bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clathrin‐independent internalization of the human histamine H1‐receptor in CHO‐K1 cells
Authors: Self Timothy J , Oakley Sarah M , Hill Stephen J 
Published: August 2005

The aim of the present study was to investigate the cellular pathway involved in histamine‐stimulated internalization of the human H1‐receptor in CHO‐K1 cells expressing N‐terminal myc‐tagged H1‐receptor (Myc‐H1) or N‐terminal myc‐C‐terminal green fluorescent protein (Myc‐GFP H1) versions of the receptor.Studies of3H‐mepyramine binding and histamine‐stimulated3H‐inositol phosphate accumulation in these cells showed that the Myc‐H1and Myc‐GFP H1‐receptors had identical pharmacology to the wild‐type H1‐receptor.The Myc‐H1‐receptor was rapidly internalized in CHO‐K1 cells following stimulation with histamine (0.1 mM). This response occurred within 15 min, and could be prevented by the quaternary H1‐receptor antagonistα‐pirdonium. Similar data were obtained with the Myc‐GFP H1‐receptors.Internalization of the Myc‐GFP H1‐receptor was maintained in the absence of extracellular calcium and was not inhibited by the CAM kinase II inhibitor KN‐62 (10 μM).Phorbol dibutyrate, an activator of protein kinase C, was also able to stimulate internalization of the H1‐receptor. However, inhibition or downregulation of protein kinase C (which significantly modified histamine‐stimulated inositol phosphate responses) was without effect on the internalization of the H1‐receptor stimulated by histamine.Hypertonic sucrose did not prevent histamine‐induced internalization of the Myc‐GFP H1‐receptor, but was able to attenuate internalization of transferrinviaclathrin‐mediated endocytosis in the same cells. In contrast, preincubation of cells with filipin or nystatin, which disrupts caveolae and lipid rafts, completely inhibited the histamine‐induced internalization of the Myc‐GFP H1‐receptor, but was without effect on the sequestration of transferrin.The H1‐receptor and cholera toxin subunit B were colocalized under resting conditions at the cell surface. Immunohistochemical studies with an antibody to caveolin‐1 confirmed that this protein was also localized predominantly to the plasma membrane. However, following stimulation of CHO‐Myc‐GFP H1cells with histamine, there was no evidence for internalization of caveolin‐1 in parallel with the H1‐receptor.These data provide strong evidence that the H1‐receptor is internalizedviaa clathrin‐independent mechanism and most likely involves lipid rafts.British Journal of Pharmacology(2005)146, 612–624. doi:10.1038/sj.bjp.0706337
The role of p38 MAPK activation in auranofin‐induced apoptosis of human promyelocytic leukaemia HL‐60 cells
Authors: Park Seon‐Joo , Kim In‐Sook 
Published: August 2005

In a previous study, we reported an antileukaemic activity of auranofin (AF), demonstrating its dual effects: on the induction of apoptotic cell death and its synergistic action with retinoic acid on cell differentiation. In this study, we investigated the downstream signalling events of AF‐induced apoptosis to determine the molecular mechanisms of AF activity.
Treatment of HL‐60 cells with AF induced apoptosis in a concentration‐ and time‐dependent manner. Western blot analysis showed that AF‐induced apoptosis was accompanied by the activation of caspase‐8, caspase‐9, and caspase‐3, and the release of cytochrome c from the mitochondria.
The phosphorylation and kinase activities of p38 mitogen‐activated protein kinase (p38 MAPK) increased gradually until 12 h after AF (2 μM) treatment, and p38 MAPK was also activated concentration‐dependently. Pretreatment with SB203580, a specific inhibitor of p38 MAPK, significantly blocked DNA fragmentation and the cleavage of procaspase‐8, procaspase‐3, and poly‐ADP‐ribose polymerase (PARP), whereas SB203580 alone had no effect.
Reactive oxygen species (ROS) were also detected within 1 h after AF treatment, and the antioxidant N‐acetyl‐L‐cysteine (NAC) effectively protected the cells from apoptosis by inhibiting the phosphorylation of p38 MAPK and the activation of caspases.
These results suggest that ROS generation and the subsequent activation of p38 MAPK are essential for the proapoptotic effects of AF in human promyelocytic leukaemia HL‐60 cells.

