Uridine and purine nucleoside phosphorylase activity in human and rat heart.
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Animals↗
Biomedical subjects
M Janssen
Publications and source records attributed to M Janssen.
Lower xanthine oxidoreductase activity in isolated perfused hearts if xanthine replaces hypoxanthine as substrate.
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Animals↗
Effects of metformin on haemorheology, lipid parameters and insulin resistance in insulin-dependent diabetic patients (IDDM).
We have evaluated the effect of metformin on haemorheology, lipid levels and insulin resistance in insulin-dependent diabetic patients over a 6-week period. Rheological parameters remained unaltered except for the whole blood clogging rate which decreased significantly. No effect on lipid levels was seen. The main effect of metformin was limited to daily insulin requirement and insulin units/kg bw. Bearing in mind the negative effects of high insulin levels, metformin could be useful in the prevention of atherogenesis in insulin-dependent diabetic patients.
Diabetes Mellitus, Type 1↗
Muscle cramps in the calf as presenting symptom of sarcoidosis.
A patient is described, who presented with pain in the calf due to a palpable nodule as the presenting symptom of sarcoidosis. The patient was treated with rest and diclofenac, followed by intralesional injections with triamcinolone hexacetonide and became free from pain.
Anti-Inflammatory Agents↗
Disseminated lung cancer or extragonadal germ cell tumour?
Two patients are reported in whom an initial diagnosis of disseminated non small cell bronchogenic carcinoma was subsequently changed into a final diagnosis of extragonadal germ cell tumour. The clinical importance of the differential diagnosis between these two malignancies is highlighted and the management of extragonadal germ cell tumours is discussed.
Antineoplastic Combined Chemotherapy Protocols↗
Intracellular inhibition of mono(ADP-ribosylation) by meta-iodobenzylguanidine: specificity, intracellular concentration and effects on glucocorticoid-mediated cell lysis.
meta-Iodobenzylguanidine (MIBG) is a high-affinity substrate for mono(ADP-ribosyl)transferase of cholera toxin and turkey erythrocyte membranes (Loesberg, C., Van Rooij, H. and Smets, L.A.(1990) Biochim. Biophys. Acta 1037, 92-99). In the present study the drug was investigated as a potential inhibitor of intracellular ribosyltransferases by competition with endogenous acceptors. To this end, MIBG was compared with the conventional ADP-ribosylation inhibitors nicotinamide and 3-aminobenzamide in cell-free ribosylation systems and in intact L1210 leukemia cells. Poly(ADP-ribose)polymerase (poly-ADPRP) was assayed by the DNAse-I-induced incorporation of [14C]NAD in nuclei of permeabilized L1210 cells. Mono(ADP-ribosyl)transferase (mono-ADPRT) was assayed as NAD linkage to [125I]iodoguanyltyramine catalysed by turkey erythrocyte membranes or activated cholera toxin. Poly-ADPRP was inhibited by nicotinamide (IC50 = 0.03 mM) and by 3-aminobenzamide (IC50 less than or equal to 0.03 mM) but was insensitive to MIBG. Conversely, mono-ADPRT was inhibited by MIBG (IC50 = approx. 0.1 mM) but not by 3-aminobenzamide and only weakly so by nicotinamide in high concentration (10 mM). In L1210 cells, intracellular levels of nicotinamide equilibrated at 60-70% of the extracellular drug concentrations assayed at 1 and 10 mM. In contrast, MIBG was concentrated 15-fold by nonspecific uptake. The preferential interference of the drugs with endogenous mono- or poly-ADP ribosylations, predicted from inhibitory capacity in vitro and intracellular concentrations, was confirmed by their effect on dexamethasone-induced lysis of L1210 cell lines. Inhibition of endogenous mono-ADPRT with 0.03 mM MIBG or 10 mM nicotinamide induced sensitivity to glucocorticoids in refractory L1210-wt cells. In contrast, inhibition of poly-ADPRP by 3-aminobenzamide or nicotinamide (1 mM each) did not confer susceptibility to refractory cells but enhanced the lytic process in the sensitive subline L1210-H7 or in L1210-wt cells sensitized by MIBG. These results indicate that MIBG is the first substrate for guanidino-specific mono-ADPRT which accumulates in intact mammalian cells and effectively competes with intracellular acceptors for endogenous enzymes.
