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H Hecker

Publications and source records attributed to H Hecker.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Surgical therapy of hepatoblastoma in childhood].

Hepatoblastoma is a rare but highly malignant liver tumour, predominantly occurring during early childhood. Clinical data of 71 children treated from 1988 to 1993 according to the protocol of the multicentre liver tumour study (HB89) of the German Society for Paediatric Oncology and Haematology were evaluated to assess the effects of surgical therapy in these patients. The protocol prescribed an initial laparotomy for all children with a liver tumour, except for infants with distant metastases and a high serum-alpha-fetoprotein; for small hepatoblastomas confined to one liver lobe primary resection by a lobectomy; and for those extending into both lobes and metastasizing tumours tumour reductive chemotherapy including ifosfamide, cisplatin and adriamycin (IPA), preparatory to resection at second-look surgery. All patients received adjuvant IPA chemotherapy after tumour resection. In 20 of the 71 cases, the hepatoblastomas were completely resected at initial laparotomy (stage I), while in 6 cases microscopic residues were left (stage II). In 38 of 45 children with extended hepatoblastomas (stage III, 38 patients) or distant metastases (stage IV, 7 patients) the tumour was resected during later surgery, and 1 patient received a liver transplant. Thus, the overall resection rate was 92% (65 of 71 hepatoblastomas). After a median follow-up of 3.8 years (range 1.0-5.9 years), 53 (75%) of the patients were tumor-free and 18 (25%) had died. Recurrence-free survival was 100% for stage I, 50% for stage II, 71% for stage III and 29% for stage IV patients (P = 0.0009).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Controlled trial of high- versus low-dose aspirin treatment after percutaneous transluminal angioplasty in patients with peripheral vascular disease.

Percutaneous transluminal angioplasty of aortoiliac and femoropopliteal atherosclerotic lesions can provide long-lasting hemodynamic improvement. High-dose aspirin is commonly prescribed as reocclusion prophylaxis, but low doses would be preferable because of fewer adverse effects. We performed a double-blind, randomized, controlled clinical trial in patients with peripheral vascular disease with lesions appropriate for angioplasty. We compared the efficacy and side effects of two doses of aspirin (50 mg vs. 900 mg daily) during a period of 12 months after angioplasty. A total of 359 patients were evaluated: 175 were randomly assigned to treatment with 900 mg aspirin daily and 184 to 50 mg aspirin daily. Thirty-nine patients developed restenosis at the angioplasty site; the cumulative percentage of event-free survival after 1 year (patency rate) was 85% in 900 mg group and 84% in 50 mg group. An equivalence test showed the two groups equivalent with respect to restenosis rates (P = 0.0003 for an equivalence region of < 10% difference. Nine patients (5%) in the 900 mg group had serious gastrointestinal side effects (peptic ulcer, 8; erosive gastritis requiring transfusion, 1) compared to two ( peptic ulcer) in the 50 mg group (P = 0.03). The results of our study show that a dose of 50 mg aspirin a day is as effective as 900 mg for the prevention of restenoses after lower limb angioplasty, and that severe gastrointestinal side effects are less frequent.

Aged↗
PubMed1994

Characterization of the histones of Trypanosoma brucei brucei bloodstream forms.

Five groups of histones were shown in Trypanosoma brucei brucei, displaying qualitative and quantitative differences between two stages of the parasite's life-cycle. The influence of the histones of T. b. brucei bloodstream forms on the compaction pattern of the chromatin was investigated and their extractability in diluted acids and their amino acid composition were analysed. While nonhistone proteins barely influenced the formation of higher-order chromatin structures, the histone H1-like proteins were essential for the regular spacing of the nucleosomes and the salt-dependent condensation of the nucleosome filament. Differences were seen in the amino-acid composition of histones of bloodstream forms as compared to procyclic culture forms and higher eukaryotes which may explain the disparities seen in the condensation of the chromatin between the two stages of the life cycle as well as the lack of a salt-dependent condensation into a 30 nm fiber. They point to an alternative method of organizing and processing the genetic information in the nucleus of the trypanosome as compared to higher eukaryotes, the possible hosts of the parasite.

