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Biomarkersinpriondisease2010 4-5-100405151856-phpapp02
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Biomarkersinpriondisease2010 4-5-100405151856-phpapp02

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  • SmartArt custom animation effects: vertical chevron list with dark colors(Basic)To reproduce the SmartArt effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank. On the Insert tab, in the Illustrations group, click SmartArt. In the Choose a SmartArt Graphic dialog box, in the left pane, click List. In the List pane, click Vertical Chevron List (fourth row, fourth option from the left), and then click OK to insert the graphic into the slide. To create a fourth chevron, select the third chevron at the bottom of the graphic, and then under SmartArtTools, on the Design tab, in the CreateGraphic group, click the arrow next to AddShape, and select AddShapeAfter.To add bullets for the fourth chevron, select the fourth chevron, and then under SmartArtTools, on the Design tab, in the CreateGraphic group, click AddBullet.To enter text, select the SmartArt graphic, and then click one of the arrows on the left border. In the Type your text here dialog box, enter text for each level. (Note: In the example slide, the first-level text boxes contain “One,” “Two,” “Three,” and “Four.” The second-level text is “Supporting Text.”)On the slide, select the SmartArt graphic and drag the right center sizing handle to the right edge of the slide.With the SmartArt graphic still selected, on the DesignTab, in the Themes group, click Colors, and then under Built-In select Median. (Note: If this action is taken in a PowerPoint presentation containing more than one slide, the theme will be applied to all of the slides.)With the SmartArt graphic still selected, under SmartArtTools, on the Design tab, in the SmartArtStyles group, click MoreStyles, and then under 3-D select Inset (first row, second option from the left). Also under SmartArtTools, on the Design tab, in the SmartArtStyles group, click ChangeColors, and then under Colorful select Colorful -AccentColors (first option from the left). To reproduce the chevron effects on this slide, do the following:Press and hold CTRL, and select all four chevrons in the SmartArt graphic. On the Home tab, in the Font group, in the Font list select Franklin Gothic Medium Cond, and then in the FontSize box select 28.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click TextBox in the left pane, and in the TextBox pane do the following:Under Textlayout, in the Verticalalignment list select Bottom.Under Internalmargin, do the following: In the Left box, enter 0”. In the Right box, enter 0”. In the Bottom box, enter 0”. In the Top box, enter 0.6”.To reproduce the rectangle effects on this slide, do the following:Press and hold CTRL, and the four of the rectangles (with bulleted text). On the Home tab, in the Font group, do the following:In the Font list, select FranklinGothicBook.In the FontSize box, enter 21.In the FontColor list, under ThemeColors select White, Background 1 (first row, first option from the left).On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Black, Text 1 (first row, second option from the left).In the Transparency box, enter 100%. Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Black, Text 1 (first row, second option from the left).In the Transparency box, enter 45%. Also in the FormatShape dialog box, click Shadow in the left pane, and in the Shadow pane, in the Presets list, select NoShadow.Also in the FormatShape dialog box, click 3-DFormat in the left pane, and in the 3-DFormat pane, under Bevel, in the Top list select NoBevel.Select the top rectangle with bulleted text.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click LineColor in the left pane, select Gradientfill in the LineColor pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Orange, Accent 2 (first row, sixth option from the left).In the Transparency box, enter 100%. Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Orange, Accent 2 (first row, sixth option from the left).In the Transparency box, enter 0%. Select the second rectangle from the top with bulleted text.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click LineColor in the left pane, select Gradientfill in the LineColor pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Olive Green, Accent 3 (first row, seventh option from the left).In the Transparency box, enter 100%. Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Olive Green, Accent 3 (first row, seventh option from the left).In the Transparency box, enter 0%. Select the third rectangle from the top with bulleted text.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click LineColor in the left pane, select Gradient fill in the LineColor pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Gold, Accent 4 (first row, eighth option from the left).In the Transparency box, enter 100%. Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Gold, Accent 4 (first row, eighth option from the left).In the Transparency box, enter 0%. Select the fourth rectangle from the top with bulleted text.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click LineColor in the left pane, select Gradient fill in the LineColor pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Green, Accent 5 (first row, ninth option from the left).In the Transparency box, enter 100%. Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Green, Accent 5 (first row, ninth option from the left).In the Transparency box, enter 0%. To reproduce the animation effects on this slide, do the following: On the Animations tab, in the Animations group, click CustomAnimation.Select the SmartArt graphic, and then in the CustomAnimation task pane do the following:Click AddEffect, point to Entrance, and select MoreEffects. In the AddEntranceEffect dialog box, under Moderate select Grow & Turn.Click the arrow to the right of the animation effect (grow & turn effect for the graphic), select EffectOptions, and then in the Grow & Turn dialog box, do the following:On the Timing tab, in the Speed list, select 0.5 seconds (Very Fast).On the SmartArtAnimation tab, in the Groupgraphic list, select Onebyone.Click the double arrow to expand the contents of the list in the CustomAnimation task pane.Press and hold CTRL, and select the second, fourth, sixth, and eighth effects (grow & turn entrance effects), and then do the following:Click Change, point to Entrance and select MoreEffects. In the ChangeEntranceEffect dialog box, under Moderate select EaseIn.With the four ease-in entrance effects still selected, under Modify: Ease In do the following:In the Start list, select WithPrevious.In the Speed list, select Fast.Select the grow & turn entrance effect (first effect in the list), and under Modify: Grow & Turn, in the Start list, select WithPrevious. To reproduce the background effects on this slide, do the following:Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Radial.Click the button next to Direction, and then click From Center (third option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 20%.Click the button next to Color, and then under ThemeColors select White, Background 1, Darker 25% (fourth row, first option from the left). Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Black, Text 1 (first row, second option from the left).
