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Biomedical subjects

S Marcelis

Publications and source records attributed to S Marcelis.

At least 19 recordsLinked to original sources
PubMed2000

Two novel 14-Epi-analogues of 1,25-dihydroxyvitamin D3 inhibit the growth of human breast cancer cells in vitro and in vivo.

The biological activity of two novel 14-epi-analogues of 1,25(OH)2D3, 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527), is described. Both analogues were at least 10 times more potent than 1,25(OH)2D3 in inhibiting in vitro cell proliferation and had much lower in vivo calcemic effects than 1,25(OH)2D3. Treatment with 1,25(OH)2D3, TX 522, or TX 527 in vitro was accompanied by an accumulation of cells in the G1 phase of the cell cycle. Protein levels of cyclin C and cyclin D1 in in vitro cultures of MCF-7 cells were down-regulated to 50 and 30%, respectively, of control levels at 72 and 120 h after stimulation. Protein levels of p21 and p27 at 72 h were significantly enhanced by 1,25(OH)2D3 and TX 522 but surprisingly not by TX 527. The inability of TX 527 to up-regulate p21 seemed to be cell type specific because p21 was induced in other cell types. Diminished phosphorylation of the retinoblastoma protein after treatment with 1,25(OH)2D3, TX 522, or TX 527 may ultimately contribute to the growth inhibition caused by these compounds. According to the data presented, the induction of apoptosis seemed not to be a major mechanism responsible for the growth-inhibitory effect of 1,25(OH)2D3 and analogues. Both 14-epianalogues significantly retarded tumor progression (40% reduced compared with control mice) in an in vivo model of MCF-7 breast cancer cells established in nude mice. In conclusion, these novel analogues have the eligible profile to be tested as therapeutic agents for the treatment of hyperproliferative diseases such as breast cancer.

Alkynes↗
PubMed1999

Modifications of the elbow induced by the practice of handball on radiography, US and MRI.

The objective of this study was to evaluate plain radiographs, US and MRI in detection of occult lesions of the elbow in asymptomatic handball players. Comparative plain films of both elbows were obtained in an anteroposterior and lateral projection. A bilateral comparative ultrasound examination was performed with measurement of the thickness of the flexor and extensor tendons, the triceps tendon, the lateral collateral ligament and the anterior bundle of the medial collateral ligament (MCL). Echogenicity of these structures was evaluated. Articular recesses were scanned for fluid and loose bodies. Axial and coronal MRI of the dominant elbow was performed using a T1W sequence after intravenous injection of gadolinium 30 minutes before the examination and by a FISP 3D T2W echo gradient sequence in coronal plane and reconstruction in a sagittal plane. Twenty-eight male asymptomatic members of the national handball team with 7 to 25 years of experience and undergoing 3 to 4 training sessions per week were studied. Paraphysiological modifications such as hypertrophy of bone and muscles were evidenced. Flexion deformity of the elbow was present even in the youngest players, but valgus deformity occurred preferentially in the more experienced players. US was more efficient in detection of small loose bodies and gave more precise information on the structure of the MCL and the tendons compared with MRI. Plain film and US were sufficient for the detection of chronic lesions of the elbow. MRI did not add significant findings.

Adolescent↗
PubMed1998

Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells.

1,25(OH)2D3 is a known growth inhibitor and differentiation inducer of several cancer cell lines. To establish the molecular mechanism of 1,25(OH)2D3 as an antiproliferating agent, its effect on proliferation and gene regulation was studied in human breast cancer MCF-7 cells. 1,25(OH)2D3 inhibited cell proliferation dose dependently through G1 arrest. Cyclin D1 transcription levels decreased rapidly in 1,25(OH)2D3-treated cells while protein levels only decreased after 72 h of treatment. Transcription levels of p21 and p27 were upregulated with chronologically consistent changes in cell cycle distribution. Experiments with TGF-beta neutralising antibodies revealed that the largest effect of 1,25(OH)2D3 on cell proliferation is likely due to a TGF-beta independent mechanism of action. The cell cycle regulatory genes, cyclin D1 and p27, are probably involved herein as their expression was not affected by the presence of neutralising antibodies. However, upregulation of p21 was completely abrogated. Therefore, the TGF-beta signalling pathway is thought to be responsible for p21 upregulation.