Amino Acids↗
PubMed1994

The chromatin of trypanosomes.

The nuclear chromatin of trypanosomes is organised in the form of nucleosome filaments. When soluble chromatin is prepared under suitable conditions, a regular array of nucleosomes can be shown by electron microscopy. Chromatin of blood stream as well as procyclic culture forms of Trypanosoma brucei brucei and of T. cruzi shows limited compaction at salt concentrations increasing from 1 to 100 mM. No 30 nm fibres, typical for higher eukaryotes, are formed. Digestion of the nuclear chromatin with micrococcal nuclease and analysis of the histone proteins with various techniques reveal that the basic organisation of the trypanosome chromatin is similar but not identical as compared to that of higher eukaryotes. Distinct differences are present with respect to biochemical properties of the histones as well as to their interaction with the DNA. The primary structure of the histones also differs significantly from that found in other lower and higher eukaryotes. The function of the recently described H1-like proteins in trypanosomes is currently being investigated. The differences that have already been found in the structure and compaction of the trypanosome chromatin compared to that of higher eukaryotes lead us to expect differences of gene expression which, in turn, might offer targets for the control of trypanosomiasis.

Animals↗
PubMed1994

Evolution of coronary stenoses is related to baseline severity--a prospective quantitative angiographic analysis in patients with moderate coronary disease. INTACT Investigators. International Nifedipine Trial on Antiatherosclerotic Therapy.

A correlation of the angiographic evolution of coronary stenoses (stenosis diameter > or = 20%) with morphological stenosis parameters at baseline could help to identify the risk of progressive stenoses. Therefore, the data of the prospective INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy) were reviewed. In 348 patients with moderate coronary artery disease, standardized coronary angiograms were taken 3 years apart and were quantitatively analysed. Changes in the minimal diameter of the 1063 preexisting coronary stenoses compared between both angiograms were set in relation to a number of conventional stenosis parameters at baseline. Regression analysis demonstrated a significant correlation of the changes in minimal diameter with baseline % diameter stenosis (r = 0.30; P < 0.001), minimal diameter (r = -0.28; P < 0.001) and reference diameter of stenoses (r = -0.14; P < 0.001). The changes were not correlated with stenosis length and plaque area. The baseline parameters of 22 preexisting stenoses progressing to occlusions differed from those remaining patent only with regard to the % diameter stenosis (43 +/- 9% vs 39 +/- 11%; P < 0.05). Additional progression of coronary disease became manifest through development of 228 stenoses and 19 occlusions at arterial sites free from definitive stenoses in the baseline angiograms. Thus, progression of atherosclerosis predominantly occurred in mild preexisting coronary stenoses and developed at previously angiographically normal sites. Since the conventional angiographic parameters analysed in this study failed to identify individual arterial sites with an increased risk for progression, definition of new angiographic parameters or application of new techniques seem mandatory to this end.

Constriction, Pathologic↗
PubMed1993

[Dose-dependent side effects of acetylsalicylic acid therapy. Results of a prospective randomized clinical study in patients with peripheral arterial occlusive disease].

BACKGROUND AND METHODS: In 359 patients with peripheral arterial occlusive disease who had undergone percutaneous transluminal angioplasty (PTA), a randomized double-blind, controlled clinical study was done to investigate the tolerability of acetyl salicylic acid (ASA) given for reocclusion prophylaxis. A comparison was made between a conventional daily dose of 900 mg ASA and a dose of 50 mg ASA. RESULTS: Within an observation period of one year following PTA, 35 patients (20%) in the 900 mg group, and 32 patients (17%) in the 50 mg group left the trial because of side effects (p = NS). Under the higher dose, however, severe gastrointestinal side effects (ulcer, haemorrhagic gastritis requiring transfusion) were significantly more common (nine patients delta 5.1% vs two patients delta 1.1%, respectively; p = 0.03). Overall, 107 patients (30%) reported subjective side effects such as upper abdominal pain, a sensation of fullness or nausea during the course of the trial. 62 of these patients were from the 900 mg group (35%) as compared with 45 patients (24%) in the 50 mg group (p = 0.02). Self-scoring of epigastric pain on the basis of a visual analogue scale revealed a score of 1.3 (95% confidence interval 0.9 to 1.6) in the 900 mg group and 0.8 (95% confidence interval 0.6 to 1.0) in the 50 mg group. The subjective pain intensity showed a uniform time course for all three types of symptom, with a maximum after three months. CONCLUSION: Our results confirm the superior tolerability of the lower dose, in particular in elderly patients. For long-term treatment, the smallest possible effective dose should be chosen.

