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F Lang

Publications and source records attributed to F Lang.

At least 415 records · Page 23Linked to original sources

On the nature of delayed repolarization during sustained sodium coupled transport in frog proximal tubules.

In proximal tubules of the frog kidney, stimulation of coupled transport of sodium with phenylalanine leads to depolarization of the cell membrane, followed by repolarization within a few minutes. The repolarization is due to a delayed increase of potassium conductance at the peritubular cell membrane. The present study was designed to test for the role of depolarization, of calmodulin and of arachidonic acid metabolites for the delayed increase of potassium conductance. To this end, the potential difference across the peritubular cell membrane of proximal convoluted tubules (PDpt) has been recorded continuously during exposure of the lumen to phenylalanine or during galvanic current injection into a neighbouring cell. During control conditions, PDpt averages -68.6 +/- 1.0 mV (n = 45). Phenylalanine leads to a depolarization of the peritubular cell membrane by +31.5 +/- 1.3 mV (n = 20), followed by a repolarization by -12.9 +/- 1.1 mV (n = 20) within 3 min. Injection of currents from 10 to 80 nAmps leads to a depolarization by +0.83 +/- 0.01 mV/nAmps which is again followed by repolarization. A linear correlation is observed between the magnitude of depolarization (dep) and repolarization (rep) within 3 min: rep (mV) = -(0.24 +/- 0.01) dep (mV) +(2.45 +/- 0.12) mV (r = 0.90). Thus, depolarization is capable to trigger delayed repolarization. The extent of repolarization is a function of the magnitude of depolarization. The possible involvement of calmodulin or arachidonic acid metabolites has been tested for by inducing sodium coupled transport in the presence of 100 mumol/l mepacrine, 10 mumol/l indomethacin or 10 mumol/l trifluoperazine.

Animals↗

Osmotic diuresis.

Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs.

Animals↗

Cytoadherence of lymphocytes from type I diabetic subjects to insulin-secreting cells. Marker of anti-beta-cell cellular immunity.

We studied the ability of lymphocytes from type I (insulin-dependent) diabetic patients to adhere to murine beta-cells. Lymphocytes from 17 recent-onset type I diabetic subjects (less than 6 mo) displayed enhanced ability to form rosettes with RINm5F cells (P less than .001) compared with lymphocytes from 27 healthy subjects forming background rosettes, whereas the number of RIN cytoadherent lymphocytes was unimpaired in 12 type II (non-insulin-dependent) diabetic subjects. This phenomenon tended to decline in 21 subjects with long-standing diabetes (greater than 1 yr) who taken as a group presented a normal number of RIN rosetting lymphocytes. The islet specificity of these diabetic rosettes was confirmed because, compared with controls, lymphocytes from recent-onset type I diabetic subjects also displayed a greater intensity of adherence to normal mouse islets but not to unrelated K562 and TS cell lines. As demonstrated by indirect immunofluorescence studies, these diabetic rosettes contained 54% of T-lymphocytes (OKT3+, OKT4+, or OKT8+), whereas only 20% of T-lymphocytes were found in background rosettes. The high percentage (66%) of la+ cells found in diabetic rosettes suggests that at least some of the cytoadherent T-lymphocytes from recent-onset type I diabetic subjects are activated. Natural killer (NK) cells do not seem to be the major cell type implicated in this phenomenon, because Leu 11+ cells were less represented in diabetic rosettes (25%) than in background rosettes (53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Production of and response to interleukin 2 by blood mononuclear cells from some type 1 diabetic patients.

Production of and response to interleukin 2 (IL-2) were studied using peripheral blood mononuclear cells (PBMC) from 23 patients with type 1 diabetes. When compared to PBMC from 18 control subjects, mean PHA-stimulated IL-2 synthesis in the diabetic group was found unimpaired (1.2 +/- 0.1 vs 1.5 +/- 0.2 U/ml). However, 3 subgroups could be distinguished with regard to IL-2 synthesis: IL-2 production was significantly increased in 5 patients and decreased in 2 patients, while the remaining 16 diabetics produced normal levels of IL-2. The diabetic group displayed a curve of PBMC proliferation in response to a range of recombinant IL-2 which was not significantly altered. However, an abnormally high blastogenic response was detected in 5 patients, correlating to an increased percentage of Ia-bearing T lymphocytes, while a markedly low response was seen in 2 other patients. These alterations of the IL-2 system could be related duration of diabetes. Indeed, high synthesis of IL-2 was more frequent in patients with long-standing disease than in recent onset diabetics: 44% and 7%, respectively. Conversely, increased response to IL-2 was found more often in the latter group than in the former (28% vs 11%) while decreased sensitivity was seen only in the latter group (14%). No correlations were found between these results and basal or glucagon-stimulated C peptide levels, percent of glycosylated hemoglobin, presence of autoantibodies, lymphocyte subsets, or HLA typing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Protein biosynthetic activity of polymorphonuclear leukocytes in inflammatory arthropathies. Increased synthesis and release of fibronectin.

