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G Klaus

Publications and source records attributed to G Klaus.

At least 37 records · Page 2Linked to original sources
PubMed1998

Interaction of IGF-I and 1 alpha, 25(OH)2D3 on receptor expression and growth stimulation in rat growth plate chondrocytes.

Growth plate cartilage cell express receptors for, and are affected by both IGF-I and 1 alpha, 25(OH)2D3. The studies were undertaken to investigate interaction between these two hormone systems, that is, (i) to study effects of 1 alpha, 25(OH)2D3 on IGF-type 1 receptors (IGFIR), on IGF-I stimulated cell replication, colony formation, and on alkaline phosphatase activity (AP), and conversely, (ii) to study the effect of IGF-I on vitamin D receptor (VDR) expression on 1 alpha, 25(OH)2D3 stimulated growth parameters and on AP activity. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures, (serum-free) or in agarose stabilized suspension cultures (0.1% FCS). Vitamin D receptor and IGFIR were visualized by immunostaining with the monoclonal antibody (mAb) 9A7 gamma and mAb alpha IR3, respectively, and quantitated by RT-PCR for mRNA and by Scatchard analysis using [3H]-1,25(OH)2D3 and [125I]-alpha IR3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures, and by colony formation in agarose-stabilized suspension cultures. IGF-I dose-dependently increased [3H]-thymidine incorporation. 1 alpha, 25(OH)2D3, but not 1 beta, 25(OH)2D3 was stimulatory at low ((10-12 M) and slightly inhibitory at high (10-8 M) concentrations. The effect of IGF-I was additive to that of 1 alpha, 25 (OH)2D3 [IGF-I 60 ng/ml, 181 +/- 12.7; 1 alpha, 25(OH)2D3 10(-12) M, 181 +/- 9.8%, IGF-I + 1 alpha, 25(OH)2D3, 247 +/- 16.7%, P < 0.05 by ANOVA] and specifically obliterated by polyclonal IGF-I antibody (AB-1). Interaction could also be confirmed in suspension cultures. IGFIR mRNA and [125I]-alphaIR3 binding was increased by low (10(-12) m) but not by high (10(-8) M) concentrations of 1 alpha, 25(OH)2D3. Homologous up-regulation by IGF-I (60 ng/ml) was specifically inhibited by AB-1 and markedly amplified by coincubation with 1 alpha, 25(OH)2D3 (10(-12)m). Immunostaining with alpha IR3 showed specific IGFIR expression in rat growth cartilage, but not liver tissue. Stimulation of chondrocytes with 1 alpha, 25(OH)2D3 or IGF-I suggested some increase of receptor expression in single cells, but the predominant effect was increased recruitment of receptor positive cells, Vitamin D receptor expression was markedly stimulated (fourfold) by IGF-I (60 ng/ml), but not IGF-II and inhibited by actinomycin D. This study shows that IGF-I and 1 alpha, 25(OH)2D3 mutually up-regulate their respective receptors in growth plate chondrocytes. In parallel, they have additive effects on cell proliferation and colony formation suggesting independent effector pathways.

Animals↗
PubMed1998

Sonographic determination of the thickness of the peritoneum in healthy children and paediatric patients on CAPD.

BACKGROUND: Prolonged peritoneal dialysis and frequent episodes of peritonitis lead to structural changes and thickening of the peritoneum. Ultrasonography investigations may provide the opportunity to detect morphological changes early, but no systematic investigations have been performed yet. METHODS: Normal values of peritoneal thickness were obtained by systematically examining 131 healthy children (0-15 years) by ultrasound. Parietal peritoneal thickness was best measured at the sternal-umbical line distal from the xiphoid. Growth charts with 95% intervals were prepared. The data of 26 patients with end-stage renal failure (5-18 years) were compared to those of the normal children. RESULTS: The variation coefficient for the consecutive measurements was only 5%, interobserver error was approximately 7%. Whereas gender did not have any influence, peritoneal thickness was significantly correlated to age, weight and most obviously to height (r = 0.81; P<0.001). Children treated only by haemodialysis had normal values, while an increased thickness, loss of movement, and adhesion of the two peritoneal layers were found in children on CAPD. These changes were only noted in patients who had a history of peritonitis. CONCLUSION: Ultrasound examination is a simple, noninvasive and precise method to measure the peritoneal changes in children on CAPD.

