Biomedical subjects
M Janssen
Publications and source records attributed to M Janssen.
Cell lineage characteristics of human prostatic stromal cells cultured in vitro.
BACKGROUND: An in vitro model of prostatic stromal cells suitable for experimental studies of the pathogenesis of BPH is still lacking. We therefore standardized the isolation, cultivation, and characterization of human prostatic stromal cell lineages. METHODS: Stromal cells were isolated from a surgical specimen of BPH. Using antibodies specific for either epithelial or stromal cells of the human prostate, the isolated cells were morphologically and immunohistochemically characterized. Viability and functional activity were assessed by proliferation assays and stimulation experiments. Gene expression was monitored by RT-PCR. RESULTS: In early passages (P8), cells showed a high purity (>/=98%) for stromal markers; about 60% displayed the characteristics of fibroblasts, and the remaining 40% were classified as smooth muscle cells. In late passages (P20), the proportion of muscle cells declined to 10%. Stimulation experiments including basic fibroblast growth factor (bFGF) resulted in enhanced proliferation, whereas dihydrotestosterone (DHT), estrogen, and flutamide did not influence proliferation. Gene expression studies demonstrated a positive signal for androgen receptor and keratinocyte growth factor (KGF). CONCLUSIONS: Prostatic stromal cells can be propagated several times and show karyotypic stability for up to 18 subculture experiments. The ratio of myoid and fibroblastic cells can be used for standardization of cell cultures with stable characteristics.
Efficiency of light utilization of Chlamydomonas reinhardtii under medium-duration light/dark cycles.
The light regime inside a photobioreactor is characterized by a light gradient with full (sun)light at the light-exposed surface and darkness in the interior of the bioreactor. Consequently, depending on the mixing characteristics, algae will be exposed to certain light/dark cycles. In this study the green alga Chlamydomonas reinhardtii was cultivated under five different light regimes: (1) continuous illumination; (2) a square-wave light/dark cycle with a light fraction (epsilon) of 0.5 and a duration (t(c)) of 6.1 s; (3) epsilon=0.5, t(c)=14.5 s; (4) epsilon=0.5, t(c)=24.3 s and (5) epsilon=0.8, t(c)=15.2 s. The biomass yield on light energy, protein per photons, decreased under light/dark cycles (epsilon=0. 5) in comparison to continuous light (CL), from 0.207 (CL) to 0.117-0.153 g mol(-1) (epsilon=0.5). Concomitantly, the maximal specific photosynthetic activity, oxygen production per protein, decreased from 0.94 (CL) to 0.64-0.66 g g(-1) h(-1) (epsilon=0.5). Also the quantum yield of photochemistry, yield of the conversion of light energy into chemical energy, decreased from 0.47 (CL) to 0. 23 (epsilon=0.5, t(c)=24.3 s). Apparently, C. reinhardtii is not able to maintain a high photosynthetic capacity under medium-duration light/dark cycles and since specific light absorption did not change, light utilization efficiency decreased in comparison to continuous illumination.
Images in Cardiovascular Medicine. Aberrant right subclavian artery mimics aortic dissection.
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Carcinoid crisis during transesophageal echocardiography.
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Dysphagia lusoria: clinical aspects, manometric findings, diagnosis, and therapy.
OBJECTIVE: The lusorian artery is a rare anomaly of the right subclavian artery. This artery arises from the aortic arch distal of the left subclavian artery, crossing the midline behind the esophagus. Normally this anomaly causes no symptoms. Sometimes dysphagia first appears above the age of 40 yr. METHODS: In the period of 1992-1997, the diagnosis of an aberrant right subclavian artery was made in five patients with dysphagia who were referred to a small community hospital. A sixth patient had a right-sided aorta with an aberrant left subclavian artery. RESULTS: Endoscopy revealed a pulsating impression in the esophagus of three patients. Four patients had coexisting esophageal abnormalities. Barium contrast examination of the esophagus showed a characteristic diagonal impression at the level of the fourth thoracic vertebra in all patients. Computed tomography and angiography confirmed the diagnosis and excluded aneurysms. Manometric investigation of the esophagus revealed nonspecific abnormalities in five patients. Drug treatment was sufficient in three patients (mean follow-up, 6.2 yr). Three patients were operated upon because of persistent dysphagia. Through a cervical approach the artery was ligated near its root and connected with the right carotid artery. Postoperatively two patients became symptom-free, the other patient still has intermittent dysphagia. CONCLUSION: Dysphagia can be caused by a rare anomaly of the subclavian artery. The diagnosis can be overlooked at endoscopy, but barium contrast study of the esophagus will reveal the abnormality. In patients with coexisting esophageal abnormalities the finding may be incidental and specific conservative treatment may be sufficient. Manometry cannot be used to diagnose this condition or to predict surgical outcome. When the symptoms are intractable, surgical correction should be considered even if coexisting esophageal abnormalities are present.