3-Iodobenzylguanidine↗
Extragranular storage of the neuron blocking agent meta-iodobenzylguanidine (MIBG) in human neuroblastoma cells.
Human SK-N-SH neuroblastoma cells accumulate and store the adrenal imaging agent metaiodobenzylguanidine (MIBG) with minor involvement of specialized cytoplasmic storage granules (Smets LA et al., Active uptake and extravesicular storage of meta-iodo-benzylguanidine in human neuroblastoma SK-N-SH cells. Cancer Res 49: 2941-2944, 1989). In the present study the mechanism of extravesicular MIBG retention was investigated and compared with granular storage of MIBG and norepinephrine (NE) in PC-12 pheochromocytoma cells. SK-N-SH cells concentrated both MIBG and NE by neuron-specific Uptake-1 but long-term retention was only observed with MIBG. Retention of accumulated NE was, however, promoted by inhibition of intracellular catecholamine degradation with pyrogallol. Drug release by controlled cell permeabilization and by KCl-induced exocytosis indicated that MIBG was mainly stored as freely diffusible, cytoplasmic molecules. SK-N-SH cells were depleted from stored MIBG by the Uptake-1 inhibitor imipramine but poorly so by the granule-depleting drug reserpine. Conversely, PC-12 cells were depleted by reserpine but insensitive to imipramine. The data suggest that extravesicular retention of MIBG in SK-N-SH cells is not based on intracellular sequestration but is solely due to efficient re-uptake of accumulated drug after leaking from the cells. The accumulation of MIBG in SK-N-SH cells, reflecting "pure" Uptake-1, appears to be a powerful system for exploring various cellular and molecular aspects of catecholamine uptake.
3-Iodobenzylguanidine↗
Superoxide production by broncho-alveolar cells is diminished in parainfluenza-3 virus treated guinea pigs.
Guinea pig airways isolated 4, 8 and 16 days (but not 2 days) after intra-tracheal inoculation with parainfluenza-3 virus In Vivo respond hyperreactive to contractile stimuli. In the present study it is shown that the virus-induced airway hyperresponsiveness is associated with a decreased Superoxide production by broncho-alveolar cells after additional stimulation with parainfluenza-3 virus.
Animals↗
Antigenic relationship between the venom of the night adder Causus maculatus and venoms of other viperids.
Monovalent antivenoms were raised in mice against the venoms of Causus maculatus, Vipera ammodytes, Echis carinatus, Cerastes cerastes, Bitis arietans, Agkistrodon rhodostoma and Bothrops atrox. These antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or ELISA. Cross-reactive protein bands were determined by immunoblot. ELISA cross-reactions of C. maculatus antivenom were low with all heterologous venoms. When investigating the other viperine antivenoms in ELISA stronger cross-reactions were observed with several heterologous venoms. In immunoblot, two heterologous antivenoms cross-reacted with one or two protein bands of C. maculatus venom whereas there were at least four heterologous antivenoms cross-reacting with each of the other venoms. The findings indicate that there is little antigenic affinity between C. maculatus venom and the other venoms investigated. Broad in vitro cross-reactions between viperine antivenoms and Causus venom which were reported in literature seem to be attributable to the use of antivenoms of commercial grade. Specificity of commercially produced, mono- or polyvalent antivenoms may not be strictly limited to those venoms, against which potency is claimed on the label of the product.
Animals↗
Parainfluenza-3 induced hyperreactivity of the guinea pig trachea coincides with an increased number of bronchoalveolar cells.
Guinea pigs were inoculated intra-tracheally with bovine parainfluenza type 3 virus (PI-3) to investigate whether airway hyperreactivity was associated with an increase in the number of broncho-alveolar cells. Two days after saline or PI-3 inoculation no difference in histamine reactivity of the isolated tracheal spirals was observed. The number of broncho-alveolar cells was also not changed. However, 4 days after PI-3 inoculation the histamine-induced contraction of the tracheal spirals was increased by 45% and the number of inflammatory cells in the airways by 150% as compared with the control group. In conclusion, PI-3 infection of the guinea pig respiratory airways induces tracheal hyperreactivity which is associated with an increase in broncho-alveolar cells.
