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EVIAN, France — The consumer has taken control.
This story first appeared in the July 19, 2002 issue of WWD. Subscribe Today.
So concluded a panel of beauty industry executives representing retail, manufacturing and consulting firms at the WWD CEO Beauty Summit here in June.
Maybe there had been a time when manufacturers steered the industry with marketing prowess and brands. Then, conventional wisdom held that retailers prevailed in the marketplace with their real estate control and efficient distribution systems.
But, as noted by Marc Pritchard, vice president, global cosmetics and personal care at Procter and Gamble, a recent study found that 66 percent of women said they would walk out of a store if they got bad service, even if it has the product they want.
"The consumer is empowered; the consumer in is charge," suggested Pritchard, who moderated the one and a half hour panel discussion on what it will take to bond with this new educated and demanding shopper. "Her expectations are growing."
Pritchard is convinced that the $60 billion global beauty industry could expand further "if we focus on the desires of consumers across the world."
Several suggestions were offered on how to respond to the new consumer values from redefining service to the opening of distribution channels to the simplifying of product offerings to make shopping easier.
Women are cross-shopping and they are becoming less brand loyal, agreed the panelists. During a recent trip to Moscow, Pritchard interviewed one woman whose broad beauty stock included items from Lancôme, Black Opal, Avon and Rimmel. "There is cross-shopping even in developing countries," he pointed out.
Consumers are also becoming more comfortable with buying unfamiliar brands. In one recent study, 50 percent of consumers said they were willing to buy unfamiliar brands, according to Pritchard.
Beth Pritchard, president and chief executive officer of Bath and Body Works, (no relation to Marc Pritchard) said that brand loyalty "has to be earned. You have to make that emotional connection between customer and brand." In BBW stores, customers are treated to a hand massage. "Remember," stressed Beth Pritchard, "shopping is fun; it is not a necessity. You have to entertain the customer."
In some newer stores, BBW is offering spa treatments, not as a profit center, but as a service to expose customers to its new spa treatment products, she explained.
At Selfridges, said Claudia Lucas, head buyer, beauty, for the U.K.-based department store, "women want choice." She explained that her shoppers are more willing to experiment and "are looking for brands that are not mainstream." At present the retailer sticks to premium offerings keeping in sync with its overall store presentation.
"We have some things in the store that are not there to generate cash but to add to the experience of the buy," commented Lucas on the importance of service. She pointed to its integrated nail bar as an example. The store also held a Bollywood event honoring the Indian film industry to draw and entertain consumers.
Timra Carlson, vice president, NPD BeautyTrends, noted that 69 percent of beauty shoppers buy beauty while they are out shopping in stores for other things. "Women and men today have less planned purchases," she said, adding, "If the consumer is unhappy, it is a loss for that department as well as another department. Retailers really need to look at themselves as brands."
In mass stores, the shopping experience needs to be made easier, said P&G's Pritchard, who noted that P&G has been using interactive computer technology to aid in shade selection and also to guide women to the right skin treatment items.
Patricia Fuchs-Wenzlau, director and chief executive officer of European Forecasts, said that the industry should ease up on imitation products. "Show the courage to do the unexpected," she instructed. "The flipside of that is 'show the courage not to change and not run with a trend.' When you know you have something good stick with it and stay with it."
The industry will benefit most, concluded Pritchard, when retailers and manufacturers jointly focus on the consumer.
Pritchard recalled his early resistance to a mass store movement toward universal fixtures, which replace manufacturer- supplied displays. But the joint effort between retailer and manufacturer to create a new look has been rewarded with sales increases.
Shashi Batra, senior vice president of merchandising at Sephora USA, remarked that there were challenges too when open sell came into the prestige market in the U.S. "It was a huge learning experience for retailer and manufacturer. After a lot of pain and resources, the communication at point of sale, whether the person is assisted or not, is ultimately going to drive the success of that product," said Batra. "We have totally underestimated the power of merchandising."
Hilary Dart, president of Calvin Klein Cosmetics cautioned that "we have to be careful that mass practices at retail don't become the norm, the method. We have to make sure that it doesn't distort the brand image.
"People shop the department store because they have an expectation of service. To take the mass approach, it could lower the expectation of the consumer and drive her away from the store. You have to have the merging of methods."
The most direct challenge of the retail status quo bubbled forth from an audience member. "Why does there have to be a difference between prestige and mass? I don't understand why the brands can't sell in both."
Dart responded, "The U.S. market tends not to offer a go between in the retail environment. [In the U.K.] Boots the Chemist does a really good job selling prestige and mass brands under one roof.
"I think if there is going to be a new move on the part of retailing in the U.S. it has to be quite a brave move, not just more of the same."
Below are 10 suggestions from the panel to help the industry connect with the modern consumer.
Balance the selection of new products and classics.
Explore new channels of distribution.
Manufacturers and retailers should partner to improve merchandising.
Redefine customer service.
Develop category-management programs for all retail formats.
Better define and target your consumer.
Sell brands in both prestige and mass environments.
Distort efforts toward the biggest- selling products to draw customers.
Simplify product offerings to improve the shopping experience.
Keep product and retail marketing ideas fresh."


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|11 Reviews
|Property type
|Minimum Stay
|14 nights
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Sit on the Lanai and enjoy unbelievable ocean scenery from this unit. With the expanse of Preservation Land next to the ocean, the view of the ocean from this unit is simply one of the best available on Oahu. This unit is in impeccable condition and is ready to be your home away from home while you are visiting Ko'Olina. Kai Lani is a gated community and one of the premier locations to live in Ko'Olina, a resort area on the western side of Oahu in Kapolei.
Within walking distance of Kai Lani are the beautiful Lagoons of Ko'Olina, a perfect place for leisure strolls while the sun sets. Along the Lagoons are various hotel restaurants and outdoor bars to enjoy yourself at, including the JW Marriott Ihilani and the new Aulani Disney Resort Hotel. Further down at the Marina you'll find boats that can be chartered as well as snorkeling and diving adventures that actually occur within view of the Lanai of this Kai Lani unit, in which you will literally be swimming with wild dolphins and turtles and tropical fish.
Minutes away by car is the Wet'n'Wild Water Park for those with kids (or who are kids at heart), as well as the Kapolei Theaters. Kapolei itself, a rapidly expanding town, has all the restaurants and shopping you need during your stay in Hawaii.
This unit is fully furnished with the highest quality furniture some of which is antique, and professional decor. The over 100 year old antique armoire in the living room contains something that the makers of the armoire couldn't have imagined - a 3D HDTV (with four pairs of 3D glasses) hooked up to a surround sound system, a blu-ray player (& DVD) which is connected to the Internet allowing web surfing. An HD Movie Service is available for your families movie night. The quality is superb - up to 1080p which is amazing to see. If that's not good enough, you can press '2D - 3D' on the TV's remote and watch the movie rendered in 3D. For game night a number of classic games are available including Scrabble, Monopoly, Jenga, Stratego, and Yahtzee.
For those with toddlers there is a gate available for the top of the stairs. Some beach supplies are available such as folding chairs, mats, boogie boards, and beach umbrellas.
Military, firefighter, and law enforcement enjoy a special discount. Please ask for details.
Keywords: Ocean View, Kai Lani, Ko'Olina
Idyllic setting with everchanging views of the ocean, sunsets, sailboats and whale spouts. This is a well appointed condo within an easy walk of the condo pool and hot tub as well as easy access to the many amenities offered by Ko Olina. Greg is an outstanding owner who is approachable, responsive and helpful. Highly recommend booking a stay here
What a beautiful location! My husband I stayed 7 weeks at this condo and had a wonderful time. The property has a beautiful ocean view and the condos are surrounded by a stunning variety of flowering tropical plants. The owner Greg was very responsive and helpful as was his property manager. Our favorite part was walking down by the Marriott and Aulani resorts and along the beautiful ocean lagoons at sunset. We appreciated having beach towels, beach chairs and boogie boards available at the condo for our use. The condo itself is well furnished and has nice high-end finishes. Of course, the view off the lanai is the real attraction! We rented the Jeep and it provided good transportation all around the island. We felt completely safe and secure - it was a home away from home. We highly recommend this property and its owner.
Just the perfect spot for a quite family getaway, Greg was excellent to deal with, condo was neat & clean, everything we expected and more. Paradise Cove Lagoon was easy walking distance, turtles every day our favourite spot on the Island. Erin & Jodi, Saskatchewan
What a joy it was to be in such a place of beauty with all the amenities we needed at our fingertips. The chance to visit my granddaughters (who are on the military base) and love them up with lots of fun in the sun, good food, visiting their hot spots, shopping, golf cart rides and late night talks. What a piece of heaven we got to embrace. Thank you Greg, and to all who played a part in helping us have such a wonderful experience.
Hawaiian vacation at a great location means memories to spare. Photos can't compare to real thing in showing off how wonderful this place truly is for your holiday. Our stay at Kai Lani was made all the more memorable by the service we received from the owner. From arranging a pick-up at the airport, making a vehicle available at a fair price, a fully equipped kitchen, bikes and beach toys - this unit had it all. The Ko'Olina area is perfect for those who have had the hustle of Waikiki and are looking for the beauty of a Hawaiian vacation. Golf at a top resort course - swim in any of four lagoons, each one more beautiful than the next - walk along the waterfront and see whales (winter season) - snorkeling in lagoons or off one of numerous tour boats from harbor - shop in nearby Kapolei at Costco, Safeway, Target etc. - dine in or at one of several great restaurants in hotels. Just a short walk from the unit is Paradise Cove and if ever a name fit, this is it - crystal clean water, endless ocean view, tide pools and "sea turtles" every time you visit!! The time for us flew by. We look forward to our next stay.
