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Biomedical subjects

G Ruhenstroth-Bauer

Publications and source records attributed to G Ruhenstroth-Bauer.

At least 19 recordsLinked to original sources

In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver.

We are elaborating on the kinetics and mechanisms of septic rabbit liver to de novo biosynthesize acute-phase response (APR) proteins under in vitro conditions of deepening ischemia in reference to their in vivo prevalence in serum and cerebrospinal fluids (CSF) collected at predetermined times. The significance of the data is interpreted as relevant to grafting cadaveric liver into end-stage liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic APR was induced by CCl(4)-intubation, and the administration of cholera toxin (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency, in terms of biosynthesis of APR proteins in closed circuit perfusion of the isolated intoxicated liver with oxygenated saline or L-15 media paralleled the two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma proteins by isolated perfused liver is the result of in vivo decoded and retained APR inflammatory signals; and (b) decoded inflammatory signals are expressed not withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic perfusion in saline or L-15 medium precipitated mitochondrial aberrations which resulted in further deterioration of de novo biosynthesis of APR plasma proteins. Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations rendered the perfused organ a biologically inert tissue mass that was incapable of resuming biological function upon perfusion with oxygenated L-15 medium. This is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in vitro aberrations of mitochondrial function(s) critically limit the capability of the isolated liver to resume its organic function to sustain biosynthesis of de novo plasma proteins. Extrapolation of these results to the surgical management of end-stage liver diseases points to the importance of the status and the handling protocol(s) of the cadaver donor liver prior to successful grafting. We conclude that although histology of a cadaver liver may reveal well-preserved hepatic cellular organelles with at least minimal intra- and intercellular communication required for viable hepatic function, we deem it essential to further define acceptable minimal capabilities to de novo biosynthesize plasma proteins by a cadaver liver as a measure of its functional viability and suitability for transplantation. Ultimately, this measure may improve the success of liver transplants with minimal surgical and drug interventions.

Acute-Phase Proteins↗

Cardiac heart disease in the era of sucrose polyester, Helicobacter pylori and Chlamydia pneumoniae.

Recent evidence associates inflammatory mediators with coronary heart disease. Elevation of acute-phase reaction (APR) proteins such as serum amyloid A, fibrinogen, CRP and haptoglobin in response to Helicobacter pylori (H. pylori) infection was shown to initiate gastritis and ischemic heart disease. Positive Chlamydia pneumoniae (C. pneumoniae) serology is associated with increased levels of inflammatory cytokines and tumor necrosis factor-alpha (TNF-alpha), which stimulates endothelial cell activation, procoagulant activity and angiogenesis in patients with coronary heart disease. As a final example, interleukin-6 (IL-6) has been proposed to mediate cardiovascular disorders. Public awareness of risks of excessive body weight and high levels of serum cholesterol propelled the development of synthetic dietary components such as sucrose polyester (SPE) to substitute for natural lipids. SPE is a synthetic lipid whose physical properties are similar to a natural triacylglycerol with a similar assortment of fatty acids and is resistant to lipolysis by gastric and pancreatic enzymes. Intake of SPE in lieu of natural lipids is expected to decrease absorption of essential fatty acids (EFA) and fat-soluble vitamins among other essentials. Deficiency of EFA leads to the formation of faulty cellular membranes, which is manifested as skin lesions, growth failure, erythrocyte fragility, impairment of fertility and uncoupling of oxidation and phosphorylation. Possibilities of absorption of these synthetic lipids into the circulation may represent an unexpected health hazard. We have shown that subcutaneous (sc) administration to rabbits of a range of lipolysis-resistant lipid-like sorbitol, mannitol and arabitol esters of palmitic (P) and lauric (L) acids was found to evoke a mild APR, which in humans could contribute to CHD incidence. We suggest a reversal in the commonly accepted role of SPE as a sequestor of dietary lipid: SPE may be the lipophilic solute contained within the dietary lipid solvent micelle. An alternative conclusion regarding the biological effects of excessive dose of SPE in human and pig for a short time span should be considered.

Chlamydophila Infections↗

Kinetics and mechanisms of hepatic acute phase response to subtotal partial hepatectomy and cultural impact on environmental hepatic end-stage liver injury in the homeless.

