‘Bijwerken, overschilderen, vernissen of vernieuwen’, honderd jaar restauratiegeschiedenis van de schilderingen

Since 1903 a lot of wall paintings have been discovered in the main church in Breda, on the walls as well as on the pillars and vaults. Detailed attention has been paid to the art-historical aspects of the paintings in various publications. However, the techniques, the materials used and the considerations that led to the choice of a specific approach have hardly been accounted for. The archival documentation (photographs, letters, notes, reports and accounts) at the National Service for Cultural Heritage and the Municipality of Breda, however, provide important although still incomplete information. Even the latest restorations, executed in the nineties of the previous century, were not properly mapped by the parties involved. It seems that in Breda it was not until long after the Reformation that the paintings were whitewashed; the paintings in the Prinsenkapel (Princes’ chapel) not until after 1819. It turned out that the paintings were already damaged and dirty before being whitewashed, and in some cases they had even been restored or touched up before. The whitewashing contributed to the preservation of the paintings to a considerable extent, because the paintings were protected by the whitewash. When in the early twentieth century the paintings emerged, they were once again exposed to negative factors (moist, pollution, and the like). The various restorations, however, have also had a great impact on the preservation of the authenticity of the paintings. When the first paintings were discovered, many of them proved to be in a bad condition. Uncovering them too roughly, the earlier damage to them, but also the damp walls had seriously affected the paintings. Consequently, the restoration of the paintings was started very quickly. These first restorations took approximately thirty years. After these restorations, however, the work was not completed yet and three more periods of large-scale restorations followed, which were to last the entire twentieth century. From the beginning of the restoration activities there was detailed discussion on the restoration method. The discussion was not so much about technical or material questions, but mainly about the degree of touching-up and completing and about the starting point that in principle restoration should consist of mere conservation, without additions and with the utmost limitation of touch-ups. In 1915 the Netherlands Society of Antiquarians (KNOB) formulated as one of its principles: ‘preservation has priority over renovation’. This starting point always served as a guideline in the restorations, although in their execution touching-up or filling up voids nevertheless took place frequently. Restoration is a question of choosing and the choices were often personal and a product of the times. It is striking that from the 1990s onwards there was a growing desire among the church council of the main church to restore the paintings as much as possible to their ‘former glory’. The restorer concurred with this to a large extent. The painting of the Annunciation and the vault paintings of choir and transept are distinct examples of this. After objections from the supervisory committee of the restoration somewhat more reserve was exercised in the restoration of the paintings in the nave

‘Bijwerken, overschilderen, vernissen of vernieuwen’, honderd jaar restauratiegeschiedenis van de schilderingen

Since 1903 a lot of wall paintings have been discovered in the main church in Breda, on the walls as well as on the pillars and vaults. Detailed attention has been paid to the art-historical aspects of the paintings in various publications. However, the techniques, the materials used and the considerations that led to the choice of a specific approach have hardly been accounted for. The archival documentation (photographs, letters, notes, reports and accounts) at the National Service for Cultural Heritage and the Municipality of Breda, however, provide important although still incomplete information. Even the latest restorations, executed in the nineties of the previous century, were not properly mapped by the parties involved. It seems that in Breda it was not until long after the Reformation that the paintings were whitewashed; the paintings in the Prinsenkapel (Princes’ chapel) not until after 1819. It turned out that the paintings were already damaged and dirty before being whitewashed, and in some cases they had even been restored or touched up before. The whitewashing contributed to the preservation of the paintings to a considerable extent, because the paintings were protected by the whitewash. When in the early twentieth century the paintings emerged, they were once again exposed to negative factors (moist, pollution, and the like). The various restorations, however, have also had a great impact on the preservation of the authenticity of the paintings. When the first paintings were discovered, many of them proved to be in a bad condition. Uncovering them too roughly, the earlier damage to them, but also the damp walls had seriously affected the paintings. Consequently, the restoration of the paintings was started very quickly. These first restorations took approximately thirty years. After these restorations, however, the work was not completed yet and three more periods of large-scale restorations followed, which were to last the entire twentieth century. From the beginning of the restoration activities there was detailed discussion on the restoration method. The discussion was not so much about technical or material questions, but mainly about the degree of touching-up and completing and about the starting point that in principle restoration should consist of mere conservation, without additions and with the utmost limitation of touch-ups. In 1915 the Netherlands Society of Antiquarians (KNOB) formulated as one of its principles: ‘preservation has priority over renovation’. This starting point always served as a guideline in the restorations, although in their execution touching-up or filling up voids nevertheless took place frequently. Restoration is a question of choosing and the choices were often personal and a product of the times. It is striking that from the 1990s onwards there was a growing desire among the church council of the main church to restore the paintings as much as possible to their ‘former glory’. The restorer concurred with this to a large extent. The painting of the Annunciation and the vault paintings of choir and transept are distinct examples of this. After objections from the supervisory committee of the restoration somewhat more reserve was exercised in the restoration of the paintings in the nave

Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the pituitary adenoma cultures, a comparison was made with the effects of the dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was determined by ligand binding studies and by in situ hybridization to detect sst1, sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of alpha-subunit, FSH, and/or LH. In the other cultures, hormone and/or subunit release was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM) in 7 of 11, and by octapeptide SS-analogs (10 nM) in 3 of 10 cultures. In three NFA cultures, hormone release was sensitive to SS but not to SS-analogs. In all cultures, except for one, DA-agonists were the most effective in inhibiting hormone release. In the prolactinoma cultures, PRL release was inhibited by DA-agonists (10 nM) in 7 of 7, by SS in 4 of 4, and by octapeptide SS-analogs in 3 of 7 cultures. A dissociation between the effects of SS and SS-analogs was found in 3 cases. In the cultures sensitive to both bromocriptine and SS-28, bromocriptine was the most potent compound in 2 out of 4 cultures. In the 2 other cultures, both compounds were equally effective. In 2 insulinoma cultures, insulin release was inhibited by SS, and by octapeptide SS-analogs in only one. The presence or absence of an inhibitory effect by octreotide was in all cases in parallel with the presence or absence of the inhibitory effect by BIM-23014 and RC-160. Autoradiographic studies using [125I-Tyr0]SS28 showed specific binding in 4 of 5 NFAs, 1 of 2 prolactinomas, and 1 of 1 insulinoma. Specific [125I-Tyr3]octreotide binding was found in 2 of 5 NFAs, in 1 of 2 prolactinomas, and in the insulinoma. Two NFAs showed binding of SS28, but not of the sst2.5 specific ligand octreotide. The tumors showed variable sst1 and/or sst3 mRNA expression, whereas no sst2 expression was found. In conclusion, a dissociation between the inhibitory effects of SS on the one hand and of the octapeptide SS-analogs octreotide, BIM-23014 and RC-160 on the other hand, is observed in a small subgroup of NFAs, prolactinomas, and insulinomas, suggesting that novel sst subtype specific SS-analogs might be of benefit in the treatment of selected patients with somatostatin receptor positive secreting tumors not resp

17-β-Estradiol-dependent regulation of somatostatin receptor subtype expression in the 7315b prolactin secreting rat pituitary tumor in vitro and in vivo