We stayed with our three boys, ages 7 and under for a month.
The condo is beautiful. It is decorated very nice. It has everything to make your vacation perfect. Lots of pool and beach toys.
The view is beyond amazing. I spent every morning drinking my coffee on the balcony and watching the ocean.
Greg was so helpful and patient. He answered all my questions super quickly and gave me lots of great ideas. The property manager was also very helpful and accommodating.
Paradise lagoon was really close and had great snorkeling. We left on a couple of day trips but found that everything we left to see was actually better right in Ko Olina.
The vacation was perfect and we look forward to staying at this condo again. (I have a feeling it is the nicest condo in all of Kai Lani, with the best condo owner!)
|Rate Period
|Weekend Night
My Standard Rate
14 night minimum stay
|Cleaning Fee actual cost
|Tax Rate
Due to Kai Lani Association rules, the minimum Rental Period is one month. A request for a stay of less than one month will still require a Rental Period of one month, however, you may arrive and depart as you wish within the Rental Period. The rate does not change if you arrive later in your Rental Period, or depart earlier than the end of your Rental Period. The property will remain empty during those periods if you do so. Please be aware the one month Rental Period rate is $3840 as listed, and a request for a period of less than one month will result in an incorrect quote being generated automatically by the system.
Additional Military, Law Enforcement, and Firefighter discounts may apply.
Hawaii Registration #: W55644440-01 Provided in compliance with HB2078


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Correspondence to: Huan-Long Qin, MD, Department of Surgery, The Sixth People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China. moc.liamtoh@niqgnolnauh
Telephone: +86-21-64361349 Fax: +86-21-64368920
AIM: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.
METHODS: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay.
RESULTS: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05).
CONCLUSION: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
Biliary tract surgery in patients with obstructive jaundice is associated with high a morbidity and mortality rate[1]. Evidence accumulated over the past several years indicates that the absence of bile in the gastrointestinal tract promotes bacterial overgrowth and increases intestinal permeability, leading to significant translocation of bacteria and endotoxin following bile duct obstruction[2,3]. The mechanism underlying the increased intestinal permeability in obstructive jaundice has been obscure. However, recent experimental studies have shown that the regional decrease in tight junction (TJ)-associated protein levels in the intestinal epithelium[4], increased apoptosis of enterocytes in intestinal crypts[5], and intestinal oxidative stress[6] are the key factors in the pathogenesis of hepatic and intestinal injury in obstructive jaundice[7].
Probiotic bacteria have been shown to have beneficial effects in the intestinal barrier function. For example, live Bifidobacterium lactis has been shown to inhibit toxic effects in epithelial cell culture[8]. Lactobacillus plantarum (L. plantarum) has been found to inhibit epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-α[9] and prevent cytokine-induced apoptosis in intestinal epithelial cells[10]. L. plantarum stabilizes the cellular TJ, thereby preventing enteropathogenic Escherichia coli-induced redistribution of integral TJ proteins[11]. Based on the excretion of orally administered 14C, White et al[12] demonstrated that enteral administration of the probiotic bacterium L. plantarum 299 reduced intestinal hyperpermeability associated with experimental biliary obstruction. However, these authors did not clarify the mechanism for the protective effect of the probiotics on the intestinal barrier in obstructive jaundice. A recent clinical study reported that preoperative oral administration of synbiotics could enhance immune responses, attenuate systemic post-operative inflammatory responses, and improve the intestinal microbial environment after hepatobiliary surgery for obstructive jaundice[13].
TJs, which represent the uppermost basolateral connection between neighboring enterocytes, are important components of the epithelial barrier[14]. TJ assembly and paracellular permeability are regulated by a network of signaling pathways that involves different protein kinase C (PKC) isoforms[15]. A substantial body of experimental data indicates that PKC regulates paracellular permeability of the epithelial barrier[16,17]. PKC regulates the assembly of TJ proteins through phosphorylation of zonula occludens-1 (ZO-1)[15]. Seth et al[18] suggested that PKCβI activation may be one of the initial events in the probiotic-mediated protection of TJs. PKCε may play a role in the downstream events of the signaling pathway involved in this process. These data suggest that PKC plays a crucial role in the mediation of intestinal epithelial TJ proteins.
This study aims to investigate the effects of L. plantarum on the intestinal mucosal barrier, oxidative stress, epithelial TJ-protein structure and phosphorylation, especially its impact on the expression and activity of PKC.
Rabbit polyclonal anti-occludin, rabbit polyclonal anti-junction adhesion molecule (JAM)-A, rabbit polyclonal anti-claudin-1, mouse monoclonal anti-claudin-4, and rabbit polyclonal anti-phosphoserine antibodies were supplied by Zymed (Invitrogen, Carlsbad, CA, United States). Rabbit polyclonal anti-ZO-1 and rabbit polyclonal anti-PKC were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, United States). Fluorescein isothiocyanate (FITC)-phalloidin was obtained from Sigma (St. Louis, United States). FITC-conjugated secondary antibodies were supplied by Zymed (Invitrogen). Biotin-labeled goat anti-rabbit immunoglobulin G (IgG) and horseradish peroxidase (HRP)-labeled streptavidin were supplied by DAKO (Glostrup, Denmark). All other reagents of analytical grade were purchased from Sigma (St. Louis, United States).
The L. plantarum (strain CGMCC No. 1258) used in this study was a gift from Dr. Xiao-Ming Hang (Onlly Institute of Biomedicine, Shanghai Jiao Tong University, Shanghai, China). L. plantarum cultures were prepared exactly as described previously[11].
Forty male albino Wistar rats weighing 250-320 g were purchased from Fudan University Medical Animal Center (Shanghai, China). They were housed in stainless-steel cages, three rats per cage, at controlled temperature (23 °C) and humidity and with a 12 h/12 h dark/light cycle. They were maintained on a standard laboratory diet with tap water ad libitum, except for an overnight fast before surgery. The study was conducted according to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health, and it was approved by the Ethics and Research Committee of Shanghai Sixth People's Hospital, Shanghai, China.
Animals were randomly divided into five groups of eight rats each as described below.
Group I, sham-operation: A 2.0-cm upper midline abdominal incision was made, and the common bile duct (CBD) was freed from the surrounding tissues without ligation or transection.
Group II, bile duct ligation: The CBD was double ligated in its middle third with a 4-0 silk suture and transected between the two ligatures.
Group III, bile duct ligation + L. plantarum: After bile duct ligation (BDL), a volume of 10 mL live L. plantarum (activity, 2 × 108 CFU/mL) divided into two equal doses was administrated daily to the rats by gavage for 10 d. After 10 d, the animals were sacrificed under ketamine anesthesia.
Group IV, BDL + IBD: The CBDs of animals were ligated and isolated. A polyethylene tube PE-10 (American Health and Medical Supply International Corp. Co., Ltd., Scarsdale, New York, United States) was inserted into the proximal CBD in a cephalad direction and fixed. The drainage end was tied and positioned in the right hepatorenal recess. After 5 d of obstructive jaundice, the abdomen was reopened through the previous incision. After releasing the biliary obstruction by transecting the tube, a distal 3-cm segment of the catheter was inserted into the duodenum for internal biliary drainage. The animals were sacrificed after another 5 d.
Group V, BDL + IBD + L. plantarum: Ten days after BDL, live L. plantarum was infused as described for Group III.
All non-L. plantarum control groups, including sham-operation (SHAM), were gavaged with the same volume of the same vehicle (Dulbecco's phosphate buffered saline) used for the L. plantarum groups. The animals were sacrificed after 10 d.
All surgical procedures were performed under strict sterile conditions and ketamine anesthesia. At the end of the experiment on day 10, 4-5 mL blood sample was collected from each animal by puncturing the portal vein.
The serum total bilirubin and alanine aminotransferase (ALT) levels were determined using a kit (Jiancheng Biological Co., Ltd., Nanjing, China) and a Hitachi Model 7600 series automatic analyzer (Hitachi Co., Tokyo, Japan).
Endotoxin concentrations were determined using a quantitative chromogenic Limulus Amebocyte Lysate test kit (Shanghai Med. and Chem. Institute, Shanghai, China). Samples were processed according to the manufacturer's instructions[19].
Plasma D-lactate levels were measured by an enzymatic spectrophotometric assay[20] using a serum D-lactate quantitative colorimetric detection kit according to the manufacturer's instructions (GMS19038.6, Genmed, Boston, MA, United States). Results were expressed as mol/mL. Plasma diamine oxidase (DAO) activities were determined with an enzymatic spectrophotometric assay[21] using a Serum DAO detection kit according to the manufacturer's instructions (Jiancheng Biological Co., Ltd., Nanjing, China). Results were expressed as U/L.
Plasma glutathione (GSH) and glutathione (GSSG) were determined by an enzymatic spectrophotometric assay[22] using the GSH and GSSG detection kits according to the manufacturer's instructions (Jiancheng Biological Co., Ltd.). Results were expressed as mol/mL.
