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Biomedical subjects

A Kaiser

Publications and source records attributed to A Kaiser.

At least 19 recordsLinked to original sources

A fluorescent substrate of transglutaminase for detection and characterization of glutamine acceptor compounds.

A fluorescent dipeptide was designed to discover glutamine acceptor proteins of transglutaminase. Starting materials for synthesis were the commercially available compounds carbobenzoxy-L-glutaminylglycine (CBZ-Gln-Gly) and monodansylcadaverine (C-DNS) which were coupled to obtain CBZ-Gln-Gly-C-DNS 1 [1-N-(carbobenzoxy-L-glutaminylglycyl)-5-N- (5'-N', N'-dimethylamino-1'-naphthalenesulfonyl)- diamidopentane]. The glutamine peptide is a substrate of bacterial transglutaminase from Streptoverticillium mobaraense as well as of the guinea pig liver enzyme. This could be shown by incorporating 1 into alpha s1-casein resulting in a significant increase in fluorescence intensity and a concomitant inhibition of cross-linking reaction. Additionally, dipeptide 1 is a useful tool to characterize the specificity of transglutaminase toward small primary amines. We established a sensitive HPLC assay and determined the kinetic parameters of several alkylamines. Hydrolysis of 1 is suppressed in the presence of the nucleophiles as it could be demonstrated with different concentrations of butylamine in semiquantitative studies. Together with labeled primary amines, reagent 1 seems to be a particularly suitable tool for examining acceptor-donor relationships of transglutaminase substrates.

Dipeptides

Factors associated with work resumption: a 5 year follow-up with cardiac patients.

Physiological and psychological parameters of 41 cardiac patients who retired after an inpatient rehabilitation treatment in Germany were compared with those of 41 patients (matched exactly according to sex, age, and diagnosis) who worked after a 5 year follow-up. Both samples were selected from a large pool of 733 consecutive cardiac patients participating in the rehabilitation program with follow-ups at 1, 3 and 5 years. The following physiological parameters were assessed: clinical characteristics such as biochemical variables and functional parameters of the left ventricle, performance and electrocardiogram during ergometric exercise, and medication. Psychological parameters assessed with questionnaires comprised: life satisfaction, physical complaints, and illness behavior, socioeconomic and anamnestic data. No substantial differences were observed for medical data, but psychological parameters showed striking differences. Retired patients were characterized by lower work satisfaction, complaints of being more handicapped by the disease, higher 'propensity for pension', more frequent complaints concerning their general state of health, and lower education level.

Alcohol Drinking

Rapid stimulation of a soybean protein-serine kinase that phosphorylates a novel bZIP DNA-binding protein, G/HBF-1, during the induction of early transcription-dependent defenses.

The G-box (CACGTG) and H-box (CCTACC) cis elements function in the activation of phenylpropanoid biosynthetic genes involved in the elaboration of lignin precursors, phytoalexins and the secondary signal salicylic acid as early responses to pathogen attack. We have isolated a soybean cDNA encoding a novel bZIP protein, G/HBF-1, which binds to both the G-box and adjacent H-box in the proximal region of the chalcone synthase chs15 promoter. While G/HBF-1 transcript and protein levels do not increase during the induction of phenylpropanoid biosynthetic genes, G/HBF-1 is phosphorylated rapidly in elicited soybean cells, almost exclusively on serine residues. Using recombinant G/HBF-1 as a substrate, we identified a cytosolic protein-serine kinase that is rapidly and transiently stimulated in cells elicited with either glutathione or an avirulent strain of the soybean pathogen Pseudomonas syringae pv. glycinea. Phosphorylation of G/HBF-1 in vitro enhances binding to the chs15 promoter and we conclude that stimulation of G/HBF-1 kinase activity and G/HBF-1 phosphorylation are terminal events in a signal pathway for activation of early transcription-dependent plant defense responses.

Amino Acid Sequence

Retinoic acid receptor beta regulates growth and differentiation in human pancreatic carcinoma cells.