Adolescent↗
PubMed1998

Hospital pager systems may cause interference with pacemaker telemetry.

Electromagnetic interference (EMI) is a well-known cause of pacemaker dysfunction. The communication between pacemakers and programmers, enabled by telemetry, is also susceptible to EMI. We have observed that hospital pager systems have the potential to interfere with pacemaker telemetry. Measurements in our pacemaker clinic and in a technical laboratory have shown that inductive pager systems may disturb telemetry in the form of inaccurate battery voltage, current and impedance measurements, disturbances in intracardiac electrogram tracings, or total interruption of telemetric communications. The reason for EMI was an overlap of carrier frequencies of some pacemaker programmers (32-37 kHz) with those of our inductive pager system (36.11 kHz). Radiofrequency pager systems using higher frequencies (in MHZ range) are unlikely to cause such interference. Awareness of this interference potential may have practical implications in choosing the carrier frequencies of inductive hospital pager systems, as well as pacemaker programmers, and in planning the location of pacemaker clinics.

Electromagnetic Fields↗
PubMed1998

Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes.

Growth depression as a side effect of glucocorticoid therapy in childhood is partially mediated by alterations of the somatotropic hormone axis. The mechanisms of interaction between glucocorticoids and somatotropic hormones on the cellular and molecular level are poorly understood. In an experimental model of primary cultured rat growth plate chondrocytes, basal as well as GH (40 ng/ml) or insulin-like growth factor (IGF)-I (60 ng/ml)-stimulated growth was suppressed dose dependently (10(-l2)-10(-7)M) by dexamethasone (Dexa). An IGF-I antibody specifically and dose dependently inhibited the GH- but not the basic fibroblast growth factor (bFGF)-stimulated cell proliferation. GH increased the IGF-I concentration in conditioned serum-free culture medium; this was reversed by concomitant Dexa. Dexa time dependently suppressed the transcription of GH receptor (GHR) messenger RNA (mRNA) and down-regulated the basal and GH-stimulated expression of GHR. Whereas no suppressive effect on basal type I IGF-receptor (IGFR) was observed, Dexa blocked the IGF-I induced increase of IGF binding. These results were confirmed by GHR and IGFR immunostaining. We conclude that Dexa impairs the GH-induced stimulation of local secretion and paracrine action of IGF-I and reduces the homologous increase of IGFR and GHR expression. The above experiments give further insight on the interaction between GH and glucocorticoids on the cellular and molecular level of growth plate chondrocytes.

Animals↗
PubMed1997

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation.

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3-24.3 (median 15.0) years who had been transplanted 1.5-8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m2. Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants.

Adolescent↗
PubMed1997

Custom-made root analogue titanium implants placed into extraction sockets. An experimental study in monkeys.

The aim of this investigation was to evaluate clinically and histologically a new custom-made, root analogue titanium implant placed into extraction sockets in monkeys (Macaca fascicularis). Three adult monkeys were used in this investigation. After raising full thickness flaps on the buccal and lingual side, the upper central and lateral incisors were extracted. Each tooth root was machine copied to 1 titanium analogue using a new CAD/CAM-system. The implants were installed in the respective extraction sockets and the flaps sutured back. After 6 months of healing biopsies were taken and processed according to the cutting-grinding technique. The percentage of mineralized bone-to-implant contact was measured as a fraction of the rough implant surface using computer-assisted analysis. The main clinical problem that occurred during implant placement was the fracture of the buccal alveolar wall. The histometric evaluation showed a mean mineralized bone-to-implant contact of 41.2 +/- 20.6%. In this investigation it could be shown that implants fabricated by laser copying will osseointegrate. The presented data encourage the performance of clinical and experimental trials evaluating the new system utilizing improved second generation CAD/CAM equipment. Such studies are currently underway.

