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Biomedical subjects

E Braun

Publications and source records attributed to E Braun.

At least 19 recordsLinked to original sources

Effects of density and gating of delayed-rectifier potassium channels on resting membrane potential and its fluctuations.

The aim of this study is to evaluate directly, using a reduced experimental system, the nature of interactions between voltage-gated potassium channels and the resting membrane potential. Xenopus oocytes were injected with various concentrations of cRNA coding for a delayed-rectifier potassium channel Shaker-IR. The effects of the density and kinetics of the expressed channels on resting membrane potential is explored in isolated ("inside-out") patches. The channel density is given in terms of maximal conductance (Gmax), measured from the maximal slope of the I-V curve under voltage clamp conditions. The capacitance of the experimental setup is approximately 1 pF. At high channel densities (Gmax > 10 pA/mV) the mean membrane potential is stabilized at approximately -60 mV. This resting membrane potential is more than 35 mV positive to the reversal potential for potassium ions under the same experimental conditions. Analyses of voltage clamp experiments indicate that at high channel densities the mean membrane potential is determined by the rates of channel activation and deactivation, but is not affected by the rates involved in the process of slow (C-type) inactivation. In contrast, at lower channel densities membrane potential is very unstable, and its mean value and amplitude of fluctuations are strongly affected by the process of slow (C-type) inactivation.

Animals

Modulation of histamine release by sodium, potassium adenosine triphosphatase inhibition.

BACKGROUND: Previous studies have shown that a sodium, potassium adenosine triphosphatase inhibitor is present in the plasma of allergic subjects in whom enhanced histamine releasability has also been reported. PURPOSE: The purpose of this study was to determine the effect of in vitro sodium, potassium adenosine triphosphatase inhibition on whole blood histamine release. METHODS: Samples obtained from 12 patients with allergic rhinitis and 12 nonallergic subjects were incubated in duplicate for 30 minutes with anti-IgE antibody (100 micrograms/mL) or control buffer following a 0-, 10-, 20-, 30-, 60-, 120- and 180-minute preincubation with ouabain (3.0 mM) or diluent. Cell supernatants were assayed for histamine by radioimmunoassay and results were expressed as a percentage of total histamine release. RESULTS: Mean (+/- 1 SEM) anti-IgE induced release, in the presence and absence of ouabain, respectively, for allergic subjects was 27.5 +/- 5.5 and 21.0 +/- 4.5 (ten minutes, P < 0.05), 30.3 +/- 6.0 and 22.4 +/- 4.8 (20 minutes, P < .025), 28.9 +/- 5.2 and 23.5 +/- 4.1 (30 minutes), 33.8 +/- 7.1 and 26.7 +/- 5.4 (60 minutes, P < .05), 43.2 +/- 7.5 and 24.3 +/- 4.6 (120 minutes, P < .001), and 34.5 +/- 5.0 and 29.8 +/- 5.4% (180 minutes). Spontaneous histamine release in allergic subjects was also significantly increased by ouabain. Mean (+/- SEM) spontaneous release, in the presence and absence of ouabain, respectively, for allergic subjects was 2.0 +/- 0.5 and 0.9 +/- 0.2 (60 minutes, P < .025), 2.8 +/- 0.5 and 1.9 +/- 0.4 (120 minutes, P < .05), and 5.4 +/- 1.5 and 3.9 +/- 0.8% (180 minutes, P < .005). Ouabain did not significantly alter histamine release in non-allergic subjects. CONCLUSIONS: These data show that ouabain induced a significant increase in both spontaneous and induced histamine release in allergic subjects. In vivo, sodium, potassium adenosine triphosphatase inhibition may have an effect on histamine release in allergic subjects.

Adult

Rich dynamics in a simplified excitable system.

The study aims at exploring effects of microscopic channel fluctuations on macroscopic dynamics of excitable systems. Molecular biology techniques are used in order to construct a minimal excitable system that is built of cloned channels embedded in a small (approximately 1 micron 2) isolated patch of membrane. This simple synthetic "point" system exhibits dynamics in time scales that are several orders of magnitude longer then a single spike.

