Search PubMed⌕ Search

Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 145 records · Page 8Linked to original sources
PubMed1996

Requirement of distal and proximal promoter sequences for chromatin organization of the osteocalcin gene in bone-derived cells.

The osteocalcin (OC) gene encodes a 10 Kda bone-specific protein which is expressed with the onset of mineralization during the differentiation of normal diploid osteoblasts. We have previously reported that transcriptional activation of this gene is accompanied by the presence of two DNase I hypersensitive sites, both located in the promoter region spanning key basal (proximal site, -170 to -70) and steroid-dependent enhancer (distal site, -600 to -400) elements. Here, we have examined stably transfected ROS 17/2.8 cell lines carrying OC promoter-reporter transgenes which contain a series of 5'-deletions and determined the effects of these truncations on the chromatin organization. It has been found that: (1) DNase I hypersensitivity at -600 is not a requirement for vitamin D-dependent transcriptional upregulation; (2) basal transcriptional activity and proximal nuclease hypersensitivity depend exclusively on protein-DNA interactions occurring within the proximal promoter region, and (3) within the chromatin context, the proximal 100 bp promoter fragment, containing essential elements such as the OC box (-99 to -76) and TATA box (-44 to -31), is insufficient to support formation of the proximal nuclease hypersensitive site and transcriptional activity.

Animals↗
PubMed1996

Changes in chromatin structure support constitutive and developmentally regulated transcription of the bone-specific osteocalcin gene in osteoblastic cells.

Transcription of the osteocalcin gene, which encodes a 10 kDa bone-specific protein, is controlled by modularly organized basal regulatory sequences and hormone-responsive enhancer elements. We have previously shown that in the ROS 17/2.8 rat osteosarcoma cell line, which continuously expresses the osteocalcin gene, key regulatory elements reside in two DNase I hypersensitive sites that are fucntionally correlated with transcriptional activity. We now report that a specific nucleosomal organization supports this constitutive expression in ROS 17/2.8 cells, and that chromatin remodeling directly correlates with the developmentally regulated transcriptional activation of the osteocalcin gene during differentiation of normal diploid rat osteoblasts. By combining DNase I, micrococcal nuclease, and specific restriction endonuclease digestion analysis, we observed that the presence of DNAse I hypersensitive sites (-170 to -70 and -600 to -400) and a selective nucleosome positioning over the OC gene promoter are directly associated with developmental stage-specific transcriptional activation in bone-derived cells.

Animals↗
PubMed1996

Predictors of flares and long-term outcome of systemic lupus erythematosus during combined treatment with azathioprine and low-dose prednisolone.

Many patients with systemic lupus erythematosus (SLE) receive long-term treatment with azathioprine and prednisolone to control disease activity. In a retrospective study we evaluated the efficacy of combined treatment with azathioprine (2 mg/kg body weight/d) and low-dose prednisolone (7-12 mg/d) and the predictors of disease flares during this therapy regimen in 61 patients with SLE. We found three predictors of flares: renal disease, persistence of dsDNA antibodies for at least 1 year after the beginning of treatment and reduction in azathioprine dosage to below 2 mg/kg/d. The occurrence of flares was significantly associated with a higher rate of disease-related death. Furthermore, the persistence of dsDNA antibodies for at least 2 years was associated with progression of renal disease. We concluded that suppression of production of dsDNA antibodies with high avidity is a suitable parameter to determine efficacy of treatment and long-term outcome during combined therapy with azathioprine and low-dose prednisolone in SLE.

Adolescent↗
PubMed1996

Quantitative analysis of pyridinium crosslinks of collagen in the synovial fluid of patients with rheumatoid arthritis using high-performance liquid chromatography.

The pyridinium crosslinks are important and definite biomarkers of mature hard tissue collagen degradation. A gradient ion-paired reversed-phase high-performance liquid chromatographic method was used for the simultaneous determination of both crosslinks in synovial fluid (SF) samples of 25 patients with rheumatoid arthritis (RA). The mean +/- SD levels of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) in SF were 107.7 +/- 182.3 nmol/l and 4.8 +/- 8.3 nmol/l, respectively. The Pyd/Dpyd ratio, which indicates the amount of Pyd released from cartilage rather than bone, amounted to 30.8 +/- 29.5. This value is significantly higher than in urine or serum of the same patients. These data suggest increased destruction of joint cartilage in patients with RA and the release of collagen II fragments in SF. In addition, the levels of the crosslinks in SF reflect considerable interindividual variation, indicating substantial individual differences in the amount of collagenous material that is degraded.

Adolescent↗
PubMed1996

Prevalence of dialysis-related amyloidosis in diabetic patients. Diabetes Amyloid Study Group.

It has recently been shown that beta 2-microglobulin isolated from amyloid deposits in dialysis patients is modified by advanced glycation (AGE). In this context it appeared of interest to examine in a cross-sectional multicentre study whether dialysis-related amyloidosis, as evaluated by X-ray assessment of cysts in the metacarpal bones, was different in diabetic patients on maintenance haemodialysis for more than 5 years time compared with matched non-diabetic controls. We evaluated the hand skeleton of 75 diabetic patients (9 type I, 66 type II; 35 male, 40 female; median age 64 years, range 31-86; median duration of dialysis 7 years, range 5-17). They were compared with 150 patients without diabetes mellitus who were matched for age, gender and duration of dialysis. Hand X-rays were centrally evaluated by one radiologist unaware of the underlying clinical diagnosis. The overall frequency of amyloid cysts was 9/75 (12%) in diabetic patients (95% confidence interval 4.6-19.3%) and 28/150 (19%) in matched controls (95% confidence interval 12.4-24.9%). The results indicate that diabetes mellitus does not confer an increased risk of dialysis-related amyloid cysts. The results are of interest with respect to the mechanism of amyloid formation.