Animals↗
PubMed1997

Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro.

1,25(OH)2D3 has an antiproliferative effect on growth plate chondrocytes when given in high doses, whereas low doses stimulate chondrocyte proliferation. In the present in vitro study we investigated the effects of parathyroid hormone (PTH) when given concomitantly with 1,25(OH)2D3 on cell proliferation and vitamin D receptor (VDR) regulation. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures or in agarose stabilized suspension cultures (10% charcoal-treated FCS). VDR expression was determined by RT-PCR generating a 297 bp fragment and by binding assays (Scatchard analysis) with [3H]-1,25(OH)2D3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures and by colony formation in agarose-stabilized suspension cultures. Optimal concentration of 1,25(OH)2D3 (10(-12) M) and of PTH fragments [bPTH(1-34) or hPTH(28-48), 10(-10)M] showed additive effects on DNA synthesis of and colony formation by growth plate chondrocytes. This may be explained in part by an up-regulation of VDR by PTH: PTH increased both mRNA expression of VDR and binding capacity. 1,25(OH)2D3 (10(-12) M) induced an up-regulation of the VDR within 24 hours followed by a down-regulation after incubation for more than 24 hours. PTH fragments added concomitantly prevented the down-regulation seen with 1,25(OH)2D3. These findings provide evidence that PTH is a growth promoting hormone that also modulates the effects of 1,25(OH)2D3 by regulating the VDR status of 1,25(OH)2D3 target cells.

Animals↗
PubMed1995

Calbindin-D28K and -D9K and 1,25(OH)2 vitamin D3 receptor immunolocalization and mineralization induction in long-term primary cultures of rat epiphyseal chondrocytes.

Rat epiphyseal plat chondrocytes were grown on glass slides, as nonadhering monolayer cultures for up to 6 weeks. Chondrocyte growth, differentiation and maturation, matrix formation and mineralization, and the temporospatial distribution of the vitamin D-dependent calcium-binding proteins, calbindin-D9K and -D28K, and the 1,25(OH)2D3 receptor (VDR), were all monitored. Chondrocytes became confluent in 2.5 weeks, differentiated to acquire a chondrocyte (polygonal) morphology, produced extracellular matrix, and finally formed a true monolayer mineralizing cartilaginous tissue, with all the stages of chondrocyte development within a single culture. beta-Glycerophosphate promoted initial matrix mineralization in 4 weeks and accelerated cell differentiation. High nominal calcium and ascorbic acid were needed for abundant matrix formation. VDR occurred at all differentiation stages, in the nuclei and nucleoli and in the cytoplasm. Calbindin-D28K and -D9K were not coexpressed. Calbindin-D28K was found in prechondroblasts, chondroblasts, and in newly differentiated chondrocytes. It was cytoplasmic in prechondroblasts and subsequently also in the perinuclear region and in nuclei, suggesting migration to the nuclear chromatin. Calbindin-D28K was nuclear only in newly differentiated chondrocytes in vitro and was not found in mature chondrocytes. In contrast, calbindin-D9K was present in the cytoplasm of mature and hypertrophic chondrocytes only. It was first in the cell body and eventually migrated within and to the far end of long cell processes with a decreasing cytoplasmic concentration showed by decreased immunostaining intensity, and ultimately hypertrophy of chondrocytes in culture. These in vitro patterns of calbindins-D and VDR accurately reflect their in vivo distributions. The genomic action of vitamin D, in vitro, resulted in the synthesis of nuclear VDR and calbindins-D.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Preoperative diagnostics and surgical management of tertiary hyperparathyroidism after chronic renal failure in a child.