Superoxide dismutase (SOD) activity was detected using Sun et al's[23] nitroblue tetrazolium method. Malondialdehyde (MDA) levels were measured using the thiobarbituric acid test according to Ohkawa et al[24]. Intestinal tissue samples were thawed, weighed, and homogenized 1:9 (w/v) in 0.9% saline. The homogenates were centrifuged at 3000 × g for 10 min at 4 °C, and the supernatant was removed for the measurement of MDA content, SOD activity, and total protein. Total intestinal protein concentration was determined by a Coomassie blue method, with bovine serum albumin (BSA) as a standard. SOD activity and MDA levels were detected with kits according to the manufacturer's instructions (Jiancheng Bioengineering Ltd., Nanjing, China). Results were expressed as U/mg protein and nmol/mg protein.
Samples 1 cm in length were collected from the terminal ileum. To avoid mucosal damage, the intestinal lumen was carefully cannulated and gently washed with normal saline before sampling. Specimens were fixed by immersion in 10% buffered formaldehyde solution and embedded in paraffin. Sections (5 µm thick) were cut and stained for routine light microscopy using HE.
Samples 3-4 mm in length were collected from the terminal ileum. These samples were longitudinally cut and immersed in 2.5% phosphate-buffered glutaraldehyde solution for 24 h at 4 °C. Specimens were then washed with phosphate-buffered solution (PBS), fixed in 1% osmium tetroxide for 2 h at 4 °C, dehydrated in ethanol and propylene oxide, and embedded in Epon 812 for 48 h. Sections (1 µm thick) were cut and stained with methylene blue. Ultrathin sections were then cut with a diamond knife, stained with uranyl acetate and lead citrate, and observed under transmission electron microscopy (TEM).
Four-μm thick sections were collected on poly-L-lysine-coated glass slides. The nuclear DNA fragmentation of apoptotic cells was labeled in situ by the terminal deoxyuridine nick-end labeling immunohistochemical method[25] using an ApopTag® Plus Peroxidase In Situ Apoptosis Detection Kit (CHEMICON, Billerica, MA, United States) according to the manufacturer's instructions.
Terminal ileum tissues were fixed in 3% paraformaldehyde for 3 h, washed with PBS, and embedded in paraffin. Sections (5 μm thick) were cut and attached to glass slides. After deparaffinization and rehydration, sections were permeabilized with 0.2% Triton X-100 in PBS for 20 min. Slides were washed with PBS extensively and blocked with 5% normal goat serum PBS containing 0.05% Tween-20 and 0.1% BSA for 20 min at room temperature. Primary antibodies were added to the slides and incubated overnight at 4 °C in a humidity chamber. After washing, sections were incubated with FITC-conjugated specific secondary antibody (Sigma) at room temperature for 2 h in the dark. The slides were again washed extensively and then mounted with Vectashield mounting medium (Vector Laboratories, Inc., Burlingame, CA, United States). Sections were observed under a confocal laser microscope (LSM 510, Zeiss, Jena, Germany).
After the rats were sacrificed, terminal ileum tissues were excised and fixed in Bouin's solution and embedded in paraffin. Immunohistochemistry was performed on 5-µm thick paraffin sections. After deparaffinization and dehydration, endogenous peroxidase was blocked with 30 mL/L H2O2 for 15 min. After blocking of nonspecific binding sites with 5% normal goat serum, slides were incubated with specific primary antibody overnight at 4 °C. Primary antibodies were diluted 1:50 (rabbit polyclonal anti-human PKC, Santa Cruz Biotechnology, Inc., United States) in PBS. Next, the slides were washed three times for 5 min each with PBS and incubated with biotinylated goat anti-rabbit IgG at 37 °C for 30 min, washed as before, and developed with HRP-labeled streptavidin. The incubation and the subsequent washing were exactly the same as done before. Finally, diaminobenzidine chromogen, a peroxidase substrate, was added for color development. The reaction was stopped with a tap water rinse. The sections were counterstained with hematoxylin and mounted for examination.
Terminal ileum samples were homogenized in ice-cold radioimmunoprecipitation assay (RIPA) buffer [150 mmol NaCl, 50 mmol Tris·HCl (pH 7.4), 0.5 mmol phenylmethylsulfonyl fluoride, 2.4 mmol EDTA, and 1 mmol sodium orthovanadate with 1% nonidet-40 (NP-40) and Sigma protease inhibitor cocktail (1:100)] for 30 min at 4 °C. After centrifugation at 10 000 × g for 10 min at 4 °C, the protein concentration of each sample was quantified by the Bradford method. An equal amount of total protein was separated on 10% sodium dodecyl sulfate (SDS)-polyacrylamide gels and then transferred to a nitrocellulose membrane. After blocked overnight in tris-buffered saline (TBS) containing 0.05% tween (TBS-T) and 5% dry powdered milk, membranes were washed three times for 5 min each with TBS-T and incubated for 2 h at room temperature in primary antibody (rabbit anti-claudin-1, rabbit anti-occludin, rabbit anti-JAM-A, or rabbit anti-ZO-1). After three washes with TBS-T, the membranes were incubated for 1 h with HRP-conjugated secondary antibody. Following two washes with TBS-T and one wash with TBS, the membranes were prepared for visualization of protein by the addition of enhanced chemiluminescence (ECL) reagent (Amersham, Princeton, NJ, United States). Densitometric analysis was performed using an Alpha Imager 1220 system (Alphainotech Co., San Leandro, CA, United States).
The levels of occludin, ZO-1, claudin-1, claudin-4, JAM-A and UGT1A mRNA were measured by real-time reverse transcription-PCR (RT-PCR) using SYBR1 green[26]. Total RNA was isolated from terminal ileum samples with the TRIzol reagent (Invitrogen) according to the manufacturer's protocol. Real-time RT-PCR was performed with an ABI prism 7000 Real-Time PCR System (Applied Biosystems, Foster City, CA, United States). The primers were designed using the Primer Express® Program (Applied Biosystems). Their sequences are shown in Table Table1.1. The following procedure used 2 μg of RNA. In a sterile RNase-free microcentrifuge tube, 1 μL of 20 μm oligo (dT) 15 primer was added to a total volume of 15 μL water. The tubes were heated to 70 °C for 5 min, cooled immediately on ice, and spun briefly. The following reagents were added to the annealed primer/template: 5 μL of 5 × M-MLV reaction buffer, 1.25 μL of 10 mmol dNTPs and 25 units of RNasin RNase inhibitor, and 200 units of M-MLVRT RNAse H were added to the reagent to yield a 25 μL total reaction volume. All were mixed gently and then incubated for 60 min at 42 °C before the reaction was terminated at -20 °C.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was used as a house-keeping gene control. Separate PCR reactions (25 μL) were conducted for each transcript and contained 2.0 μL cDNA, 12.5 μL of 2 × SYBR Premix Ex Taq™ (TaKaRa, Ltd., Shiga, Japan), and 0.5 μL each of 10 μmol/L gene-specific forward and reverse primers. PCR conditions were optimized to 95 °C (30 s), followed by 40 cycles (45 s each) at 95 °C, 60 °C (5 s), and 72 °C (30 s), and the reaction was completed at 37 °C for 30 s. Five serial dilutions of cDNA were analyzed for each target gene and used to construct linear standard curves. To compensate for variations in the RNA input and in the efficiency of the real-time RT-PCR, we used a normalization strategy based on the house-keeping gene GAPDH.
The terminal ileum tissues were homogenized and extracted with the buffer used for Western blotting assays for 30 min at 4 °C. After centrifugation at 10 000 × g for 10 min at 4 °C, the protein concentration of each sample was quantified by the Bradford method. The supernatant was treated with protein G plus protein A agarose beads (Sigma) and incubated overnight at 4 °C with rabbit anti-occludin antibody (Zymed) and protein G + protein A agarose beads. The beads were washed with PBS and ice-cold RIPA buffer, and immunoprecipitated proteins were separated on 10% SDS-polyacrylamide gel electrophoresis gels and transferred onto nitrocellulose membranes (Invitrogen). The membranes were blocked with 1% BSA in PBS overnight at 4 °C and then incubated with rabbit anti-phosphoserine antibodies (Zymed) for 2 h at room temperature, followed by HRP-conjugated secondary antibody (Santa Cruz Biotechnology, Inc., United States). The reaction was visualized by an enzyme chemiluminescence kit from Pierce (Rockford, IL, United States). Western blotting was performed with an anti-occludin rabbit polyclonal antibody (Zymed) followed by an anti-rabbit secondary antibody coupled with peroxidase (Santa Cruz Biotechnology, Inc.) and ECL. For Western blotting of ZO-1, the same protocol was used with the rabbit polyclonal anti-ZO-1 antibody and a rabbit anti-β-actin antibody (both from Santa Cruz Biotechnology, Inc.).
