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On the first day of spring—the vernal equinox—day and night are each approximately 12 hours long (with the actual time of equal day and night, in the Northern Hemisphere, occurring a few days before the vernal equinox). The Sun crosses the celestial equator going northward; it rises exactly due east and sets exactly due west.
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PARADISE — Four people who have made important contributions to the ridge community will be honored Feb. 16 during a Paradise Elks Lodge Citizens of the Year dinner at the lodge, 6309 Clark Road.
To be honored are:
Man of the Year, former Town Mayor Dan Wentland, who has lived on the ridge for 40 years. He has also been a planning commissioner and an officer for the Chamber of Commerce.
Woman of the Year, Senior Center Board Member Loretta Griffin, who has also been a planning commissioner, active with the Fire Safe Council and lived on the ridge for 33 years.
Senior Citizen of the Year, retired school administrator Al Keller, who has been active with the Elks Lodge as exalted ruler in 2003-2004, as well as starting the annual hoop shoot and running the scholarship committee. He has also belonged to Paradise Rotary.
Junior Citizen of the Year, Paradise High School senior, Julianna Wiggins, who has taken part in Girls State, her school band, volunteered at her church and has received the Coach's Award in 2010.
This will be the 41st year for the dinner. Reservations should be made by Feb. 11 by calling 877-2231.


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Property ID : 10128
For Rent £425 per Month | Bond £400 - Flat
We are pleased to be able to offer this two bedroom third floor flat. The property comprises two bedrooms, lounge / kitchen and WC with separate shower. The property has great views over Scarborough cricket ground to the rear and sea views to the front. There is a communal laundry room, free Wi-Fi to the building and water rates are included in the rent.
A working mature person is preferred but DSS applicants will also be considered. Sorry no children or pets.
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Tenant/Guarentor reference fee no long applies.
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A couple looking to rent a house with a monthly rent of £520 will require;
Rent: £520
Bond: £600
Reference fee: £0.00
Total £1120


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Try Not to Laugh Challenge | YEEEEET
Views: 1392073 | Likes: 59381 | Dislikes: 1818 | 2017-02-10 01:07:15 |
Watch as SSundee heads back to the internet to watch more Try not to laugh challenges!! Will he be able to grow up and not laugh at every little thing?! Most likely not, he will be a man child the rest of his life… Lol, Thanks for watching, I appreciate the support and any ratings would be greatly appreciated also!
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by Tarek Said
Filmed at Ignite Sydney
We always think of doom and gloom when we think of refugees. What if they were allowed to tell funny stories, too? Video created by Hunting With Pixels. http://www.huntingwithpixels.com Hunting With Pixels is a Sydney and Melbourne based social video strategy and production agency.
Petra Williams at Ignite Sydney
Jeremy Cheung at Ignite Hong Kong Green Building Week
What Kayak Racing Taught Me About Business
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By Civilnet | Saturday, 02 April 2016
The Azerbaijani side utilized artillery weapons, tanks, military helicopters and attempted to infiltrate and take over several posts of the NKR Defense Army. Nagorno Karabakh defense Army's press release states that, "In addition to the border offensive, the enemy targeted civilian areas and permanent military units deployed away from the Contact Line." An updated release stats that an Azerbaijani air raid on the Marduni region has resulted in the death of 12 year old Vaghinag Grigoryan and two other children were wounded.
The NKR Defense Army has retaliated and pushed back the advancement of Azerbaijani military units. There are casualties on both sides. According to a 09:10 am update on the Nagorno Karabakh Defense Ministry website, the Armenian side has shot down an enemy helicopter.
Officials Light Pan-Armenian Games Torch Near Musa Ler
UN Secretary-General Appoints Movses Abelian to New Post
Azerbaijan Again Skips OSCE Monitoring Mission
Council of Europe Group Says Baku Has Not Implemented Key Priorities
Leaders of Armenia, Cyprus, Greece to meet in Yerevan
Mkhitaryan to Skip Europa League Final in Baku
Azerbaijan Vows to Guarantee Mkhitaryan's Safety in Baku
Stratfor Ranks Artsakh as De Facto Independent State
Armenia in contact with New Zealand authorities to find out details of Armenian note found on gun of mosque attackers
Some parts of Rovshan Askerov's interview related to Armenia are surprising – MFA Armenia comments on Azerbaijani expert's announcement


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Chardonnay - Zinfandel - Red Wine
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Top Red Wine brandsFrancis Ford Coppola - Red Wine Domaine Faiveley - Red Wine Colgin - Red Wine Nickel & Nickel - Red Wine Bruno Giacosa - Red Wine
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Berries with hints of flowers, minerals and spice in the aroma; multi-layered and rich flavor on the broad and supple middle palat...e; and an intense, clean and lingering impression on the finish. A touch of Viognier is added to enhance the intriguingly... read more
As the 105th vintage crafted from the Lewis Family Vineyard, their 2011 Centennial Zinfandel continues to be a reflection of these... old growth vines. Their traditional hands-off approach to winemaking allows the natural richness and complexity of this... read more
The Jack's Cabin Zinfandel has a reputation of being the most fruit forward of the Rockpile Zins. Across the board, the 2014 Rockp...ile Zinfandels are richer and fuller. Aromas of high-toned black cherry are overlaid with cocoa powder and sweet baking... read more
Blackberry, raspberry and other brambly fruit characteristic of Alexander Valley. "Graham crust" undertones typical of the Home Ra...nch terroir. Subtle hints of oak, briary acidity and soft, ripe fruit tannins. Pairs well with well-marbeled cuts of beef... read more
The wine begins with lovely aromatics and a hint of forest floor. It is balanced withbright lively black and red fruits. Notes of ...sassparilla and anise evolve into a velvety full mouth feel that is rich and dense. The finish is long and silky. Blend:... read more
Forgotten Vines Zinfandel opens brilliantly with bright fruit aromatics that are complemented by hints of warm spice and cocoa. Fl...avors of blackberry, blueberry, currant, tobacco and milk chocolate envelope the palate and lead to an opulent, smooth... read more
Aromas of wild blueberry, briary raspberry patch and baking spice give way to a palate of juicy, ripe blackberry and black plum. S...oft tannins, a rich mouthfeel and focused acidity lead to a long finish, creating a delightful wine to pair with red... read more
Aromas of currant, cassis and spice box give way to a palate of freshly picked ripe cherry and hints of earth. Fine tannins, an el...egant mouthfeel and focused acidity lead to a long finish, creating a delightful wine topair with cured meats, duck... read more
The aromas are reminiscent of late summer dusty roads, blackberry pie, and vanilla oak. The flavors are true to the terrior; compl...ex with milk chocolate, grilled meats and an integrated dark fruit and oak finish. Sleek and supple, with lively black... read more
Medium to deep garnet-purple, the 2016 Hartford Zinfandel Dina's Vineyard comes leaping forth from the glass with arresting, gorge...ous floral scents of violets, lavender and roses with a core of cherry cordial, blueberry compote, blackberry tart and... read more
Zinfandel from Lagier Meredith vineyard. Aged for 17 months in neutral French oak barrels, this 2012 has everything you loved abou...t the previous vintage and more. The same exotic spice but more richness all around. Tribidrag was the ancient name for... read more
Raspberry and pomegranate aromas are laced with hints of white pepper, and vanillin spice. The palate entry has gobs of fruit, wit...h cherry, bramble and ripe strawberry at the core. Smooth, round tannins anchor a great depth and concentration of flavor... read more
Robust black cherry and pomegranate aromas are laced with hints of white pepper, Occidental dust, and cinnamon. The palate entry c...enters on flavors of black cherry, bramble and ripe strawberry, while smooth, round tannins anchor a great depth and... read more
Aged for 18 months in neutral French oak barrels. The wine has the usual exotic spice and balance, but this vintage also offers up... some flowers. Tribidrag was the ancient name for Zinfandel in the Middle Ages, when it was widely grown along the... read more
The Dry Creek Valley Zinfandel is an "appellation wine" and we attempt to make a wine that represents what we think the appellatio...n is; rich, but not overripe, fruit-forward, but not a bomb, structured, but not tannic. The 2015 is a blend of Treborce,... read more
D-cubed Cellars Howell Mountain Zinfandel has intense aromas of dried cherries, raspberries, and cranberries. These fruit aromas a...re balanced by aromas of black pepper and cardamom. Very nice body and smooth round tannins with flavors of raspberries,... read more
Dark red to black fruits and the lovely florals, so common in the delta sands, are prominent and engaging.