  • Known to exist since the 18th century. Occur in sheep and goat. No evidence of human transmission. Sx’s start with mildly impaired social behavior: unusual restlessness and signs of nervousness. Overt illness lasts 2 wks-6 mo. Scratch against objects, ataxia.
  • First described by Jakob in 1921, in which he referred to a case described by Creutzfeldt in 1920. Pathologic review of those specimens confirmed only 2/5 cases to be true CJD.
  • “spastic pseudosclerosis”
  • AD inheritance with various mutations, P102L most commonClinically characterized by dominant cerebellar syndrome, pyramidal signs, and cognitive decline. Onset 4th-6th decade of life. Duration of months to 6 years.Neuropathologically characterized by PrP-amyloid plaques in cerebellar cortex. Transmission studied first performed by Masters et al in 1981.
  • Transition effect for timeline, slide 1(Basic)Recognized similarity in neuropathology between scrapie and kuruTip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows click Chevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 9.48”.Drag the chevron until the right end is beyond the right edge of the slide, and the left end of the chevron is approximately one inch to the right of the left edge of the slide.Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, point to Gradient, and then click MoreGradients. In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left)Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane, and then do the following in the Shadow pane: Click the button next to Presets, and then under Outer click OffsetBottom (first row, second option from the left).In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Condensed from the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click AlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click DistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover click PushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • Transition effect for timeline, slide 2(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows,click Chevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 11.03”.Drag the chevron until it extends past both the left and right edges of the slide. Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, click Gradient, and then click MoreGradients.In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click OffsetBottom (first row, second option from the left), and then do the following: In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Cond from the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click AlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click DistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover click PushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • Transition effect for timeline, slide 2(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows,click Chevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 11.03”.Drag the chevron until it extends past both the left and right edges of the slide. Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, click Gradient, and then click MoreGradients.In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click OffsetBottom (first row, second option from the left), and then do the following: In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Cond from the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click AlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click DistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover click PushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • Transition effect for timeline, slide 3(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows,click Chevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 9.48”.Drag the chevron so that the left end is beyond the left edge of the slide, and the right end is approximately one inch left of the right edge of the slide. Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, click Gradient, and then click MoreGradients. In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click OffsetBottom (first row, second option from the left), and then do the following: In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Cond from the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click AlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click DistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover click PushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • In 1974, Ignazio Roiter, an Italian doctor,whose wife’s aunt died with depression and insomnia, despite appearing to sleep all the time. In 1979 a second aunt became ill. Then they noticed a pattern in the family. Then an uncle became ill in 1984 and was sent to Elio Lugaresi, a sleep expert who sent the brain to Gambetti
  • Transition effect for timeline, slide 2(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows,click Chevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 11.03”.Drag the chevron until it extends past both the left and right edges of the slide. Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, click Gradient, and then click MoreGradients.In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click OffsetBottom (first row, second option from the left), and then do the following: In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Cond from the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click AlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click DistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover click PushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • FFI=19kdal, CJD=21 kdalBrain vs brainstem
  • Excludes known iatrogenic and inherited cases. tEngland and Wales only for theperiod 1970-84. *Numbers in brackets indicate patients alive. Died before May1990.
