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F Wilhelm

Publications and source records attributed to F Wilhelm.

51 records · Page 3Linked to original sources
PubMed1986

Specific binding of 24R,25-dihydroxyvitamin D3 to chick intestinal mucosa: 24R,25-dihydroxyvitamin D3 is an allosteric effector of 1,25-dihydroxyvitamin D3 binding.

We have previously described a significant decrease in the positive cooperativity level and affinity of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] binding to its chick intestinal chromatin receptor induced in vitro by a physiological 10-fold molar excess of (24R)-25-dihydroxyvitamin D3 [24R,25(OH)2D3] [F. Wilhelm and A. W. Norman (1985) Biochem. Biophys. Res. Commun. 126, 496-501]. In this report, we have initiated a comparative study of the binding of 24R,25(OH)2[3H]D3 and 1,25(OH)2[3H]D3 to the the intestinal chromatin fraction obtained from vitamin D-replete birds. 24R,25(OH)2[3H]D3 specific binding to this chromatin fraction was characterized by a dissociation constant (Kd) of 34.0 +/- 6.4 nM, a positive cooperativity level (nH) of 1.40 +/- 0.13, and a capacity (Bmax) of 47 +/- 8 fmol/mg protein. The very low relative competitive index (RCI) of 24R,25(OH)2D3 (0.11 +/- 0.03%) for the 1,25(OH)2D3 binding site/receptor, as well as the inability of 1,25(OH)2D3 to displace 24R,25(OH)2D3 from its binding site at a physiological molar ratio of 1:10, strongly suggest the independence of 24R,25(OH)2D3 and 1,25(OH)2D3 binding sites. Stereospecificity of the 24R,25(OH)2D3 binding sites was attested by the displacement of only 45 +/- 6% of 24R,25(OH)2D3 specific binding by equimolar concentrations of 24S,25(OH)2D3. Collectively these results suggest the existence of a binding domain/receptor for 24,25(OH)2D3 in the chick intestine which is independent of the 1,25(OH)2D3 receptor.

24,25-Dihydroxyvitamin D 3↗
PubMed1986

1 alpha, 25-dihydroxyvitamin D3 modulates the growth of 3T3 cells and human skin fibroblasts stimulated by platelet-derived growth factor.

We investigated the effect of 1 alpha,25-dihydroxyvitamin D3 (1,25 (OH)2 vit D3) on the 3H-thymidine uptake by Balb/c 3T3 cells and by human skin fibroblasts stimulated by normal human serum or by purified PDGF. We found an inhibitory effect of 1,25 (OH)2 vit D3 on the DNA synthesis of Balb/c 3T3 cells grown in the presence of human serum as well as in the presence of PDGF. At 5% human serum this effect is minimal at 10(-12) M 1,25 (OH)2 vit D3 and is maximal at 10(-9) M. On the DNA synthesis of human fibroblasts stimulated by human serum or by PDGF a modulatory effect of 1,25 (OH)2 vit D3 was shown. On these cells the vitamin had a stimulatory effect between 10(-11) and 10(-9) M and an inhibitory effect at very high concentrations (10(-7) M). Our results suggested that the effect of 1,25 (OH)2 vit D3 on fibroblast DNA synthesis could be mediated by interactions with its specific intracellular receptor. 1,25 (OH)2 vit D3 had no any action on the growth of human fibroblasts stimulated by fibroblast growth factor.

Animals↗
PubMed1985

Biochemical characterization of positive cooperativity in the binding of 1 alpha, 25-dihydroxyvitamin D3 to its chick intestinal chromatin receptor.

