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Biomedical subjects

K Scott

Publications and source records attributed to K Scott.

At least 73 records · Page 4Linked to original sources

The Drosophila light-activated conductance is composed of the two channels TRP and TRPL.

SUMMARY: Drosophila phototransduction is a G protein-coupled, calcium-regulated signaling cascade that serves as a model system for the dissection of phospholipase C (PLC) signaling in vivo. The Drosophila light-activated conductance is constituted in part by the transient receptor potential (trp) ion channel, yet trp mutants still display a robust response demonstrating the presence of additional channels. The transient receptor potential-like (trpl) gene encodes a protein displaying 40% amino acid identity with TRP. Mammalian homologs of TRP and TRPL recently have been isolated and postulated to encode components of the elusive I(crac) conductance. We now show that TRP and TRPL localize to the membrane of the transducing organelle, together with rhodopsin and PLC, consistent with a role in PLC signaling during phototransduction. To determine the function of TRPL in vivo, we isolated trpl mutants and characterized them physiologically and genetically. We demonstrate that the light-activated conductance is composed of TRP and TRPL ion channels and that each can be activated on its own. We also use genetic and electrophysiological tools to study the contribution of each channel type to the light response and show that TRP and TRPL can serve partially overlapping functions.

Amino Acid Sequence↗

Evaluating asymptomatic patients with abnormal liver function test results.

Asymptomatic patients with abnormal results on liver function test pose a diagnostic challenge. In general, determinations of routinely ordered tests of liver function are neither sensitive nor specific for liver disease. Fatty liver, alcohol-related liver damage and chronic viral hepatitis are the most common causes of abnormal liver function test results in asymptomatic patients. Causes of asymptomatic liver disease include hemochromatosis, Wilson's disease, drug toxicity, chronic autoimmune hepatitis, biliary cirrhosis, sclerosing cholangitis, alpha1-antitrypsin deficiency and sarcoidosis. The most efficient screening tests for liver damage are alanine transaminase, alkaline phosphatase and bilirubin. Repeat testing when results are abnormal, and use of ancillary tests, such as creatine phosphokinase or gamma-glutamyl-transferase, may confirm liver damage. Imaging studies help exclude biliary obstruction or neoplasm. Treatable illnesses should be ruled out. Three to six months of observation for progressive symptoms and liver dysfunction may follow. After the period of observation, further laboratory tests, a diagnostic liver biopsy and/or referral to gastroenterologist may be needed.

Aftercare↗

Production of extracellular matrix, fibronectin and steroidogenic enzymes, and growth of bovine granulosa cells in anchorage-independent culture.

A proportion of the granulosa cells from bovine antral follicles will survive, like stem cells, in anchorage-independent culture. To study these cells, bovine granulosa cells were isolated from medium-sized follicles (3-5 mm), plated out (in aliquots of 2.5 x 10(4) viable cells) onto a 1 mL agar base, and overlaid with 1 mL of methycellulose solution in culture medium (control). The cells were cultured (14 days) and then processed for histology (n = 14) or Western immunoblotting (n = 5). Under control conditions or after treatment with basic fibroblast growth factor (bFGF; 50 ng mL-1), a proportion of the granulosa cells divided to produce colonies; individual cells remained small. bFGF increased the number of cells harvested (15.8 +/- 7.3-fold, as measured indirectly by the relative amount of the nuclear La antigen), increased the average diameter of the colonies from 88.9 +/- 13.5 microns to 136.5 +/- 4.9 microns and stimulated the production of fibronectin 5.7 +/- 1.5-fold (P < 0.05). An extracellular matrix, which has previously been shown to be a basal lamina, was observed in 19.1% of the colonies (total of 350 colonies examined; n = 8 experiments). Cells treated with dibutyryl cAMP (1 mM) hypertrophied and had 50 +/- 28.7-fold and 102.6 +/- 55.8-fold higher levels of cholesterol side-chain cleavage cytochrome P450 (P < 0.001) and 3 beta-hydroxysteroid dehydrogenase (P < 0.01) respectively (n = 5). Thus, granulosa cells with characteristics of stem cells can divide and produce extracellular matrix, or be induced to differentiate when in culture without anchorage.

3-Hydroxysteroid Dehydrogenases↗

The new reality: academic medical centers partner with the community.

As academic medical centers face a price-sensitive market dominated by managed care, their survival, says Association of American Medical Colleges' Robert Dickler, will depend on the combination of strategies they use in response. HSL looks at three centers' solution--building alliances to secure patient bases, focusing on expanding primary care capabilities, and downsizing and reorganizing for greater cost savings.

Academic Medical Centers↗

Dark-light: model for nightblindness from the human rhodopsin Gly-90-->Asp mutation.