  • Total=216
  • Found 3 appendectomy samples with prion protein

Transcript

  • 1. The Historical Significance of Biomarkers in Prion Diseases Biomarkers in Neurodegeneration Seminar Johns Hopkins Bayview Medical CenterPresented by: Brian Appleby, M.D.April 5, 2010
  • 2. • History of prion diseasesOne • Spongiform encephalopathy and transmissibility as biomarkers of prion diseaseTwo • PrPres as a biomarker of prion diseaseThree • Describe biomarkers in different types of prion Four diseases
  • 3. SPONGIFORMENCEPHALOPATHY
  • 4. Brown P, CNS Neurol Disord Drug Targets 2009
  • 5. Brown P, CNS Neurol Disord Drug Targets 2009
  • 6. Creutzfeldt-Jakob diseaseHans Gerhard Creutzfeldt Alfons Maria Jakob
  • 7. “…this is a disease of middle and late life which begins with…disturbances of the motor apparatus and of sensation…the patient’s gait is strikingly uncoordinated…striking mental changes appear, in theform of apathy, negativism, and delirious and hallucinatoryconfusional states…The course of the disease is subacutely progressive…of several weeks to a year.” Jakob A. Med Klin 1921
  • 8. Jones DP & Nevin S. JNNP 1954
  • 9. Jones DP & Nevin S. JNNP 1954
  • 10. Brown P, CNS Neurol Disord Drug Targets 2009
  • 11. Gerstmann-Sträussler-Scheinker (GSS) Gerstmann J, et al. Z Gesamte Neurol Psych 1935
  • 12. TRANSMISSIBILITY
  • 13. Brown P, CNS Neurol Disord Drug Targets 2009
  • 14. KuruGajdusek DC & Zigas V. NEJM 1957
  • 15. 1958 1959 1960 Hadlow WJ. Lancet 1959
  • 16. 1960 1961 1962 Chandler RL. Lancet 1961
  • 17. 1965 1966 1967 Gajdusek DC, et al. JAMA 1967
  • 18. 1967 1968 1969 Gibbs CJ, et al. Science 1968
  • 19. Brown P, CNS Neurol Disord Drug Targets 2009
  • 20. Fatal Familial Insomnia (FFI)
  • 21. Lugaresi E, et al. NEJM 1986
  • 22. Lugaresi E, et al. NEJM 1986
  • 23. Tateishi J, et al. Nature 1995
  • 24. PRIONSProteinaceous and infectious particles
  • 25. “…the evidence that no inactivation results from exposure to a huge dose of ultraviolet light, of wave- length specifically absorbed by nucleic acids, suggests that the agent may be able to increase in quantity without itself containing nucleic acid.” Alper T, et al. Biochem Biophys Res Commun 1966 Alper T, et al. Nature 1967
  • 26. S1 + G1 = S1G G0 S2 + G2 = S2G S S1 + G2 = S2S+G=S S2 + G1 = 0 X M M+G=S P1 = normal P2 = normal P1 + P2 = scrapie Griffith JS. Nature 1967
  • 27. α2 + α = α3 α3 + α = α4 α4 2α2 α + α α2 α2 α’ α – ΔF1 α+α α2 + ΔF2 α2 + α = α3 + ΔF3 α3 + α’ = α4 + ΔF4 α4 2α2 + ΔF5ΔF5 = -2ΔF1 + ΔF2- ΔF3 - ΔF4 > 0
  • 28. Prusiner SB. Science 1982
  • 29. “…for his discovery of Prions - a new biological principle of infection."Prusiner SB. Science 1982
  • 30. control100 μg/mLProteinase K500 μg/mLProteinase K McKinley MP, et al. Cell 1983
