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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 289 records · Page 16Linked to original sources

Regulation of Na+ channels in frog lung epithelium: a target tissue for aldosterone action.

Sodium transport across isolated lung tissue of the frog Xenopus laevis was measured in Ussing chambers under voltage-clamp conditions. Perfusing the lungs with NaCl-Ringer's solutions on both sides, a basal distinct amiloride-blockable Na+ current was present. Incubating the lungs with 1 mumol/l aldosterone from the pleural side raised the short circuit current after a 1-h latent period. Maximal values were reached after 4-5 h of aldosterone treatment, at which time the transepithelial Na+ current was more than doubled compared to the control. The stimulatory effect was totally inhibited when the aldosterone treatment was preceded by incubation of the lung tissues with spironolactone in 2000-fold excess. In the presence of amiloride (0.5-8 mumol/l) in the alveolar compartment, a Lorentzian noise component appeared in the power spectrum of the fluctuations in the short circuit current. This enabled the calculation of single Na+ channel current and Na+ channel density under both experimental conditions. Aldosterone stimulation did not change single Na+ channel current. On the other hand, the number of conducting Na+ channels increased in parallel with the transepithelial Na+ transport. This suggests that the alveolar epithelium may be a physiological target tissue for aldosterone. Since fluid absorption in the lung is secondary to active Na+ transport, aldosterone may be a potent regulator for maintaining the relatively fluid-free state of the lumen of the lung in some cases of fluid accumulation.

Aldosterone↗

Radiotherapy with and without cisplatin in bladder cancer.

From October 1985 to December 1988, 67 patients with invasive bladder carcinoma T1-4 N0-2 M0 were treated with irradiation (50.4 Gy in 28 fractions in 6 weeks) and simultaneous cisplatin (25 mg/m2 per day on 5 consecutive days in the first and fifth irradiation week). After transurethral resection and irradiation plus cisplatin, complete remissions were achieved in 8/11 T1-, 14/16 T2-, 27/36 T3- and 1/4 T4-tumors. The complete remission rate 6 weeks after treatment according to the extent of preceeding transurethral surgery (TUR) was: R0: 67% (8/12); R1: 83% (20/24); R2: 70% (21/30); Rx: 1/1. In patients with incomplete TUR (R1-2), the complete remission rate was 76% (41/54). This was superior to the results of a historical control (76% vs. 45%, p less than 0.01). The estimated 3-year survival according to T-stage was: T1: 73%, T2-3: 68%, T4: 25%. The overall 3-year survival was unchanged as compared to our historical control (66% each). Severe complications have not been observed. We conclude that cisplatin will likely increase the local control rate after incomplete transurethral surgery. An improvement of survival seems unlikely.

Aged↗

[Idiopathic hypereosinophilia syndrome].

The author describes a case of rare idiopathic hypereosinophilia demonstrated by a 26 years old man. General symptoms were founded 4 years before and now disease takes a progressive course including a rapid decrease of visual functions. Several alterations of organic findings were also found in heart, liver, lung, spleen and brain. A marked musculatur dystrophia in regions of upper arms and calf muscles was demonstrated by the young man. Using ophthalmoscope infarctions, edema and hemorrhage in the retina were found, also new growth of vessels, hemorrhage into the vitreous body and detachment of retina.

Eosinophilia↗

Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation.

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.

Antigens, Differentiation↗

Aldosterone regulation of basolateral potassium channels in alveolar epithelium.

To reveal the regulatory mechanism of the mineralocorticoid aldosterone on basolateral K+ channels, the aldosterone-sensitive lung epithelium of Xenopus laevis was investigated in Ussing chambers under voltage-clamp conditions. Transepithelial measurements were supplemented by current fluctuation analysis of short-circuit current noise in nonstimulated and aldosterone-stimulated lung tissues. The addition of 10(-6) M aldosterone stimulated short-circuit current from 11.3 +/- 2.0 to 27.8 +/- 4.8 microA/cm2 (n = 11) within 4-5 h. In the presence of an alveolar-to-pleural K+ gradient, transepithelial K+ currents were induced by permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B. When the local anesthetic lidocaine (25-1,000 microM) was added to the pleural solution, macroscopic K+ current was dose dependently depressed. Lidocaine induced a Lorentzian component in the power density spectra, and the corner frequency increased linearly with blocker concentration. Aldosterone treatment did not affect mean single K+ channel current, which was 1.5 +/- 0.12 pA corresponding to a 15-pS channel conductance, whereas the number of basolateral K+ channels doubled. We conclude that the basolateral K+ channels in alveolar epithelia are a target site of aldosterone action.

Aldosterone↗

Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting.

Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA fingerprint pattern. However, differences in the DNA fingerprint patterns were shown to occur depending upon the above mentioned parameters.

Animals↗

Regulation of phospholipid biosynthesis during cholesterol influx and high density lipoprotein-mediated cholesterol efflux in macrophages.