The PKC activity assay was conducted according to the instructions of the PepTag non-radioactive PKC assay kit (Promega, Madison, WI, United States). Briefly, terminal ileum tissues were homogenized and lysed in cold lysis buffer, containing 20 mmol/L tris-HCl, 0.5 mmol/L ethylene glycol tetraacetic acid, 2 mmol/L ethylenediaminetetraacetic acid, 2 mmol/L phenylmethanesulfonyl fluoride, and 10 mg/L leupeptin (pH 7.5). Assays were then performed at 30 °C in a total volume of 25 μL containing 5 μL PKC reaction 5 × buffer, 5 μL PLSRTLSVAAK peptide, 5 μL PKC activator, 1 μL peptide protection solution, and 9 μL sample. Reactions were initiated by the addition of the 9 μL sample and terminated after 30 min by incubation of the reaction mixture at 95 °C for 10 min. After added with 1 μL of 80% glycerol, each sample was separated by 0.8% agarose gel electrophoresis at 100 V for 15 min. The intensity of fluorescence of phosphorylated peptides reflected the activity of PKC. All experiments were carried out in triplicate, with each data point representing the results from a separate culture.
Quantification of the immunohistochemical and immunofluorescence staining was performed on stored images of completely scanned tissue sections. Images were acquired with an AxioCam MRc (Carl Zeiss, Jena, Germany) connected to an Axioplan 2 fluorescence microscope (Carl Zeiss), at × 40 magnification. Each microscopic field was individually autofocused before acquisition. Five fields were selected from each slide and a total of five slides per group were examined. All image acquisition and processing were done using custom-written macros in KS400 image analysis software (version 3.0, Carl Zeiss).
Results were presented as mean ± SD of three experiments. The data were analyzed using GraphPad PRISM (GraphPad Software Inc., San Diego, CA, United States) and SPSS 11.0 (SPSS Inc., Chicago, IL, United States). All data were analyzed using one-way analysis of variance with Bonferroni/Dunnett T3 post-hoc test for multiple comparisons to determine differences between two experimental groups. P values < 0.05 were considered to be significant.
All animals survived throughout the experiment. Bile duct ligated rats were clinically jaundiced within 3 d. At reoperation on day 3, the ligation and division of the CBD were successful in all cases and resulted in significant dilatation of the CBD remnant proximal to the ligature with obvious cholestatic appearance of the liver. At reoperation on day 10, the CBD diameter had returned to a normal size in the BDL + IBD group, and the cholestatic livers also appeared improved visually (Figure (Figure11).
Obstructive jaundice led to significantly elevated serum levels of total bilirubin [153.73 mmol/L vs 3.0 ± 1.63 mmol/L] and ALT [543.83 U/L vs 60.8 ± 5.69 U/L, P < 0.05]. Administration of L. plantarum significantly reduced levels of total bilirubin (132 ± 23.9 mmol/L vs 9.0 ± 1.87 mmol/L) and ALT (218.38 ± 91.09 U/L vs 97 ± 10.37 U/L) in the portal serum (Table (Table22).
Group II ( BDL + L. plantarum) animals presented with significantly elevated endotoxin concentrations in portal blood compared with those in Group I ( SHAM ) (P < 0.05). Treatment with L. plantarum in the BDL + L. plantarum and BDL + IBD + L. plantarum groups significantly reduced endotoxin levels in the portal serum (Table (Table22).
Plasma D-lactate levels increased significantly in the BDL group compared with the SHAM group. Administration of L. plantarum significantly decreased the plasma D-lactate levels in the BDL + L. plantarum and IBD + L. plantarum groups (Table (Table33).
DAO activity in the BDL group was significantly higher than that in the SHAM group. Plasma DAO activity became significantly lower after the use of probiotics in the BDL + L. plantarum and IBD + L. plantarum groups (Table (Table33).
Plasma GSH was significantly reduced in Group II (BDL) animals compared with those in Group I (P < 0.05). Administration of L. plantarum significantly increased the levels of GSH in the Group IV (BDL + IBD) animals, whereas GSSG was found to be significantly increased in BDL animals. Administration of L. plantarum significantly reduced the levels of GSSG in the BDL + IBD group (Table (Table33).
Ileum mucosal MDA was significantly increased in BDL group compared with SHAM. Administration of L. plantarum significantly decreased the levels of MDA in the BDL + IBD group. The trend in ileum mucosal SOD levels among the groups was opposite to the results of MDA (Table (Table33).
Specimens collected from the terminal ileum in the BDL group showed subepithelial edema and blunting of the villi, mostly located at the tip of the villi, with a large number of lymphocytes and plasma cells infiltrated in the intestinal mucosa (Figure (Figure2).2). Under TEM, cell ultrastructure was disordered, with loss or disruption of microvilli and large dense secondary lysosomes that resembled partially degraded bacteria within the enterocyte cytoplasm. Inflated vacuolization of the cells, swollen mitochondria with partial or complete absence of interior cristae, disruption of desmosomes and formation of oedematous spaces, and expansion of endoplasmic reticulum were observed. Cells often showed serious damage to the plasma membrane and complete loss of junctional specialization between adjacent cells. Additionally, spherical and rod-shaped bacteria in the ileum were seen near enterocytes. These features are typical of prenecrotic and necrotic injury of the intestinal mucosa. However, in the BDL + L. plantarum group, cells were aligned regularly, with less swelling of mitochondria, no expansion of the endoplasmic reticulum, while the morphology was nearly normal in the IBD + L. plantarum group (Figure (Figure33).
Apoptotic nuclei were significantly more abundant in the markedly atrophic villi in the BDL group than in the SHAM group. The apoptotic nuclei were mostly distributed at the top of villi (Figure (Figure4A).4A). Administration of L. plantarum significantly decreased the number of apoptotic nuclei in the BDL + IBD + L. plantarum group (Figure (Figure4B4B).
PKC appeared as brown spots in the perinuclear structure. Its expression was decreased in the BDL group compared with the SHAM group. Administration of L. plantarum significantly enhanced the expression of PKC in the BDL + L. plantarum and IBD + L. plantarum groups (Figure (Figure55).
Confocal imaging was performed to assess the distribution of the TJs in each group. TJ-associated proteins were continuously distributed in bright green or red color along the membrane of the cells. The F-actin staining showed a continuous line at the cell borders and along the cytoskeleton. Their borders were very clear in the SHAM group, where TJ-associated proteins were present at the apical intercellular borders in a belt-like manner, encircling the cells and delineating the cellular borders. In the BDL group, the fluorescence was dispersed and even became punctate, with loss of membrane fluorescence as against the uniform membrane staining in controls. Administration of L. plantarum enhanced the expression of TJ-associated proteins in the BDL + L. plantarum and IBD + L. plantarum groups (Figure (Figure66).
Western blotting analyses were performed to determine the relative protein levels of the target proteins occludin, claudin-1, claudin-4, JAM-A, ZO-1 and PKC in the terminal ileum. The intensity of the whole-cell proteins was determined from ratios of the integrated intensity of the target protein bands to the integrated intensities of the β-actin bands in the same sample. Compared with samples obtained from rats in the SHAM group, levels of target proteins were decreased in protein extracts from ileal mucosal scrapings of rats subjected to BDL. Administration of L. plantarum significantly enhanced the expression of TJ-associated proteins in the BDL + L. plantarum and IBD + L. plantarum groups (Figure (Figure77).
Intragastric administration of L. plantarum resulted in changes in the levels of occludin, ZO-1, claudin-1, claudin-4, JAM-A and PKC. This result raised the question whether these altered protein levels were a consequence of changes in mRNA levels. We, therefore, used real-time RT-PCR to determine the levels of mRNA in the terminal ileum in each group. The levels of mRNA of occludin, ZO-1, claudin-1, claudin-4, JAM-A, PKC and UGT1A1 were found significantly lower in the BDL group than in the SHAM group. Administration of L. plantarum significantly increased the mRNA levels of target proteins in both the BDL + L. plantarum and IBD + L. plantarum groups (Table (Table44).
We examined the phosphorylation status of occludin and ZO-1 using immunoprecipitation and immunoblotting assays. Occludin and ZO-1 were phosphorylated at serine residues. BDL lowered p-occludin and p-ZO-1 proteins levels compared with the SHAM group. Administration of L. plantarum improved the expression of the p-occludin and p-ZO-1 proteins from the terminal ileum in the BDL + L. plantarum and BDL + IBD + L. plantarum groups (Figure (Figure88).
As shown in Figure Figure9,9, PKC activity was significantly decreased in the BDL group compared with SHAM group. Intragastric administration of L. plantarum partly restored PKC activity in both the BDL + L. plantarum and BDL + IBD + L. plantarum groups.
The present study demonstrated that oral administration of L. plantarum significantly reduced bilirubin, ALT and endotoxin levels in the systemic circulation in an experimental obstructive jaundice animal model with internal biliary drainage for 10 d. Moreover, oral L. plantarum administration to the rats in the BDL + L. plantarum group and the BDL + IBD + L. plantarum group not only reduced the serum endotoxin levels, but also substantially improved liver function. This result is consistent with the conclusions reported in previous literature[12].