Aged↗
PubMed1993

Structural analysis of Trypanosoma brucei brucei chromatin by limited proteolysis. An electrical-birefringence study.

The sensitive electric-birefringence method was used to reveal structural differences between the soluble chromatin of procyclic Trypanosoma brucei brucei and the chromatin of the higher eukaryotes. The orientation of the nucleosomal chains and the presence of extended DNA were analysed from the sign and amplitude of the steady-state birefringence, and the conformational properties (overall dimensions and flexibility) were studied in relation to the orientational relaxation times. In contrast to the higher eukaryotes, the birefringence of T. brucei brucei is negative and of low amplitude, corresponding to that of H1-depleted rat liver nucleosomes. Furthermore, the relaxation times are very small, about 10 microseconds. If salt is added, the birefringence as well as the relaxation time decreases dramatically, indicating that condensation affects T. brucei brucei chromatin although it behaves like nucleosome filaments, with less stable DNA-protein interaction than for the higher eukaryotes. However, this condensation does not induce the formation of regular higher-order structure. This complies with the hypothesis that typical histone H1 is absent from T. brucei brucei chromatin and that a protein or protein domain fulfils the role of histone H1. The accessibility and structural role of histone-like proteins in T. brucei brucei chromatin were also investigated using limited proteolysis with enzymes covalently bound to nylon spheres. The analysis of protein products obtained after digestion with immobilized trypsin and subtilisin shows that proteins a and d, which are classified as H3 and H4 histones, respectively, are the first to be attacked. The changes in chromatin conformation indicate that chromatin undergoes a structural transition, leading to decondensation, as indicated by increases in negative birefringence and relaxation time, and to a change in its orientation mechanism, indicated by the appearance of a permanent moment. This result is very interesting since, in rat liver, H4 was very resistant and was the last histone to be attacked, suggesting internal location and its involvement in nucleosome stabilization rather than higher-order condensation. Therefore, in T. brucei brucei chromatin, the characteristic properties of proteins a and d (their composition and interaction with DNA), as well as their external location on the nucleosome surface, suggest that if these proteins play a role similar to that played by H3 and H4 in higher eukaryotes, probably through their N-terminal regions and interaction either with DNA or protein domains, the mechanisms involved in chromatin compaction are quite different.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Biochemical and functional characterization of histone H1-like proteins in procyclic Trypanosoma brucei brucei.

Four variants and/or posttranslational modifications of histone H1-like proteins of Trypanosoma brucei brucei procyclic culture forms were extracted with 0.25 N HCl from isolated nuclei and analyzed by two-dimensional gel electrophoresis. The amino acid composition of these proteins, their ability to space nucleosomes regularly and to induce salt-dependent condensation of the chromatin indicated their histone H1 nature. On the other hand, the histone H1-like proteins clearly differed from their higher-eukaryote counterparts by their weak interaction with DNA under low-salt conditions. As a consequence, intact nucleosome filaments were prepared according to a new preparation protocol especially adapted to the unstable chromatin of T. b. brucei. Our results indicate that the biochemical properties of the histone H1-like proteins contribute to the structural and functional differences between the chromatin of procyclic T. b. brucei and that of higher eukaryotes.

Amino Acids↗
PubMed1993

Quantitative angiographic follow-up studies on the development of coronary artery disease: which coronary segments should be analyzed? Experience from INTACT.

