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Biomedical subjects

J Willems

Publications and source records attributed to J Willems.

At least 37 records · Page 2Linked to original sources

Pseudodystrophy at the lower limb in children.

The authors describe a 12-year old girl with a painful syndrome at the distal side of the left leg, resulting in limping, incapacity and severe muscle atrophy. Full investigation - no inflammatory laboratory signs, diffuse osteoporosis at the left leg, decreased bone mineral content at the same place, marked hypofixation on bone and vascular scintigraphy - suggested pseudodystrophy (5), which is often induced by psychological factors. Successful treatment was obtained by physiotherapy, hydrotherapy, slight doses of NSAID and psychological assistance. With regard to recent literature, the authors believe that reflex sympathetic dystrophy (RSD) in children is often over-diagnosed, since there are no recognised criteria for diagnosing RSD. Besides the clinical picture, changes on radiography (focal osteoporosis) and on scintigraphy (disturbed vascular scintigraphy with increased pooling in the initial phase and hyperfixation on bone scintigraphy) are necessary. When these are not available, pseudodystrophy is a more correct diagnosis.

Child↗

D-penicillamine-induced myositis in rheumatoid arthritis.

D-penicillamine, an agent still used in the treatment of rheumatoid arthritis (RA) may produce inflammatory myopathy or myositis. Some reported cases are documented with muscle biopsy. We report a 34-year old female, receiving the drug for more than 4 years, who consulted us with recently developed proximal muscle pain and weakness. EMG-findings were typical for inflammatory muscle disease; muscle enzymes remained normal. D-penicillamine was stopped and she was started on prednisolone with rapid improvement. The EMG-findings, with follow-up within three months, proved to be a good diagnostic tool, in the absence of laboratory muscle enzymes abnormalities.

Adult↗

Cyclic AMP-induced differentiation increases the synthesis of extracellular superoxide dismutase in rat C6 glioma.

The effect of membrane permeable cAMP analogues on the expression of extracellular superoxide dismutase (EC-SOD) was studied in rat C6 glioma. EC-SOD is constitutively expressed but stimulation with cAMP analogues still increased the EC-SOD transcription and the secreted SOD activity. The potency to enhance EC-SOD expression is correlated with the ability of the cAMP analogue to induce cAMP-dependent differentiation in C6. The increase in EC-SOD mRNA and in secreted activity depended on the concentration of the cAMP analogues and on the cultivation time. Twenty-four hours after addition of 0.5 mM N6, O'2-dibutyryl cAMP (dbcAMP) or N6-monobutyryl cAMP (N6-mbcAMP) EC-SOD mRNA expression increased approximately twofold, while stimulation for 68 h with 0.5 mM N6-mbcAMP or 1 mM 8-Chloro cAMP (ClcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell three- and fivefold, respectively. O'2-monobutyryl cAMP (O'2-mbcAMP) did not affect EC-SOD synthesis. The enhancement in EC-SOD activity did not require activation of protein kinase A. ATP, TGF-beta, IFN-gamma, and LPS did not affect EC-SOD synthesis. The presented data point to a cAMP-dependent pathway for the enhanced expression of EC-SOD by glial cells in brain.

8-Bromo Cyclic Adenosine Monophosphate↗

Cadherin-dependent cell aggregation is affected by decapeptide derived from rat extracellular super-oxide dismutase.

A synthetic HAV-containing decapeptide homologous to the amino acid sequence 44R-Q53 in rat extracellular superoxide dismutase B affects cadherin-dependent cell aggregation. Cell lines, some of them transfected, expressing different types of cadherins were tested using in vitro cell aggregation and cell dissociation assays. A concentration-dependent inhibition of aggregation by the EC-SOD-derived HAV-containing peptide was detected only in N-cadherin expressing cells. These results suggest the localisation and possible protective role of EC-SOD B for cells expressing N-cadherin.

Amino Acid Sequence↗

Information about drugs in family magazines.

Family magazines can play an important role in the diffusion of medical information and information regarding drugs to a 'lay audience'. We describe what kind of drugs are discussed in the family magazines and which information regarding these drugs is given. Furthermore, we look into the information sources for journalists; special attention is paid to the role of the pharmacist: is (s)he recognized by journalists as one of the experts on drugs? Two approaches were used in order to answer the above described research questions: a content analysis of family magazines and in-depth interviews of journalists. Gynaecological products as well as drugs for the central nervous system receive much attention in family magazines. The kind of information given about drugs is limited. Only part of the publications pays attention to side-effects. Patients asking questions about drugs in response to publications in family magazines know the name of a drug but are rarely informed about other aspects of the therapy, such as side-effects. In the provision of information physicians and medical specialists play an important role as sources of information for journalists. There is, however, until now no role for the pharmacist as a source of information on drugs in family magazines.

Drug Therapy↗

Polar agents with differentiation inducing capacity potentiate tumor necrosis factor-mediated cytotoxicity in human myeloid cell lines.

