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Biomedical subjects

R F Weber

Publications and source records attributed to R F Weber.

At least 37 records · Page 2Linked to original sources

Restructuring routinely collected patient data: ORCA applied to andrology.

Hospital information systems do not always cover all required detail per specialty. This may lead to scattering of data over disparate systems and the paper record. The ORCA (Open Record for CAre) CPR offers a generic structure for record sharing, and record keeping tailored to specific needs. We studied whether a semantic integration of existing and new data was possible, using the ORCA structure. Existing andrology data, originating from separate sources, were utilized for this purpose. During normalization, validation and explication steps, latent problems in the source data were exposed and removed, followed by a merge with new data items. By conversion of source data to ORCA, a unique representation of medical concepts in the database was attained, facilitating retrieval of univocal data for multiple purposes. We conclude that the expansion to the andrology domain, including transparent integration of existing data, provides support for the generality of ORCA.

Ambulatory Care Information Systems↗

Growth hormone responses to growth hormone-releasing hormone and clonidine in patients with type I diabetes and in normal controls: effect of age, body mass index and sex.

OBJECTIVE: Increased plasma concentrations of GH and increased GH responses to provocative stimuli are reported in patients with poorly controlled type I diabetes and are suggested to be related to complications. Our aim was to investigate GH concentrations in moderately controlled patients. PATIENTS AND MEASUREMENTS: We have investigated IGF-I concentrations and fasting GH concentrations and the response to 1 microgram/kg body weight GH-releasing hormone (GHRH) intravenously and/or to 150 micrograms clonidine intravenously in 77 moderately controlled patients with type I diabetes and in 46 healthy controls. RESULTS: Median HbA1c in the patients was 8.5% (upper level of normal 6.3%). Fasting GH and GH concentrations after the administration of GHRH were not significantly different in patients with type I diabetes compared with normal controls. Fasting and stimulated GH concentrations after the administration of clonidine were significantly higher in the patients, but this could be explained by their lower age and body mass index compared with controls. In controls but not in patients there was a negative correlation between GH and glucose concentrations. IGF-I was significantly lower in patients with diabetes than in controls, even after correction for age, body mass index and sex. CONCLUSIONS: Patients with moderately controlled type I diabetes mellitus have normal baseline and stimulated GH concentrations after the administration of GHRH or clonidine compared with healthy controls, when corrected for age, body mass index and sex. However, these 'normal' GH concentrations must be considered inappropriately high in view of the hyperglycaemia in these patients. The low plasma IGF-I concentrations might be responsible for the GH over-production.

Adolescent↗

Sexual arousal and the quality of semen produced by masturbation.

The influence of sexual arousal on the quality of semen produced by masturbation was investigated. One group of 29 patients referred to our andrology outpatient clinic (group A) and one group of 14 healthy potential sperm donors filled out a questionnaire after having produced two semen samples, at least 1 month apart, by masturbation. Changes in questionnaire scores between first and second visit were compared with changes in semen characteristics between those two occasions to identify statistically significant correlations. A second group of 23 subfertility patients (group B) were asked to produce a semen sample by masturbation in a designated room at the hospital without additional sexual stimulation, and a second sample while viewing a sexually explicit video. Differences in questionnaire scores and semen characteristics obtained with visual erotic stimulation (VES) and without VES were analysed. In group A, the change in sexual arousal and change in intensity of orgasm correlated with change in semen volume (r = 0.38, P < 0.05; r = 0.48, P < 0.01 respectively). In healthy donors and group B, however, no such correlation was found. With VES in group B, significantly higher scores were given for 'feeling at ease/relaxed' (P < 0.01), 'sexual arousal' (P < 0.001), 'quality of erection' (P = 0.01), 'intensity of orgasm' (P < 0.05), 'satisfaction after orgasm' (P < 0.05), and 'ease with which orgasm was achieved' (P < 0.001) with VES compared to without VES. There was no statistically significant improvement in semen quality with VES compared to without VES. It is concluded that sexual arousal has no significant influence on the quality of an ejaculate produced by masturbation. On the other hand, providing a patient with a sexually stimulating video is obviously a facilitative factor when the patient 'has to' produce a semen sample for analysis. The use of visual erotic stimulation is recommended when patients and donors have to produce a semen sample in the university surroundings of a fertility clinic.