Dark, yet fresh, brambly fruit dominate the nose with upfront notes of blackberry, raspberry, plum and dark cherry. Forward berry-...driven fruit is accented by classic Dry Creek Valley baking spice and more subtle dried fruit notes. Palate and texture... read more
This unique Oakville Zinfandel has developed a powerful structure that is sweet on the front palate and spicy on the back. On the ...nose; ripe blackberry, wild huckleberries, and candied raspberry. On the palate, this Zinfandel is medium bodied with... read more
This Zinfandel is unique in that it's blended with the best selections of Petite Sirah. Even though the Zinfandel from this terrif...ic vintage showed great complexity on its own, Petite Sirah was added to enhance the structure of the wine. A combination... read more
Zinfandel from Lagier Meredith's vineyard. Aged for 17 months in neutral French oak barrels. Not at all a fruit bomb, this wine of...fers exotic spice and great balance. Tribidrag was the ancient name for Zinfandel in the Middle Ages, when it was widely... read more
The 2017 Hartford Russian River Valley Zinfandel is showing aromas of ripe plum, blackberry, black cherry which are highlighted wi...th hints of white pepper and allspice. Blueberry, red raspberry, nutmeg and mocha ?avors lead into a long, bright ?nish... read more
Boysenberries, hint of eucalyptus, a bit of white pepper. In the mouth it is all about rich but bright fruit with good acidity bal...ancing a good dose of alcohol. An unabashed big zin, but not at all over-ripe. A fine finish to a long run with this... read more
At 1000 feet above sea level at the top of Bradford Mountain, the Grist Vineyard in Dry Creek Valley is where Joseph Jewell source...s their Zinfandel. The vineyard, which was planted in 1974, consists of red volcanic soils and receives lots of direct... read more
Nice dark-red in color, this wine offers aromas of blueberry-blackberry fruit and spicy-chocolatey oak. On the palate, nicely focu...sed acidity enhances mineral flavors, with elegantly structured tannins and a super plush long finish. read more
If you tasted this not knowing it was zinfandel, the wine's herb-edged earth-tone aromas of green olive, beetroot and black loam m...ight have you thinking blaufrankisch. From a relatively warm hillside in Sonoma's cool coastal hills, it's an unusual... read more
This is the sixteenth release of our popularly-priced Amador County Zinfandel. It is made from grapes that grow on our beautiful, ...rolling mountain sites that have the classic, vermilion-colored, Amador decomposed granite soil. The 2012 has full black... read more
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Fresh black cherry fruit aromas, with black pepper accents. Shows juicy blackberry, blueberry, and raspberry flavors. Beautiful de...pth and concentration with soft and supple fine-grain tannins. Finishes with a touch of mocha. read more
A beautiful purple or red color leads to aromatics that showcase very ripe and concentrated aromatics of black fruits and bramble.... Deep and dark in all aspects this vintage showcases more of the seductive aspect of this vineyard's magic. Raspberry and... read more
Dark red cherries, plums, lavender and sweet spices make a hugely positive first impression in the 2013 Zinfandel Jolene's Vineyar...d. Violets, smoke, mint and darker stone fruits develop in the glass, all supported by veins of bright acidity and tannin,... read more
Maddalena Zinfandel shows flavors of ripe red fruit, including bright raspberry and spicy black plum. Barrel-aging contributes not...es of cocoa and oak spice. The mouth is round with a rich, silky texture that is framed by soft tannins. Black plum,... read more
Dried fruit aromas, deep flavors, full body and moderate tannins add up to a robust, berry-drenched wine that packs a big punch. B...lackberries, dried figs and light spicy accents fill out the palate and linger a bit on the finish. Commentary: Sobon... read more
The inky-indigo color suggest the depth of flavors to follow. Wild blackberry, dried cranberry and brown sugar aromas tickle your ...nose. Hints of cedar and cinnamon tease and meld effortlessly with the vibrant fruit flavors. The wine begins with a lush... read more
Aromas of wild blueberry, briary raspberry patch and baking spice give way to a palate of juicy, ripe blackberry and black plum. S...oft tannins, a rich mouthfeel and focused acidity lead to a long finish, creating a delightful wine to pair with red... read more
#45 Wine Spectator Top 100 of 2018 Epitomizes fine Sierra Foothills Zinfandel, offering vibrant, briary raspberry, smoked pepper a...nd wild sweet anise flavors that stretch out on the zesty finish. Drink now through 2023. read more
Our classic California Zinfandel is dark purple-ruby, with a bright crimson hue. On the nose, concentrated aromas of blackberry an...d raspberry meld with clove and spice. Lush flavors of raspberry, blackberry jam, plums and vanilla flood the palate,... read more
Purity and focus in the black-fruit flavors and a powerful structure of tannins and good acidity come together nicely in this big ...but balanced wine. Blackberries, black plums and a pinch of black pepper give it a delicious classic profile read more
This is a full-blown wine, saturated with berry and bramble flavors, full bodied and pushing the edge of sweetness. It's big, mout...hfilling but light on tannins, giving a jammy sensation that's supplemented with traces of dried sage and black pepper. read more
The wine is crafted from head trained vines that create beautiful fruit with aromas of plum and raspberry. This lush and concentra...ted Zinfandel bares rich flavors of chocolate covered cherries with hints of mild tobacco and baking spice that play out... read more
Deep magenta core and scarlet rim sparkle with crystalline clarity. A swirl of the glass reveals Venezuelan chocolate commingled w...ith embers that lead into creamy vanilla bean. Hallmark characteristics of hibiscus blossom, exotic Asian apple, and rose... read more
