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H Hecker

Publications and source records attributed to H Hecker.

At least 91 records · Page 5Linked to original sources
PubMed1992

Structural differences between the chromatin of procyclic Trypanosoma brucei brucei and of higher eukaryotes as probed by immobilized trypsin.

Soluble chromatin of Trypanosoma brucei brucei procyclic culture forms was submitted to digestion with free or immobilized trypsin. Digestion with trypsin in salt solutions of low and high ionic strengths generated characteristic sets of limit histone peptides. After incubation of chromatin with immobilized trypsin in a solution of low ionic strength, histones were not degraded, whereas a selective proteolysis occurred at 50 mM NaCl. Histones a and d, which correspond to H3 and H4 of higher eukaryotes, were rapidly attacked. Histones b and c, the counterparts of H2A and H2B, were more resistant. The results indicated that probably the basic N-terminal tails of the proteins a and d are located on the surface of the core particle. The location of d on the surface differs from the internal one proposed for histone H4. The salt-induced increase of susceptibility of histones to proteolysis reflects structural changes of T.b. brucei chromatin, which may result in partial chromatin compaction.

Animals↗
PubMed1992

Sequence differences between histones of procyclic Trypanosoma brucei brucei and higher eukaryotes.

Four histones, a, b, c, d from procyclic Trypanosoma brucei brucei, which show similarities with the amino acid composition of the core histones H3, H2A, H2B and H4, were isolated and cleaved with Endoproteinase Glu-C. The fragments were separated by FPLC reversed phase chromatography and a subset of the fragments (a5, a9, b6, c8, d3, d9, d11) was subjected to sequence analysis. A 54-71% identity was found in the sequences of the fragment c8 and the C-terminal half of H2B and of three fragments of protein d covering the N-terminal half as well as the C-terminal region of H4. The amino acid sequence of the fragment a9 showed a 57 and 54% identity with H3 sequences of Saccharomyces cerevisiae and Xenopus laevis. Neither the a5 nor the b6 sequence could be aligned with histone sequences of other eukaryotes. The significant differences of 21-48% between the T.b. brucei histone sequences and those of calf thymus histones, which are more pronounced than the differences of Tetrahymena pyriformis and the higher eukaryote, resulted partially from replacements of amino acids with different properties and indicate specific patterns of histone-histone and/or histone-DNA contact sites in the nucleosome of T.b. brucei. These differences, together with the lack of a functional histone H1, may be sufficient to explain the lack of a salt-dependent formation of the nucleosome filament into the 30 nm fibre, which reflects alternative methods of organizing and processing the genetic information in the nucleus of the protozoan parasite and which may be of chemotherapeutic significance.

Amino Acid Sequence↗
PubMed1991

Biochemical properties of histone-like proteins of procyclic Trypanosoma brucei brucei.

Four histone-like proteins a, b, c, d were extracted with 0.2 M H2SO4 from soluble nuclear chromatin of Trypanosoma brucei brucei procyclic culture forms and purified by FPLC reversed phase chromatography. The amino acid composition of these proteins and their electrophoretic mobilities in three different gel systems strongly indicated their core histone nature. Similarities were found between a, b, c and d with the core histones H3, H2A, H2B and H4 of higher eukaryotes, respectively. On the other hand, these proteins also showed differences as compared to higher eukaryotes; proteins a and d clearly differed from their counterparts H3 and H4 on the basis of their hydrophobic properties. The results indicate the occurrence of core histone variants in T.b. brucei which may influence DNA-histone and histone-histone interactions as well as the chromatin compaction in the nucleus of this protozoan parasite.

Amino Acids↗
PubMed1991

Surface coat synthesis and turnover from epimastigote to bloodstream forms of Trypanosoma brucei.

Monoclonal antibodies to metacyclic surface coat glycoproteins of Trypanosoma brucei brucei STIB 247LG were produced for a study of the synthesis of metacyclic variable surface glycoproteins (VSGs) within the salivary gland of Glossina morsitans morsitans, and of the first exchange of the surface glycoproteins after infection in mice. Immunofluorescence antibody tests and protein A-gold labelling revealed that the VSGs are continuously integrated into the whole surface of the trypanosome while it is still attached to the gland epithelium. A pool of 8 antibodies recognized about 50% of the metacyclic forms present in the saliva of an infected tsetse fly, which confirmed the heterogeneity of the metacyclic VSG-generation. The labelling experiments showed that the integration of the first VSG-generation into the surface of bloodstream forms takes place in the same way as in the metacyclics. This process started on day 3 after infection and was finished on day 6.