Erotica↗

Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro.

Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of alpha- or beta-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nM inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective alpha-adrenergic receptor antagonist, prazosin, an alpha 1-receptor antagonist, and yohimbine, an alpha 2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective beta-adrenergic receptor antagonist, atenolol, a beta 1-receptor antagonist, and ICI-118,551, a beta 2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an alpha-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of alpha-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an alpha-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, alpha-, but not beta-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an alpha-adrenergic mechanism which activates the CRH-secreting neurone.

Adrenergic alpha-Antagonists↗

[Improved diabetes control through strict observance of the standard 'Type II Diabetes Mellitus' from the Dutch College of Family Physicians].

OBJECTIVE: Comparison of diabetes regulation by strict or less strict observance of the relevant standard protocol of the Netherlands College of General Practitioners (NHG standard). SETTING: Two general practices in the region 'Nieuwe Waterweg Noord', near Rotterdam, the Netherlands. DESIGN: Cross-sectional comparative descriptive study. METHOD: Type II diabetic patients from two general practices were investigated for diabetic symptoms, type of medication, metabolic abnormalities and (risk factors for) complications in relation to their HbA1c as a measure of mean blood glucose regulation. One GP strictly observed the NHG standard as a protocol, the other GP used it as a guideline. RESULTS: Metabolic control was significantly better in the 'strictly observing' general practice than in the 'guideline' practice: HbA1c 7.3% (SD: 1.7) versus 8.1% (1.5) (p < 0.01). Systolic blood pressure was also significantly lower in the 'strict' practice: 141 mmHg (23) versus 155 mmHg (21) (p < 0.01), but mean age was lower and mean duration of diabetes was significantly shorter. The prevalence of macrovascular complications, diabetic retinopathy and nephropathy did not differ significantly in these practices; symptoms of polyneuropathy, however, were found more often in the patients of the 'strict' practice (41% versus 20%; p < 0.05). CONCLUSION: Good metabolic control in patients with type II diabetes mellitus is made possible by strict application of the NHG standard for general practitioners.

Adult↗

High dose testosterone therapy for reduction of final height in constitutionally tall boys: does it influence testicular function in adulthood?

OBJECTIVE: We have studied the effect of treatment with high doses of androgens during puberty on testicular function in adult men with constitutionally tall stature, taking into account confounding factors interfering with sperm quality, since existing published data do not include whether testicular function is impaired by such treatment. DESIGN: Historical cohort study. PATIENTS: Forty-three previously androgen treated tall men (cases) and 30 non-treated tall men (controls). MEASUREMENTS: Physical examination, semen analysis and plasma levels of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and inhibin. RESULTS: Sperm quality and testis volume were comparable between cases and controls. Mean sperm concentration was 66.4 x 10(6)/ml in cases and 66.2 x 10(6)/ml in controls. A left-sided varicocele was found in 45% of the cases and 37% of the controls. In cases we observed a significant effect of the age at start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%, P = 0.048). In addition, testicular size at start of therapy had a significant effect on sperm concentration (regr. coeff. (SE): 5.57 (1.54) x 10(6)/ml, P = 0.0012) and on total sperm count (regr. coeff. (SE): 43.1 (7.73) x 10(6), P = 0.0001). Plasma levels of T, SHBG and inhibin were not statistically different between the groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2) vs 2.1 (0.8) IU/I, P = 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9) vs 3.1 (1.4) IU/I, P = 0.019). We found a significant effect of age at start of therapy on plasma FSH level in the treated men (regr. coeff. (SE): -0.73 (0.18) IU/I, P = 0.0003). CONCLUSIONS: Treatment with high doses of androgens for reduction of final height in constitutionally tall stature has no long-term side-effect on sperm quality, testicular volume or plasma testosterone levels. However, treated men had significantly higher plasma levels of FSH compared with controls. The meaning of this difference remains to be established. Varicocele was present in 42% of the adult tall men.