Intoxication and liver damage induced by carbon tetrachloride (CCl(4)), aflatoxin B1, diabetes, and subtotal partial hepatectomy (PH(90)) in rats in which approximately 90% of the total hepatic tissue mass is surgically removed produces an acute-phase response (APR) whose initial stage prior to regression closely mimics the APRs associated with the life-threatening hepatic failure seen in the homeless. Rats treated by PH(90)were either healthy, CCl(4)-intoxicated, diabetic, or alflatoxin B1 (AFB1) intoxicated to the point of 75% liver insufficiency. It is well documented that high rates of mortality following PH(90)in aseptic rats could be minimized by supplementing drinking water with 20% glucose, organic components of L-15 medium and housing animals in cages maintained at 33-35;C. Aseptic rats showed a mild 20-30% decrease in APR proteins during the first 4-5 days following PH(90), while a maximal APR was noted 9-12 days post PH(90)and lasted for ~30 days when it returned to values close to those of healthy controls. This delay in hepatic APR of the remnant caudate lobe favoured replacement of lost basophilic clumps and ribosomes. The newly synthesized ribosomes of the nascent hepatocytes quantitatively maintained the APR signals of the injured caudate hepatocytes, and biosynthesized and released a typical spectrum of APR proteins. We suggest that massively injured liver has decoded an already stored and irreversible DNA-biochemical sequence of events in which priority is given to recovery of lost tissues by delaying an APR response to injury. In PH(90)of diabetic and CCl(4)-intoxicated rats, the hepatic dual functions of regeneration and APR processes associated with intoxication-initiated catabolic signals, created a heavy metabolic burden on the remnant caudate lobe leading to higher rates of mortality. APR of healthy rats to AFB1 parallels that of alpha-amanitin-induced intoxication. Similarly, within shorter time scale proportional to the severity of surgery, livers undergoing 75% partially hepatectomy (PH(75)) delayed both the onset and regression of APR. We are therefore led to believe that approaches other than liver transplantation should be considered as viable alternatives in the treatment of various acute and chronic liver diseases to avoid rejection and retransplantation. Scarcity of cadaveric liver has forced the medical community to investigate xenotransplantation with its unknown risks. Concomitantly, it is suggested that in view of the incalculable risks of indifference, the homeless must receive much improved medical care as we have found that two-dimensional immunoelectrophoretic assay of their serum is indicative of acute and chronic liver injury. The scientific and moral interrelationships of related matters are illuminated.

Acute-Phase Reaction↗

Natural atmospherics and occurrence of seizures in six adolescents with epilepsy: a cross correlation study.

As already seen in a former study of 315 epileptic seizures in adults, subsequent investigation of 3333 epileptic seizures in six adolescents revealed a significant increase of the seizure frequency during days with a higher mean frequency of 28 kHz atmospherics, and a decrease during days with a (Baumer apparatus) distinctly higher amount of 10 kHz when compared with the daily mean frequency within the whole period. However, one patient showed an opposite behaviour regarding the correlations of 28 and 10 kHz atmospherics and the mean numbers of seizures.

Adolescent↗

Influence of the earth's magnetic field on resting and activated EEG mapping in normal subjects.

We found in a former investigation that by measuring sleep parameters, the REM latency is shortened in the E-W position of sleepers compared with the N-S position. This paper reports on a further neurological observation in humans concerning the influence of the earth's magnetic field: there are statistically significant differences in the EEG of normal subjects, depending on whether the subjects sit facing the N-S or E-W direction. The difference is especially pronounced in the alpha-power.

Adult↗

Partially hepatectomized rats: a model for the study of the effect of toxins on the plasma protein profiles of nascent hepatocytes.

A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.

Acute-Phase Proteins↗

Significant correlations between atmospheric spectra according to Baumer and the in vitro incorporation of [3H]thymidine into the nuclear DNA of C6-glioma cells.

Significant correlations between certain spectra of atmospherics (spherics) according to Baumer (a.t.B), i.e. naturally occurring electro-magnetic impulses in the range of 4-50 kHz, and several diseases or biological parameters have been published earlier. Now we show that there exists a highly significant negative correlation (r = -0.61, P greater than 0.004) between the occurrence of 28 kHz impulses (a.t.B.) and the in vitro incorporation of thymidine into the nuclear DNA of C6-glioma cells. The positive correlation with the 10 kHz impulses (a.t.B) (r = 0.39), however, is statistically not significant (P greater than 0.055).

Animals↗

Suppression of experimental autoimmune encephalomyelitis by sulfasalazine.

