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Biomedical subjects

B Walter

Publications and source records attributed to B Walter.

At least 37 records · Page 2Linked to original sources

Influence of hypoxia and hyperthermia upon peroxidative and glutathione status in growth-restricted newborn piglets.

Normal weight (NW) and spontaneously intra-uterine growth-restricted newborn piglets (IUGR) were submitted to 1 hour hypoxia and hyperthermia followed by 3 hours reoxygenation. Glutathione (GSH, GSSG), lipid peroxidation products (TBAR) and cytochrome P450 dependent production of reactive oxygen species were studied by determination of H2O2 production and amplified chemiluminescence (CL) in brain and peripheral organs of NW and IUGR. A severe decrease of GSH was accompanied by enhanced H2O2 formation and lipid peroxidation in the brain of both NW and IUGR after hypoxia/hyperthermia and reoxygenation. In the other organs studied, only muscles showed enhanced lucigenine amplified CL and TBAR production. Nearly the same results in NW and IUGR reveal no higher risk of IUGR.

Animals

Body weight distribution and organ size in newborn swine (sus scrofa domestica) -- a study describing an animal model for asymmetrical intrauterine growth retardation.

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

Animals

Estimation of nonlinear couplings on the basis of complexity and predictability--a new method applied to cardiorespiratory coordination.

Nonlinear coordination is an essential property of the complex functioning of the autonomic nervous system. Therefore, the coupled behavior of heart rate fluctuations (HRF) and respiratory movements (RM) was analyzed on the basis of their joint reconstruction in the phase space. Independence measures of complexity and predictability were approximated from the correlation integrals which enabled the strength of cardiorespiratory couplings to be quantified. These measures were validated in a simulation study of two coupled nonlinear oscillators in dependence on their coupling strength and respective synchronization effects. The cardiorespiratory coordination during quiet sleep and active sleep of newborn piglets was quantified by means of the proposed independence measures of complexity and predictability. The difference of those measures between the sleep states investigated was more significant than the difference of the respective linear coherence peaks.

Animals

CDRH3 length is the target of selection of disease-associated IgM autoantibodies.

The experiments outlined here provide evidence for positive selection of B-1 lymphocytes secreting IgM autoantibodies in the autoimmune mev mice as a result of the reduced threshold of responsiveness to autoantigens because of PTP1C deficiency, which is targeted at the CDR3 length of the variable region of the heavy chain. In addition, characteristic differences in the size, hydrophobicity pattern, and relative local charge of the CDR3 of the heavy chain of disease-associated IgM autoantibodies from moth-eaten mice help distinguish them from physiological natural autoantibodies present in normal mice.

Animals

Validation of the multiple colored microsphere technique for regional blood flow measurements in newborn piglets.

The use of multiple colored microspheres (CMS) for the measurement of regional blood flow (RBF) in almost all organs and tissues of newborn piglets was validated. For this purpose mixtures of different CMS and/or radio-labeled microspheres (RMS) were injected into the left ventricle of eight newborn piglets. Regional blood flows (RBF) were quantified using the reference sample method. Flow rates estimated by RMS and CMS were compared for each tissue sample. An excellent correlation (r = 0.995-0.999) between CMS and RMS flow rates was found even for organs with low perfusion and tissue samples containing 400-750 CMS. We conclude that the CMS technique is a valid alternative for RBF measurement in newborn piglets, and that all disadvantages arising from radioactive labeling are thereby avoided.

Animals

Changed systemic and cerebral hemodynamics and oxygen supply due to gradual hemorrhagic hypotension induced by an external PID-controller in newborn swine.