Although hyperparathyroidism if a rare condition in young children, the pediatric surgeon is asked occasionally to participate in the management of a child with parathyroid disease. In this paper we report on a girl with global glomerulosclerosis, an unsuccessful renal transplantation and a long-term peritoneal dialysis, who developed an autonomous hyperparathyroidism. Emphasis is placed on the preoperative diagnosis and surgical management in children.

Child, Preschool↗
PubMed1995

Treatment of peritoneal dialysis-associated peritonitis with continuous versus intermittent vancomycin/teicoplanin and ceftazidime in children: preliminary results of a prospective randomized trial. Members of APN Arbeitsgemeinschaft Paidiatrische Nephrologie.

A recent treatment update for continuous peritoneal dialysis (CPD)-associated peritonitis recommends first-line use of continuously or intermittently administered intraperitoneal vancomycin and ceftazidine. Teicoplanin has recently been introduced as a potentially less toxic alternative glycopeptide antibiotic. However, efficacy and safety have not been demonstrated for intermittent treatment schedules or for the use of teicoplanin in prospective studies. Therefore, a prospective trial on the treatment of CPD-associated peritonitis was started in 15 pediatric dialysis units using vancomycin or teicoplanin, in combination with ceftazidine. Vancomycin or teicoplanin was administered either continuously with each bag of dialysate for 10 days or as a single dose on days 1 and 8, and ceftazidime either continuously or in one bag of dialysate per day. Until December 31, 1994, 81 episodes of peritonitis including 16 relapses occurred in a cohort of 120 patients. The incidence of peritonitis was 1 episode/13.7 months, regardless of treatment modality [continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD)]. Thirty-six (57%) primary peritonitis episodes were caused by staphylococci (21 Staphylococcus aureus, 15 coagulase-negative), 12 (19%) by gram-negative bacteria, 7 by other germs, and in 8 (13%) cases cultures remained sterile. Primary treatment response was achieved in 43/46 (93%) gram-positive and 4/12 (33%) gram-negative peritonitis episodes. Relapses occurred only with gram-positive bacteria (16/63, 25%). In cases of gram-positive peritonitis, no differences in primary response (25/25 vs 15/18) or relapse rates (10/36 vs 6/27) were observed between groups on continuous and intermittent treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Synergistic effects of parathyroid hormone and 1,25-dihydroxyvitamin D3 on proliferation and vitamin D receptor expression of rat growth cartilage cells.

We investigated possible interaction of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and PTH on: 1) proliferation (monolayer culture) and colony formation (agarose stabilized suspension cultures); 2) expression of 1,25-(OH)2D3 receptor (VDR); and 3) cAMP response to PTH, using primary cultures of chondrocytes from rat tibia proximal epiphysis. 1 alpha,25-(OH)2D3 stereospecifically stimulated DNA synthesis, cell counts, and colony formation at low concentration (10(-12) M). Within 6 h bovine PTH (bPTH)(1-34), human PTH (hPTH)(28-48) (10(-10) M), (Bu)2cAMP (1-2 mM), and 12-O-tetradecanoyl-13-acetate (10(-8) M) increased [3H]thymidine incorporation in the absence and presence of 1,25-(OH)2D3. Both PTH fragments also stimulated chondrocyte growth and colony formation in a Ca-dependent fashion. Prolonged exposure to bPTH(1-34) or hPTH(28-48) did not affect baseline DNA synthesis but increased the stimulatory effect of 1,25-(OH)2D3. This increase was inhibited in the presence of H7 (inhibition of PKC) or the monoclonal hPTH(1-38) antibody A1-70. In subconfluent chondrocyte cultures VDR was up-regulated by bPTH(1-34) and hPTH(28-48) (10(-10) M) or activators of protein kinase C (PKC), but not by (Bu)2cAMP. It was blocked by cycloheximide and actinomycin D and persisted in the presence of Ca-channel blockers. Inhibition of PKC by H7 also blocked the effect of bPTH(1-34) on VDR. The cAMP response to bPTH(1-34) was not affected by 1,25-(OH)2D3. We conclude that: 1) DNA synthesis, cell proliferation, and colony formation in chondrocyte monolayer or suspension cultures is increased by aminoterminal and midregional PTH fragments and by cAMP analogs in a Ca- dependent fashion; 2) bPTH(1-34) and hPTH(28-48) up-regulate VDR by cAMP-independent, PKC-dependent steps requiring transcriptional and translational processes; both PTH fragments also amplify the effect of 1,25-(OH)2D3 on DNA synthesis; and 3) no difference is found between the bPTH(1-34) and hPTH(28-48) fragments with respect to chondrocyte proliferation and VDR up-regulation, although the two differ with respect to stimulation of cAMP production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia.

Intermyocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, is commonly found in uremic patients and animals. The volume density of interstitial tissue in the left papillary muscle of uremic animals was found to be increased (from 1.9 +/- 0.7 to 4.2 +/- 1.1%; P < 0.001). The nuclei of interstitial cells, but not of endothelial cells, were enlarged, pointing to an activating signal that specifically acts on interstitial cells. Because of the known action of parathyroid hormone (PTH) on the heart, a potential role of PTH in the genesis of fibrosis was explored by comparing subtotally nephrectomized (NX) parathyroidectomized (PTX) rats receiving by osmotic minipump either saline or rat 1,34 PTH (100 ng/kg per hour dissolved in NaCl). Animals were on a standard 0.95% Ca diet. After PTX, they were switched to a high-calcium (3%) diet. At the end of the 14-day experiments, NX-PTX-PTH animals and NX-PTX-solvent animals were comparable with respect to mean body weight (335 versus 338 g), serum creatinine (1.2 versus 1.2 mg/dL), and serum-Ca (2.66 versus 2.63 mmol/L). The volume densities of cardiac interstitium were 4.71 +/- 0.87 versus 1.49 +/- 0.49, and those of capillaries were 8.07 +/- 1.54 versus 7.94 +/- 2.62, respectively (P < 0.001 by analysis of variance). Thus, PTX abolished and PTH restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.

Animals↗
PubMed1994

Single-dose oral calcitriol and changes of plasma 1,84iPTH in uremic children.

Both intravenous and oral 1,25(OH)2 D3 pulse therapy are effective in decreasing iPTH in patients with chronic renal failure. In order to understand why intermittent application of calcitriol is effective, we investigated 10 children with advanced renal failure (4 female, 6 male; median age 6.5 [3-16] years; body surface area 0.58-1.57m2; CCR 7 [5-47] mL/min/1.73m2) with elevated baseline concentrations of 1,84iPTH (median 63.5 [9.4-300] pmol/L). After a standard dose of 2 micrograms calcitriol per os (equal to 1.27-3.45 micrograms/m2), serum 1,25(OH)2D3 concentrations increased. The peak concentration occurred after 6 h (3-12), and 1,25(OH)2D3 serum levels returned to baseline by 48 h. 1,84iPTH concentrations were significantly suppressed by 6-72 h. The median maximal decrease was 51.4% of baseline (22.3%-74%). The decrement was a function of baseline 1,84iPTH, but not of 1,25(OH)2D3 serum peak concentration, area under the curve, body surface area, or change in ionized serum calcium. We conclude: (i) oral 1,25(OH)2D3 has a prolonged (up to 72 h) suppressive effect on 1,84iPTH concentrations in uremic patients, and (ii) the wide interindividual variation in suppression of 1,84iPTH was not explained by the kinetics of 1,25(OH)2D3 concentration, which implies that additional factors influence the 1,84iPTH response to 1,25(OH)2D3.

Administration, Oral↗