We have studied the rate of phospholipid synthesis and turnover in mouse peritoneal macrophages in reaction to cholesterol influx and high density lipoprotein (HDL)-mediated cholesterol efflux, using three different radioactive precursors, 32PO4(3-), [3H]choline, and [14C]oleic acid. The cells were loaded with cholesterol for up to 18 h with acetyl-low density lipoprotein (LDL), and phospholipid synthesis was measured at various time intervals and compared with nonloaded macrophages. In the first 2 h of cholesterol loading, a twofold increase in the rate of synthesis for sphingomyelin, phosphatidylcholine, phosphatidylserine-inositol, and phosphatidylethanolamine was observed. After this initial up-regulation, the rate of phospholipid synthesis continuously declined upon further cholesterol loading, while the turnover rate of cellular phospholipids was not affected under the same conditions. The lysosomal inhibitor chloroquine abolished the down-regulation, revealing a strong correlation between phospholipid synthesis and lysosomal enzyme activity which was presumably dependent on the release of cholesterol from the lysosome. The reduction in phospholipid synthesis induced by cholesterol loading is reversible by the addition of HDL3 to the cells. When HDL3 was added to the culture medium, a two- to threefold increase in phosphatidylcholine synthesis and a twofold increase in sphingomyelin formation was observed after 3 h. Ca2+ antagonists of the dihydropyridine type, which down-regulate HDL-receptor activity and promote the formation and cellular release of lamellar bodies derived from the lysosomal compartment (Schmitz, G., et al. 1988. Arteriosclerosis. 8: 46-56, and Robenek, H., and G. Schmitz. 1988. Arteriosclerosis. 8: 57-67), specifically enhance the synthesis of sphingomyelin in cholesterol-loaded macrophages. Inhibitors of acyl-CoA:cholesterol acyltransferase (Octimibate, progesterone) increase both the synthesis of sphingomyelin and phosphatidylcholine, and enhance HDL-receptor activity. The results indicate that cholesterol and phospholipid metabolism are coordinately regulated in macrophages. Moreover, the formation of phosphatidylcholine and sphingomyelin seems to be an important factor for the promotion of HDL-receptor-mediated cellular cholesterol efflux.

Animals↗

[Possibilities and limitations of rapid radiologic detection of selected chemicals in acute poisoning of unknown origin].

Knowledge of the radiopacity of bromine-containing hypnotics and of halogenated hydrocarbons has led to numerous recommendations and speculations. Supported by own investigations the sensible application of a rapid radiological determination in the practice of clinical toxicology is discussed. This should always be carried out, if solvent residues, gastric contents or gastric lavage fluid are available, a ingestion is suspected, and the result of chemical analysis is not promptly obtainable. However, a hint at the group of halogenated hydrocarbons is only possible, if additional information about miscibility with water is accessible. Revealing the presence of radiopaque material in tablet or liquid form by radiologic studies of the abdomen may be very helpful for the rapid evaluation of symptomatology and first therapeutic consequences, but it does not allow any chemical identification of the poison.

Gastric Lavage↗

[Repeating antidepressive sleep deprivation therapy (partial sleep deprivation)].

UNLABELLED: Repeated partial sleep deprivation (in the second half of the night) is investigated in respect of therapeutic effectivity as part of antidepressive treatment. 31 inpatients suffering from endogenous depression were subjected to walking therapy three times at intervals of one week. RESULTS: The antidepressive efficacy of sleep deprivation is individually (both interindividually and intraindividually) very different. Regular response is rare, but so is repeated non-response. Even if one or several waking therapies remain ineffective, further attempts can eventually result in marked antidepressive effects. Hence a repetition of this antidepressive measure is indicated, the more so since it is easy to carry out and does not produce side effects.

Adult↗

[Ocular side effects of added sympathomimetics in local anesthetics].

In facial dermatosurgery, the addition of sympathomimetics to local anesthetics produces a desirable topical effect as they provide an almost bloodless operation field due to temporary vasoconstriction. In an 87-year-old woman, who had lost her left sight owing to a meningoma, we removed a basal-cell carcinoma from the right side of her nose. The local anesthetic applied contained noradrenaline at a concentration of 1:50,000. After the operation, the patient complained of a headache and a transitory loss of sight. We suppose that noradrenaline reached the arteria centralis retinae via arterial periorbital anastomoses, thus causing a vasoconstriction of this artery. As far as dermatosurgery of the middle and upper face is concerned, patients with severe vision disorders should be considered as a risk group; in local anesthesia of those patients an addition of sympathomimetics should be avoided.

Aged↗

An unusual polyanion from Physarum polycephalum that inhibits homologous DNA polymerase alpha in vitro.

From extracts of microplasmodia of Physarum polycephalum and their culture medium, an unusual substance was isolated which inhibited homologous DNA polymerase alpha of this slime mold but not beta-like DNA polymerase and not heterologous DNA polymerases. Analysis, especially NMR spectroscopy, revealed the major component to be an anionic polyester of L-malic acid and the inhibition to be due to poly(L-malate) in binding reversibly to DNA polymerase alpha. The mode of inhibition is competitive with substrate DNA and follows an inhibition constant Ki = 10 ng/mL. Inhibition is reversed in the presence of spermine, spermidine, poly(ethylene imine), and calf thymus histone H1. According to its ester nature, the inhibitor is slightly labile at neutral and instable at acid and alkaline conditions. Its largest size corresponds to a molecular mass of 40-50 kDa, but the bulk of the material after purification has lower molecular masses. The inhibitory activity depends on the polymer size and has a minimal size requirement.

Binding Sites↗