Spontaneous formation of rosettes by autologous human monocyte-macrophages and lymphocytes in cell cultures.
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Adult↗
Biomedical subjects
I Novak
Publications and source records attributed to I Novak.
Effect of bicarbonate on potassium conductance of isolated perfused rat pancreatic ducts.
The aim of this study was to investigate the role of the K+ conductance in unstimulated and stimulated pancreatic ducts and to see how it is affected by provision of exogenous HCO3-/CO2. For this purpose we have applied electrophysiological techniques to perfused pancreatic ducts, which were dissected from rat pancreas. The basolateral membrane potential PDbl of unstimulated duct cells was between -60 mV and -70 mV, and the cells had a relatively large K+ conductance in the basolateral membrane as demonstrated by (a) 20-22 mV depolarization of PDbl in response to increase in bath K+ concentration from 5 mmol/l to 20 mmol/l and (b) the effect of a K+ channel blocker, Ba2+ (5 mmol/l), which depolarized PDbl by 30-40 mV. These effects on unstimulated ducts were relatively independent of bath HCO3-/CO2. The luminal membrane seemed to have no significant K+ conductance. Upon stimulation with secretin or dibutyryl cyclic AMP, PDbl depolarized to about -35 mV in the presence of HCO3-/CO2. Notably, the K+ conductance in the stimulated ducts was now only apparent in the presence of exogenous HCO3-/CO2 in the bath solutions. Upon addition of Ba2+, PDbl depolarized by 13 +/- 1 mV (n = 7), the fractional resistance of the basolateral membrane, FRbl increased from 0.66 to 0.78 (n = 6), the specific transepithelial resistance, Rte, increased from 52 +/- 13 omega cm2 to 59 +/- 15 omega cm2 (n = 11), and the whole-cell input resistance, Rc, measured with double-barrelled electrodes, increased from 20 M omega to 26 M omega (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Perioperative monitoring of total body water by bio-electrical impedance in children undergoing open heart surgery.
UNLABELLED: Knowledge of the changes in total body water (TBW) following cardiac surgery (OHS) in children would be of value in fluid therapy and in researching the causes and management of capillary leak. We have validated a bioelectrical impedance technique (BEI) for non-invasive estimation of TBW in children after OHS. We report the use of this method in a longitudinal study. Twenty patients (mean age 4.7 years +/- 3.5 (SD), mean weight (WT) 16.2 kg +/- 1 kg) undergoing a variety of complex OHS procedures were studied from 1 day preoperatively to 4 days postoperatively. Anaesthetic and basic bypass (CPB) techniques were uniform. Six patients underwent CPB at less than 20 degrees C, 10 at 20 degrees - 25 degrees C and 4 at 26 degrees - 33 degrees C. TBW (BEI), core (ctemp) and peripheral (ptemp) temperatures and fluid balance (TFB) were recorded at frequent intervals. TBW (by BEI) rose (P less than 0.001) following CPB in all patients from 62% +/- 9% (SD) body weight preoperatively to 73% +/- 13% in the ICU (an increase of 11% +/- 5%). TBW remained significantly elevated until the 3rd postoperative day. Multivariate analysis (MVA) confirmed that TBW was significantly related to TFB, but not to ctemp or ptemp. MVA also revealed smaller patient size (height and weight), younger age and longer CPB time as incremental risk factors for the rise in TBW. CONCLUSIONS: (1) BEI permits the non-invasive study of TBW in children after OHS, when TBW variation may be considerable. (2) The smaller the child and the longer the CPB, the greater the rise in TBW. (3) The technique should be a valuable tool in researching the major water fluxes associated with CPB in children.
Body Composition↗
Salivary secretion: studies on intact glands in vivo and in vitro.
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Acetylcholine↗
Cation transport by sweat ducts in primary culture. Ionic mechanism of cholinergically evoked current oscillations.
