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Biomedical subjects

J Hagemann

Publications and source records attributed to J Hagemann.

At least 19 recordsLinked to original sources

Vascular smooth muscle cells (VSMC) proliferation of streptozotocin-diabetic animals induced by diadenosine polyphosphates.

UNLABELLED: Specific binding sites for diadenosine polyphosphates (Ap (4)A, Ap (5)A, Ap (6)A) exist in VSMC (cultured vascular smooth muscle cells). These compounds may regulate VSMC growth and proliferation which is a key event in atherogenesis. Since diabetes is a known risk factor for atherosclerosis, the proliferation of VSMC from normoglycemic (control) and hyperglycemic (diabetic) rats were compared and the possibly involved receptors for diadenosine polyphosphates inducing this effect were investigated. Diabetes was induced by streptozotocin (66 mg/kg i.p.) and VSMC were prepared from rat aorta (primary culture). ( (3)H)thymidine incorporation was a measure of cell proliferation. For all diadenosine polyphosphates tested a stimulatory effect was observed as a bell-shaped concentration-response curve and a maximum effect at 10 micro M (physiological concentration). Ap (6)A has the most prominent effect (247.8 +/- 33.2 % increase over basal). In VSMC of diabetic rats the effects were even more prominent (Ap (5)A: 430.1 +/- 62.7 %). ATP (a degradation product of Ap (6)A) is able to increase the maximum effect of 10 micro M Ap (6)A. UTP (P2Y (2) agonist) exhibits a weaker proliferation. 1 micro M suramin (P2 receptor antagonist) shifts the concentration response curve of ATP and of Ap (6)A to the right. In contrast, 10 micro M PPADS (P2 X receptor antagonist) has no effect. There is no difference between VSMC of normal and diabetic rats in this respect. ADP, AMP, and adenosine exhibit a dual proliferative effect. The effect of either of these 3 compounds is much higher in VSMC of diabetic rats than of controls. 2MeSATP (P2Y (1) agonist) and alpha,beta-Methylen-ATP (P2X agonist) were not effective in VSMC of both normoglycemic and diabetic rats. IN CONCLUSION: The proliferative effect of diadenosine polyphosphates and some degradation products is more pronounced in VSMC of diabetic than of normal rats. Ap (6)A acts maximally by itself and not by its degradation product ATP. Adenosine receptors or an unknown P2Y (ApxA) receptor may be involved in proliferative effects, but not P2X and P2Y (1) receptors irrespective of a diabetic situation.

Adenosine Triphosphate↗

Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates.

BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined. METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods. RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01]. CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.

Animals↗

Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets.

Dinucleoside diphosphates, Ap(2)A, Ap(2)G, and Gp(2)G represent a new class of growth-promoting extracellular mediators, which are released from granules after activation of platelets. The presence of theses substances was shown after purification from a platelet concentrate. The substances were identified by UV spectrometry, retention time comparison with authentic substances, matrix-assisted laser desorption/ionization mass spectrometry, post-source-decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic analysis. Ap(2)A, Ap(2)G, and Gp(2)G have growth-stimulating effects on vascular smooth muscle cells in nanomolar concentrations as shown by [(3)H]thymidine incorporation measurements. The calculated EC(50) (log m; mean +/- S.E.) values were -6.07 +/- 0.14 for Ap(2)A, -6.27 +/- 0.25 for Ap(2)G, and -6.91 +/- 0.44 for Gp(2)G. At least 61.5 +/- 4.3% of the dinucleoside polyphosphates are released by platelet activation. The intraplatelet concentrations suggest that, in the close environment of a platelet thrombus, similar dinucleoside polyphosphate concentrations can be found as in platelets. Intraplatelet concentration can be estimated in the range of 1/20 to 1/100 of the concentration of ATP. In conclusion, Ap(2)A, Ap(2)G, and Gp(2)G derived from releasable granules of human platelets may play a regulatory role in vascular smooth muscle growth as growth-promoting mediators.

Animals↗

Congenital and acquired penile deviation treated with the essed plication method.