BACKGROUND & AIMS: Retinoic acid receptor beta (RAR beta) expression is lost or decreased during malignant transformation in human pancreatic adenocarcinoma. The aim of this study was to evaluate the role of RAR beta expression in the propagation of a malignant phenotype in human pancreatic carcinoma cells. METHODS: Overexpression of RAR beta in the human pancreatic carcinoma cell line DAN-G was achieved by selecting stable transfected cell clones. Genomic integration and expression were verified by Southern and Northern blotting and electrophoretic mobility shift assays. Growth was determined by cell number and xenografts transplanted into nude mice. Differentiation was examined by immunohistochemistry. RESULTS: Overexpression of RAR beta in DAN-G cells inhibited cellular proliferation in vitro and in vivo. Furthermore, RAR beta overexpression resulted in induction of cellular differentiation in xenografted tumors as evidenced by increased tumor cell expression of duct cell differentiation markers carcinoembryonic antigen (CEA), CA19-9, and cytokeratin 7. CONCLUSIONS: Decreased expression of RAR beta plays a key role in the maintenance of a malignant phenotype in human pancreatic adenocarcinoma and therefore represents a novel target for experimental strategies in the treatment of pancreatic cancer patients.

Animals

Retinoids inhibit adhesion to laminin in human pancreatic carcinoma cells via the alpha 6 beta 1-integrin receptor.

BACKGROUND & AIMS: The initial step in tumor invasion and metastasis is determined by adhesion of tumor cells to basement membranes. To evaluate their potential therapeutic use in controlling local growth and metastasis, the effects of retinoids on the adhesive properties in the human pancreatic carcinoma cell line DAN-G were examined. METHODS: The effects of retinoids on cellular adhesion were assessed by adhesion assays in vitro. The expression of laminin-binding proteins was characterized by Northern blotting, radioimmunoprecipitation, and flow-cytometric analysis. RESULTS: Treatment with retinoids results in a time- and dose-dependent inhibition of DAN-G cell adhesion to fibronection and laminin but not to collagens I, IV, and VI. The adhesion of DAN-G cells to laminin could be blocked completely by anti-alpha 6 and anti-beta 1 antibodies but not by the synthetic peptide YIGSR. Flow-cytometric analysis of DAN-G cells showed no quantitative difference for alpha 6-integrin expression in retinoid-treated and -untreated DAN-G cells. Furthermore, radioimmunoprecipitation showed no difference in the appearance of alpha 6 beta 1-integrin expression after retinoid incubation. CONCLUSIONS: Retinoids decrease pancreatic carcinoma cell adhesion to laminin via an as yet unidentified mechanism involving alteration of the alpha 6 beta 1-integrin receptor function and thereby open interesting perspectives for the modulation of infiltrative growth and metastasis in pancreatic cancer.

Animals

Dispersal behavior of adult snow melt mosquitoes in the Upper Rhine Valley, Germany.

The dispersal behavior of female snow melt mosquitoes was studied in two forests in Rhineland-Palatinate, Germany, from April to August 1993. Both CDC-light-traps and human bait collections were used to collect mosquitoes. Sampling sites were chosen along a west-east and a north-south transect in treated and untreated parts of a forest with a village in its center. Around this settlement, breeding sites within a radius of 1.5 to 2.5 km were treated. It could be shown that this buffer zone is sufficient to prevent a nuisance caused by snow melt mosquitoes in the village. The results lead to the conclusion that snow melt mosquitoes do not regularly migrate over large distances but stay near their breeding sites. In a detailed study of the behavior of Aedes rusticus, it could be observed that these mosquitoes were resting in the interior of the forest during daytime and leaving it with increasing dusk up to 50 m from the forest edge. A comparison of landing rate counts near a row of trees and in the open field showed higher activity near the row of trees indicating visual orientation of the mosquitoes. Although the Ae. rusticus females left the forest regularly, no nuisance occurred in nearby villages. The treatment of breeding sites near settlements appeared to be sufficient to prevent a nuisance caused by the snow melt mosquitoes.

Aedes

Brainstem connections of the macula lagenae in the chicken.

