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117-469: It was developed by head chemist Maurice Treneer. Alka-Seltzer is marketed for relief of minor aches, pains, inflammation , fever , headache , heartburn , stomach ache , indigestion , acid reflux , and hangovers while neutralizing excess stomach acid . It was launched in 1931. Its sister product, Alka-Seltzer Plus, treats cold and flu symptoms. A wide variety of formulae, many using acetaminophen (paracetamol) instead of aspirin, are available under

234-470: A Russian Jewish family. He was the son of Jeanne (Baer) and William J. Silberman, a manufacturer and salesman of novelty items. Wilder first became interested in acting at age eight, when his mother was diagnosed with rheumatic fever and the doctor told him to "try and make her laugh." At the age of 11, he saw his sister, who was studying acting, performing onstage, and the experience enthralled him. He asked her teacher if he could become his student, and

351-399: A chemotactic gradient created by the local cells to reach the site of injury. The loss of function ( functio laesa ) is probably the result of a neurological reflex in response to pain. In addition to cell-derived mediators, several acellular biochemical cascade systems—consisting of preformed plasma proteins—act in parallel to initiate and propagate the inflammatory response. These include

468-401: A lipid storage disorder, is now understood as a chronic inflammatory condition involving the arterial walls. Research has established a fundamental role for inflammation in mediating all stages of atherosclerosis from initiation through progression and, ultimately, the thrombotic complications from it. These new findings reveal links between traditional risk factors like cholesterol levels and

585-538: A $ 2-million budget. After Everything You Always Wanted to Know About Sex* (*But Were Afraid to Ask) , Wilder began working on a script he called Young Frankenstein . After he wrote a two-page scenario, he called Mel Brooks, who told him that it seemed like a "cute" idea, but showed little interest. A few months later, Wilder received a call from his agent, Mike Medavoy , who asked if he had anything where he could include Peter Boyle and Marty Feldman , his two new clients. Having just seen Feldman on television, Wilder

702-499: A bandstand. I don't want to run for president in 2008. I will write another book instead." Wilder donated to Barack Obama's 2008 presidential campaign . Wilder died on August 29, 2016, at the age of 83, at home in Stamford, Connecticut , from complications of Alzheimer's disease . He had been diagnosed three years before his death but kept knowledge of his condition private. Wilder's nephew Jordan Walker-Pearlman said that this

819-454: A collection of stories called What Is This Thing Called Love? His third novel, Something to Remember You By: A Perilous Romance , was released in April 2013. When asked in a 2013 Time Out New York magazine interview whether he would act again if a suitable film project came his way, Wilder responded, "I'm tired of watching the bombing, shooting, killing, swearing and 3-D. I get 52 movies

936-568: A company scientist of Dr. Miles Medicine Company, who also helped direct its development. Print advertising was used immediately, and in 1932 the radio show Alka-Seltzer Comedy Star of Hollywood began, with National Barn Dance following in 1933, along with many more. The radio sponsorships continued into the 1950s, with the Alka-Seltzer Time show airing from 1949 to 1957. In his 1976 revival, American actor and radio performer Richard Beals proclaimed Alka-Seltzer's virtues and sang

1053-454: A construction site – for the purpose of aiding phagocytic debridement and wound repair later on. Some of the exuded tissue fluid is also funneled by lymphatics to the regional lymph nodes, flushing bacteria along to start the recognition and attack phase of the adaptive immune system . Acute inflammation is characterized by marked vascular changes, including vasodilation , increased permeability and increased blood flow, which are induced by

1170-493: A cult following and an Oscar nomination for Best Score, as well as a Golden Globe award nomination for Wilder. When Woody Allen offered him a role in one segment of Everything You Always Wanted to Know About Sex* (*But Were Afraid to Ask) , Wilder accepted, hoping this would be the hit to put an end to his series of flops. Everything ... was a hit, grossing over $ 18 million in the United States alone against

1287-445: A cure-all; at one time, its ads even suggested taking it for "the blahs". Subsequent promotion has taken into consideration that aspirin is a drug that is not tolerated by everyone, and the product is no longer advertised in this fashion. Alka-Seltzer marketed as an antacid no longer contains aspirin (ASA). The original effervescent formula has aspirin as its main active ingredient, and is marketed for pain relief. Though important to