The Korte Ranch is a classic old St. Helena Vineyard, planted around 1910. Korte Ranch is head-trained and dry-farmed planted on t...he St. George rootstock and produces wonderful Zinfandel. read more
This Zinfandel has a luscious velvety mouthfeel and rich, gorgeous spices on the nose. Even though the tannins are fairly subdued,... the wine has robust character from its earthy nuances and seasoned oak. read more
Hand crafted from 46 year old dry-farmed, organically certified grown grapes can only say: "let the grapes rule!" Minimal new Fren...ch oak to keep the individuality and jubilant character of this bench land Zin buoyant. read more
The Terra d'Oro Deaver Zinfandel has a deep garnet color with lifted aromas of dark fruit, clove and spicy oak. The palate is focu...sed with crisp and juicy layers of ripe blackberry, spicy plum and soft chewy tannins. The baked spice components add... read more
A harmonious expression of dark fruits and subtle nuances from 12 months of French and American oak aging. Deep red in color with ...a great mouthfeel, our Reserve Zinfandel exudes aromas of tobacco, cola, plum, and clove. Wild raspberry, plum, cherry and... read more
The Novy Russian River Valley Zinfandel is a reflection of the quality of the vineyards selected to comprise this wine. This Zin c...omes almost exclusively from the Jensen Lane Vineyard (planted in 1915, the Limerick Lane Vineyard (planted in 1910), and... read more
A spicy, smoky wine with plum and pepper notes and vibrant food-friendly acidity. Pair with full flavored spicy fish, turkey and c...hicken. read more
The wine is bright and lively with concentrated "Zini" aromas; predominately dark cherry, blueberry, plum with some typical raisin.... The fine oak barrel aging brings in subtle aromas of vanilla, brown sugar, cinnamon and slight toast and smokiness. The... read more
The Pelissa vineyard is located on Oakville Crossroads directly behind Ghost Block's family winery, creating one of the only true ...Estate grown and produced Zinfandels from the Oakville Ava. With Napa Valley elegance, this single vineyard Zinfandel... read more


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Inner Harbour, Victoria, BC
On Sunday, August 4, 2019, tens of thousands of people will take to Victoria's Inner Harbour for the 30th annual Victoria Symphony Splash. From a floating stage in the Inner Harbour, the VS orchestra and special guests will perform, ending with a grand finale performance of Tchaikovsky's 1812 Overture – with fireworks of course!
Many people arrive early to ensure they have a good view of the barge for the orchestra performance at 7:30 pm.
1:00 – 4:00 pm – The TD Family Zone is open on the Fairmont Empress lawn.
3:00 pm – The Beverage Garden and Culinary Corner open.
4:00 pm – The opening act performs on the barge in the Inner Harbour.
6:20 pm – The orchestra parade.
7:30 pm – Maestro Kluxen and the Victoria Symphony.
10:00 pm – Splash concludes.
This event is 'free' but …
Victoria Symphony Splash is a "by donation" event produced entirely by the Victoria Symphony. While we do receive support from generous sponsors and "heroes," we ask that you donate $5 per person to make this event a reality. Every $5 donation will receive a Splash Button which you can wear proudly to show your support for the Symphony. You'll find volunteers with donation buckets roaming the crowds or you can track down one of our donation barrels. All proceeds go to support the Victoria Symphony's artistic and education programs.


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It's hard to believe, but we are now just one week and two days away from the 2016 election. In addition to a heated presidential race, there are five states voting on the legalization of cannabis for those 21+. Below are these five states, all of which have the opportunity on November 8th to legalize …
Tag: cannabis votes
One Week Until These Five States Vote on Legalizing Cannabis
- By Anthony Martinelli in News
October 30, 2016
Recent Posts
- How Cannabis Can Help Seniors Improve Their Quality Of Life
- Study: Strong Majority of Hospice Professionals Support Medical Marijuana
- What is CBD Microdosing?
- New Mexico Adds Opioid Use Disorder and Other Ailments as Qualifying Medical Marijuana Condition
- Presence Of THC In Blood is Not Associated With Crash Culpability, Finds Study
- Study: Medical Marijuana Legalization Associated With Lower Opioid Prescription Rates
- Illinois Senate Approves Bill to Legalize Marijuana
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The Devonshire Regiment was a line infantry regiment of the British Army which served under various titles and served in many wars and conflicts from 1685 to 1958, such as the Second Boer War, the First World War and the Second World War. In 1958 the regiment was amalgamated with the Dorset Regiment to form the Devonshire and Dorset Regiment which, in 2007, was amalgamated with the Royal Gloucestershire, Berkshire and Wiltshire Regiment, the Royal Green Jackets and The Light Infantryto form a new large regiment, The Rifles.
The Duke of Wellingtons, West Riding Regiment Cap Badge
WW2 Royal Canadian Engineers Cap Badge
7th Dragoon Guards Cap Badge
Reconnaissance Corps Cap Badge
The Hertfordshire Regiment Cap Badge. Brooch Fitting
WW2 Royal Army Service Corps Cap Badge British Army George VI
North Staffordshire Cap Badge British Army
The First Life Guards Enameled Badge
WW2 Yorkshire (Green Howards) Regiment Cap Badge British
Yorkshire Brigade Officers Cap Badge Dress
Worcestershire Regiment Bronze Officers cap badge.
The Hertfordshire Regiment Cap Badge
Mobile Defence Corps Cap Badge
British Army Royal Hampshire Regiment Cap Badge
WW2 Royal Fusiliers Plastic Economy Cap Badge.
The Oxfordshire And Buckinghamshire Light Infantry Cap Badge.
Womens Auxiliary Army Corps Cap Badge W.A.A.G.
