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Biomedical subjects

A Schwab

Publications and source records attributed to A Schwab.

At least 55 records · Page 3Linked to original sources
PubMed1993

20-OH-ecdysone swells nuclear volume by alkalinization in salivary glands of Drosophila melanogaster.

Ecdysteroids play an important role in the larval moulting process of insects. Ecdysone-induced stimulation causes specific "puffs" in polytene chromosomes of salivary gland cells resulting in nuclear swelling. During this process, changes of intracellular ion composition are thought to act as an early regulatory mechanism of gene activation. By use of video-imaging analysis and electrophysiological techniques, we examined ecdysone-induced nuclear swelling in Drosophila salivary glands in situ and its dependence on pH and calcium. Isolated glands of the third larval stage were superfused with a solution mimicking the haemolymph. Addition of 5 x 10(-6) mol/1 20-OH-ecdysone led, after a lag period of 50 min, to a sustained Ca(2+)-dependent increase of nuclear volume by 23.0 +/- 2.3%. Amiloride, a blocker of plasma membrane Na+/H+ exchange, prevented 20-OH-ecdysone-induced nuclear swelling. Decreasing pH in the superfusate from 7.15 to 6.8 led to nuclear shrinkage by 16.9 +/- 3.9%. Measurements of pH in salivary gland cells with ion-sensitive microelectrodes disclosed an alkalinization of 0.23 +/- 0.05 pH units after stimulation with 20-OH-ecdysone. We postulate that 20-OH-ecdysone activates the amiloride-sensitive plasma membrane Na+/H+ exchanger. This leads to intracellular alkalinization and concomitant decondensation of the nuclear chromatin visible as nuclear swelling. Thus, cell alkalinization could be a potentially important stimulatory mechanism in mediating ecdysteroid-induced activation of the cell nucleus.

Alkalies↗
PubMed1993

Spontaneously oscillating K+ channel activity in transformed Madin-Darby canine kidney cells.

Intracellular alkalinization is known to be associated with tumorigenic transformation. Besides phenotypical alterations alkali-transformed Madin-Darby canine kidney (MDCK) cells exhibit a spontaneously oscillating cell membrane potential (PD). Using single-channel patch clamp techniques, it was the aim of this study to identify the ion channel underlying the rhythmic hyperpolarizations of the PD. In the cell-attached patch configuration, we found that channel activity was oscillating. The frequency of channel oscillations is 1.1 +/- 0.1 min-1. At the peak of oscillatory channel activity, single-channel current was -2.7 +/- 0.05 pA, and in the resting state it was -1.95 +/- 0.05 pA. Given the single-channel conductance of 53 +/- 3 pS for inward (and of 27 +/- 5 pS for outward) current the difference of single-channel current amplitude corresponded to a hyperpolarization of approximately 14 mV. The channel is selective for K+ over Na+. Channel kinetics are characterized by one open and by three closed time constants. The channel is Ca2+ sensitive. Half maximal activation in the inside-out patch mode is achieved at a Ca2+ concentration of 10 mumol/liter. In addition, we also found a 13-pS K+ channel that shows no oscillatory activity in the cell-attached patch configuration and that was not Ca2+ sensitive. We conclude that the Ca(2+)-sensitive 53-pS K+ channel is underlying spontaneous oscillations of the PD. It has virtually identical biophysical properties as a Ca(2+)-sensitive K+ channel in nontransformed parent MDCK cells. Hence, alkali-induced transformation of MDCK cells did not affect the channel protein itself but its regulators thereby causing spontaneous fluctuations of the PD.

Animals↗
PubMed1992

Oscillations: a key event in transformed renal epithelial cells.

Intracellular pH (pHi) plays a critical role in the entry of cells into the DNA-synthesis phase of the cell cycle. Alterations in pHi may contribute to abnormal proliferative responses such as those seen in tumorigenic cells. We observed that alkaline stress leads to genomic transformation of Madin-Darby canine kidney (MDCK) cells. Transformed cells (F cells) form "foci" in culture, lack contact inhibition, and are able to migrate, typical characteristics of dedifferentiated tumorigenic cells. F cells exhibit spontaneous biorhythmicity. Rhythmic transmembrane Ca2+ flux activates plasma membrane K+ channels and Na+/H+ exchange. This leads to periodic changes of membrane voltage and pHi at about one cycle per minute. We conclude that endogenous oscillatory activity could be a trigger mechanism for DNA synthesis, proliferation, and abnormal growth of renal epithelial cells in culture.

Alkalosis↗
PubMed1992

Spontaneous membrane potential oscillations in Madin-Darby canine kidney cells transformed by alkaline stress.

