AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

The theoretical small signal impedance of the frog node,Rana pipiens

Summary The small signal impedance of the frog node is calculated for frequencies from 1 Hz to 10,000 Hz and transmembrane potentials from –80 mV to –30 mV by linearizing the voltage clamp equations of Dodge [7] and Hille [8]. The modulus of the impedance is presented for the total system, and separately for the potassium and sodium systems as a function of frequency and voltage. There is a broad resonance in the total impedance with a voltage-dependent peak frequency. At 22°C, in the range –75 mV to –45 mV, the peak frequencies occur between 50 and 500 Hz. Removing the potassium system leaves a relatively shapr resonance centered around 200 Hz at –45 mV.     

Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus.

Human CD4 was expressed on a range of mammalian cell lines. CD4+ non-primate cells, derived from rat, hamster, mink, cat, and rabbit, bind recombinant gp120 of human immunodeficiency virus type 1 (HIV-1) but are resistant to HIV-1 infection. CD4 expression on various human, rhesus, and African green monkey cell lines confers differential susceptibilities for HIV-1, HIV-2, and simian immunodeficiency (SIV) strains. For example, CD4+ TE671 rhabdomyosarcoma cells are sensitive to HIV-1 and HIV-2 but resistant to SIV, whereas CD4+ U87 glioma cells are resistant to HIV-1 infection but sensitive to HIV-2 and SIV. HIV-1 infection was not dependent on human major histocompatibility class I expression. Studies of cell fusion and of infection by vesicular stomatitis virus pseudotypes bearing HIV-1 and HIV-2 envelopes showed that the differential cell tropisms of HIV-1, HIV-2, and SIV are determined at the cell surface.     

Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein

Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.     

Cloning and expression of a rat cardiac delayed rectifier potassium channel.

We have cloned a cDNA (designated RAK) coding for a delayed-rectifier K current (IRAK) from adult rat heart atrium and expressed it in Xenopus oocytes. RAK differs from the cloned rat brain K current, BK2 [McKinnon, D. (1989) J. Biol. Chem. 264, 8230-8236], by one amino acid at residue 411. RAK expressed in oocytes compares closely to the intrinsic adult rat atrial delayed-rectifier current measured by using whole-cell recording of single isolated cells. Northern blot analysis confirmed the presence of the channel in adult rat atrium, and to a lesser extent, in rat ventricle. IRAK activates with time constants ranging from 58 ms at -20 mV to 6 ms at +60 mV and does not show significant inactivation over 800 ms. It is blocked by 4-aminopyridine greater than barium much greater than tetraethylammonium chloride, which is similar to the relative potencies of these blockers on the native delayed rectifier current. We conclude that the main delayed rectifier K current in adult rat atria is virtually identical to a neuronal delayed rectifier, BK2.     

Wound infection,dressings and pain,is there a relationship in the chronic wound?

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management.     

Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition

During the mitochondrial permeability transition, a large channel in the inner mitochondrial membrane opens, leading to the loss of multiple mitochondrial solutes and cell death. Key triggers include excessive reactive oxygen species and mitochondrial calcium overload, factors implicated in neuronal and cardiac pathophysiology. Examining the differential behavior of mitochondrial Ca²⁺ overload in Drosophila versus human cells allowed us to identify a gene, MCUR1, which, when expressed in Drosophila cells, conferred permeability transition sensitive to electrophoretic Ca²⁺ uptake. Conversely, inhibiting MCUR1 in mammalian cells increased the Ca²⁺ threshold for inducing permeability transition. The effect was specific to the permeability transition induced by Ca²⁺, and such resistance to overload translated into improved cell survival. Thus, MCUR1 expression regulates the Ca²⁺ threshold required for permeability transition.The mitochondrial permeability transition (MPT) pore is large, and its opening collapses the mitochondrial membrane potential (ΔΨ), depleting the matrix of solutes <1.5 kDa. The osmotic imbalance swells and disrupts mitochondria, leading to cell death. The molecular structure of the MPT pore is unknown, although cyclophilin D [peptidyl-prolyl isomerase F (PPIF)], the ADP/ATP translocase, the F1-FO-ATP synthase, and spastic paraplegia 7 are key for its function (1–5).Key triggers for the MPT include oxidative damage and Ca²⁺ overload. Reactive oxygen species attack a cysteine residue in mammalian PPIF (6, 7), but how Ca²⁺ overload activates the pore is unknown. Elimination of the known regulators typically inhibits the sensitivity of the MPT globally, not favoring any particular trigger (8–10). Because Ca²⁺ overload promotes cell death in excitable cells, targeting this pathway selectively may prove beneficial.To discover novel regulators specific to mitochondrial Ca²⁺ overload, we studied MPT in Drosophila S2R+ cells, a system where screens have identified molecules involved in Ca²⁺ transport (11–13). We found that mitochondria within these cells were resistant to Ca²⁺ overload (14) but did possess an MPT. Moreover, we identified a mammalian gene, mitochondrial calcium uniporter regulator 1 (MCUR1), with no known Drosophila homolog, which is able to alter the MPT Ca²⁺ threshold. Inhibiting this gene confers resistance from cell death mediated by mitochondrial Ca²⁺ overload.