Angiographic follow-up studies on the evolution of coronary artery disease are of increasing relevance. It has still to be evaluated which coronary segments are predominantly involved in the process of atherosclerosis and, thus, should be preferably included in the analysis. Therefore, the correlation of progression and regression of coronary disease with the diameter and location (proximal, mid or distal) of coronary segments was investigated from the data of the INTACT-study, in which 25 different coronary segments were defined including anatomic variants of rather distal segments. In 348 patients with coronary artery disease, standardized coronary angiograms were repeated within 3 years and were quantitatively analyzed (CAAS). In 1063 coronary stenoses (% diameter stenosis > 20%) compared from both angiograms, progression and regression were not influenced by diameter nor location of arterial segments. In the follow-up angiograms, the number of new lesions (stenoses and occlusions) per coronary segment differed with regard to segment diameter (> 3 mm: 64/1125 (6%); 2-3 mm: 139/1967 (7%); < 2 mm: 44/1756 (2%); p < 0.001) and location of segments (proximal: 86/1285 (7%); mid: 84/1193 (7%); distal: 77/2370 (3%); p < 0.001). Out of 77 distal new lesions, only 25 (32%) were found in segments < 2 mm in diameter. Since the absolute number of new lesions was high in distal coronary segments, but low in segments with diameters < 2 mm, angiographic follow-up studies should analyze coronary segments at any location, but may neglect segments with diameters smaller than 2 mm.

Coronary Angiography↗
PubMed1993

Progression of coronary artery disease is dependent on anatomic location and diameter. The INTACT investigators.

OBJECTIVES: This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter. BACKGROUND: The progressive course of coronary artery disease has been documented in many angiographic follow-up trials. METHODS: The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (< 2 mm, 2 to 3 mm, > 3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries. RESULTS: Decreases in the minimal diameter of preexisting stenoses were largest in segments that were > 3 mm in diameter (mean +/- SD 0.23 +/- 0.5 mm vs. 0.10 +/- 0.4 mm and 0.02 +/- 0.3 mm, p < 0.001), in a proximal position (0.14 +/- 0.5 mm vs. 0.09 +/- 0.4 mm and 0.06 +/- 0.3 mm, p = 0.081) and in the right coronary artery (0.14 +/- 0.4 mm vs. 0.07 +/- 0.4 mm and 0.07 +/- 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were < 2 mm in diameter and in a distal position (p = NS). The number of new stenoses/segment was lowest in segments that were < 2 mm in diameter (44 of 1,756 vs. 139 of 1,967 and 64 of 1,125, p < 0.001) and in a distal position (77 of 2,370 vs. 84 of 1,193 and 86 of 1,285, p < 0.001) and was highest in segments of the right coronary artery (100 of 1,546 vs. 66 of 1,496 and 72 of 1,492, p = 0.044). CONCLUSIONS: Progression of coronary artery disease occurs most frequently in coronary segments that are > 2 mm in diameter, in a proximal or midartery position and in the right coronary artery.

Coronary Angiography↗
PubMed1993

Trypanosoma brucei brucei: differences in the nuclear chromatin of bloodstream forms and procyclic culture forms.

Nucleosome filaments of two stages of the life-cycle of Trypanosoma brucei brucei, namely bloodstream forms and procyclic culture forms, were investigated by electron microscopy. Chromatin of bloodstream forms showed a salt-dependent condensation. The level of condensation was higher than that shown by chromatin from procyclic culture forms, but 30 nm fibres as formed in rat liver chromatin preparations were not found. Analysis of histones provided new evidence for the existence of H1-like proteins, which comigrated in the region of the core histones in SDS-PAGE and in front of the core histones in Triton acid urea gels. Differences were found between the H1-like proteins of the two trypanosome stages as well as between the core histones in their amount, number of bands and banding pattern. It can be concluded that T. b. brucei contains a full set of histones, including H1-like proteins, and that the poor condensation of its chromatin is not due to the absence of H1, but most probably due to histone-DNA interaction being weak. It is obvious that structural and functional differences of the chromatin exist not only between T. b. brucei and higher eukaryotes, but also between various stages of the life-cycle of the parasite. It is therefore not adequate to investigate the chromatin only of the procyclic culture forms as a model for all stages of the life-cycle of T. b. brucei.

Animals↗
PubMed1993

Dose-dependent effect of aspirin on carotid atherosclerosis.

