Biomedical subjects

F Verbeek

Publications and source records attributed to F Verbeek.

4 recordsLinked to original sources

PubMed2001

Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis.

The aristaless-related homeobox genes Prx1 and Prx2 are required for correct skeletogenesis in many structures. Mice that lack both Prx1 and Prx2 functions display reduction or absence of skeletal elements in the skull, face, limbs and vertebral column. A striking phenotype is found in the lower jaw, which shows loss of midline structures, and the presence of a single, medially located incisor. We investigated development of the mandibular arch of Prx1(-/-)Prx2(-/-) mutants to obtain insight into the molecular basis of the lower jaw abnormalities. We observed in mutant embryos a local decrease in proliferation of mandibular arch mesenchyme in a medial area. Interestingly, in the oral epithelium adjacent to this mesenchyme, sonic hedgehog (Shh) expression was strongly reduced, indicative of a function for Prx genes in indirect regulation of SHH: Wild-type embryos that were exposed to the hedgehog-pathway inhibitor, jervine, partially phenocopied the lower jaw defects of Prx1(-/-)Prx2(-/-) mutants. In addition, this treatment led to loss of the mandibular incisors. We present a model that describes how loss of Shh expression in Prx1(-/-)Prx2(-/-) mutants leads to abnormal morphogenesis of the mandibular arch.

Animals↗

PubMed1992

Method-dependent differences in apparent sodium concentrations in plasma after exchange transfusions with citrated blood.

Shortly after exchange transfusions (n = 7) with citrate-dextrose-phosphate (CDP)-treated blood, but not after regular transfusions (n = 9), sodium concentrations in plasma were significantly and paradoxically lower (3-10 mmol/L) by Ektachem 700 XR determination [with use of electrolyte reference fluid (ERF) generation 00] than by flame photometry. Similar between-method differences could also be generated by in vitro supplementation of plasma pools with CDP solution, with trisodium citrate, or to a lesser extent with Na2HPO4. For four potentiometric methods the analytical recovery of sodium added as CDP was significantly lower than by flame photometry. Within each potentiometric method the recovery was also less than the value for sodium added as NaCl. A significant association of sodium ions with citrate3- ions and, to a lesser extent, HPO4(2-) ions could theoretically account for at least part of the observations, conferring greater medical relevance to potentiometric measurements in this particular clinical situation.

Citrates↗

PubMed1990

[The importance of the endogenous agent and environmental factor thiocyanate for nonspecific and specific resistance from the hygienic viewpoint].

Thiocyanate (previous designation rhodanide, SCN-) is a physiological substance which is ubiquitously spread in the animate nature. As an essential constituent of cell it participates in important physiological resp. biochemical processes. From the hygienic and microbiological point of view the occurrence of SCN- as environmental factor, its alimentary significance and its vitalizing effect (stimulation of nonspecific and specific warding off, stimulation of proliferation, protective effect at toxic loading) are of interest for the fundamental and applied research.

Animals↗

PubMed1983

Antitumor activity, induction of cross-resistance, and nephrotoxicity of a new platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate, and of cis-diamminedichloroplatinum(II) in an immunocytoma model in the LOU/M rat.

A newly synthesized platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate (TNO-6), was compared with cis-diamminedichloroplatinum(II) (cis-DDP) for antitumor activity and nephrotoxicity. Antitumor activity was determined in an IgM immunocytoma model in the LOU/M rat. Tumor cells were inoculated on the left flank, and therapy was started when a tumor diameter of 10 to 30 mm was reached. At the start of the therapy, the primary tumor had already metastasized to the draining lymph node and liver. Both platinum compounds, dissolved in 5% glucose water, induced an almost complete tumor regression within 10 to 14 days (average, 84% tumor load reduction) and prolonged survival, compared to that of nontreated animals. The antitumor activity induced by repeated i.p. administration of cis-DDP and TNO-6 reached its maximum at a dose of 1.0 mg/kg body weight (twice a week for 7 weeks). This treatment regimen resulted in a highest tolerable dose for cis-DDP of 1.0 mg/kg and for TNO-6 of 2.0 mg/kg. However, when rats were treated with a 2.0-mg/kg dose of TNO-6, no increase in antitumor activity was obtained. For both platinum compounds, tumor recurrence occurred in almost all animals within 2 to 7 days after the maximum tumor load reduction. Tumors that recurred were found to be cross-resistant to both platinum compounds tested but were sensitive to treatment with doxorubicin (Adriamycin). With regard to toxicity, repeated administration of TNO-6 (1.0 mg/kg twice a week for 7 weeks) induced less decrease of body weight than did cis-DDP. For TNO-6, even in the highest dose investigated (2.0 mg/kg twice a week for 7 weeks), no nephrotoxicity was observed on histological examination of kidney and blood urea and creatinine values, whereas for cis-DDP nephrotoxicity was still present in the lowest dose investigated (0.5 mg/kg). From the comparison of the antitumor activity and nephrotoxicity of TNO-6 and cis-DDP, administered i.p. in 5% glucose solution, it is concluded that both drugs have comparable antitumor activity and potency. In contrast to the effects of cis-DDP, no nephrotoxicity was observed with TNO-6; thus, TNO-6 might be a good alternative to cis-DDP in avoiding nephrotoxicity during platinum therapy.

Animals↗