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J Brouwer

Publications and source records attributed to J Brouwer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cardiac abnormalities in SLE: pancarditis.

Many patients with systemic lupus erythematosus (SLE) develop cardiac manifestations during the course of their disease. Pericarditis is most commonly seen, with a reported prevalence of 60%. Myocardial involvement is present in only a minority of patients. In recent years, due to better noninvasive diagnostic techniques, valvular abnormalities can be demonstrated in an increasing number of patients. Depending on the technique used, valvulopathy can be demonstrated in up to 77% of SLE patients. Although most of the valvular lesions will be present without any symptoms, valve incompetence can result in congestive heart failure. Valvular lesions are associated with IgG anticardiolipin antibodies (aCL) and disease duration. We present a patient with SLE and secondary antiphospholipid syndrome (APS) who developed acute congestive heart failure due to pancarditis. Endocarditis, together with left ventricular dysfunction and pericardial effusion, were present. The endocarditis caused hemodynamically significant mitral valve insufficiency due to thickening of the mitral cusps. Just two weeks prior to the occurrence of congestive heart failure echocardiography had been normal. Treatment with high dose corticosteroids resulted in a gradual, almost complete recovery. Literature concerning cardiac manifestations in lupus is reviewed.

Adult↗
PubMed1999

Characterization of the rhp7(+) and rhp16(+) genes in Schizosaccharomyces pombe.

The global genome repair (GGR) subpathway of nucleotide excision repair (NER) is capable of removing lesions throughout the genome. In Saccharomyces cerevisiae the RAD7 and RAD16 genes are essential for GGR. Here we identify rhp7 (+), the RAD7 homolog in Schizosaccharomyces pombe. Surprisingly, rhp7 (+)and the previously cloned rhp16 (+)are located very close together and are transcribed in opposite directions. Upon UV irradiation both genes are induced, reaching a maximum level after 45-60 min. These observations suggest that the genes are co-regulated. Schizo-saccharomyces pombe rhp7 or rhp16 deficient cells are, in contrast to S.cerevisiae rad7 and rad16 mutants, not sensitive to UV irradiation. In S.pombe an alternative repair mechanism, UV damage repair (UVDR), is capable of efficiently removing photolesions from DNA. In the absence of this UVDR pathway both rhp7 and rhp16 deficient cells display an enhanced UV sensitivity. Epistatic analyses show that rhp7 (+)and rhp16 (+)are only involved in NER. Repair analyses at nucleotide resolution demonstrate that both Rhp7 and Rhp16, probably acting in a complex, are essential for GGR in S.pombe.

Amino Acid Sequence↗
PubMed1999

Removal of cyclobutane pyrimidine dimers by the UV damage repair and nucleotide excision repair pathways of Schizosaccharomyces pombe at nucleotide resolution.

In Schizosaccharomyces pombe two different repair mechanisms remove UV-induced lesions from DNA, i.e. nucleotide excision repair (NER) and UV damage repair (UVDR). Here, the kinetics of removal of cyclobutane pyrimidine dimers (CPDs) by both pathways is determined at base resolution in the transcribed strand (TS) and the non-transcribed strand (NTS) of the sprpb2 +gene. UVDR does not remove lesions in a strand-specific manner, indicating that UVDR is neither stimulated nor inhibited by RNA polymerase II transcription. In contrast, in a UVDR-deficient strain the TS is repaired preferentially. This strong strand bias suggests that in S.pombe, as in other species, NER is coupled to transcription. In repair-proficient S.pombe the TS is repaired very rapidly, as a consequence of two efficiently operating pathways, while the NTS is repaired more slowly, mainly by UVDR. Furthermore, we demonstrate that UVDR is not always faster than NER.

DNA Damage↗
PubMed1999

Different effects of bisoprolol on heart rate in patients with ischemic or idiopathic dilated cardiomyopathy (a 24-hour Holter substudy of the Cardiac Insufficiency Bisoprolol Study [CIBIS]).

The effect of beta blockade on heart rate in patients with either idiopathic or ischemic cardiomyopathy was studied. It was found that beta blockade reduced the early morning increase in heart rate to a greater extent in patients with idiopathic dilated cardiomyopathy than in those with ischemic dilated cardiomyopathy.

Adolescent↗
PubMed1999

Rad26, the yeast homolog of the cockayne syndrome B gene product, counteracts inhibition of DNA repair due to RNA polymerase II transcription.