  • 31. Soto C, et al. Trends Biochem Sci 2006
  • 32. “Protein X” A. PrPc (blue) and PrPSc (red) undergo endocytosis B. Co-factor (yellow) on lipid raft assists conversion of PrPc to PrPScTaylor D & Hooper N. Semin Cell Dev Biol, 2007
  • 33. “These findings provide strong support for the protein-only hypothesis of TSE diseases, as well as argue that cofactors such as nucleic acids, other polyanions or lipids are nonobligatory for prion protein conversion to the infectious form.” Kim J, et al. JBC [In Press]
  • 34. BIOMARKERS IN PRION DISEASE SUBTYPES
  • 35. Importance of donor PrPres strain Telling GC, et al. Science 1996
  • 36. Brown P, CNS Neurol Disord Drug Targets 2009
  • 37. Bovine Spongiform Encephalopathy (BSE) Wells GAH, et al. Vet Rec 1987 Wilesmith JW, et al. Vet Rec 1988
  • 38. Will RG, et al. Lancet 1996
  • 39. Clinical Differences Will RG, et al. Lancet 1996
  • 40. Neuropathologic Differences “Florid plaques” Ironside JW. FEMS Immunol Med Microbiol 1998
  • 41. Neuroradiologic Differences “pulvinar sign” Zeidler M, et al. Lancet 2000
  • 42. Met-ValMet-Met Val-Val codon 129 PRNP
  • 43. http://www.cjd.ed.ac.uk/vcjdworld.htm
  • 44. Andrews NJ. Incidence of variant Creutzfeldt-Jakob disease deaths in the UK 2010
  • 45. Met-ValThe Transfusion Medicine Epidemiology Review
  • 46. Peden A, et al. Haemophilia 2010
  • 47. “…estimated prevalence of 237 per million individuals…” 0/63,007 samples were positive Hilton DA, et al. J Path 2004 Clewley J, et al. BMJ 2009
  • 48. Peripheral tissues shown to contain PrPres in vCJD Notari S, et al. PLoS ONE 2010
  • 49. Synopsis of PrPres analyses in the brain and other tissues Notari S, et al. PLoS ONE 2010
  • 50. Kaski D, et al. Lancet 2009
  • 51. Strain Individual variability sCJD gCJD *connected circles represent animals inoculated at same time with identical aliquots Brown P, et al. Ann Neurol 1994
  • 52. Incidence of iCJD cases from hGH Huillard d’Aignaux J, et al. Neurology 1999
  • 53. Telegraph.co.uk, 18 Dec 2008Nurmi MH, et al. Acta Neurol Scand 2003
  • 54. Protease sensitive prionopathy (PSPr) Gambetti P, et al. Ann Neurol 2008
  • 55. Summary• Prion disease cause spongiform encephalopathies and are transmissible*• Prion disease are characterized by an abnormal isomer of the native prion protein that is incompletely digested by proteinase K• Prion disease characteristics are affected by PrPres strain and host genotype.
  • 56. AcknowledgementsPatients and families CJD Foundation, CJD Insight, CJD Aware! Florence KranitzPaul Brown (CEA/DSV/iMETI/SEPIA) Deana SimpsonBob Will (National CJD Surveillance Unit, UK) NPDPSCJohns Hopkins Pierluigi GambettiPeter Rabins Sally BerriKostas LyketsosBarbara Crain FTD/YOD ClinicAvi Nath Chiadi Onyike Mary Anne Wylie Rebecca Rye Kate Hicks