Animals↗
PubMed1991

Blood digestion in the mosquito, Anopheles stephensi Liston (Diptera: Culicidae): activity and distribution of trypsin, aminopeptidase, and alpha-glucosidase in the midgut.

The activities of trypsin, aminopeptidase, and alpha-glucosidase were studied in the whole midgut, anterior and posterior midgut, and posterior midgut lumen and epithelium of the mosquito Anopheles stephensi Liston. Trypsin activity was restricted entirely to the posterior midgut lumen. No trypsin activity was found before the blood meal, but activity increased continuously up to 30 h after feeding, and subsequently returned to baseline levels by 60 h. Aminopeptidase was active in anterior and posterior midgut regions before and after feeding. In whole midguts, activity rose from a baseline of approximately 3 enzyme units (EU) per midgut to a maximum of 12 EU at 30 h after the blood meal, subsequently falling to baseline levels by 60 h. A similar cycle of activity was observed in the posterior midgut and posterior midgut lumen, whereas aminopeptidase in the posterior midgut epithelium decreased in activity during digestion. Aminopeptidase in the anterior midgut was maintained at a constant low level, showing no significant variation with time after feeding. alpha-glucosidase was active in anterior and posterior midguts before and at all times after feeding. In whole midgut homogenates, alpha-glucosidase activity increased slowly up to 18 h after the blood meal, then rose rapidly to a maximum at 30 h after the blood meal, whereas the subsequent decline in activity was less predictable. All posterior midgut activity was restricted to the posterior midgut lumen. Depending upon the time after feeding, greater than 25% of the total midgut activity of alpha-glucosidase was located in the anterior midgut. The enzyme distributions are consistent with described structural models for digestion in mosquitoes. After blood meal ingestion, proteases are active only in the posterior midgut. Trypsin is the major primary hydrolytic protease and is secreted into the posterior midgut lumen without activation in the posterior midgut epithelium. Aminopeptidase activity is also luminal in the posterior midgut, but cellular aminopeptidases are required for peptide processing in both anterior and posterior midguts. alpha-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in the anterior midgut is consistent with a nectar-processing role for this midgut region.

Aminopeptidases↗
PubMed1991

Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.

BACKGROUND: It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS: Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION: Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis.

Antithrombin III↗
PubMed1990

Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). INTACT Group Investigators.

425 patients showing mild coronary artery disease (CAD) on arteriography were enrolled in a multicentre trial and randomised to treatment with nifedipine (80 mg/day) or placebo. The two groups were well matched for age, sex, and risk factors. 348 patients (82%) underwent repeat arteriography 3 years later; 282 (134 nifedipine, 148 placebo) had received treatment throughout, but treatment had been stopped in 39 nifedipine-treated and 27 placebo-treated patients after average periods of 354 and 467 days. Computer-assisted measurements of arteriograms from all restudied patients (175 placebo, 173 nifedipine) showed no significant differences in the number or severity of lesions on initial arteriograms, or in the progression or regression of existing lesions over 3 years. In contrast, the number of new lesions per patient was significantly lower in the nifedipine group than in the placebo group (0.59 vs 0.82 lesions per patient, a 28% reduction). Thus in patients with mild CAD nifedipine substantially suppresses disease progression as shown by the appearance of new lesions detectable by quantitative coronary arteriography.

Administration, Oral↗
PubMed1990

Reproducible uniform coronary vasomotor tone with nitrocompounds: prerequisite of quantitative coronary angiographic trials.