An experimental design including an external closed-loop PID-(proportional-integral-differential-)controller is presented which enables the induction of gradual hemorrhagic hypotension at different stages of blood flow reduction up to stages of critically disturbed systemic and regional hemodynamics and oxygen supply. For this purpose nine newborn piglets (12-26 hours old, body weight 1626+/-160 g) were anesthetized and artificially ventilated. Gradual hemorrhagic hypotension was induced at four different steady state stages (stage 1 = 60 mmHg; stage 2 = 50 mmHg; stage 3 = 40 mmHg; stage 4 = 35 mmHg) every 30 minutes by gradual blood withdrawal using external PID controller equipment. Cardiac output and brain regional blood flows were measured by the colored microsphere technique. Systemic and brain regional hemodynamics and O2 supply, metabolic parameters and blood catecholamine concentrations were obtained under baseline conditions and at every 25th minute of the four different steady state stages. About 35 percent of the calculated total blood volume (cTBV) was withdrawn in order to reach the first stage of hemorrhagic hypotension. Further blood withdrawal of about 10 percent of the cTBV, about 5 percent of the cTBV, and about 3 percent of the cTBV were necessary to reach the other respective hypotensive stages. Gradual hemorrhagic hypotension led to an increasing reduction of the cardiac output at every hypotensive stage up to about 20 percent of the baseline value (p<0.05). This was accompanied by a concomitant increase of the total peripheral resistance to about 2.5 fold (p<0.05) and a huge increase in the blood catecholamine concentrations (epinephrine: about 64 fold; norepinephrine: about 35 fold). The induced redistribution of the circulating blood volume was shunted to the vital organs. Therefore, brain cortical blood flow was slightly increased at stage 1 and stage 2. A significant reduction of rCBF did not occur until stage 4 (p<0.05). Regional cerebrovascular resistance was concomitantly reduced at stage 1 and stage 2 (p<0.05) and thereafter again slightly elevated. Brain cortical oxygen consumption was maintained up to stage 2, reduced by about 20% at the next stage of hemorrhagic hypotension (p<0.05) and reached the lowest level of about 50% from baseline at stage 4 (p<0.05). Excellent accuracy and stability was shown at each stage for the external PID controller equipment, so that each given setpoint of the instantaneous mean arterial blood pressure was reached and stabilized even at the lowest hypotensive stage (stage 1: 59.53+/-0.23; stage 2: 50.03+/-0.56; stage 3: 39.18+/-1.75; stage 4: 35.28+/-0.45 mmHg (mean+/-SD)). We conclude that the experimental design presented, with an external PID controller to induce gradual hemorrhagic hypotension in newborn piglets is sufficient for producing functional states with changed systemic and cerebral features with high stability and accuracy, enabling a systematic study of disturbed regional hemodynamics and energy metabolism under steady state conditions even under critically changed states of the systemic cardiovascular regulation.

Animals

Restricted CDR3 length of the heavy chain is characteristic of six randomly isolated disease-associated VH J558+ IgM autoantibodies in lupus prone motheaten mice.

To investigate the origin of disease-associated IgM autoantibodies (AAb), we compared the genetic and structural characteristics of IgM AAb from autoimmune prone motheaten (mev) mice with natural autoantibodies (NAAb) from normal background C57/BL6 strain. Six hybridoma-derived IgM molecules each were obtained both from mev mice, at the terminal stage of systemic autoimmune disease, and from mitogen-stimulated C57/BL6 mice. These were randomly selected for VH J558 gene expression (aberrantly expressed in mev mice). The variable regions of the IgM molecules, both from autoimmune and normal mice, were encoded by unmutated germline VH genes. Disease-associated AAb from mev mice were predominantly encoded by the J558 subfamily 186.2, whereas five J558 subfamilies were utilized in NAAb originating from normal mice. Junctional diversity as a result of N or P nucleotide insertions and D-D fusions was noted among IgMs originating from both mev (mostly B-1 lymphocytes) and C57BL/6 (mostly B-2 lymphocytes) mice. Interestingly, all six J558+ IgMs from mev mice showed a restricted CDR3 length of 10 amino acids, with similar hydrophobicity indices. Four unique V-D-J rearrangements were observed among these IgMs. None of the IgMs were polyreactive and three of the six were subsequently observed to express monospecific autoreactivity with synthetic peptides (residues 81-92 and 37-53) representing segments of the T cell CD4-accessory molecule. Three IgM antibodies had hydrophilic arginine residues in their CDR3 heavy chain region. By contrast, all six J558+ IgMs from C57/BL6 mice had variable CDR3 length, distinct VDJ rearrangements and a local negative charge in the CDR3 region. Four of these IgMs demonstrated polyreactivity with multiple conserved autoantigens and, hence, were classified as NAAb. These findings provide evidence for either positive or impaired negative selection of B-1 lymphocytes secreting disease-associated IgM AAb in mev mice. This likely results from a reduced threshold of responsiveness to autoantigens due to PTP1C deficiency, which is targeted at the CDR3 length of the variable region of the heavy chain. In addition, characteristic differences in the size and hydrophobicity pattern of the CDR3 of the heavy chain allow structural distinction between monospecific disease-associated IgM AAb and the polyreactive IgM NAAb.