British Journal of Pharmacology (2005) 146, 506–513. doi:10.1038/sj.bjp.0706360
The regulatory subunits of fission yeast protein phosphatase 2A (PP2A) affect cell morphogenesis, cell wall synthesis and cytokinesis
Authors: Kinoshita Kazuhisa , Nemoto Takeshi , Nabeshima Kentaro , Kondoh Hiroshi , Niwa Hajime , Yanagida Mitsuhiro 
Published: August 2005

Background:  Protein phosphatase 2A (PP2A) holoenzymes have a trimeric structure, consisting of a catalytic subunit C and two regulatory subunits A (PR65) and B (PR55). In fission yeast the C subunits, being 80% identical to their mammalian counterparts, are essential for viability and negatively regulate the entry into mitosis. Genetic analyses in budding yeast and Drosophila show that the regulatory subunits are implicated in chromosome segregation, cell morphogenesis and/or cytokinesis. Results:  We isolated fission yeast genes paa1+ and pab1+ encoding the regulatory subunits PR65 and PR55, respectively. Gene disruption showed that the paa1+ gene was essential for viability while pab1+ was not required at 26–33°C. Microtubule and actin distributions were anomalous in gene disrupted Δpaa1 cells which were incapable of forming a polarized cell shape. Gene disrupted Δpab1 cells were pear‐ or round‐shaped, and lost the polar distributions of actin and microtubules. In addition, Δpab1 cells were defective in cell wall synthesis and sporulation at permissive temperatures. At restrictive temperatures, Δpab1 cells showed an osmoremedial temperature‐sensitive phenotype and delayed in cytokinesis. However, chromosome segregation was normal. Conclusion:  Fission yeast PPZA regulatory subunit plays a critical role in cell morphogenesis, probably through regulation of the cytoskeletal network and cell wall synthesis.
Minimal Access Surgical Techniques in the Management of the Painful Lumbar Motion Segment
Authors: German John W. , Foley Kevin T. 
Published: August 2005

Study Design.
Review article.

Objectives.
To provide an overview of current minimally invasive lumbar fusion techniques.

Summary of Background Data.
Minimally invasive lumbar fusion techniques have only recently been developed. The goals of these procedures are to reduce approach-related soft tissue injury while allowing the surgery to be conducted in an effective manner.

Methods.
Pertinent literature and the authors’ clinical experience are reviewed.

Results.
Minimally invasive techniques have been developed for intertransverse process, posterior lumbar interbody, and transforaminal lumbar interbody fusions. The indications, advantages, and disadvantages of each technique are described. It is emphasized that while they appear promising, the clinical results of these techniques remain preliminary with few long-term studies available for critical review.

Conclusions.
Preliminary clinical evidence suggests that minimally invasive lumbar fusion techniques will benefit patients with spinal disorders.
Indications for Surgical Fusion of the Cervical and Lumbar Motion Segment
Authors: Bambakidis Nicholas C. , Feiz-Erfan Iman , Klopfenstein Jeffrey D. , Sonntag Volker K. H. 
Published: August 2005

Study Design.
A literature review and the authors’ clinical experience for the indication of fusion in the degenerative lumbar and cervical spine is provided.

Objective.
To establish absolute and relative criteria for the indication for fusion in the degenerative cervical and lumbar spine.

Summary of Background Data.
Fusion in the cervical and lumbar degenerative spine is indicated under certain strict criteria. However, fusion in circumstances not meeting these criteria is controversial.

Method.
A review of the literature and the authors’ experience concerning indication and criteria of fusion in degenerative, lumbar, and cervical spine is provided.

Results.
Fusion for the unstable spine related to trauma, infection, and tumors is relatively accepted. However, indications for fusion for degenerative, cervical, and lumbar spine are more controversial.

Conclusion.
Lumbar and cervical fusion in the degenerative spine is frequently performed. Certain criteria have been established when a fusion should be considered. However, even these are not universally accepted. Strict prospective studies are needed to determine when a fusion of the degenerative, cervical, and lumbar spine is indicated. Patients with severe radicular pain may be considered for surgery after a comprehensive trial of conservative management. Fusion is usually necessary after a cervical discectomy, especially when spondylosis or osteophytic compression is present. Lumbar fusion is rarely indicated for routine discectomy. In patients with mechanical back or neck pain, surgery should only be considered after conservative measures have been exhausted and a radiographic abnormality is present at the symptomatic level, perhaps with pain concordant with discographic findings. Careful patient selection is the key to obtaining favorable surgical outcomes. In many cases, the goal may be a return to functionality rather than achieving a completely asymptomatic state.
Current Treatment Strategies for the Painful Lumbar Motion Segment
Authors: Wang Jeremy C. , Mummaneni Praveen V. , Haid Regis W. 
Published: August 2005

Study Design.
Review of the literature.