Animals

Colorectal cancer in the Ukraine: analysis and statistical data.

Colorectal cancer is the third most common cause of death due to malignancy in the Ukraine (21.7 per 100,000 in 1992). Only lung cancer (43.6) and stomach cancer (30.6) occur more frequently. Mortality is high; 47.9% and 38% of patients dying from colon and rectal cancer, respectively, within 1 year. The majority of patients present with advanced disease; 71.5% of patients with colon cancer and 60.1% of patients with rectal cancer have stage 3 or 4. Only 20.4% of patients with colon cancer and 29.4% with rectal cancer are suitable for radical surgery. The range of operative procedures performed reflects the stage of disease. Improvement in operability and survival figures in the Ukraine will result from improved facilities, increased public awareness of colorectal disease, introduction of screening programmes and closer links forged between the Ukraine and other European centres.

Colorectal Neoplasms

Centrally tinted contact lenses. A useful visual aid for patients with achromatopsia.

Achromatopsia (rod monochromacy) is a congenital color-vision defect of autosomal recessive inheritance due to severely abnormal or totally absent cone function. The disease is characterized by markedly reduced visual acuity, nystagmus, and, often, ametropia. Even under normal daylight conditions, these patients are extremely handicapped by glare because of a lack of rod inhibition by the abnormal or deficient cones. Light-absorbing glasses (absorption > 90%) can ameliorate this visual impairment to a certain extent but are sometimes not accepted by the patient since they are felt to disfigure the face. Especially during the first few years of school, this can lead to psychological problems. A special contact lens (Hydroflex, Wöhlk Company, Kiel) with a centrally tinted area (absorption 80%) that is slightly greater in diameter than the pupil under daylight conditions can correct ametropia and reduce light exposure and dazzle in a cosmetically much better way. Our first experience with this kind of visual aid in a 9-year-old girl suffering from incomplete achromatopsia is presented.

Child

Delivery of cytokines by liposomes. I. Preparation and characterization of interleukin-2 encapsulated in long-circulating sterically stabilized liposomes.

In an attempt to enhance the therapeutic efficacy of interleukin-2 (IL-2), recombinant human IL-2 was encapsulated either in large conventional liposomes or in small (mean diameter 65 nm), unilamellar, long-circulating, extravasating liposomes [referred to as sterically stabilized liposomes (SSLs)]. The SSL-IL-2 activity was assessed in vitro and in mice in comparison with soluble IL-2, IL-2 in conventional liposomes (non-SSL-IL-2), and pegilated IL-2 (PEG-IL-2). The main observations were as follows: (a) SSLs were far better carriers than conventional liposomes with regard to encapsulation efficiency and pharmacokinetics; (b) > 85% of IL-2 biological activity was consistently encapsulated in SSLs; (c) SSL-IL-2 was much more stable than soluble IL-2 at 4 and 37 degrees C; (d) SSL-IL-2, but not "empty" liposomes, bound in vitro to IL-2 receptor-bearing T-cells, indicating that the domain of the cytokine molecule involved in binding to the receptor is exposed on the outer liposome membrane; (e) release of IL-2 from the liposomes was not required for its in vitro biological activity; (f) plasma half-lives (t1/2 alpha, t1/2 beta) and area under the curve (AUC) of SSL-IL-2 were 10-30 times greater than those of soluble IL-2 and similar to those of PEG-IL-2; and (g) IL-2 is released from the SSLs in vivo with a t1/2 of approximately 40 min, although the SSL-IL-2s retained their steric stabilization in the plasma for > 4 h, with little liposome accumulation in the reticuloendothelial system. These data, together with the improved immunomodulatory and antitumor activity of SSL-IL-2 in mice, suggest that SSL-IL-2 might be a therapeutic agent superior to soluble IL-2.

Animals

Delivery of cytokines by liposomes. II. Interleukin-2 encapsulated in long-circulating sterically stabilized liposomes: immunomodulatory and anti-tumor activity in mice.

