Regulation of ionic channels by G proteins.
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Animals↗
Biomedical subjects
B Schubert
Publications and source records attributed to B Schubert.
[Evaluating thyroid gland function in patients with protein anomalies].
The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.
Blood Protein Disorders↗
[Iodine supplementation in the province of Styria].
As far back as 1898 the Austrian Nobel price winner Wagner von Jauregg was the first to recommend iodination of salt as prophylaxis against endemic goitre (prevalence 48%) and cretinism (greater than 10%). In 1923 he achieved in a voluntary iodine supplementation of 5 mg KJ/kg table salt, which only lasted for a number of years. It was in 1963 when finally a mandatory iodized salt prophylaxis was introduced at the rate of 10 mg KJ/kg. In this study the effect of 25 years of iodine supplementation is investigated: Endemic cretinism, hypothyroidism, and goitre in newborns disappeared generally and endemic goitre in pupils was significantly reduced. However, due to epidemiological studies at elementary and secondary schools and army recruitment examinations we still found out endemic goitre grade I (according to WHO) mainly in female juveniles. Examinations were done by palpation, ultrasonography and urinary iodine excretion. In the above as well as in the urine of newborns and in mother's milk the iodine content was significantly lower than in iodine rich countries. Consequently a higher iodination of salt at the rate of 20 mg KJ/kg was recommended by the Austrian Society of Nuclear Medicine in 1985. This suggestion was taken up by the Austrian authorities and it will finally be instituted by law in May 1990 for the benefit of coming generations.
Adolescent↗
Inhibition of cardiac Na+ currents by isoproterenol.
The mechanism by which the beta-adrenergic agonist isoproterenol (ISO) modulates voltage-dependent cardiac Na+ currents (INa) was studied in single ventricular myocytes of neonatal rat using the gigaseal patch-clamp technique. ISO inhibited INa reversibly, making the effect readily distinguishable from the monotonic decrease of INa caused by the shift in gating that customarily occurs during whole cell patch-clamp experiments (E. Fenwick, A. Marty, and E. Neher, J. Physiol. Lond. 331: 599-635, 1982; and J. M. Fernandez, A. P. Fox, and S. Krasne, J. Physiol. Lond. 356: 565-585, 1984). The inhibition was biphasic, having fast and slow components, and was voltage-dependent, being more pronounced at depolarized potentials. In whole cell experiments the membrane-permeable adenosine 3',5'-cyclic monophosphate (cAMP) congener 8-bromo-cAMP reduced INa. In cell-free inside-out patches with ISO present in the pipette, guanosine 5'-triphosphate (GTP) applied to the inner side of the membrane patch inhibited single Na+ channel activity. This inhibition could be partly reversed by hyperpolarizing prepulses. The nonhydrolyzable GTP analogue guanosine-5'-O-(3-thiotriphosphate) greatly reduced the probability of single Na+ channel currents in a Mg2(+)-dependent manner. We propose that ISO inhibits cardiac Na+ channels via the guanine nucleotide binding, signal-transducing G protein that acts through both direct (membrane delimited) and indirect (cytoplasmic) pathways.
8-Bromo Cyclic Adenosine Monophosphate↗
Acute renal failure in man: new aspects concerning pathogenesis. A morphometric study.
The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.
ADP-Ribosylation Factor 6↗
[Malignant angioendotheliomatosis or intravascular lymphoma/angiotropic lymphoma].
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Adult↗
Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways.
The signaling pathways by which beta-adrenergic agonists modulate voltage-dependent cardiac sodium currents are unknown, although it is likely that adenosine 3'5'-monophosphate (cAMP) is involved. Single-channel and whole-cell sodium currents were measured in cardiac myocytes and the signal transducing G protein Gs was found to couple beta-adrenergic receptors to sodium channels by both cytoplasmic (indirect) and membrane-delimited (direct) pathways. Hence, Gs can act on at least three effectors in the heart: sodium channels, calcium channels, and adenylyl cyclase. The effect on sodium currents was inhibitory and was enhanced by membrane depolarization. During myocardial ischemia the sodium currents of depolarized cells may be further inhibited by the accompanying increase in catecholamine levels.
8-Bromo Cyclic Adenosine Monophosphate↗
Fusarium moniliforme Sheld. A fungus producing a broad spectrum of bioactive metabolites.