We have characterized a positive cooperativity mechanism in the binding of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to its chick duodenum chromatin receptor. The Hill plot which can take account of the possibility of cooperativity resulted in a much better fitting of the experimental data than the Scatchard model (r = +0.998 versus r = -0.94). Concentrating the chromatin receptor preparation from 10 to 40% resulted in an increase of the Hill coefficient (nH) from 1.09 +/- 0.08 to 1.46 +/- 0.08 (S.D.). Increasing the temperature of incubation from 1 degree C to 40 degrees C resulted in a decrease of nH from 1.46 +/- 0.08 to 1.10 +/- 0.02 (S.D.). The calculation of the thermodynamics of the interaction of 1,25-(OH)2D3 with the second binding site of the receptor (from a Van't Hoff plot) showed that this process occurred spontaneously (delta G0 = -11.6 kcal X mol-1 at 1 degree C), was entropy-driven (delta S0 = +26 cal degree-1 mol-1), and was energy-requiring (delta H0 = -4.37 kcal X mol-1). The temperature controlled reversibility of the cooperativity demonstrates that this phenomenon is not an artifact. Finally, in a study of the rate of dissociation of [3H]1,25-(OH)2D3 from the duodenal receptor preparation, we have found two slopes (k-1 = 32 X 10(-3) min-1; k-2 = 3.2 X 10(-3) min-1); this suggests the existence of two species of receptor. These receptor species could result possibly from either a monomer-dimer system or from a conformational change of a monomer via site-site interactions. In conclusion, the positive cooperativity in the binding of 1,25-(OH)2D3 to the two binding sites of its intestinal receptor is an entropy-driven process and requires energy, is reversible with temperature, and has been shown to take place in concentrated chromatin aggregates.

Animals↗
PubMed1985

24R,25-dihydroxyvitamin D3 regulates 1,25-dihydroxyvitamin D3 binding to its chick intestinal receptor.

We have studied the binding of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to its crude chromatin chick intestinal receptor in the absence or presence of a ten-fold excess of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] for each concentration of [3H]-1,25(OH)2D3 studied. We have found a significant shift to the right in the binding of 1,25(OH)2D3 to its receptor in the presence of this excess of 24R,25(OH)2D3. As a result, the affinity was found to be significantly reduced, the apparent dissociation constants varied from 0.97 +/- 0.09 (n = 5) to 1.36 +/- 0.04 nM (p less than 0.01). This reduction was related to a significant decrease in the positive cooperativity for the apparent Hill coefficient from nH = 1.49 +/- 0.06 to nH = 1.26 +/- 0.06 (p less than 0.03) in the binding of 1,25(OH)2D3 to its receptor. There was no significant change in the capacity of the receptor (189 +/- 11 compared to 200 +/- 9 fmoles/mg protein). These results suggest that the intestinal 1,25(OH)2D3 receptor must also have a binding recognition site for 24R,25(OH)2D3 which is postulated to play a regulatory role in the 1,25(OH)2D3 receptor's ligand binding properties.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Influence of triamcinolone, estradiol-17 beta and testosterone on 1,25-dihydroxyvitamin D3 binding performances to its chick intestinal receptor.

We have investigated the effects of large molar excesses (20,000) of triamcinolone, estradiol-17 beta and testosterone on the binding performances of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to its receptor. The source of receptor was a duodenal chromatin fraction of vitamin D replete chickens which exhibited a high level of positive cooperativity (Hill coefficient = 1.50 +/- 0.12; n = 4) in the binding of 1,25(OH)2D3 to the two sites of its intestinal receptor. Triamcinolone did not modify the affinity, cooperativity level and maximum binding capacity of the 1,25(OH)2D3 receptor. Estradiol-17 beta induced a slight but significant increase of 13 +/- 1% (P less than 0.01) of the receptor capacity and testosterone a 29 +/- 6% (P less than 0.02) increase of the receptor affinity. A combination of estradiol-17 beta and testosterone did not modify the 1,25(OH)2D3 receptor's binding performances. In conclusion, the effects of corticoids, estradiol-17 beta and testosterone under in vitro conditions on the 1,25(OH)2D3 receptor's binding performances were found to be marginal in our system. Other studies under in vivo conditions, possibly at the pre-transcriptional level, of these steroids effects on the 1,25(OH)2D3 receptor gene regulation expression would be of great interest.

Animals↗
PubMed1985

[Thoracic outlet syndrome and its significance for surgery of the hand (on the etiology and pathogenesis of epicondylitis, tendovaginitis, median nerve compression and trophic disorders of the hand)].