We have recently demonstrated that recombinant human interleukin-2 (IL-2) can be successfully encapsulated in small (mean size, 65 nm), unilamellar, long-circulating, sterically stabilized liposomes (SSL, also known as Stealth liposomes). The present study was undertaken to assess in mice the immunomodulatory and anti-tumor effects of SSL-IL-2 in comparison with soluble, unmodified IL-2 and pegilated IL-2 (PEG-IL-2). The main findings were as follows: (a) SSL-IL-2 was significantly more effective than IL-2 in increasing leukocyte number in the blood and spleen (p < 0.05) and triggering spleen lymphokine-activated killer cell activity (p < 0.01; t test). (b) In mice with advanced metastatic carcinoma previously treated with chemotherapy (cyclophosphamide), the survival was two to six times greater following administration of SSL-IL-2 as compared with IL-2 (p < 0.05; log-rank test). Moreover, successful treatment with SSL-IL-2 required lower cumulative doses (1.25 x 10(5) vs. 2.5 x 10(5) CU) and fewer (two versus five) administrations. (c) PEG-IL-2 was a more potent immunostimulator than SSL-IL-2 in normal mice and as effective therapeutically as SSL-IL-2 in tumor-bearing mice. The former agent, however, often caused marked toxicity (up to 40% mortality in some experiments), including severe thrombocytopenia. These findings suggest that SSL-IL-2 is an immunopotentiating agent superior to IL-2 in both normal mice and in tumor-bearing mice pretreated with chemotherapy.

Adjuvants, Immunologic

Stationary phase in the yeast Saccharomyces cerevisiae.

Growth and proliferation of microorganisms such as the yeast Saccharomyces cerevisiae are controlled in part by the availability of nutrients. When proliferating yeast cells exhaust available nutrients, they enter a stationary phase characterized by cell cycle arrest and specific physiological, biochemical, and morphological changes. These changes include thickening of the cell wall, accumulation of reserve carbohydrates, and acquisition of thermotolerance. Recent characterization of mutant cells that are conditionally defective only for the resumption of proliferation from stationary phase provides evidence that stationary phase is a unique developmental state. Strains with mutations affecting entry into and survival during stationary phase have also been isolated, and the mutations have been shown to affect at least seven different cellular processes: (i) signal transduction, (ii) protein synthesis, (iii) protein N-terminal acetylation, (iv) protein turnover, (v) protein secretion, (vi) membrane biosynthesis, and (vii) cell polarity. The exact nature of the relationship between these processes and survival during stationary phase remains to be elucidated. We propose that cell cycle arrest coordinated with the ability to remain viable in the absence of additional nutrients provides a good operational definition of starvation-induced stationary phase.

Cyclic AMP

Bcy1, the regulatory subunit of cAMP-dependent protein kinase in yeast, is differentially modified in response to the physiological status of the cell.

The regulatory subunit of cAMP-dependent protein kinase in yeast, encoded by the BCY1 gene, is known to be required under certain conditions such as growth on nonfermentable carbon sources and entry into stationary phase. We have identified novel isoforms of Bcy1 in cells under these conditions. The isoforms are distinguishable by their migration on one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2-dimensional nonequilibrium pH gradient gel electrophoresis. The isoforms observed by one-dimensional SDS-PAGE bind cAMP, as determined by [32P]8-azido-cAMP labeling (diagnostic of Bcy1 protein). Proteins isolated from cells grown to stationary phase in rich medium exhibit five antibody-reactive bands, by one-dimensional SDS-PAGE immunoblot analysis, with apparent molecular masses of 50, 52, 55, 59 and 61 kDa. Total Bcy1 protein increases at least 8-fold between exponential and stationary phase. Analysis of proteins from a variety of yeast mutants indicated that 1) many of the observed modifications of Bcy1 are dependent upon the presence of the Ser-145 phosphorylation site; 2) the appearance of the 59- and 61-kDa bands is dependent upon the presence of Yak1 kinase; and 3) Bcy1 protein is modified even in the absence of cAMP-dependent protein kinase catalytic subunits. Cells carrying the bcy1(ala145) allele exhibit non-wild type growth, indicating that these modifications may be functionally significant.