Adult↗

Plasma levels of luteinizing hormone during hyperprolactinemia: response to central administration of antagonists of corticotropin-releasing factor.

Since high concentrations of prolactin (PRL) enhance the hypothalamic release of corticotropin-releasing factor (CRF), and CRF decreases the hypothalamic secretion of luteinizing hormone (LH)-releasing hormone (LHRH), it could be that CRF is involved in the suppressed secretion of LH during hyperprolactinemia. The aim of this study was to explore this possibility in hyperprolactinemic male rats. Hyperprolactinemia, induced by insertion of 3 pituitary glands under the kidney capsule, decreased plasma LH levels by 68% and caused a 2-fold increase in plasma corticosterone. Intracisternal administration of the CRF antagonist alpha-helical CRF(9-41) induced both in pituitary-grafted rats and in normoprolactinemic controls a 2 to 3-fold increase of LH in the plasma sample taken 1 h after injection of alpha-helical CRF(9-41). Plasma levels of LH in pituitary-grafted rats were 2-3 times higher during intracerebroventricular infusion for 7 days with CRF antiserum than during saline infusion. Furthermore, after infusion of CRF antiserum for 7 days into the lateral brain ventricle plasma LH levels had increased by 270% in normoprolactinemic male rats. These results indicate that hypothalamic CRF is involved in the control of LH release in male rats. To further investigate whether CRF is involved in the effect of PRL on LH secretion, we infused PRL, alone or together with CRF antiserum, for 7 days into the lateral brain ventricle of normoprolactinemic male rats. After 7 days of PRL infusion, LH levels had decreased by 45%, whereas plasma corticosterone was 150% higher. This action of PRL on LH and corticosterone was prevented when besides PRL also CRF antiserum was infused.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

ARIS: integrating multi-source data for research in andrology.

Although the concept of distributed systems for the storage of patient data is more and more commonly accepted, for some considerable time yet most patient data will be stored in centralized rather than departmental systems. An important advantage of storage in a central system is hospital-wide access to much of the patient data. Disadvantages are however that these data cannot be reviewed through one user interface, and that the structure of the data does not lend itself to exploitation for other purposes. We describe the implementation of an Andrology Research Information System in which these data are integrated in a well-structured database facilitating multiple views on the patient data through a graphical user interface, and clinical research, quality control and summary reports. The data can be analyzed directly using the Hermes workstation. In this way the strengths of the centralized system are combined with those of the dedicated ARIS system.

Computer Graphics↗

Glucagon stimulation test: assessment of beta-cell function in gestational diabetes mellitus.

OBJECTIVE: Because women with gestational diabetes mellitus have a risk of up to 60% for the later development of type II diabetes, we used the intravenous glucagon stimulation test to evaluate beta-cell function in pregnant women. PATIENTS: Twenty-seven pregnant women with one or more risk factors for gestational diabetes had an intravenous beta-cell stimulation test. Glucose, C-peptide and insulin levels were measured at baseline and 5, 10 and 15 min after the administration of 1 mg glucagon. The women were classified using the 75-g oral glucose tolerance test according to World Health Organization criteria. During the oral glucose tolerance test glucose, C-peptide and insulin levels were measured at baseline and at 2 h. RESULTS: Insulin and C-peptide responses were significantly lower in pregnant women with impaired glucose tolerance and diabetes compared with women with normal glucose tolerance. CONCLUSION: This study shows gradually decreasing insulin secretion from normal to subnormal in pregnant women without and with glucose intolerance, and diabetes mellitus, respectively.

Adult↗

Involvement of corticotropin-releasing hormone and endogenous opioid peptides in prolactin-suppressed gonadotropin-releasing hormone release in vitro.

