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Biomedical subjects

K Schramm

Publications and source records attributed to K Schramm.

17 recordsLinked to original sources
PubMed1998

De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on fibronectin.

Changes in integrin expression during malignant transformation have been observed in many tumors. Colon-carcinoma cells show reduced expression or even loss of the alpha5beta1 integrin compared to normal or adenoma cells. To determine the significance of absent alpha5beta1 integrin signaling, we transfected the cDNA coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line HT29, which constitutively lacks this subunit but does express the beta1 subunit. We show here that the newly expressed fibronectin receptor alpha5beta1 generates multiple signals, causing marked changes in cytoskeletal arrangements within a few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin exhibit the formation of actin stress fibers and focal adhesions, as well as the induction of tyrosine phosphorylation of several proteins, within 10 min. We identified the focal adhesion kinase pp125FAK and the cytoskeletal protein paxillin as major phosphorylation substrates in these cells. These proteins remained hypophosphorylated when alpha5-negative control cells were plated on fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation of cellular proliferation and constitutively over-expressed in HT29 and in colon-carcinoma cells, showed reduced intrinsic kinase activity in unstimulated HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1 increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor during malignant transformation may contribute to tumor-cell autonomy, while reduced activity of pp60c-src in HT29alpha5-cells may participate directly in growth control.

Cell Adhesion↗
PubMed1997

Interstitial tissue fraction. The prognostic marker in membranoproliferative glomerulonephritis in children.

OBJECTIVE: To explain the differences in the clinical course of membranoproliferative glomerulonephritis (MPGN) in children and to find some prognostic markers at the disease onset that correlate with the disease outcome. STUDY DESIGN: We reviewed clinical histories and laboratory findings, reexamined kidney biopsies performed at the disease onset and evaluated volume relations between kidney components in children with the diagnosis of MPGN. RESULTS: Children were divided into three groups based on their final clinical status: I. children without features of active nephropathy, II. children with persistent nephropathy, and III. children who died of kidney disease and those who had chronic renal insufficiency. Reevaluation of kidney biopsies led to a change in the histopathologic diagnosis in several cases in all three groups. Morphometric analysis showed increasing interstitial tissue volume from group I through group III in MPGN and other forms of glomerulonephritis diagnosed after reevaluation. All the morphologic, clinical and laboratory features estimated by means of multivariate analysis of variance showed statistically significant individual characteristics of each group defined by clinical outcome. CONCLUSION: Increased interstitial tissue volume in the kidney biopsy at the disease onset is a negative prognostic factor in MPGN.

Biomarkers↗
PubMed1994

Phosphorylation of c-Raf-1 by protein kinase A interferes with activation.

c-Raf-1 is a serine/threonine-specific protein kinase which is regulated by phosphorylation. A putative c-AMP dependent protein kinase PKA phosphorylation site with the consensus sequence RRXS, Ser43, and a predominant phosphorylation site of c-Raf-1, Ser259, can be phosphorylated by PKA in vitro as shown by comparison of phosphopeptide maps of recombinant wild-type c-Raf-1 and the corresponding mutants. In vivo stimulation of the PKA pathway by treatment of A431 cells with Forskolin results in increase of phosphorylation in Ser43. Forskolin reduces the upshift of c-Raf-1 induced by EGF-treatment. It inhibits the EGF-activation of the c-Raf-1 protein kinase activity tested in vitro with a peptide substrate.

Adenosine Triphosphate↗
PubMed1991

Effects of dextroamphetamine on the cognitive and social play of a preschooler with ADHD.

This study investigates how deficits in attention and impulse control are reflected in the social and cognitive play of a 4-year-old boy with attention-deficit hyperactivity disorder. In addition, an A-B-A-B reversal design was employed to evaluate the effectiveness of dextroamphetamine (2.5 mg, twice a day) for treatment of preschool attention-deficit hyperactivity disorder. The most dramatic effects of medication were observed on the level of sustained attention and the pattern of cognitive play. Sustained attention during play and in a structured group activity improved, and play became more sequentially organized and symbolic. Results are discussed with respect to the following: 1) attention-deficit hyperactivity disorder and preschool play; 2) the efficacy of psychostimulant medication; and 3) the adequacy of teacher ratings versus direct observation in measuring medication response.

Attention↗
PubMed1987

Photoaffinity labeling with [3H]RU 28362: a powerful tool for the study of rat brain glucocorticoid receptors.

In order to study the receptor system for adrenocortical steroids in rat brain the synthetic glucocorticoid RU 28362 (11 beta, 17 beta-dihydroxy-6-methyl-17 alpha-(1-propynyl) androsta-1,4,6-trien-3-one) has been used for photoaffinity labeling. Competition and dissociation studies revealed a single class of binding sites for RU 28362 in rat brain cytosol. Photoaffinity labeling was performed by u.v.-irradiation for 2 min with a coupling efficiency of about 25%. The high efficiency permitted investigation of crude cytosolic preparations under denaturating conditions. Sodium dodecyl sulfate (SDS) and high resolution two-dimensional gel electrophoresis confirmed the high specificity of the photoaffinity labeling. The molecular weight (93 kD) as well as the isoelectric point (5.6) evaluated by these methods corresponded well to data reported for the classical glucocorticoid receptor in rat liver.

Affinity Labels↗
PubMed1982

Mesangial proliferative glomerulonephritis in children.

Over a ten year period 105 children with a histological diagnosis of a mesangial proliferative glomerulonephritis were diagnosed. Patients were divided into two groups according to their clinical presentation at the time of diagnosis. Ninety two children presented with nephrotic syndrome (NS) of whom 82 received steroid therapy. No response was observed in 26 children and in 56 remissions were short in duration and subsequent relapses were frequent. Eighty nine children with the nephrotic syndrome were treated with cyclophosphamide (CP) of whom 26 had a steroid resistant NS, 53 were steroid dependent and 10 were previously untreated. Eighty four entered remission with a mean duration of 46 months. Only 5 children did not respond to treatment with CP. No correlation could be found between the results of therapy and the degree of morphological changes on examination of renal biopsy. The second group consisted of 13 children presenting with a persistent nephritic syndrome and or proteinuria. These children were untreated and no progression of renal disease was observed after several years follow up.

Child↗
PubMedDate not supplied

Prognostic factors in the hemolytic-uremic syndrome.

During 1972-1986, 142 children with the hemolytic-uremic syndrome were treated. Most of them were infants (73%). The total mortality rate reached 25.4%. Computer analysis revealed the following risk factors of a fatal outcome: severe gastrointestinal symptoms during the prodromal period, coma, convulsions, malignant hypertension, persistence of prodromal symptoms over 7 days, hyperkalemia over 7 mmol/l, acidosis with bicarbonate level less than 15 mmol/l, a delay of over 5 days in starting dialysis, and transport to dialysis unit of over 100 km. The greatest risk of death existed during the first 3 weeks from onset. Among 142 children, 106 survived the acute phase. They were followed up from 2 to 16 years. Nine were lost to follow-up. Twelve children developed chronic renal failure.

Discriminant Analysis↗