The macula lagenae, an otolithic hair-cell organ with probable vestibular function, lies close to the apical end of the avian auditory hair-cell epithelium, the papilla basilaris. In an earlier study in the pigeon in which lesioning techniques were used, Boord and Rasmussen ([1963] J. Comp. Neurol. 120:463-473) reported finding a projection of lagenar fibers to parts of the cochlear nuclei (nucleus magnocellularis and nucleus angularis). Subsequent to this report, it has been generally assumed that at least part of the cochlear nuclei has a vestibular or a combined vestibular-auditory function. In this study, we labeled fibers innervating the macula lagenae of the chicken by using a lipophilic fluorescent tracer. The analysis of Vibratome sections of the brainstem with epifluorescence illumination showed no projection to the cochlear nuclei. In cases in which the apical part of the papilla basilaris was contaminated with tracer, however, we found labeling of the cochlear nuclei in the same areas as described with the lesioning technique in the pigeon. Our results thus imply that there is no processing of information from the macula lagenae in the cochlear nucleus of the chicken. In addition, we studied the origin of the few labeled efferent neurons in the brainstem. The location of all somata encountered was restricted to an area medial to the nucleus facialis dorsalis and corresponded to the dorsal efferent cell group, from which efferents to other vestibular organs also originate.

Afferent Pathways

Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes.

BACKGROUND: The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood. AIM: To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines. METHODS: The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies. RESULTS: Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2. CONCLUSION: Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.

Blotting, Western

Edema and intrapancreatic trypsinogen activation precede glutathione depletion during caerulein pancreatitis.

Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the presence of activated digestive enzymes within the pancreas. The secretagogue-induced model of acute pancreatitis is also characterized by pancreatic acinar cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall in pancreatic glutathione levels. We have performed time-dependence studies to determine the sequence with which these phenomena appear and to establish their cause-and-effect relationship. Evidence of lysosomal enzyme redistribution and trypsinogen activation within the pancreas could be detected within 10-15 min of the onset of supramaximal secretagogue stimulation, while hyperamylasemia (30 min), pancreatic edema (60 min), and acinar cell vacuolation (60 min) occurred at later times. Pancreatic glutathione levels were either unchanged (15 and 30 min) or elevated (60 min) during the early times of supramaximal stimulation and were only noted to be decreased at a later time. These results support the conclusion that intrapancreatic digestive enzyme activation, possibly occurring by a mechanism involving lysosomal hydrolase redistribution, is an early and likely a critical event in the evolution of secretagogue-induced pancreatitis but that glutathione depletion is neither early nor critical to the evolution of this model of pancreatitis.

Amylases

Glucocorticoid receptor concentration modulates glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.

In this study we investigated the effects of altered intracellular glucocorticoid receptor (GR) concentrations on glucocorticoid-regulated gene expression in the rat pancreatic acinar cell line AR42J. Incubation of AR42J cells with dexamethasone results in a time-dependent transcriptional stimulation of amylase gene expression (about 5-fold) and a transcriptional inhibition of bombesin receptor (BR) gene expression. Decreasing the intracellular GR concentration to 50% by preincubation with RU 38486 results in a significant attenuation of dexamethasone-regulated amylase and BR gene expression. In contrast, increasing the intracellular GR concentration 2-fold by preincubation with the phosphodiesterase inhibitor IBMX significantly enhances the glucocorticoid inhibition of BR gene expression whereas amylase mRNA concentrations remain unaltered. These data demonstrate that intracellular GR concentrations determine the sensitivity of glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.

1-Methyl-3-isobutylxanthine

Differential growth regulation by all-trans retinoic acid is determined by protein kinase C alpha in human pancreatic carcinoma cells.

We have investigated the role of protein kinase C (PKC) isoenzymes in the differential growth regulation of human pancreatic carcinoma cell lines by all-trans retinoic acid (RA). RA treatment results in dose-dependent stimulation of anchorage-independent growth in AsPc1 cells and growth inhibition in Capan 2 cells. Both cell lines express an identical pattern of nuclear RA and retinoid X receptors as determined by RT-PCR. Western blotting using monospecific antibodies revealed that both cell lines express PKC isoenzymes alpha and zeta, whereas beta, gamma, delta, and epsilon were not detected. Incubation with RA in the growth-stimulated AsPc1 cell line resulted in induction of PKC alpha expression, whereas PKC alpha expression was decreased by RA in the growth-inhibited Capan 2 cell line. In contrast, PKC zeta expression was not affected by RA in either cell line. Incubation of AsPc1 cells with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate resulted in a time- and dose-dependent selective down-regulation of PKC alpha but not zeta. The dose-dependent decrease of intracellular PKC alpha concentration correlated well with the anchorage-independent growth rate of AsPc1 cells. Furthermore, selective down-regulation of PKC alpha blocks subsequent growth stimulation by RA in AsPc1 cells. When PKC alpha concentration was decreased by stably transfecting AsPc1 cells with a PKC alpha complementary DNA antisense construct, RA-stimulated growth could also be partially blocked. These data, therefore, suggest that differential regulation of PKC alpha expression plays a central role in determining the bidirectional effects of RA on growth in pancreatic carcinoma cells.