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1404-597: A fencing choreographer. After three years of study with Berghof and Uta Hagen at the HB Studio, Charles Grodin told Wilder about Lee Strasberg 's method acting . Grodin persuaded him to leave the studio and begin studying with Strasberg in his private class. Several months later, Wilder was accepted into the Actors Studio . Feeling that "Jerry Silberman in Macbeth " did not have the right ring to it, he adopted

1521-410: A few days. Cytokines and chemokines promote the migration of neutrophils and macrophages to the site of inflammation. Pathogens, allergens, toxins, burns, and frostbite are some of the typical causes of acute inflammation. Toll-like receptors (TLRs) recognize microbial pathogens. Acute inflammation can be a defensive mechanism to protect tissues against injury. Inflammation lasting 2–6 weeks

1638-421: A guest on The Tonight Show Starring Johnny Carson . Raft told Carson that it took more than 7 hours to tape the 30-second commercial. Raft was enraged by the end of the day, thus making his inmate portrayal that much more convincing for the final editing. The film crew gave Raft his crumpled tin cup, which he showed to Carson and the audience. An animated mid-1960s commercial, animated by R. O. Blechman , shows

1755-416: A hat. Buster Keaton appeared along with the animated Speedy Alka-Seltzer figure in a series of 1950s commercials based on the product slogan, "Relief is just a swallow away." Speedy Alka-Seltzer was voiced by Dick Beals . Paul Margulies (father of actress Julianna Margulies ) created the famous "Plop, plop, fizz, fizz" ad campaign when he worked as a Madison Avenue ad executive. The ubiquitous jingle

1872-404: A man and his own stomach sitting opposite each other in chairs, having an argument moderated by their therapist in a voiceover. The stomach (voiced by Gene Wilder ) accuses the man of purposely trying to irritate it. The man accuses his stomach of complaining too much about the foods he likes. The therapist suggests Alka-Seltzer and that the two must take care of each other. The closing words are of

1989-464: A progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells , and involves simultaneous destruction and healing of the tissue. Inflammation has also been classified as Type 1 and Type 2 based on the type of cytokines and helper T cells (Th1 and Th2) involved. The earliest known reference for the term inflammation is around the early 15th century. The word root comes from Old French inflammation around

2106-465: A relatively flat business, Bayer revived several of the vintage spots. During the race for space in the early 1960s before the Moon landing, there was a commercial with Speedy in a space suit and a jingle with the lyrics "On Man's first trip through space, I only hope that I'm aboard, securely strapped in place. They'll track our ship with radar and telescopes and soon, imagine seeing Speedy Alka-Seltzer on

2223-429: A romantic musical comedy about a brother of Sherlock Holmes . Marty Feldman and Madeline Kahn agreed to participate in the project, and Wilder began writing what became his directorial début, 1975's The Adventure of Sherlock Holmes' Smarter Brother . In 1975, Wilder's agent sent him a script for a film called Super Chief . Wilder accepted, but told the film's producers that he thought the only person who could keep

2340-822: A special benefit performance held at the Westport Country Playhouse to aid families affected by the September 11 attacks . Also in 2001, Wilder donated a collection of scripts, correspondences, documents, photographs, and clipped images to the University of Iowa Libraries . On March 1, 2005, Wilder released his highly personal memoir, Kiss Me Like a Stranger: My Search for Love and Art , an account of his life covering everything from his childhood up to Radner's death. Two years later, in March 2007, Wilder released his first novel, My French Whore , which

2457-406: A specific cell type. Such an approach may limit side effects that are unrelated to the tumor of interest, and may help preserve vital homeostatic functions and developmental processes in the organism. There is some evidence from 2009 to suggest that cancer-related inflammation (CRI) may lead to accumulation of random genetic alterations in cancer cells. In 1863, Rudolf Virchow hypothesized that

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2574-540: A stage name. He chose "Wilder" because it reminded him of Our Town author Thornton Wilder , while "Gene" came from the character Eugene Gant in Thomas Wolfe 's first novel, Look Homeward, Angel . He also liked "Gene" because as a boy, he was impressed by a distant relative, a World War II bomber navigator who was "handsome and looked great in his leather flight jacket". He later said that he could not see Gene Wilder playing Macbeth , either. After joining

2691-403: A systemic response known as anaphylaxis . Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle, leading to signs of muscle inflammation. They may occur in conjunction with other immune disorders, such as systemic sclerosis , and include dermatomyositis , polymyositis , and inclusion body myositis . Due to the central role of leukocytes in