Fusarium moniliforme Sheldon (perfect stage Gibberella fujikuroi (SAW. Wollenweber), an ubiquitous fungus belonging to the section Liseola (Booth), is one of the widespread, phytopathogenic fungi. This field fungus common on many crops, including rice, oats, wheat, maize, barley and soybeans was well known because of the ability to produce gibberellins in high quantities. Today beside of the very important gibberellic acid (GA3) other gibberellins such as GA4 and GA7 are of significance for agriculture and horticulture. Moreover, this fungus produces further biologically active metabolites, e.g. pigments, mycotoxins, phytotoxins, oestrogens and extracellular enzymes. Fusarium moniliforme strains are able to produce 2 pigment groups - the karotenoids and the bikaverins, the last of which has antibiotical activity against Leishmania brasiliensis. The biosynthesis of some mycotoxic substances, such as moniliformin, fusaric acid, fusarin C and fusariocin C, is described. From enzymes the milk-clotting rennin, cellulolytic and amylolytic enzymes, pectinases and phenol-degrading enzymes are of economical interest. Therefore, Fusarium moniliforme is a source of different bioactive metabolites. The production is dependent on the conditions and strain specifity.
Chemical Phenomena↗
[Myocardial damage following lightning injury].
In a 27-year-old woman, struck by lightning behind the left ear, the ECG showed signs of an acute posterior-lateral myocardial infarction after 1 h of unconsciousness and loss of memory. Her serum enzymes were increased as is typical of myocardial infarction, but the patient did not complain of cardiac symptoms. Besides clear signs of lightning injury, the patient showed a hemorrhage throughout the left breast and transient pericardial effusion was observed by echocardiography. In the course of two months, the ECG revealed a regression to unspecific ST-T-deviations and serum enzymes became normal. TI-201-myocardial-scintigraphy (SPECT), done six days and two months after lightning injury, excluded reversible and irreversible perfusion defects.
Adult↗
[Acute renal failure--clinical aspects and morphology].
This study reports the pathological-anatomical diagnoses in 180 cases in which a diagnosis of acute renal failure (ARF) had been made on clinical grounds. The clinical and pathological diagnoses were in agreement in 43.3% of the cases. In 56.7%, the pathological-anatomical diagnosis differed from the clinical diagnosis. Glomerulonephritis (GN) was particularly often concealed behind ARF, in particular rapidly progressive GN, but also acute interstitial nephritis or hemolyticuremic syndrome. In addition, the clinical diagnoses in cases with a pathological-anatomical diagnosis of ARF are presented. Finally, the clinical diagnoses made in cases with a pathological-anatomical diagnosis of GN with ARF are reported. It is thus shown that the pathologist is in a position to distinguish GN with true compensated retention from GN with transient ARF simulating compensated retention.
Acute Kidney Injury↗
Transmission and scanning electron microscopy investigations on the structure of the ultrafilter of glomeruli in human acute renal failure.
In 4 cases of human acute renal failure (ARF) with oligo-anuria, normuria and polyuria the following findings were made. (1) The diameter of endothelial cell fenestrae is on average larger than that of the control values, but not significantly. (2) In ARF the ratio of the endothelial cell fenestral area to the total endothelial area is not significantly lower than in control kidneys. (3) In ARF the average density of fenestrae per unit of area is not significantly lower than in control kidneys. (4) The structure of the podocytes does not differ from that of control kidneys.
Acute Kidney Injury↗
Cell-attached patch clamp measurement of macroscopic rapid inward sodium current in cultured heart cell reaggregates.
A megaohm seal, cell-attached patch clamp technique utilizing plastic suction pipettes for measuring macroscopic rapid inward sodium current (INa) was applied to cell membrane patches 30 to 100 micron2 in area at the periphery of reaggregates of myocardial cells from newborn rats cultured for 3 to 7 days. The reaggregates were composed of about 20 to several thousand of electrically well-coupled cells, the latter forming spheroidal reaggregates with a diameter of maximally 300 microns. This system was shown to guarantee satisfactory voltage-clamp control during ionic current measurements. The time and voltage dependence of the INa recorded during periods of up to 90 min was similar to that observed in single cardiac cell preparations from adult rats. INa inactivation was described by two time constants (tau h1, and tau h2). For maximal INa tau h1 and tau h2 had values of 1.5 +/- 0.25 ms and 8.7 +/- 3.9 ms (n = 4), respectively. The time course for recovery of INa from inactivation at the reaggregate resting potential exhibited also two time constants (tau re1 = 9.8 +/- 3 ms, tau re2 = 193 +/- 50 ms, n = 5). Estimated current density was about 10 pA/micron2. The concentration of tetrodotoxin needed to reduce maximal INa by 75% was 85 times lower in the reaggregates than it was in freshly isolated heart muscle cells from adult rats. The present system offers a combination of features that should make it well-suited for the study of both short- and long-term effects on the sodium channels in neonatal heart cells: Easy handling of the object, great electric stability, high time and amplitude resolution during ionic current measurements, and viability for at least one week.