Cotreatment or pretreatment of several human myeloid cell lines (KG1, HL60, U937, THP1) with the differentiation inducer DMSO was found to potentiate the antiproliferative and cytotoxic effects of TNF. In addition, TNF-resistant monocytic cell lines could be sensitized to TNF cytotoxicity by DMSO treatment. Other highly polar molecules, known to be potent differentiation inducers, showed similar effects to those of DMSO. The potentiating effect of DMSO was related neither to an up-regulation of TNF receptor expression nor to an alteration in the rate of TNF internalization and degradation. We present evidence that the TNF activities are p55 TNF receptor-mediated and are not due to insertion of TNF into lipid bilayers, an effect that could be susceptible to DMSO, as this component has been described to modify cell membrane characteristics. DMSO-induced potentiation of TNF cytostasis/cytotoxicity was restricted to myeloid leukemia cell lines. In non-myeloid cells such as fibrosarcomas, myosarcomas, thymomas, or carcinomas, DMSO was found either not to alter or to inhibit TNF-induced cell death. The latter results are in good agreement with data reported by others who suggested that DMSO could act as a scavenger of TNF-induced toxic radical formation. The potential correlation in myeloid cells between DMSO-induced changes in the cells' differentiation status and DMSO-enhanced TNF-susceptibility is discussed.

Animals↗

Reduction of extracellular superoxide dismutase activity by decapeptide derived from FGF-receptor.

Several synthetic decapeptides containing an HAV tripeptide motif were tested for their ability to modulate the enzymatic activity of rat extracellular SOD, an enzyme which also contains an HAV motif. Out of nine decapeptides that were tested, only a FGF-receptor derived peptide was active as a negative modulator of enzyme activity. These results strengthen the thesis that HAV motifs are not only involved in homophilic interactions and suggest that soluble FGF-receptor molecules might moderate the activity of extracellular SOD.

Amino Acid Sequence↗

Setting the agenda: does the medical literature set the agenda for articles about medicines in the newspapers?

The source of ideas and information on medicines most important to journalists in the Netherlands, and most commonly consulted by them, is known to be the scientific medical literature. In this study we therefore, explored the relation between the kind of medicines discussed in the scientific medical literature and those discussed in newspapers. A content analysis of scientific medical journals was combined with a content analysis of Dutch daily newspapers. The results show an agreement in the main groups of medicines discussed in the scientific medical literature and newspapers. In both the newspapers and the professional journals anti-infective medication and drugs for the central nervous system are the groups of medicines most frequently discussed. Although it has been suggested that 'bad news' is more newsworthy then 'good news', the negative consequences of the use of medicines received proportionally more attention in the professional literature than in the newspapers.

Drug Therapy↗

Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue.

A protein was isolated from rat C6 glioma-conditioned medium and was biochemically characterized. The heparin-binding protein has a native molecular mass of 55-75,000 Da, a molecular mass of 40-48,000 Da under denaturing conditions, and a pI of 5.0-6.0. Based on the determined partial amino acid sequences, the full lenght cDNA encoding the rat and human proteins were cloned. The cDNA sequences identified the isolated rat and human protein as the homologue of a recently reported mouse osteoblast-transforming-growth-factor-beta 1-inducible protein, encoded by the TSC-36 gene [Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T. & Nose, K. (1993) Eur. J. Biochem. 217, 13-19]. Analysis of the human, rat and mouse amino acid sequences indicates that these proteins are highly conserved (> 92% sequence identity). Sequence similarities with follistatin and the follistatin-like domain of agrin are revealed. The relationship with follistatin and agrin points to possible common functions for the cloned follistatin-related proteins (FRP). The protein has no effect on the inhibitory action of transforming growth factor-beta 1, on CCl-64 cell growth.

Agrin↗

Discrepancy between visual estimation and computer-assisted measurement of lesion severity before and after coronary angioplasty.

One hundred fourteen coronary stenoses were quantified before and after percutaneous transluminal coronary angioplasty (PTCA) using a semi-automated digital system. The values obtained were considered as standard for comparison with visual estimation by the PTCA operator as well as by independent consensus-reading. The measured percent stenosis was 62.7 +/- 13.7% before and 27.7 +/- 12.4% after angioplasty. Before PTCA, the operator consistently overestimated stenosis severity (87.8 +/- 8.5%, P < 0.0001) and consensus-reading reduced but did not eliminate this overestimation (78.0 +/- 12.3%, P < 0.05). The error in visual estimation was inversely correlated with the measured degree of stenosis: coefficients were -0.79 (P < 0.0001) and -0.51 (P < 0.0001) for operator and consensus-readers, respectively. After PTCA, the operator underestimated the residual stenosis (21.2 +/- 9.9%, P < 0.0001) but there was no systematic bias by consensus-reading (29.4 +/- 12.0%, NS). Again the error in visual estimation was inversely correlated with the measured degree of residual stenosis: coefficients were -0.76 (P < 0.0001) and -0.58 (P < 0.0001) for operator and consensus-reading, respectively. In conclusion, the operator overestimates lesion severity before and underestimates moderate residual stenoses after PTCA, a problem only partially corrected by independent consensus-readers.