In quantitative analysis of repeated coronary angiograms, a variable vasomotor tone of the epicardial coronary arteries may influence the accuracy of the results. Therefore, we evaluated the extent and reproducibility of coronary artery dilation with nitrocompounds. In 32 patients with coronary artery disease, the vasodilatory response of angiographically normal coronary segments to different nitrocompounds was analyzed with the computer-assisted contour detection system CAAS. Twenty patients received 5 mg or 10 mg of isosorbide dinitrate sublingually. After 10 to 15 min, a maximal diameter increase was measured with an average of 16 +/- 11% (5 mg: P less than 0.01) and 28 +/- 13% (10 mg: P less than 0.001) from control. Another 12 patients received 0.025 mg per kg body weight of SIN-1, the active metabolite of molsidomine, as an intravenous infusion over 5 min. A comparable maximal dilation (29 +/- 5%; P less than 0.001) occurred after 10 to 15 min and could not be enhanced further with 0.8 mg nitroglycerin administered sublingually (28 +/- 7%; n.s.). One hour after square root of Sin-1, coronary dilation was still 24 +/- 8% (P less than 0.001 compared with control), and 0.8 mg of nitroglycerin sublingually reestablished the previous maximal dilation of 28 +/- 8%. We conclude that high doses of nitrocompounds induce a reproducible maximal coronary dilation that eliminates a substantial source of error in quantitative analysis of repeated coronary angiograms. At present, sublingual administrations of either 10 mg isosorbide dinitrate once or 0.8 mg nitroglycerin repeatedly seem to represent the easiest practicable modes to achieve maximal coronary vasodilation for an adequate period.

Angiography↗
PubMed1990

Development and interactions of Trypanosoma rangeli in and with the reduviid bug Rhodnius prolixus.

Two strains of Trypanosoma rangeli and three strains of Rhodnius prolixus were used in various combinations to transmit the trypanosomes via the reduviid bug. A persisting infection in the midgut lumen posterior to the stomach resulted in all 2,500 bugs being third and fourth instars. Infectious, metacyclic forms developed exclusively in the salivary glands; forms excreted with bug feces were noninfectious to mice. The midgut epithelium was the main barrier to transmission of the parasite. In only 2%-5% of the infected bugs was it penetrated, and no correlation with any parameter tested could be found. The trypanosomes passed through the gut epithelium by an intracellular route; they were contained in a parasitophorous vacuole. The salivary glands of R. prolixus were found to be infected whenever the hemolymph was infected, after a successful penetration of the gut epithelium, or after injection of T. rangeli. On the other hand, hemolymph infections in Triatoma infestans were eliminated within a few days, and the salivary glands of this bug were never invaded. Pathogenic effects of T. rangeli on R. prolixus could be seen in midgut epithelial cells by a loss of cytoplasm and in muscle and salivary gland cells by very high parasite densities. However, as the penetration rate of the gut is low, T. rangeli is not likely to prove to be efficient in natural control of R. prolixus.

Animals↗
PubMed1990

Elimination of variable vasomotor tone in studies with repeated quantitative coronary angiography.

In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +/- 4% (p less than 0.01; n = 11). In another 11 patients (study no. II) coronary angiograms were obtained using the nonionic contrast medium iopamidol 300 at 5, 8, 10 and 11 min after the control acquisition; this protocol was repeated in the same patients with diatrizoate 76%. With iopamidol, coronary diameter changes were not significant at any time; with diatrizoate, however, coronary dilation was measured at 10 min (2 +/- 2%; p less than 0.01) and at 11 min (10 +/- 3%; p less than 0.001). In a third study it was tested, whether standardization of coronary vasomotor tone (e.g. in coronary angiographic follow-up studies) is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds. In 12 patients, the mean diameters of angiographically normal coronary segments were analyzed before and at various times after i.v. administration (over 4 min) of 0.025 mg SIN-1/kg bodyweight. Coronary dilation was maximal at 10 or 15 min after the onset of the SIN-1-infusion (29 +/- 5%; p less than 0.001). 0.8 mg nitroglycerin given s.l. at 15 min did not further dilate the coronary arteries (28 +/- 7%). One hour after SIN-1, coronary dilation still amounted to an average of 24 +/- 8% (p less than 0.001) and became 'maximal' again, when 0.8 mg nitroglycerin was again administered sublingually (28 +/- 8%; p less than 0.001). In conclusion, short-term variability of coronary vasomotor tone induced by ionic radiographic contrast media can be eliminated by the use of nonionic contrast agents and observation of injection intervals of at least 2 min. In quantitative coronary angiographic follow-up studies, as well as during acute interventions (e.g., PTCA), identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds.