Kings Own Scottish Borderers Cap/Glengarry badge Victorian ORs 1889 - 1902 issue
Northamptonshire Yeomanry Cap Badge
WW2 The Devonshire Regiment Cap Badge British Army
Grenadier Guards Cap Badge, other ranks
Indian Army Ordnance Corps Cap Badge
Dorsetshire Regiment Cap Badge. 1901 - 1956.
WWII ATS Officers Bronze Cap Badge
The Welsh Guards Cap Badge
WW2 The Devonshire Regiment Plastic Economy Cap Badge
WW1 The Devonshire Regiment Economy Cap Badge
Royal Artillery Staybrite Cap/Beret Badge Dowler Birmingham
WW1 Army Service Corps ASC Cap Badge
WW2 Parachute Regiment Cap Badge
British Army Military Bandsman Musician Cap Badge
Notts & Derby Regiment Sherwood Foresters Officers Gilded Cap Badge
Royal Army Pay Corps Cap Badge British Army
4th Battalion Border Regiment Cumberland And Westmorland Cap Badge
The Light Infantry Brigade Staybrite Cap Badge
British Army 12th Royal Lancers Cap Badge
The Royal Sussex Regiment Cap Badge
The Green Howards (Alexandra Princess of Wales west Yorkshire Regiment) Plastic Economy Cap Badge
Queens Own Yorkshire Yeomanry Cap Badge
Mewar State Police Cap Badge Indian
5th Maratha Light Infantry Cap Badge Indian Army
The Royal Army Pay Corps Cap Badge
Adjutant General's Corps Staybrite Cap Badge
4th/7th Royal Dragoon Guards Cap Badge British Army
WW2 The Devonshire Regiment Cap Badge
Royal Berkshire Regiment Cap Badge
Queens Own Yorkshire Yeomanry Cap Badge British Army
Royal Artillery Staybrite Beret badge Briitsh Army
WW1/2 Royal Navy Chief Petty Officer Bullion Cap Badge
The Kings Regiment Liverpool & Manchester Staybrite Cap Badge
Control Commission Germany Cap Badge
WWII British ATS Cap Badge Auxiliary Territorial Service Home Front
Wessex Regiment Cap Badge Staybrite
Royal Norfolk Regiment Cap Badge.
Royal Ulster Constabulary Cap Badge And Collars
The Royal Rifle Brigade Shoulder Belt Plate British Army
The Somerset Light infantry Cap Badge
Royal Corps Of Signals Cap Badge
WW2 Royal Navy WRENS Petty Officer Cloth Cap Badge
Royal Army Physical Training Corps Cap Badge
Alexandra Princess Of Wales Own Yorkshire Yeomanry, Hussars Cap Badge
WW2 The Kings Royal Rifle Corps Plastic Economy Cap
20th Hussars Cap Badge
The Essex Regiment Cap Badge British Army WW2
Royal Jersey Light Infantry Regiment Cap Badge
WW1 Kings Dragoon Guards Cap Badge
Royal Navy Petty Officer Cap Badge
Royal Welsh Fusiliers Collar Badge Converted To a Pugri
Air Defence Cadet Corps Cap Badge and Stick pin
7th Duke of Edinburghs Own Gurkha Rifles Cap Badge
Dorsetshire Regiment Officers Bladed Cap Badge
Gloucestershire Regiment Back Badge Gilded
The Worcestershire Regiment Cap Badge 1925 - 1966
WW2 Royal Army Service Corps Cap Badge British Army
British American Squadron Cap Badge
Canadian Toronto Scottish Cap Badge
7th Ghurka Rifles Cap Badge
The West Riding Officers Cap Badge
Royal West Surrey Regiment Cap Badge
Royal Australian Infantry Corps Cap Badge
Indian Jodhpar Lancers Cap Badge
WW1 21st Lancers All Brass Economy Cap Badge
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The Devonshire Regiment Cap Badge World War Two
The Kings Own Royal Lancaster Regiment Cap Badge British Army
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17th/21st Lancers Staybite Cap Badge
Intelligence Corps WW2 Plastic Economy Cap Badge
Prince of Wales Own Regiment of Yorkshire
Royal Air Force Medical Corps Cap Badge RAF British
Sherwood Foresters Notts & Derby Regiment Cap Badge British Army
WW2 REME Royal Electrical and Mechanical Engineers Cap Badge
Durham Light Infantry Cap Badge British Army
48th Battalion, The Torrens Regiment Cap Badge Australia
Royal Regiment Of Fusiliers Staybrite Cap Badge
Duke of Wellingtons Regiment Cap Badge.
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To test these websites, you'll be asked to visit the site in question and record your reactions and thoughts as you go through it. To get started making extra money online by testing websites, sign up for some of the most popular services like UserTesting.com, Userlytics, TryMyUI, Userfeel, TestingTime (for people outside the U.S), or Side Income Jobs.
The world becomes a better place when people learn new things, and if you are a good writer, you can put your skills to use and help educate the world. If you love to write, consider being a freelance writer. Freelance writers are always needed for blog entries, magazines, websites, and more. Business owners are often willing to pay a good price for a well-written article they can use, and you will get some fast cash as a result. There are several different ways in which you can embark on a freelance writing career. You can register for an article writing website, look through the writing job boards, or contact a publication on your own and pitch your ideas. The sky is the limit to how much you can earn.


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He supports patients at Sunnybrook's Odette Cancer Centre and other hospitals in Toronto.
Patient story: Vivian hopes to lift spirits with music
Vivian has founded Bands of Colour, an entertainment program that will bring professional local musicians into our Odette Cancer Centre for mini...
Sunnybrook is taking a personalized approach to breast cancer care
A bold new path to treat breast cancer with precision-based medicine.
A bold new program aims to improve outcomes for older patients with cancer
For older patients with cancer, treatment can be challenging. And they may not always get the care they need because of their age.
Behind the research: pancreatic cancer care in Ontario
One third of people with metastatic pancreas cancer in Ontario don't see a medical oncologist, a study published today in CMAJ found.
Behind the research: opening up conversations about sex and intimacy after cancer
Sex and intimacy after cancer treatment can be a challenge for many couples. A Sunnybrook research project aims to help couples overcome that.
New electromagnet guidance for brachytherapy aims to improve targeting
When Debbie Vaz heard about a research trial testing a new navigation system for brachytherapy, she says the decision to participate was a "no...
Colorectal cancer: test your knowledge
Strong evidence supports screening for colorectal cancer, which means checking for the disease before symptoms appear to prevent cancer or detect it...
Patient story: A new focused ultrasound and glioblastoma trial
Paul Hudspith is one of the first participants in a world-first trial at Sunnybrook examining the use of focused ultrasound to open the blood-brain...