Objectives.
We discuss the indications and contraindications for posterolateral lumbar fusion and posterior approaches to lumbar interbody fusion. We also review the advances in minimal access surgical techniques, graft materials, and osteobiologics.

Summary of Background Data.
Previously published data and our own surgical experience form the basis of this report.

Methods.
A Pub Med online internet search for the keywords was performed. The pertinent articles were then cited.

Results.
Posterior interbody fusion techniques have theoretical and demonstrable advantages over posterolateral fusion, but the former is also associated with greater morbidity. There are several approaches one may use to perform posterior interbody fusion, as well as multiple minimally invasive techniques and interbody spacer graft options. Bone morphogenetic protein offers an attractive alternative for achieving fusion.

Conclusion.
Fusion of painful motion segments is widely used to treat patients with degenerative low back pain. Successful arthrodesis may be achieved using either posterolateral fusion with pedicle screw fixation or posterior interbody fusion, depending on the patient's situation. These techniques may be accomplished with a variety of minimal access strategies and various graft and spacer technologies. The modern spine surgeon should be proficient in using all these options to treat the painful lumbar motion segment.
Are Somatostatin Analogs Therapeutic Alternatives in the Management of Head and Neck Paragangliomas?
Authors: Duet Michele , Guichard Jean Pierre , Rizzo Nathalie , Boudiaf Mourad , Herman Phillippe , Tran Huy Patrice 
Published: August 2005

AbstractBackground: Although mostly benign, head and neck paragangliomas require active management because of injury to adjacent neurovascular structures. Surgery, usually preceded by embolization, allows for complete tumor removal. However, surgery carries a significant risk of iatrogenic injury, related to tumor volume. Because paragangliomas express somatostatin receptors with high density, we investigated the effect of a long‐acting somatostatin analogue (OCT‐LAR) on the size of such tumors to reduce iatrogenic injury and related the percentage of tumor shrinkage to a tracer uptake index calculated on somatostatin receptor scintigraphy (SRS).Methods: In eight of the first nine patients, 30 mg of OCT‐LAR was given intramuscularly every 28 days for 3 doses; one patient withdrew after the first dose because of side effects. Conventional imaging with computed tomography (CT) scan or magnetic resonance imaging plus SRS revealed 18 paraganglioma sites. For each lesion, a tracer uptake index was calculated on pretreatment SRS. All 18 tumors were measured by CT scan before treatment and 1 month after the third injection.Results: The average percent tumor shrinkage was 4.0 ± 10.0%, and the average tumor reduction was 1.0 ± 3.8 cm3 (P = .27, NS). Only 2 of the 18 paragangliomas shrank by more than 20%; these two tumors belonged to the only one secreting patient. There was no significant relation between tracer uptake index and tumor response.Conclusion: These results suggest 1) that SRS results do not predict OCT‐LAR efficacy on paraganglioma size, and 2) OCT‐LAR is not useful in the preoperative management of paragangliomas.
Supraglottic Laryngeal Cancer: Analysis of Treatment Results
Authors: Sessions Donald G. , Lenox Jason , Spector Gershon J. 
Published: August 2005