It has recently been suggested that the sulfidopeptide leukotriene C4 (LTC4), a 5-lipoxygenase product of the arachidonic acid metabolism and one of the most potent mediators of vascular permeability, might be involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Subsequently, 20 guinea pigs with EAE were treated with sulfasalazine, a substance with a proved leukotriene inhibiting effect, which has previously been described as exerting beneficial effects in patients with inflammatory bowel disease and rheumatoid arthritis. The sulfasalazine-treated guinea pigs showed a significantly better clinical outcome, as well as a significantly lower histological inflammation score compared with 19 controls.

Animals↗

On the possibility of differential diagnosis at elevated erythrocyte sedimentation rate by analysis of the concentrations of blood plasma proteins--a model study.

An elevated erythrocyte sedimentation rate is generally regarded as an unspecific and mostly pathological indicator of inflammation or tumour. However, we have determined the concentrations of plasma/serum proteins that influence the erythrocyte sedimentation rate in numerous samples from several groups of patients with different diseases, including 2 forms of cancer. Equations have been developed by which the 1 h value of erythrocyte sedimentation rate can be expressed as the sum of disease-specific coefficients for each protein multiplied by the measured concentrations of the respective proteins. These equations are shown to be disease-specific with 64-93% probability. Such equations may thus form the basis for differential diagnosis.

Adult↗

Study of hepatotoxicity in isolated perfused liver versus cultures of rat hepatocytes.

Isolated perfused liver and cultures of rat hepatocytes were assessed for the quantitative evaluation of hepatotoxicity. Release of de novo biosynthesized plasma proteins and acid hydrolases into perfusion or culture media was taken as an indication of the integrity of hepatocytes in both systems. The activities of six acid hydrolases, alpha-L-fucosidase, alpha-D-galactosidase, beta-D-galactosidase, beta-D-N-acetylgalactosaminidase, beta-D-N-acetylglucosaminidase, and cathepsin D, were assayed in collagenase-segregated hepatocytes and in monolayer cultures of rat liver cells obtained via collagenase perfusion of rat liver. In situ, liver perfusion with collagenase led to a loss of 45 +/- 5% of the total acid hydrolase activity in the mitochondrial-lysosomal pellet of the liver cells with concomitant increase of these enzymes in the cytosol. In monolayer cultures over a period of 30 h, increased activity of cathepsin D, beta-D-galactosidase, and beta-D-N-acetylglucosaminidase in the mitochondrial-lysosomal pellet and the cytosol fraction was evident with concurrent biosynthesis of plasma proteins. The use of radioactive tracing techniques with the isolated perfused liver revealed that the rate of catabolism of intracellular protein was approximately 5 times that of plasma protein synthesis. Both methods described here are suitable for the study of the effects of toxins on the function of hepatocytes.

Animals↗

Suppression of experimental autoimmune encephalomyelitis by dual cyclo-oxygenase and 5-lipoxygenase inhibition.

The release of leukotriene C4 (LTC4), an important 5-lipoxygenase product of the arachidonic acid metabolism from polymorphonuclear leucocytes (PMNLs) of guinea pigs with experimental allergic encephalomyelitis (EAE), the animal model of MS, has been found to be significantly increased compared with healthy animals. Subsequently, the dual cyclo-oxygenase and 5-lipoxygenase inhibitor BW755C was applied to 15 guinea pigs with EAE. Two control groups (15 each) were treated with the cyclo-oxygenase inhibitor indomethacin or physiological saline, respectively. In the BW755C treated group, no animal developed symptoms of the disease in contrast to, respectively, 5 and 3 animals in the 2 other groups. Histological examination of the CNS revealed a highly significantly lower inflammation score in the BW755C treated animals, and the release of LTC4 from PMNLs was highly significantly decreased in this group compared with each of the others. The findings suggest that the vascular permeability enhancing LTC4 plays a pathogenetic role in EAE and indicate that inhibition of this sulfidopeptide leukotriene suppresses the disease. Therefore, the application of leukotriene inhibitors could contribute to the future treatment of MS.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

The stability of the circadian rhythm of green finches (Carduelis chloris) under the influence of a weak electrical field.

Free-running activity rhythms of nine green finches (Carduelis chloris) were studied under the influence of a 10-Hz square-wave electrical field. With a field strength of magnitude of E = 2.5 V/m in the empty cage, the population had a mean period of 23.64 +/- 0.77 hr. In the same experiment, but without the electrical field, the period was 23.66 +/- 0.80 hr. These results are in contradiction to Wever's description of a field-induced shortening of the period. A series of experiments with 10-Hz pulses of the same square-wave form, yet with various field strengths (8.7 and 65.2 V/m), also gave no effects.

Animals↗