[Chorea due to acute rheumatic fever in a 9 year old girl].
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Fibronectin in human prostatic cells in vivo and in vitro: expression, distribution, and pathological significance.
In the present study we examined the expression and release of the extracellular matrix glycoprotein fibronectin (FN) in a prostate cancer cell line (LNCaP) and in primary prostatic stromal cells using the reverse transcription-polymerase chain reaction (RT-PCR) and by an enzyme-linked immunosorbent assay. Perturbation experiments in vitro using antibodies directed against FN and the FN receptor were also performed. Immunohistochemistry was used to show the in vivo distribution of FN and the FN receptor in tissue sections of normal human prostate, benign prostatic hyperplasia, and prostate carcinoma. The expression of the oncofetal FN ED-B segment in benign prostatic hyperplasia and prostate carcinoma tissue was investigated by RT-PCR. The FN mRNA was expressed by LNCaP and primary prostatic stromal cells, respectively. Both cell types released FN into the medium in a time-dependent manner, whereby FN secretion was about 2.5-fold higher in cultures of stromal cells relative to LNCaP cells. Blocking FN with anti-FN antibodies resulted in a significant decrease in cell adhesion for LNCaP cells and a change in morphology for the primary stromal cells. FN was located mainly in the stromal compartment of the prostate, showing a distinct distribution pattern in prostate carcinoma, whereas the FN receptor was detectable only in the prostate epithelia. RT-PCR experiments showed the expression of the oncofetal FN ED-B segment in benign prostatic hyperplasia and prostate carcinoma tissue, with a 3.5-fold higher expression in the prostate carcinoma probes. Our data point to an important role for FN in cell adhesion of prostatic cells and show that an alternatively spliced FN mRNA is upregulated in the pathologically altered human prostate.
Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts.
STUDY DESIGN: Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. RESULTS: The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS: The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence.
Neurogenic origin of human prostate endocrine cells.
OBJECTIVES: To determine the histogenetic origin of prostate neuroendocrine cells in human embryos. METHODS: Prostatic tissue in human fetuses, ranging in gestational age from early week 10 to term, and infantile and pubertal glands were studied immunohistochemically. The distribution of neuroendocrine cells within the developing gland was semiquantitatively determined. Antibodies against the neuroendocrine markers chromogranin A (CgA) and protein gene product 9.5 (PGP), along with markers of prostatic secretion (prostate-specific antigen [PSA], prostatic acid phosphatase [PAP]), were used. They were applied either individually or in double-labeling experiments, as well as in experiments combining CgA immunohistochemical analysis with in situ hybridization or in situ end-labeling. RESULTS: In embryos of less than 65-mm crown-rump length (CRL) (ie, younger than 12 weeks of gestation), the epithelium of the urogenital sinus was free of endocrine cells. On either side of the future prostatic mesenchyme, paraganglia containing CgA-immunoreactive cells are present, which start to penetrate the urogenital mesenchyme. In the late 10th week, these CgA-immunoreactive cells are found dispersed in the urogenital mesenchyme. In embryos of 65-mm CRL, when prostatic anlagen start to sprout from the urogenital epithelium, very few (but typically shaped) neuroendocrine cells appear in the urogenital sinus epithelium. Later, after the 12th week, when solid prostatic ducts have started forming, CgA-immunoreactive neuroendocrine cells are also present in these buds. The number of neuroendocrine cells in the urethral epithelium is considerably increased, and with the continuous sprouting and lumen formation of prostatic anlagen, neuroendocrine cells are transported into the future gland. Neuroendocrine cells observed in stroma of prenatal and postnatal prostates may also contribute to the neuroendocrine cell population of the gland. CONCLUSIONS: Our results provide the first evidence that human prostate neuroendocrine cells represent a cell lineage of their own, being of neurogenic origin and therefore distinct from the urogenital sinus-derived prostate secretory and basal cells.
Internal organ motion in prostate cancer patients treated in prone and supine treatment position.