High pH is known to be associated with normal cell growth and neoplastic transformation. We observed that Madin-Darby canine kidney (MDCK) cells grown under sustained alkaline stress (pH 7.7) develop "foci" composed of spindle-shaped cells lacking contact inhibition and exhibiting only poor adhesion to the culture support. Foci-developing (F) cells were cloned and grown in control medium (pH 7.4), where they maintained their neoplastic features indicating a stable pH-induced genetic transformation. After F cells had been fused to giant cells with polyethylene glycol, the cell membrane potential (Vm) was measured by means of microelectrodes. In contrast to non-transformed MDCK cells, Vm of F cells showed spontaneous biorhythmicity caused by periodic opening of Ca2(+)-activated K+ channels. Spiking activity was blunted by the Ca2+ channel blocker nifedipine, by the K+ channel blocker Ba2+, by the Na+/H+ exchange blocker amiloride and its analogue ethylisopropylamiloride, and by an extracellular pH of 7.6 and 6.8. We conclude that MDCK cells transformed by sustained alkaline stress have lost their stable plasma membrane potential but, instead, exhibit endogenous Ca2(+)- and pH-sensitive oscillations.

Animals↗
PubMed1992

[The treatment of distal radius fractures using the external fixator].

This is a report on the stabilisation of fractures of the distal end of the radius type C2 and C3 and open fractures by external fixator. Between 1982 and 1989 38 patients with 43 fractures were treated. A follow-up was done 8 to 80 months after operation including 35 patients. 14 patients were polytraumatised. Especially in this group of patients, the advantages of this procedure can be seen. This advantages are a small stress for the patient, involving only a short time of assembling of the external fixator besides a high stability of the system. Our results show, as well as the results of the literature, that the external fixator has its place in a differentiated therapeutic concept of intraarticular fractures, open fractures and fractures with a defect of the distal radius.

Adult↗
PubMed1990

Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.

Compounds 1a-g consisting of enalaprilat covalently bonded to aryl sulfonamides, including several known thiazide diuretics, were synthesized and tested for ACE inhibitory and diuretic and overall antihypertensive effects. All compounds were potent ACE inhibitors in vitro, with IC50 = 6.5-85 nM. At 10 mg/kg iv or ip in the rat, 1a-g inhibited the AI pressor response by 76-100%; inhibition declined significantly upon oral dosing. Compounds 1a and 1f at 100 mg/kg ip in the sodium-depleted, spontaneously hypertensive rats reduced blood pressure 28-35% and 41-42%, respectively. Compounds 1a and 1f elicited natriuresis and kaliuresis without accompanying volume increases in the rat; 1c at 25 mg/kg iv induced delayed diuresis. Compound 1f has been chosen for further development.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Regulation of small-conductance K+ channel in apical membrane of rat cortical collecting tubule.

We used the patch-clamp technique to study the activity and regulation of single potassium channels in the apical membrane of isolated cortical collecting tubules (CCT) of rat kidney. With 140 mM K+ in the pipette the inward conductance of the channel in cell-attached patches at 37 degrees C was 35 pS (n = 106, NaCl-Ringer or 70 mM KCl and 70 mM NaCl in the bath), and the outward conductance was 15 pS (n = 15, 70 mM NaCl + 70 mM KCl in the bath). Mean open probability (Po) of the channel is voltage independent and 0.96 (n = 106). The channel displayed one open state with a mean lifetime of 18.6 ms and one closed state with a mean lifetime of 0.7 ms (n = 20). Selectivity ratio between K+ and Na+ is 20 (n = 5). High-potassium diet increased channel incidence from control 32% (53 patches with channel from 165 patches) to 64% (53 patches with channels from 83 patches). The channel could be blocked by 1 mM Ba2+ (n = 7, Ba2+ in the pipette); however, 5 mM tetraethylammonium (n = 9, TEA in the pipette) did not block the channel activity. The channel was very sensitive to intracellular pH (n = 6). Changing bath pH facing cytoplasmic side of inside-out patches from 7.4 to 6.9 reversibly reduced Po from 0.9 to 0.1. Addition of 1 mM ATP (n = 7) to bath almost completely inhibited channel activity in inside-out patches. This ATP-induced inhibition was fully reversible and was found to be dependent on the ratio of ATP to ADP, since adding 0.5 mM ADP to bath solution relieved the ATP-induced blockade. Results indicate that intracellular pH, concentration of ATP, and ratio of ATP to ADP are important regulators of potassium channel activity in the apical membrane of rat CCT, and the properties of the channel make it a strong candidate for K+ secretion in this nephron segment.

Adenosine Triphosphate↗
PubMed1990

[The concentration of ionized and total calcium in the blood of female dogs with uterine inertia].

Blood values of calcium, inorganic phosphate and magnesium were estimated in 26 bitches one day before parturition, on the day of parturition and daily for 6 days post partum. In 17 of these 26 animals the diagnosis was dystocia because of uterine inertia. A comparison of calcium levels between those bitches giving birth spontaneously and those requiring assistance gave no indication that blood calcium deficiency was the cause of uterine inertia.

Animals↗
PubMed1988

Trans- and paracellular K+ transport in diluting segment of frog kidney.

