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H J Mulder

Publications and source records attributed to H J Mulder.

17 recordsLinked to original sources

The transcription factor HACA mediates the unfolded protein response in Aspergillus niger, and up-regulates its own transcription.

The unfolded protein response (UPR) involves a complex signalling pathway in which the transcription factor HACA plays a central role. Here we report the cloning and characterisation of the hacA gene and its product from Aspergillus niger. ER (endoplasmic reticulum) stress results in the splicing of an unconventional 20-nt intron from the A. niger hacA mRNA, and is associated with truncation of the 5'-end of the hacA mRNA by 230 nt. In this study the UPR was triggered by over expressing tissue plasminogen activator (t-PA), and by treatment of mycelia with dithiothreitol (DTT) or tunicamycin. Overexpression of the processed form of hacA not only led to the up-regulation of bipA, cypB and pdiA--mimicking the UPR--but also led to the up-regulation of the hacA gene itself. In vitro binding assays confirmed that the HACA protein binds to the promoters of genes encoding ER-localised chaperones and foldases, and to the promoter of the hacA gene itself. Finally, a GFP-HACA fusion was shown to localise in the nucleus.

Amino Acid Sequence↗

The continued utility of needle localised biopsy for non-palpable breast lesions.

AIM: To analyse the results of needle localised biopsy (NLB) for non-palpable breast lesions in our hospital and to compare them with data on stereotactic large-core biopsy (SCB), which has been recently introduced as a new less invasive method for evaluating mammographic abnormalities. METHODS: We evaluated the results of all consecutive NLB procedures in our hospital in the period 1998-2000 and compared them with data from literature. Clinical, mammographic and pathological data were reviewed. RESULTS: In the present study 314 patients with 319 non-palpable mammographic abnormalities were included. Seventy percent of patients were referred to us from the national screening program. In all but one patient the NLB procedure was successful. The mean duration of hospital stay was 3 (1-10) days. Histological diagnosis was invasive carcinoma in 31%, invasive carcinoma with DCIS in 32%, DCIS alone in 13% and benign in 24%. The invasive carcinoma group scored tumour-free margins after the first operation in 77% of patients, for both the DCIS with invasive carcinoma group and DCIS alone group the tumour-free margin rate was 47%. Patients with invasive carcinoma and/or DCIS were re-operated in 88%. Of all procedures, 91% was performed without complications. CONCLUSION: NLB is a safe, relatively simple procedure with a high diagnostic accuracy combined with a lower failure and false-negative rate compared to SCB.

Adult↗

Cervical mediastinoscopy in The Netherlands: past or present? A retrospective analysis of 218 procedures.

BACKGROUND: Cervical mediastinoscopy (CM) has been considered the gold standard for the evaluation of mediastinal lymph nodes in the staging of non-small cell lung cancer (NSCLC) for many years. Recent publications on the value of PET scanning might reduce the use of CM in the near future. The aim of this study was to analyse the data of our CM procedures for their reliability and contribution in the assessment of mediastinal lymph nodes. METHODS: In the period 1995-1999, 219 patients underwent CM. Data were available on 218 procedures and were analysed retrospectively. CM was performed in 162 men and 56 women with a median age of 56 years [range 29 to 80 years]. RESULTS: Median hospitalisation time was three days. There was no mortality and morbidity was 6%. In 96% of procedures representative lymphoid tissue was obtained. In 24%, biopsies contained malignancy. CONCLUSIONS: CM is a relatively safe procedure with a high diagnostic yield. As long as PET scanning remains available at a limited level, CM remains the gold standard in The Netherlands for patients with apparently operable NSCLC.

Adult↗

[Injury to the right A. pulmonalis due to blunt thoracic trauma].

Immediately after a moped accident a 16-year old patient was haemodynamically unstable. Following adequate drainage of a haematopneumothorax in the hospital the patient collapsed into a shock. Thoractomy revealed a tear of the right A. pulmonalis. The hilus was clamped and a lobectomy was performed. After this the patient was haemodynamically stable; due to bone and nerve damage he was transferred to a rehabilitation centre. Laceration of the A. pulmonalis as a consequence of blunt thoracic trauma is rare and mostly fatal. In the case of a patient with a massive haematothorax rapid transport to the nearest hospital is preferable to thorax drainage at the site of the accident.

Accidents, Traffic↗

[Interactive cd-rom on the choice between breast-sparing treatment and mastectomy: positive responses from patients and surgeons].

OBJECTIVE: To assess how breast cancer patients and surgeons rate an interactive decision aid, using CD-ROM technology, developed to support a choice between breast-conserving therapy and mastectomy. DESIGN: Questionnaire investigation. METHOD: Written questionnaires were presented to patients as soon as they had finished using the CD-ROM. They responded on a 5-point scale. Surgeons (n = 14) were sent a written questionnaire to investigate their experiences of using the CD-ROM program. RESULTS: The interactive CD-ROM was offered to 92 consecutive breast cancer patients. Responses were obtained from 86 (93%) of the patients. The remainder were inadvertently not given the questionnaire. All of the patients evaluated the program as positive. Most of the patients found the program to be 'interesting', 'clear', 'useful', 'encouraging', and 'reassuring'. A majority (n = 76) expressed the view that the amount of information received was 'just right'. The interactive, computer-based method was evaluated as 'agreeable' by 74 patients. Almost all of the patients (n = 82) recommended that the program be shown to other patients. All of the surgeons (n = 14) stated that their patients' evaluations of the program were positive. Moreover, most of the surgeons (n = 10) were of the opinion that the program 'considerably contributed' to the provision of information. With the exception of one surgeon (n = 13), they all held the view that the program can be offered to breast cancer patients facing a choice between breast-conservation or mastectomy on a standard basis. CONCLUSION: Interactive decision-making support by means of a CD-ROM for patients with breast cancer, received positive evaluations from both the patients and surgeons.

