Kinematic analysis of shear displacement as a means for operating mechanotransduction channels in the contact region between adjacent stereocilia of mammalian cochlear hair cells

In sensory hair cells of the cochlea, deflection of the stereociliary bundle results in direct mechanical gating of mechanoelectrical transduction channels, a function generally attributed to the tip link running between the tips of short stereocilia and the sides of adjacent taller ones. However, immunocytochemical experiments indicate that the channels may not be associated with the tip link but occur just below it in a region of contact between the stereocilia. To determine whether transduction channels in this location could be operated during physiologically appropriate deflections as effectively by shear displacement as if they were associated with the tip link, a two dimensional kinematic analysis of relative motion between stereocilia has been performed assuming contact between stereocilia is maintained during deflection. Bundle geometry and dimensions were determined from transmission electron micrographs of hair cells from several frequency locations between 0.27 and 13.00 kHz in the guinea-pig cochlea. The analysis indicates that for a 10 nm deflection of the tallest stereocilia of both inner and outer hair cells, i.e. within the range of the maximum sensitivity of mammalian hair bundles, the average shear displacement in the contact region would be 1.6 nm, but that it increases systematically towards higher frequency regions for outer hair cells. This displacement is comparable in magnitude to tip-link elongation for individual stereociliary pairs.     

Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: a possible mechanism of action of PUVA therapy

The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20-55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.     

Sympathetic response to stimulation of the pontine A5 region in conscious rabbits

OBJECT: This study is a retrospective analysis of clinical data obtained in 28 patients affected by obstructive hydrocephalus who presented with signs of midbrain dysfunction during episodes of shunt malfunction. METHODS: All patients presented with an upward gaze palsy, sometimes associated with other signs of oculomotor dysfunction. In seven cases the ocular signs remained isolated and resolved rapidly after shunt revision. In 21 cases the ocular signs were variably associated with other clinical manifestations such as pyramidal and extrapyramidal deficits, memory disturbances, mutism, or alterations in consciousness. Resolution of these symptoms after shunt revision was usually slow. In four cases a transient paradoxical aggravation was observed at the time of shunt revision. In 11 cases ventriculocistemostomy allowed resolution of the symptoms and withdrawal of the shunt. Simultaneous supratentorial and infratentorial intracranial pressure recordings performed in seven of the patients showed a pressure gradient between the supratentorial and infratentorial compartments, with a higher supratentorial pressure before shunt revision. Inversion of this pressure gradient was observed after shunt revision and resolution of the gradient was observed in one case after third ventriculostomy. In six recent cases, a focal midbrain hyperintensity was evidenced on T2-weighted magnetic resonance imaging sequences at the time of shunt malfunction. This rapidly resolved after the patient underwent third ventriculostomy. CONCLUSIONS: It is probable that in obstructive hydrocephalus, at the time of shunt malfunction, the development of a transtentorial pressure gradient could initially induce a functional impairment of the upper midbrain, inducing upward gaze palsy. The persistence of the gradient could lead to a global dysfunction of the upper midbrain. Third ventriculostomy contributes to equalization of cerebrospinal fluid pressure across the tentorium by restoring free communication between the infratentorial and supratentorial compartments, resulting in resolution of the patient's clinical symptoms.     

Pseudomutagenesis. The persistent increase in the level of cellular variability induced by radiation and some other agents

Electron microscopic investigation of capillary endothelium cells in myocardium of irradiated rats revealed an unusual effect of persistent increase of probability of cell damage, similar in many relations to that described earlier for various unicellular species. New effect, unlike those traditionally studied, is characterised by non-stochastic nature, large number of the involved cells, reveals itself even after faint influences, and can be induced as well by agents other than radiation. The question is put on the probable commonness between these changes and the pseudomutagenesis which has the similar phenomenology.     

Growth hormone treatment in pediatric burns: a safe therapeutic approach

In the recovery period after strenuous exercise, there is increased O2 uptake, termed the excess postexercise O2 consumption (EPOC). One of the mechanisms suggested to explain EPOC is activation of the triglyceride/fatty acid (TG/FA) cycle by catecholamines. The purpose of this study was to determine the effect of selective beta1- and nonselective beta-adrenoceptor blockade on EPOC and the TG/FA cycle. Seven healthy young men each participated in three control and three exercise experiments in a randomized and balanced sequence. In the exercise experiments, subjects exercised for 90 minutes at 58% +/- 2% (mean +/- SD) of maximal O2 uptake on a cycle ergometer, followed by a 4.5-hour bedrest. The control experiments followed the same protocol, but without exercise. In one control and one exercise experiment, the selective beta1-adrenoceptor antagonist atenolol (0.062 mg.kg(-1) body weight) was administered intravenously immediately after the exercise (EXAT) and at the corresponding time in the rest-control experiment (REAT). In a second set of control and exercise experiments, the nonselective beta-adrenoceptor antagonist propranolol (0.15 mg.kg(-1) body weight) was administered (REPRO and EXPRO). In a third set of rest and exercise experiments, an injection of saline was given instead of beta-antagonist (RE and EX). TG/FA cycling was calculated by combining results obtained with a two-stage glycerol infusion and indirect calorimetry. O2 uptake was significantly increased above control levels throughout the recovery period after exercise with the nonselective beta-adrenoceptor antagonist, beta1-adrenoceptor antagonist, and saline. However, there was no difference between the time course or magnitude of EPOC in the three situations. After 4.5 hours of bedrest, the mean increase in O2 uptake was 8% to 9% in all three conditions. TG/FA cycling was increased after exercise, but no effects of beta-antagonists were observed. We conclude that EPOC and the rate of TG/FA cycling are not attenuated by selective beta1- or nonselective beta-adrenoceptor blockade after an acute prolonged exercise protocol.     

Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy

BACKGROUND: The relationship of the burn wound flora to microbial pathogens in the tracheobronchial tree has important implications for antimicrobial therapy in the severely burned patient. Management of septic complications is bolstered by surveillance quantitative wound cultures (QWC) and bronchial lavage fluid (BLF) cultures. OBJECTIVES: To compare the organisms present in BLF with those found in QWC and to determine if QWC can predict BLF results. DESIGN: Results of BLF cultures from all patients who underwent bronchial lavage from January 1, 1996, to December 31, 1996, at our institution were compared with QWC data from the same date. Criteria for a positive match included an identical antibiotic susceptibility pattern and biotype. Match rates were calculated qualitatively and quantitatively. RESULTS: In 30 (48%) of the 62 BLF cultures, there was a match between the organism identified in the BLF and the QWC. When strict quantitative criteria were applied, the match rate was only 9 (14%) of 62. Burn size and inhalation injury had no significant effect on match rate. CONCLUSIONS: Whereas the microbial pathogens were similar in the QWC and BLF, linear regression showed no value of QWC in predicting BLF culture results. The difference between qualitative and quantitative match rates suggests cross-colonization between the burn wound and tracheobronchial tree, but little to no cross-infection. The QWC and BLF cultures must be performed independently in determining antimicrobial specificity in the burned patient.     

Range of validity of alpha and beta for a generalized diversity index H (alpha, beta) due to Good

1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.