BACKGROUND: Antiplatelet treatment with aspirin is well established as secondary prophylaxis after a transient ischemic attack or minor ischemic stroke, but the effect of aspirin treatment on the course of carotid atherosclerosis is unknown. We investigated the effect of aspirin on the initial stages of carotid atherosclerosis. METHODS AND RESULTS: Patients were recruited from a prospective, randomized, double-blind clinical trial to compare two doses of aspirin (900 mg versus 50 mg daily) with regard to restenoses after lower limb angioplasty. Of the 383 patients admitted to the angioplasty trial, 27 patients with 104 small carotid atheroma (< 50% lumen narrowing) were examined at entry and after 1 year of aspirin treatment with the use of a high-resolution ultrasound duplex system. Disease progression and regression were defined by a change of maximal plaque area (as measured by longitudinal ultrasound sections) of more than 2 SDs of the method. The change in plaque area was significantly different for the treatment groups: Average plaque size remained unchanged after treatment with 900 mg aspirin daily but increased markedly after treatment with 50 mg aspirin daily (p = 0.011). There were significantly more lesions in the 50-mg group showing progression than in the 900-mg group (23 plaques [47%] versus 13 plaques [24%], p = 0.025). Ultrasonic disappearance of a lesion was observed only in the 900-mg group in nine cases (seven soft plaques and two ulcerative plaques, p = 0.018). The six patients on 50 mg aspirin who continued smoking during the study showed significantly more progression compared with the seven nonsmokers in the 50-mg group (17 plaques [59%] versus six plaques [30%], p = 0.038). CONCLUSIONS: The results of our study indicate that aspirin treatment slows carotid plaque growth in a dose-dependent fashion, with a dose of 900 mg daily more efficient than 50 mg daily.

Aspirin↗
PubMed1993

[Atrial arrhythmias after modified Fontane operation: effect of preoperative hemodynamics and the kind of operation (atriopulmonary vs. total cavopulmonary anastomosis)].

UNLABELLED: Between October 1986 and March 1992, occurrence of supraventricular tachycardia and sinus node dysfunction was investigated pre- and postoperatively by serial ECG and Holter monitors in 63 consecutive patients with univentricular circulation after modified Fontan operation (total cavopulmonary connection 39 patients, atriopulmonary connection 24 patients). Mean age at operation was 7.2 (0.1-20.3) years. Of the 63 patients, 14 (22%) had early (< 14 d) supraventricular tachycardia or sinus node dysfunction, which was not related to the type of operation. None of nine patients with a preoperative mean right atrial pressure < or = 2.5 mm Hg had early supraventricular tachycardia or sinus node dysfunction, in contrast to 16/54 patients (30%) with a preoperative mean right atrial pressure > or = 2.5 mm Hg. 6/63 patients died during the early (< 14 d) postoperative period. In only one child death was related to a dysrhythmia (junctional ectopic tachycardia). During a mean follow-up of 2.5 years, 12 patients (21%) had late supraventricular tachycardia or sinus node dysfunction. Early supraventricular tachycardia/sinus node dysfunction was a predictor of late atrial dysrhythmias, as it occurred in eight of the surviving 14 patients with early dysrhythmias, in contrast to four children without early atrial dysrhythmias (p < 0.001). After creation of an atriopulmonary connection, 10/22 patients (45%) had late supraventricular tachycardia/sinus node dysfunction, but only 2/35 patients (6%) with a total cavopulmonary connection had late atrial dysrhythmias (p < 0.001). CONCLUSIONS: Early atrial dysrhythmias after the Fontan operation were related to preoperative hemodynamics. Early supraventricular tachycardia/sinus node dysfunction and the atriopulmonary type of Fontan connection were significant risk factors for late atrial dysrhythmias.

Adolescent↗
PubMed1993

[Correlation between Doppler echocardiography and invasive determination of left ventricular hemodynamic valve parameters. A comparative study under routine conditions in a cardiology center].