Transcription-coupled DNA repair (TCR) is responsible for the preferential removal of DNA lesions from the transcribed strands of RNA polymerase II transcribed genes. Saccharomyces cerevisiae rad26 mutants and cells from patients suffering from the hereditary disease Cockayne syndrome display a TCR defective phenotype. Whether this lack of preferential repair has to be explained by a defect in repair or in general transcription is unclear at present. To discriminate between both possibilities, we analyzed repair of UV-induced cyclobutane pyrimidine dimers at single base resolution in yeast cells lacking RAD26, the homolog of the Cockayne syndrome B gene. Disrupting RAD26 affects nucleotide excision repair of transcribed DNA irrespective of the chromatin context, resulting in similar rates of removal for individual cyclobutane pyrimidine dimers throughout the transcribed strand. Notably, repair of transcribed sequences in between core nucleosomal regions is less efficient compared with nontranscribed DNA at these positions, pointing to a nucleotide excision repair impediment caused by blocked RNA polymerase. Our in vivo data demonstrate that the TCR defect in rad26 mutant cells is not due to a general transcription deficiency but results from the inability to release the transcription complex trapped at sites of base damage.

Cell Cycle Proteins↗
PubMed1999

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity.

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

Aged↗
PubMed1999

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats.

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.4 +/- 0.6 sites. After 24 hours, pacing was stopped and the electrophysiological study and recording of the AA intervals was repeated at 4, 8, 16, and 24 hours after cessation of pacing. Time- and frequency-domain parameters were computed from each 500 AA interval recording. After 24 hours of rapid pacing the AERP had shortened significantly (147 +/- 5.6 to 102+/- 6.4 ms, P < 0.0001). No significant changes in HRV and dispersion of refractoriness (AAERP) (47 +/- 7.1 to 44 +/- 4.2 ms) were observed. After cessation of pacing, the AERP prolonged again (102 +/-6.4 to 135+/-8.8 ms, P < 0.0001) and was paralleled by a significant increase in AAERP (44 +/- 4.2 to 63+/- 7.1 ms, P = 0.01). Furthermore, HRV increased significantly. At each time point an inverse relation between the logarithmically transformed vagal parameter HF (InHF) and AERP was observed. We calculated the mean InHF for each goat using all time points and used the median value to divide the 12 goats into high and low vagal tone groups. We compared the degree of ERA and recovery from ERA for both groups. The AERP shortened 47.4 +/- 6.5 versus 43.0+/-5.0 ms (NS) for goats with high and low vagal tone, respectively. During recovery from ERA the AERP lengthened 23.6 +/- 4.0 versus 42.5 +/- 1.7 ms (P = 0.001) for goats with high and low vagal tone, respectively. Multivariate regression analysis indicated a short AERP as the single independent determinant of the inducibility of AF during ERA and recovery from ERA (P < 0.0001). During recovery from ERA, the AERP prolonged and vagal tone and AAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.

Animals↗
PubMed1999

RNA polymerase II transcription suppresses nucleosomal modulation of UV-induced (6-4) photoproduct and cyclobutane pyrimidine dimer repair in yeast.

The nucleotide excision repair (NER) pathway is able to remove a wide variety of structurally unrelated lesions from DNA. NER operates throughout the genome, but the efficiencies of lesion removal are not the same for different genomic regions. Even within a single gene or DNA strand repair rates vary, and this intragenic heterogeneity is of considerable interest with respect to the mutagenic potential of carcinogens. In this study, we have analyzed the removal of the two major types of genotoxic DNA adducts induced by UV light, i.e., the pyrimidine (6-4)-pyrimidone photoproduct (6-4PP) and the cyclobutane pyrimidine dimer (CPD), from the Saccharomyces cerevisiae URA3 gene at nucleotide resolution. In contrast to the fast and uniform removal of CPDs from the transcribed strand, removal of lesions from the nontranscribed strand is generally less efficient and is modulated by the chromatin environment of the damage. Removal of 6-4PPs from nontranscribed sequences is also profoundly influenced by positioned nucleosomes, but this type of lesion is repaired at a much higher rate. Still, the transcribed strand is repaired preferentially, indicating that, as in the removal of CPDs, transcription-coupled repair predominates in the removal of 6-4PPs from transcribed DNA. The hypothesis that transcription machinery operates as the rate-determining damage recognition entity in transcription-coupled repair is supported by the observation that this pathway removes both types of UV photoproducts at equal rates without being profoundly influenced by the sequence or chromatin context.

DNA Repair↗
PubMed1998

Defective Kin28, a subunit of yeast TFIIH, impairs transcription-coupled but not global genome nucleotide excision repair.

