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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 145 records · Page 8Linked to original sources

A physiological model of dark-adapted and light-adapted photoreceptors of the honeybee.

A physiological model of dark-adapted and light-adapted photoreceptors in the honeybee worker (Apis mellifera) has been developed. Almost all of the electrophysiological components of photoreceptors known up to date, e.g. the phototransduction cascade, the ion channels of the membrane, phototransduction gain and optical adaptation mechanisms, are adequately described by simple biophysical and biochemical models. The connections of these components were tried out in synthetic simulations for best fits of simulated to intracellularly recorded membrane potentials. Although the parameters of the best model were determined exclusively for the measured membrane potentials of dark-adapted photoreceptors, the model also accurately describes the light-adapted photoreceptor membrane potentials. Furthermore, the model correctly predicts the time-courses of measured photoreceptor responses with respect to squared-modulated flicker lights up to 200 Hz. This clearly demonstrates that the presented photoreceptor model is indeed a physiologically adequate description of the essential components of the phototransduction and the electrical membrane processes in the photoreceptors of the honeybee worker.

Adaptation, Physiological↗

Infants with "Colic"-mothers' perspectives on the crying problem.

OBJECTIVES: This study was designed to evaluate relationships between infant crying behavior and fussing behavior and the mother's causal attributions of the crying, her emotional responses to the crying, as well as her later perception of infant temperament. METHODS: Twenty mothers who presented their 3-9-week-old infants in pediatric practices because of excessive crying ("colic complaint group") and 20 mothers who visited for public preventive screening ("control group") were compared. Mothers kept a "baby diary." A highly structured interview with the mothers was conducted. When the babies were 4 months old, mothers completed a temperament questionnaire. The colic complaint group was subdivided using the Wessel criteria. RESULTS: Infants from the colic complaint group who did not meet these criteria did not differ from control subjects in any of the parameters derived from the diaries. However, the mothers of this group described significantly heightened negative affect and cognitions of being rejected in response to the crying. In contrast, mothers of infants who conformed to Wessel's definition, and thereby far exceeded the other subjects in crying duration, did not differ from control mothers in respect of the aforementioned feelings and cognitions. Mothers' "negative affect and feelings of being rejected" were associated with the perception of high negative emotionality 4 months later. CONCLUSION: In regard to the colic problem, attention must be paid not only to the characteristics of the child, but also to aspects of maternal perception and processing of the crying problem.

Affect↗

Riboflavin deficiency and preeclampsia.

OBJECTIVE: To examine in a prospective study riboflavin deficiency as a predisposing factor for preeclampsia in a high-risk collective of pregnant women in Zimbabwe. METHODS: At an antenatal clinic in Bulawayo, Zimbabwe, 154 women at increased risk for preeclampsia were observed prospectively until delivery. Riboflavin status was determined using the erythrocyte glutathione reductase activation coefficient test on the day of antenatal booking. Riboflavin deficiency was expressed by erythrocyte glutathione reductase activation coefficient of 1.4 or greater. RESULTS: Riboflavin deficiency was frequently found among the study population (33.8%). Incidence rose toward the end of pregnancy (27.3% at 29-36 weeks' gestation compared with 53.3% at over 36 weeks). In the riboflavin-deficient group, mothers were more likely to develop preeclampsia (28.8%) than in the riboflavin-adequate group (7.8%; P <.001, odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8-12.2). The calculated concentrations of intracellular free flavin adenine dinucleotide were significantly lower in patients who developed preeclampsia than in normal pregnancies (P <.05). CONCLUSION: Riboflavin deficiency should be considered a possible risk factor for preeclampsia. Insufficient concentrations of the riboflavin-derived cofactors flavin adenine dinucleotide and flavin adenine mononucleotide could contribute to the established pathophysiologic changes including mitochondrial dysfunction, enhanced oxidative stress, and disturbances in nitric oxide release.

Adult↗

Intensive care unit management of the stroke patient.

