0.05), respectively). No statistically significant differences in patterns of change over time were noted between groups. CONCLUSIONS AND RELEVANCE: This pilot study highlighted a pattern of reduced quality of life parameters in OCSCC patients at baseline with similar improvements over time compared to the OPSCC cohort. Although different in cancer etiology and treatment plans, HPV+ OPSCC and tobacco-related OCSCC patients both require multidisciplinary cancer care plans that address psychosocial concerns. LEVEL OF EVIDENCE: 2B.

Smoking-induced control of miR-133a-3p alters the expression of EGFR and HuR in HPV-infected oropharyngeal cancer.

PURPOSE: Human papillomavirus (HPV) infected oropharyngeal squamous cell carcinoma (OPSCC) patients have a better prognosis compared to HPV(-) counterparts. However, a subset of HPV(+) patients with a smoking history fail to respond to the standard of care treatments such as radiation and chemotherapy. To understand the underlying mechanism driving HPV(+) OPSCC patient resistance to treatment and recurrence, we sought to identify and characterize the differentially expressed miRNAs and their target genes in HPV(+) smokers and non-smokers. EXPERIMENTAL DESIGN: MicroRNA expression analysis was performed using Nanostring in tumor tissues isolated from a prospective cohort of HPV(+) smoking (n = 9) and HPV(+) (n = 13) non-smoking OPSCC patients. Identified miRNAs of interest were further validated using qRT-PCR in cigarette smoke extract (CSE) treated HPV(+) and E6/E7 overexpressing HPV(-) cells. RESULTS: In comparison to OPSCC HPV(+) non-smokers, 38 miRNAs were significantly altered in the HPV(+) smoker patients cohort and out of that 9 were downregulated. Altered miRNA expression was also detected in the serum and metastatic lymph nodes of HPV(+) smokers versus non-smokers. Expression of miR-133a-3p was significantly downregulated in OPSCC smokers, HPV(+) cells and E6/E7 overexpressing HPV(-) cells treated with CSE. Reduction of miR-133a-3p induced the upregulation of miR-133a-3p target mRNAs EGFR and HuR. CONCLUSIONS: Our results indicate that miR-133a-3p is a target of smoking-induced changes in HPV(+) patients and alters the expression of EGFR and HuR which may promote HPV associated oropharyngeal cancer. Therefore, future treatment strategies for HPV(+) OPSCC smokers should focus on EGFR inhibition and the development of selective therapies to target HuR.

Outcomes and prognostic factors for parotid acinic cell Carcinoma: A National Cancer Database study of 2362 cases.

OBJECTIVES: To evaluate the demographics, clinical features, survival outcomes, and prognostic indicators of patients with acinic cell carcinoma (ACC) of the parotid gland with emphasis on the roles of grade, tumor size, and nodal status in survival. MATERIALS AND METHODS: A retrospective analysis of cases diagnosed between 2004 and 2012 from the National Cancer Database was performed. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: 2362 cases were identified. Most patients were females (61.3%) and Caucasian (85.4%) with a median age of 54 years (range, 18-90 years). Most tumors were <3 cm in size (75.8%). Regional metastases and high-grade histology were rare (8.2%, 5.1%). All patients received surgery as primary treatment with 42.7% of patients receiving adjuvant radiation therapy or chemoradiotherapy. 5 year overall survival was 88.6%. On multivariable analysis, age >70 years (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 5.64-17.91), high-grade (HR: 5.30, 95% CI: 3.39-8.29), tumor size of 3 to 6 cm (HR: 1.53, 95% CI: 1.10-2.12), tumor size >6 cm (HR: 2.98, 95% CI: 1.681-5.289), pN2+ (HR: 3.14, 95% CI: 2.10-4.69), T4 (HR: 2.89, 95% CI: 1.74-4.80) were significant prognosticators. CONCLUSION: Although patients with ACC generally are considered to have a favorable prognosis, an aggressive subgroup with poor outcomes was identified. This group is characterized by high-grade, advanced T classification, tumors larger than 3 cm, with regional metastases and age greater than 70 years. Histologic grade is a substantially stronger predictor of survival than T and N classifications.