Adult↗
PubMed1990

Vasodilatory effects of nisoldipine on coronary arteries--correlation with plasma levels.

Vasomotion of angiographically normal and stenotic epicardial coronary arteries was analyzed up to 15 minutes after the onset of an intravenous infusion (4 minutes) of 0.5 mg (13 patients, group A) or 1 mg nisoldipine (13 patients, group B). After both doses the maximal increase of the mean diameters of normal coronary segments was achieved not before the 15th minute, averaging 11 +/- 6% in group A (p less than 0.001) and 18 +/- 9% in group B (p less than 0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5-80% and 15-70%, respectively. The nisoldipine concentration reached maximal levels at the end of the infusion (fourth minute) with an average of 8 +/- 4 ng/ml and 17 +/- 7 ng/ml in groups A and B, respectively. A significant correlation between nisoldipine plasma levels and dilation of normal coronary segments was obtained only with the individual maxima of these parameters and only in group A (p less than 0.01). The hysteresis of the coronary dilation in relation to the drug plasma levels may be due to the high receptor affinity of nisoldipine. In either group nisoldipine provoked a persistent increase in coronary sinus oxygen saturation (p less than 0.01) and a substantial and prolonged drop in systolic and diastolic aortic pressure (p less than 0.001). Both doses of nisoldipine induced a rise in heart rate (p less than 0.01) and a slight drop in the rate-pressure product (p less than 0.05).

Adult↗
PubMed1990

Features of the angiographic evaluation of the INTACT study. International Nifedipine Trial on Antiatherosclerotic Therapy.

INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy) is a prospective, placebo-controlled, randomized, double-blind, multicenter trial analyzing the influence of 80 mg nifedipine/day on the angiographic progression of early stage coronary atherosclerosis. Coronary angiograms were taken in identical projections before and after a treatment period of 3 years. Quantitative analysis of the angiograms was performed with the computer-assisted contour detection system CAAS. For definition purposes, the coronary artery system was subdivided into 25 different segments, including all anatomic variants. Measurement parameters of segments were mean and minimal diameter, and of stenoses minimal diameter, percentage diameter reduction (at least 20%), length, and plaque area. The variable extent of the changes of these parameters in the different projections analyzed per patient in the two study angiograms was considered by separate computation of the maximal, mean, and minimal changes over these projections; the comparison of the parameter changes between the two treatment groups was performed separately according to these three modes. For all parameters, this comparison was performed on the basis of the individual 25 segments, as well as after aggregation of individual segments to arteries (RCA, LAD, and LCX), to groups of large and small segments, and to the entire coronary artery system. Assessment of changes of the coronary (patho)morphology by quantitative analysis of coronary angiograms is associated with a number of methodical limitations, which may lead to a certain variability of the results. However, due to the double-blind feature of INTACT, this variability should be comparable in the two groups of this study, allowing for a conclusive comparison.

Angiography↗
PubMed1990

Retardation of coronary artery disease in humans by the calcium-channel blocker nifedipine: results of the INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy).

Experimental studies have demonstrated a 30-50% reduction in the development of atheromatous lesions of the aorta in rabbits fed a diet rich in cholesterol when they were treated with nifedipine. Based on these favorable results, we designed a multicenter, placebo (PL)-controlled, randomized, double-blind study, to test the effect of 80 mg nifedipine (NIF) per day versus placebo on the progression of mild coronary artery disease (CAD) (further development of existing stenoses, especially formation of new stenoses and occlusions) over a duration of 3 years. Progression of CAD was assessed by coronary angiograms performed at entrance and at completion of the study, using a computer-assisted analysis system (CAAS) to quantitate various stenosis parameters (percent degree of stenosis and minimal stenosis diameter). Of the 425 patients enrolled, 348 (82%) underwent a second angiogram; 66 of them, however, terminated treatment prematurely after an average of 359 (placebo) and 467 days (nifedipine). A total of 282 patients (148 on placebo, 134 on nifedipine) completed the trial with full-length treatment. There were no differences between the two groups in the progression of the existing stenoses. Patients on nifedipine, however, demonstrated significantly fewer new lesions (stenoses greater than 20% or occlusions) than those on placebo: In the 282 patients undergoing the full-length treatment, there were 73 patients on placebo (49%) with 118 new lesions (0.8/patient) and 54 patients on nifedipine (40%) with 78 new lesions (0.58/patient), a difference of -27% (p = 0.031 by Cochran's linear trend test). The difference was greatest in the left anterior descending branch, with 28 patients on placebo developing 33 new lesions (0.22/patient), versus 16 patients on nifedipine with 18 new lesions (0.13/patient) (-40%; p = 0.045); and in the left circumflex branch, where 34 patients on placebo exhibited 39 new lesions (0.26/patient) versus 23 patients on nifedipine with 22 new lesions (0.16/patient) (-38%, p = 0.033). No differences were observed in the right coronary artery, the vessel with the highest number of existing and new lesions [PL] versus 0.27 [NIF] new lesions/patient) (-7.6%, p = 0.381). Hence, INTACT confirmed the previous experimental studies and demonstrates a significant reduction in newly formed coronary lesions in patients on nifedipine when compared with those on placebo, especially in the presence of early coronary artery disease.