Although the majority of patients with acute stroke do not require intensive care, it is important to recognize when admission to an intensive care unit (ICU) is warranted. Patients undergoing thrombolytic therapy, those with brainstem infarcts referable to the basilar artery, those with large space occupying hemispheric infarcts, and those with fluctuating neurological examinations should be admitted to the ICU for monitoring and treatment.

Critical Care↗

Cardiac beta-adrenoceptors in chronic uremia: studies in humans and rats.

OBJECTIVES: The purpose of this study was to elucidate whether cardiac beta-adrenergic effects may be blunted in patients on maintenance hemodialysis (HD) and may help to explain autonomic dysfunction. BACKGROUND: Patients on HD often suffer from autonomic dysfunction. METHODS: We investigated the cardiovascular response of five HD patients (age: 46.1+/-7.9 years) and six healthy volunteers (age: 48.2+/-7.5 years) to isoprenaline, pirenzepine and phenylephrine. For analysis of underlying mechanisms of beta-adrenoceptor hyporesponsiveness, six-week-old male Wistar rats were rendered uremic by 5/6-nephrectomy (n = 9; SNX) and were killed for removal of the heart after six to seven weeks. Sham-operated rats (n = 15) served as controls. RESULTS: In the patient study, isoprenaline (3.5, 7, 17, 35 ng/kg/min, i.v.) led to an increase in heart rate, and shortening of the heart rate corrected duration of the electromechanical systole (QS2c), both of which were significantly reduced in HD patients. Baroreflex sensitivity was significantly reduced in HD patients. The response to low parasympathomimetic doses of pirenzepine was unchanged. In the rat study, left ventricular strips were placed in an organ bath, electrically driven and exposed to isoprenaline (10(-11) to 10(-6) mol/liter). While pD2 values were unchanged, maximum effect at the highest concentration was significantly reduced in SNX rats. The response to carbachol was not altered, nor was the M2-cholinoceptor density. There was no difference in beta-adrenoceptor density, or in immunodetectable amount of Gs and Gi protein. Activation of adenylyl cyclase evoked by isoprenaline was significantly reduced in left ventricular membranes of SNX rats, whereas effects of 10 micromol/liter GTP, 10 mmol/liter NaF, 10 micromol/liter forskolin and 10 mmol/liter Mn2+ were not altered. CONCLUSIONS: Cardiac beta-adrenergic responses are blunted in chronic uremia due to reduced isoprenaline-dependent activation of adenylyl cyclase. This might be caused by an "uncoupling" of the receptor or by an inhibition of the receptor by uremic toxins.

Adenylyl Cyclases↗

Studies on the nutritional composition and antinutritional factors of three different germplasm seed materials of an under-utilized tropical legume, Mucuna pruriens var. utilis.

Two different germplasms of a white variety and one germplasm of a black variety of Mucuna pruriens var. utilis were evaluated for their physicochemical properties as well as their nutritional and antinutritional characteristics. All germplasms had higher grain weight, density, hydration, and swelling capacity than other common legumes. The dehulled samples contained 303.2-335.5 g(-1) protein and 46.1-53.5 g x kg(-1) lipid, and these values were higher than the respective whole seeds. The levels of macro- and microelements in both whole and dehulled seeds were comparable to those in common pulses. All germplasms had a high dietary fiber content (18-19.5%), made up of mainly insoluble dietary fiber (DF). Seed lipids were high in unsaturated fatty acids (64.7-66.9%), specifically linoleic acid (48-49%). Whole and dehulled seeds of the white variety from Salem were particularly rich in sulfur-containing amino acids with significantly higher levels of in vitro protein digestibility than the other two germplasms. All germplasms had high levels of total phenols and phytate, trypsin, and chymotrypsin inhibitor activities, but were low in tannins, saponins, and alpha-amylase inhibitor activity. Only weak hemagglutinating activity against cow erythrocytes and no hemagglutinating activity against human erythrocytes (O) was observed in all the samples. Dehulled seeds were higher in total starch, including resistant starch and oligosaccharides (with verbascose as the major fraction) than the respective whole seeds. Both whole and dehulled samples of the white variety of Salem germplasm showed significantly lower concentrations of L-dopa, nonmethylated, and methylated tetrahydroisoquinolines than the respective whole and dehulled samples of other germplasms. In general, dehulling didn't affect the overall nutritional status in any of the presently investigated samples.