Amino Acid Sequence

The adenovirus E3-10.4K/14.5K complex mediates loss of cell surface Fas (CD95) and resistance to Fas-induced apoptosis.

Cytotoxic T cells use Fas (CD95), a member of the tumor necrosis factor (TNF) receptor superfamily, to eliminate virus-infected cells by activation of the apoptotic pathway for cell death. The adenovirus E3 region encodes several proteins that modify immune defenses, including TNF-dependent cell death, which may allow this virus to establish a persistent infection. Here we show that, as an early event during infection, the adenovirus E3-10.4K/14.5K complex selectively induces loss of Fas surface expression and blocks Fas-induced apoptosis of virus-infected cells. Loss of surface Fas occurs within the first 4 h postinfection and is not due to decreased production of Fas protein. The decrease in surface Fas is distinct from the 10.4K/14.5K-mediated loss of the epidermal growth factor receptor on the same cells, because intracellular stores of Fas are not affected. Further, 10.4K/14.5K, which was previously shown to protect against TNF cytolysis, does not induce a loss of TNF receptor, indicating that this complex mediates more than one function to block host defense mechanisms. These results suggest yet another mechanism by which adenovirus modulates host cytotoxic responses that may contribute to persistent infection by human adenoviruses.

Adenovirus E3 Proteins

Adjustment of reduced arterial blood pressure--a tool for investigations into gradually reduced brain function.

Hypoxic-ischemic disorders of the neonatal brain function depend in particular on critical decrease of arterial blood pressure (ABP) below the limited range of cerebral autoregulation. An experimental design including an extracorporal ABP controller is presented which enables the induction of gradual hemorrhagic hypotension at different stages of blood flow reduction up to stages of critically disturbed systemic and regional hemodynamics and oxygen supply. In nine newborn piglets several levels of critically reduced ABP (60, 50, 40, 35 mmHg, normal about 75 mmHg) were stabilized over 30 min, and heart rate, breathing, blood gases, systemic and cerebral hemodynamics, and electrocorticogram were recorded. It was found that the reduced circulating blood volume was redistributed in favour of the vital organs. Therefore, brain cortical blood flow was slightly increased at ABP = 60 and ABP = 50 mmHg. A significant reduction of cortical blood flow occurred only at ABP = 35 mmHg. The experimental design which was based on an extracorporal ABP controller is necessary and sufficient for producing functional states of gradual hemorrhagic hypotension with high stability and accuracy, enabling a systematic study of disturbed regional hemodynamics and disturbed energy metabolism under steady state conditions, even under critically changed states of the systemic cardiovascular regulation.

Animals

Effects of low-frequency magnetic fields on electrocortical activity in humans: a sferics simulation study.

A previously recorded electromagnetic impulse of natural origin, a 10 kHz-sferic, was simulated and presented to 20 subjects. The magnetic component of the signal with a maximum field amplitude of 50 nT and a duration of 500 microseconds was applied over a duration of 10 minutes with a pulse repetition rate that varied statistically between 7 and 20 Hz. After sferics exposure, an additional 20 minutes without treatment were recorded in order to examine possible prolonged effects of sferics stimulation. The control group (n = 20) received no treatment. As a dependent measure, electrocortical changes throughout the course of the experiment were determined by means of EEG spectral analysis and compared between the two groups. Sferics exposure provoked increases in alpha and beta power. The effect was present during stimulation and continued for 10 minutes after the end of treatment. A longer lasting influence of sferics exposure was displayed by subjects with a high degree in weather sensitivity, somatic complaints, and neuroticism, who continued to stay on an enhanced alpha power level until the end of registration (20 minutes after the end of exposure). With these results a general electrocortical sensitivity towards sferics as well as individual differences in sferics reactivity could be demonstrated.

