[Therapy of spontaneous esophageal perforation].
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Adult↗
Biomedical subjects
G Becker
Publications and source records attributed to G Becker.
Influence of microvascular adherence on neutrophil leukotriene generation. Evidence for cooperative eicosanoid synthesis.
Profile and quantity of leukotriene (LT) and hydroxyeicosatetraenoic acid (HETE) generation upon selective stimulation of isolated polymorphonuclear neutrophils (PMN) compared with neutrophils in a model of pulmonary leukostasis were investigated. Freshly prepared human PMN (2 x 10(8) were injected into the pulmonary artery of isolated, ventilated, and bloodfree perfused rabbit lungs, resulting in nearly quantitative sticking in the microvasculature. The sequestered neutrophils and, in parallel, aliquots of isolated PMN were stimulated with mAb in the presence of C, known to activate PMN arachidonate metabolism via formation of membrane attack complexes. In the isolated cells, a typical LT profile including LTB4 and its omega-oxidation products, 5-HETE and nonenzymatic hydrolysis products of LTA4 was evoked. The latter indicate secretion of LTA4 in considerable amounts. In the model of pulmonary leukostasis, no nonenzymatic LTA4-derivatives were detected, coincident with a predominance of cysteinyl-LT. This finding gives indirect evidence for an efficient LTA4-transfer between PMN feeder cells and vascular acceptor cells with glutathione-S-transferase activity. Moreover, a threefold increase in the total amount of LTA4-derived products was noted in the model of leukostasis, paralleled by a marked decrease in 5-HETE liberation. This effect was further enhanced by inhibition of lung cyclooxygenase. These findings were corroborated in a homologous system, in which rabbit PMN, sticking in the rabbit lung microvasculature, were stimulated with calcium-ionophore A23187. Collectively, these data suggest a complex interaction between microvascular tissue and adhering neutrophils in LT synthesis, involving transcellular LTA4-shift, modulation of the PMN 5-lipoxygenase pathway, and amplification of LT generation. These findings may be relevant for inflammatory events with neutrophils involved.
Animals↗
Plasma exchange in progressive IgA nephropathy.
A therapeutic trial of plasma exchange was performed in 13 patients with documented progressive IgA nephropathy. Comparison of the rate of deterioration in renal function before, during, and after plasma exchange demonstrated significant improvement during plasma exchange. Seven patients had a slowed rate of deterioration by plasma exchange, but achieved a decrease in serum creatinine level. Favourable response was correlated with rapidity of deterioration preplasma exchange (P less than 0.01) and was apparent within 4 weeks of commencing therapy in those patients who responded. There was no overall difference between the deterioration rates pre- and postplasma exchange. In patients in whom creatinine decreased on plasma exchange, the initiation of subsequent dialysis was delayed.
Adolescent↗
Mafosfamide induces less sister chromatid exchange in Ph-positive cells than in normal bone marrow.
The frequency of induced sister chromatid exchange (SCE) is a sensitive tool for the monitoring of DNA damage and has been shown to indicate chemotherapy resistance. Mafosfamide is presently used for the purging of bone marrow in autologous bone marrow transplantation in the treatment of acute leukemia. We studied the SCE-inducing effect of mafosfamide on leukemic cells of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) as a model for leukemic cells. Corresponding data from normal bone marrow were analyzed for comparison. A positive linear correlation (r = 0.99, P = 0.0005) was found between the dose of mafosfamide and induced SCE in Ph-positive CML and normal bone marrow. The concentration of mafosfamide used was 0.1, 0.2, 0.4, and 0.8 micrograms/ml. Additionally, we analyzed five cases of CML and six cases of normal bone marrow. A significant difference in the frequency of induced SCE/metaphase was found between CML and normal bone marrow even after addition of 0.8 micrograms/ml mafosfamide. Also, spontaneous SCE was significantly lower in CML. Our data indicate a lower sensitivity of the leukemic cells to mafosfamide as shown by the induction of a lower frequency of SCE events.
Bone Marrow↗
Transcranial color-coded real-time sonography in adults.