The essential Saccharomyces cerevisiae KIN28 gene encodes a subunit of general transcription factor TFIIH, a multiprotein complex required for RNA polymerase II transcription initiation and nucleotide excision repair (NER). Kin28 is implicated in the transition from transcription initiation to transcription elongation by phosphorylation of the carboxy-terminal domain (CTD) of the largest subunit of the RNA polymerase II complex. Here, we explore the possibility that Kin28 like the other subunits of TFIIH is involved in NER in vivo, using yeast cells carrying either a wildtype or a thermosensitive KIN28 allele. The removal of UV induced cyclobutane pyrimidine dimers (CPDs) was monitored at base resolution from both strands of the RNA polymerase II transcribed genes RPB2 and URA3. Cells carrying the thermosensitive KIN28 allele display a transcription-coupled repair (TCR) defect at the non-permissive temperature, which was most pronounced directly downstream of transcription initiation, probably as an indirect result of a general decrease in the level of RNA polymerase II transcription. The fact that CPD removal in non-transcribed DNA is completely unaffected in these cells indicates that Kin28 is not essential for general NER in vivo, providing the first example of a TFIIH subunit that is required for TCR but not for NER in general.

Cyclin-Dependent Kinases↗
PubMed1998

Preferential binding of yeast Rad4.Rad23 complex to damaged DNA.

The yeast Rad4 and Rad23 proteins form a complex that is involved in nucleotide excision repair (NER). Their function in this process is not known yet, but genetic data suggest that they act in an early step in NER. We have purified an epitope-tagged Rad4.Rad23 (tRad4. Rad23) complex from yeast cells, using a clone overproducing Rad4 with a hemagglutinin-tag at its C terminus. tRad4.Rad23 complex purified by both conventional and immuno-affinity chromatography complements the in vitro repair defect of rad4 and rad23 mutant extracts, demonstrating that these proteins are functional in NER. Using electrophoretic mobility shift assays, we show preferential binding of the tRad4.Rad23 complex to damaged DNA in vitro. UV-irradiated, as well as N-acetoxy-2-(acetylamino)fluorene-treated DNA, is efficiently bound by the protein complex. These data suggest that Rad4.Rad23 interacts with DNA damage during NER and may play a role in recognition of the damage.

Acetoxyacetylaminofluorene↗
PubMed1998

Reactive oxygen species are required for the phagocytosis of myelin by macrophages.

Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). In this study we showed that the phagocytosis of myelin by macrophages triggers the production of ROS. We also demonstrated that ROS play a crucial role in the myelin phagocytosis. Blocking the ROS production with NADPH oxidase inhibitors (100 microM DPI or 10 mM Apocynin) essentially prevented the phagocytosis of myelin. Furthermore, scavenging of ROS with catalase (H2O2) or mannitol (OH-) decreased the phagocytosis of myelin by macrophages, whereas superoxide dismutase (O2-) did not show this effect. In addition, Lipoic acid (LA), a non-specific scavenger of ROS, also decreased the phagocytosis of myelin by macrophages. In our results, we demonstrate for the first time that ROS appear to play a regulatory role in the phagocytosis of myelin.

Animals↗
PubMed1998

Effect of spinal cord stimulation on heart rate variability and myocardial ischemia in patients with chronic intractable angina pectoris--a prospective ambulatory electrocardiographic study.

BACKGROUND AND HYPOTHESIS: Spinal cord stimulation is an effective treatment for chronic refractory angina pectoris. Its efficacy is related to an anti-ischemic action, possibly as a result of modulation of the autonomic nervous system. Therefore, the influence of spinal cord stimulation on the autonomic nervous system and myocardial ischemia was prospectively studied in 19 consecutive patients with intractable angina pectoris. METHODS: Patients were included when demonstrating > 0.1 mV STsegment depression on the exercise electrocardiogram (ECG) during two separate treadmill tests. After enrollment, heart rate variability together with ischemic indices were studied with 48 h ambulatory ECG monitoring. Assessments were made at baseline and after 6 weeks of spinal cord stimulation therapy. RESULTS: After 6 weeks, no significant changes in heart rate variability were detected. However, ischemic indices on the ambulatory ECG, as well as anginal attacks and consumption of sublingual nitrate tablets, were significantly decreased. CONCLUSION: Autonomic modulation assessable with heart rate variability analysis may not be the explanatory mechanism of action for the decrease of anginal attacks and ischemia, exerted by spinal cord stimulation used as an adjuvant therapy in patients with chronic intractable angina pectoris.