Corticotropin-releasing hormone (CRH) has been shown capable of inhibiting hypothalamic gonadotropin-releasing hormone (GnRH) release through activation of an endogenous opioid peptide (EOP)-dependent mechanism. Recently, we have shown that prolactin (PRL) stimulates CRH release and inhibits GnRH release by hypothalami explanted from male rats. Thus, the present study was undertaken to investigate whether the inhibitory effect of PRL on GnRH release in vitro is mediated by CRH and/or EOP. To this aim, the release of GnRH in response to PRL was evaluated in presence of CRH9-41 alpha-helical (CRH-9-41), a CRH receptor antagonist, and/or naloxone (NAL), a nonselective opioid receptor antagonist, using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated longitudinally halved hypothalamic. As previously shown, PRL at the concentration of 100 nmol/l inhibited basal iGnRH release by about 35%. CRH9-41 or NAL overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. The simultaneous co-incubation with both antagonists was not more effective than each single antagonist. CRH9-41 did not have any effect on basal iGnRH release whereas NAL, as previously reported, increased it. In addition, PRL at the concentration of 100 nmol/l stimulated basal hypothalamic beta-endorphin (beta-EP) release. In conclusion, these data show that antagonism to CRH receptors counteracts the suppressive effects of PRL upon GnRH release and that PRL is able to stimulate hypothalamic beta-EP release in vitro.

Animals↗

Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor.

TNF-alpha can enhance the proliferation of human thymocytes stimulated by the comitogen Con A. To determine which of the two different TNF receptors is responsible for signaling this cellular response, we investigated the proliferation of human thymocytes in response to agonistic antibodies specific for the two TNF receptor types. In contrast to previously examined TNF activities in human cells, thymocyte proliferation was stimulated in response to rabbit polyclonal antibodies directed against the 75-kDa TNF receptor (TNF-R2), but not those directed against the 55-kDa TNF receptor (TNF-R1). Lymphotoxin (TNF-beta) was also shown to stimulate human thymocyte proliferation, demonstrating that TNF-beta can initiate a biologic response that is mediated by TNF-R2. TNF-R2-mediated T-cell proliferation was not restricted to the immature T cells within the thymus, as the anti-TNF-R2 antibodies also stimulated the proliferation of peripheral T cells. As a first step toward identifying a specific agonist of TNF-R2 with therapeutic potential, 10 anti-TNF-R2 mAb were examined for potential agonist activity. Nine of these significantly stimulated human thymocyte proliferation with maximal responses ranging from twofold to significantly greater than that obtained with TNF-alpha by itself.

Antibodies, Monoclonal↗

Biochemical characterization of the extracellular domain of the 75-kilodalton tumor necrosis factor receptor.

An expression plasmid encoding the extracellular domain of the 75-kDa human tumor necrosis factor (TNF) type 2 receptor (TNF-R2) was constructed and used to generate a stable cell line secreting soluble TNF-R2 (sTNF-R2). Purified sTNF-R2 was resolved by SDS-PAGE into one band of approximate M(r) 43,000, consistent with a molecular weight of 36,000 +/- 4800 obtained by sedimentation equilibrium analysis. The apparent molecular weight observed by gel filtration chromatography was approximately 136,000. Glycosylation analysis revealed that Asn-149 is fully glycosylated, while Asn-171 is incompletely glycosylated (approximately 50%), and that a proline-, serine-, and threonine-rich region (residues 175-234) contains O-linked carbohydrate structures. Scatchard analysis of [125I]TNF-alpha and [125I]TNF-beta binding to sTNF-R2 gave dissociation constants (Kd) of 0.3 and 0.75 nM, respectively, comparable to those observed for intact cell-surface TNF-R2. The sTNF-R2 was found to block the cytotoxicity of both TNF-alpha and TNF-beta in a murine L-M cell assay. The sizes of the sTNF-R2.TNF-alpha and sTNF-R2.TNF-beta complexes determined by gel filtration chromatography were approximately 322 and 204 kDa, respectively. The stoichiometry of the sTNF-R2.TNF-alpha and sTNF-R2.TNF-beta complexes were examined by size-exclusion chromatography, sedimentation equilibrium, and cross-linking. The data from these studies suggest that at least two molecules of sTNF-R2 can bind to a single TNF-alpha or TNF-beta trimer.

Amino Acid Sequence↗

The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function.