Early feasibility of hypoglossal nerve upper airway stimulator in patients with cardiac implantable electronic devices and continuous positive airway pressure-intolerant severe obstructive sleep apnea.

BACKGROUND: Implantable hypoglossal nerve upper airway stimulation (HNS) is a novel strategy approved by the US Food and Drug Administration for the management of moderate-to-severe obstructive sleep apnea (OSA) in patients with continuous positive airway pressure therapy intolerance or failure. Because of the proximity of a cardiac implantable electronic device (CIED) to this stimulator, interaction between these devices is theoretically possible. OBJECTIVE: The purpose of this study was to assess interactions between an implantable HNS device and a CIED. METHODS: We retrospectively analyzed 14 ad hoc patients with continuous positive airway pressure-intolerant, moderate-to-severe OSA and pre-existing transvenous CIEDs undergoing HNS implantation (Inspire II, Inspire Medical Systems). We assessed these devices for their pre and postimplant OSA outcomes and for possible device-device interaction. All patients were followed up for 1 year. RESULTS: Of the 14 patients, 9 had a pacemaker (8 dual-chamber, 1 single-chamber), 4 had an implantable cardioverter-defibrillator (2 dual-chamber, 1 single-chamber), and 1 had a cardiac resynchronization therapy device. All the HNS devices were implanted on the opposite side of the CIED. All CIEDs were programmed bipolar. HNS were programmed either unipolar or bipolar. During implant, intraoperative testing was performed to confirm that bipolar and unipolar HNS stimulation did not impact CIED sensing. During the follow-up period, no oversensing episodes were noted on the CIEDs. CONCLUSION: In this early experience, simultaneous use of a novel hypoglossal nerve upper airway stimulation device with transvenous CIEDs seems to be safe, effective, and without any device-device interactions.

Nonsurgical management of human immunodeficiency virus-associated parotid cysts: A systematic review and meta-analysis.

BACKGROUND: The purpose of this clinical review was to analyze the effectiveness of nonsurgical management options for human immunodeficiency virus (HIV)-associated parotid cysts. METHODS: We conducted systematic and meta-analysis reviews. Primary outcomes were complete or partial responses. RESULTS: Systematic review identified 12 relevant studies. The average rates of complete response for antiretroviral therapy (ART), sclerotherapy, and fine-needle aspiration (FNA) were 52.8%, 55.5%, and 33.3%, respectively. Three radiotherapy studies, totaling 104 patients, were included in a meta-analysis. Patients receiving high-dose therapy achieved complete and partial response rates of 65.8% (95% confidence interval [CI] 54.3%-76.2%) and 25.2% (95% CI 16.1%-36.3%), respectively. Patients receiving low-dose therapy achieved complete and partial response rates of 23.2% (95% CI 1.2%-60.9%) and 22.3% (95% CI 5.2%-87.8%), respectively. The rate of complete response was significantly greater for high-dose radiotherapy compared to low-dose (P < .001). CONCLUSION: Among nonsurgical treatment modalities for HIV-associated parotid cysts, radiotherapy has the highest number of reported outcomes in the literature and our analysis suggests that higher dose radiotherapy has higher rates of achieving complete response.

Predictors of contralateral-bilateral nodal disease in oropharyngeal cancer: A National Cancer Data Base Study.

BACKGROUND: Oropharyngeal squamous cell carcinoma (SCC) frequently presents with cervical metastasis. Roles of human papillomavirus (HPV) status, among other factors, on laterality are elusive. METHODS: The National Cancer Database was reviewed for oropharyngeal SCC diagnosed from 2010-2014. Predictors of clinically evident contralateral or bilateral nodal disease were identified. RESULTS: A total of 15 517 patients with oropharyngeal SCC met criteria. The majority was HPV-positive. Histologically poorly differentiated tumors were more frequent in the HPV-positive group (55.7% vs 37.6%; P < .001). By incidence, there was no statistical difference in contralateral or bilateral nodal disease between HPV-positive and HPV-negative patients (14.2% vs 14.5%, respectively; P = .769). On multivariable analysis, notable predictors of contralateral or bilateral nodal disease included HPV-positivity (odds ratio [OR] 1.26; 99% confidence interval [CI] 1.10-1.44), base of tongue (BOT) location (OR 2.15; 99% CI 1.88-2.45), poorly differentiated tumor (OR 1.72; 99% CI 1.20-2.46), and T4 classification (OR 6.65; 99% CI 5.34-8.28). CONCLUSION: Patients with HPV-associated oropharyngeal SCC have increased likelihood of contralateral or bilateral nodal disease. Tumor grade, tumor location, and tumor size are also independent predictors.