OBJECTIVES: To evaluate our results with the Essed procedure for the correction of penile curvature, either congenital or due to Peyronie's disease, and compare it with the data from the literature, both for the Essed and the Nesbit procedure. METHODS: From 1991 to 1996 the Essed procedure was performed in 61 patients. 65.6% (n = 40) had congenital deviation and 34.4% (n = 21) suffered from secondary deviation due to Peyronie's disease. In all patients 2-6 nonabsorbable inverting interrupted sutures were placed bringing the knot between the plicated tunica. RESULTS: Patients' ages ranged from 15 to 65 (mean 31.3) years and the mean follow-up time was 39.8 (12-75) months. The preoperative penile deviation was between 20 and 90 degrees (mean 47.4 degrees ). Eighteen patients (29.5%) had a recurrent deviation following surgery. This failure rate was higher in the patient group with Peyronie's disease (42.9%) than in the group with congenital deformation (22.5%). Postoperatively, 2 patients (3.3%) with Peyronie's disease reported de novo erectile dysfunction. Twenty patients (32.8%) complained of persistent discomfort or pain at the area of the still palpable plication sutures, but this inhibited sexual intercourse only in 1 case. 45.9% stated penile shortening after surgery but only 21.3% felt bothered by this. CONCLUSION: The results reported are in accordance with the literature showing a higher recurrence rate of the deviation with the Essed compared to the Nesbit procedure. For both methods the risk of recurrent disease is higher in patients with Peyronie's disease and with both techniques, an equally low incidence of erectile dysfunction is evident. However, since with the Essed technique one third of all patients complained of discomfort from the nonabsorbable sutures, the Nesbit procedure seems to be superior.

Adolescent↗

Sulfate-reducing bacteria in periodontal pockets and in healthy oral sites.

The aim of this study was to monitor the presence of sulfate-reducing bacteria (SRB) at different sites in the mouths of both healthy individuals and periodontitis patients. In 20 healthy subjects and 21 periodontitis patients, samples were taken from the palate, vestibulum, dorsum of the tongue, supragingival plaque, and periodontal pockets. In order to demonstrate growth of SRB, samples were incubated in an anoxic chamber in a reduced growth-medium for SRB, with an iron-indicator for sulfide production. The SRB were detected throughout the oral cavity. They were found on the mucosa in 10% of both healthy subjects and periodontitis patients. On the tongue and in supragingival plaque, the frequency of detection was slightly higher (22% of the subjects). In contrast, 86% of the periodontitis patients harbored SRB in one or more pockets. In 1/3 of the patients, SRB were present in all 3 pockets that were sampled. The data indicated that SRB belong to the normal oral microbiota, and have a preference for periodontal pockets.

Adult↗

Diadenosine polyphosphates in cultured vascular smooth-muscle cells and endothelium cells--their interaction with specific receptors and their degradation.

The role of diadenosine polyphosphates (ApnA, where "A" denotes "adenosine" and "n" denotes the number of phosphate groups "p") as vasoconstrictors of smooth-muscle cells and as blood-pressure regulating and insulin-releasing compounds has been described. It was the aim of this study to investigate whether specific receptors for these compounds, mediating the above mentioned effects, occur in cultured vascular smooth-muscle cells (VSMC) and in endothelium cells, and whether these compounds are degraded during incubation. Saturable binding sites for diadenosine polyphosphate [3H]Ap4A with an extremely quick saturation equilibrium, even at low temperature (4 degrees C), are present in vascular smooth-muscle cells. Diadenosine polyphosphates at micromolar concentrations displaced [3H]Ap4A from binding sites; the ranking order was Ap4A > Ap3A > Ap5A approximately Ap6A. Compounds interacting with purinergic P2X receptors such as suramin, alpha,beta-methylene ATP and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), albeit at high concentrations, displaced [3H]Ap4A from its binding sites. Surprisingly, at low concentrations the compounds tested increased the binding of [3H]Ap4A, which might imply the occurrence of positive receptor cooperativity or inhibition of [3H]Ap4A degradation. By use of thin-layer chromatography it was observed that [3H]Ap4A was quickly degraded (half-life approx. 12 min) in the extracellular medium to (mainly) adenosine and inosine. [3H]Ap4A and its degradation products were quickly taken up by the cells. Degradation can be inhibited by Ap6A, alpha,beta-methylene ATP or PPADS. Rather similar degradation and uptake results were also obtained when endothelium cells were used. These data indicate that specific binding sites for [3H]Ap4A are present in vascular smooth-muscle cells and that diadenosine polyphosphates at physiological concentrations displace binding. The receptors involved might be distinct diadenosine polyphosphate receptors, although the involvement of others, such as P2X receptors, is also possible. Ap4A is quickly degraded in the extracellular space and compounds that inhibit degradation result in an increase in [3H]Ap4A binding. It should be remembered that when diadenosine polyphos-phates are being investigated in physiological and pathophysiological studies of their impact on smooth-muscle cell proliferation and on vasoconstriction (blood-pressure regulation), results obtained from long-term incubations might be critical.

Animals↗

The treatment of uraemic hyperphosphataemia with calcium acetate and calcium carbonate: a comparative study.

