ATP synthase motor components: proposal and animation of two dynamic models for stator function.

Recent research indicates that ATP synthases (F(0)F(1)) contain two distinct nanomotors, one an electrochemically driven proton motor contained within F(0) that drives an ATP hydrolysis-driven motor (F(1)) in reverse during ATP synthesis. This is depicted in recent models as involving a series of events in which each of the three alphabeta pairs comprising F(1) is induced via a centrally rotating subunit (gamma) to undergo the sequential binding changes necessary to synthesize ATP (binding change mechanism). Stabilization of this rotary process (i.e., to minimize "wobble" of F(1)) is provided in current models by a peripheral stalk or "stator" that has recently been shown to extend from near the bottom of the ATP synthase molecule to the very top of F(1). Although quite elegant, these models envision the stator as fixed during ATP synthesis, i.e., bound to only a single alphabeta pair. This is despite the fact that the binding change mechanism views each alphabeta pair as going through the same sequential order of conformational changes which demonstrate a chemical equivalency among them. For this reason, we propose here two different dynamic models for stator function during ATP synthesis. Both models have been designed to maintain chemical equivalency among the three alphabeta pairs during ATP synthesis and both have been animated.

Quantitative structure-activity relationships for chemical toxicity to environmental bacteria.

Quantitative structure-activity relationships (QSARs) were developed for nonreactive chemical toxicity to each of four groups of bacteria of importance in environmental engineering: aerobic heterotrophs, methanogens, Nitrosomonas, and Microtox. The QSARs were based on chemicals covering a range of structures and including important environmental pollutants (i.e., chlorinated and other substituted benzenes, phenols, and aliphatic hydrocarbons). QSARs were developed for each chemical class and for combinations of chemical classes. Three QSAR methods (groups of chemical describing parameters) were evaluated for their accuracy and ease of use: log P, linear solvation energy relationships (LSER), and molecular connectivity. Successful QSARs were found for each group of bacteria and by each method, with correlation coefficients (adjusted r2) between 0.79 and 0.95. LSER QSARs incorporated the widest range of chemicals with the greatest accuracy. Log P and molecular connectivity QSARs are easier to use because their parameters are readily available. Outliers from the QSARs likely due to reactive toxicity included acryls, low pKa compounds, and aldehydes. Nitro compounds and chlorinated aliphatic hydrocarbons and alcohols showed enhanced toxicity to the methanogens only. Chemicals with low IC50 concentrations (log IC50 mumol/liter less than 1.5) were often outliers for Nitrosomonas. QSARs were validated statistically and with literature data. A suggested method is provided for use of the QSARs.

Longitudinal followup of patients with Menière's disease.

The etiology, pathophysiology, and natural history of Menière's syndrome are poorly understood. The reported studies have had inadequate followup or insufficient numbers of patients to allow conclusions about the natural history. Our study group was 119 patients who had the classic symptom complex of episodic vertigo, tinnitus, and hearing loss in the year 1970. After initial review of these charts, follow-up information was obtained by questionnaire, telephone interview, chart review, or repeat examination, when possible, both in 1983 and in 1988, for a total followup of 18 years. In the patients with followups of at least 14 years, vertiginous episodes had disappeared completely in 50% of patients and somewhat resolved in 28%; hearing was absent in 48% and worse in 21%. Surprisingly, 43% of patients underwent surgery at some point for control of vertigo. Bilateral disease was present initially in 13% and developed subsequently in 45% of patients. Other areas reviewed included the efficacy of long-term medical treatment, frequency and severity of vertiginous attacks, and contralateral ear symptoms.

Gamma heavy-chain disease involving upper airway.

Gamma heavy-chain disease is a rare disorder. It is a plasma cell dyscrasia, with the patient's age at onset being 9 to 87 years. Identification of IgG heavy chains in the serum and urine is diagnostic. Histopathologic features are nonspecific. Although the clinical presentation is diverse, many signs and symptoms lead to early otorhinolaryngologic consultation. For this reason gamma-heavy-chain disease should be considered in the differential diagnosis of inflammatory lesions of the upper aerodigestive tract.

Effect of maturation on the sensitivity of laryngeal resistance to chemoreceptor stimulation in the dog.