The Incidence and Characterization of Globus Sensation, Dysphagia, and Odynophagia Following Surgery for Obstructive Sleep Apnea.

STUDY OBJECTIVES: To determine the incidence, duration, and predictors of swallowing-related symptoms following upper airway surgery for obstructive sleep apnea. METHODS: Adults (age 18 years or older) who underwent surgery for obstructive sleep apnea at a tertiary care institution from January 2012 to December 2015 were retrospectively reviewed. The incidence, duration, and associated factors of postoperative swallowing complaints were evaluated. RESULTS: A total of 130 patients (135 surgical encounters) met criteria for inclusion. There were 91 men (70.0%) and 39 women (30.0%) with a median age of 60 years (range: 19-79). Presurgical diagnosis of gastroesophageal reflux disease was present in 57 patients (43.8%). An average of 2.1 procedures (± 0.8) were conducted at each encounter. Uvulopalatopharyngoplasty (54.8%) was the most common followed by radiofrequency ablation of the soft palate (34.8%) and tongue base (29.6%). Postoperatively, 25 patients (19.8%) complained of dysphagia, 14 (10.9%) of globus, and 9 (6.7%) of odynophagia. Preoperative gastroesophageal reflux (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.41-11.91) and hyoid myotomy with suspension (OR 4.88, 95% CI 1.34-17.77) were significant predictors for dysphagia. Radiofrequency ablation of the tongue base (OR 5.00, 95% CI 1.28-19.50) was a predictor for globus sensation. Median symptom durations, in months, were 4.0 for dysphagia, 7.3 for globus, and 3.0 for odynophagia. CONCLUSIONS: Preoperative gastroesophageal reflux and hyoid myotomy with suspension procedure were associated with postoperative dysphagia whereas radiofrequency ablation of the tongue base was associated with globus. These findings can assist surgeons in providing preoperative counseling and postoperative supportive measures regarding dysphagic symptoms following sleep surgery.

Extracapsular Dissection vs Superficial Parotidectomy of Benign Parotid Lesions: Surgical Outcomes and Cost-effectiveness Analysis.

Importance: The clinical implications of extracapsular dissection over superficial parotidectomy are controversial and limited in data on cost-effectiveness. Objective: To compare extracapsular dissection with superficial parotidectomy for benign parotid tumors with respect to surgical outcomes and cost-effectiveness. Design, Setting, and Participants: This was a retrospective medical record review and cost-effectiveness analysis performed from August 2012 to November 2015 at a tertiary care institution. Adult patients (age ≥18 years) who underwent parotidectomy for benign parotid lesions were included. Exposures: Treatment by extracapsular dissection or superficial parotidectomy. Main Outcomes and Measures: Differences in postoperative complication rates and health services outcomes, including procedure time, anesthesia time, length of stay, and charges for surgeon, anesthesia, operating room, and hospital. Results: A total of 46 parotidectomies consisting of 26 extracapsular dissections and 20 superficial parotidectomies met criteria. Of the 46 patients, 33 were women. Patient ages ranged from 18 to 83 years. Lesion features were similar between groups with most being pleomorphic adenoma. Procedure time (effect size, -1.31; 95% CI, -1.93 to -0.65), anesthesia time (effect size, -1.37; 95% CI, -1.99 to -0.70), and length of stay (effect size, -0.66; 95% CI, -1.25 to -0.05) were significantly shorter for extracapsular dissection compared with superficial parotidectomy. Moreover, anesthesia (effect size, -1.55; 95% CI, -2.19 to -0.86), operating room (effect size, -1.09; 95% CI, -1.69 to -0.45), and total hospital charges (effect size, -1.13; 95% CI, -1.74 to -0.49) were significantly less for extracapsular dissection while remaining charges, including surgeon, showed no difference. Finally, facial nerve weakness, great auricular nerve dysesthesia, and other relevant postoperative complications were comparable between groups. Conclusions and Relevance: In the hands of an experienced surgeon, extracapsular dissection is a shorter, less costly, and equally safe alternative to traditional superficial parotidectomy when treating benign parotid lesions. Further follow-up is needed to ensure these perceived advantages are maintained over time.