In frog diluting segment transepithelial K+ net flux (JKte) occurs via trans- and paracellular transport routes. Inhibition of transcellular K+ transport discloses JKte across the shunt-pathway. By means of K+-sensitive microelectrodes we have measured secretory JKte induced by an acute K+ load, in the diluting segment of the isolated and doubly-perfused frog kidney. Transcellular K+ transport was inhibited by blocking the luminal K+ permeability either directly by barium or indirectly by the diuretic drug amiloride (via intracellular acidification induced by inhibition of Na+/H+ exchange), by the Na+/K+ pump inhibitor ouabain or by inducing an acute acid load. All experimental maneouvers led to a reduction of secretory JKte to about 50% of the control JKte. The apparent permeability coefficient for K+ of this nephron portion after inhibition of transcellular secretory JKte was reduced to a similar extent. We conclude: In frog diluting segment the ratio of trans- over paracellular JKte is close to unity. This ratio represents a minimum estimate because inhibition of the transcellular K+ pathway by barium, amiloride or an acute acid load may have been incomplete. Acidosis and/or amiloride exert large antikaliuretic effects due to the inhibition of the luminal K+ permeability.

Amiloride↗
PubMed1988

Thrombocytosis elevates serum potassium.

Spurious elevation of the serum potassium can be seen if the platelet count exceeds 1,000 x 10(9)/L in patients with myeloproliferative disease. To see if serum potassium is increased at more modest elevations of the platelet count we studied these parameters in 283 controls and 161 patients with reactive thrombocytosis. The incidence of hyperkalemia was 34% in patients with over 500 x 10(9) platelets/L compared with 9% if the platelet count was below 250 x 10(9)/L. Over this range there was a significant correlation of potassium increasing with the platelet count. The higher potassium values could not be explained on the basis of leukocytosis, renal insufficiency, or acidosis, suggesting that the elevated serum levels were often spurious. In support of this conclusion, the serum potassium exceeded plasma potassium by a larger amount in patients with thrombocytosis. We conclude that serum potassium rises in direct proportion to the platelet count in normal patients and in those with thrombocytosis, and that this increment is an artifact.

Humans↗
PubMed1988

[Proctomucosectomy and colo-anal anastomosis in rectovaginal fistula following the use of suppositories containing ergotamine].

We observed a rectovaginal fistula in 2 patients who had applied ergotamine suppositories against migraine headaches. The local effect of ergotamine on the rectum mucosa as well as the higher systemic concentration after rectal application seem to promote the development of a rectovaginal fistula. Different methods for the surgical fistula repair are discussed, depending on location and diameter of the fistula. In our patients we have carried out the abdomino-transanal resection of the rectum with sutured colo-anal anastomosis.

Adult↗
PubMed1986

Angiotensin-converting enzyme inhibitors: new orally active 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.

The preparation of a series of 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) in vitro and in vivo were examined. These compounds are assumed to act as prodrugs since they undergo rapid ring-opening reactions to give the corresponding biologically active free SH compounds when incubated with rat plasma or when treated with aqueous 0.1 N HCl or phosphate buffer (pH 7.4). The thiazepines 23-25 and 30 are potent inhibitors of ACE when administered po to rats and are comparable in potency to captopril (1). The most active thiazines in rats, po, were 42 and 45. Of the benzothiazepines studied, 22a was the most active in inhibiting ACE in the conscious normotensive rat, ID50 = 0.15 mg/kg, po. The acute antihypertensive effects of oral administration of a number of these compounds on mean arterial pressure and heart rate were studied in spontaneously hypertensive rats (SHR) maintained on a sodium-deficient diet.

Administration, Oral↗
PubMed1986

Amiloride reduces potassium conductance in frog kidney via inhibition of Na+-H+ exchange.

The existence of a carrier-mediated Na+-H+ exchange has been described recently in many epithelial and nonepithelial tissues including the diluting segment of the amphibian kidney. In this preparation the Na+-H+ exchanger is dramatically stimulated by so-called K+ adaptation (chronic exposure of animals to high potassium) and completely inhibited by the diuretic drug amiloride. We performed electrophysiological experiments in diluting segments of the isolated perfused frog kidney to investigate whether amiloride affects the conductance properties of this epithelium. Amiloride dramatically increased the transepithelial resistance and the ratio of lumen over peritubular cell membrane resistance. Cell membrane potential changes, induced by luminal K+ concentration steps, were blunted by luminal application of amiloride, by luminal Na+-free perfusates, or by acidification of the kidney perfusion solution. K+ secretory net flux, measured by K+-sensitive microelectrodes, decreased by half in presence of the diuretic. The experiments reveal that amiloride reduces the K+ conductance of the luminal cell membrane of frog diluting segment via inhibition of the luminal Na+-H+ exchanger. This decreases transepithelial K+ net secretion in this nephron segment.

Amiloride↗