Adult

The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis.

The c-ros gene was originally identified in mutant form as an oncogene. The proto-oncogene encodes a tyrosine kinase receptor that is expressed in a small number of epithelial cell types, including those of the epididymis. Targeted mutations of c-ros in the mouse reveal an essential role of the gene in male fertility. Male c-ros -/- animals do not reproduce, whereas the fertility of female animals is not affected. We demonstrate that c-ros is not required in a cell autonomous manner for male germ cell development or function. The gene, therefore, does not affect sperm generation or function in a direct manner. The primary defect in the mutant animals was located in the epididymis, showing that c-ros controls appropriate development of the epithelia, particularly regionalization and terminal differentiation. The epididymal defect does not interfere with production or storage of sperm but, rather, with sperm maturation and the ability of sperm to fertilize in vivo. Interestingly, sperm isolated from c-ros -/- animals can fertilize in vitro. Our results highlight the essential role of the epididymis in male fertility and demonstrate a highly specific function of the c-ros receptor tyrosine kinase during development of distinct epithelial cells.

Animals

Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics.

The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CGP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 microCi) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUC) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371.

Adult

The development of a measure of enculturation for Native American youth.

Enculturation is the process by which individuals learn about and identify with their ethnic minority culture. It is distinguished from acculturation which refers to the process by which an ethnic minority individual is assimilated into the majority culture. Three studies with Native American youths are reported that describe the development of a measure of enculturation for Native American youths. Development of a measure of enculturation provides a foundation upon which to build a body of literature that focuses on strengths in a youth's life rather than on deficits. Results of the first study (n = 120), a confirmatory factor analysis, indicated that cultural affinity, native American identity, and family involvement in traditional activities adequately represent the construct of ecnulturation. The study also provides some convergent validity for this interpretation. The second study examines factor invariance for enculturation among youths with data from over 2 years (n = 69). The factor structure was similar across time. The third study replicates the factor structure and validity analyses with a new sample (n = 42). Usefulness of the measure for assessing protective factors and stressing ethnicity over simple assessment of race categories is discussed.

Adolescent

Hypothalamic and olfactory control of sexual behavior and partner preference in male rats.

Sexually active male rats prefer a sexually receptive female to a nonreceptive female, and partner-preference tests provide one way of studying sexual motivation. Surgical deafferentation of the olfactory bulbs from all the known chemosensory systems of the nasal septum renders rats anosmic. In Experiment 1, we show that, although bulb deafferentation of male rats decreases some aspects of sexual performance, most deafferented males copulate and partner preference is not affected. In Experiment 2, we show that large excitotoxin lesions of the preoptic hypothalamus eliminate copulation, an effect that is correlated with damage to the anterior portions of the medial and lateral preoptic area. Lesions also decrease partner preference, an effect that is correlated (r = 0.82) with damage to a small part of the bed nucleus of the stria terminalis. Most males who do not copulate after hypothalamic lesions show a persistent, albeit reduced, preference for receptive females over nonreceptive females. This preference appears to depend on olfactory ability because bulb deafferentation of lesioned, noncopulating males virtually eliminates partner preference.

Animals

Colored microsphere technique as a new method for quantitative-multiple estimation of regional hepatic and portal blood flow.

A new method for multiple, quantitative estimation of regional splanchnic blood flow is presented which overcomes all the limitations of the radionuclide microsphere technique. By direct comparison of two methods, i.e., simultaneous blood flow measurement with radionuclide-labeled and colored microspheres, it was shown that the quality of flow measure was quite similar. Simultaneous measurement using paired radionuclide-labeled microspheres yielded an excellent correlation between both values of r = 0.997, a variability of 4.58 +/- 3.84% and a SEE-value of 0.167 ml/g/min. The colored microsphere technique produced corresponding values with r = 0.998, a variability of 5.94 +/- 7.80% and a SEE-value of 0.212 ml/g/min (n.s.). This is also shown for five different abdominal organs and tissues with quite different flow rates under normal physiological conditions. Thus, the colored microsphere technique is a suitable experimental method for making multiple and quantitative measures of the nutritive blood flow through splanchnic organs and tissues and yields values of arterial blood inflow into the liver and into the circulatory bed which is drained by the portal vein.