Angioplasty, Balloon, Coronary↗

Journalists and their sources of ideas and information on medicines.

In this article we describe from which sources science writers who write about medicines in daily newspapers get their ideas and information. This study was undertaken because mass media, and therefore newspapers, can play an important role in the diffusion of information about medicines. Two approaches, interviews and a content analysis, were used to answer the research questions. Both methods show the importance of professional medical journals and information from universities and their hospitals as sources of ideas and information. Although the pharmaceutical industry did not seem to play a role as source of ideas and information according to the journalists, it is the third most frequently cited source of information in the newspaper articles. To gain a better insight in the role of the pharmaceutical industry as source of ideas and information for newspaper journalists further research is necessary.

Drug Industry↗

Acute and subacute organophosphate poisoning in the rat.

The intermediate syndrome in organophosphate poisoning is clinically characterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. It occurs between the acute cholinergic crisis and the usual onset of organophosphate-induced delayed neurotoxicity. The weakness has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizing myopathy in rats in relation to the clinical course and the acetylcholinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of cholinergic symptoms and of AChE inhibition after either paraoxon and mipafox, or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studied. Maximal muscle involvement occurs within the first 2 days of the poisoning with all organophosphates studied. The myopathy is not aggravated by a further decline in AChE activity in fenthion poisoning. Our data argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE inhibition being involved.

Animals↗

Purification and sequence of rat extracellular superoxide dismutase B secreted by C6 glioma.

An enzyme which converts radical oxygen, produced by phorbol 12-myristate 13-acetate activated neutrophils, into nonluminescent products is secreted by rat C6 glioma. The enzyme was purified from chemically defined conditioned media and identified as an extracellular superoxide dismutase (EC-SOD). The purified enzyme is distinct from human EC-SOD C (Hjalmarsson, K., Marklund, S. L., Engström, A., and Edlund, T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6340-6344) by its elution from heparin-Sepharose at 300-400 mM NaCl, its pI of 6.1-7.2, and its native M(r) of 85,000 +/- 20,000. The rat EC-SOD is a dimer with a subunit M(r) of 34,000-36,000 and is extensively modified by post-translational processing. Although rat EC-SOD has a high sequence homology with the catalytic center and the polybasic heparin-binding site near the COOH terminus of human EC-SOD C, its NH2-terminal sequence and the sequences flanking the heparin-binding site differ substantially. The sequence of the isolated rat EC-SOD cDNA fully confirms the data obtained from amino acid sequence analysis. The amino acid sequence of the enzyme and its biochemical properties support its identification as the rat EC-SOD B.

Amino Acid Sequence↗

"In vitro" effect of interleukin-1 beta on human glioma cell lines: regulation of cell proliferation and IL-6 production.

The human glioma cell lines U251 and HP591 were chosen as "in vitro" models for functional astrocytes. When cultured in the presence of IL-1 beta these cell lines demonstrated a marked increase in interleukin-6 production and in [3H]-thymidine uptake. The addition of dbcAMP could mimic the first effect of IL-1 beta but at the same time suppressed cell proliferation. These results suggest that IL-1 beta possibly exerts one of its biological effects (IL-6 synthesis) by means of the cyclic AMP pathway.

Bucladesine↗

Posttreatment itraconazole levels in the nail. New implications for treatment in onychomycosis.

BACKGROUND: A problem in the treatment of onychomycosis is the lengthy duration of therapy. The pharmacokinetics of itraconazole suggest a potential for briefer treatment. OBJECTIVE: This study was designed to investigate itraconazole nail kinetics in 39 patients with onychomycosis in relation to their therapeutic outcome. METHODS: All patients received itraconazole for 3 months at a dose of 100 or 200 mg daily. Itraconazole levels of distal nail clippings were determined during a 6-month posttherapy period. RESULTS: Therapeutic itraconazole concentrations were found in the nail plates of fingernails and toenails for up to 6 months after treatment. Cure of the toenails was observed in 79% of the patients treated with the 200 mg dosage and in 26% of those treated with 100 mg at 6 months after therapy. CONCLUSION: The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment.

Antifungal Agents↗

Isolated single coronary artery: a review of 50,000 consecutive coronary angiographies.

Single coronary artery is a rare congenital anomaly of the coronary arteries where only one coronary artery arises from the aortic trunk by a single coronary ostium, supplying the entire heart. A database consisting of the angiographic reports of 50,000 consecutive coronary angiographies performed in adult patients in the University Hospital of Leuven between March 1973 and August 1991 was searched for the diagnosis of single coronary artery. All films concerned were reviewed and classified according to their anatomical type. Thirty-three cases of single coronary artery were retrieved, yielding an incidence of 0.066%. Patient characteristics and clinical data are described, with a discussion on the pathological importance of this finding.

Adult↗