Blotting, Northern↗
PubMed1998

Evaluation of patellar cartilage surface lesions: comparison of CT arthrography and fat-suppressed FLASH 3D MR imaging.

The aim of this study was to evaluate the sensitivity and specificity of fat-suppressed fast low-angle shot (FLASH) 3D MR imaging in the detection of patellar cartilage surface lesions in comparison with CT arthrography. Fifty patients, with or without symptoms of chondromalacia, were prospectively examined by CT arthrography and fat-suppressed 3D gradient-echo MR imaging. All MR examinations were evaluated by three observers, two of them reaching a consensus interpretation. The lesions were graded according to their morphology and their extent. The CT arthrography was considered as the reference examination. For both sets of observers, the final diagnosis of chondromalacia was obtained in 92.5 %. The specificity was 60 % on a patient-by-patient basis. Fissures were missed in 83 and 60 %, respectively, but were isolated findings only in 2.5 % of the cases. Considering ulcers involving more than 50 % of the cartilage thickness, 65 and 88 %, respectively, were recognized. Fat-suppressed FLASH 3D is an adequate pulse sequence for the detection of patellar cartilage ulcers. It can be applied on a routine clinical basis, but it does not show as many fissures as CT arthrography and is less precise for grading of lesions.

Adolescent↗
PubMed1998

[Inflammatory spondylodiscitis as a unique radiological manifestation of the SAPHO syndrome].

We describe two cases of SAPHO with an exclusive spinal involvement. Diagnosis was established by sterno-clavicular arthralgias, palmar and plantar pustulosis and by radiological signs of inflammatory spondylodiscitis and vertebral osteitis. Spondylodiscitis and medullary edema resolved as shown by MRI after administration of steroids in one case and methotrexate in the other.

Acne Vulgaris↗
PubMed1997

Ultrasound examination of the wrist.

Ultrasonography of the wrist requires knowledge of the normal anatomy and dedicated ultrasound equipment. The patient's complaints orientate the examination. Real time dynamic examination provides essential information. In tendon pathology, ultrasound demonstrates better than MRI partial rupture, different types of synovitis and nodular deposits such as tophi, amyloid or pannus. In opposition to ganglion cysts, a joint communication is seen in arthrosynovial cysts. In carpal tunnel syndrome, the surface of the median nerve exceeds 15 sqmm. Ultrasound can demonstrate in specific cases traumatic lesions of bony surfaces or lesions of the triangular fibro-cartilage.

Adipose Tissue↗
PubMed1997

Ultrasound of the elbow.

Ultrasound examination of the elbow should be performed in a comparative way, exploring joint spaces and fossas. Ultrasound is the method of choice for the detection of joint fluid and loose bodies. Tendinitis and microfissures can be demonstrated in case of tennis and golfer elbow. On the posterior aspect of the elbow, ultrasound shows the different types of bursitis, and allows evaluation of the ulnar nerve in cases of impingement.

Bursitis↗
PubMed1997

Low back pain and nuclear medicine.

Low back pain (LBP) is a major cause of disability in many patients during some time of their lives. In this article the role of nuclear medicine, and more in particular the role of single photon emission tomography (SPECT), in the investigation of LBP is discussed by reviewing the literature. Because of the improved anatomical localization of lesions in the vertebral body when up-to-date SPECT is used, this technique is a powerful imaging modality in patients with LBP. Bone scintigraphy therefore can contribute significantly in the diagnosis of patients with LBP. In cases where conventional radiological techniques fail to elucidate the cause of LBP performing a bone scintigraphy with SPECT should strongly be recommended.

Diagnosis, Differential↗
PubMed1996

Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific.