Base Sequence

[The significance of lymph- and hemangiosis carcinomatosa in colorectal carcinoma].

Between 1.1.1988 and 31.12.1989 306 patients underwent curative surgery for colorectal cancer at the surgical center of Nurnberg City hospital. The pathohistological findings showed that a carcinomatous lymphangiosis and hemangiosis (LH+) was present in 57 (18.6%) cases. The rate of metachronic metastases of the liver was significantly higher (38.2% vs. 19.6% p < 0.001) compared to patients without lymphangiosis and hemangiosis (LH-). There were also significant differences between the survival rates (5-year survival rate 50% vs. 63% p < 0.02). Analysing the lymph node stage and LH+ situation it was found that carcinomatous lymphangiosis and hemangiosis were already present in 7.2% of patients who didn't have tumorous infiltration of the lymph nodes (p NO/LH+). The 5-year survival rate was bad in both groups (54% vs. 49%).

Aged

[Alcohol and myocarditis].

The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic findings in endomyocardial biopsy in about 30% of all cases was myocarditis with a lymphocytic infiltrate in association with myocyte degeneration or focal necrosis. In myocarditis, the network of microtubules and intermediate filaments is also disrupted by the inflammatory reaction which involves resident cells (myocytes, fibroblasts, endothel cells) and systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. After all, in patients with alcohol abuse and myocarditis the immune functioning appears to be compromised. Several studies suggest that heavy drinking alters both lymphocyte and granulocyte production and function. Alcohol consumption per se might harm the immune system. Furthermore, the myocardial damage due to alcohol consumption could initiate autoreactive mechanisms comparable to those in viral or idiopathic myocarditis. Patients with alcohol abuse and myocarditis have a poor prognosis: signs of biventricular failure including tachycardia, hepatomegaly, and peripheral and lung edema are observed. These symptoms are as nonspecific as are various echocardiographic and electrocardiographic changes such as atrial and ventricular arrhythmias which may be associated both with myocarditis, alcoholic cardiomyopathy and acute effects of drinking without hemodynamic alterations. For the management of patients with alcohol abuse the prevention of further alcohol intake is mandatory to reverse the myocardial damage and the unfavorable predisposition for infection. Specific treatment of myocarditis is the second important option, and treatment of heart failure by reducing the size of the dilated heart and alleviating the signs and symptoms of heart failure is a logical third step.

Acetaldehyde

Northrhine Westphalian data on the locus F13B.

A population study was carried out on 301 ethnic Germans from Düsseldorf (Northrhine Westphalia) using the short tandem repeat (STR) system HumF13B (Coagulation Factor XIIIB). Five different alleles were detected. No deviations from the Hardy-Weinberg equilibrium could be observed. In spite of the successfulness of the system only a few population data exist. A pooled sample from Northrhine Westphalia has to be used as preliminary database for forensic and anthropological purposes.

Alleles

The potential for malaria control with the biological larvicide Bacillus thuringiensis israelensis (Bti) in Peru and Ecuador.

A study on the efficacy of Bti spraying in mosquito breeding places was undertaken in the Pacific coast of Peru and Ecuador and in the Amazon area of Peru. It was shown that Bti is a powerful larvicide for Anopheles larvae, although it sinks quickly, whereas Anopheles larvae feed at the water surface. The duration of its effect was less than 7 days with the exception of the Amazon area of Peru, where it was approximately 10 days. In two study areas, Bti was sprayed weekly over periods of 10 and 7 weeks, respectively, and the adult mosquito densities were monitored. The Anopheles adult density (bites per person per hour on human baits) was reduced by an average of 70% in one area and by up to 50% in the other. This means that Bti spraying can potentially be an important component of a modified malaria control strategy.