At present, the term "thoracic outlet syndrome" (TOS) is used as a term to include all factors compressing the nerves and vessels situated in the outlet of the thorax and the costo-clavicular area. It is marked by neurological and vascular disorders; their manifestation can be either spontaneous or posttraumatic. In case of surgical treatment the transaxillary approach (according to Roos) proved to be the best, and is indicated in therapy-resistant TOS, in certain cases of arterial complications and in outlet obstructions of the subclavian vein. Complete resection of the first rib and the most careful removal of all fibro-muscular structures affecting the artery, vein and brachial plexus are of importance to the result of the operation. In the evaluation of cases we found surprising success with cases of lateral epicondylitis. Thus, the nerve irritation asserted as a cause in 1962 is once more confirmed. The postoperative development of 38 median nerve compressions proved to be particularly astonishing. Twenty-five of those vanished without any need for additional measures, and in eight cases definite improvement was achieved. Another important fact was observed when five median nerve compressions, previously operated upon, disappeared only after a secondary TOS-operation. These observations led to a new pathogenetic concept of median nerve compression. Apart from the common causes, the primary predisposing factor for median nerve compression is a chronic oedema due to a functional blockage of the subclavian vein, clinically and radiologically substantiated. This oedema eventually leads to a carpal tunnel syndrome, either directly on account of swelling of fibrous structures or via metabolic disorders and oxygen deficiency, thereby causing an infiltrative and proliferative reaction. In this connection, it seems interesting that the results of recent pathohistological researches suggest that the chronic oedema is the greater pathogenetic factor. The improvement of painful tendovaginitis and different disturbances in wound healing after surgical treatment of the TOS shows the importance of subclavian vein compressions. Phlebographic examination of patients who suffer from Sudeck's atrophy demonstrates significant narrowing of the subclavian vein. The increasing pressure in the subfascial space and the irritation of the lower cervical plexus and the subclavian artery can promote Sudeck's atrophy.

Adolescent↗
PubMed1984

6-Fluoro-vitamin D3: a new antagonist of the biological actions of vitamin D3 and its metabolites which interacts with the intestinal receptor for 1 alpha,25(OH)2-vitamin D3.

The biological activity and the binding affinity for the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] intestinal receptor of a new fluorine-containing vitamin D compound, namely 6-fluoro-vitamin D3 (6-F-D3), is reported. A significant interaction of 6-F-D3 with the 1,25(OH)2D3 receptor was found, with a relative competitive index (RCI) of 0.26 +/- 0.04, which is intermediate between 25-hydroxyvitamin D3 (0.14 +/- 0.01) and 1 alpha-hydroxyvitamin D3 (0.46 +/- 0.08), where the RCI of 1,25(OH)2D3 is defined to be 100. In contrast, vitamin D3 was unable to interact with the 1,25(OH)2D3 receptor. Also, the biological activity of 6-F-D3 was assessed in vivo in the vitamin D-deficient chick. 6-F-D3 at doses up to 130 nmol displayed no biological action on either intestinal calcium absorption (ICA) or bone calcium mobilization (BCM) over the time interval of 14-48 h after dosing. However, when 130 nmol 6-F-D3 was given 2 h before and 6 h after vitamin D3 (1.62 nmol), a significant inhibition of vitamin D-mediated ICA was noted. Also, a dose of 130 nmol 6-F-D3 given 2 h before and 6 h after 1,25(OH)2D3 (0.26 nmol) significantly inhibited ICA, as measured at 12 h. 6-F-D3 is the first vitamin D analog found which has an ability to both bind to the 1,25(OH)2D3 receptor and to antagonize the production of biological responses by 1,25(OH)2D3.

Animals↗
PubMed1984

Cooperativity in the binding of 1 alpha,25-dihydroxyvitamin D3 to the chick intestinal receptor.

The binding of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to its chick intestinal receptor does not fit well to the linear regression line of Scatchard's model (r = -0.79; dissociation constant, Kd = 0.51 nM). In fact, a concave 'hook' curve describes the data better. By using the Hill analysis the linear fitting was improved (r = 0.99), the Kd was found to be 0.14 nM and the Hill coefficient (nH) 1.42, which indicates a positive cooperativity in the binding of 1,25(OH)2D3 to its receptor. Further we found that Kd and nH are strongly correlated (p less than 0.001). These data suggest the existence of two ligand binding sites located in subunits for the 1,25(OH)2D3 receptor.

Animals↗
PubMed1984

Biological activity assessment of the 26,23-lactones of 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 and their binding properties to chick intestinal receptor and plasma vitamin D binding protein.