We investigated the diagnostic potential of transcranial color-coded real-time sonography in 52 individuals using a phased-array ultrasound system with color-coded blood flow representation. Ultrasound scans in the axial and coronal planes were feasible through temporal acoustic bone windows in 49 subjects, enabling depiction of the main parenchymal and vascular structures as well as the ventricular system. Color-coded representation of blood flow in the cerebral vessels allowed unequivocal identification of the circle of Willis within the anatomic black-and-white B-mode image of the parenchymal structures. In Doppler mode, vascular blood flow phenomena may be analyzed semiquantitatively using the Doppler frequency spectrum. This noninvasive, serially applicable, mobile beside method may complement conventional neuroradiologic imaging methods, allowing on-line studies of functional processes within the adult brain.
Carotid Arteries↗
Genetic and molecular analysis of six tumor suppressor genes in Drosophila melanogaster.
Six Drosophila melanogaster tumor suppressor genes causing malignant or benign tumors in specific cell types are described. The wild-type alleles of these genes are instrumental in the differentiation of particular cell types. In the homozygous state, recessive mutations in the genes interrupt the differentiation of the cells and thus cause their uncontrolled, autonomous, lethal proliferation. The tumors show all major characteristics of malignant and benign neoplastic growth. Genomic sequences of four of the genes have been identified and are currently being characterized.
Animals↗
Modulation by oxygen of the actions of noradrenaline, sympathetic nerve stimulation and prostaglandin F2 alpha on carbohydrate metabolism and hemodynamics in perfused rat liver.
Rat liver was perfused in situ via the portal vein without recirculation of the perfusate. The perfusion medium contained 5mM glucose, 2mM lactate and 0.2mM pyruvate, and it was equilibrated with different oxygen concentrations so as to vary the rate of oxygen delivery from 4 (normal) to either 12 or 0 mumol x min-1 x g-1 (U/g). 1) Basal glucose and lactate output were clearly increased, when oxygen delivery and therefore uptake were decreased from 4 to 2 and 0 U/g. 2) Noradrenaline caused a marked increase in the output of glucose and lactate and a slight increase in oxygen uptake; it also decreased the rate of flow of the perfusate. Decrease of the oxygen supply did not affect this alteration in the glucose and lactate balance, but it abolished the increase in oxygen uptake and decreased the magnitude of the effect on the perfusion rate. 3) Sympathetic nerve stimulation strongly increased glucose and lactate output and clearly reduced oxygen uptake and perfusate flow. Decreased oxygen delivery caused a decrease in the magnitude of all these changes. 4) Prostaglandin F2 alpha increased glucose and lactate release and decreased perfusate flow. Decrease of the oxygen supply did not affect the increased glucose and lactate release, but it decreased the magnitude of the effect on the perfusion rate. These results lead to the following major conclusions. Oxygen strongly regulates basal carbohydrate metabolism, while it does not affect the metabolic actions of noradrenaline and prostaglandin F2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Peritoneal calcification in a peritoneal dialysis patient: a case report.
A case of peritoneal calcification in a 44-year-old female treated with peritoneal dialysis for 13 years is reported. The patient, who had secondary hyperparathyroidism and had suffered repeated episodes of catheter-related peritonitis, presented with intraperitoneal bleeding and underwent laparotomy and excision of some of the calcified peritoneal plaques. She remains well on peritoneal dialysis 1 year later with occasional mild intraperitoneal bleeding and reduced peritoneal filtration.
Adult↗
Multiple indicators of side preference in the rat.
This study tested the hypothesis that a general factor underlies a number of measures of side preference in the rat. The results support such a latent variable, but one with correlated errors, that accounts for the intercorrelations among four of the prospective indicators of side preference. It was suggested that multiple indicators be used to represent the construct of side preference in the rat to avoid problems associated with the presence of method and error variance found in single indicators.
Animals↗
Entrainment of anticipatory activity to various durations of food access.