A comparative study of long-term haemodialysis patients investigated the effects of calcium acetate and calcium carbonate on concentrations of serum phosphate, calcium, and parathyroid hormone. It was demonstrated that both substances led to a significant decrease in phosphate and serum parathyroid hormone. Administration of calcium acetate reduced the serum phosphate concentration in 7 weeks from an initial value of 2.08 +/- 0.53 mmol/l to 1.51 +/- 0.39 mmol/l (P less than 0.01). Following a 1-week wash-out period, calcium carbonate reduced the serum phosphate concentration in the same patients from 1.99 +/- 0.62 mmol/l to 1.34 +/- 0.40 mmol/l (P less than 0.01). Of particular significance, however, is the fact that in relation to daily elementary calcium intake, calcium acetate was a considerably more effective binder of intestinal phosphate than calcium carbonate. During administration of calcium acetate only 1.02 g of elementary calcium were required daily in order to reduce the serum phosphate concentration. The same patients, however, required 1.88 g of elementary calcium during calcium carbonate therapy. Complementary studies investigated the influence of an accompanying calcitriol medication. In this instance, too, calcium acetate was shown to be more effective; although the patients developed hypercalcaemia with calcium acetate, this happened more often with calcium carbonate. In summary it can be said that daily calcium loading of the uraemic organism under calcium acetate therapy is reduced by nearly half as compared to calcium carbonate therapy, and that this can be achieved with the same effective decrease of the serum phosphate concentration.

Acetates↗

Atrial natriuretic peptide plasma levels during hemodialysis and hemofiltration in patients with end-stage renal disease.

Using a cross-over protocol we repeatedly measured the plasma levels of alpha-hANP (atrial natriuretic peptide) during one week by radio-immunoassay in eight patients with end-stage renal disease treated with chronic hemodialysis or hemofiltration. Before each hemodialysis or hemofiltration session mean plasma ANP levels (353 +/- 112, and 337 +/- 99 pg.ml-1, respectively) were significantly above normal (50 - 166 pg.ml-1). In all but one patient, the values fell significantly towards but not reaching the normal range. Plasma ANP concentrations returned to normal at the end of the treatment in only two of the eight subjects. There was a positive correlation between the increase in body weight from one treatment to the next and the plasma ANP concentration (r = +0.35, p less than 0.05). The net loss of fluid volume during each treatment did not correlate significantly with the change in plasma ANP levels. There was no difference between hemodialysis and hemofiltration. Plasma ANP measurement may be helpful in the judgement of volume status in patients with end-stage renal disease treated by hemodialysis or hemofiltration.

Adult↗

[Kidney function in the course of compensatory hypertrophy following unilateral nephrectomy in the Wistar rat].

Unilateral nephrectomy was performed in 109 male Wistar rats, 35 animals served as controls. Determinations of glomerular filtration rate (GFR) using slope clearance of 99mTc-DTPA and of tubular function using an orally water-loading test were made. The tests were performed 2 and 5 days as well as 2, 4, 5 and 6 weeks after nephrectomy. In all examinations the GFR was more than 50% of the level of two-kidney control animals. Fractional maximum diuresis was increased in the first 2 examinations after nephrectomy from 8.9 +/- 2.1 to 15.4 +/- 4.2% of the GFR and fractional clearance of osmotically free water from 6.8 +/- 1.9 to 10.9 +/- 3.5%. In the fourth and sixth week the proximal tubular reabsorption was increased and the glomerulo-tubular balance had been recovered. However, the minimal urine osmolarity was increased to 107.8 +/- 17.7 mmol/l and the osmotic load of the nephrons remained elevated. Possible clinical implications of the results are discussed.

Animals↗

Different handling of beta 2-microglobulin during hemodialysis and hemofiltration.

Very recently it was reported that the amyloid associated with chronic hemodialysis contains, as a major component, a new form of amyloid fibril protein which is homologous to beta 2-microglobulin. As beta 2-microglobulin has a molecular weight of 11,600 daltons, investigations were carried out to see whether or not this protein would be handled differently by hemodialysis and hemofiltration, because the latter method especially is capable of eliminating solutes with such a high molecular weight. The results clearly indicate that hemofiltration removes substantial amounts of beta 2-microglobulin (about 190 mg per treatment, which represents 80% of daily production). It remains to be clarified whether or not hemofiltration is therefore superior to hemodialysis with regard to amyloid deposit formation.

Cellulose↗

[B-mode sonography of the neck. Comparison of results of sonography, computer tomography and pathomorphology].

High-resolution B-scan sonography has so far been hardly utilized in the investigation of neck tumours. The results of B-scan sonography, computed tomography, and anatomic pathology are compared and discussed. Lymph node tumours of the neck are easily and precisely recognized by ultrasonography. The rate of false positive tumours diagnoses is higher in B-scan sonography than by computed tomography. The rate of false negative diagnoses is the same with both methods. The technical development of B-scan sonography will widen its application in E.N.T. surgery.

Calcinosis↗