Adult↗
PubMed1996

Decreased efficacy of combined benzodiazepines and unilateral ECT in treatment of depression.

In a retrospective study, 124 patients with depression who were concomitantly receiving ECT and benzodiazepines were compared with patients (matched for age, sex, diagnosis, and laterality of ECT) receiving ECT without benzodiazepines in order to investigate the efficacy of ECT in terms of therapeutic response and length of stay in hospital. Most of the subjects (84% of cases and 89% of controls) improved on ECT, but the benzodiazepine group of patients receiving unilateral ECT showed a significantly poorer response and a longer stay in hospital. No such difference was detected with the bilateral ECT. It is therefore concluded that prescription of benzodiazepines with ECT does compromise the therapeutic effect of unilateral ECT for depression.

Adult↗
PubMed1996

Influence of recombinant human erythropoietin therapy on in vivo chemotaxis and in vitro phagocytosis of polymorphonuclear cells of hemodialysis patients.

Recombinant human erythropoietin (rhu-EPO) mainly stimulates erythropoiesis, but also influences the production and function of polymorphonuclear granulocytes (PAN). We evaluated the influence of rhu-EPO therapy in patients on maintenance hemodialysis without iron overload on both phagocytic and chemotactic activity of polymorphonuclear leukocytes (PMN) obtained from blood and a skin chamber. The study comprised 28 dialysis patients (15 females, 13 males, age 22-78 years, dialysis sessions three times weekly 4-5 h, mean duration of dialysis treatment 4-99 months) and 20 healthy subjects (9 females, 11 males, age 18-56 years). The absolute number of leukocytes in the peripheral blood, the leukocyte mobilization (chemotactic activity) and the phagocytic activity of PMNs were tested in patients before (n = 28), and after (n = 18) reaching the target hematocrit of 30% and during the follow-up period. No alteration in the total leukocyte number (PMN, monocytes, lymphocytes) in the peripheral blood during rhu-EPO therapy could be seen. The phagocytic activity of PMNs slightly improved during the follow-up period whereas the decreased chemotactic activity remained unchanged.

Adolescent↗
PubMed1996

The German Glomerulonephritis Therapy Study: 10 years of controlled randomized trials for the treatment of idiopathic glomerulonephritis.

The German Collaborative Glomerulonephritis Therapy Study, which celebrated its 10th anniversary in 1996, has collected data on more than 1,000 patients with biopsy-proven glomerulonephritis. 929 patients could be evaluated and 500 were treated according to at least one of various protocols developed for a randomized controlled trial. Current results show that prednisolone is effective in minimal-change nephropathy, and in combination with other immunosuppressants it can reduce proteinuria in individual cases of focal and segmental glomerulosclerosis, membranous glomerulonephritis and nephrotic IgA nephropathy. The majority of tested treatment protocols did not prove to be superior to symptomatic therapy for long-term outcome.

Adolescent↗
PubMed1996

Control of pulsatile and tonic parathyroid hormone secretion by ionized calcium.

To investigate the effect of changes in ionized calcium on instantaneous PTH secretion, we examined seven young healthy volunteers by 1-min blood sampling under conditions of normo-, hypo-, and hypercalcemia. After a baseline period of 75 min, ambient ionized calcium was either increased or decreased by 0.2 mmol/L for 105 min by clamped infusion of calcium gluconate or sodium citrate. The characteristics of PTH secretion were analyzed by a deconvolution technique, accounting for subject-specific plasma PTH disappearance half-life, as measured during the first 15 min of calcium infusion (range, 2.04-2.93 min). The process regularity of pulsatile PTH secretion was evaluated by an approximate entropy statistic. Under baseline conditions, 32% of total PTH secretion was released in a pulsatile fashion, with a burst frequency of 6.9 +/- 0.8 h-1 and a PTH mass per burst of 2.6 +/- 0.9 pmol/L. The remaining 68% of total secretion was attributed to tonic hormone release. During the initial 30 min of induced hypocalcemia, pulsatile secretion increased by 1140%, whereas tonic secretion did not change. The preferential increase in pulsatile PTH secretion was mediated by a combined rise in burst frequency and mass released per burst. During subsequent steady state hypocalcemia, the tonic secretion rate increased (255% of baseline), whereas burst frequency and burst mass decreased (to 103% and 189% of the baseline values), restoring the baseline ratio of tonic to pulsatile PTH secretion. The regularity of PTH release increased during steady state hypocalcemia. During hypercalcemia, tonic secretion, burst mass, and burst frequency decreased by 75%, 82%, and 32%, respectively, and remained constant throughout the clamp period. We conclude that acute hypocalcemia elicits an immediate pulsatile and a delayed tonic secretory response of the parathyroid gland with increased regularity of PTH release. Acute hypercalcemia suppresses both the pulsatile and the tonic component of PTH secretion.

Adult↗