Rats with lesions of the suprachiasmatic nuclei (SCN) and intact rats were maintained on restricted feeding with the duration of food access ranging from 4 to 12 hr. All rats with SCN lesions displayed at least some anticipatory activity (AA) at all food access durations. The amount of AA diminished when food access was extended to 12 hr and was lowest in a group that was exposed only to a 10-hr access period. The onset of AA (phase angle of entrainment) appeared to be more sensitive to the time of food availability than to its termination. Most intact rats maintained in constant light displayed some AA at food access durations between 4 and 10 hr. In most cases the period of the free running rhythm increased as it crossed food access and the free running rhythm became increasingly disrupted as the experiment progressed in all rats. In some cases the free running rhythm appeared to force AA out of entrainment. These results demonstrate that AA occurs in conditions that impose only minor deficits on the energy balance of rats. Furthermore, they provide additional evidence of interactions between two separate circadian pacemaking systems.
Animals↗
Effect of chronic dietary ethanol consumption on the initiation and promotion of chemically-induced esophageal carcinogenesis in experimental rats.
Preliminary dose finding studies showed that 22 mg/kg of N-nitrosomethylbenzylamine (NMBZA) delivered over 5 days did not induce esophageal lesions, but 18 mg/kg administered over a period of 2 or 3 weeks did induce these lesions. Based on these results, Sprague-Dawley rats were treated with 2.5 mg/kg NMBZA three times a week for 3 weeks to initiate esophageal carcinogenesis. The experimental animals were administered isocaloric ethanol diet either before and during NMBZA initiated carcinogenesis, or after initiation as a tumor promoter. The esophagi of rats that died or who were terminated at 18 months of age were examined for nodules and tumors. When ethanol was administered before and during initiation, the mean frequency of esophageal lesions was 8.04 +/- 3.04/rat with an average size of 1.44 +/- 0.27 mm versus 12.41 +/- 2.12/rat and 0.92 +/- 0.17 mm respectively for the controls. Only three out of 13 of the ethanol-fed rats had tumors (mainly squamous papillomas) versus 10 out of 26 of the control-fed animals. Ethanol consumption before and during initiation, therefore, decreased the incidence of esophageal nodules and tumors. With ethanol administered as a promoter, on the other hand, while incidence of the total lesions was not affected appreciably, the incidence of tumors was remarkably increased. With ethanol promotion the mean frequency of lesions was 8.75 +/- 1.07/rat with an average size of 1.02 +/- 0.09 mm versus 10.94 +/- 1.49/rat and 1.32 +/- 0.13 mm respectively for the controls. In this case, the ethanol-consuming rats had tumors in 14 out of 75 animals versus one small tumor in 32 of the controls. The results indicate that the occurrence of esophageal tumors is inhibited by simultaneous ethanol administration, but promoted when ethanol is administered post-initiation ostensibly by allowing extensive dysplastic proliferation of the carcinogen-induced lesions.
Animals↗
Synthesis of thiol-functionalized N-acetylmuramyl peptide congeners suitable for their conjugation to target molecules.
N-Acetylmuramyl-dipeptide and tripeptide derivatives containing at the C-terminus a masked thiol function, i.e. the S-tert-butylthiocysteamine residue, were synthesized via direct condensation of N-acetylmuramic acid with the peptide moiety using the dicyclohexylcarbodiimide/N-hydroxysuccinimide procedure. Reduction with tributylphosphine in aqueous organic media generates the free thiol function for a selective conjugation of these immunomodulants with target molecules via unsymmetrical disulfide bridging with a second thiol group by the sulfenohydrazide procedure or via thio-ether linkage by the addition to maleimido--or aziridine-derivatives.
Acetylmuramyl-Alanyl-Isoglutamine↗
[Recording movement traces in field studies].
A method is presented for the simultaneous recording of body movements in space and electrophysiological data in field studies in order to obtain criteria for the evaluation of muscular and mental effort, with the aim of improving the design of workplaces--here exemplified the driver's cab of a railway engine. Eight light-emitting diodes were attached to certain parts of the body and their positions recorded by means of a video system. The positions of the diodes were computed off-line with the aid of image-processing system. In comparison with the resolution of the video camera the accuracy of determining the coordinates of a diode can clearly be improved by computing the center of its imaged bright area. In combination with recordings of the eye movements and the railway track by means of an extra video camera, evaluation of the movement traces permits a differentiated study of specific movements and actions.
Arousal↗
Specific antibody response towards predicted epitopes of the epidermal growth factor receptor induced by a thermostable synthetic peptide adjuvant conjugate.