We have investigated protein synthesis and release by polymorphonuclear leukocytes (PMN) to compare the protein biosynthetic activity of peripheral blood PMN and inflammatory synovial fluid (SF) PMN from patients with inflammatory arthropathies. We analyzed and compared the protein profiles produced by these cells, using patient matched peripheral blood and SF PMN as well as peripheral blood PMN from normals. Twenty-five patients with either rheumatoid arthritis, psoriatic arthritis or gout were studied. Fluorographs of SDS-polyacrylamide slab gels, performed using cell supernatants from metabolically labelled cells, revealed an increased release of de novo synthesized proteins by inflammatory SF PMN compared to peripheral blood PMN. Under reducing conditions, 4 clearly distinguishable high molecular mass products were observed (Mr 230,000, 185,000, 170,000 and 95,000). Two of the protein bands were found to be gelatin binding (Mr 230,000 and Mr 95,000). By Western blot, the Mr 230,000 protein was found to be fibronectin and the Mr 95,000 protein was shown to be identical to a recently described gelatinase. Thus, the activation of PMN in inflammation is accompanied by an increased release of a number of de novo synthesized proteins, including fibronectin. Our studies directly pertain to the in vivo inflammatory process since the PMN were not activated artificially in vitro.

Arthritis↗

Influence of potassium depletion on potassium conductance in proximal tubules of frog kidney.

In order to test for the contribution of intracellular potassium activity to the link of sodium/potassium-ATPase activity and potassium conductance, studies with conventional and potassium selective microelectrodes were performed on proximal tubules of the isolated perfused frog kidney. The peritubular transference number for potassium (tk), i.e., the contribution of peritubular slope potassium conductance to the slope conductance of the cell membranes (luminal and peritubular), was estimated from the influence of peritubular potassium concentration on the potential difference across the peritubular cell membrane (PDpt). During control conditions, PDpt is -65 +/- 1 mV, intracellular potassium activity (Ki) 57 +/- 2 mmol/l and tk 0.41 +/- 0.05. The resistance in parallel of the luminal and peritubular cell membranes (Rm) is 44 +/- 4 k omega cm, the resistance of the cellular cable (Rc) 137 +/- 13 M omega/cm. When the cells are exposed 10 min to potassium free perfusates (series I), PDpt increases by -28 +/- 3 mV within 2 min and then decreases gradually to approach the control value within 10 min. Ki decreases by 22 +/- 3 mmol/l and Rc increases by 35 +/- 10%. After a transient decrease, Rm increases by 36 +/- 9%. Readdition of peritubular potassium leads to a transient increase of PDpt, a gradual decrease of Rm and Rc as well as a gradual increase of Ki. tk recovers only slowly to approach 65 +/- 8% of control value within 3 and 79 +/- 10% within 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Apparent chloride conductance of subconfluent Madin Darby canine kidney cells.

In incompletely confluent Madin Darby canine kidney (MDCK)-cells continuous measurements of the potential difference across the cell membrane (PD) were made with conventional microelectrodes during rapid changes of extracellular chloride concentration. During control conditions mimicking in vivo situation, PD averages -50.3 +/- 0.7 mV. Reduction of extracellular chloride concentration from 122 mmol/l to 64.5 mmol/l depolarizes the cell membrane by +1.8 +/- 0.2 mV while reduction to 16 mmol/l leads to a transient, variable depolarization followed by a hyperpolarization of the cell membrane by -11.8 +/- 1.4 mV. 1 mmol/l anthracene-9-COOH hyperpolarizes the cell membrane by -10.7 +/- 1.0 mV, and abolishes the effect of altered extracellular chloride concentration (-0.6 +/- 0.5 mV), 1 mumol/l diphenylamine-2-carboxylate hyperpolarizes the cell membrane by -11.7 +/- 1.4 mV. 10 mumol/l furosemide hyperpolarize the cell membrane by -11.4 +/- 1.4 mV. Step increases of extracellular potassium concentration from 5.4 to 20 mmol/l depolarize the cell membrane by +14.9 +/- 1.0 mV in the absence of inhibitors, by +24.2 +/- 1.3 mV in the presence of anthracene-9-COOH and by +28.8 +/- 0.7 mV in the presence of furosemide. 10 mumol/l isoproterenol depolarize the cell membrane by +2.4 +/- 0.3 mV and increase the depolarizing effect of reducing extracellular chloride concentration to 64.5 mmol/l (+2.9 +/- 0.4 mV). 1 mumol/l forskolin depolarizes the cell membrane by +5.8 +/- 1.0 mV. In conclusion, chloride conductance of subconfluent MDCK-cells may be small during control conditions, is apparently decreased by anthracene-9-COOH and reduction of extracellular chloride concentration but is enhanced by isoproterenol.