Amino Acids↗

Tannins in tropical browses: effects on in vitro microbial fermentation and microbial protein synthesis in media containing different amounts of nitrogen.

Four species of browses (Acacia angustissima, Acacia salicina, Calliandra calothyrsus, andDichrostachys cinerea) were used to study the effect of tannins on microbial fermentation and microbial protein synthesis in incubation media containing high nitrogen (HN) and low nitrogen (LN) in the presence and absence of polyethylene glycol (PEG, MW 6000). The additional nitrogen in HN medium was supplied through ammonium bicarbonate. The use of HN medium significantly (P < 0.05) increased the in vitro gas and short-chain fatty acid (SCFA) production and microbial protein synthesis compared to the LN medium. Incubation of tannin-containing browses alone produced significantly (P < 0.05) lower gas and SCFA compared to in the presence of PEG in both HN and LN media. Inclusion of PEG in tannin-containing browses significantly (P < 0.05) reduced the molar proportion of propionate compared to in its absence. Higher N in the media resulted in 10.4 and 9.9% increases in in vitro gas and SCFA production, respectively, whereas inclusion of PEG to tannin-containing feed to remove the effect of tannins increased the in vitro gas and SCFA production by 186 and 195%, respectively, indicating that the low fermentation of tannin-containing browses could be due to the depressive effects of tannins on microbial activity and only partially accounted for by unavailability of N for rumen microbes. Incubation of browses with straw significantly (P < 0.05) decreased ammonia nitrogen concentration but increased the in vitro gas and SCFA production and microbial protein synthesis compared to straw alone.

Bacterial Proteins↗

Antigen uptake and trafficking in human intestinal epithelial cells.

Primary intestinal epithelial cells, human colonic adenocarcinoma cell lines (DLD-1, Caco-2, and HT-29), and monocytes were used as model systems to study antigen uptake, antigen-presenting cell properties, as well as the kinetics of antigen uptake in intestinal epithelial cells (IEC). Intracellular staining of fluoresceinated tetanus toxoid was not evident in the IEC until after 30 min of incubation at 37 degrees C, whereas in monocytes intracellular punctate staining of fluoresceinated tetanus toxoid was evident after 5 mins. In polarized Caco-2 cells antigen could be internalized at both the apical and basolateral surfaces with polarized transport. When analyzed by electron microscopy, gold-labeled tetanus toxoid was internalized and found within endosomes and multivesicular bodies, but not within the lysosomal compartments by 60 min. By 2 hrs, gold-labeled tetanus toxoid was evident in the secondary lysosomes. These results demonstrate that tetanus toxoid follows an endocytic pathway in intestinal epithelial cells and that the kinetics of antigen uptake is slower than that of conventional antigen-presenting cells.

Antigens↗

Factors affecting antigen uptake by human intestinal epithelial cell lines.

We assessed the role of size, solubility, and prophagocytic cytokines interferon-gamma (IFN-gamma), and granulocyte-macrophage colony stimulatory factor (GM-CSF) in antigen uptake and kinetics by intestinal epithelial cells using keyhole limpet hemocyanin and ovalbumin. Both fluoresceinated keyhole limpet hemocyanin (3000-7500 kDa) and fluoresceinated ovalbumin (45 kDa) were internalized by human colonic epithelial cell lines, with kinetics similar to those of fluoresceinated tetanus toxoid, and there was decreased uptake of insoluble immune complexes and no enhancement in the uptake of soluble immune complexes. In addition, neither IFN-gamma nor GM-CSF altered the kinetics of uptake nor enhanced antigen internalization by the intestinal epithelial cell lines. These data suggest that regardless of the size of the soluble antigen, the presence of prophagocytic cytokines, or the formation of soluble immune complexes, fluid phase endocytosis of antigen by intestinal epithelial cells appears to be a relatively stable process.

