Evidence for opening of hair-cell transducer channels after tip-link loss

The mechanosensitive transducer channels of hair cells have long been proposed to be gated directly by tension in the tip links. These are thin, elastic extracellular elements connecting the tips of adjacent stereocilia located on the apical surface of the cell. If this hypothesis is true, the channels should close after destruction of tip links. The hypothesis was tested pharmacologically using receptor currents obtained in response to mechanical stimulation of the stereociliary bundle of outer hair cells isolated from the adult guinea pig cochlea. Application of elastase (20 U/ml) or 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetra-acetic acid (BAPTA; 5 mM), both of which are known to disrupt tip links in other hair-cell preparations, led to the expected irreversible loss of receptor currents. However, the cells then displayed a maintained inward current, implying that channels were left permanently open. This current was similar in magnitude to the receptor current before treatment and was reduced reversibly by known blockers of mechanosensitive channels, namely, dihydrostreptomycin (100 microM), amiloride (300 microM), and gadolinium ions (1 mM). These observations suggest that the maintained current flows through the mechanosensitive channels. Electron microscopical analysis of isolated hair cells, exposed to the same concentrations of elastase or BAPTA as in the electrophysiological experiments, demonstrated an almost total loss of tip links in hair bundles that showed no evidence of other mechanical damage. It is concluded that although the tip links are required for mechanoelectrical transduction, the channels are not gated directly by the tip links.     

A comparison of clustering solutions for cognitive heterogeneity in schizophrenia

This study investigated semantic priming for literal (stinging-mosquito) and metaphoric (stinging-insult) associates presented to either the left or right visual fields (RVF/LVF) across stimulus-onset-asynchronies (SOA) of 200 and 800 ms. For the short SOA condition, facilitation was found for metaphorically related targets in both visual fields (VFs) while literally related targets were facilitated only in the RVF. For the long SOA condition, metaphorically related targets were facilitated in the LVF whereas literally related targets were facilitated in the RVF. These results support previous findings indicating an enhanced role of the RH in metaphoric comprehension. In addition, the present results are in accordance with current models of hemispheric semantic processing.     

Role of neutrophil-endothelial cell adhesion in inflammatory disorders

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.     

Comparative evaluation of college football officials' attitudes toward NCAA mouthguard regulations and player compliance

A 12-item questionnaire addressing attitudes of football officials toward the 1990 National Collegiate Athletic Association (NCAA) mouthguard regulation was sent to all officials in the Southeastern Conference (N = 62). The response rate was 95% (59). Twenty-seven per cent of officials reported that all players were in compliance; 74% believed the new rule to be at least somewhat beneficial in determining player compliance, and 20% reported that the rule had resulted in more frequent player use. Twenty-two per cent reported they would ignore a mouthguard violation and none had charged a time-out or called a penalty during the 1991 season. Significant differences in the responses of Big East officials surveyed in a previous study were noted by the authors, when compared to the SEC, but both groups of officials strongly supported the idea that wearing mouthguards should be the responsibility of coaches rather than officials.     

Long-term treatment with abecarnil does not induce diazepam-like dependence in mice

Abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate) is a metabolically stable anxiolytic and anticonvulsant beta-carboline derivative with few sedative and muscle relaxant effects in rodents. Abecamil binds with high affinity to benzodiazepine receptors. Because long-term treatment with benzodiazepines leads to development of dependence, we evaluated in mice whether abecarnil also possesses a potential for producing dependence, using electroencephalographic and electromyographic monitoring, and behavioral assessment of anxiety to detect withdrawal responses after chronic treatment. Diazepam was used as a reference. Mice withdrawn from chronic treatment with diazepam (15 mg/kg/day for 12 days) showed a time-related evolution of anxiety, muscle rigidity and seizures between days 4 and 21 after discontinuation of the treatment. A period between withdrawal days 1 and 3 was symptom free. Mice withdrawn from chronic administration of abecarnil (6 mg/kg/day for 12 days) showed no anxiety and no changes in seizure susceptibility and muscle tone. The doses of diazepam and abecarnil used for chronic treatment were equivalent in terms of kinetics and binding to benzodiazepine receptors. These data indicate that long-term treatment with abecarnil does not induce benzodiazepine-like dependence in mice. Thus, it may be predicted that chronic treatment with abecarnil in humans may offer an important alternative to benzodiazepines in the treatment of anxiety.     

Clinical evaluation of sodium fluoride chewable tablets in dental caries

Chewable tablets containing low dosage fluoride content were prepared using two varieties of celluloses and their in vitro parameters were evaluated. An eighteen month clinical trial revealed that both these formulations were effective in controlling the caries. However, ethyl cellulose is proved to be superior to methylcellulose as a controlled release matrix material in controlling caries. Thus this study recommends ethylcellulose matrix tablets containing low fluoride content is an efficacious and cost effective drug device in controlling dental caries.     

Nuclear pore complex number and distribution throughout the Saccharomyces cerevisiae cell cycle by three-dimensional reconstruction from electron micrographs of nuclear envelopes

The number of nuclear pore complexes (NPCs) in individual nuclei of the yeast Saccharomyces cerevisiae was determined by computer-aided reconstruction of entire nuclei from electron micrographs of serially sectioned cells. Nuclei of 32 haploid cells at various points in the cell cycle were modeled and found to contain between 65 and 182 NPCs. Morphological markers, such as cell shape and nuclear shape, were used to determine the cell cycle stage of the cell being examined. NPC number was correlated with cell cycle stage to reveal that the number of NPCs increases steadily, beginning in G1-phase, suggesting that NPC assembly occurs continuously throughout the cell cycle. However, accumulation of nuclear envelope observed during the cell cycle, indicated by nuclear surface area, is not continuous at the same rate, such that the density of NPCs per unit area of nuclear envelope peaks in apparent S-phase cells. Analysis of the nuclear envelope reconstructions also revealed no preferred NPC-to-NPC distance. However, NPCs were found in large clusters over regions of the nuclear envelope. Interestingly, clusters of NPCs were most pronounced in early mitotic nuclei and were found to be associated with the spindle pole bodies, but the functional significance of this association is unknown.     

Unsuspected aortic valve vegetation detected during intraoperative transesophageal echocardiographic monitoring for coronary artery bypass grafting

The literature at this time does not give convincing evidence for use of pyridoxine as the sole treatment when confronted with a patient with idiopathic CTS. It may be of value as an adjunct in conservative therapy through altered perception of pain and increased pain threshold. For patients not responsive to conservative therapy, surgical decompression of the carpal canal is the treatment of choice.     

Semantic and visual determinants of face recognition in a prosopagnosic patient

Prosopagnosia is the neuropathological inability to recognize familiar people by their faces. It can occur in isolation or can coincide with recognition deficits for other nonface objects. Often, patients whose prosopagnosia is accompanied by object recognition difficulties have more trouble identifying certain categories of objects relative to others. In previous research, we demonstrated that objects that shared multiple visual features and were semantically close posed severe recognition difficulties for a patient with temporal lobe damage. We now demonstrate that this patient's face recognition is constrained by these same parameters. The prosopagnosic patient ELM had difficulties pairing faces to names when the faces shared visual features and the names were semantically related (e.g., Tonya Harding, Nancy Kerrigan, and Josee Chouinard -three ice skaters). He made tenfold fewer errors when the exact same faces were associated with semantically unrelated people (e.g., singer Celine Dion, actress Betty Grable, and First Lady Hillary Clinton). We conclude that prosopagnosia and co-occurring category-specific recognition problems both stem from difficulties disambiguating the stored representations of objects that share multiple visual features and refer to semantically close identities or concepts.