The respiratory system undergoes many changes with maturation, resulting in increased capacity and efficiency. In an effort to determine the effects of maturation on airway control, laryngeal airway resistance was studied from infancy to adulthood in dogs. Reflex regulation of laryngeal airway resistance in response to chemoreceptor stimulation was found in puppies 1 day of age and older. Chemoreceptor-mediated laryngeal reflexes were qualitatively similar in all age groups. However, a significant quantitative difference was found. With maturation, an increase in the sensitivity of both central and peripheral chemoreceptors regulating laryngeal resistance is realized.

Age-related responses of laryngeal airway resistance to peripheral and central chemoreceptor stimulation.

Laryngeal airway resistance was measured in anesthetized dogs ranging in age from one day to adult during central and peripheral chemoreceptor stimulation by hypoxia and hypercapnia. Chemoreceptor-mediated regulation of airway resistance was found to be qualitatively similar in all age groups; however, there was a progressive increased sensitivity to both hypoxia and hypercapnia with increasing age. The reduced sensitivity of the laryngeal airway to hypoxic and hypercapnic stimulation in the young animal may predispose the young animal to airway obstruction during periods of hypoxia or hypercapnia. This may bear some relevance to the etiology of certain cases of sudden infant death syndrome.

Current thinking on tonsillectomy and adenoidectomy.

Tonsillectomy and adenoidectomy, though less frequently performed now than in the 1930s, remain among the most common surgical procedures in the United States. The need for and benefits of tonsillectomy and adenoidectomy have been a source of controversy for several decades. Nonetheless, there are situations in which these procedures definitely are beneficial. Tonsillectomy and adenoidectomy are two distinct procedures with separate indications, and they are performed concurrently only when the specific indications for each coexist. Tonsillectomy is indicated by recurrent tonsillitis, peritonsillar abscess, chronic tonsillitis, tonsillar neoplasm, or tonsillar hypertrophy that is obstructive to the upper aerodigestive tract (respiratory distress, dysphagia, or interference with performance of an adenoidectomy). Adenoidectomy is indicated for nasal airway obstruction due to adenoidal enlargement from hypertrophic or inflammatory processes. Although correlation exists among obstructive adenoids, mouth breathing, and dentofacial anomalies, present evidence is not sufficient to justify adenoidectomy solely on the basis of craniofacial or dentofacial abnormalities. Today, elimination of an occult source of infection (once called focal infection) in patients with disorders such as rheumatic fever or serous otitis media is not a valid indication for either operation. Contraindications to tonsillectomy and adenoidectomy include bleeding disorders, familial anesthetic intolerance, velopharyngeal insufficiency, and concurrent disease that may enhance operative risks. Like all surgical procedures, tonsillectomy and adenoidectomy entail morbidity and risk of mortality. The most frequent complication of these operations is hemorrhage. Risk of mortality is approximately 0.006%. Mortality and morbidity can be minimized by appropriate preoperative evaluation, complete control of the airway with endotracheal anesthesia, and meticulous surgical technique.

Effect of chemoreceptor and pulmonary receptor stimulation on dilator nares EMG activity in the dog.

To define the relationship between central control of upper airway muscles and respiratory muscle function, the electromyographic responses of the dilator nares muscles to stimulation of chemoreceptors and pulmonary receptors were studied in six anesthetized dogs. Only at maximal levels of hypoxia was the inspiratory activity of the dilator nares significantly increased. Hypercapnic stimulation increased the inspiratory activity with each incremental increase in CO2. Pulmonary stretch receptor stimulation produced by lung inflation inhibited dilator nares activity. Pulmonary irritant receptor stimulation by intravenously administered histamine increased dilator nares activity, as did pulmonary J receptor stimulation by the intravenous administration of capsaicin.

Septic necrosis of the internal carotid artery: a complication of peritonsillar abscess.

Septic necrosis of the internal carotid artery is a major complication of peritonsillar abscess. Although once a common complication, its occurrence is rare since the introduction of antibiotics. A 12-year-old girl was referred to our institution after a false aneurysm of the internal carotid artery had been entered during routine tonsillectomy for a peritonsillar abscess. Review of the literature and features of the present case demonstrate the following findings suggestive of erosion of the internal carotid artery as a result of peritonsillar abscess: (1) spontaneous hemorrhage from a peritonsillar abscess, (2) persistent peritonsillar swelling after resolution of symptoms of peritonsillar abscess, (3) ipsilateral Horner's syndrome, and (4) otherwise unexplained cranial nerve palsies (nerves IX, X, XI, and XII).