Antigen-Antibody Complex↗

Hamster pancreatic beta cell lines with altered sensitivity towards apoptotic signalling by phosphatase inhibitors.

Specific inhibitors of serine/threonine phosphatases like okadaic acid can induce apoptotic cell death in the pancreatic beta cell line HIT. Cultivation in stepwise increased concentrations of okadaic acid enabled the isolation of HIT100R cells which proliferate at 100 nM okadaic acid (8 - 10 times the initially lethal concentration). These two cell lines were used to characterize the events triggered by okadaic acid that led to apoptosis. Biochemical markers, e.g. cytochrome c release from mitochondria and increase of caspase-3-like activity, revealed that induction of apoptosis by 100 nM okadaic acid in parental HIT cells started with the release of cytochrome c. In HIT100R cells 500 nM okadaic acid were necessary to induce alterations comparable to those observed with 100 nM okadaic acid in non-resistant HIT cells. In contrast to okadaic acid, the potency of the structurally different phosphatase inhibitor cantharidic acid to induce cytochrome c release, increase of caspase-3-like activity and DNA fragmentation was comparable in HIT and HIT100R cells. Thus, no cross-resistance between these phosphatase inhibitors seemed to exist. Phosphatase activity in extracts from HIT and HIT100R cells did not differ in its total amount or in its sensitivity for okadaic acid. Since higher concentrations of okadaic acid were needed to induce apoptosis in HIT100R cells, a compromised intracellular accumulation of the toxin appeared likely. Functional and structural analysis revealed that this was achieved by the development of the multidrug resistance phenotype in HIT100R cells. The underlying mechanism appeared to be the enhanced expression of the pgp1 but not the pgp2 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

FP-receptor mediated trophic effects of prostanoids in rat ventricular cardiomyocytes.

The aim of this study was to characterize the receptor subtype involved in cardiac effects of prostanoids. For this purpose we determined in neonatal and adult rat cardiomyocytes effects of prostanoids on inositol phosphate (InsP)-formation (assessed as accumulation of total [(3)H]-InsP's in myo-[(3)H]-inositol pre-labelled cells) and on rate of protein synthesis (assessed as [(3)H]-phenylalanine incorporation), and on contractile force in left ventricular strips of the rat heart. For comparison, effects of prostanoids on InsP-formation and contractile force were determined in rat thoracic aorta, a classical TP-receptor containing tissue. Prostanoid increased InsP-formation and rate of protein synthesis in neonatal as well as adult rat cardiomyocytes; the order of potency was in neonatal (PGF(2alpha)>PGD(2)> or =PGE(2)> or =U 46619>PGE(1)) and adult (PGF(2alpha)>PGD(2)> or =PGE(2)>U 46619) rat cardiomyocytes well comparable. Moreover, in electrically driven left ventricular strips PGF(2alpha) caused positive inotropic effects (pD(2) 7.5) whereas U 46619 (up to 1 microM) was uneffective. In contrast, in rat thoracic aorta U 46619 was about 100 times more potent than PGF(2alpha) in increasing InsP-formation and contractile force. The TP-receptor antagonist SQ 29548 only weakly antagonized prostanoid-induced increases in rate of protein synthesis (pK(B) about 6) in rat cardiomyocytes but was very potent (pK(B) about 8-9) in antagonizing prostanoid-induced increases in InsP-formation and contractile force in rat aorta. We conclude that, in cardiomyocytes of neonatal and adult rats, the prostanoid-receptor mediating increases in InsP-formation and rate of protein synthesis is a FP-receptor. Moreover, stimulation of these cardiac FP-receptors can mediate increases in contractile force.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Enhanced apoptosis of T cells in common variable immunodeficiency (CVID): role of defective CD28 co-stimulation.

