Systemic corticosteroids for subcutaneous panniculitis-like T-cell lymphoma.

BACKGROUND: Primary cutaneous γ/δ T-cell lymphoma (PCGD-TCL) is aggressive and has a poor prognosis. In contrast, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) of the α/ß T-cell receptor phenotype is known to follow an indolent course and have a more favourable prognosis. In the past, PCGD-TCL and SPTCL were often considered to be a manifestation of the same disease, and aggressive systemic polychemotherapy has commonly been the first-line therapy for both. Given the understanding that SPTCL is a separate and less aggressive entity, clinical data exclusively evaluating the efficacy of conservative treatment in SPTCL are needed. OBJECTIVES: To assess the overall clinical response to systemic corticosteroids in the treatment of SPTCL. METHODS: This was a retrospective cross-sectional study based on a patient data repository from two tertiary care university hospitals in Zürich (Switzerland) and Tübingen (Germany). The repository spanned 13 years. RESULTS: In four of the five patients (80%) with SPTCL, treatment with systemic corticosteroids induced a complete remission. CONCLUSIONS: Systemic corticosteroids may be an excellent first-line single-agent therapy for SPTCL.

Fatal case of Weeksella virosa sepsis.

Weeksella virosa is an aerobic Gram-negative rod that has rarely been reported to cause infection. We describe a fatal case of W. virosa sepsis in a young female with end-stage renal disease, report three additional cases of W. virosa infection, and review the literature regarding this infection.

The anion paradox in sodium taste reception: resolution by voltage-clamp studies.

Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway.

An important early event in mammalian gustatory transduction with respect to sodium chloride has been found to be the passage of sodium ions through specific transport pathways in the apical region of the taste bud. The inward current caused by sodium chloride placed on the mucosal surface of an in vitro preparation of rat dorsal lingual epithelium can be substantially reduced by the blocker of sodium ion transport, amiloride. The data show (i) that amiloride is a specific blocker of the chorda tympani response to sodium chloride, but not to potassium chloride, (ii) that the sodium and potassium gustatory systems are largely independent at the peripheral level, and (iii) that the classical ion taste "receptor" is actually a specific transport pathway permitting the cation to enter the taste-bud cell and thereby to spread depolarizing current.

Active ion transport in dog tongue: a possible role in taste.

An in vitro preparation of the dorsal epithelium of the dog tongue actively transports ions, producing a transepithelial potential difference characteristic of the ions and their concentration. Hypertonic sodium chloride solutions generally cause increased potentials and short-circuit currents and reduced resistances when placed on the mucosal surface. This hypertonic flux is eliminated by ouabain and is not found in ventral lingual epithelia. When either sodium acetate or tetramethylammonium chloride is substituted for sodium chloride in the mucosal medium, the currents are diminished but their sum at a given concentration approximates that for sodium chloride at the same concentration. This result suggests a current composed of inward sodium ion movement and outward chloride ion movement. Actively regulated potentials and currents, whether generated in the taste buds or in supporting cells, may be important in both normal chemotransduction and in taste responses evoked by currents passing through the tongue.

Ferroin-collodion membranes: dynamic concentration patterns in planar membranes.

Patterns and waves of the Belousov-Zhabotinskii reaction are produced in membranes in which one reactant is immobilized. Convection is eliminated, the generation and deformation of wave forms are studied, and patterns are permnanently fixed. Wave shape, frequency, length, and phase velocity are explained theoretically by the interactions of diffusion with reaction.

Pneumococcal vaccination during pregnancy for preventing infant infection.