In the present study, we have investigated the role of estrogens in the regulation of somatostatin receptor subtype (sst) expression in 7315b PRL- secreting rat pituitary tumor cells in vitro and in vivo. sst were undetectable in freshly dispersed cells of the transplantable 7315b tumor. When 7315b cells were cultured in medium containing 10% FCS, the number of high affinity sst increased with prolonged culture time. However, when the medium was supplemented with 10% horse serum (HS) instead of FCS, no sst were detectable on 7315b cells even after three weeks of culturing. In contrast to HS, FCS contains high E2-levels (HS, 8 pM; FCS, 134 pM). The antiestrogen tamoxifen (0.5 μM) significantly inhibited the sst number to 50.5% of the value of untreated FCS-grown cells, suggesting that E2 stimulates sst expression in 7315b rat pituitary tumor cells. E2 (l0 nM) induced a rapid increase in sst number in HS-grown 7315b cells. Octreotide (1μM) significantly inhibited PRL release and the intracellular PRL concentration of 7315b cells that were cultured in medium supplemented with FCS or with HS + l0 nM E2 but not in HS alone. This indicates that the sst present on these cells are biologically active. RT-PCR analysis revealed that none of the five currently known sst subtypes were present in freshly dispersed 7315b pituitary tumor cells. The expression of sst2- and sst3- messenger RNA (mRNA) was unequivocally correlated to the presence of E2 because these sst subtypes were detected only in cells that were cultured for7 and 14 days in medium supplemented with FCS or with HS + 10 nM E2. sst1, sst4 and sst5 messenger RNA could not be detected. The 7315b tumor itself synthesizes and secretes huge amounts of PRL. The high PRL levels in tumor-bearing rats inhibit the ovarian E2-production. No detectable E2 levels could be measured in the serum of 7315b tumor-bearing rats. The sc administration of 20 μg/day E2-benzoate normalized the circulating E2 levels in 7315b tumor- bearing rats. Moreover, E2-treatment indeed induced sst expression in vivo as shown by ligand binding studies using membrane homogenates and [125I- Tyr3]-octreotide as radioligand and by autoradiography on tissue sections. In agreement with the in vitro studies, the expression of the sst2 subtype was established by RT-PCR analysis in 7315b tumors of E2-treated rats. However, in contrast to the in vitro studies. E2-treatment did not effectuate the expression of the sst3 subtype, suggesting that the in vitro stimulus of E2 is stronger. In conclusion: 1) sst2 and sst3 expression in the 7315b rat prolactinoma model is primarily dependent upon the presence of estrogens; 2) the antihormonal action of octreotide in 7315b tumor cells in vitro is mediated via the sst2 and/or sst3 subtypes; 3) the absence of sst expression in vivo can be explained by the hormonal environment of the 7315b tumor cells. The 7315b tumor cells in vivo may down-regulate their own receptor status via their host, because of the ensuing hyperprolactinemia results in a hypo-estrogenic state.</p

The Pharmacological Chaperone N-butyldeoxynojirimycin Enhances Enzyme Replacement Therapy in Pompe Disease Fibroblasts

In spite of the progress in the treatment of lysosomal storage diseases (LSDs), in some of these disorders the available therapies show limited efficacy and a need exists to identify novel therapeutic strategies. We studied the combination of enzyme replacement and enzyme enhancement by pharmacological chaperones in Pompe disease (PD), a metabolic myopathy caused by the deficiency of the lysosomal acid α-glucosidase. We showed that coincubation of Pompe fibroblasts with recombinant human α-glucosidase and the chaperone N-butyldeoxynojirimycin (NB-DNJ) resulted in more efficient correction of enzyme activity. The chaperone improved α-glucosidase delivery to lysosomes, enhanced enzyme maturation, and increased enzyme stability. Improved enzyme correction was also found in vivo in a mouse model of PD treated with coadministration of single infusions of recombinant human α-glucosidase and oral NB-DNJ. The enhancing effect of chaperones on recombinant enzymes was also observed in fibroblasts from another lysosomal disease, Fabry disease, treated with recombinant α-galactosidase A and the specific chaperone 1-deoxygalactonojirimycin (DGJ). These results have important clinical implications, as they demonstrate synergy between pharmacological chaperones and enzyme replacement. A synergistic effect of these treatments may result particularly useful in patients responding poorly to therapy and in tissues in which sufficient enzyme levels are difficult to obtain

Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression: a prospective, open-label, multicenter, randomized, phase 3 study

Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size