OBJECTIVE: Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome. PATIENTS: Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria. MEASUREMENTS: Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG. RESULTS: There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients. CONCLUSIONS: The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Adult↗

Effects of rat prolactin on gonadotropin-releasing hormone secretion by the explanted male rat hypothalamus.

Chronic hyperprolactinemia in the rat is associated with suppression of plasma gonadotropin concentrations. The reduction of gonadotropins is considered to be due to either an inhibitory effect of prolactin (PRL) on pituitary gonadotropin secretion and/or suppression of hypothalamic gonadotropin-releasing hormone (GnRH) release. In contrast to the in vivo effects of PRL on hypothalamic GnRH release, it has recently been reported that endogenous hypothalamic PRL exerts a tonic stimulatory effect on GnRH release in vitro. The present study was undertaken to further evaluate the role of PRL on GnRH release. To accomplish this, we set up a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release by individually incubated longitudinally halved hypothalami. PRL at the concentrations of 100 and 1,000 nM (2,300 and 23,000 ng/ml) inhibited iGnRH release. This suppressive effect of PRL was apparently specific since growth hormone, a PRL-related molecule, did not have any significant effect on iGnRH release at the concentration of 1,000 nM (21,500 ng/ml) and a PRL antiserum completely suppressed the inhibitory effect of exogenously added PRL. On the other hand, this antiserum had no effect on basal iGnRH release suggesting that hypothalamic PRL does not regulate GnRH release. Based on the observation that PRL exerts a sexually dimorphic effect on plasma gonadotropin levels, we also evaluated the effects of testosterone (T), dihydrotestosterone (DHT), 17 beta-estradiol (E2), and progesterone (P) on PRL-inhibited iGnRH release in vitro. T, DHT and E2 did not have any detectable effect on PRL-suppressed iGnRH release whereas P, at the concentration of 0.1 nM (0.03 ng/ml), completely abolished the effect of PRL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion.

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.

Adolescent↗

Epstein-Barr virus-derived vectors for transient and stable expression of recombinant proteins.

The transient expression level of foreign proteins in primate cells can be enhanced by incorporating the replication elements derived from Epstein-Barr virus (EBV). Specifically, we have constructed expression plasmids with the replication origin region (OriP) from EBV and an adenovirus-transformed cell line that expresses the EBV nuclear antigens-1 (EBNA-1). As EBV vectors can replicate as episomes in the nuclei, such vectors can have a stable transfection efficiency as high as 25% and provide a straightforward way of obtaining large amounts of recombinant proteins transiently or stably.

Antigens, Viral↗

Biochemical properties of the 75-kDa tumor necrosis factor receptor. Characterization of ligand binding, internalization, and receptor phosphorylation.

An expression plasmid encoding the human 75-kDa tumor necrosis factor (TNF) type 2 receptor (TNF-R2) was constructed and used to generate a stable human cell line (293/TNF-R2) overexpressing TNF-R2. Ligand binding analysis revealed high affinity binding (Kd = 0.2 nM) with approximately 94,000 +/- 7,500 sites/cell for 125I-TNF-alpha and approximately 5-fold lower affinity for TNF-beta (Kd = 1.1 nM) with 264,000 +/- 2,000 sites/cell. Cross-linking of 125I-TNF-alpha and 125I-TNF-beta to 293/TNF-R2 cells yielded predominant complexes with apparent molecular weights of 211,000 for TNF-alpha and 205,000 and 244,000 for TNF-beta, suggesting these complexes contain two or three TNF-R2 molecules. Immunoprecipitation of TNF-R2 from 32P-labeled 293/TNF-R2 cells demonstrated that the receptor is phosphorylated. The majority (97%) of 32Pi incorporation was found in serine residues with a very low level of incorporation (3%) in threonine residues. TNF-alpha treatment of 293/TNF-R2 cells did not significantly affect the degree or pattern of phosphorylation. Cell surface-bound 125I-TNF-alpha was slowly internalized by the 293/TNF-R2 cell line with a t1/2 = 25 min. Shedding of the extracellular domain of TNF-R2 was induced by 4 beta-phorbol 12-myristate 13-acetate but not by TNF-alpha or TNF-beta.

Chromatography, Affinity↗