BACKGROUND: Each year at least one million children worldwide die of pneumococcal infections. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but does not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection. OBJECTIVES: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to June 2004), EMBASE (January 1985 to June 2004), and reference lists of articles. SELECTION CRITERIA: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing or with another vaccine to prevent infant infections. DATA COLLECTION AND ANALYSIS: Two authors independently assessed methodological quality and extracted data using a data collection form. Study authors were contacted for additional information. MAIN RESULTS: Three trials (280 participants) were included. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (one trial, 149 pregnancies, relative risk (RR) 0.51; 95% confidence interval (CI) 0.18 to 1.41). Although the data suggest an effect in reducing pneumococcal colonisation in infants by 16 months of age (one trial, 56 pregnancies, RR 0.33; 95% CI 0.11 to 0.98), there was no evidence of this effect in infants at two months of age (RR 0.28; 95% CI 0.02 to 5.11) or by seven months of age (RR 0.32; 95% CI 0.08 to 1.29). AUTHORS' CONCLUSIONS: There is insufficient evidence to support whether pneumococcal vaccination during pregnancy could reduce infant infections.

An alternative to allosteric interactions as causes of sigmoid dose versus response curves. Application to glucose-induced secretion of insulin.

It is shown that a sigmoid dose vs. response curve will occur in any biological system in which the stimulant compound must diffuse significant distances to reach responding cells, even when the cells themselves respond according to Michaelis-Menten kinetics. Isolated pancreatic islets releasing insulin in response to glucose stimulation have been used as a specific example. Since diffusion and/or other physical processes can produce global effects which could account for the sigmoidal nature of a dose vs. response curve, the existence of complex molecular mechanisms of hormone-receptor interaction can not be inferred solely from the character of a dose vs. response relation.

Potential dependence of unidirectional chloride fluxes across isolated frog skin.

Isolated frog skins were voltage clamped at transepithelial potentials (Vt) ranging from -60 mV to 60 mV to measure transepithelial 36Cl- fluxes from the apical to the basolateral bathing solution (J13) and in the opposite direction (J31). The potential dependence of fluxes obtained in Na+-free choline Ringer's indicates the presence of conductive and nonconductive components that probably correspond to fluxes through paracellular and cellular pathways, respectively. Rectification of fluxes with reversal of the potential reflects a structural asymmetry, presumably in surface charge density. The data are consistent with a charge density of one negative charge per 280 A2 on the apical side. A new model for passive Cl- transport was developed that includes surface charge asymmetry and specifically accounts for the observed variation of conductance with potential. In normal frog Ringer's, J13 was larger than J31 at zero potential (active Cl- transport), J13 rose exponentially with increasing positive potential to reach a maximum at 40 mV (approximately open-circuit), and the predicted partial Cl- conductance exceeded the measured conductance leading to the conclusion that when J13 is largely driven by Na+ transport, much of the coupling occurs via nonconductive pathways. Theophylline stimulates Cl- transport that also occurs via nonconductive pathways as Vt becomes more positive.

Ion transport across the frog olfactory mucosa: the action of cyclic nucleotides on the basal and odorant-stimulated states.

The action of cyclic nucleotides on the short-circuit current across the isolated bullfrog olfactory mucosa was studied both in the absence and presence of odorants. 8-Bromo-cAMP applied to the ciliated side of the mucosa caused a concentration-dependent, reversible increase in the basal short-circuit current, but not when it was applied to the submucosal side. The current had a sigmoidal concentration dependence described by the Hill equation. The magnitude of the odorant-evoked current was enhanced after bathing the ciliated side with cAMP analogs or modulators of intracellular cAMP. GTP gamma S added to the ciliated side increased the odorant-evoked current, while GDP beta S caused a decrease. Current transients induced by stimulating the ciliated side with either pulses of odorant or 8-bromo-cAMP were partially suppressed by amiloride, but only when amiloride and stimulant were presented simultaneously. Pulses of 8-bromo-cAMP and odorant presented simultaneously resulted in currents that added nonlinearly. In the absence of odorant, 8-bromo-cGMP caused a concentration-dependent decrease in net inward current that was reversed by 8-bromo-cAMP. Odorant-evoked currents were also reduced by 8-bromo-cGMP, and these could not be reversed by 8-bromo-cAMP. The results indicate that one type of olfactory transduction process involves the activation by cAMP of an inward current through an amiloride-sensitive apical ion channel and that this mechanism is mediated by a stimulatory G-protein.