Angina Pectoris↗
PubMed1998

High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.

OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.

Adult↗
PubMed1998

Fecal lysozyme in assessment of disease activity in inflammatory bowel disease.

This study was undertaken to determine whether measurement of fecal lysozyme is helpful in determining disease activity in inflammatory bowel disease. In 112 patients with Crohn's disease, 46 patients with ulcerative colitis, and 40 controls, fecal lysozyme concentration was measured. Results were correlated with CDAI and AI in Crohn's disease and with Truelove and Witts' grading in ulcerative colitis. Fecal lysozyme concentration (mean +/- SEM) was significantly (P < 0.001) higher in Crohn's disease (75 +/- 14 microg/g) and ulcerative colitis (238 +/- 33 microg/g) than in controls (6 +/- 1 microg/g). There was only a weak correlation between fecal lysozyme concentration and CDAI (r = 0.32; P = 0.001) and AI (r = 0.38; P < 0.0005) in patients with Crohn's disease and with Truelove and Witts' grading (r = 0.47; P = 0.001) in ulcerative colitis. When CDAI > or = 150 or AI > or = 100 were used as the standard for active disease, fecal lysozyme concentration was elevated in 78% of patients with active colonic Crohn's disease. In ulcerative colitis fecal lysozyme concentration was increased in active disease (95% in grade II and 94% in grade III) as compared 33% in grade I. Measurement of fecal lysozyme is of little help in diagnosing and determining disease activity of inflammatory bowel disease as whole, but it may be of help for diagnosis and assessment of activity of colonic IBD.

Adult↗
PubMed1997

Saccharomyces cerevisiae mms19 mutants are deficient in transcription-coupled and global nucleotide excision repair.

The recently cloned Saccharomyces cerevisiae MMS19 gene appears to be involved in both nucleotide excision repair (NER) and transcription, which is also the case for components of the NER/transcription complex TFIIH. Unlike TFIIH however, the Mms19 protein does not affect NER in a highly purified in vitro system. In order to investigate the role of Mms19 in NER, we have analysed the repair capacity of the mms19 disruption mutant. We find that a cell-free extract of this mutant is deficient for NER in vitro. Since mms19 mutants are only moderately sensitive to irradiation with ultraviolet (UV) light, it is possible that such mutants are specifically deficient in one of the two modes of NER, i.e. transcription-coupled or global genome repair. To investigate this possibility, we have analysed the removal of cyclobutane-pyrimidine dimers (CPDs) at the nucleotide level in an mms19 mutant. Repair of CPDs was not detectable for both transcribed and non-transcribed sequences in this mutant, demonstrating a requirement for Mms19 in both transcription-coupled and global genome repair. Our data, combined with those obtained by others, suggest that Mms19 is required for NER in yeast, although it seems likely that the protein plays an indirect role in this process.

DNA Repair↗
PubMed1997

Heart rate variability in patients with atrial fibrillation is related to vagal tone.

BACKGROUND: Analysis of heart rate variability (HRV) has thus far not been applied in patients with atrial fibrillation, probably because of the presumed absence of any form of patterning of the ventricular rhythm, particularly vagally mediated respiratory arrhythmia. However, such patterning is theoretically conceivable given the function of the atrioventricular node in atrial fibrillation and its susceptibility to autonomic influences. METHODS AND RESULTS: Sixteen patients (mean age, 56+/-4 years) with long-term atrial fibrillation on fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm were used as control subjects. HRV (standard deviation of RR intervals [SD], coefficient of variance [CV], the root-mean-square of successive difference [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed during 500 RR intervals at baseline, after administration of propranolol (0.2 mg/kg I.V.), and after subsequent administration of methylatropine (0.02 mg/kg I.V.). HRV at baseline and changes in HRV after methylatropine were then related to vagal tone (vagal cardiac control), quantified as the decrease in mean RR after methylatropine. Baseline HRV was higher in the atrial fibrillation group than in the control group; after propranolol, HRV increased in both groups; after methylatropine, HRV neared zero in the control group, whereas it returned to baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at baseline were significantly (P<.05) correlated with vagal tone in the control group but also in the atrial fibrillation group (correlation coefficients of .60, .61, .57, and .64, respectively). Even stronger correlations were observed between changes in these parameters after methylatropine and vagal tone, particularly in the atrial fibrillation group (correlation coefficients of .89, .87, .72, and .90, respectively). CONCLUSIONS: This study shows that HRV in patients with atrial fibrillation is related to vagal tone.

Atrial Fibrillation↗