Case Western Reserve University

About: Case Western Reserve University is a education organization based out in Cleveland, Ohio, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 54617 authors who have published 106568 publications receiving 5071613 citations. The organization is also known as: Case & Case Western.

Toward Understanding Tryptophan Fluorescence in Proteins

Abstract: A general approach to dissecting the complex photophysics of tryptophan is presented and used to elucidate the effects of amino acid functional groups on tryptophan fluorescence. We have definitively identified the amino acid side chains that quench tryptophan fluorescence and delineated the respective quenching mechanisms in a simple model system. Steady-state and time-resolved fluorescence techniques, photochemical H-D exchange experiments, and transient absorption techniques were used to measure individual contributions to the total nonradiative rate for deactivation of the excited state, including intersystem crossing, solvent quenching, and excited-state proton and electron transfer rates. Eight amino acid side chains representing six functional groups quench 3-methylindole fluorescence with a 100-fold range in quenching rate constant. Lysine and tyrosine side chains quench by excited-state proton transfer; glutamine, asparagine, glutamic and aspartic acid, cysteine, and histidine side chains quench by excited-state electron transfer. These studies provide a framework for deriving detailed structural and dynamical information from tryptophan fluorescence intensity and lifetime data in peptides and proteins.

A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression

Abstract: Background More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. Methods Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. Results Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. Conclusion Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.

Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I

Abstract: Membrane-type matrix metalloproteinase I (MT1-MMP)-deficient mice were found to have severe defects in skeletal development and angiogenesis. The craniofacial, axial, and appendicular skeletons were severely affected, leading to a short and domed skull, marked deceleration of postnatal growth, and death by 3 wk of age. Shortening of bones is a consequence of decreased chondrocyte proliferation in the proliferative zone of the growth plates. Defective vascular invasion of cartilage leads to enlargement of hypertrophic zones of growth plates and delayed formation of secondary ossification centers in long bones. In an in vivo corneal angiogenesis assay, null mice did not have angiogenic response to implanted FGF-2, suggesting that the defect in angiogenesis is not restricted to cartilage alone. In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation in vivo.

Visual Experience in Infants: Decreased Attention to Familiar Patterns Relative to Novel Ones

Abstract: A complex visual pattern presented for ten successive 1-minute exposure periods was fixated progressively less than comparable novel stimuli by infants 2 to 6 months old. This indicates the occurrence of recognition and habituation of visual responsiveness to specific patterns, and suggests that familiarization with the environment begins through visual exploration before more active exploration is possible.