Proteoglycan-binding peptides were designed based on consensus sequences in heparin-binding proteins: XBBXBX and XBBBXXBX, where X and B are hydropathic and basic residues, respectively. Initial peptide constructs included (AKKARA) n and (ARKKAAKA) n (n ‫؍‬ 1-6). Affinity coelectrophoresis revealed that low M r peptides (600 -1300) had no affinities for low M r heparin, but higher M r peptides (2000 -3500) exhibited significant affinities (K d Х 50 -150 nM), which increased with peptide M r . Affinity was strongest when sequence arrays were contiguous and alanines and arginines occupied hydropathic and basic positions, but inclusion of prolines was disruptive. A peptide including a single consensus sequence of the serglycin proteoglycan core protein bound heparin strongly (K d Х 200 nM), likely owing to dimerization through cysteine-cysteine linkages. Circular dichroism showed that high affinity heparin-binding peptides converted from a charged coil to an ␣-helix upon heparin addition, whereas weak heparin-binding peptides did not. Higher M r peptides exhibited high affinities for total endothelial cell proteoglycans (K d Х 300 nM), and ϳ4-fold weaker affinities for their free glycosaminoglycan chains. Thus, peptides including concatamers of heparin-binding consensus sequences may exhibit strong affinities for heparin and proteoglycans. Such peptides may be applicable in promoting cell-substratum adhesion or in the design of drugs targeted to proteoglycan-containing cell surfaces and extracellular matrices. Proteoglycans (PGs)1 are composed of a core protein to which are covalently attached one or more sulfated glycosaminoglycans (GAGs). PGs are ubiquitous components of cell surfaces and the extracellular matrix, and their GAG chains contribute to myriad biological functions, such as modulation of enzyme activities, regulation of cell growth, and control of assembly of the extracellular matrix (1). PGs are thus potential targets for therapeutic intervention. For example, heparin antagonists are needed to take the place of protamine, a heterogeneous, sometimes toxic protein mixture commonly used to neutralize the anticoagulant activity of heparin in humans (2, 3); in the design of drugs to be targeted to PG-rich tissues, such as cartilage (4); and to be used to promote cell adhesion in a variety of situations, e.g. by promoting binding of cells that express abundant amounts of PGs, such as endothelial cells (5), to synthetic vascular graft surfaces. To develop a rationale for the design of such reagents, it is useful to examine known features of protein structure required for high affinity interactions with GAGs. Thus, analysis of the structural features of many known heparin-and heparan sulfate (HS)-binding proteins has revealed the presence of conserved motifs, through which GAG binding has been postulated to occur. Cardin and Weintraub (6) identified two clusters of basic charge in known heparin-binding proteins in which amino acids tend to be arranged in the patterns XBBXBX or XBBBXXBX, where B represents an ...

Not all patients with a diagnosis of superior canal dehiscence syndrome will have classic symptoms and signs. A high index of suspicion with careful clinical examination and properly performed ancillary testing is required to confirm this diagnosis.

Otalgia of unclear cause can be related to migraine mechanisms. Our group showed a high prevalence of migraine characteristics, including headache, migraine-associated symptoms, patterns of triggerability, and response to migraine treatment. Clinical criteria for diagnosis of migraine-associated otalgia are suggested for future prospective study.

Neck dissection without primary tumor resection before definitive chemoradiotherapy for oropharynx cancer is a safe and effective management program and warrants further exploration.

Objectives To describe the histopathologic findings in the temporal bones of a patient with who had been diagnosed during life with superior canal dehiscence (SCD) syndrome. Methods The patient was diagnosed with SCD at the age of 59. She became a temporal bone donor, and died of unrelated causes at the age of 62. Both temporal bones were prepared in celloidin and examined by light microscopy. Results She developed bilateral aural fullness, pulsatile tinnitus and difficulty tolerating loud noises after minor head trauma at age 53. Symptoms were worse on the right. She also had valsalva-induced dizziness and eye movements, as well as sound-induced dizziness (more prominent on the right), consistent with SCD. Audiometry showed a small air bone gap of 10 dB in the right ear. VEMP testing showed an abnormally low threshold of 66 dB on the right, and CT scan showed dehiscence of the superior canal on the right. Histopathology of the right ear showed a 1.4 × 0.6 mm dehiscence of bone covering the superior canal. Dura was in direct contact with the endosteum and the membranous duct at the level of the dehiscence. No osteoclastic process was evident within the otic capsule bone surrounding the dehiscence. The left ear showed thin but intact bone over the superior canal. Both ears showed focal microdehiscences of the tegmen tympani and tegmen mastoideum. The auditory and vestibular sense organs on both sides were normal. No endolymphatic hydrops was observed. Conclusions The findings were consistent with the hypothesis put forth by Carey and colleagues that the SCD may arise from failure of postnasal bone development, and that minor trauma may disrupt thin bone or stable dura over the superior canal.