Behind the Research: Exploring focused ultrasound to enhance chemo delivery to glioblastoma
In a new trial, Sunnybrook researchers are exploring the use of focused ultrasound (FUS) to open the blood brain barrier (BBB) and enhance the...


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Papillon-Lefevre Syndrome: Mutations and Polymorphisms in the Cathepsin C Gene
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MUTATION REPORTPapillonLefevre Syndrome: Mutations and Polymorphisms inthe Cathepsin C GeneAoi Nakano, Kazuo Nomura,* Hajime Nakano, Yoshio Ono, Sal LaForgia, Leena Pulkkinen,Isao Hashimoto, and Jouni UittoDepartments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, Jefferson Institute ofMolecular Medicine, and the DebRA Molecular Diagnostics Laboratory, Thomas Jefferson University, Philadelphia, U.S.A.; *Department ofDermatology and Department of Dentistry and Oral Surgery, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Dermatology,Hirosaki University School of Medicine, Hirosaki, JapanThe PapillonLefevre syndrome, inherited in anautosomal recessive pattern, manifests withpalmoplantar keratoderma and early, destructiveperiodontitis. Recently, mutations in the geneencoding cathepsin C have been disclosed in alimited number of families with PapillonLefevresyndrome. We have examined two multiplexfamilies with PapillonLefevre syndrome, andevaluated the gene encoding cathepsin C formutations. The mutation detection strategy con-sisted of polymerase chain reaction amplicationof all seven exons and anking intronic sequences,followed by direct nucleotide sequencing. Thisstrategy identied two missense mutations, W39Sand G301S, affecting highly conserved amino acidresidues within the cathepsin C polypeptide. Theaffected individuals were homozygotes whereasheterozygous carriers of the mutations were clini-cally unaffected, conrming the recessive nature ofthe mutations. Addition of these cathepsin C genemutations into the expanding PapillonLefevresyndrome mutation database allows further devel-opment of genotype/phenotype correlationstowards understanding this severe genodermatosis.Key words: keratoderma, periodontitis, genodermatoses.J Invest Dermatol 116:339343, 2001The PapillonLefevre syndrome (PLS; OMIM no.245000) is a relatively rare autosomal recessivecondition manifesting with palmoplantar keratoder-ma, combined with a rapidly progressive periodontitis(Papillon and Lefevre, 1924; for reviews see Haneke,1979; Hart and Shapira, 1994; Siragusa et al, 2000). The estimatedprevalence is one to four per 106 (Verma et al, 1979). The initialclinical signs of skin involvement are usually evident during the rst4 y of life, and a histopathologic examination of the affected skinshows hyperkeratosis with psoriasiform parakeratosis. The gingivalinvolvement may be noticeable as early as 3 or 4 y of age. Both thedeciduous teeth and permanent teeth are lost prematurely, and ingeneral the patients affected by PLS are edentulous by the age of15 y. Calcication of the dura mater has been suggested to be thethird component of the syndrome (Gorlin et al, 1964).A number of suggestions for pathoetiology in PLS have beenadvanced over the years, including immune abnormalities andsusceptibility to bacterial infections (see Hart and Shapira, 1994);however, the link between the cutaneous and gingival ndings hasnot been clear. Originally, the PLS locus was placed on humanchromosome 11q14 by homozygosity linkage mapping (Fischeret al, 1997; Laass et al, 1997; Hart et al, 1998, 2000c), and quiterecently a number of mutations in patients with PLS have beenreported in the gene encoding human cathepsin C (CTSC)(Toomes et al, 1999; Hart et al, 1999, 2000a, b). This gene consistsof a total of seven exons and the corresponding mRNA, 1.8 kb,encodes a polypeptide of 463 amino acids. The deducedpolypeptide consists of a 24 amino acid signal peptide, a 206amino acid propeptide, and 233 amino acid mature enzyme (Raoet al, 1997). Cathepsin C, also known as dipeptidyl-peptidase I (EC18.104.22.168), is a lysosomal cysteine proteinase, and apparently plays animportant role in intracellular degradation of proteins and inactivation of many serine proteinases within immune/inammatorycells, including polymorphonuclear leukocytes, monocyte-macro-phages, and mast cells.In this study, we report CTSC mutations in two families withPLS, and the rst polymorphisms in the gene.MATERIALS AND METHODSClinical material and diagnostic featuresFamily 1 The proband (I-2, Family 1 in Fig 1) was a 49-y-old female ofPuerto Rican origin, with severe periodontitis and characteristic cutaneousndings diagnostic of PLS. Specically, she had a history of bilateral scalypatches on the feet, palms, and elbows since childhood. She also hadpremature loss of both deciduous and permanent teeth, which requiredreplacement with dentures at the age of 12 y. She denied recurrent skin orsystemic infections.The proband had 10 siblings, three of which (I-3, I-4, and I-5, Family 1in Fig 1) were similarly affected. For example, the younger brother (I-5)was noted to have yellow, ssured hyperkeratotic palms and soles withslight pseudoainhum. Scaly hyperkeratotic plaques were present in elbowsand knees.Histopathology of the brother's (I-5) skin from right elbow and rightpalm revealed conuent parakeratosis, tortuous capillaries in the dermalManuscript received August 23, 2000; revised November 10, 2000;accepted for publication November 14, 2000.Reprint requests to: Dr. Jouni Uitto, Department of Dermatology andCutaneous Biology, Jefferson Medical College, 233 South 10th Street,Suite 450 BLSB, Philadelphia, PA 19107; Email: firstname.lastname@example.com: PLS, PapillonLefevre syndrome; CTSC, cathepsin Cgene.0022-202X/01/$15.00 Copyright # 2001 by The Society for Investigative Dermatology, Inc.339papillae, and a sparse inltrate of lymphocytes around venules of thesupercial plexus, changes reported to be indistinguishable from psoriasis(Angel et al, 2001).The proband's parents were dead but they were not known to have skinor dental ndings similar to their affected children, and there was knownparental consanguinity.Family 2 The proband at the time of initial examination was a 4-y-oldfemale, the second child of consanguineous Japanese parents (II-2, Family 2in Fig 1). She had an older, clinically unaffected brother (II-1), whereas ayounger brother, 1 y of age (II-3), was clearly affected. The parents wereclinically normal, and the inheritance was therefore consistent with anautosomal recessive pattern. The affected children had