Adult↗

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial.

OBJECTIVE: To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial. DESIGN: A double blind, randomised, placebo controlled, multicentre study. SETTING: Four hospitals in the Netherlands. PATIENTS: 63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29). INTERVENTIONS: The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively. MAIN OUTCOME MEASURES: The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery. RESULTS: Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05). CONCLUSIONS: Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.

Acetylcholine↗

Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial).

The Regression Growth Evaluation Statin Study (REGRESS) is a placebo-controlled multicenter study designed to assess the effect of 2-year treatment with pravastatin on the progression and regression of angiographically documented coronary artery disease. One of the secondary end points was the occurrence of 2-year restenosis in the percutaneous transluminal coronary angioplasty (PTCA) block. We randomly assigned eligible patients to receive pravastatin 40 mg once daily or placebo. The end point was the percent diameter stenosis of the target lesion at 24 months, as assessed by (semi)quantitative coronary angiography. Two hundred twenty-one patients underwent scheduled PTCA, which was considered successful in 201 patients. One hundred seventy-eight patients underwent angiographic restudy (89%). The patients in the pravastatin group (n = 109) and placebo group (n = 112) were similar at baseline. Percent diameter stenosis before angioplasty was 78 +/- 14% (mean +/- SD) in the pravastatin group and 80 +/- 14% in the placebo group (p = 0.46). At follow-up, the percent diameter stenosis was 32 +/- 23% in the pravastatin group and 45 +/- 29% in the placebo group (p < 0.001). Clinical restenosis was significantly lower in the pravastatin group (7%) compared with the placebo group (29%) (p < 0.001). Risk reduction for all events was 58%. We conclude that treatment with pravastatin reduces 2-year clinical and angiographic restenosis.

Angioplasty, Balloon, Coronary↗

[Initial results with breast screening in the Enschede area. I. Effectiveness].

After one year, the effects of breast cancer screening in the region of Enschede were evaluated by means of seven parameters indicating the long-term health benefits. These parameters were: attendance rate, predictive value of a positive screening test, detection rate, incidence rate, tumour stage, surgical possibilities and type of surgical operations. The results were compared with figures from the national cost-effectiveness analysis. The attendance rate (79%), the predictive value (57%) and the detection rate (0.74%) were well over the national figures of 70%, 41% and 0.64%, respectively. The incidence of breast cancer in the age group 50-69 was 2.5 times higher, as expected. The tumour stage differed significantly (p less than 0.001) from the stages of regularly detected tumours; there was a shift to the lower stages (average tumour size was halved). The surgical possibilities increased significantly (p less than 0.01) and surgical operations performed were mostly less mutilating (not significant). We conclude that the screening for breast cancer in the Enschede region fulfills the criteria of efficacy. It is particularly the combination of a high predictive value and a relatively high detection rate compared with the clinical incidence in the previous years that is indicative of the efficacy. This does not mean that the results prove the long term health benefits of screening for breast cancer. They only give an indication of the future efficacy of screening. The impact on the quality of life is still an open question.

Aged↗

[Initial results with breast screening in the Enschede area. II. Efficiency].

The efficiency of breast cancer screening in the Enschede region was evaluated after 18 months on the basis of unfavourable side effects and possible difficulties. These side effects were: 1. for women: psychological burden, period of uncertainty and increasing waiting times; 2. for general practitioners: limited referral; 3. for specialists: increased diagnostics and consultation. The results were compared with the figures derived from the national cost-effectiveness analysis. The psychological burden on women with a positive screening result appeared to be considerable, in conjunction with the length of the period of uncertainty. The final result was only known after approximately five weeks when a biopsy was required. In 83 women (41% of all referred women) the overall result of the procedure was false-positive. Occasionally the woman was not referred to a known specialist centre, in contradiction to the guidelines. The increase in the number of diagnostic and therapeutic operations was larger than expected, and is largely accounted for by the radical increase of clinically non-palpable tumours (factor 17). On average, the waiting time for the (first) biopsy was three weeks. A great deal of multi-disciplinary consultation was necessary because of the large increase of non-palpable tumours and in-situ ductal carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cat-scratch fever.

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Cat-Scratch Disease↗

[Homeland doctors].

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Education, Medical, Continuing↗

Functional heterogeneity of transferrin-bound iron: iron uptake by cell suspensions from bone marrow and liver and by cell cultures of fibroblasts and lymphoblasts.

According to the hypothesis of Fletcher and Huehns, functional differences exist between both iron-binding sites of transferrin. The site designated A should mainly be involved in the delivery of iron to erythroid cells, whereas site B should donate its iron preferentially to cells involved in the absorption and storage of iron. In the present study this hypothesis could be confirmed by in vitro experiments with various cell types. Iron transferrin preincubated with rat bone marrow cells donates less iron to rat bone marrow cells, Chinese hamster fibroblasts, human fibroblasts and human lymphoblasts than freshly prepared iron transferrin equal in iron and transferrin concentraion. Rat liver parenchymal cells, however, take up more iron from preincubated than from freshly prepared iron transferrin. Obviously, site A not only donates iron preferentially to erythroid cells but also to (rapidly) dividing nonerythroid cells in culture. From experiments with iron transferrin mixtures in which radioiron was present at low or high iron saturation, it could be concluded that rat bone marrow cells take up iron equally well from monoferric as from diferric transferrin. The observed functional heterogeneity could, therefore, not be ascribed to differences between monoferric and diferric transferrin.

Animals↗