Temporal and Physiologic Measurements of Deglutition in the Upright and Supine Position with Videofluoroscopy (VFS) in Healthy Subjects.

Cross-sectional imaging has long been employed to examine swallowing in both the sagittal and axial planes. However, data regarding temporal swallow measures in the upright and supine positions are sparse, and none have employed the MBS impairment profile (MBSImP). We report temporal swallow measures, physiologic variables, and swallow safety of upright and supine swallowing in healthy subjects using videofluoroscopy (VFS). Twenty healthy subjects ages 21-40 underwent VFS study upright and supine. Subjects were viewed in the sagittal plane and swallowed 5 mL liquid and pudding barium. Oral transit time, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, and total swallow duration were measured. Penetration/aspiration scores and 14 MBSImP variables were analyzed in both positions. All subjects completed swallows supine, although one aspirated on one liquid bolus. Temporal measures of swallowing were similar for pudding upright and supine. Pharyngeal phase swallow measures were longer for liquids in supine. MBSImP physiologic measures revealed a pharyngeal delay in both positions. Although Pen/Asp range was higher supine, more subjects penetrated upright. Temporal measures were increased for liquids in supine. Although Pen/Asp range was higher in supine, more subjects penetrated upright. These results provide support for cross-sectional supine imaging of swallowing for pudding, but perhaps not thin liquids for dysphagic patients. Slightly thicker liquids might prove reliable in supine without compromising swallow safety. Future research should examine swallow physiology in both positions in dysphagic and older healthy subjects.

Osteoradionecrosis of the subaxial cervical spine following treatment for head and neck carcinomas.

OBJECTIVE: To study MRI and positron emission tomography (PET)/CT imaging of osteoradionecrosis (ORN) of the subaxial cervical spine, a serious long-term complication of radiation therapy (RT) for head and neck cancers that can lead to pain, vertebral instability, myelopathy and cord compression. METHODS: This is a single-institution retrospective review of patients diagnosed and treated for ORN of the subaxial cervical spine following surgery and radiation for head and neck cancer. RESULTS: We report PET/CT imaging and MRI for four patients, each with extensive treatment for recurrent head and neck cancer. Osteomyelitis (OM) and discitis are the end-stage manifestations of ORN of the subaxial spine. CONCLUSION: ORN of the subaxial spine has variable imaging appearance and needs to be differentiated from recurrent or metastatic disease. Surgical violation of the posterior pharyngeal wall on top of the compromised vasculature in patients treated heavily with RT may pre-dispose the subaxial cervical vertebrae to ORN, with possible resultant OM and discitis. MRI and PET/CT imaging are complimentary in this setting. PET/CT images may be misinterpreted in view of the history of head and neck cancer. MRI should be utilized for definitive diagnosis of OM and discitis in view of its imaging specificity. ADVANCES IN KNOWLEDGE: We identify the end-stage manifestation of ORN in the sub-axial spine on PET/CT and MRI to facilitate its correct diagnosis.

Orientation of the cleavage site of the herpes simplex virus glycoprotein G-2.

During the synthesis of glycoprotein G-2 (gG-2) of herpes simplex virus type 2, the 104,000-Da gG-2 precursor (104K precursor) is cleaved to generate the 72K and the 31K intermediates. The 72K product is processed to generate the mature gG-2 (molecular mass, 108,000 Da), while the 31K product is additionally processed and secreted into the extracellular medium as the 34K component (H. K. Su, R. Eberle, and R. J. Courtney, J. Virol. 61:1735-1737, 1987). In this study, the orientations of the 31K and 72K products on the 104K precursor were determined by using two antipeptide sera produced in rabbits and a monoclonal antibody, 13 alpha C6, directed against gG-2. The sera prepared against synthetic peptides corresponding to the terminal amino acid residues 67 to 78 and an internal peptide at amino acids 247 to 260 of gG-2 recognized the 104K precursor and the 31K cleavage product but not the 72K intermediate. In contrast, 13 alpha C6 detected the 72K cleavage product and the uncleaved precursor but not the 31K cleavage component. The epitope recognized by 13 alpha C6 was mapped within amino acids 486 to 566. These results suggest that the 31K cleavage product is derived from the amino-terminal portion of the 104K precursor molecule and that the 72K intermediate is derived from the carboxyl terminus. In support of our model described above for the synthesis of gG-2, antibodies recognizing either of the cleavage products reacted with the uncleaved precursor but not with the other cleavage product. By using partial endo-beta-N-acetylglucosaminidase H analysis, two N-linked glycosylation sites were found on each of the cleavage products. The distribution of the N-linked glycosylation sites and the reactivities of the antipeptide sera allowed the cleavage region on the precursor to be mapped to within amino acids 260 to 437.

In vitro synthesis and processing of herpes simplex virus type 2 gG-2, using cell-free transcription and translation systems.

Translation of in vitro-synthesized herpes simplex virus type 2 (HSV-2) gG-2 mRNA in a reticulocyte lysate system was used to study the processing of HSV-2 gG-2. In the presence of canine pancreatic microsomal membranes, a single species that is protected from trypsin digestion was detected. This product comigrates with the 104,000-Mr (104K) high mannose intermediate seen in HSV-2-infected-cell lysates. Endo-beta-N-acetylglucosaminidase H treatment of the in vitro-synthesized 104K protein yielded a single product migrating at 100 K. The 72K and 31K cleavage products of gG-2 were not observed in the in vitro system. These data show that the molecular weight of the nonglycosylated form of the gG-2 protein is 100,000 and that the cotranslational processing of this protein in the endoplasmic reticulum yields the 104K high-mannose intermediate.

Inducible expression of herpes simplex virus type 2 glycoprotein gene gG-2 in a mammalian cell line.

The gG-2 glycoprotein gene of herpes simplex virus type 2 (HSV-2) was cloned into the mammalian expression vector pMSG under the control of the inducible mouse mammary tumor virus promoter. Transfection of this cloned gG-2 construct into NIH 3T3 cells resulted in the stable expression of gG-2 upon induction with dexamethasone. In addition, the 104,000-molecular-weight (104K) and 72K gG-2 precursors as well as the 34K secreted component were generated in the transformed cells. The synthesis of gG-2 in these transformed cells appeared to follow the same cleavage-processing pathway as gG-2 synthesis during an HSV-2 infection. These results indicate that the processing of gG-2 can occur in the absence of an HSV-2 infection.

Processing of the herpes simplex virus type 2 glycoprotein gG-2 results in secretion of a 34,000-Mr cleavage product.

Herpes simplex virus type 2 glycoprotein gG-2 undergoes a cleavage event during its synthesis and processing. The focus of this report is on the detection and fate of the small-molecular-weight component of gG-2, designated the 34K component. In cultures containing the inhibitor monensin, a 31K component accumulated within infected cells. In contrast, the intracellular accumulation of this 31K precursor was not detected in cultures grown in the absence of the inhibitor. However, the 34K component of gG-2 was found in the extracellular culture fluid. The data suggest that the 31K high-mannose cleavage product of gG-2 is further glycosylated and rapidly secreted from herpes simplex virus type 2-infected cells; however, if glycosylation is perturbed, the 31K high-mannose form remains cell associated.