Animals↗

The effect of cyanide on apparent potassium conductance across the peritubular cell membrane of frog proximal tubules.

To test for the effect of cyanide on frog proximal renal tubules the potential difference across the peritubular cell membrane (PDpt) has been recorded continuously before and during peritubular application of 1 mmol/l cyanide using conventional microelectrodes. Before application of cyanide PDpt amounts to -61.5 +/- 2.2 mV in the absence of luminal substrate. Cyanide depolarizes the peritubular cell membrane by +18.8 +/- 2.3 mV/10 min in the presence and by +4.5 +/- 0.9 mV/10 min in the absence of luminal substrate. The rapid depolarization of the cell membranes to addition of glucose to luminal perfusate is not significantly influenced by exposure to cyanide, whereas the influence of altered peritubular potassium concentration (from 3 to 9 mmol/l) is significantly reduced from +15.2 +/- 1.7 mV to +8.7 +/- 1.8 mV. Following exposure to cyanide the lumped resistance of the luminal and peritubular cell membranes increases significantly by 36 +/- 7%/6 min, and the cellular core resistance significantly by 14 +/- 6%/6 min. As a result, cyanide markedly decreases the peritubular potassium conductance, depolarizes the cell membranes and reduces the driving force for sodium coupled transport processes. Thus cyanide fully mimics the effects of ouabain, although cyanide in contrast to ouabain is expected to deplete the cells from ATP. In conclusion ATP/ADP is not likely to play a major role in the regulation of sodium coupled transport processes and peritubular potassium conductance in amphibian proximal tubules.

Adenosine Triphosphate↗

Influence of barium on the effects of phenylalanine in proximal tubules.

The present study was designed to further test for the role of peritubular potassium conductance in the repolarization of peritubular cell membrane during sustained stimulation of sodium coupled transport by phenylalanine. To this end the potential difference across the peritubular cell membrane (PDpt) has been recorded continuously, while 10 mmol/l phenylalanine (Phe) were added to the luminal perfusate, both in the presence or absence of peritubular or luminal barium (1 mmol/l). In the absence of phenylalanine and barium, PDpt amounts to -65.5 +/- 2.2 mV. Phe leads to a rapid depolarization of the peritubular cell membrane by +36.2 +/- 2.2 mV within 30 s, followed by an almost complete repolarization by -28.9 +/- 2.6 mV within 7 min. In the presence of barium in peritubular perfusate, the depolarization following Phe is +24.3 +/- 2.6 mV and the repolarization almost abolished (-4.3 +/- 0.9 mV). In the presence of barium in luminal perfusate, Phe leads to a depolarization by +35.7 +/- 2.4 mV followed by a repolarization of -17.0 +/- 3.2 mV within 7 min. It is concluded that the repolarization during sustained stimulation of sodium coupled transport is in large part due to alterations of peritubular potassium conductance.

Animals↗

Effects of ouabain and temperature on cell membrane potentials in isolated perfused straight proximal tubules of the mouse kidney.