1. The coiled reabsorptive segment of human sweat ducts was cultured in vitro. Cells were then harvested and plated onto a dialysis membrane which was glued over a hole in a small disc. Cultures were maintained in a low serum, hormone-supplemented medium that allowed the cells to grow to confluency. The disc was then placed as a partition between two compartments of a miniature Ussing chamber. The chamber was mounted on the stage of an inverted microscope and intracellular potentials were recorded under transepithelial open-circuit or voltage clamp conditions. All values are given as means +/- S.E.M. and n refers to the number of preparations or duct cells. 2. Under control conditions, the cultured epithelia developed mucosa-negative transepithelial potentials (Vt) ranging from -2.5 to -38 mV (-13.5 +/- 1.5 mV, n = 36). The basolateral membrane potential (Vb) was -39.4 +/- 0.7 mV (n = 50 cells), and the apical membrane potential (Va) was linearly correlated with Vt:Va = 1.0 Vt -39.3 mV (r = -0.78, n = 50). 3. The epithelium generated inwardly directed short-circuit currents (Isc) of 12-95 microA cm-2 (45 +/- 4 microA cm-2, n = 36) with a steady-state intracellular potential. Vc = -31.1 +/- 0.6 mV and a fractional resistance of the apical membrane, fR = 0.59 +/- 0.01 (n = 115 cells). 4. The Na+ channel blocker amiloride (mucosal bath, 10 microM) abolished Isc -0.8 +/- 0.6 microA cm-2), the cells hyperpolarized to -61.0 +/- 1.2 mV, and fR increased to 0.85 +/- 0.01 (n = 44). These effects were fully reversible. 5. During initial stimulation with the cholinergic agonist, methacholine (serosa, 5 or 10 microM), the short-circuit current increased to 80 +/- 10 microA cm-2, the cells hyperpolarized to -55.8 +/- 1.2 mV, and fR increased to 0.82 +/- 0.01 (n = 35). 6. In short-circuited preparations stimulated with methacholine an increase in mucosal potassium concentration ([K+]m) from 5 to 25 mM had no significant effect, while a similar increase in the serosal K+ concentration ([K+]s) produced a change in Vc of 44 +/- 3 mV per log10[K+]s (n = 9). In non-stimulated preparations this change was only 16 +/- 2 mV per log10[K+]s (n = 13). After blocking the apical Na+ channels with amiloride the slope was 24 +/- 5 mV per log10[K+]s in unstimulated preparations.(ABSTRACT TRUNCATED AT 400 WORDS)
Amiloride↗
Acetate stimulates secretion in the rabbit mandibular gland.
In isolated perfused rabbit mandibular glands undergoing stimulation with 0.8 microM acetylcholine, replacement of HCO3- with acetate (25 mM) increased fluid secretion by more than 100%. Other short-chain fatty acids, except for propionate, had a similar effect. We focused our further studies on acetate, and in order to find out the cause of its stimulatory effect we investigated whether acetate itself was transported. In the absence of any other transportable anions 25 mM acetate supported secretion at the same rate as 25 mM HCO3- or 25 mM Cl-, i.e. 20% of the control rate. In solutions containing acetate as the only major anion (146 mM), fluid secretion was maintained at about 50% of the control rate. Amiloride (1 mM) inhibited this secretion by about 90%. In glands perfused with acetate/Cl- solutions, when the stimulatory effect was normally observed, amiloride (1 mM) inhibited secretion by 50-60% and SITS (0.1 mM) had no effect. Probenecid reversibly inhibited 75% of secretion in these glands, but it also inhibited 92% of secretion in glands perfused without any acetate. Interestingly, the acetate effect was abolished in glands stimulated with a higher concentration of acetylcholine (80 microM). Results of this study suggest that acetate can be transported by salivary endpieces and that this transport involves an amiloride-sensitive Na+-H+ antiport. We postulate that acetate may in addition have some regulatory or modifier role in salivary secretion.
Acetates↗
Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane.
In order to study the mechanism of pancreatic HCO3- transport, a perfused preparation of isolated intra- and interlobular ducts (i.d. 20-40 microns) of rat pancreas was developed. Responses of the epithelium to changes in the bath ionic concentration and to addition of transport inhibitors was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6) within less than 10 s. When the bath K+ concentration was increased from 5 to 20 mmol/l, PDbl depolarized by 15.9 +/- 0.9 mV (n = 50). The same K+ concentration step had no effect on PDbl if the ducts were exposed to Ba2+, a K+ channel blocker. Application of Ba2+ (1 mmol/l) alone depolarized PDbl by 26.4 +/- 1.4 mV (n = 19), while another K+ channel blocker TEA+ (50 mmol/l) depolarized PDbl only by 7.7 +/- 2.0 mV (n = 9). Addition of amiloride (1 mmol/l) to the bath caused 3-4 mV depolarization of PDbl. Furosemide (0.1 mmol/l) and SITS (0.1 mmol/l) had no effect on PDbl. An increase in the bath HCO3- concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively charged, or whether it was due to decreased K+ conductance caused by lowered intracellular pH. Experiments showed that the HCO3- effect was present even when the bath Na+ concentration was reduced to a nominal value of 0 mmol/l. Similarly, the HCO3- effect remained unchanged after Ba2+ (5 mmol/l) was added to the bath. The results indicate that on the basolateral membrane of duct cells there is a ouabain sensitive (Na+ + K+)-ATPase, a Ba2+ sensitive K+ conductance and an amiloride sensitive Na+/H+ antiport. The HCO3- effect on PDbl is most likely due to rheogenic anion exit across the luminal membrane.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
Properties of the luminal membrane of isolated perfused rat pancreatic ducts. Effect of cyclic AMP and blockers of chloride transport.