In our study, oral L. plantarum administration also significantly decreased the serum DAO activity and D-lactate level in both the BDL + L. plantarum group and the BDL + IBD + L. plantarum group. These findings indicate that L. plantarum plays an important role in intestinal integrity. Previous in vitro studies have confirmed that probiotics exert direct protective effects in intestinal epithelial cell TJs via a PKC-kinase-dependent mechanism and inhibiting epithelial cell apoptosis in cell culture experiments[11,18,10]. The current experiments focused on L. plantarum effects, while several previous studies have reported the protective effects of other lactobacilli and probiotics. For example, Moorthy et al[27] reported that pretreatment with a combination of Lactobacillus rhamnosus (L. rhamnosus) and Lactobacillus acidophilus had a significant protective effect on TJ proteins (claudin-1 and occludin) in a Shigella dysenteriae 1 infection rat model. Khailova et al[28] reported that Bifidobacterium bifidum improved intestinal integrity [composition of TJ and adherens junction (AJ) proteins] in a rat model of necrotizing enterocolitis. Mennigen et al[29] found that the probiotic mixture VSL#3 protected the epithelial barrier by maintaining TJ protein expression and preventing apoptosis in a murine model of colitis. These studies support the findings that a number of probiotic agents have the protective effects in gastrointestinal tract as described in the current work.
Previous studies, including experimental models and clinical cases of biliary obstruction, have shown that disruption of intestinal barrier integrity in obstructive jaundice is associated with high intestinal oxidative stress, as evidenced by increased lipid peroxidation and oxidation of proteins, non-protein, and protein thiols[6,30]. Increased intestinal oxidative stress, a factor in cellular injury, may also play a critical role in regulating important cellular alterations of the intestinal mucosa in obstructive jaundice, such as increased apoptosis and altered TJ expression[5,31]. The results of this study strongly suggest that obstructive jaundice induces oxidative stress in the intestine.
We also found that apoptotic nuclei were significantly more abundant in markedly atrophic villi in the BDL group. Administration of L. plantarum significantly decreased apoptosis of the terminal ileum and improved the histology of the terminal ileum, which also was affected by obstructive jaundice. The protective effect of L. plantarum may be related to amelioration of oxidative stress. Previous studies of L. rhamnosus GG, a member of the same genus as L. plantarum, showed that this bacterium attenuated the H2O2-induced disruption of barrier function[18]. Our studies also revealed that administration of L. plantarum significantly reduced the levels of GSSG, MDA and SOD in rats of the BDL + L. plantarum group and the BDL + IBD + L. plantarum group.
Intestinal epithelial TJs prevent diffusion of potential injurious factors from the gastrointestinal lumen into the tissue. TJs located at the subapical aspect of the lateral membranes contain a large number of membrane-associated proteins, including occludin, JAM and claudins, which are responsible for forming the physical connections between cells that confer the basic barrier properties. Using immunohistochemistry and immunoblotting, previous studies have demonstrated that intestinal mucosal barrier dysfunction in obstructive jaundice is associated with a regional loss of occludin expression in the intestinal epithelium[4,31]. Similarly,our study showed that levels of TJ-associated proteins such as occludin, ZO-1, claudin-1, claudin-4 and JAM-A were reduced in the intestinal epithelium, especially at the upper part of villi. These data support the conclusion that oral L. plantarum administration can enhance the expression of TJ-associated proteins.
A significant body of evidence indicates that PKC is involved in the regulation of the integrity of TJs and AJs. Recent studies have shown differences between Tyr-phosphorylation and Ser/Thr-phosphorylation of occludin. Tyr-phosphorylation of occludin is clearly associated with the disruption of TJs. Ser/Thr-phosphorylation may be required for the assembly of occludin into the TJs. PKC-ζ prevents oxidant-induced iNOS upregulation and protects microtubules and gut barrier integrity[32]. Thus, PKC-ζ appears to be an endogenous stabilizer of the microtubule cytoskeleton and of intestinal barrier function against oxidative injury[33].
The probiotic bacterium L. plantarum has been shown to improve intestinal barrier function in a range of experimental models of colitis, pancreatitis, liver injury and biliary obstruction[8,34-37]. Recent studies have shed some light on the mechanisms involved in the beneficial effects of probiotics in the gastrointestinal tract. PKC activity may be involved in epidermal growth factor-mediated protection of the intestinal epithelial barrier function against oxidative stress[38]. Seth et al[18] suggested that PKCβI activation may be one of the initial events in the probiotic-mediated protection of TJs and AJs. PKCε may play a role in the downstream events of the signaling pathway involved in this process. TJ-protein phosphorylation mediated by PKC may be related to the mechanism of protection by L. plantarum in obstructive jaundice. Previous studies have shown that phosphorylation is a key mechanism for regulating the biological function of TJ proteins. Highly phosphorylated occludin molecules are selectively concentrated at TJs, whereas non- or less phosphorylated occludin molecules are localized in the cytoplasm[39].
To determine whether PKC mediates the disruption of the intestinal barrier in obstructive jaundice, we examined the phosphorylation status of occludin and ZO-1 using Western blotting analysis with antibodies against phosphoserine. We found that obstructive jaundice decreased p-occludin and p-ZO-1 protein levels compared with sham-operation. Our study also demonstrated that obstructive jaundice resulted in a significant decrease in PKC activity. Co-incubation with L. plantarum partly restored PKC activity and increased phosphorylation of serine residues on TJ proteins in both the BDL + L. plantarum group and the BDL + IBD + L. plantarum group. Phosphorylation of these proteins occurred on Ser residues that have been described as substrates for PKC activity[40-42]. Our results suggest that the PKC pathway is involved in the process of L. plantarum-induced TJ redistribution.
In conclusion, administration of probiotics before and after operation in rats with experimental obstructive jaundice can substantially protect the gut barrier. The protective mechanisms of probiotics are associated with decreased intestinal epithelial cell apoptosis, reduction of oxidative stress, and protection of intestinal mucosal TJs. L. plantarum can prevent TJ disruption in biliary obstruction by activating the PKC pathway.
Biliary tract surgery in patients with obstructive jaundice is associated with a high morbidity and mortality rate, and obstructive jaundice increased gut permeability and bacterial translocation. Lactobacillus plantarum (L. plantarum) has been shown to have beneficial effects on intestinal barrier function. Protein kinase C (PKC) plays a crucial role in the mediation of intestinal epithelial tight junction (TJ) proteins, and L. plantarum may prevent TJ disruption in biliary obstruction by activating the PKC pathway. However, there had been few studies about the mechanism for the protective effect of probiotics on the intestinal barrier in obstructive jaundice. This study focused on the effects of L. plantarum on the intestinal mucosal barrier, oxidative stress, epithelial TJ-protein structure and phosphorylation, especially its impact on the expression and activity of PKC.
Previous in vitro studies have confirmed that probiotics could protect intestinal epithelial cell TJs via a PKC-kinase-dependent mechanism and inhibit epithelial cell apoptosis in cell culture experiments. TJ-protein phosphorylation mediated by PKC may be related to the protective effects of L. plantarum in obstructive jaundice.
The administration of L. plantarum before and after operation in rats with experimental obstructive jaundice could substantially protect the gut barrier. Protective mechanisms of L. plantarum are associated with decreased intestinal epithelial cell apoptosis, reduction of oxidative stress, and protection of intestinal mucosal TJs. L. plantarum can prevent TJ disruption in biliary obstruction by activating the PKC pathway.
By understanding the mechanism and effects of L. plantarum on the intestinal mucosal barrier, this study may represent a future strategy in the treatment of patients with obstructive jaundice.
This is a very well done experimental study for evaluating the effect of L. plantarum on the intestinal mucosal barrier, oxidative stress, epithelial TJ protein structure and phosphorylation, with special regard to its impact on the expression and activity of PKC in experimental obstructive jaundice.
Supported by The National Natural Science Foundation of China, No. 30471687; and Chinese Ministry of Science and Technology, No. 2008CB517403
Peer reviewers: Julio Mayol, MD, PhD, Department of Digestive Surgery, Hospital Clinico San Carlos, Martin-Lagos S/N, 28040 Madrid, Spain; Mathias Chamaillard, PhD, Center for Infection and Immunity of Lille, INSERM U1019-CNRS UMR 8204-Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Professeur Calmette, 59019 Lille Cedex, France; Tamara Vorobjova, MD, PhD, Senior Researcher in Immunology, Department of Immunology, Institute of General and Molecular Pathology, University of Tartu, Ravila, 19, 51014 Tartu, Estonia; Fang Yan, MD, PhD, Research Associate Professor, Division of Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, MRB IV, Room 1035J, Nashville, TN 37232, United States
S- Editor Cheng JX L- Editor Ma JY E- Editor Xiong L
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Don't forget to spring forward for Daylight Savings Time tonight. Clocks should be moved one hour forward by 2 a.m.
Jazzercise classes held at local churches
Jazzercise, the world's leading dance-fitness program, recently honored local franchise owner Nessa Brinkley with the prestigious Achiever award.
As an Achieveer, Brinkley is one of the top Jazzercicse franchisees for the area and has been in operation in Amarillo for almost six years. Brinkley has served the West Texas area as a Jazzercise Franchise Owner and Fitness Consultant for 18 years.
Jazzercise classes are held at Trinity Baptist Church and Amarillo South Church. Anyone interested in teaching Jazzercise should attend a free workout at 8:45 a.m. today at Trinity Baptist Church Recreation Outreach Center, 1608 Wolflin St., where a free information meeting/movement screening is set for 9:45 a.m.
A free Jazzercise Open House will be Monday through Thursday at Trinity Baptist Church and Amarillo South Church. Open house festivities will include information on the Jazzercise program and a free workout.
Trinity UMC schedules brisket dinner, trimmings
TRINITY UNITED METHODIST CHURCH will have a brisket dinner with all the trimmings from 5 to 7 p.m. today at the church, 3402 S. JACKSON ST. Cost is $6.50 for adults, $3.50 for children under 12 and children under 3 eat free. There will be a bake sale in the fellowship hall.