AbstractObjective: This study reports the results of treatment for supraglottic laryngeal cancer with nine different treatment modalities with long‐term follow‐up.Study Design: Retrospective study of 653 patients with supraglottic laryngeal squamous cell cancer treated from April 1955 to January 1999.Methods: The study population included previously untreated patients with cancer of the supraglottic larynx treated with curative intent by one of nine treatment modalities and who were eligible for 5‐year follow‐up. The treatment modalities included subtotal supraglottic laryngectomy (SSL), SSL with neck dissection (SSL/ND), total laryngectomy (TL), TL/ND, radiation therapy (RT), SSL/RT, SSL/ND/RT, TL/RT, and TL/ND/RT. Multiple diagnostic, treatment, and follow‐up parameters were studied using standard statistical analysis to determine significance.Results: None of the nine treatment modalities produced a survival advantage, either overall or within the stages. Overall disease specific survival (DSS) by treatment modality included SSL 88.9%, SSL/ND 75.8%, TL 83.3%, TL/ND 66.7%, RT 47.2%, SSL/RT 68.9%, SSL/ND/RT 68.1%, TL/RT 59.3%, and TL/ND/RT 46.7%. Improved DSS and cumulative disease specific survival rates were associated with patients under the age of 65 years (P = .0001), early stage disease, N0 disease (P = .0001), clear resection margins (P = .0094), and no recurrence (P = .0001). Posttreatment function showed that 90% of patients were functional in everyday life, 90.7% were eating satisfactorily, 91.4% were breathing naturally, and 83% of SSL patients, 85.7% of RT patients, and 52.8% of TL patients had “good” voices. Laryngeal preservation was accomplished in 86.1% of SSL patients and 72.7% of RT patients (P = .0190).Conclusions: No treatment modality produced a survival advantage. Because SSL produced the best rate of laryngeal preservation, we recommend its use in treating the primary in eligible patients. The importance of clear resection margins is stressed. Patients with N+ disease should have the neck treated. Patients with N0 disease may be observed safely with no loss of survival advantage. Because of the pattern of recurrence and the high rates of distant metastasis and second primary cancers, follow‐up for a period of not less than 8 years is recommended.
The Magnanimous Professional Life and Tragic Demise of J. H. Douglas, MD
Authors: Bentz Brandon G. , Strong Elliot W. , Woodson Gayle E. , Shah Jatin P. 
Published: August 2005

AbstractObjectives/Hypothesis: Many of the hallmarks of a very successful medical career, such as recognition as a leader in a field of medicine, making important contributions to medical knowledge of the day, and a steadfast dedication to patient care, had already been achieved by Dr. John Hancock Douglas. Therefore, the mystery surrounding his dismissal from membership of the newly formed American Laryngology Society (now the ALA) and his tragic demise stand in stark contrast. We discuss the model professional life and mysterious but tragic final days of this very important laryngologist of the 19th century.Study Design/Methods: A historical vignette.Results: Dr. Douglas's professional qualities of leadership of the American Sanitary Commission, his various contributions to the advancement of medical knowledge during that era, and his steadfast dedication to the care of his patients represent highlights of a very honorable professional career. His final demise, bankrupt, in an ill state of health, and stripped of his professional appointment to the ALA, seems an unjust end to the life of this notable and magnanimous laryngologist.Conclusions: We offer this historical review of the life and demise of Dr. John H. Douglas as a tribute to this important figure in our profession's history.
Creation of a Cholesteatoma Model using Three‐Dimensional Cultured Skin Equivalents
Authors: Tanaka Yasuhiro , Yaguchi Yuichiro , Wada Kota , Kojima Hiromi , Moriyama Hiroshi 
Published: August 2005

AbstractObjectives/Hypothesis: Recent years have seen success in establishing methods for cell culture that lead to the creation of a three‐dimensional tissue architecture, and this represents a great advance for the ability to carry out research in vitro. Accordingly, the present studies were carried out with the objective of using three‐dimensional cultured skin equivalents for the in vitro creation of a model of middle ear cholesteatoma, something that has heretofore been considered to be very difficult.Study Design: A cholesteatoma model was created in vitro, and discussion is presented regarding the immigration theory and the retraction theory that have been proposed as explanations of the causation of cholesteatoma.Methods: Cultured skin equivalents were prepared, followed by creation of an epidermal and dermal defect in them. Then, the changes in the epidermis were investigated histologically. In addition, immunohistochemical studies were performed with regard to the effects exerted on the epidermis when the skin equivalents were cultured in a retracted state.Results: It was confirmed that, as a result of the defect in the epidermis and dermis of the cultured skin equivalents, the epidermis at the edge of the defective site migrated subepidermally, and a stratified structure was formed. On the other hand, the retraction of the epidermis and dermis exerted almost no effect on the epidermal cells themselves.Conclusions: These results lend credence to the immigration theory as an explanation of the growth of the epidermis from the defective site. Conversely, it was surmised that the retraction theory requires some other factors in addition to retraction.
Effect of Comorbidity on Quality of Life and Treatment Selection in Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Gourin Christine G. , McAfee William J. , Neyman Kimberly M. , Howington Jed W. , Podolsky Robert H. , Terris David J. 
Published: August 2005