BACKGROUND AND PURPOSE: To compare supine and prone treatment positions for prostate cancer patients with respect to internal prostate motion and the required treatment planning margins. MATERIALS AND METHODS: Fifteen patients were treated in supine and fifteen in prone position. For each patient, a planning computed tomography (CT) scan was used for treatment planning. Three repeat CT scans were made in weeks 2, 4, and 6 of the radiotherapy treatment. Only for the planning CT scan, laxation was used to minimise the rectal content. For all patients, the clinical target volume (CTV) consisted of prostate and seminal vesicles. Variations in the position of the CTV relative to the bony anatomy in the four CT scans of each patient were assessed using 3D chamfer matching. The overall variations were separated into variations in the mean CTV position per patient (i.e. the systematic component) and the average 'day-to-day' variation (i.e. the random component). Required planning margins to account for the systematic and random variations in internal organ position and patient set-up were estimated retrospectively using coverage probability matrices. RESULTS: The observed overall variation in the internal CTV position was larger for the patients treated in supine position. For the supine and prone treatment positions, the random components of the variation along the anterior-posterior axis (i.e. towards the rectum) were 2.4 and 1.5 mm (I standard deviation (1 SD)), respectively; the random rotations around the left-right axis were 3.0 and 2.9 degrees (1 SD). The systematic components of these motions (1 SD) were larger: 2.6 and 3.3 mm, and 3.7 and 5.6 degrees, respectively. The set-up variations were similar for both treatment positions. Despite the smaller overall variations in CTV position for the patients in prone position, the required planning margin is equal for both groups (about 1 cm except for 0.5 cm in lateral direction) due to the larger impact of the systematic variations. However, significant time trends cause a systematic ventral-superior shift of the CTV in supine position only. CONCLUSIONS: For internal prostate movement, it is important to distinguish systematic from random variations. Compared to patients in supine position, patients in prone position had smaller random but somewhat larger systematic variations in the most important coordinates of the internal CTV position. The estimated planning margins to account for the geometrical uncertainties were therefore similar for the two treatment positions.
Long-term psychosocial adjustment following pediatric liver transplantation.
This study assessed long-term psychosocial adjustment to pediatric liver transplantation in 146 patients aged 4-25 yr, who had received a transplant 2-12 yr previously. Evaluations of psychosocial adjustment and related variables were based on the Harter Self-Perception Profiles for children, Child Behavior Checklist (CBCL), and children's academic level. Up to the age of 8 yr, transplant children as a group did not perceive themselves as less competent than healthy peers. Gender effects were characterized by older girls perceiving significantly less scholastic cognitive competence than their healthy peers. Adolescent and young adult boys had significantly lower global self-worth and lower perceived athletic competence than their healthy peers. In comparison to normative data of healthy children, CBCL parent-reported scores revealed significant deficits in competences for all age groups. Only for the older boys, however, did these deficits reported by the parents reach a pathological level. The majority of transplant children also had significantly higher problem scores, but they remained within the normal range, except for the older boys whose internalizing problems reached a borderline level. Our results suggest that liver transplantation does not substantially affect schooling. Regardless of statistically significant differences in psychosocial adjustment, the majority of the transplant children functioned at a normal level. For adolescent and young adult boys, however, the presence of problems and the lack of competences observed by parents and by the youngsters themselves reached borderline to pathological levels. Our findings stress the importance of psychological post-transplant follow-up with increased attention of caregivers to child and parental concerns about their long-term psychosocial adjustment process.
Post-streptococcal reactive arthritis: a clinical and serological description, revealing its distinction from acute rheumatic fever.