Christ's Community sets parenting conference
CHRIST'S COMMUNITY FELLOWSHIP CHURCH OF VEGA will have a parenting conference at 5:30 p.m. today, 10:30 a.m. Sunday and 5:30 p.m. Monday at the church, 607 COKE, VEGA. Brenda Bird will be the guest speaker at "Focusing on the Family."
Bird has spoken to Region 16 Center and is known for teaching positive parenting skills to strengthen families.
Child care will be provided.
Guest minister Sunday at Friends and Family
Kim Kirkwood will be the minister at 3 p.m. Sunday at FRIENDS AND FAMILY WORSHIP CENTER, 1111 N. BUCHANAN ST. Kerry Krikwood from Trinity Fellowship in Tyler will be the guest minister at 3 p.m. April 8. Other weekly service times are Prayer and Worship at 7 p.m. Mondays, and Bible Teachings at 7 p.m. Wednesdays.
Comanche Trail church offers special classes
COMANCHE TRAIL CHURCH OF CHRIST will offer a special class beginning at 9:15 a.m. Sunday through June 25 at the church, 2700 E. 34TH AVE. "Being A Christian in the Post 9-1-1 World" will be taught by Jerry L. Klein, one of the ministers at Comanche Trail.
Klein previously served as the chairman of the Religion Department at Amarillo College. The class will focus on how God can allow bad things to happen to God's people, how has this change affected the way Christians perceive their world and how Christians should behave under the circumstances they now find themselves in.
Call 373-4190 or 353-6293.
Westview Christian plans Open House
WESTVIEW CHRISTIAN CHURCH, 6810 HILLSIDE ROAD, will have Open House after the 10 a.m. worship service Sunday at the church, 6810 Hillside Road. Snacks will be served. There will be balloons for the kids and a gift for each visiting family. Sunday School starts at 9 a.m.
Methodist women slate monthly meeting
United Methodist Women Of COVENANT FELLOWSHIP CHURCH will have their monthly meeting and luncheon at noon Wednesday at the church, 1739 S. AVONDALE ST. Guest speaker will be Benita Medford, Director Of Resettlement For Refugee Services of Texas.
Medford was raised in Crosbyton and graduated from Texas Tech University in Lubbock. She is married to Landrum Medlock, pastor of Pleasant Valley Methodist Church.
Central Baptist Church starts Spring Revival
CENTRAL BAPTIST CHURCH will have its annual Spring Revival at 7 p.m. Thursday through April 8 and at 11 a.m. April 9 at the church, 4808 S. BONHAM ST. Paul Schwanke will be the guest evangelist.
Schwanke, from Phoenix, has been an evangelist for 22 years and has preached in 45 states and 30 different countries. CDs of his messages and music will be available.
Following the service on April 9, the church will celebrate its 75th anniversary. Activities include dinner following the morning service, men and boys of the church will preach, and members will present music specials. There will be no evening service.
A nursery will be provided, and transportation is available. Call 372-1464.
Knights of Columbus set annual fish fry
The St. Francis Chapter of the Knights of Columbus will have its "All You Can Eat" Fish Fry from 6 to 8 p.m. Friday at ST. FRANCIS CATHOLIC CHURCH HALL, LOCATED ON HIGHWAY 60, ABOUT 10 MILES EAST OF AMARILLO. Cost is $7 for adults and $3.50 for children 7-12.32
The MaHarreys to sing at Nazarene church
The MaHarreys will be in concert at 7 p.m. Friday at VALLEY VIEW CHURCH OF NAZARENE, 7601 WESTERN ST.
The MaHarreys are a family group from Alabama. They have been traveling and signing for more than 30 years. Their music stretches from southern Gospel, Christian country and bluegrass.
Other concert appearances are: 7 p.m. April 9 at Temple Baptist Church, 3208 S. Van Buren St.; 11 a.m. April 9 at Avenue Baptist Church, 130 N. 25 Mile Ave. Hereford; and 6 p.m. April 9 at South Georgia Baptist Church, 5209 S. Georgia St.
Ceta Canyon center to have Open House
Ceta Canyon Camp and Retreat Center will have an Open House at 2 p.m. April 8 at the center, 37201 FM 1721, Happy.
Activities include hiking, fishing, tours of the camp, wagon rides, challenge course, inflatable bouncers and basketball. Summer camp registration forms will be available.
Call (806) 488-2268 or visit www.cetacanyon.org. Ceta Canyon Camp and Retreat Center is a United Methodist Ministry.
Westover Fellowship begins revival in April
WESTOVER FELLOWSHIP CHURCH will have a revival at 8 p.m. April 9-12 at the church, 8501 S. COULTER ST. Mark Urquhart will be the guest speaker, and Shane Chadwick with Revolution 2K praise team will lead worship.
Women's Connection plans guest speaker
Patty Curl will speak at the monthly Christian Women's Connection Luncheon at 11:30 a.m. April 10.
Curl, a speaker, concert soloist, recording artist and artist, will have a mini-concert and talk about discovering her value in an approval-oriented world
The Christian Women's Connection meets from 11:30 a.m. to 1 p.m. every second Monday of each month at the Ambassador Hotel, 3100 Interstate 40 West. The cost is $13.50 per person.
Reservations for this month's luncheon are due by Wednesday. To make a reservation call 322-4088 or e-mail email@example.com. Resrvatons must be honored, shared or canceled. Nursery is available by reservation.
Any woman in the community can attend.
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7th Documented Video Test of a *NEW* DUAL 4 Plate HHO Cell w/ Tap Water and Baking Soda as Electrolyte (1/2...
7th Documented Video Test of a *NEW* DUAL 4 Plate HHO Cell w/ Tap Water and Baking Soda as Electrolyte (1/2 teaspoon). HHO-Cell Test: 1 Liter per Minute Output This is just a TRIAL RUN @ idle: Nissan Altima (1998) 2.4Liter Engine - 4 Cylinder. MPG: (Stock) 28-city/36-highway Heat is a HUGE consideration when dealing with these type of hho-cells. First off, you will get a type of run-away effect once you get temperature spike of upwards 140°-180°F. Once this occurs your run-away results in HUGE Amperage increase on the hho-cell. This is something to consider because it is under your hood of your car with an engine specifically set-up to run @ 220°F or more if stuck in traffic. Ideas for cooling must be thought about, especially with a small cell like ours that you see here. Plus the winter is near, so I believe the placement near the exhaust header is perfect. Also, another bump in the road is the fact of freezing temperatures in our cell when not in use during the cold months. Possibly Alcohol additive for a type of Anti-freeze??? Anyone with any ideas please be sure to share them with us. Other modifications prior to this video included: newer design upgraded to weatherproof enclosure, modified with a plexiglass (quarter inch think) viewing window for study. Further upgraded to the cell Stinger 4-gauge wire with the addition of 8-gauge audio power cables also. With electrician grade heavy duty crimp down connectors, similar to stay-cons. The actual plates are 98% of the components being stainless steel (non magnetic) screws/bolts to further our experiments. Spacing is around 1/16th of an Inch. This set-up is regarding a dual 4 wall plate config, store bought from Home Depot. Baking Soda is our electrolyte. The plates are configured to be 2+(pos) and 2-(neg) .. or can be switched around. [+][-][+][-] x2 Thanks for viewing my videos..


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What platform is better for Prototype 2? PS3 or 360?
I got the PS3 version based on Digital Foundry's verdict:
"As it stands right now though, it's the PS3 version that comes recommended without much reservation. It simply plays out better overall during combat and travel alike, and considering it offers the same basic assets and rendering techniques as the 360 version, albeit minus the incessant tearing, it can often end up looking better in motion too."
Most of my multiplatform games are on 360, but I don't mind getting the PS3 version of this game.


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Subscribe To our E-Newsletter
Jack M. Barrack Hebrew AcademyCost:
For more information and to register for courses, call 610-922-2412 or go to: www.jbha.org/barrackU.
272 S Bryn Mawr Ave
Bryn Mawr, PA 19010
Barrack U!
December 2, 2012 1:00 PM-4:00 PM
The Jack M. Barrack Hebrew School will host a day of learning for the community.
Session 1, set to begin at 2:15 p.m., will feature:
"Amichai's Jerusalem" presented by Andrea Rock, [email protected] Director; English and Tanach Faculty
"Human Impact on the Environment: A Hot Topic for Debate," presented by Darin Katz, Ph.D., Academic Dean; Rabbi Judd Kruger Levingston, Ph.D., Director of Jewish Studies
"Introduction to Rock Drumming" presented by Harrison Horowitz, Art Faculty
"Proving the Existence of God" presented by Barnett Kamen, Jewish Studies Faculty
Session 2, beginning at 3:15 p.m., will include:
"Fun With Math: Patty Paper Parabolic Play" presented by Bill Enos, Match Faculty
"It's All Greek to Me: Jews in the Hellenistic Age" presented by Minna Ziskind, History Faculty
"Make a Mezzuzah" presented byLaura Lyn Stern, Art Faculty and Professional Artist
"The Rabbi and the Ugly Man (Taanit 20a)" presented by Elisha Stein, Jewish Studies Faculty
Registration: $20. Early registration (by Nov. 26): $15.
