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Biomedical subjects

D Krämer

Publications and source records attributed to D Krämer.

At least 19 recordsLinked to original sources
PubMed2004

Human skeletal muscle cell differentiation is associated with changes in myogenic markers and enhanced insulin-mediated MAPK and PKB phosphorylation.

AIM: We hypothesized that myogenic differentiation of HSMC would yield a more insulin responsive phenotype. METHODS: We assessed expression of several proteins involved in insulin action or myogenesis during differentiation of primary human skeletal muscle cultures (HSMC). RESULTS: Differentiation increased creatine kinase activity and expression of desmin and myocyte enhancer factor (MEF)2C. No change in expression was observed for big mitogen-activated protein kinase (BMK1/ERK5), MEF2A, insulin receptor (IR), hexokinase II, and IR substrates 1 and 2, while expression of glycogen synthase, extracellular signal-regulated kinase 1 and 2 (ERK1/2 MAP kinase) and the insulin responsive aminopeptidase increased after differentiation. In contrast to protein kinase B (PKB)a, expression of (PKB)b increased, with differentiation. Both basal and insulin-stimulated PI 3-kinase activity increased with differentiation. Insulin-mediated phosphorylation of PKB and ERK1/2 MAP kinase increased after differentiation. CONCLUSION: Components of the insulin-signalling machinery are expressed in myoblast and myotube HSMC; however, insulin responsiveness to PKB and ERK MAP kinase phosphorylation increases with differentiation.

Biomarkers↗
PubMed2002

Bis(1H-2-indolyl)-1-methanones as inhibitors of the hematopoietic tyrosine kinase Flt3.

Aberrant expression and activating mutations of the class III receptor tyrosine kinase Flt3 (Flk-2, STK-1) have been linked to poor prognosis in acute myeloid leukemia (AML). Inhibitors of Flt3 tyrosine kinase activity are, therefore, of interest as potential therapeutic compounds. We previously described bis(1H-2-indolyl)-1-methanones as a novel class of selective inhibitors for platelet-derived growth factor receptors (PDGFR). Several bis(1H-2-indolyl)-1-methanone derivatives, represented by the compounds D-64406 and D-65476, are also potent inhibitors of Flt3. They inhibit proliferation of TEL-Flt3-transfected BA/F3 cells with IC(50) values of 0.2-0.3 microM in the absence of IL-3 but >10 microM in the presence of IL-3. Ligand-stimulated autophosphorylation of Flt3 in EOL-1 cells and corresponding downstream activation of Akt/PKB are effectively inhibited by bis(1H-2-indolyl)-1-methanones whereas autophosphorylation of c-Kit/SCF receptor or c-Fms/CSF-1 receptor is less sensitive or insensitive, respectively. Flt3 kinase purified by different methods is potently inhibited in vitro, demonstrating a direct mechanism of inhibition. 32D cells, expressing a constitutively active Flt3 variant with internal tandem duplication are greatly sensitized to radiation-induced apoptosis in the presence of D-64406 or D-65476 in the absence but not in the presence of IL-3. Thus, bis(1H-2-indolyl)-1-methanones are potential candidates for the treatment of Flt3-driven leukemias.

Animals↗
PubMed1997

[Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors].

BACKGROUND AND OBJECTIVE: In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function. Treatment regimens which reduce proteinuria and hypertension improve prognosis. The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest. PATIENTS AND METHODS: The studied cohort consisted of 11 patients with CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks, doubly blinded and randomized according to a "Latin-square design": Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo. There was a two-week wash-out phase between each of the four treatment phases. At the end of each treatment phase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid (PAH) clearance. Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase. During this period blood pressures were measured with a continuous 24-hour blood pressure monitor. RESULTS: Mean arterial blood pressure (MAP) was significantly reduced, compared with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/- 12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109 ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was slightly, but not significantly, reduced by celiprolol and atenolol. Filtration fraction remained unchanged with atenolol and celiprolol, while it was slightly, but not significantly, reduced with ramipril. Compared with the placebo, all three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and 1.4 +/- 1.4 g/24 h with ramipril. CONCLUSION: These data indicate that, in addition to ACE inhibitors, the new generation of beta-receptor blockers in particular, because of their vasodilator action, favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension.

Adrenergic beta-Antagonists↗
PubMed1996

Randomized controlled trial of ACE-inhibitors and beta-blockers with and without vasodilating activity in chronic glomerulonephritis.