Applying computer-assisted epitope prediction to the amino-acid sequence of the epidermal growth factor receptor (EGFR), the extracytoplasmic domain EGFR(516-529) was selected as a putative antigenic region. EGFR(516-529) was synthesized on a solid-phase matrix and N-terminally linked to the low mol. wt adjuvant tripalmitoyl-S-glyceryl-cysteinyl-serine (Pam3 Cys-Ser). The conjugation to this B cell and macrophage-activating lipopeptide considerably enhanced the immunogenicity of the EGFR peptide. Using the conjugate Pam3 Cys-Ser-EGFR(516-529), a peptide-specific monoclonal antibody was produced. By flow cytometry and immunoprecipitation the antibody was demonstrated to recognize EGFR on A431 cells, expressing large numbers of EGFR. With this novel approach synthetic immunogens can be prepared which could serve as thermostable synthetic vaccines with great potential in countries where a functional cold chain cannot be maintained.
Adjuvants, Immunologic↗
Limb salvage in high-risk patients with multisegmental disease.
Is percutaneous iliac angioplasty before distal bypass a logical limb salvage option in a high-risk patient? A retrospective review of 113 iliac angioplasty procedures identified 10 patients in this situation. Angioplasty preceded femoropopliteal bypass (five), femorotibial bypass (three) and, in one case each, femorofemoral bypass or profundoplasty. There were no interventional deaths or complications. Ankle/brachial pressure index improvement followed intervention: 0.28 + 0.2 vs. 0.92 + 0.08, (p less than 0.0005). Limb salvage was 90% at one month, 80% at six months and 70% at one to three years by Life-Table analysis. Two patients with a patent bypass lost limbs from uncontrolled infection within two months. One patient required an amputation 311 days after the only failure of angioplasty and distal bypass. During this study period, 56% of the patients died. This review supports an angioplasty/bypass combined intervention as a valuable treatment option in high-risk patients facing limb loss.
Aged↗
Studies on long-acting aryl carboxylic acid esters of testosterone.
A series of aryl carboxylic acid esters of testosterone have been synthesized as possible agents for long-acting steroid therapy. The solubilities, partition coefficients and hydrolysis rate constants of the compounds have been determined. The results show that the partition coefficients increase with increasing chain length and are in keeping with calculated values. The hydrolysis rates decrease with increasing chain length except for the first member of the series (benzoate ester) which exhibits the slowest rate, possibly due to the hydrolytic attack being hindered by steric and electronic effects.
Carboxylic Acids↗
High yield enzymatic conversion of intravascular leukotriene A4 in blood-free perfused lungs.
Experiments to investigate the fate of intravascularly administered leukotriene (LT) A4, an unstable intermediate of LT generation, were performed in isolated, ventilated, and blood-free perfused rabbit lungs. LT extracted from the lung effluent were separated by different reverse phase and straight phase HPLC procedures as methylated and nonmethylated compounds. Identity of eluting LT was confirmed by UV spectrum analysis and immunoreactivity. Pulmonary artery injection of 75 to 300 nmol of LTA4 resulted in the rapid appearance of cysteinyl-LT as well as LTB4 in the recirculating perfusate. The yield of these enzymatically generated LTA4 metabolites vs non-enzymatic hydrolysis products (6-trans-LTB4, 5-trans-epi-LTB4, 5,6-dihydroxyeicosatetraenoic acids) ranged above 90%. Experiments with application of tritiated LTA4 showed exclusive origin of the detected LT from the exogenously applied precursor. The time course of cysteinyl-LT appearance in the perfusate suggested metabolism of LTC4 via LTD4 to LTE4, whereas there was no evidence for LTB4 omega-oxidation. In the dose range of LTA4 used, the enzymatic conversion of this LT precursor did not approach saturation. Collectively, these data indicate that the intact pulmonary vasculature contains a hitherto not described capacity for enzymatic conversion of intravascularly offered LTA4 to both cysteinyl-LT and LTB4. This may be of biological significance for a putative transcellular biosynthesis of LT in the pulmonary microcirculation upon contact with LTA4 feeder cells, such as activated granulocytes.
Animals↗