In isolated perfused segments of the mouse proximal tubule, the potential difference across the basolateral cell membrane (PDbl) was determined with conventional microelectrodes. Under control conditions with symmetrical solutions it amounted to -62 +/- 1 mV (n = 118). The potential difference across the epithelium (PDte) was -1.7 +/- 0.1 mV (n = 45). Transepithelial resistance amounted to 1.82 +/- 0.09 k omega cm (n = 28), corresponding to 11.4 +/- 0.6 omega cm2. Increasing bath potassium concentration from 5 to 20 mmol/l depolarized PDbl by +24 +/- 1 mV (n = 103), and PDte by +1.6 +/- 0.1 mV (n = 19). Thus, the basolateral cell membrane is preferably conductive to potassium. Rapid cooling of the bath perfusate from 38 degrees C to 10 degrees C led to a transient hyperpolarization of PDbl from -60 +/- 1 to -65 +/- 1 mV (n = 21) within 40 s followed by gradual depolarization by +18 +/- 1% (n = 14) within 5 min. The transepithelial resistance increased significantly from 1.78 +/- 0.11 k omega cm to 2.20 +/- 0.21 k omega cm (n = 15). Rapid rewarming of the bath to 38 degrees C caused a depolarization from -61 +/- 2 mV (n = 17) to -43 +/- 2 mV (n = 16) within 15 s followed by a repolarization to -59 +/- 2 mV (n = 10) within 40 s. Ouabain invariably depolarized PDbl. During both, sustained cooling or application of ouabain, the sensitivity of PDbl to bath potassium concentration decreased in parallel to PDbl pointing to a gradual decrease of potassium conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrical properties of Madin-Darby-canine-kidney cells. Effects of extracellular sodium and calcium.

In incompletely confluent Madin Darby canine kidney cells continuous measurements of the potential difference across the cell membrane (PD) were made with conventional microelectrodes during rapid changes of extracellular sodium and/or calcium concentration. During control conditions PD averages -50.6 +/- 0.7 mV. Reduction of extracellular sodium concentration from 131.8 to 17.8 mmol/l leads to a reversible hyperpolarization of the cell membrane to -65.3 +/- 1.1 mV. This hyperpolarization is not significantly reduced by omission of glucose or presence of amiloride (1 mmol/l) in the perfusates. Instead, 1 mmol/l amiloride depolarizes the cell membrane by +5.2 +/- 0.4 mV. 1 mmol/l barium depolarizes the cell membrane to -31.3 +/- 1.1 mV. Step increases of extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarize the cell membrane by +5.5 +/- 0.5 mV and +16.5 +/- 1.8 mV respectively. In the presence of barium, the depolarizing effect of increasing extracellular potassium concentration and of amiloride is almost abolished. Reduction of extracellular sodium concentration in the presence of barium, however, leads to a transient hyperpolarization of the cell membrane. During this transient hyperpolarization, increasing extracellular potassium concentration depolarizes the cell membrane despite the continued presence of barium. Omission of extracellular calcium (EDTA) depolarizes the cell membrane by +36.7 +/- 3.2 mV. In the absence of extracellular calcium, the hyperpolarizing effect of reduced extracellular sodium concentration is markedly reduced (-4.5 +/- 1.2 mV). 2 mumol/l A23187 in the presence of extracellular calcium hyperpolarizes the cell membrane to -72.5 +/- 0.6 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of epinephrine on electrical properties of Madin-Darby canine kidney cells.

The present study has been performed, to test for the influence of epinephrine on the potential difference across the cell membrane (PD) of Madin-Darby canine kidney (MDCK) cells. Under control conditions, mimicking the in vivo situation, PD averages - 53.3 +/- 0.9 mV (n = 37). Increasing extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarizes the cell membrane by +4.3 +/- 0.4 mV (n = 5) and +15.8 +/- 1.2 mV (n = 5), respectively. The application of 1 mumol/l epinephrine leads to sustained hyperpolarization of the cell membrane to -71.5 +/- 0.7 mV (n = 37). In the presence of epinephrine, increasing extracellular potassium concentration from 5.4 to 20 mmol/l depolarizes the cell membrane by +30.6 +/- 0.2 mV (n = 5); 1 mmol/l barium depolarizes the cell membrane by +14.8 +/- 0.7 mV (n = 20) and abolishes the effect of step increases of extracellular potassium concentration from 5.4 to 10 mmol/l. In the presence of barium, epinephrine leads to a transient hyperpolarization by -31.2 +/- 1.2 mV (n = 18). During this transient hyperpolarization, the cell membrane is sensitive to extracellular potassium concentration despite the continued presence of barium; 10 mumol/l verapamil depolarizes the cell membrane to -41.0 +/- 2.6 mV (n = 11). In the presence of verapamil, the hyperpolarizing effect of epinephrine is only transient; 10 mumol/l phentolamine depolarizes the cell membrane by +3.0 +/- 0.6 mV (n = 8). In the presence of phentolamine, the effect of epinephrine is virtually abolished (+0.4 +/- 0.6 mV, n = 8); 1 mumol/l isoproterenol depolarizes the cell membrane by +2.8 +/- 0.8 mV (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sex hormone binding globulin in women with anorexia nervosa.