Animals↗
Increased visualization of antral gastrin-producing G-cells after acute stimulation of gastrin release in the rat.
The effect of acute stimulation of gastrin release on the number of antral gastrin-producing G-cells stained by conventional immunohistology was investigated in two experimental models. The substituted benzimidazole derivate BY 308 was administered at a dosage that induces complete achlorhydria and thereby led to marked hypergastrinaemia. Two hours after drug administration, antral G-cell density was increased by 14% and 35% in 12-h and 48-h fasted rats, respectively. Both serum gastrin levels and G-cell density further increased after 3 and 8 days' treatment with BY 308 whereas the somatostatin (D)-cell count did not change prior to 8 days' administration. In the isolated, vascularly perfused rat stomach, acetylcholine was perfused for 36 min; this regimen increased gastrin release four-fold and enhanced the G-cell count by 24% whereas 8 min acetylcholine perfusion did not alter G-cell density significantly but stimulated gastrin output. The results of this study suggest that acute changes in the secretory activity of the gastrin cell are accompanied by an alteration of the staining characteristics thus indicating that an increase in the antral G-cell count does not solely depend upon formation of new cells.
Acetylcholine↗
Inhibition of calcium channels in neuroblastoma x glioma hybrid cells by verapamil, D600, diltiazem and nisoldipine.
The action of verapamil, /+/-D600 and nisoldipine on the inward calcium current (ICa) was studied in mouse neuroblastoma x rat glioma hybrid cells of the line 108CC5 under voltage clamp conditions by means of a suction pipette method.
Animals↗
[Photochemotherapy of eyelid lesions].
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Aged↗
A patch clamp study of the action of ethacyzine on the rapid inward sodium current in single rat heart muscle cells.
The effect of ethacyzine (a diethylamine analogue of ethmozine) on the rapid inward sodium current (INa) was studied in single rat ventricular muscle cells by a patch clamp technique. Extracellular application of 3 microM ethacyzine depressed the INa in a use-dependent fashion. Rest recovery from the use-dependent block by ethacyzine followed an exponential time course with a time constant of about 215 +/- 40 s (n = 4, mean +/- S.E.).
Animals↗
[Frequency-dependent blockade of sodium channels in isolated rat myocardial cells by the anti-arrhythmia agent ethmozine].
A patch-clamp method was used to study the effects of the phenotiazine antiarrhythmic drug ethmozine (E) on the fast sodium inward current (INa) in freshly isolated heart muscle cells of adult rats. At a concentration of 10(-5) M E caused INa inhibition that could be enhanced by increasing the frequency of depolarization. This inhibition was reversible. After the termination of repetitive depolarization the amplitude of INa recovered with a time constant of about 10 sec. These findings may help to explain the therapeutic efficiency of E in high frequency cardiac rhythm disturbances.
Animals↗
[The role of disturbed DNA synthesis in the genesis of cervical carcinomas. Results of histoautoradiographic studies].
Histoautoradiographic and histopathologic studies are presented for normal and atypical cervical squamous epithelium from biopsies in 129 women. Labelling indices were obtained using in vitro labelling of biopsy specimens with H3-thymidine. In 38 cases with normal squamous epithelium, different indices were observed depending on the indication for operation. The index for normal epithelium with nearby preneoplastic changes was 5.3 +/- 1.8; for normal epithelium of patients with other diseases (uterus myomatosus, descensus uteri) it was 2.8 +/- 1.3. The index for virus-induced koilocytic dysplasias (6.3 +/- 2.9) lay between those of mild (5.3 +/- 1.4) and moderate dysplasias (7.2 +/- 1.8) without histopathological signs of virus infection. Carcinoma-in-situ (11.7 +/- 4.0) and microcarcinomas (12.6 +/- 4.2) showed higher values. There were no significant differences between the labelling indices of the microcarcinomas and preneoplastic lesions. Early stages of tumor development may histoautoradiographically offer hints of proliferative activity. In later stages the proliferative heterogeneity of the tumors limits the interpretability of the indices. The results are discussed in light of the possible role played by papilloma virus in the genesis of cervical cancer.
Autoradiography↗