Browse the Calendar
The Calendar
Mon. Sep 26
Reform Congregation Keneseth Israel
Mon. Sep 26
Mon. Sep 26
Old York Road Temple-Beth Am


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How to Disable Dashboard in OS X Snow Leopard
7 July 2010 25,497 views No Comment
If you have an older Mac or portable, a silent thief could be hoarding resources and draining your battery without your knowledge — Dashboard. Introduced in Mac OS X 10.4 Tiger, this feature was heralded as something of revolution and even Microsoft fielded their own version in Windows 7, which Redmond unashamedly named "Gadgets."
Whether you're trying to squeeze more performance out of an older Mac or every drop of power from your MacBook, the Dashboard could draining valuable clock cycles and watts behind your back. Here's how to turn it off.
To turn Dashboard off:
defaults write com.apple.dashboard mcx-disabled -boolean YES
To turn Dashboard on:
defaults write com.apple.dashboard mcx-disabled -boolean NO
Lastly, restart the Dock to effect the change (either process)
killall Dock
For the command-line averse, there is the Disable & Enable Dashboard Utility, which makes the process as simple as clicking a button. Get your copy here.
via Mac OS X Hints


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Jack Holmes and His Friend
White, Edmund
Library Classification:
Adult Fiction
BIC Subjects:
Modern & contemporary fiction (post c 1945)
Bloomsbury Publishing PLC
Bloomsbury Publishing PLC
Publication Date:
Place of Publication:
United Kingdom
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Many straight men and gay men are best friends, but if the phenomenon is an urban commonplace it has never been treated before as the focus of a major novel. Jack Holmes is in love, but the man he loves never shares his bed. The other men Jack sleeps with never last long and he dallies with several women. He sees a shrink and practices extreme discretion about his gay adventures since the book begins in the 1960s, before gay liberation, and ends after the advent of AIDS in the 1980s. Jack's friend, Will Wright, comes from old stock, has aspirations to be a writer, and like Jack works on the Northern Review, a staid cultural quarterly. Will is shy and lonely-and Jack introduces him to the beautiful, brittle young woman he will marry. Over the years Will discovers his sensuality and almost destroys his marriage in doing so. Towards the end of the 1970s Jack's and Will's lives merge as they both become accomplished libertines.
Edmund White has three voices. First there is the storyteller, relaxed, conversational, an anecdotalist, an inspired flaneur. Then there is the poet: on every page there lies in wait a metaphor of startling precision, an image that holds and reattracts the eye. And then there is the laic philosopher, who observes human life from the highest altitudes, held aloft by vast infusions of erudition and experience. In Jack Holmes and His Friend, White's trio is in frictionless accord Martin Amis Edmund White is one of the best writers of my generation; he's certainly the contemporary American writer I reread more than any other, and the one whose next book I look forward to reading most John Irving I can't remember the last time I had this much fun with a novel. Jack Holmes and His Friend is a brilliant, moving and hilarious book from America's wittiest and most urbane writer ... Entirely unforgettable and true. A top-shelf addition to the Edmund White canon Gary Shteyngart The acuity of Edmund White's descriptions and the elegance of his imagery are a constant delight Literary Review Tender prose ... an elegant study of the paradoxes and half-truths that emerge in long-standing friendships' New Yorker White is a marvellous writer. Barely a page passes without some arresting metaphor [and] the social observation is just as sharp Spectator His are beautiful explorations of sexuality and sensibility in American society Observer Wonderful ... White's writing is beautiful, and he has a superb intimacy with his utterly convincing characters Saga A simple, rather moving celebration of platonic friendship TLS His narrative [has] a real density and weight ... in the dramatization of suburban life there are elements and echoes of Richard Yates's Revolutionary Road and T.C. Boyle's The Tortilla Curtain; in the exploration by an outsider of class and privilege there are elements and echoes of The Great Gatsby, Brideshead Revisited, and The Line of Beauty. It is also possible to find traces of The Age of Innocence in the way a changing city and a disappointed sensual hero are drawn ... Jack Holmes and His Friend is a comedy of manners, which ingeniously uses the system of doubling the gay hero by offering him an alter ego who is straight. This allows White to move with relish between a man who makes his friends his family and a man who makes a family Colm Toibin, New York Review of Books Truly comes to life when White is writing about character's sexual adventures ... White's understanding of the perverse nature of the human heart is as vivid and engaging as it is frustrating Gay Community News
Title: Jack Holmes and His Friend
By (author)
Edmund White
Publisher: Bloomsbury Publishing PLC
Imprint: Bloomsbury Publishing PLC
Publication Date: 5/01/2012
Place of Publication:
United Kingdom
Edition: Export/Airside ed
BIC Subjects:
Modern & contemporary fiction (post c 1945)
NBS Classification: General & Literary Fiction
Format: Paperback
Pages: 400
Height: 234mm
Width: 153mm
Thickness: 29mm
Weight: 523g
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I'm back here in After Effects. If you've downloaded the project files that came with this training, go ahead and do Command+O or Ctrl+O to open. Go up to Chapter 3 folder/After Effects/videowall composite3_starter. Open up and that brings in the same two video sources we had earlier to play with. Now, I want to import my multi- pass render and again, it's important. You don't do O to Open, but you do Command+I or Ctrl+I to Import a Cinema .aec file.
Command+I, I'm going to go to my multipass renders folder. There is my .aec file. You see all of these other layers. Videowall.mov is my normal render but there is the ambient, diffuse, object buffer, reflection, rgb, which is redundant to the whole render, shadow and specular. So, I'm going to go ahead and import just the aec and it will bring in all of those other special passes for me. Here is my videowall object. There is my normal render. Here is the RGB render, but also inside the videowall folder, I have my ambient, diffuse, reflection, shadow and specular properties.
Let's open up this comp and see what's all in here. Here is my Camera and lights, as I expected. This particular project in Cinema, I used a null object instead of a solid to note where the videowall's face is. That's why that looks a little bit different. Here's these individual properties. Let's solo them. Reflections, you see a little bit down here in the bottom. Ambient, just that self-illumination on the wall or around the text edges. Shadow, normally a white render, the black with the shadows are supposed to be factored in.
Specular, that hot spot, and all these are factored on top of Diffuse, the flat, overall lighting of the scene. What's really instructive is to click on Toggle Switches / modes, again, F4 is a shortcut and see the Blending modes used to create this composite. Reflections are typically done in Add mode. If you find the reflections are too strong, you can try something weaker like Screen but Add tends to work better for things like this. Ambient is also added. It's another form of illumination, which is added into the scene.
Shadow is Multiplied. It actually darkens the scene. That's why it was mostly white. When you multiply white, you have no change, but when you multiply black, it darkens the underlying composite. Specular highlights are also added onto the underlying footage and there is our Diffuse down at the bottom. Now the really cool thing about this is not only can I change the modes, I can change the transparency of these layers to change how they're blended. I'll Type T for Opacity.
Let's say that I want less Reflection. That's too much reflection. Let's go ahead and reduce its Opacity to reduce the amount of reflection in the scene. No reflection, just to hint, full strength reflection. Ambient light, where I got some self- illumination on that wall, if I find the wall a bit too flat, I want something more dramatic on in or if I want to use my lighting inside this scene to help boost it, I can pull out the Ambient lighting, or just factor it back in as much as I like, maybe around there.
Shadows, same thing. Here are my Shadows. If that's too strong, I can go ahead and pull them back out of the scene. There is no Shadows present or just a hint of a shadow. And same thing with the Specular highlight, a little hot spot on the wall I can reduce, or put back in. Now the problem with Opacity, and with this approach in general, is that they all come at 100% and you can't go greater than 100. However, there are things you can do to heighten these effects.
If you're already inside After Effects, you can pick something like the Specular highlight, duplicate the layer and now you've got double the Specular effect. Type T for your duplicate and decide just how much extra specular do you want to match in. So, there I have gone basically to 100 plus 16 or 116% Specular, versus what came out of Cinema. So, I can do that to over-amp the Specular. Let's say in the case of the Shadow. The shadow wasn't dark enough. I can do the same thing. I can duplicate it to darken my shadows or keep the one original layer.
Let's say that I don't like black as my shadow. Well if I wanted to, I could even colorize my shadow, just to add more of a surreal look to the scene. In that case, I would use something like Effect>Color Correct>Tint. Leave White at White, but Map Black To a different color, so just say something in a more of an Amber sort of look here. Let's go ahead and go a little darker, pull it back down on that sort of look. Now I've got a tinted shadow in the scene rather than my normal straight black shadow.
In the case of reflections, they default to being perfectly sharp. Let's say I want a blurry reflection. I will go ahead and pick my Reflection Pass and go Effect>Blur & Sharpen. Pick something like Box Blur, which is very flexible. I can either increase that go get a boxy sort of blur on my reflection or maybe increase the Iterations a little bit to get a smoother blur to the reflection. But now I've got that classic blurred reflection look, rather than a perfectly clear sharp reflection. Now, this is very cool because I'm doing all this mixing and matching after the fact, inside After Effects.
I'm not having to go back into the 3D program and re-render. Again, this is a fantastic way to accommodate client changes. Indeed, if I know I'm going to be working this way in the future, what I might do is go back to my Cinema project, in CINEMA 4D and over-amp some of these properties. For example, let's go ahead and go to my key light, open up its properties, look at Shadow and I might even make the Shadow Density say more than 100% inside Cinema because I can always cut the Opacity back inside After Effects.