erythematoushyperkeratotic lesions, which were rst noted on their feet at 4 mo of age,and the lesions subsequently developed on their hands, elbows, and knees(Fig 2ad). Histopathology of the skin from the proband's brother (II-3) atthe age of 5 y revealed acanthosis with hyperkeratosis and parakeratosis(Fig 3). There was evidence of follicular hyperkeratosis. The proband alsohad a history of a liver abscess at the age of 5 y.At the current age of 24 and 21 y, the two individuals with skin lesions(II-2 and II-3) have minimal dental complaints and do not display overttooth loss. Panoramic X-ray examination of the teeth of the affected male(II-3), however, revealed extensive alveolar resorption (Fig 2e).Examination of his older sister's (II-2) teeth revealed similar but lesspronounced changes (not shown).Leukocyte function studies, including neutrophil killer activity andneutrophil phagocytic activity, were essentially normal (87% and 92%95%of the controls) in both patients at 24 and 21 y of age. Among the ninelymphocyte surface markers tested, the affected sister's (II-2) values werewell within the normal range, whereas some of the affected brother's (II-3)values (and specically those for CD56, CD11b, CD11c, CD 57, and CD16) were at the lower end of the normal values or just below the lowerlimit.DNA extraction DNA was isolated from peripheral blood specimensfrom the probands and other available members of the nuclear families, asindicated in Fig 1, by phenol-chloroform extraction using standardprocedures (Sambrook et al, 1989). Control DNA was obtained from 50unrelated individuals with no evidence of a skin disease. DNA was used as atemplate for polymerase chain reaction (PCR) amplication of exons formutation detection analysis.PCR The PCR amplication of CTSC exons and of anking intronicsequences was performed using primers as previously indicated (Toomeset al, 1999), except for the following newly developed primer pairs forexons 1 and the 5 half of exon 7: exon 1F, 5-TCTTCACC-TCTTTTCTCAGC-3; exon 1R, 5-GGTCCCCGAATCCAGTC-AAG-3; exon 7-1F, 5-TAAGCAGAGATACAGAGAAG-3; exon 7-1R, 5-GTAGTGGAGGAAGTCATCATATAC-3.The PCR reactions were performed in a total volume of 50 mlcontaining 1 3 PCR buffer and 1.25 U of Amplitaq polymerase (Perkin-Elmer Cetus, Foster City, CA), in the presence of 4% dimethyl sulfoxide,12.8 pmol of each primer, and 200 ng of genomic DNA. The amplicationconditions were as follows: 5 min at 94C for one cycle, followed by 38cycles of 45 s at 94C, 45 s at the annealing temperature of the primers(exon 1, 55C; exon 7-1, 53C), and 45 s at 72C in a thermal cycler(Hybaid, Teddington, U.K.). Five microliter aliquots of the PCR productswere analyzed by 2% agarose gel electrophoresis.DNA sequencing and verication of the mutations by restrictionendonuclease digestion PCR products were directly sequenced byusing an ABI Prism 377 automated sequencing system (Perkin-ElmerFigure 1. Pedigrees of Family 1 and Family 2 with PapillonLefevresyndrome. The solid symbols refer to affected individuals, whereas thehalf-solid symbols refer to clinically unaffected individuals shown to beheterozygous carriers of a mutation. The open symbols refer to clinicallyunaffected individuals. DNA from individuals indicated by a number undertheir symbol were studied for mutations in the CTSC gene. Note that theparents of the affected individuals in the two families are related.Figure 2. Clinical ndings in Family 2. Thepalms and soles of individual II-3 at the age of 21y (a, b) show severe erythema and hyperkeratosis.There was evidence of development of pseudoain-hums on the ngers (arrowhead in panel a). The24-y-old sister had well-dened erythematous pla-ques on her elbows and knees (c, d). PanozamicX-ray of the teeth of individual II-3 at the age of21 y (e) shows general alveolar and tooth resorp-tion (arrows).340 NAKANO ET AL THE JOURNAL OF INVESTIGATIVE DERMATOLOGYCetus). Verication of the mutation was performed by digestion of PCRproducts amplied from DNA obtained from the probands and his/herimmediate family members by restriction endonucleases. The PCRproducts were digested at 37C for AciI or MnlI for 15 h. The fragmentswere examined on 3% or 3.5% agarose gel.RESULTSIn Family 1, screening of CTSC for pathogenetic mutationsrevealed that the four affected individuals were homozygous for aGC substitution at the nucleotide position 116 (Fig 4). Aclinically unaffected child (II-1) of an affected individual (I-4) was aheterozygous carrier of this mutation (Fig 4). This novel nucleotidesubstitution resulted in a change from tryptophan (TGG) to serine(TCG) at the amino acid position 39, and this mutation wasdesignated W39S (Table I). This novel amino acid substitutionmutation affects an evolutionarily conserved tryptophan residue.The nucleotide substitution also creates a new restriction enzymesite for MnlI, which was used for verication of the mutation in thisfamily. MnlI digestion also revealed that an unaffected older brother(I-1) is not a carrier of this mutation (Fig 4). Screening of 100chromosomes in healthy, unrelated control subjects by MnlIdigestion demonstrated the absence of the W39S mutation,suggesting that it was indeed pathogenetic.Screening of Family 2 for CTSC mutations revealed that theparents (I-1 and I-2) were heterozygous for a GA substitution atnucleotide position 901, whereas the two affected children (II-2and II-3) were homozygous for this mutation. This nucleotidesubstitution resulted in a change from glycine (GGC) to serine(AGC) at the amino acid position 301, and this mutation wasdesignated G301S (Table I). This mutation has been previouslynoted in another unrelated family with PLS, and its presence hasFigure 4. Identication and verication of the homozygous mis-sense mutation in Family 1. Direct nucleotide sequencing of the PCRproduct spanning exon 1 revealed a homozygous 116GC in the affectedindividuals (I-2, I-3, I-4, and I-5) (top panel), whereas an unaffected child(II-1) of the patient I-4 was heterozygous for this nucleotide change (middlepanel), compared with the normal sequence also found in an unaffectedbrother (I-1) (lower panel). The mutation was designated W39S. Verica-tion of the mutation by digestion with MnlI (bottom panel). The mutationcreated a new restriction enzyme site for MnlI, which cuts the 338 bp PCRproduct in the case of the normal allele to 161 bp, 114 bp, 37 bp, 19 bp,and 7 bp bands, and in case of the mutant allele to 114 bp, 81 bp, 80 bp, 37bp, 19 bp, and 7 bp bands (the smaller bands are not visible). MW,molecular weight markers