Animals

Deterministic--chaotic and periodic properties of heart rate and arterial pressure fluctuations and their mediation in piglets.

OBJECTIVE: Only the simultaneous analysis of periodic and nonlinear properties of heart rate fluctuations (HRF) can describe completely this complex physiological process. Up to now there is, apart from a study of our own, no systematic and correlative investigation using both parameter groups, also not in early development. Thus, we tried to describe in this manner these properties of HRF, the corresponding mean arterial pressure fluctuations (MAPF) and respiratory movements (RM) and their mutual relations in neonatal pig. METHODS: In 6 term newborn piglets, periodic properties of HRF, RM, and MAPF were analyzed by spectral and coherence analysis, and deterministic-chaotic properties by calculation of correlation dimension (CD), Lyapunov exponent (LE), and construction of phase space plots. The assumption of deterministic chaotic components was supported by Theiler's test for nonlinearity, by always positive leading LEs, and by the results of a nonlinear deterministic model. These analyses were done in sleep states, general anaesthesia, hypoxic hypoxia, in ventilated state, and during cholinergic and additional beta-adrenergic blockade. RESULTS: In all experimental states, HRF and MAPF have periodic and nonlinear, very probably deterministic-chaotic properties, but in different relations. In anaesthetized piglets, periodic properties of HRF and MAPF dominate. In hypoxia the decreasing LE and CD of HRF and CD of MAPF were connected with increasing MAPF power density. Cholinergic blockade caused a decreased overall HRF and MAPF power and a decreasing LE and CD, but beta-adrenergic blockade decreased a small part of power density of both in 0.02-0.08 Hz only. The results of CD, LE, Theiler's test and the low dimensional deterministic model data suggested mainly deterministic-chaotic properties in the nonlinear part of HRF and MAPF. CONCLUSIONS: Already in neonatal piglets, both periodic and nonlinear, very probably deterministic chaotic properties of HRF and MAPF exist which change both during hypoxia and cholinergic blockade. They are partly cholinergically and--to a small extent--also beta-adrenergically mediated. The decrease of nonlinear complexity of HRF and MAPF during hypoxia suggests characteristic pathological change even in early development.

Anesthesia, General

Brain peroxidative and glutathione status after moderate hypoxia in normal weight and intra-uterine growth-restricted newborn piglets.

In order to investigate the pathogenetic factors causing the relatively frequent occurrence of brain injury in intrauterine growth-restricted newborns, lipid peroxidation products (TBAR), glutathione (GSH, GSSG) and in vitro production of reactive oxygen species (chemiluminescence, stimulated lipid peroxidation, H2O2 formation) were studied in the brain of normal weight (NW) and intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour of hypoxia (FiO2 11%) and 90 min reoxygenation. Cardiocirculatory parameters and catecholamine release into the blood were also measured. In the cerebellum, higher GSH content, but also higher in vitro production of lucigenin amplified chemiluminescence were found in comparison to other brain regions, independent of growth restriction and hypoxia. Moderate hypoxia without acidosis and hypercapnia resulted in GSH depletion especially in the brain of IUGR, but no changes in GSSG concentrations were measured. Though TBAR decreased after hypoxia/reoxygenation, in some brain areas of IUGR higher TBAR values were found in comparison to NW. H2O2 formation, stimulated lipid peroxidation and lucigenin and luminol amplified chemiluminescence in the 9000 x/g supernatant of brain tissue did not reveal special response of IUGR to hypoxia/reoxygenation. Hypoxia-induced circulatory centralisation due to increased release of catecholamines into the plasma prevented oxygen deficiency also in the brain of IUGR. The role of brain monoamine metabolism in the production of reactive oxygen species, followed by greater GSH depletion and higher in vivo formation of lipid peroxides in IUGR is discussed.

Animals