UNLABELLED: Simultaneously performed combined Doppler/catheter studies have shown excellent correlations regarding the comparison of invasively and non-invasively obtained valve gradients. To reflect daily clinical life the current study compared the valve parameters obtained by Doppler echocardiography to those obtained later by catheterization in all consecutive patients who underwent invasive procedure between October 1988 and December 1990. A total of 113 patients was included in the study, 76 with aortic and 37 with mitral stenosis. Regarding the mean aortic valve gradient the following correlations were obtained: all patients: r = .79, patients with an ejection fraction > 50% (n = 59): r = .81, patients with an ejection fraction < 50% (n = 17): r = .67, patients with additional aortic insufficiency (n = 21): r = .77. When the mean mitral valve gradient was compared the correlation was r = .71 for all patients and r = .44 when additional mitral regurgitation was present (n = 10). The comparison of the mitral valve orifice area (n = 30) showed a correlation of r = .58. CONCLUSION: Non-simultaneously performed combined Doppler/catheter studies in unselected patients do reflect daily clinical life, however, correlations are not as good as in corresponding simultaneously performed investigations, thus emphasizing the impact of the study conditions on the final results.

Adult↗
PubMed1992

Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro-urokinase (TCL 598) in acute myocardial infarction. German Preactivated Pro-Urokinase Study Group.

In a multicenter dose-finding study, the thrombolytic potency of urokinase preactivated pro-urokinase was evaluated. Sixty-two patients were randomly assigned to receive 250,000 U of urokinase plus either 4.5 mega U (group I: n = 33) or 6.5 mega U (group II: n = 29) of pro-urokinase. Patency rates were 36.4% (20.4-54.9%) vs. 54.5% (36.3-71.9%) (n = 27) at 60 minutes and 55.6% (32.5-70.6%) vs. 62.1% (42.3-79.3%) at 90 min into thrombolysis (n.s.). In a third group of 12 patients treated with 500,000 U of urokinase plus 6.5 mega U of pro-urokinase patency was achieved in 33.3% (9.9-65.1%) and 41.7% (15.2-72.3%) at 60 and 90 min, respectively. Patency rates at 24 hr follow-up angiography (n = 35) were 78.6% (49.2-95.3%), 85.7% (57.2-98.2%), and 85.7% (42.1-99.6%). Coagulation analysis in 37 patients revealed similar alterations in the three treatment groups with minor decreases in fibrinogen levels, moderate drops in plasminogen and alpha-2-antiplasmin levels, and moderate increases in the concentrations of the total fibrinogen/fibrin degradation products, the differences between the groups not being significant. Bleeding complications were observed in 12.9%, 13.8%, and 25% of patients in groups I, II, and III, respectively, mainly related to catheter sites. Hence, the safety profile of urokinase preactivated pro-urokinase seems comparable to other thrombolytic regimens. Reopening of occluded coronary arteries, however, is achieved relatively slowly. Thus, in its use for thrombolysis in myocardial infarction, urokinase preactivated pro-urokinase does not seem to offer superior advantages.

Coronary Angiography↗
PubMed1992

Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators.

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

Animals↗
PubMed1992

Histone-DNA interactions in the chromatin of procyclic Trypanosoma brucei brucei.

The dissociation of histone proteins a-d from the chromatin of Trypanosoma brucei brucei procyclic culture forms was investigated by removing the proteins from the DNA by centrifugation of soluble chromatin through isokinetic sucrose gradients in the presence of NaCl. The dissociation of the T. b. brucei histones was compared with that of their higher-eukaryote counterparts H3, H2A, H2B and H4. All four histones of T. b. brucei remained bound to the DNA at 500 mM NaCl, were partially released at 750 mM NaCl and were completely dissociated from the DNA at 1 M NaCl. These interactions of histones a-d with the DNA were comparable with those of the H2 histones in the chromatin of higher eukaryotes, and histones a and d interacted with the DNA more weakly than did their higher-eukaryote counterparts H3 and H4. Substoichiometric amounts of an additional protein were recovered in the top fractions of the gradients under all dissociation conditions. This protein migrated in the H1 region of rat-liver chromatin in various gel systems. Its early release from the DNA also indicated a resemblance to histone H1. The presence of only small amounts of this protein and the relatively weak interactions of histones a and d with the DNA suggest that the mechanisms involved in chromatin compaction in T. b. brucei are different from those in higher eukaryotes.

Animals↗