jX174/HaeIII; C, control.Figure 3. Histopathologic ndings in a skin biopsy from the knee ofindividual II-3 of Family 2 at the age of 5 y. Note acanthosis andhyperkeratosis with follicular hyperkeratosis, parakeratosis, and perivascularinammatory cell inltrates (scale bar: 300 mm; hematoxylin and eosin stain).Table I. Nucleotide variations in the CTSC geneLocation Nucleotide positiona Nucleotide change Amino acid substitution Restriction enzyme site Allele frequenciesMutationsExon 1 (Family 1) 116 G (Trp) C (Ser) W39S Mnll Exon 7 (Family 2) 901 G (Gly) A (Ser) G301S Acll PolymorphismsIntron 1 172 + 106 G A HaeIII 0.714/0.286Exon 7 1173 T (Thr) G (Thr) T391T Bsll 0.953/0.047Exon 7 1357 A (Ile) G (Val) I453V Msll 0.953/0.047aNucleotide numbers refer to the open reading frame, the translation-initiation codon (ATG) being +1/+3 in CTSC cDNA sequence (GenBank accession no.NM001814).VOL. 116, NO. 2 FEBRUARY 2001 CTSC MUTATION IN PLS FAMILIES 341been excluded from a control population of 200 unrelated healthycontrol individuals (Toomes et al, 1999). This nucleotide substitu-tion also abolished a restriction enzyme site for AciI, which wasused for verication of the mutation. AciI digestion conrmed thatthe parents were heterozygous carriers of the mutation whereas theaffected individuals were homozygotes. The AciI digestion alsorevealed that an unaffected brother (II-1) is not a carrier of thismutation.During the search for pathogenetic mutations in these twofamilies, three additional sequence variants were discovered(Table I). One of them was an intronic nucleotide substitutionwhereas another was a neutral polymorphism in exon 7 (T391T).The third one, 1357 AG, substituted an isoleucine in position543 by a valine (I453V). The allele frequencies of these apparentpolymorphisms are indicated in Table I.DISCUSSIONIn this study, we have identied homozygous missense mutationsW39S and G301S in two families with PLS. Discovery of the novelCTSC mutation W39S brings the total number of distinctmutations found in different families with PLS to 15 (Fig 5). Nineof them are missense mutations, whereas ve are nonsensemutations or small deletion mutations resulting in prematuretermination codon for translation. In addition, one family has asplicing mutation (486-1GA) at the intron 2/exon 3 border.The missense mutations, including W39S, affect critical, highlyconserved amino acids (Hart et al, 2000a), and eight out of ninemissense mutations reside within the mature enzyme domain of thepolypeptides (Fig 5). Also, three of the amino acid substitutionslead to incorporation of a cysteine in the polypeptide. It isconceivable therefore that these missense mutations result inconformational changes that abolish the catalytic activity of theenzyme. In fact, the activity of this enzyme has been shown to beessentially undetectable in peripheral blood leukocytes of affectedindividuals in two families with PLS as a result of missensemutations V249F and Y347C (Toomes et al, 1999).The novel missense mutation identied in this study, W39S, wasfound in homozygous state in all four affected individuals in Family1, whereas a heterozygous carrier had no evidence of PLS.Furthermore, this mutation was not present in 100 alleles inunrelated control individuals, thus indicating that it is not apolymorphism. This tryptophan residue is precisely conserved incathepsin C during evolution in various species between humansand Schistosoma japonicum (see Fig 6). Interestingly, however, theW39S mutation resides at the amino-terminal end of the propeptide(Fig 5), which is cleaved off during processing of the polypeptide tomature enzyme (Muno et al, 1993). It is conceivable then that theW39S mutation interferes either with the transport of the proformpolypeptide from endoplasmic reticulum to lysosomes or impedesthe subsequent proteolytic processing of the polypeptide to matureenzyme.It is of interest that Family 2 with the G301S mutation hadclinical features not entirely typical of PLS. Specically, the twoaffected individuals in this family had retained their teeth up to theircurrent age of 24 and 21 y whereas classic cases with PLS areedentulous by the age of 15 y. Such late onset of periodontitis hasbeen noted before (Willett et al, 1985; Brown et al, 1993; Fardalet al, 1998). It is also of interest that the specic cathepsin Cmutation, Y347C, is associated with severe periodontitis but theindividuals homozygous with this mutation have no evidence ofsyndromic skin manifestations (Hart et al, 2000b). Finally, anotherautosomal recessive condition with palmoplantar keratoderma andFigure 5. Schematic illustration of the cathepsin C polypeptide, deduced from cDNA, with domain organization, and positions of all CTSCmutations disclosed thus far in patients with PLS. The premature termination codon and the putative splice site mutation are shown above themolecule, whereas missense mutations are shown below. The mutations disclosed in this study are shown in bold. The amino acid positions at the domainborders are indicated above the polypeptide.Figure 6. Conservation of peptide segments encoded by exon 7 of the CTSC gene. The partial human sequences are compared with those in othervertebrates indicated, as well as in Schistosoma japonicum (SchJp) and mansoni (SchMa). The conserved amino acids are boxed, and the positions of missenseand nonsense mutations are indicated by arrows. The dashed lines indicated additional sequences not shown. A similar comparison of sequences encoded byexons 16 is presented elsewhere (Hart et al, 2000a).342 NAKANO ET AL THE JOURNAL OF INVESTIGATIVE DERMATOLOGYearly periodontal destruction, the HaimMunk syndrome (OMIMno. 