Animals

Retinoids: effects on growth, differentiation, and nuclear receptor expression in human pancreatic carcinoma cell lines.

BACKGROUND & AIMS: Advanced pancreatic carcinoma has a dismal prognosis despite extensive chemotherapeutic trials. The aim of this study was to evaluate the role of retinoids as an experimental therapeutic approach for pancreatic cancer. METHODS: Four ductal and one acinar pancreatic tumor cell lines were investigated. Growth was determined by cell number and a human tumor clonogenic assay. In vivo growth was assessed by xenografts transplanted into nude mice. Differentiation was characterized by immunofluorescence microscopy and carbonic anhydrase II gene expression. Retinoid receptors were characterized by Northern blotting and reverse-transcriptase polymerase chain reaction. RESULTS: Retinoid treatment results in a time- and dose-dependent growth inhibition in vitro and in vivo of ductal but not acinar pancreatic tumor cells. Retinoid treatment induces a more differentiated phenotype in ductal tumor cells as shown by morphological criteria and increased expression of carbonic anhydrase II. All pancreatic tumor cell lines expressed a broad panel of cellular retinoid binding proteins and nuclear retinoid receptors. Retinoic acid receptor gamma and cellular retinoic acid binding protein II were found in all retinoid-sensitive ductal tumor cell lines but not in the retinoid-resistant acinar cell lines. CONCLUSIONS: Detailed knowledge of nuclear retinoid receptor expression may provide rational strategies for retinoid treatment of pancreatic cancer.

Animals

Biochemical and morphological changes that characterise recovery from necrotising biliary pancreatitis in the opossum.

The events that characterise recovery from severe biliary pancreatitis have not been defined. This study used a reversible model of necrotising pancreatitis, induced by obstructing the opossum common bile pancreatic duct (CBPD), to evaluate this phenomenon. The CBPD of opossums was obstructed with a balloon tipped catheter for five days and then decompressed by removal of the catheter. Recovery was evaluated 0-90 days after relief of obstruction. Serum bilirubin and amylase values rapidly declined, reaching control values 7-14 days after removal of the obstructing catheter. Pancreatic protein and amylase values were transiently increased shortly after relief of obstruction but returned to control values 21 days after decompression. Pancreatic ornithine decarboxylase activity and incorporation of [3H]-thymidine into DNA were transiently increased 14 days after duct decompression suggesting that regeneration occurs at approximately that time. Foci of pancreatic necrosis involved roughly 40% of the gland at time of decompression but these foci gradually disappeared and the gland resembled that of control animals 60 days after decompression. Evidence of fibrosis or collagen deposition in the pancreas was not noted at any time. These studies show that recovery after necrotising biliary pancreatitis occurs comparatively rapidly and the restitution ad integrum occurs. Recovery from necrotising acute pancreatitis in this model is not associated with the development of chronic pancreatitis.

Acute Disease

[Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials].

There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory of intraoperative events. Five patients in group I, one patient in group II, and no patients in group III showed implicit memory of the intraoperative tape message. They remembered Robinson Crusoe spontaneously when they were asked their associations with Friday. In the awake state AEP peak latencies were in the normal range. During general anaesthesia in group I, the peaks Na, Pa did not increase in latency or decrease in amplitude before and after the audiotape presentation. The primary cortical complex Na/Pa could be identified as in the awake state. In contrast, in group II Na, Pa showed a marked increase in latency and a decrease in amplitude or were completely suppressed. CONCLUSIONS. During general anaesthesia auditory information can be processed and remembered postoperatively by an implicit memory function, when the electrophysiological conditions of primary cortical stimuli processing is preserved. Implicit memory can be observed more often when high-dose opioid analgesia is combined with receptor-binding agents like the benzodiazepines than under non-specific anaesthetics like isoflurane. Non-specific anaesthetics seem to provide a more effective suppression of auditory stimuli processing than receptor-specific agents.

Adult