Adult↗
PubMed1990

Extracellular space, blood volume, and the early dumping syndrome after total gastrectomy.

Extracellular space and blood volume were measured using 82Br dilution and 51Cr-tagged erythrocytes in 24 tumor-free patients after total gastrectomy. Eleven of the patients suffered from early dumping. Age, blood volume, and extracellular space were significantly smaller in dumpers (P less than 0.05). The dumping score could be predicted by a multiple regression model considering blood volume per lean body mass and extracellular space (r = 0.637; P = 0.0039). Rapid (t1/2 less than 360 seconds) emptying of the gastric substitute, assessed using a 99Tc-labeled solid test meal, was significantly associated with dumping in addition to extracellular space and blood volume (r = 0.876; P = 0.0018). Both rapid emptying and a narrow extracellular space seem to contribute to the early dumping syndrome.

Blood Volume↗
PubMed1989

Lectin-binding sites in the midgut of the mosquitoes Anopheles stephensi Liston and Aedes aegypti L. (Diptera: Culicidae).

The presence and distribution of binding sites for eight different lectins, Con A, DBA, HPL, LFA, RCA I, SBA, UEA I, and WGA, were compared in the midguts of Plasmodium gallinaceum-infected Aedes aegypti and Plasmodium berghei-infected Anopheles stephensi. Lectins with high specificity for N-acetyl-D-glucosamine (GlcNAc) exhibited high binding preference for the peritrophic membrane and microvillar glycocalyx of Ae. aegypti; the same structures were preferentially labeled by N-Acetyl-D-galactosamine (GalNAc)-specific lectins in An. stephensi. No differences could be observed in the lectin-binding patterns of the intercellular spaces or cellular organelles and structures. The Plasmodium ookinete surface did not react with any of the lectins tested. It appears that sugars are involved in vector recognition by the parasite and that the peritrophic membrane and/or glycocalyx may be crucial structures for the penetration of the gut epithelium by the ookinete.

Aedes↗
PubMed1989

Cytochemical demonstration of lectin binding-sites in the cuticle and tissues of Acanthocheilonema viteae (Filarioidea).

The lectin-gold technique was used for the ultrastructural localization of lectin binding sites on thin sections of Lowicryl K4M embedded adult females, infective larvae and SDS-2-mercaptoethanol-insoluble cuticle components of Acanthocheilonema (Dipetalonema) viteae. Helix pomatia lectin (HPL) coupled to 14 nm gold particles, was used for the demonstration of N-acetyl-D-galactosamine-containing glycoconjugates. Triticum vulgaris (wheat germ) agglutinin (WGA) coupled to 10 nm gold particles after cross-linking to BSA or ovomucoid-gold after application of unlabeled WGA, demonstrated WGA binding sites (N-acetyl-D-glucosamine). With both lectins no surface labelling of the cuticle was observed, but subcuticular layers reacted positively. HPL-gold was bound to cuticular fibers, the matrix and to the electron dense layer within the cortical zone of the cuticle of female worms. WGA-gold complexes were bound mainly to the cuticle matrix and somatic tissues. The results support the hypothesis that tissue-dwelling parasitic nematodes have reduced their surface carbohydrates perhaps as a consequence of their parasitic life.

Acetylgalactosamine↗