245010), has been shown to be allelic with PLS (Hart et al,2000a). A recurrent missense mutation, Q286R, in exon 6 of theCTSC gene has been identied in several nuclear families with theHaimMunk syndrome, all of the same ancestry (Hart et al, 2000a).The same study reported a nonsense mutation, Q286X, in the samecodon of CTSC in a family with classic features of PLS (Hart et al,2000a). Collectively, this phenotypic variability of the CTSCmutations suggests either phenotype/genotype correlations orphenotypic modulation by associated genetic and/or epigeneticfactors that are not yet evident from the relatively small cohort ofpatients.The pathomechanistic implications of absent or markedlyreduced cathepsin C activities in PLS are not entirely clear but ithas been suggested that lack of functional CTSC may be associatedwith reduced host response against bacteria in dental plaque andpossibly other sites (Oguzkurt et al, 1996; Czauderna et al, 1999).CTSC plays an essential role in activating serine proteinasesexpressed in the granules of bone marrow derived cells both ofmyeloid and lymphoid series (McGuire et al, 1993). These serineproteinases are implicated in a variety of inammatory and immuneprocesses, including phagocytic destruction of bacteria. In fact,previous leukocyte function studies have suggested depressedneutrophil phagocytic and lytic activity and depressed chemotacticresponse (Bullon et al, 1993; Ghaffar et al, 1999; Liu et al, 2000).Although these leukocyte functions were well within the normallimits in the two patients in Family 2, a number of lymphocytesurface markers were at the low end of normal values or slightlybelow the normal limits, suggesting immunologic deciencies.Mechanistically, decient activation of leukocyte serine proteinasesdue to lack of CTSC activity could possibly explain the severeperiodontitis in PLS. The mechanisms leading to hyperkeratoticskin lesions are unclear, however. One could speculate that CTSCplays a role in epithelial differentiation leading to characteristiccutaneous ndings in PLS.We thank Drs. Sylvia Hsu-Wong and Steven Kornbleuth for clinical assistance.This study was supported by USPHS/NIH Grant PO1 AR38923, and by agrant for clinical research from the Aomori Prefectural Central Hospital.REFERENCESAngel TA, Hsu S, Kornbleuth SI, Kornbleuth J, Kramer EM: PapillonLefevresyndrome: a case report of four affected siblings. J Am Acad Dermatol in press:2001Brown RS, Hays GL, Flaitz CM, O'Neill PA, Abramovitch K, White RR: Apossible late onset variation of PapillonLefevre syndrome: report of 3 cases. JPeriodontol 64:379386, 1993Bullon P, Pascual A, Fernandez-Novoa MC, Borobio MV, Muniain MA, CamachoF: Late onset PapillonLefevre syndrome? A chromosomic, neutrophil functionand microbiological study. J Clin Periodontol 20:662667, 1993Czauderna P, Sznurkowska K, Korzon M, Roszkiewicz A, Stoba C: Association ofinammatory pseudotumor of the liver and PapillonLefevre syndrome: casereport. Eur J Pediatr Surg 9:343346, 1999Fardal , Drangsholt E, Olsen I: Palmar plantar keratosis and unusual periodontalndings: observations from a family of 4 members. J Clin Periodontol25:181184, 1998Fischer J, Blanchet-Bardon C, Prud'homme J-F, Pavek S, Steijlen PM, Dubertret L,Weissenbach J: Mapping of PapillonLefevre syndrome to the chromosome11q14 region. Eur J Hum Genet 5:156160, 1997Ghaffar KA, Zahran FM, Fahmy HM, Brown RS: PapillonLefevre syndrome:neutrophil function in 15 cases from 4 families in Egypt. Oral Surg Oral MedOral Pathol Oral Radiol Endod 88:320325, 1999Gorlin RJ, Sedano H, Anderson VE: The syndrome of palmar-plantar hyperkeratosisand premature periodontal destruction of the teeth: a clinical and geneticanalysis of the PapillonLefevre syndrome. J Pediatr 65:895908, 1964Haneke E: The PapillonLefevre syndrome: keratosis palmoplantaris withperiodontopathy. Hum Genet 51:135, 1979Hart TC, Shapira L: PapillonLefevre syndrome. Periodontology 2000:88100, 1994Hart TC, Bowden DW, Ghaffar KA, et al: Sublocalization of the PapillonLefevresyndrome locus on 11q14-q21. Am J Med Genet 79:134139, 1998Hart TC, Hart PS, Bowden DW, et al: Mutations of the cathepsin C gene areresponsible for PapillonLefevre syndrome. J Med Genet 36:881887, 1999Hart TC, Hart PS, Michalec MD, et al: HaimMunk syndrome and PapillonLefevresyndrome are allelic mutations in cathepsin C. J Med Genet 37:8894, 2000aHart TC, Hart PS, Michalec MD, et al: Localisation of a gene for prepubertalperiodontitis to chromosome 11q14 and identication of a cathepsin C genemutation. J Med Genet 37:95101, 2000bHart TC, Walker SJ, Bowden DW, Hart PS, Callison SA, Bobby PL, Firatli E: Anintegrated physical and genetic map of the PLS locus interval on chromosome11q14. Mamm Genome 11:243246, 2000cLaass MW, Hennies HC, Preis S, et al: Localisation of a gene for PapillonLefevresyndrome to chromosome 11q14-q21 by homozygosity mapping. Hum Genet101:376382, 1997Liu R, Cao C, Meng H, Tang Z: Leukocyte functions in 2 cases of PapillonLefevresyndrome. J Clin Periodontol 27:6973, 2000McGuire MJ, Lipsky PE, Thiele DL: Generation of active myeloid and lymphoidgranule serine proteases requires processing by the granule thiol proteasedipeptidyl peptidase I. J Biol Chem 268:24582467, 1993Muno D, Ishidoh K, Ueno T, Kominami E: Processing and transport of the precursorof cathepsin C during its transfer into lysosomes. Arch Biochem Biophys306:103110, 1993Oguzkurt P, Tanyel FC, Buyukpamukcu N, Hicsonmez A: Increased risk ofpyogenic liver abscess in children with PapillonLefevre syndrome. J PediatSurg 31:955956, 1996Papillon MM, Lefevre P: Deux cas de keratodermie palmaire et plantairesymmetrique familiale (maladie de Meleda) chez le frere et la soeur:coexistense dans les duex cas d'alterations dentaires gravis. Bull Soc FrDermatol Syphilis 31:8187, 1924Rao NV, Rao GV, Hoidal JR: Human dipeptidyl-peptidase I: gene characterization,localization, and expression. J Biol Chem 272:1026010265, 1997Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: a Laboratory Manual.Plainview, NY: Cold Spring Harbor Laboratory Press, 1989, pp 9.169.19Siragusa M, Romano C, Batticane N, Batolo D, Schepis C: A new family withPapillonLefevre syndrome: effectiveness of etretinate treatment. Cutis65:151155, 2000Toomes C, James J, Wood AJ, et al: Loss-of-function mutations in the cathepsin Cgene result in periodontal disease and palmoplantar keratosis. Nat Genet23:421424, 1999Verma K, Chadda M, Joshi R: PapillonLefevre syndrome. Int J Dermatol18:146149, 1979Willett L, Gabriel S, Kozma C, Bottomley W: Papillon-Lefevre: report of a case. JOral Med 40:4345, 1985VOL. 116, NO. 2 FEBRUARY 2001 CTSC MUTATION IN PLS FAMILIES 343
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Batz et al v. Progressive Northwestern Insurance Company
|Steven A. Batz and Lindsey L. Batz
|Progressive Northwestern Insurance Company
|Case Number:
|May 16, 2019
|US District Court for the Western District of Washington
|Nature of Suit:
|Cause of Action:
|Jury Demanded By:
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|Date Filed
|Document Text
|May 16, 2019
|Filing 1 NOTICE OF REMOVAL from King County Superior Court, case number 19-2-10704-9 KNT; (Receipt # 0981-5770357), filed by Progressive Northwestern Insurance Company. (Attachments: #1 Civil Cover Sheet, #2 Exhibit A, #3 Exhibit B, #4 Exhibit C, #5 Exhibit D, #6 Exhibit E, #7 Exhibit F, #8 Exhibit G, #9 Exhibit H)(Lether, Thomas)
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