The binding of the natural and unnatural diastereoisomers 25-hydroxyvitamin D3-26,23-lactone and 1,25 dihydroxyvitamin D3-26,23-lactone to the vitamin D-binding protein (DBP) and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] chick intestinal receptor have been investigated. Also, the biological activities, under in vivo conditions, of these compounds, in terms of intestinal calcium absorption (ICA) and bone calcium mobilization (BCM), in the chick are reported. The presence of the lactone ring in the C23-C26 position of the seco-steroid side chain increased two to three times the ability of both 25(OH)D3 and 1,25(OH)2D3 to displace 25(OH)[3H]D3 from the D-binding protein; however, the DBP could not distinguish between the various diastereoisomers. In contrast, the unnatural form (23R,25S) of the 25-hydroxy-lactone was found to be 10-fold more potent than the natural form, and the unnatural (23R,25S)1,25(OH)2D3-26,23-lactone three times more potent than the natural 1,25-dihydroxy-lactone in displacing 1,25(OH)2[3H]D3 from its intestinal receptor. While studying the biological activity of these lactone compounds, it was found that the natural form of the 25-hydroxy-lactone increased the intestinal calcium absorption 48 h after injection (16.25 nmol), while bone calcium mobilization was decreased by the same dose of the 25-hydroxy-lactone. The 1,25-dihydroxyvitamin D3-26,23-lactone in both its natural and unnatural forms was found to be active in stimulating ICA and BCM. These results suggest that the 25-hydroxy-lactone has some biological activity in the chick and that 1,25(OH)2D3-26,23-lactone can mediate ICA and BCM biological responses, probably through an interaction with 1,25-(OH)2D3 specific receptors in these target tissues.

Animals↗
PubMed1980

[Treatment of the buttonhole phenomenon and similar functional deficiencies].

In the last 20 years we performed 28 operations in cases of button-hole deformities and 6 reconstructive procedures in similar cases caused by destruction of the extensor aponeurosis. In 15 cases of the first mentioned group we reinserted the central slip, which we advanced at the same time by a Lengemann suture, which works also by blocking the PIP-joint; in one case we reinserted according to KAPLAN as modified by VERDAN; in the other 12 cases the deformities were operated according to the methods of DOLPHIN, FOWLER, HELLMANN, LITTLER and EATON, MATEV, PIEPER, NICHOLS, and VERDAN. Based on these experiences the problem of the button-hole deformity can be regarded as sufficiently solved, provided that there is no substantial defect of the central slip. Of all the procedures we prefer the reinsertion of the central slip. For the treatment of deformities with loss of substance we have different surgical procedures at our disposal, the techniques of which are discussed. Due to the small number of cases of buttonhole deformity, there are a priori no optimal conditions for comparative studies, so that we could not evaluate the different surgical methods. Due to this, our therapeutic decision depends much more on the findings in each single case. Even in case of extensive destruction of the extensor aponeurosis we recommend reconstruction. We have seen that the patients in many cases estimate the results more highly than we had supposed, based purely on postoperative measurements.

Female↗
PubMed1979

[Treatment of arthroses of the carpal bones and the first carpometacarpal joint with liquid silastic implants].

In cases of resection arthroplasties of the carpometacarpal joint of the thumb we implant liquid silastic. This implant provides a good adaptation to the individual local situation and shows a good resistance to deformation. On the basis of our initial experience with this procedure we regard it as highly apt to provide an exactly fitting substitute in the wrist--especially in cases of an extirpation of the lunate bone.

Arthritis↗
PubMedDate not supplied

[Correlation between prognostically predicted and actually attained refraction].

BACKGROUND: In cataract surgery high quality is demanded. That is why high precision in calculation of IOL power is necessary for predicting postoperative refraction. MATERIALS AND METHODS: In a series of 103 patients the predicted refraction--calculated by the SRK II formula for only one type of IOL (A-constant 118.9)--was compared to the received early and late (3 month) postoperative refraction. RESULTS: The accuracy of IOL calculations in 95% was acceptable--within a range of 2 diopters. The prediction errors of extended values were only shown in cases of axial length of more than 26 millimeters. CONCLUSIONS: The results confirm the fact that by means of SRK II formula the accuracy of IOL calculation is satisfactory in respect of predicted refraction. In eyes of elongated axial length the accuracy is limited.

Adult↗