Clinical features of ectomesenchymal chondromyxoid tumors: A systematic review of the literature.

Ectomesenchymal chondromyxoid tumors are rare, benign neoplasms of the head and neck most commonly found within the oral cavity. While histopathological evaluation has been the primary focus of prior studies, clinical characterization of this rare entity currently remains sparse. Thus, this study was performed to provide insights into the clinical characteristics of ectomesenchymal chondromyxoid tumors to aid clinicians in distinguishing the lesion from other benign and malignant processes for a more accurate diagnosis and treatment. Moreover, this study includes a unique case of ectomesenchymal chondromyxoid tumor arising in the base of tongue, now the fourth to arise at that anatomic site. Including this case, a systematic review of the literature identified only 60 individual cases reported thus far. This study provides a detailed analysis of all 60 cases including demographics, clinical presentation, radiographic imaging, follow-up, and recurrence rate.

Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program.

CD4(+) T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells. Because type I IFNs are often generated in immune responses, we set out to investigate whether these factors are relevant to TFH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized TFH-expressed genes. However, we show that type I IFNs (IFN-α/ß) induced B cell lymphoma 6 (Bcl6) expression, the master regulator transcription factor for TFH cells, and CXCR5 and programmed cell death-1 (encoded by Pdcd1), key surface molecules expressed by TFH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for TFH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5, and Pdcd1 loci. These data suggest that type I IFNs (IFN-α/ß) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset.

Stable emulsions with thermally responsive microstructure and rheology using poly(ethylene oxide) star polymers as emulsifiers.

Poly(ethylene oxide) star polymers (PEO stars) were prepared by atom transfer radical polymerization of 2000 molecular weight PEO methacrylate macromonomer with divinylbenzene as a crosslinking co-monomer. With an average of 460 arms per star, these PEO stars had a 12 nm radius of gyration that is consistent with a dense polymer core surrounded by an extended PEO corona. The PEO stars were extremely efficient emulsifiers, stabilizing cyclohexane-in-water or xylene-in-water emulsions against coalescence for several months at aqueous phase concentrations as low as 0.008 wt% or 0.01 wt%, respectively. Consistent with their emulsifying performance, PEO star adsorption decreased interfacial tension by approximately 22 mN/m and imparted significant dilatational elasticity to the xylene/water interface. PEO stars were thermally responsive, displaying a cloud point upon heating in water that was tuned by addition of kosmotropic electrolytes, and they in turn produced xylene-in-water emulsions that were thermally responsive in terms of the dispersion state of the emulsion droplets and the emulsion rheology. Emulsions prepared at room temperature mainly had non-flocculated droplets. Heating such an emulsion above the cloud point temperature triggered droplet flocculation, but not coalescence, that in turn was associated with increased viscous and elastic moduli of the emulsion measured after cooling back to room temperature. Emulsions that initially were homogenized above the cloud point temperature and then cooled showed neither droplet flocculation nor rheological thickening relative to emulsions that were prepared and held at room temperature. A mechanism based on the bridging behavior of PEO stars adsorbed at the droplet/water interface is postulated to explain this thermal response of the emulsion microstructure.

Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer's disease.