The aim of the present study was to investigate by what transport mechanism does HCO-3 cross the luminal membrane of pancreatic duct cells, and how do the cells respond to stimulation with dibutyryl cyclic AMP (db-cAMP). For this purpose a newly developed preparation of isolated and perfused intra- and interlobular ducts of rat pancreas was used. Responses of the epithelium to inhibitors and agonists were monitored by electrophysiological techniques. Addition of HCO-3/CO2 to the bath side of nonstimulated ducts depolarized the PD across the basolateral membrane (PDbl) by about 9 mV, as also observed in a previous study [21]. This HCO-3 effect was abolished by Cl- channel blockers or SITS infused into the lumen of the duct: i.e. 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 10(-5) M) hyperpolarized PDbl by 8.2 +/- 1.6 mV (n = 13); 3',5-dichlorodiphenylamine-2-carboxylic acid (DCl-DPC, 10(-5) M) hyperpolarized PDbl by 10.3 +/- 1.7 mV (n = 10); and SITS hyperpolarized PDbl by 7.8 +/- 0.9 mV (n = 4). Stimulation of the ducts with db-cAMP in the presence of bath HCO-3/CO2 resulted in depolarization of PDbl, the ductal lumen became more negative and the fractional resistance of the luminal membrane decreased. Together with forskolin (10(-6) M), db-cAMP (10(-4) M) caused a fast depolarization of PDbl by 33.8 +/- 2.5 mV (n = 6). When db-cAMP (5 x 10(-4) M) was given alone in the presence of bath HCO-3/CO2, PDbl depolarized by 25.3 +/- 4.2 mV (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
Effect of K+ and K+ channel blockers on pancreatic HCO3-transport.
The present study investigated whether there is a K+ conductive pathway on the basolateral membrane of pancreatic duct cells. Small inter- and intralobular ducts were isolated from rat pancreas and perfused in vitro. Duct cells were impaled and the potential across the basolateral membrane (PDbl) was measured. The resting potential was -61 +/- 1 mV. Ouabain (3 mmol/l) depolarized PDbl by 11 mV. Increase in the bath K+ concentration from 5 to 20 mmol/l depolarized PDbl by 15-16 mV. The effect of K+ channel blockers was tested. Ba2+ (1 mmol/l) added to the bath depolarized PDbl by 23-26 mV, whereas TEA+ (50 mmol/l) depolarized PDbl only by 7-8 mV. Dibutyryl cyclic AMP (0.5 mmol/l) depolarized PDbl by 20-30 mV. The results show that on the basolateral membrane of pancreatic duct cells there is a (Na+ + K+)-ATPase and a K+ conductive pathway sensitive to Ba2+.
Animals↗
Two independent anion transport systems in rabbit mandibular salivary glands.
Cholinergically stimulated Cl and HCO3 transport in perfused rabbit mandibular glands has been studied with extracellular anion substitution and administration of transport inhibitors. In glands perfused with HCO3-free solutions, replacement of Cl with other anions supported secretion in the following sequence: Br = greater than Cl greater than I = greater than NO3 greater than isethionate. Furosemide, 1.0 and 0.1 mmol/l, inhibited Cl-supported secretion by 97-99% and 70-78%, respectively. SITS, 0.1 mmol/l, had no effect and amiloride, 1.0 mmol/l, caused a 55-65% inhibition. Addition of SITS to amiloride-treated glands produced no further effect. In glands perfused with Cl-free solutions, but containing 25 mM HCO3, amiloride, 1.0 mmol/l, inhibited secretion by 95% and methazolamide, 0.1 mmol/l, by 55%. In glands perfused with solutions containing both HCO3 and Cl, furosemide had smaller effects than in glands perfused with solutions containing only Cl - a dose of 1.0 mmol/l inhibited 60% of the initial fast phase of secretion, and 90% of the later plateau phase, while a dose of 0.1 mmol/l inhibited 30% of the initial phase, but had no effect on the plateau. SITS, 0.1 mmol/l, actually stimulated secretion by about 30%, but when infused in addition to furosemide (0.1 mmol/l), it inhibited by about 20%. Amiloride (1.0 mmol/l) caused no inhibition. The results suggest that there are at least three distinct carriers in the rabbit mandibular gland. One is a furosemide-sensitive Na-coupled Cl (probably Na-K-2Cl) symport, responsible for the bulk of normal secretion. The others are an amiloride-sensitive Na-H antiport and a SITS-sensitive Cl-HCO3 antiport.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
Choline evokes fluid secretion by perfused rat mandibular gland without desensitization.
