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Biomedical subjects

D Kinder

Publications and source records attributed to D Kinder.

14 recordsLinked to original sources

Peptide inhibitors of src SH3-SH2-phosphoprotein interactions.

Activated pp60c-src has been implicated in a number of human malignancies including colon carcinoma and breast adenocarcinoma. Association of the src SH2 domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus, of great interest in defining the role(s) of src in signal transduction pathways. To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay measures inhibition of binding of a fusion construct (glutathione S-transferase src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain. Activities of phosphopeptide segments derived from potential src SH2 cognate phosphoprotein partners were determined, with the focal adhesion kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity. Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac-Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2 A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and provided a useful framework for understanding the structure-activity relationships. Additionally, Ac-Y*EEIE was able to block interactions between src and its cellular phosphoprotein partners in vanadate-treated cell lysates from MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate proliferation of MDA-MB-468 cells in culture, presumably because of poor cell penetration and/or lability of the phosphate group on tyrosine.

Amino Acid Sequence↗

History strategy instruction: problem-solution-effect analysis, timeline, and vocabulary instruction.

This multiple baseline study investigated the effectiveness of history strategy instruction emphasizing the linkage of knowledge in teaching junior high students with behavior disorders. The intervention included 24 students and 3 teachers across three classes for 3-6 weeks. The strategy included a scripted curriculum involving brisk student-teacher interchanges; student note taking and constructing of timelines and vocabulary definitions; and reciprocal questioning, using a carefully selected history textbook. Results indicate that the history strategy was effective; students in each class showed immediate and educationally significant improvement compared with baseline instruction that employed traditional history instruction.

Adolescent↗

Pediatric submersions: prehospital predictors of outcome.

This retrospective cohort study was conducted to test prehospital prognostic indicators in pediatric submersion victims. The authors studied all less than 20 years old victims submerged in the non-icy waters of King County, WA who were treated by Seattle or King County Emergency Medical Services between 1985 and 1989 and were hospitalized or died. Seventy-seven victims were identified from emergency medical services incident logs, hospital discharge records, and medical examiner's registries. Outcome predictors were correlated with the victim's condition at hospital discharge. Of 29 victims in cardiac arrest, 13 had return of spontaneous circulation following field resuscitation. Of these, 6 (21%) survived, with mild (n = 2) and severe (n = 4) neurologic impairment at hospital discharge. The best outcome predictors were obtained in the field. These were, for death or severe neurologic impairment, submersion durations > 10 minutes (6/6) and resuscitation durations > 25 minutes (17/17), and for good outcome, sinus rhythm (37/37), reactive pupils (43/43), and neurologic responsiveness (40/40) at the scene. Field-determined factors were reproducibly good outcome predictors. Aggressive emergency medical services may save the lives of pediatric victims in cardiac arrest following short submersion durations. The data support pronouncing dead in the field those pediatric victims of non-icy submersions who do not respond to advanced life support within 25 minutes.

Adolescent↗

The search for a unified social studies curriculum: does history really repeat itself?

A bulwark of democracy is an informed electorate. Recently, disturbing evidence has been presented indicating that young Americans lack the knowledge of democratic principles and history required by our democracy. One explanation for this complex problem concerns the nature of the social studies instruction that our children are receiving. In this article, common practices in social studies instruction are described and critiqued, and an alternative, more conceptually based model of history instruction that is of potential benefit to students with learning disabilities is proposed.

Adolescent↗

Pathological changes in peripheral nerves in experimental fetal alcohol syndrome.

The peripheral nerve pathology is described in experimental fetal alcohol syndrome. The marked retraction and shrinkage of axons with vacuolar spaces in the periaxonal area are the striking features. The direct toxicity of ethanol or its metabolites on the nerve fibers is considered to be the cause for pathological changes. Additional biochemical factors, pyridoxal phosphate dependent enzyme-depletion in the genesis of nerve damage, is proposed.

Animals↗

Absence of myophosphorylase in ethanol induced cardiomyopathy.

The enzyme myophosphorylase is found to be decreased progressively on the basis of histochemical stain in the myocardium of chronically ethanol intoxicated rats. The enzyme completely disappears by the 12th week of ethanol intoxication. The possibility of deficient myophosphorylase playing one of the important roles in the pathogenesis of cardiomyopathy is stressed.

Alcoholism↗

Ethanol induced cardiomyopathy--role of periodic fasting.

The periodic fasting in presence of continuous ethanol feeding produces pronounced morphological changes in the myocardium and its organelles of the rats. This effect of ethanol could be directly related to the sensitive state of myocardium to the former, specially when ethanol becomes an important source of energy. This is proved further by intraperitoneal injection of 40% ethanol, when profound mitochondrial morphological changes, even leading to formation of lysosome like structures, are evident in the myocardium. The study has stressed the pronounced direct effect of ethanol and its metabolites in the development of morphological changes of the myocardium.

Alcoholism↗

Ethanol induced skeletal muscle degeneration--role of calcium.

The ethanol induced skeletal muscle degeneration is multi-factorial. The morphological changes of the skeletal muscle are more pronounced in the mitochondria. The excessive concentration of calcium in the mitochondria, as shown by the electron-probe micro-analysis, within the first week of ethanol intoxication, even before the appearance of ultrastructural changes suggests that the calcium influx provokes the mitochondrial degeneration.

Alcoholism↗

DMBA induced DNA damage and repair in mammary epithelial cells in vitro measured by a nick translation assay.

A new E. coli DNA polymerase I directed nick translation assay was used for measuring 7,12-dimethylbenz[a]anthracene-induced in situ DNA damage and repair in mouse mammary epithelial cells in monolayer culture. The nick translation assay was capable of detecting a DMBA-dose dependent significant increase of DNA damage, and the same assay also allowed monitoring of the DNA repair activity provoked by DMBA treatment of the epithelial cells. This relatively simple method thus provides a rapid assay for carcinogen-induced in situ DNA damage and repair in an epithelial cell tumorigenic system.

9,10-Dimethyl-1,2-benzanthracene↗

Use of power Doppler in pediatric neurosonography: a pictorial essay.

In pediatric neurosonography, conventional color Doppler imaging has been the primary adjunct to routine gray-scale imaging. Power Doppler sonography is a relatively recent development that does not have the limitations of conventional color Doppler ultrasound. The power Doppler technique measures the energy of moving red blood cells instead of the velocity and direction of flow. Advantages of this technique include increased sensitivity for identifying flow in slow-flow states, more complete evaluation of a vessel, and more accurate evaluation of the course of the vessel. Power Doppler sonography is helpful in evaluation of the neonatal brain in a variety of clinical situations: identifying the exact locations of extraaxial fluid collections, differentiating intraventricular clot from normal choroid plexus, detecting intraventricular hemorrhage, and demonstrating asymmetries in cerebral perfusion. However, in certain difficult cases, use of both conventional color Doppler sonography and power Doppler sonography produces increased diagnostic accuracy because these techniques furnish complementary information.

Adolescent↗