Ion transport across the frog olfactory mucosa: the basal and odorant-stimulated states.

The Ussing method was adapted to study the basal electrolyte transfer as well as the events that occur upon odorant stimulation in frog olfactory mucosa. The unstimulated short-circuit current was due mainly to a furosemide-sensitive ion transport system on the apical side of the olfactory mucosa. This current was not amiloride sensitive. The current-voltage relationship of the unstimulated state was linear. That of the odorant-evoked current was non-linear and amiloride-sensitive. Ouabain caused collapse of both the unstimulated and odorant-stimulated short-circuit current. In this case, voltage-clamping the tissue to non-zero values restored the odorant-evoked current with polarity depending on that of the clamping voltage. This suggested that the direction of the current is determined by that of the sodium electrochemical potential difference. Our results indicate that the unstimulated short-circuit current occurs through an apical sodium cotransport system, while the odorant-evoked current is due to odorant-activated, passive sodium channels that are amiloride sensitive.

The identity of the current carriers in canine lingual epithelium in vitro.

Ion transport across the lingual epithelium has been implicated as an early event in gustatory transduction. The fluxes of isotopically labelled Na+ and Cl- were measured across isolated canine dorsal lingual epithelium under short-circuit conditions. The epithelium actively absorbs Na+ and to a lesser extent actively secretes Cl-. Under symmetrical conditions with Krebs-Henseleit buffer on both sides, (1) Na+ absorption accounts for 46% of the short-circuit current (Isc); (2) there are two transcellular Na+ pathways, one amiloride-sensitive and one amiloride-insensitive; (3) ouabain, added to the serosal solution, inhibits both Isc and active Na+ absorption. When hyperosmotic (0.25 M) NaCl is placed in the mucosal bath, both Isc and Na+ absorption increase; net Na+ absorption is at least as much as Isc. Ion substitution studies indicate that the tissue may transport a variety of larger ions, though not as effectively as Na+ and Cl-. Thus we have shown that the lingual epithelium, like other epithelia of the gastrointestinal tract, actively transports ions. However, it is unusual both in its response to hyperosmotic solutions and in the variety of ions that support a transepithelial short-circuit current. Since sodium ion transport under hyperosmotic conditions has been shown to correlate well with the gustatory neural response, the variety of ions transported may likewise indicate a wider role for transport in taste transduction.

Effects of voltage perturbation of the lingual receptive field on chorda tympani responses to Na+ and K+ salts in the rat: implications for gustatory transduction.

Taste sensory responses from the chorda tympani nerve of the rat were recorded with the lingual receptive field under current or voltage clamp. Consistent with previous results (Ye, Q., G. L. Heck, and J. A. DeSimone. 1993. Journal of Neurophysiology. 70:167-178), responses to NaCl were highly sensitive to lingual voltage clamp condition. This can be attributed to changes in the electrochemical driving force for Na+ ions through apical membrane transducer channels in taste cells. In contrast, responses to KCl over the concentration range 50-500 mM were insensitive to the voltage clamp condition of the receptive field. These results indicate the absence of K+ conductances comparable to those for Na+ in the apical membranes of taste cells. This was supported by the strong anion dependence of K salt responses. At zero current clamp, the potassium gluconate (KGlu) threshold was > 250 mM, and onset kinetics were slow (12 s to reach half-maximal response). Faster onset kinetics and larger responses to KGlu occurred at negative voltage clamp (-50 mV). This indicates that when K+ ion is transported as a current, and thereby uncoupled from gluconate mobility, its rate of delivery to the K+ taste transducer increases. Analysis of conductances shows that the paracellular pathway in the lingual epithelium is 28 times more permeable to KCl than to KGlu. Responses to KGlu under negative voltage clamp were not affected by agents that are K+ channel blockers in other systems. The results indicate that K salt taste transduction is under paracellular diffusion control, which limits chemoreception efficiency. We conclude that rat K salt taste occurs by means of a subtight junctional transducer for K+ ions with access limited by anion mobility. The data suggest that this transducer is not cation selective which also accounts for the voltage and amiloride insensitive part of the response to NaCl.