Same thing for Reflections, I've got my Texture on my white flooring. Open up the Texture Settings, go to Reflection and increase the Mix Strength for my floor or do other things to go ahead and really amp up the look of this project. I can always back it down in After Effects far easier than I can duplicate and mix in more of an effect in After Effects. So, I might purposely overplay things in 3D, just so I can pull them back later or keep them hot, if that's what the client wants.
Now, this approach, of just doing a Multi-Pass on Ambient, Diffuse, Specular, Reflection, Shadow alone gives you a lot more flexibility, whether you're doing motion graphics or visual effects, but you can take this to the next level and even control the individual intensity of each light and the color of each light. I will show that one next.
Chris Meyer—a long-time user of both programs—explains how to move 3D worlds from Maxon's CINEMA 4D into Adobe's After Effects and add additional 3D elements that blend perfectly. Chris shows how to transfer 3D cameras, lights, and position data from CINEMA 4D to After Effects; create track mattes to composite new elements into the middle of a scene; and take advantage of multi-pass rendering to quickly remix and even recolor lights, shadows, reflections, and more. Paced comfortably for beginners, this course also reveals numerous advanced tricks and techniques, such as the use of blending modes and how to cast shadows from new 3D layers in After Effects onto rendered 3D elements from CINEMA 4D. Exercise files accompany this course.
- Locating objects for export from CINEMA 4D
- Adding layers to a composition after importing into After Effects
- Separating lights in CINEMA 4D and remixing in After Effects
- Understanding the problems with shadows during integration
- Refining 3D shadows in After Effects


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Trash fills White Rock Creek, calling volunteers to action
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Charlie Sheen pays for therapy dog for girl hurt in Dells amusement park accident
A Florida teenager who plummeted 100 feet from a Wisconsin Dells amusement park ride in 2010 is getting some help from actor Charlie Sheen.
Teagan Marti suffered brain, spine, pelvis and internal injuries when nets and air bags that were supposed to catch riders on the free-fall ride were not raised at Extreme World in Wisconsin Dells. She was paralyzed initially but through physical therapy is now able to walk with a walker. »Read Full Article(12)
In Tandem Theatre moves back to funny, perceptive 'Apartment 3A'
Can one argue that really great sex proves the existence of God? Can a play in which a woman verbally counts out her simulated, onstage orgasms still be described as wholesome and old-fashioned? Is actor Jeff Daniels' "Apartment 3A," the comedy triggering these questions, really funny?
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- 06-11-2013, 02:46 AM Thread Author #1
SMS/Texting from your computer
Hey guys,
I'm wanting to find out if there's an app or software that I can use to send SMS's through my phone using my computer. The requirements I'm after, if possible are:
1. Don't want all my SMS's synchronised through Google or some third party website or service. if possible a solution just involving my phone and computer would be ideal
2. Lightweight/simple. I don't need all the extra features, just after SMS'ing
Searching on the app store shows up a fair few results of computer/sms solutions but most of them seem to be quite bulky or sync through google or third party services etc, just wondering if anyone has any suggestions?
- Posts
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Re: SMS/Texting from your computer
How do you expect to sync between devices unless you use a web service?
Sent from my Nexus 4 using AC Forums mobile app
- 06-13-2013, 12:55 AM Thread Author #3
Re: SMS/Texting from your computer
I'm not sure that there is a solution for this. Every app that I found requires some sort of gmail or third-party access. Is there a reason why you don't want to use any of these soutions? Privacy?
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Re: SMS/Texting from your computer
Do they have to be through your phone? You can send SMS's fine through email (but they wouldn't be coming through your phone). But I guess email would be "3rd party service" which you seem concerned about for some reason that I don't comprehend.
I am so confused by this request since SMS is such a basic feature that I can't figure out why you want to make it complicated. You do know SMS doesn't even go through Google or anything, right? It's delivered right over your carrier's airwaves? It doesn't even use data or anything (MMS is another story, but AFAIK it still doesn't go through any company's server).
- 06-13-2013, 09:15 PM Thread Author #6
Re: SMS/Texting from your computer
Yes the reason I don't want all of my SMS's to be uploaded to Google or some other website I don't know is privacy! I'm not sure how anyone could not be concerned with this. But it seems to me that a lot of Android/Google users seem to not give privacy much concern at all. After all I guess they already have EVERYTHING else. (Email, calendars, correspondence, chats, locations, work schedules, etc etc) Why not upload ALL OF YOUR SMS's too?
I'm not after a 'complicated' solution, was just wondering if there's a basic app/software that lets me read/type sms's using my computers keyboard and computer screen due to its larger and much more efficient interface. I have a couple of friends who like to communicate mainly via SMS, so while at work if there was a way I could read/respond via the computer rather than having to type on the small screen it would be really nice!
I can't imagine what the technical barrier in developing this would be . Some computer software would just need to be able to speak with the phone (or an app on the phone) to get a list of the sms's currently there, and to be able to 'send' an sms from the phone?
I don't mind if it has to be directly connected (bluetooth or cable etc). I don't need the 'remote' sms'ing feature etc
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Re: SMS/Texting from your computer
Who's your wireless providers? I have Verizon, and there's functionality on the Verizon website to compose and send SMS messages. It goes through Verizon, not Google. So you could check your wireless provider's website to see if there is a similar functionality.
I think we all have concerns about privacy, but I also think it's a little unrealistic to think that we can have this massive thing called the Internet, with massive and not-so-massive companies trying to succeed (i.e., make money), without giving up some privacy. The huge majority of services available on the web and via wireless communications is not exactly free--otherwise, where would be the incentive to innovate and compete?
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Re: SMS/Texting from your computer
Sent from my SPH-D710 using Tapatalk 2
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Vaadin Plug-in for NetBeans - plugin detail
Provides support for Vaadin application development in NetBeans IDE 8 and 7.4.
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User Comments
Creating vaadin project without maven
You can do it manually, by managing dependencies and using e.g. ANT. But the plugin probably don't help you much in this case.
Posted by vaadin-addons on Nov 18, 2015
Creating vaadin project without maven.
I am using netbeans 8.0.2 and 1.1.3 version of this plugin. Is there any way to create vaadin project in netbeans without maven, If yes then how?
Posted by Rahul.khandelwal on Jan 19, 2015


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With a 15-second clip, Florida Gov. Rick Scott joined the Venezuela SOS movement. He joined a slew of other local elected leaders who have openly voiced support for Venezuelans amid protests and unrest in the South American country. In the Vatican, Pope Francis has called for an end to the violence. NBC 6's Gilma Avalos reports.
Published at 7:25 AM GMT on Feb 27, 2014


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|Low Growing
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Planting: In early spring, when danger of hard frost is over, sow seeds in well-worked, fertile soil in full sun. Space seeds 1" apart in rows 8" - 10" apart, or broadcast thinly for bed planting. Firming soil well over these irregularly shaped seeds will ensure best germination. If first sowing comes up unevenly, sow more seeds as seedlings will catch up fast. When large enough to handle, carefully thin seedlings to 2" - 4" apart so growing beets have room to size up.
Growing: For best quality, tender roots, sow seeds before midsummer heat and again in late summer to early fall — in cold climates, allow at least 10 weeks before fall frosts. Keep soil evenly moist throughout the season. Be sure to thin seedlings several times when plants are small, as beets grow best if given enough room.
Harvest & Use: After thinning seedlings, use tender young tops for nutritious, flavorful steamed greens. Harvest baby beets at 1" - 2" in diameter, or let roots grow as large as desired. Garden fresh beets cook quickly. They are delicious steamed, boiled or baked whole in their skins like potatoes, then peeled for wonderful color and sweet concentrated flavor. Golden color does not "bleed" like red beets.
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Today's Quiet Moment
Friday, September 30, 2016
Memorial of St. Jerome
The face is the mirror of the mind, and eyes without speaking confess the secrets of the heart. read more »
Do people who commit suicide go to hell?
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21 years of experience
Accepting new patients
2699 Atlantic Ave
Long Beach, CA 90806 Phone number & directions
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Deborah Milligan:
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Read all about venous thromboembolism symptoms and treatments by reading our patient education guide.Before Visiting Dr. Milligan Learn More
Specialties & Research
Dr. Deborah Milligan, MD is board certified in Internal Medicine, Critical Care Medicine, and Pulmonary Disease.
- She has special expertise in 1 area:
- Asthma
Education & Awards
Dr. Milligan graduated from University of Virginia, Charlottesville.
Dr. Milligan has 10 hospital affiliations:
- St. Mary Medical Center
- Pacific Hospital of Long Beach
- English
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- Dr. Deborah Helen Milligan MD is a female Internist, has 21 years of experience and practices in Internal Medicine, Critical Care Medicine, and Pulmonary Disease.
- Where does Dr. Deborah H. Milligan practice?
- Dr. Deborah Milligan has 3 office locations.
Dr. Deborah Milligan practices Internal Medicine, Critical Care Medicine, and Pulmonary Disease near Long Beach, CA.
Additional practice locations include: Costa Mesa, CA.
See Long Beach Internists, Long Beach Critical Care Practitioners, and Long Beach Pulmonologists.