CVID is a primary immune disorder in which hypogammaglobulinaemia may be associated with a number of T cell defects including lymphopenia, anergy, impaired lymphocyte proliferation and deficient cytokine secretion. In this study we show that T cells of CVID subjects, in comparison with control T cells, undergo spontaneous apoptosis in culture and markedly accelerated apoptosis after gamma-irradiation. Although costimulation of the CD28 receptor following engagement of the TCR/CD3 receptor normally provides a second signal necessary for IL-2 secretion, CD28 costimulation in CVID does not significantly increase IL-2 production, nor does this combination of activators enhance the survival of irradiated CVID T cells, as it does for cultured normal T cells. Addition of IL-2 enhances CVID T cell survival, suggesting that the IL-2 signalling pathways are normal. CVID T cells have similar expression of Bcl-2 to control T cells. CD3 stimulation up-regulates T cell expression of bcl-xL mRNA for normal T cells, but anti-CD28 does not augment bcl-xL expression for CVID subjects with accelerated apoptosis. Defects of the CD28 receptor pathway, leading to cytokine deprivation and dysregulation of bcl-xL, could lead to poor T cell viability and some of the cellular defects observed in CVID.

Adolescent↗

Thioredoxin reductase two modes of catalysis have evolved.

Thioredoxin reductase (EC 1.6.4.5) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin. Thioredoxin plays several key roles in maintaining the redox environment of the cell. Like all members of the enzyme family that includes lipoamide dehydrogenase, glutathione reductase and mercuric reductase, thioredoxin reductase contains a redox active disulfide adjacent to the flavin ring. Evolution has produced two forms of thioredoxin reductase, a protein in prokaryotes, archaea and lower eukaryotes having a Mr of 35 000, and a protein in higher eukaryotes having a Mr of 55 000. Reducing equivalents are transferred from the apolar flavin binding site to the protein substrate by distinct mechanisms in the two forms of thioredoxin reductase. In the low Mr enzyme, interconversion between two conformations occurs twice in each catalytic cycle. After reduction of the disulfide by the flavin, the pyridine nucleotide domain must rotate with respect to the flavin domain in order to expose the nascent dithiol for reaction with thioredoxin; this motion repositions the pyridine ring adjacent to the flavin ring. In the high Mr enzyme, a third redox active group shuttles the reducing equivalent from the apolar active site to the protein surface. This group is a second redox active disulfide in thioredoxin reductase from Plasmodium falciparum and a selenenylsulfide in the mammalian enzyme. P. falciparum is the major causative agent of malaria and it is hoped that the chemical difference between the two high Mr forms may be exploited for drug design.

Animals↗

Thioredoxin reductase as a pathophysiological factor and drug target.

Human cytosolic thioredoxin reductase (TrxR), a homodimeric protein containing 1 selenocysteine and 1 FAD per subunit of 55 kDa, catalyses the NADPH-dependent reduction of thioredoxin disulfide and of numerous other oxidized cell constituents. As a general reducing enzyme with little substrate specificity, it also contributes to redox homeostasis and is involved in prevention, intervention and repair of damage caused by H2O2-based oxidative stress. Being a selenite-reducing enzyme as well as a selenol-containing enzyme, human TrxR plays a central role in selenium (patho)physiology. Both dietary selenium deficiency and selenium oversupplementation, a lifestyle phenomenon of our time, appear to interfere with the activity of TrxR. Selenocysteine 496 of human TrxR is a major target of the anti-rheumatic gold-containing drug auranofin, the formal Ki for the stoichiometric inhibition being 4 nM. The hypothesis that TrxR and extracellular thioredoxin play a pathophysiologic role in chronic diseases such as rheumatoid arthritis, Sjögren's syndrom, AIDS, and certain malignancies, is substantiated by biochemical, virological, and clinical evidence. Reduced thioredoxin acts as an autocrine growth factor in various tumour diseases, as a chemoattractant, and it synergises with interleukins 1 and 2. The effects of anti-tumour drugs such as carmustine and cisplatin can be explained in part by the inhibition of TrxR. Consistently, high levels of the enzyme can support drug resistance. TrxRs from different organisms such as Escherichia coli, Mycobacterium leprae, Plasmodium falciparum, Drosophila melanogaster, and man show a surprising diversity in their chemical mechanism of thioredoxin reduction. This is the basis for attempts to develop specific TrxR inhibitors as drugs against bacterial infections like leprosy and parasitic diseases like amebiasis and malaria.