Ketoconazole (keto) or liarozole (liaro), inhibitors of the cytochrome P450 enzymes that mediate vitamin D and A hydroxylations, could potentiate the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analogs. Proliferation of MCF-7 and T47-D human breast cancer cells, MG-63 human osteosarcoma cells and HL-60 human promyeloid leukemia cells was concentration dependently inhibited by 1alpha,25(OH)2D3. The vitamin D analogs KH 1060 [20-epi-22-oxa-24,26,27-trihomo-1alpha,25(OH)2D3], RO 23-6010 [16-ene-23-yne-26-trifluoro-1,25(OH)2D2D3], ZXY 835 [20-epi-23-yne-25,26-epoxy-1alpha(OH)D3], and CD 99 [11alpha-methyl-1alpha,25(OH)2D3] were 150-,58-,16- and 7-fold more potent than 1alpha,25(OH)2D3 in inhibiting the proliferation of MCF-7 cells, respectively. A similar rank order of potency was observed in other cell lines. The antiproliferative effects of the vitamin D hormone and analogs was enhanced in MCF-7 cells when coincubated with 1 microM keto (7-, 10-, 5-, 25- and 1.3-fold more potent than in the absence of keto), respectively. The antiproliferative effect was less enhanced when 1alpha,25(OH)2D3 or its analogs KH 1060, ZXY 835 and RO 23-6010 were combined with liaro (3-, 7-, 2- and 3-fold, respectively). Keto and liaro did not markedly potentiate the activity of 1alpha,25(OH)2D3 or its analogs in MG-63 or HL-60 cells. These results suggest that differences in cellular metabolism can at least partially explain the different potency of vitamin D analogs. Moreover, the metabolism of vitamin D analogs is cell-type specific.

Calcitriol↗
PubMed1995

Interpretation of abnormal lumbosacral spine radiographs. A test comparing students, clinicians, radiology residents, and radiologists in medicine and chiropractic.

STUDY DESIGN: Controlled comparison of radiographic interpretive performance based on training and experience. OBJECTIVES: This study compared each of these groups in medicine and chiropractic by testing abilities to interpret abnormal plain film radiographs of the lumbosacral spine and pelvis. SUMMARY OF BACKGROUND DATA: Low back pain is a common and costly problem that is evaluated and treated primarily by medical physicians, orthopedists, and chiropractors. Although radiology is used extensively in patients with low back pain, the radiographic interpretations of students, clinicians, radiology residents, and radiologists have never been compared. METHODS: Four hundred ninety-six eligible volunteers from nine target groups completed a test of radiographic interpretation consisting of nineteen cases with clinically important radiographic findings. The nine groups included 22 medical students, 183 chiropractic students, 27 medical radiology residents, 13 chiropractic radiology residents, 66 medical clinicians (including 12 general practice physicians, 25 orthopedic surgeons, 21 orthopedic residents, and 8 rheumatologists), 46 chiropractic clinicians, 48 general medical radiologists, 55 chiropractic radiologists, and 36 skeletal radiologists and fellows. RESULTS: The test established a high level of internal consistency reliability (0.880) and revealed that, in the interpretation of abnormal plain film radiographs of the lumbosacral spine and pelvis, significant differences were found among professional groups (P < 0.0001). Post hoc tests (P < 0.05) revealed that skeletal radiologists achieved significantly higher test results than did all other medical groups; that the test results of general medical radiologists and medical radiology residents was significantly higher than those of medical clinicians; that test results of medical students was significantly poorer than that of all other medical groups; that the performance of chiropractic radiologists and chiropractic radiology residents was significantly higher than that of chiropractic clinicians and chiropractic students; that no significant differences was revealed in the mean values of performance of chiropractic clinicians and chiropractic students; that the test results of chiropractic radiologists, chiropractic radiology residents, and chiropractic students was significantly higher than that of the corresponding medical categories (general medical radiologists, medical radiology residents, and medical students, respectively); that no significant difference in test results was identified between chiropractic radiologists and skeletal radiologists or between chiropractic and medical clinicians; and that the length of time in practice for clinicians and radiologists was not a significant factor in the test results. CONCLUSIONS: These data demonstrate a substantial increase in test results of all radiologists and radiology residents when compared to students and clinicians in both medicine and chiropractic related to the interpretation of abnormal radiographs of the lumbosacral spine and pelvis. Furthermore, the study reinforces the need for radiologic specialists to reduce missed diagnoses, misdiagnoses, and medicolegal complications.