Sugar-activated ion transport in canine lingual epithelium. Implications for sugar taste transduction.

There is good evidence indicating that ion-transport pathways in the apical regions of lingual epithelial cells, including taste bud cells, may play a role in salt taste reception. In this article, we present evidence that, in the case of the dog, there also exists a sugar-activated ion-transport pathway that is linked to sugar taste transduction. Evidence was drawn from two parallel lines of experiments: (a) ion-transport studies on the isolated canine lingual epithelium, and (b) recordings from the canine chorda tympani. The results in vitro showed that both mono- and disaccharides in the mucosal bath stimulate a dose-dependent increase in the short-circuit current over the concentration range coincident with mammalian sugar taste responses. Transepithelial current evoked by glucose, fructose, or sucrose in either 30 mM NaCl or in Krebs-Henseleit buffer (K-H) was partially blocked by amiloride. Among current carriers activated by saccharides, the current response was greater with Na than with K. Ion flux measurements in K-H during stimulation with 3-O-methylglucose showed that the sugar-evoked current was due to an increase in the Na influx. Ouabain or amiloride reduced the sugar-evoked Na influx without effect on sugar transport as measured with tritiated 3-O-methylglucose. Amiloride inhibited the canine chorda tympani response to 0.5 M NaCl by 70-80% and the response to 0.5 M KCl by approximately 40%. This agreed with the percent inhibition by amiloride of the short-circuit current supported in vitro by NaCl and KCl. Amiloride also partially inhibited the chorda tympani responses to sucrose and to fructose. The results indicate that in the dog: (a) the ion transporter subserving Na taste also subserves part of the response to K, and (b) a sugar-activated, Na-preferring ion-transport system is one mechanism mediating sugar taste transduction. Results in the literature indicate a similar sweet taste mechanism for humans.

The active ion transport properties of canine lingual epithelia in vitro. Implications for gustatory transduction.

The electrophysiological properties of the dorsal and ventral canine lingual epithelium are studied in vitro. The dorsal epithelium contains a special ion transport system activated by mucosal solutions hyperosmotic in NaCl or LiCl. Hyperosmotic KCl is significantly less effective as an activator of this system. The lingual frenulum does not contain the transport system. In the dorsal surface it is characterized by a rapid increase in inward current and can be quantitated as a second component in the time course of either the open-circuit potential or short-circuit current when the mucosal solution is hyperosmotic in NaCl or LiCl. The increased inward current (hyperosmotic response) can be eliminated by amiloride (10(-4) M). The specific location of this transport system in the dorsal surface and the fact that it operates over the concentration range characteristic of mammalian salt taste suggests a possible link to gustatory transduction. This possibility is tested by recording neural responses in the rat to NaCl and KCl over a concentration range including the hyperosmotic. We demonstrate that amiloride specifically blocks the response to NaCl over the hyperosmotic range while affecting the KCl response significantly less. The results suggest that gustatory transduction for NaCl is mediated by Na entry into the taste cells via the same amiloride-sensitive pathway responsible for the hyperosmotic response in vitro. Further studies of the in vitro system give evidence for paracellular as well as transcellular current paths. The transmural current-voltage relations are linear under both symmetrical and asymmetrical conditions. After ouabain treatment under symmetrical conditions, the short-circuit current decays to zero. The increase in resistance, though significant, is small, which suggests a sizeable shunt pathway for current. Flux measurements show that sodium is absorbed under symmetrical conditions. Mucosal solutions hyperosmotic in various sugars also induce an amiloride-sensitive inward current. In summary, this work provides evidence that the sodium taste receptor is most probably a sodium transport system, specifically adapted to the dorsal surface of the tongue. The transport paradigm of gustation also suggests a simple model for electric taste and possible mechanisms for sweet taste.