Chronic Disease↗

Fibrovascular esophageal polyp as a diagnostic challenge.

Fibrovascular polyps are rare benign esophageal tumors that usually arise from the proximal third of the esophagus. We present the case of a 48-year-old man with a history of dysphagia and 7-kg weight loss over a period of 2 months. A barium swallow showed a distended esophagus with a tumor extending from the upper esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a homogeneous intramural mass with a density of 22 Hounsfield units was seen, which extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the presence an intramural tumor beginning at the upper esophageal sphincter and reaching to the cardia. The tumor was completely covered with mucosa, except for an ulcerated area at its distal end, which herniated into the stomach. On endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the tumor suggested a leiomyoma. None of the imaging modalities used revealed evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially malignant extensive intramural tumor was suspected, and an esophagectomy was performed. Only at the time of removal of the specimen did it become evident that the tumor mass was located intraluminally with a pedicle in the region of the upper esophageal sphincter. The final pathological diagnosis was a giant fibrovascular polyp of the esophagus.

Diagnostic Imaging↗

Transient expression of NMDA receptor subunit NR2B in the developing rat heart.

NMDA receptors represent a subtype of the ionotropic glutamate receptor family, comprising three classes of subunits (NR1, NR2A-D, NR3), which exhibit distinct patterns of regional and developmental expression in the CNS. Recently, some NMDA receptor subunits have also been described in adult extraneuronal tissues and keratinocytes. However, their developmental expression patterns are currently unknown. With use of RT-PCR and western blot analysis, the expression of NMDA receptor subunit NR2B was investigated in the developing rat heart. NR2B mRNA and protein were detected in heart tissue of rats from embryonic day 14 until postnatal day 21 but disappeared 10 weeks after birth. In contrast, no NMDA receptor subunit NR1, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluR2, or anchoring postsynaptic density protein-95 could be detected in rat heart at any developmental stage. Confocal microscopy of cultured cardiac myocytes (CMs) from neonatal rats revealed distinct NR2B staining mainly of intracellular structures. However, no functional NMDA receptor could be detected on CMs by whole-cell recordings. In conclusion, high concentrations of NR2B protein can be detected in early rat heart development, but its function still remains elusive.

Animals↗

Osseous integration of bovine hydroxyapatite ceramic in metaphyseal bone defects of the distal radius.

Hydroxyapatite ceramic made of bovine spongiosa was used as structural support material in a prospective study to correct bone defects experienced after reduction in distal radius fractures. The study took place over a 3-year period (1992-1999) and comprised 14 patients. Osseous integration was analyzed via biopsies and magnetic resonance imaging. Long-term follow-up monitoring involving magnetic resonance imaging in 13 of the 14 patients showed fibrovascular growth within incorporated hydroxyapatite material. Osseous integration was demonstrated in magnetic resonance images by gadolinium uptake and by the presence of osteoid layers and endothelialized vessels. Hydroxyapatite ceramic offers a biologically acceptable alternative to autologous bone when augmenting distal radius fracture fixation.

Adult↗

[Principles and role of nucleic acid amplification and modern microbiological diagnosis].

In the recent decade, molecular tests have provided tools for highly sensitive and specific, culture-independent detection of infectious agents in clinical specimens. The rapid development of new methods and among these mainly the prototype method "polymerase chain reaction" (PCR) result in improved diagnostic procedures. Since its original description, a lot of modifications and advancements of PCR and alternative systems for in vitro amplification of nucleic acids have been developed to meet various requirements for improved detection of both DNA and RNA, quantification of the target molecules, and transfer from basic clinical research into a routine technique for clinical laboratory diagnosis. Since the purposes for which nucleic acid amplification methods should be used in the diagnosis of infectious diseases are often still uncertain, an evaluation and careful examination of the criteria for correct application of these techniques is needed. This review focuses on the recent developments in amplification procedures as well as on the use of these methods in the laboratory diagnosis of infectious diseases. The methodological limitations, future needs and perspectives are addressed.

Bacteria↗