The secretomotor action of choline on salivary secretion has been studied in the isolated perfused mandibular gland of the rat. Choline made up in substituted Ringer solutions (Na concentrations of 40, 70, or 100 mM) was an effective secretomotor agonist in the concentration range of 1-100 mM and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline concentration used exceeded approximately 80 mM. The secretomotor action of choline (46 mM) was blocked completely and reversibly by atropine (5 microM) but not by propranolol (2.5 microM) and phentolamine (2.5 microM) administered together. When acetylcholine (1.0 or 0.05 microM) was infused on a background of choline stimulation, a small additional secretory response was elicited whenever the choline stimulus was submaximal, and, regardless of the choline concentration employed, addition of acetylcholine always induced tachyphylaxis. The results suggest that choline and acetylcholine act on the same population of muscarinic receptors, but it is unclear why choline does not evoke tachyphylaxis. The response to choline allows us to exclude a number of the possible causes of tachyphylaxis that have previously been considered, so that an excessive buildup of cytosolic free Ca now remains as the most likely cause of the phenomenon.
Acetylcholine↗
The anionic basis of fluid secretion by the rabbit mandibular salivary gland.
The role played by anions in salivary secretion has been studied in experiments on the isolated, perfused mandibular gland of the rabbit, in which perfusate Cl- and/or HCO3- were replaced by other anions. Replacement of Cl- with Br- had no significant effect on salivary secretion rate, but replacement with the other anions tested caused secretory rate to fall, by 38% (I-), 50% (NO3-), 61% (isethionate, ise -), and 66% ( CH3SO4 -), respectively. Replacement of perfusate Cl- with ise - or CH3SO4 - caused the salivary HCO3- concentration to rise up to 4-fold. Replacement with Br- or I- seemed to have little effect on salivary HCO3- concentration but, in contrast to ise -, Br- and I- entered the saliva in concentrations comparable to those of Cl- during control perfusion. In glands perfused with HCO3- and ise -, the addition of methazolamide, an inhibitor of carbonic anhydrase, caused a further 60% drop in secretory rate, but the saliva remained rich in HCO3-. Replacement of perfusate HCO3- with Cl- or ise - had no effect on salivary secretion or composition. Replacement of both HCO3- and Cl- in the perfusate with ise - reduced salivary secretion to less than 2% of control levels. In control glands (i.e. perfused with both HCO3- and Cl-), administration of furosemide, an inhibitor of Na+/Cl- co-transport, reduced the secretion rate and increased salivary HCO3- in a manner indistinguishable from that seen when perfusate Cl- was replaced with ise -. In control perfused glands, administration of SITS (4-acetamido-4'- isothio cyano-2,2'-disulphonic acid stilbene), an inhibitor of Cl-/HCO3- antiports , did not cause any change in salivary HCO3- concentration. Unexpectedly, it induced a significant increase in salivary secretory rate. The results show that salivary secretion depends on two independent transport systems. One is a Cl- -dependent, furosemide-sensitive system, probably a Na+/Cl- symport. The other is an HCO3- -dependent, methazolamide-sensitive system, and is probably an Na+/H+ antiport.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
The role of buffer anions and protons in secretion by the rabbit mandibular salivary gland.