Chiropractic↗
PubMed1995

Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 alpha, 25-(OH)2D3.

The hormone 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)2D3 on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)2D3 at 5 micrograms/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)2D3 at 2 micrograms/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)2D3 might be a potential dose-reducing agent for CsA in immunosuppressive therapy.

Amino Acids↗
PubMed1994

The biological activity of 23-oxa-, 23-oxa-24-oxo-, and 23-thia-dihydroxyvitamin D3.

Three analogs of 1 alpha,25-(OH)2D3 with an oxygen or another heteroatom at position 23 were synthesized in search of separating the cell-differentiating from the calcemic effects of the vitamin D hormone. Their ability to induce superoxide production in human myeloid leukemia cells (HL-60) was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 > 23-oxa-1 alpha, 25-(OH)2D3. 23-oxa-24-oxo-1 alpha, 25(OH)2D3 was slightly more potent than 1 alpha,25-(OH)2D3 in inhibiting cell proliferation in MCF-7 cells and 23-thia- and 23-oxa-1 alpha,25(OH)2D3 were less potent. Their in vitro potency to produce osteocalcin in MG-63 cells was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 = 23-oxa-1 alpha,25-(OH)2D3. All three analogs had reduced receptor and DBP affinity compared to 1 alpha,25-(OH)2D3. When these analogs were injected in rachitic chicks, only little calcemic effects were observed. The introduction of a heteroatom in carbon 23 of 1 alpha,25-(OH)2D3 thus creates analogs with dissociated action on cell differentiation and calcium homeostasis.

Animals↗
PubMed1993

Abnormalities of articular cartilage in the knee: analysis of available MR techniques.

In an attempt to improve the detection of chondral abnormalities with magnetic resonance imaging, a fat-suppressed three-dimensional gradient-recalled acquisition in the steady state (GRASS) and spoiled GRASS (SPGR) sequence was optimized by study of five cadaveric knee specimens. Results with this optimized sequence then were compared with results with three spin-echo (T1-, proton-density-, and T2-weighted) and two three-dimensional gradient-recalled echo sequences (GRASS and non-fat-suppressed SPGR) in the assessment of naturally occurring abnormalities of the patellofemoral compartment in 10 cadaveric knees. Results with the optimized fat-suppressed SPGR sequence were significantly better (P < .02) than results with the other five sequences and had a sensitivity of 96%, a specificity of 95%, and an accuracy of 95%. In addition, normal cartilage consistently appeared as a trilaminar structure with the fat-suppressed SPGR sequence, a feature that appeared to help in identification of chondral lesions.

Aged↗
PubMed1993

Cervical spine: comparison of 45 degrees and 55 degrees anteroposterior oblique radiographic projections.

The orientation of the intervertebral foramina (IVF) at six cervical levels on transaxial images in 65 magnetic resonance (MR) studies was determined to explain variations in size and shape evident on the 45 degrees standard radiographic oblique view. Analysis of MR imaging data showed that substantial variations in the orientation of the cervical IVFs occurred throughout the cervical spine and that a 55 degrees anteroposterior (AP) oblique view with standard radiography probably would lead to better visualization of the lower cervical IVFs. These results were confirmed with a radiographic and anatomic study of two cadaveric specimens. In a prospective clinical study of 23 patients, 45 degrees and 55 degrees AP oblique views were compared by measuring the maximal transverse diameter of all the cervical IVFs. IVF size was substantially increased on the 55 degrees AP oblique projection at all lower cervical levels. The 55 degrees AP oblique view of the cervical spine is optimal for evaluating the lower cervical foramina and can be a routine alternative to the 45 degrees oblique view in the analysis of all cervical foramina.

Adult↗