Animals↗
Upper gastrointestinal manifestations in rheumatoid arthritis patients: intrinsic or extrinsic pathogenesis?
Apart from the complication of gastrointestinal vasculitis it is not known whether the upper gastrointestinal (UGI) tract has any special disease characteristics in rheumatoid arthritis (RA). However, oesophageal motility disorders have been reported in 30% of RA patients. Hypergastrinaemia has been found in 23-43% of RA patients, usually in combination with a decreased gastric acid output. Another finding suggestive of a decreased secretory state, namely a decreased level of pepsinogen A, was found in RA patients with the sicca syndrome and in patients with active disease. The risk for peptic ulcer disease with regard to nonsteroidal anti-inflammatory drugs (NSAID) is possibly higher in RA patients than in patients with other rheumatic diseases. These findings suggest that in RA patients intrinsic factors play a role in the pathogenesis of the oesophageal motility disorders, in hypergastrinaemia and hypopepsinogenaemia and the related decreased gastric secretory state, and possibly in the increased susceptibility to NSAID-related ulcers. However, there are also indications that oesophageal motility disorders, hypergastrinaemia, and NSAID-related ulcers in RA are the result of extrinsic factors, mainly the use of NSAIDs. The effects of NSAIDs and gold compounds on infection with Helicobacter pylori, a possible pathogenetic factor in ulcer disease, is discussed. It is clear that the discussion about intrinsic and extrinsic factors as a cause of the UGI manifestations in RA remains an intriguing but difficult subject for further studies.
Anti-Inflammatory Agents, Non-Steroidal↗
[Immunohistochemical studies of the human lens capsule].
In this study we made an attempt to localize components of the human lens capsule using immunohistochemical methods. Type IV collagen could be shown in all parts of the capsule in equal distribution. It could be found over the whole thickness of the lens capsule. By comparison, laminin could be detected only at the inner layer of the capsule. There was no difference concerning the contribution of these components between the anterior and the posterior capsule. No specific staining of collagen types I and III or of fibronectin could be found.
Collagen↗
Insulin-like growth factor-1 receptors and insulin-like growth factor-1-like activity in human primary breast cancer.
In the current study the authors have investigated whether human primary breast cancer specimens contain insulin-like growth factor-1 (IGF-1) receptors (IGF-1-R) or IGF-1-like activities. Simultaneously, epidermal growth factor (EGF) receptors (EGF-R) and cytosolic estrogen receptor (ER), progesterone receptor (PR), and EGF-like activity were determined. All tumors assayed contained a single class of specific iodine 125 (125I)-IGF-1 binding sites (Kd: median 106, range 48-755 pM; n = 32) with limited capacity (Bmax: median 147, range 19-11,900 fmol/mg membrane protein). Seventy percent of 44 tumors (50% ER+, PR+), displayed specific 125I-EGF binding with a wide range of values (median 13, range 2-215 fmol/mg protein, n = 31). A positive relationship was apparent between the amount of IGF-1-R with ER and PR (Spearman; 2P less than 0.02 and 2P less than 0.01, respectively; n = 32), whereas for EGF-R a negative relationship was observed (for both 2P less than 0.01; n = 44). All tumors contained endogeneous IGF-1-like and EGF-like activities as measured by radioreceptor assay on acid-ethanol extracted cytosols (median 15, range 3-131 ng/mg protein, n = 78 for IGF-1; and median 86, range 26-517 ng/mg protein, n = 142 for EGF). Tumor contents of IGF-1-like and EGF-like activities showed a negative relationship with ER (2P less than 0.1 for IGF-1, n = 78; and 2P less than 0.001 for EGF, n = 142), and with PR (2P less than 0.05, n = 78; and 2P less than 0.001, n = 142). No relationship was observed between the tumor contents of IGF-1-like and EGF-like activities. In conclusion, these data support the view that IGF-1 and EGF can act as autocrine or paracrine growth factors in human breast cancer.
Breast Neoplasms↗
Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells.