1. The role of extracellular HCO3- and H+ in the formation of primary saliva and its subsequent modification by the glandular ducts has been investigated in the isolated perfused mandibular salivary gland of the rabbit. 2. Variation of extracellular HCO3- concentration between 12.5 and 50.0 mmol/l was without effect on salivary flow rate or on Na+ and K+ excretion, even though salivary HCO3- (and Cl-) content altered with changes in the extracellular concentration of the two anions. 3. Complete replacement of perfusate HCO3- by Cl- reduced fluid secretion by 34% and almost abolished ductal Na+ absorption. However, when extracellular pH was controlled by replacing HCO3- with the hydrophilic HEPES buffer, fluid secretion but not ductal Na+ absorption was restored to normal. 4. Complete replacement of exogenous HCO3- with acetate increased fluid secretion by 110% and also stimulated ductal Na+ absorption. This effect did not appear to be related to changes in cell pH and remains unexplained. Acetate entered the saliva in concentrations comparable to those seen for HCO3- in control experiments. 5. Salivary secretion showed an almost linear dependence on extracellular pH, rising from 14% of control (pH 7.4) levels at pH 6.2 to 130% at pH 7.8. Ductal Na+ absorption showed similar pH dependence. 6. Carbonic anhydrase inhibitors did not affect fluid secretion rates (except when supramaximal doses of ACh were used to evoke secretion) but they did cause a large reduction in salivary HCO3- output. In glands perfused with acetate rather than HCO3-, carbonic anhydrase inhibitors had no effect on excretion of fluid, acetate or metabolically derived HCO3-. Duct perfusion studies suggested that the effect of the inhibitors on HCO3- output was at the site of primary secretion rather than at the ductal site of HCO3- transport.
Animals↗
[Radioimmunoassay of E antigen and anti-E antibody system of hepatitis B virus].
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Antibodies, Viral↗
Secretion of saliva by the rabbit mandibular gland in vitro: the role of anions.
Salivary glands form their secretions by first elaborating an isotonic plasma-like primary fluid in the endpieces and then modifying the composition of this secretion during its passage along the gland duct system. We have studied the role of extracellular anions in both primary secretion and ductal modification with a recently developed technique for isolation and perfusion of the rabbit mandibular gland. Neither of the major extracellular anions (Cl- or HCO-3) is essential for primary fluid secretion. HCO-3 can be removed altogether and replaced with Cl- without diminution in secretory rate, provided that extracellular pH is maintained at 7.4, and its replacement with acetate actually enhances secretion. Complete replacement of Cl- with Br- also enhances secretion and replacement with I-, NO-3, CH3SO-4 or isethionate supports secretion but at progressively diminishing rates. Our data do not yet allow us to distinguish between an electroneutral Na+-Cl- cotransport model or a double countertransport (Na+-H+ plus Cl--HCO-3) model as the basis of primary salivary secretion, or to propose any more suitable alternative model. With respect to ductal modification of the primary saliva, HCO-3 omission inhibits ductal Na+ absorption (i.e. salivary Na+ concentration rises). This inhibition is probably related to an effect of pH on the postulated Na+-H+ exchanges mechanism in the luminal duct membrane since it can also be induced by lowering perfusate pH, and reversed by substitution of perfusate HCO-3 with acetate (which enters saliva) but not HEPES (which does not enter the saliva). Substitution of perfusate Cl- with other anions seems not to inhibit ductal Na+ and K+ transport markedly.
Acetylcholine↗
Transport of bicarbonate and other anions in salivary secretion.
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Animals↗
Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines.
1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate.2. During perfusion with solutions containing acetylcholine, the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes oedematous during perfusion, the extent of this oedema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h, and often for more than 6 h.3. Acetylcholine evoked a small secretory response at a concentration of 8 x 10(-9) mol l(-1) and a maximum response at 8 x 10(-7) mol l(-1). Eserine (2 x 10(-5) mol l(-1)) evoked secretory responses comparable to those evoked by acetylcholine in a concentration of 8 x 10(-9) mol l(-1). Secretion, whether unstimulated or evoked by acetylcholine or eserine, could be blocked completely by atropine.4. During prolonged stimulation with acetylcholine, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the second period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with acetylcholine.5. The Na, K, Cl and HCO(3) concentrations and the osmolality of acetylcholine evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO(3), increased by about 25 mmol l(-1) during periods of prolonged stimulation with acetylcholine even though the salivary secretory rate was constant. The concentrations of K and HCO(3), but not Na and Cl, increased progressively as the concentration of infused acetylcholine was increased.6. Salivary protein secretion increased with increasing concentrations of acetylcholine to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion.7. The beta-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by acetylcholine, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by acetylcholine, being particularly rich in K and HCO(3). The isoproterenol-evoked saliva was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by acetylcholine.8. The alpha-adrenergic agonist phenylephrine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to acetylcholine. The drug had little or no effect on the electrolyte content of acetylcholine-evoked saliva and appeared to reduce its protein content.
Acetylcholine↗
[Synthesis of chromenocoumarins according E. Späth].
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Chemistry, Pharmaceutical↗