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Taste buds were isolated from the fungiform papilla of the rat tongue and the receptor cells (TRCs) were patch clamped. Seals were obtained on the basolateral membrane of 281 TRCs, protruding from the intact taste buds or isolated by micro-dissection. In whole-cell configuration 72% of the cells had a TTX blockable transient Na inward current (mean peak amplitude 0.74 nA). All cells had outward K currents. Their activation was slower than for the Na current and a slow inactivation was also noticeable. The K currents were blocked by tetraethylammonium, Ba, and 4-aminopyridine, and were absent when the pipette contained Cs instead of K. With 100 mM Ba or 100 mM Ca in the bath, two types of inward current were observed. An L-type Ca current (ICaL) activated at -20 mV had a mean peak amplitude of 440 pA and inactivated very slowly. At 3 mM Ca the activation threshold of ICaL was near -40 mV. A transient T-type current (ICaT) activated at -50 mV had an average peak amplitude of 53 pA and inactivated with a time constant of 36 ms at -30 mV. ICaL was blocked more efficiently by Cd and D600 than ICaT. ICaT was blocked by 0.2 mM Ni and half blocked by 200 microM amiloride. In whole-cell voltage clamp, Na-saccharin caused (in 34% of 55 cells tested) a decrease in outward K currents by 21%, which may be expected to depolarize the TRCs. Also, Na-saccharin caused some taste cells to fire action potentials (on-cell, 7 out of 24 cells; whole-cell, 2 out of 38 cells responding to saccharin) of amplitudes sufficient to activate ICaL. Thus the action potentials will cause Ca inflow, which may trigger release of transmitter.

Lingual epithelium of spontaneously hypertensive rats has decreased short-circuit current in response to NaCl.

Alterations in ion transport associated with hypertension have been found in a variety of organs. We used a modified Ussing chamber to compare the NaCl dependence of the short-circuit current across the dorsal lingual epithelium in vitro from spontaneously hypertensive rats (SHR) with that from Wistar-Kyoto rats (WKY). The short-circuit current in response to mucosal NaCl was less in SHR than in WKY at hyperosmotic concentrations (above 0.15 M and up to 2.0 M). Since ion transport in the lingual epithelium has been found to play a role in early events of salt taste transduction, the attenuation in the short-circuit current in hypertensive animals may be a factor in the enhanced salt preference of SHR compared with WKY.

Anion size of sodium salts and simple taste reaction times.

Simple taste reaction times (RT) and taste intensities were measured in adult humans for 100-mM aqueous solutions of sodium chloride, acetate, glutamate, ascorbate, and gluconate flowed over the anterodorsal tongue with a closed liquid delivery system. Results from 12 subjects showed a significant increase in RT with molecular weight of the tastant, and a correlation of 0.941 between RT and the square roots of anionic weights. A multiple regression analysis controlling for perceived taste intensity indicated that RT increased linearly with the square root of the anionic weight. These findings support a model that includes both the permeability of ions through the tight junctions between the taste receptor cells of fungiform papillae taste buds and the effects of ions at apical portions of the receptor cells. They also suggest that gustatory transduction of sodium salts in humans normally involves intercellular spaces of taste buds as part of the functional sensory structures, in addition to individual taste receptor cells.

Transduction in taste receptors.

For humans, taste plays a key role in food selection. The continuing search for low-calorie sweeteners and salt substitutes that allow less Na intake in the diet without a decline in saltiness attest to this. We are only beginning to understand how specific foodstuffs evoke taste responses. In the future, the neural, hormonal, and genetic factors that regulate the sense of taste on a long-term basis will be better understood. With this will come a better understanding of the role of taste in developing food preferences and in overall nutrition.