Radio-iodinated m-iodobenzylguanidine (MIBG), an analogue of the neurotransmitter norepinephrine (NE), is increasingly used in the diagnosis and treatment of neural crest tumors. Active uptake and subsequent retention of MIBG and NE was studied in human neuroblastoma SK-N-SH cells. Neuron-specific uptake of [125I]MIBG and [3H]NE saturated at extracellular concentration of 10(-6) M and exceeded by 20-30-fold that by passive diffusion alone. A minimum of 50% of accumulated MIBG remained permanently stored but the SK-N-SH cells were incapable of retaining recaptured [3H]NE. [125I]MIBG was displaced from intracellular binding sites by unlabeled MIBG with 10-fold higher potency than by unlabeled NE. MIBG stored in SK-N-SH cells was insensitive to depletion by the inhibitor of granular uptake reserpine (RSP) and was not precipitated in a granular fraction by differential centrifugation. Only few electron-dense granules were found in these cells by electron microscopy. In contrast, MIBG storage in PC-12 pheochromocytoma cells which contained many storage granules, was sensitive to RSP and part of accumulated drug was recovered in a granular fraction. Accordingly, storage of MIBG in the SK-N-SH neuroblastoma cells is predominantly extravesicular and thus essentially different from that of biogenic amines in normal adrenomedullary tissue or in pheochromocytoma tumors, while sharing with these tissues a common mechanism of active uptake.
3-Iodobenzylguanidine↗
Radiofrequency ablation of ventricular myocardium using active fixation and passive contact catheter delivery systems.
This study examined the qualitative and quantitative effects of radiofrequency energy using active fixation and passive contact catheter delivery systems on normal bovine atrium and ventricle and diseased human ventricle in vitro. Two active fixation (custom screw-in or suction electrode) catheters and two passive contact (custom ring or standard electrode) catheters were used with a 500 kHz radiofrequency current generator. Linear regression analysis between lesion dimensions and power output showed excellent correlation coefficients for all catheter delivery systems except the suction catheter. Lesion sizes also increased with duration of radiofrequency energy delivery at low power using the USCI quadripolar catheter. Lesion size in diseased human ventricle was considerably smaller than in the normal ventricle. Comparison of induced lesion dimensions using pulsed and continuous delivery modes showed only minor differences. Tissue impedance was relatively constant during energy delivery. Arcing was associated with a sudden increase in voltage and impedance and a sudden decline in current. This was most frequently observed at high power and with the suction electrode catheter. The use of high (50 W) power output and prolonged application (up to 180 seconds) in atrium and ventricle did not induce perforation. We conclude that a variety of catheter delivery systems can be used for effective radiofrequency energy delivery and ablation in atrial and ventricular myocardium in the pulsed or continuous mode. Impedance changes during radiofrequency ablation cannot be used to guide the extent of ablation but do detect arcing during the procedure.
Animals↗
Campylobacter species identification based on polymorphism of DNA encoding rRNA.
Total DNA from five Campylobacter species was digested with a mixture of XhoI and BglII restriction endonucleases and analyzed by Southern hybridization by using a probe complementary to the DNA coding for the 16S rRNA. Each of the Campylobacter species, including C. jejuni, C. coli, C. laridis, C. fetus, and C. upsaliensis, displayed a characteristic pattern. Although some bands may be common to different species, the simplicity of the hybridization pattern enabled us to discriminate among the different species of Campylobacter.
Bacterial Proteins↗
Haptic identification of rotated letters using the left or right hand.
The present study investigated the effects of the use of the left and right hands on haptic identification of letters which were presented in either a normal (0 degrees rotation), downward (90 degrees clockwise rotation), upside down (180 degrees rotation), or facing upward (270 degrees rotation) position. Each of the 80 right-handed subjects was given five series of randomly ordered presentations of sets of 8 letters of the alphabet. The subjects were asked to feel and then name each letter correctly as quickly but as accurately as possible. Times showed no effect of hand, but significant effects were found for different sets of letters, degree of rotation and a significant decrease in identification time was observed across the five series. Interactions occurred between hand and rotation as well as set and rotation. Errors showed a significant interaction of hand with degree of rotation; the right was superior at 0 degrees but the left was superior at 90 degrees. The results were discussed in terms of hypotheses of hemisphere function, mental rotation, and stimulus familiarity.
Adolescent↗
A double-blind parallel group comparative study of lonazolac-calcium and diclofenac in patients with rheumatoid arthritis.
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Adult↗