In 29 women with anorexia nervosa, on a blood sample withdrawn at 0900 h before and during weight gain, the binding parameters of serum sex hormone binding globulin (SHBG) were measured by a solid phase method and the levels of testosterone, oestradiol and thyroid hormones were measured by radioimmunoassay. The binding capacity of SHBG was higher than the upper limit for normally menstruating women in 23 patients whilst its affinity for binding testosterone at 37 degrees C was normal (0.32-0.53 X 10(-9) mol/l). The mean levels of testosterone, oestradiol and free thyroxine were normal and the mean level of triiodothyronine was significantly (P less than 0.005) decreased. The binding capacity of SHBG did not correlate significantly with body mass index, percent weight lost, thyroid hormone or sex hormone levels. In 9 patients, an i.v. infusion providing 1200-1400 calories daily was given for 1 week. In these patients a significant decrease (P less than 0.005) in the binding capacity of SHBG (from 74.7 +/- 26.7 to 52.9 +/- 21.8 nmol/l) and a significant increase (P less than 0.001) in T3 levels (from 0.69 +/- 0.21 to 0.95 +/- 0.13 nmol/l) was observed. In 14 patients, when a weight gain of at least 5% was obtained, the binding capacity of SHBG fell into the normal range (25.6-62.9 nmol/l) while T3 levels rose to normal (0.85-2.30 nmol/l). These findings suggested that variations of calorie intake and/or body weight may influence the binding capacity of SHBG in the human.

Adolescent↗

Electrophysiology of sodium-coupled transport in proximal renal tubules.

Effects of sodium-coupled transport on intracellular electrolytes and electrical properties of proximal renal tubule cells are described in this review. Simultaneous with addition of substrate for sodium-coupled transport to luminal perfusates, both cell membranes depolarize. The luminal cell membrane depolarizes due to opening of sodium-cotransport pathways. The depolarization of the peritubular cell membrane during sodium-coupled transport is primarily due to a circular current reentering the lumen via the paracellular pathway. The depolarization leads to a transient decrease of basolateral potassium conductance that in turn amplifies the depolarization. However, within 5-10 min of continued exposure to substrate, potassium conductance increases again, and peritubular cell membrane repolarizes. During depolarization the driving force of peritubular bicarbonate exit is reduced. As a result net alkalinization of the cell prevails despite an increase of intracellular sodium activity, which reduces the driving force for the sodium-hydrogen ion exchanger and would thus have been expected to acidify the cell. No evidence is obtained for regulatory inhibition of sodium-coupled transport by intracellular sodium or calcium. Rather, luminal cotransport is altered by the change of driving forces.

Animals↗

Electrophysiological heterogeneity of proximal convoluted tubules in Amphiuma kidney.

The present study was designed to identify functional differences between dark (early to mid) and white (late) proximal tubule segments in Amphiuma kidney. The potential difference across the peritubular cell membrane (Vb), the luminal cell membrane (Va), and the epithelium (Vte) are not significantly different between dark and white segments. Cellular and luminal cable analysis reveals that the resistance of the cell membranes in parallel is lower in dark (28.6 +/- 3.2 k omega X cm) than in white segments (63.2 +/- 5.0 k omega X cm) in contrast to the transepithelial resistance, which is higher in dark (26.6 +/- 5.5 k omega X cm) than in white (3.5 +/- 0.7 k omega X cm) segments. A step-increase of peritubular potassium (from 2.5 +/- 12.5 mmol/liter) depolarizes Vb more in white (20.1 +/- 1.2 mV) than in dark (7.2 +/- 0.4 mV) segments, whereas addition of bicarbonate to peritubular perfusate hyperpolarizes Vb more in dark (-22.4 +/- 1.6 mV) than in white (-5.9 +/- 0.7 mV) segments. An increase of luminal potassium depolarizes Va more in dark (21.3 +/- 2.0 mV) than in white (9.3 +/- 1.9 mV) segments. Similarly luminal glucose depolarizes Va more in dark (10.7 +/- 1.2 mV) than in white segments (3.2 +/- 1.4 mV). Partial peritubular replacement of NaCl and reduction of peritubular chloride polarize Vte more in white (9.6 +/- 1.0 and 28.9 +/- 2.9 mV) than in dark segments (7.0 +/- 0.5 and 15.5 +/- 1.9 mV). In conclusion, compared with white segments, dark segments have lower cell membrane and higher shunt resistances, lower potassium and higher bicarbonate conductances of the peritubular cell membrane, and a higher capacity to reabsorb glucose. Paracellular shunt chloride conductance is relatively high in both segments.

Animals↗