Blotting, Western

Improving CD4+ lymphocyte counts in HIV-infected hemophilia patients. A favorable prognostic indicator?

CD4+ lymphocyte counts of 91 HIV+ hemophilia patients were monitored for a mean of 4 years (range: 15-69 months). CD4+ lymphocytes decreased in 55 but increased in 36 patients over time. The CD4+ cell increases were persistent in 5 patients, whereas they fluctuated in 31. Of the 36 patients with increasing CD4+ counts 3 developed AIDS and 1 LAS. The other 32 patients were clinically asymptomatic (CDC II), but had immunological abnormalities, such as increased serum neopterin (N = 18) and impaired in vitro T cell responses to pooled allogenic stimulator cells (N = 15) or mitogens (N = 18). In contrast, of the 55 patients whose CD4+ cells decreased, 24 developed AIDS and 5 ARC (P less than 0.0005). Only 2 of these 55 patients had normal mitogen stimulation in vitro and normal serum neopterin levels.

Acquired Immunodeficiency Syndrome

Solitary blood cultures as a quality assurance indicator.

For patients with suspected bacteremia, at least two separate blood cultures are recommended to achieve maximum sensitivity and to properly interpret results. Since a single blood collection may signify an improper procedure with serious consequences if the diagnosis of blood stream infection is missed, we investigated this problem with studies at three teaching hospitals (A, B, and C) and by a survey of 38 other hospitals. The incidence of solitary blood cultures ranged from 1 to 99% (median 26%) at the surveyed institutions. Among the cases investigated at hospitals B and C, between 10 and 30% of solitary blood cultures were not clinically indicated, while most of the others were caused by the physician not knowing that one culture was insufficient or by failure to complete the diagnostic plan. Focused concurrent intervention at hospital B was associated with reductions in solitary blood cultures from 40.0 to 24.6% (p = 0.045) and a decline in those not indicated from 38.1 to 12.5% (p = 0.192). Global educational efforts at hospital A were associated with a decrease in solitary blood culture rates from 52 to 37% (p = 0.016). These results show that blood culture practice varies widely among institutions in spite of consensus recommendations for proper specimen collections. We estimate that, nationwide, up to 18,000 etiologic diagnoses of bacteremia are missed annually because of this problem. Monitoring institutional solitary blood cultures is recommended as a test utilization indicator and as the basis for improving blood culture practice.

Bacteremia

[Anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome) in a 29-year-old male with absolute tachyarrhythmia].

We report on a man without any symptoms until the age of 29 years when a ventricular tachyarrhythmia occurred for the first time. There were electrocardiographic signs of a previous myocardial infarction of the anterior wall, but there had not even been any episode of angina pectoris. The cause was the anomalous origin of the left coronary artery from the pulmonary trunk (Bland-White-Garland syndrome). Therapy consisted of ligation of the left coronary artery and the implantation of an aortocoronary vein graft to the left coronary artery in order to reinstall a two-coronary system. Diagnosis is easily made by coronary angiography. At a 3-year follow-up there was an increase of the ejection fraction/cardiac output, a stable sinus rhythm, and an improved physical endurance.

Adult

[Choledochal cyst. The clinical picture, diagnosis and therapy].

A 21-year-old woman who for more than one year had had epigastric pain which was unrelated to food and radiated belt-like, was found to have a marked increase in gamma-GT, slightly elevated phosphatase activity, and increased erythrocyte sedimentation rate. The diagnosis of choledochal cyst, type Ia, was confirmed by sonography, endoscopic retrograde pancreatography and intravenous cholangiography. A choledochocystojejunostomy with a Y-Roux anastomosis was constructed to stop the cholestasis and prevent complications. The patient became symptom-free after the operation.

Adult