Curcumin, which can exist in an equilibrium between keto and enol tautomers, binds to beta-amyloid (Abeta) fibrils/aggregates. The aim of this study was to assess the relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities. Curcumin derivatives with keto-enol tautomerism showed high levels of binding to Abeta aggregates but not to Abeta monomers. The binding activity of the keto form analogue of curcumin to Abeta aggregates was found to be much weaker than that of curcumin derivatives with keto-enol tautomerism. The color of a curcumin derivative with keto-enol tautomerism, which was substituted at the C-4 position, changed from yellow to orange within 30 min of being combined with Abeta aggregates in physiological buffer. This resulted from a remarkable increase in the enol form with extended conjugation of double bonds upon binding. These findings suggest that curcumin derivatives exist predominantly in the enol form during binding to Abeta aggregates, and that the enolization of curcumin derivatives is crucial for binding to Abeta aggregates. The keto-enol tautomerism of curcumin derivatives may be a novel target for the design of amyloid-binding agents that can be used both for therapy and for amyloid detection in Alzheimer's disease.

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging.

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.

Efficient delivery of antibody into living cells using a novel HVJ envelope vector system.

Introduction of antibodies which retain their function into cells using a simple and easy method would be very useful for study of the intracellular events in living cells. In this study, we developed a new method for intracellular delivery of antibody. It includes a combination of a novel IgG-capturing protein and hemagglutinating virus of Japan envelope (HVJ-E), an inactivated Sendai virus particle which can deliver a variety of molecules into mammalian cells via membrane-fusing activity. The IgG-capturing protein, which was molecularly designed to have two functions, was prepared as a fusion protein (ZZ-NP) of ZZ-dimer derived from an immunoglobulin-binding domain of protein A and nucleocapsid protein (NP), a part of the structural protein of HVJ. ZZ-NP was efficiently incorporated into the HVJ-E particle by treatment with detergent, and enhanced the incorporation of IgG. Moreover, fluorescence immunostaining revealed that the incorporated antibody was very efficiently introduced into living cells while retaining its function, i.e. anti-NPC (nuclear pore complex) monoclonal antibody was selectively located around cell nuclei. These findings suggest that this method is useful for intracellular delivery of antibody and for analysis of biological function of sub-cellular molecules in living cells.

Noncytotoxic ribonuclease, RNase T1, induces tumor cell death via hemagglutinating virus of Japan envelope vector.

Several ribonucleases, including onconase and alpha-sarcin, are known to be toxic to tumor cells. On the other hand, although its structure is related to that of alpha-sarcin, RNase T1 is noncytotoxic because of its inability to internalize into tumor cells. In this study, we internalized RNase T1 into human tumor cells via a novel gene transfer reagent, hemagglutinating virus of Japan (HVJ) envelope vector, which resulted in cell death. This cytotoxicity was drastically increased by pretreatment of HVJ envelope vector with protamine sulfate, and was stronger than that of onconase, which is in phase III human clinical trials as a nonmutagenic cancer chemotherapeutic agent. Furthermore, internalized RNase T1 induced apoptotic cell death programs. Because its cytotoxicity is unfortunately not specific to tumor cells, it cannot at present be developed as an anticancer drug. However, we believe that RNase T1 incorporated in HVJ envelope vector will be a unique anticancer drug if HVJ envelope vector can be targeted to tumor cells.

Effective magnetic labeling of transplanted cells with HVJ-E for magnetic resonance imaging.

Magnetic labeling of transplanted cells permits us to monitor their localization non-invasively using MRI. Since most transfection agents for magnetic labeling have the same cationic charge as Fe(3+), the efficiency may be reduced. The hemagglutinating virus-envelope has no charge and utilizes membrane fusion activity to deliver internalized materials. In this study, we investigated the feasibility of using the envelope to incorporate paramagnetic Fe(3+) particles into PC12 cells and astrocytes. The envelope effectively labeled both cells with Fe(3+), which showed significant decreases of signal intensity in T2-weighted MRI. Labeled cells transplanted into the rat striatum were clearly visualized by T2*-weighted MRI at a magnetic field of 2 T. The results indicate that the hemagglutinating virus-envelope is a powerful tool for magnetic labeling.