A human rhodopsin mutation, Gly-90-->Asp (Gly90Asp), cosegregated with an unusual trait of congenital nightblindness in 22 at-risk members of a large autosomal dominant kindred. Although rhodopsin mutations typically are associated with retinal degeneration, Gly90Asp-affected subjects up to age 33 did not show clinical retinal changes. Absolute threshold for visual perception was elevated nearly 3 logarithmic units in 7 individuals tested (ages 11-64), indicating greatly compromised rod threshold signaling. However, in vivo rhodopsin density was normal. Although the 38-year-old proband could not perceive dim lights, his rod increment threshold function was normal on brighter backgrounds. The impaired rod vision for dim but not bright backgrounds is consistent with a mechanism of increased basal "dark-light" from thermal isomerization equivalent to an increase of > 10(4) over that of wild-type rhodopsin. The Gly90Asp mutation on the second transmembrane helix places an extra negative charge in the opsin pocket; this could contribute to partial deprotonation of the retinal Schiff base and thereby increase photoreceptor noise. In vitro evidence had suggested that transducin is activated by the Gly90Asp mutation in the absence of both the retinal chromophore and light, termed "constitutive activity." The apparent preservation of functioning rods despite extensive and lifelong night-blindness in this kindred is inconsistent with one current hypothesis that chronic rod activation from constitutively active mutant rhodopsin necessarily contributes significantly to photoreceptor demise in human retinal dystrophies.

Adolescent↗

Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology.

Heterotrimeric G proteins mediate a variety of signaling processes by coupling seven-transmembrane receptors to intracellular effector molecules. The Drosophila phototransduction cascade is a G protein-coupled signaling cascade that utilizes a phospholipase C (PLC beta) effector. PLC beta has been shown to be activated by Gq alpha in reconstituted systems. To determine whether a Gq-like protein couples rhodopsin to PLC, and to study its function, we isolated a mutant defective in a photoreceptor-specific Gq protein, DGq. We now demonstrate that Gq is essential for the activation of the phototransduction cascade in vivo. We also generated transgenic flies expressing DGq under an inducible promoter and show that it is possible to manipulate the sensitivity of a photoreceptor cell by controlled expression of DGq. Characterization of quantum bumps in mutants expressing less that 1% of the levels of DGq revealed that the rhodopsin-G protein interaction does not determine the gain of the single photon responses. Together, these results provide significant insight into the role of Gq in regulating the output of a photoreceptor cell.

Amino Acid Sequence↗

Psychopathology, biopsychosocial factors, crime characteristics, and classification of 25 homicidal youths.

OBJECTIVE: This study investigates diagnostic, behavioral, offense, and classification characteristics of juvenile murderers. METHOD: Twenty-five homicidal children and adolescents were assessed using the Diagnostic Interview for Children and Adolescents, clinical interviews, record review, and all available collateral data. RESULTS: DSM-III-R psychopathology was found in 96% of these youths, and one half of them had experienced suicidal ideation at some point in their lives. Nevertheless, only 17% had ever received mental health treatment. Family and school dysfunction were present in virtually all subjects. Histories of abuse, prior violence, arrests, and promiscuous sexual behavior were typical. Motives were equally divided between crime-based and conflict-based causes. A weapon was used in 96% of cases. Significant differences were found between crime classification groups and victim age, physical abuse, IQ, and victim relationship. In addition, those who committed sexual homicide were significantly more likely to have engaged in overkill, used a knife, and been armed beforehand. Ten profile characteristics present in at least 70% of these juveniles were identified. All murders were readily classified according to the FBI Crime Classification Manual (CCM). CONCLUSIONS: These findings support juvenile murderers as being an inadequately treated, emotionally and behaviorally disturbed population with profound social problems. The CCM proved to be a useful instrument for the classification of this sample.

Adolescent↗

Ethics for working with communities of Indigenous Peoples.

Specific ethical guidelines for working with Indigenous Peoples have been adopted by several research institutions. Ethical principles aim at promoting cooperation and mutual respect between researchers and communities of Indigenous Peoples. These principles are meant to be continually assessed. This article reports on the content and format of current ethical guidelines and highlights directions for further development.

Canada↗

Teachers' attitudes toward increased mainstreaming: implementing effective instruction for students with learning disabilities.

To investigate the types of instructional strategies offered in mainstream classes, we asked 127 mainstream teachers in Grades 1 through 8 to complete a self-evaluation concerning instructional strategies used in their general education classes. Also, each teacher completed questionnaires concerning their attitudes toward their own efficacy and toward mainstreaming. ANOVAs comparing teachers with positive attitudes toward mainstreaming and teachers with less positive attitudes indicated that the teachers with less positive attitudes used effective mainstream instructional strategies less frequently. Implications of these results in terms of recent educational initiatives resulting in increased inclusion programs are discussed.

Adult↗

Case study. Group Health Association: can Humana resuscitate the moribund HMO?

HMO pioneer Group Health Association of Washington, DC, was hemorrhaging members and dollars when Humana bought it in 1994. Its turnaround strategies run the gamut from outsourcing and devising administrative efficiencies to creating a new physician group and network to replace a feisty, unionized medical staff.

Cost-Benefit Analysis↗