OBJECTIVE: To follow-up prospectively patients with arthritis after infection with beta-haemolytic streptococci of Lancefield group A (beta HSA), with emphasis on clinical characteristics and serological features. We additionally investigated whether these patients, though often fulfilling the Jones' criteria for acute rheumatic fever (ARF), had a disease with clinical characteristics different from ARF. DESIGN: We performed a systematic prospective observational study of consecutive patients at a Dutch Outpatient Clinic and Department of Rheumatology, with arthritis after throat infection with beta HSA presenting to rheumatologist or internist from September 1992 until September 1996. Main outcome measures were clinical and biochemical characteristics with special reference to carditis. RESULTS: A total of 23 patients (21 Dutch, two Turkish; female/male ratio 15/8; mean (SD) age 42 (14) years) with predominantly non-migratory arthritis were included. A positive throat swab culture was obtained in 17%. All patients showed a significant rise of antistreptolysine-O (ASO; normal < 200 i.u. mL-1) and antideoxyribonuclease-B (anti-DNase-B; normal < 200 i.u. mL-1) titre. The mean (SEM) maximal ASO was 1305 (195) i.u. mL-1, and anti-DNase-B titre 980 (115) i.u. mL-1. Arthritis was present in mean (SEM) 5.4 (0.9) joints: 2.2 (0.7) small, 3.2 (0.4) larger joints. The arthritis was monarticular in 23% of the patients, oligoarticular in 35%, and polyarticular in 43%. Skin abnormalities were present in 12 patients: erythema nodosum in seven patients (30%), and erythema multiforme in five patients (22%). A transient cholestatic hepatitis was found in four patients (17%). In two patients a transient first-degree conduction block was found; however, neither echocardiography nor clinical course supported carditis. All patients were advised to receive monthly penicillin prophylaxis during a period of 2 years. Two patients refused to follow medical advice: in one a non-migratory arthritis recurred 15 months after the first episode of arthritis. CONCLUSION: Commonly, arthritis secondary to beta HSA infection in the Netherlands, a prosperous West-European country with State Welfare, is not accompanied by carditis, contrary to literature on classical ARF. Other factors discriminating it from ARF are the age of onset, the non-migratory character of the arthritis, the high frequency of erythema nodosum and multiforme, as well as the presence of transient hepatitis. As arthritis is the hallmark of this syndrome, post-streptococcal reactive arthritis (PSRA) is the most proper name for this disease entity. Whether penicillin profylaxis is needed in PSRA, as it is in ARF, warrants further prospective investigation.
Employment careers of young type I diabetic patients in The Netherlands.
The factors that influence the employment careers of diabetic patients aged 20 to 34 years were studied using a mail questionnaire. The study included all members of the Dutch diabetics association (Diabetes Vereniging Nederland) in that age group. A total of 5987 questionnaires were mailed; 4300 completed questionnaires were returned, giving a response rate of about 72%. The aim of the study was to provide a better insight into the problems type I diabetic patients face in the labor market: entry into the labor market, conditions at work, and (premature) exit from the labor market owing to health reasons. This study carefully distinguished between employability and employment. Results showed that having diabetes did not decrease the chances of entry into the labor market for the subjects, although some types of jobs are still unavailable for diabetic patients. There was no higher unemployment in the study population than in the general population. Although there were problems faced by patients in the work situation, they were generally limited to a small group.
A clinical and serological comparison of group A versus non-group A streptococcal reactive arthritis and throat culture negative cases of post-streptococcal reactive arthritis.
OBJECTIVE: To identify clinical and serological differences of patients with reactive arthritis after infection with Lancefield group A beta-haemolytic streptococci (GAS), compared with non-group A-that is, group C or G streptococci (NGAS:GCS/GGS), and a group of culture negative or unidentified streptococci (GUS). METHODS: A prospective study of consecutive patients with reactive arthritis after serologically or culture confirmed infection with beta-haemolytic streptococci, presenting to the outpatient department of rheumatology from January 1992 until January 1998. Alternative causes for reactive arthritis were excluded. Main outcome measures were clinical and serological characteristics including antistreptolysine-O (ASO) and antideoxyribonuclease-B (antiDNase-B) antibody titres. RESULTS: 41 patients (female/male ratio 22/19; mean (SD) age 38 (13) years) with reactive arthritis were included. Culture of throat swab was positive in 13 cases (32%): 6 (15%) GAS, 7 NGAS (17%), that is, 5 (12%) GCS, 2 (5%) GGS. In 28 cases throat culture remained negative resulting in a group of unidentified streptococci; antibiotic pre-treatment had been given by the general practitioner in 18 cases (64%). Arthritis was non-migratory, the number of arthritic joints in GAS and NGAS was similar, whereas in NGAS patients fewer joints were involved than in GUS: mean (SEM) 36 swollen joint index: 3.3 (1.0) in NGAS v 5.6 (1.0) in GUS (p<0.005); 28 swollen joint index: 2.9 (1.0) in NGAS v 4.3 (0.8) in GUS (p<0.05). Extra-articular manifestations-that is, erythema nodosum/ multiforme, AV conduction block or hepatitis-were observed after GAS or GUS infection, but not after NGAS infection. ASO and/or antiDNase-B rose significantly in all patients. The maximal titres for ASO and antiDNase-B in 41 PSRA patients were: mean (SEM) 1242 (232) U/l and 890 (100) U/l respectively; the maximal ASO titres were similar in the three groups: mean (SEM) 1125 (185) in GAS, 625 (160) in NGAS (GAS v NGAS: p=0.17), and 1430 (320) U/l in GUS (NGAS v GUS: p=0.10). AntiDNase-B titres were: mean (SEM) 1075 (180) in GAS, 375 (105) in NGAS (GAS v NGAS: p<0.01), and 995 (125) U/l in GUS (NGAS v GUS: p<0.005). ASO: antiDNase-B ratios were: mean (SEM) 0.89 (0.21) in GAS, 2.60 (0.76) in NGAS (GAS v NGAS: p<0.05), and 1.43 (0.28) in GUS (NGAS v GUS: p=0.12). CONCLUSION: Post-streptococcal reactive arthritis occurs not infrequently. Differentiation of PSRA based on the causative streptococcal strain is frequently thwarted by negative throat cultures. Sometimes extra-articular manifestations are present that exclude NGAS as the causative organism. Serologically, lower antiDNase-B titres may be indicative for primary NGAS infection; the ASO/antiDNase-B ratio may be of additive value for differentiation in cases of a negative throat culture: the higher ASO/antiDNase-B ratios suggesting primary NGAS infection. In reactive arthritis, serological monitoring consisting of a simultaneous titration of antiDNase-B and ASO, seems to be of clinical importance to trace GAS induced cases, especially when throat cultures remain negative.
Vertical migration behaviour of diatom assemblages of Wadden Sea sediments (Dangast, Germany): a study using cryo-scanning electron microscopy.
The vertical migration behaviour of diatom assemblages inhabiting Wadden Sea sediments near Dangast (Germany) was investigated using cryo-scanning electron microscopy. The diatom assemblages were dominated by small Navicula species. Intertidal sediments which were located at different distances from the high tide level or stayed submerged even throughout low tides were chosen. Samples were prepared and cryofixed in the field. Sampling was restricted to three sets: (i) before the onset of vertical migration, (ii) 3 to 5 h after the onset of vertical migration, and (iii) before the area became flooded again or just prior to dusk. The diatom assemblages inhabiting the different types of sediments did not always show the same response. When the tidal cycle exposed the sediment surfaces during the night cell densities increased in the early morning hours with the onset of light. Later on, although the photon flux density was still increasing, cell densities stayed constant or decreased before the water flooded the areas around noon. In experiments in which the water drained off around noon and the areas became exposed throughout the entire afternoon, cell densities increased even up to dusk when the photon flux density had dropped to values below 20 microM photons m-2 s-1. In an experiment in which the last sampling occurred at 10.15 pm, when the photon flux density had already declined below 10 microM photons m-2 s-1, cell densities had decreased to lower values. This was ca. 1 h before the area was flooded again. Finally, cryo-scanning electron microscopy revealed frequently occurring micro-patches of diatom assemblages which could be differentiated into typical areas of lower and higher cell densities further complicating the pattern of light or water cover induced movements.
[The spread of a 'Dutch' methicillin-resistant Staphylococcus aureus strain].
Following isolation of a methicillin-resistant Staphylococcus aureus (MRSA) in a patient subjected to amputation below the knee because of a vasculopathy, further investigations were carried out. Nose, throat and wound cultures were taken from staff and patients who had had contact with the index patient. After taking inventory cultures and cleansing of the two wards involved, these wards were quarantined. The bacterial strain was characterized using microbiological standard methods. The MRSA was encountered in a total of nine patients and two nurses. An infection due to this MRSA was found in two patients and one nurse. Eradication in the hospital was successful. MRSA with the same phage type was found in one nurse and one patient in two nearly hospitals and in one patient in a nearby city. Anamnestically, there had been no contact between them. Tracing this sort of outbreak in time is not possible with the current preventive MRSA policy because there are no demonstrable risk groups for a MRSA occurring in the Netherlands. Routine checking for MRSA carriership among nursing personnel and long-staying surgical patients is a possibility to detect spread of this MRSA. It appears advisable to take restrictive measures even against this S. aureus with restricted resistance, because neither penicillins nor cephalosporins are efficacious. In general, more attention should be given to prevention of nosocomial transmission of S. aureus.
Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation.
Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute liver failure (n = 22). The 5-year survival was 73.6% for the 209 children grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P < 0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1 year of age at transplantation was 88.8% and 80. 3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.