A prospective double-blind, randomized study was conducted to compare the effects of the beta 1 antagonist, beta 2 agonist celiprolol (200 mg daily) on renal hemodynamics and protein excretion with those of the beta 1 antagonist atenolol (50 mg daily), the ACE-inhibitor ramipril (2.5 mg daily), and placebo in 11 patients with proteinuria > 400 mg/24 h due to chronic glomerulonephritis. All 4 substances were given in a double-blind, randomized manner according to a latin-square design over a period of 4 weeks with a wash-out period of 2 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and PAH clearance. Proteinuria was assessed by urine sampling at the end of each treatment period. Mean arterial pressure (MAP) was reduced significantly (p < 0.01) by all 3 drugs compared to placebo (108 +/- 9 mmHg placebo, 98 +/- 12 mmHg atenolol, 101 +/- 11 mmHg celiprolol, and 98 +/- 8 mmHg ramipril). Celiprolol induced a significant increase in ERPF compared to placebo (322 +/- 109 ml/min under placebo versus 391 +/- 110 ml/min under celiprolol, p < 0.05). GFR was slightly but insignificantly increased under atenolol and celiprolol. Filtration fraction (FF) remained unchanged in case of atenolol and celiprolol treatment and was slightly but not significantly reduced by ramipril. Proteinuria was significantly (p < 0.05) reduced compared to placebo by all 3 drugs (1.8 +/- 1.3 g/24 h under placebo, 1.2 +/- 1.2 g/24 h under atenolol, 1.2 +/- 1.1 g/24 h under celiprolol, and 1.4 +/- 1.4 g/24 h under ramipril). These data demonstrate that new beta-blocking agents show favorable effects on proteinuria and renal blood flow in patients with chronic glomerulonephritis and arterial hypertension. This may be attributed to their vasodilating properties.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1996

[The limits of health reporting in health planning].

Health reporting differs from traditional health statistics in (1) its claim to prospectively determine priorities and goals in the health sector, and (2) the expansion of the target group to include political decision makers and interested citizens. To date, neither has the prognostic element of health reporting been developed to satisfaction, nor has satisfactory access to the target population been gained. Forecasting requires suitable methods, an in-focus description of problems and targets, and performance control with regard to its aims. Effective access to a target population is a general problem not unique to health reporting. Forecasting and successful communication with target groups are crucial to the influence of health reporting on health planning. Both factors should be prominent goals in the future development of health reporting.

Germany↗
PubMed1996

[Tools for public health reporting on CD-ROM].

We describe the first CD-ROM published for public health use. It combines data and tools for health reporting, including health reports with full text and graphics, source data, and programming tools for the transformation, statistical evaluation, and mapping of the underlying data.

CD-ROM↗
PubMed1995

[Sentinel public health offices--a new approach to determining public health relevant data by the public health service].

The discipline of environment-related health protection lacks continuously recorded data. Therefore, a three-year pilot project "Sentinel Public Health Offices" was initiated by the Ministry of Labour, Health and Social Welfare of Baden-Württemberg in 1992. Selected public health offices were instructed to conduct a series of three cross-sectional surveys of biological and effect monitoring among children attending the fourth grade of primary schools. The surveys were coordinated by the Provincial Public Health Office. During the pilot project the system of " Sentinel Public Health Offices" has proved successful not only in the continuous recording of data relevant to health. Its continuation as a permanent institution is contemplated.

Child↗
PubMed1989

Measurement of human lumbar spine ligaments during loaded and unloaded motion.

Length changes in the ligaments of human lumbar spine motion segments were investigated in order to find conditions under which unusual stress or stress reduction is found in the longitudinal ligaments and facet joint capsules. Flexibility measurements were performed under load. Increasing load and height reduction in the motion segment increases the flexibility. The anterior and posterior longitudinal ligament normally operate in the elastic part of their stress-strain curve. Destruction of the intervertebral disc leads to a dislocation of the centers of rotation in the motion segment. Two types of facet joint capsules were observed. Height reduction in the motion segment leads to abnormal strains in one type sooner than in the other, which can be normalized by slight flexion. Injection of a silicone compound into the disc normalizes many of the changes in the motion segment due to height reduction.

Humans↗
PubMed1978

[Coincidence of malformations of the cardiovascular system as well as of the kidneys and of the efferent urinary tract (author's transl)].

Excretion urograms were prepared subsequent to angiocardiograph in a total of 115 cardiac catheter examinations. 104 of these examinations were evaluated. In 17 cases (16.3%), malformation of the kidney or the ureter was found. In consideration of the fact that such fundings are often directly linked to therapeutic consequences (plastic operations), the additional preparation of an excretion urogram is indicated during cardiac catheter examinations.

Angiocardiography↗
PubMed1977

Cortisone cataract in children with nephrotic syndrome.

In a group of 16 children with idiopathic nephrotic syndrome treated with corticosteroids for longer than 12 months, 9 developed a posterior subcapsular cataract (PSC). No correlation between the frequency of PSC and the duration of treatment and the total dose of treatment with steroids was demonstrable. However, the patients with PSC had received considerably higher average daily doses than those without PSC. Two patients with normal ophthalmologic findings at the end of treatment showed PSC 6 and 9 months later respectively. Only one patient acquired a significant impairment of visus.

Adolescent↗
PubMed1975

Testicular endocrine function and cyclophosphamide in prepubertal and pubertal patients.

Testicular function was examined by means of HCG-stimulation tests in 6 prepubertal or pubertal patients with leukemia or malignant tumours during cytostatic therapy and in 5 patients with nephrotic syndrome after discontinuation of treatment. The results of urinary testosterone assays suggest no damaging effect of cyclophosphamide on Leydig cell function.

Adolescent↗