AbstractObjectives: Comorbidity is significantly associated with diminished survival and quality of life (QOL) after treatment of head and neck squamous cell carcinoma (HNSCC). We sought to determine whether comorbidity influenced pretreatment QOL scores and treatment selection in patients with HNSCC.Methods: The medical records of all patients diagnosed with HNSCC who participated in pretreatment QOL analysis over a 15‐month period were retrospectively reviewed. Patients with a history of prior treatment for head and neck cancer, unresectable, or distant metastatic disease were excluded. The University of Washington (UW) QOL questionnaire, Performance Status Scale (PSS), and Karnofsky score were used to measure pretreatment QOL. Comorbidity was graded using the Modified Medical Comorbidity Index.Results: Of 75 patients who met study criteria, 33 underwent primary surgical therapy, and 42 underwent nonoperative (radiation or chemoradiation) therapy. Treatment groups did not differ with respect to patient demographics, UW QOL scores, PSS scores, Karnofsky score, or comorbidity. Treatment groups differed significantly by disease stage and primary site. Patients with advanced stage disease (III/IV) or oropharyngeal primary tumors were more likely to undergo nonoperative treatment, compared with patients with early stage disease (I/II) or oral cavity primary tumors (P < .005). No significant association was found between comorbidity and pretreatment QOL scores.Conclusions: Comorbidity was not significantly associated with treatment selection or pretreatment QOL scores in patients with HNSCC. Location of the primary tumor and disease stage were significantly associated with treatment selection. Further studies are required to determine the effect of comorbidity on patient and tumor responses to treatment.
Vocal Cord Paralysis after Laryngeal Mask Airway Ventilation
Authors: Chan Teresa V. , Grillone Gregory 
Published: August 2005

AbstractThe laryngeal mask airway (LMA) is being used with increasing frequency since its introduction into the United States in 1991. Currently, the LMA is being used in the United States in approximately one third of all operations or greater than 100 million surgeries. In Britain, where it was first introduced for use in 1988, the LMA is estimated to be used in up to 50% of cases. Not only has its use in elective cases increased, but the scope of indications for the LMA has also grown. Its use in emergent and difficult airway management has increased, and new LMA products have been introduced to address the limitations of the classic model. As the LMA has increased in popularity, however, so has the incidence of LMA‐related complications. Cases of mucosal trauma, hematoma, tongue cyanosis, arytenoid dislocation, and lingual, hypoglossal, and recurrent laryngeal nerve paralyses have been documented in various anesthesia journals. Reports of these injuries are sparse in the otolaryngology literature. As otolaryngologists who will manage the sequelae of LMA‐related injuries, we must remain cognizant of potential problems and their underlying mechanisms. We report a case of unilateral vocal cord paralysis, which required operative repair after the use of an LMA. We review the existing case reports, propose mechanisms of injury, and discuss practical applications of our findings.
A Single Therapy for All Subtypes of Horizontal Canal Positional Vertigo
Authors: Chiou Wen‐Yaw , Lee Hui‐Ling , Tsai Shih‐Che , Yu Tu‐Hsueh , Lee Xin‐Xian 
Published: August 2005

AbstractObjective: To demonstrate that a single therapy is effective for treating all subtypes of horizontal canal benign paroxysmal positional vertigo (HC‐BPPV).Study Design: Prospective study.Methods: Patients with HC‐BPPV (n = 89) were diagnosed when the supine to the head‐lateral test resulted in geotropic or ageotropic bilateral horizontal nystagmus. Three subtypes of HC‐BPPV were defined by their characteristic patterns of nystagmus as well as by their speculative mechanism. Canalolithiasis (Can) denotes geotropic nystagmus induced by free‐moving otoliths in the HC. Two forms of cupulolithiasis, characterized by otoliths attached either on the utricle‐sided (Cup‐U) or the canal‐sided (Cup‐C) cupula, were identified by whether ageotropic nystagmus resolved or changed to geotropic nystagmus on follow‐up tests. Forced prolonged position (FPP), lying on the healthy side for 12 hours to easily move free otoliths to the utricle, has proven successful in treating Can. Although Cup‐U and contralateral Cup‐C were associated with the same positional nystagmus pattern, FPP with lying on the side of the weaker nystagmus was found to be effective treatment, as well as consistent with the speculated underlying mechanism.Results: All HC‐BPPV patients including 49 with Can, 11 with Cup‐C and 29 with Cup‐U had complete resolution of symptoms and positional nystagmus after less than four treatment sessions.Conclusions: FPP with lying on the side of the weaker nystagmus, combined with careful observation of nystagmus evolvement, was found to be effective treatment for all subtypes of HC‐BPPV in this series.