2808-469: A theater director turned amateur detective. Three years later, Wilder guest-starred on two episodes of NBC's Will & Grace , winning a Primetime Emmy Award for Outstanding Guest Actor on a Comedy Series for his role as Mr. Stein, Will Truman 's boss. This ended Wilder's screen career; from 2003 forward, Wilder focused his creative energies on writing novels and stories, as well as painting. Wilder met his first wife, Mary Mercier, while studying at

2925-474: A urethral infection because urethral microbial invasion is the most common cause of urethritis. However, the inflammation–infection distinction is crucial in situations in pathology and medical diagnosis that involve inflammation that is not driven by microbial invasion, such as cases of atherosclerosis , trauma , ischemia , and autoimmune diseases (including type III hypersensitivity ). Biological: Chemical: Psychological: Acute inflammation

3042-608: A vascular phase that occurs first, followed by a cellular phase involving immune cells (more specifically myeloid granulocytes in the acute setting). The vascular component of acute inflammation involves the movement of plasma fluid , containing important proteins such as fibrin and immunoglobulins ( antibodies ), into inflamed tissue. Upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin , as well as eicosanoids such as prostaglandin E2 and leukotriene B4 to remodel

3159-471: A vast variety of human diseases. The immune system is often involved with inflammatory disorders, as demonstrated in both allergic reactions and some myopathies , with many immune system disorders resulting in abnormal inflammation. Non-immune diseases with causal origins in inflammatory processes include cancer, atherosclerosis , and ischemic heart disease . Examples of disorders associated with inflammation include: Atherosclerosis, formerly considered

3276-803: A worse sense of smell during a cold, or having difficulty breathing when bronchitis is present. Loss of function has multiple causes. The process of acute inflammation is initiated by resident immune cells already present in the involved tissue, mainly resident macrophages , dendritic cells , histiocytes , Kupffer cells and mast cells . These cells possess surface receptors known as pattern recognition receptors (PRRs), which recognize (i.e., bind) two subclasses of molecules: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs are compounds that are associated with various pathogens , but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage. At

3393-598: A year sent to me, and maybe there are three good [ones]. That's why I went into writing. It's not that I wouldn't act again. I'd say, 'Give me the script. If it's something wonderful, I'll do it.' But I don't get anything like that." In the 2010s, a still from the movie Willy Wonka & the Chocolate Factory featuring Wilder became a popular Internet meme known as Condescending Wonka . In 2007, Wilder stated, "I'm quietly political. I don't like advertising. Giving money to someone or support, but not getting on

3510-467: Is a generic response, and therefore is considered a mechanism of innate immunity , whereas adaptive immunity is specific to each pathogen. Inflammation is a protective response involving immune cells , blood vessels , and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair. Too little inflammation could lead to progressive tissue destruction by

3627-469: Is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus. It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. Acute inflammation occurs immediately upon injury, lasting only

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3744-775: Is associated with a 30% increased risk of developing major depressive disorder, supporting the link between inflammation and mental health. An allergic reaction, formally known as type 1 hypersensitivity , is the result of an inappropriate immune response triggering inflammation, vasodilation, and nerve irritation. A common example is hay fever , which is caused by a hypersensitive response by mast cells to allergens . Pre-sensitised mast cells respond by degranulating , releasing vasoactive chemicals such as histamine. These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation, production of pro-inflammatory molecules, cytokine release, and recruitment of leukocytes. Severe inflammatory response may mature into

3861-445: Is designated subacute inflammation. Inflammation is characterized by five cardinal signs , (the traditional names of which come from Latin): The first four (classical signs) were described by Celsus ( c.  30 BC –38 AD). Pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings. Acute inflammation of the lung (usually in response to pneumonia ) does not cause pain unless

3978-416: Is mediated by mononuclear cells such as monocytes and lymphocytes . Various leukocytes , particularly neutrophils, are critically involved in the initiation and maintenance of inflammation. These cells must be able to move to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from

4095-400: Is ruined by some comedic trial or another (comedian Ronny Graham dropping the clapperboard). By the commercial's end, Jack has eaten so many meatballs that it's "Alka-Seltzer to the rescue." With his stomach settled, Jack does a perfect take, except that the oven door falls off. The director (off-camera) sighs and says, "OK, let's break for lunch." A 1970 commercial shows a newlywed couple in

4212-426: Is set during World War I . His second novel, The Woman Who Wouldn't , was released in March 2008. In a 2008 Turner Classic Movies special, Role Model: Gene Wilder , where Alec Baldwin interviewed Wilder about his career, Wilder said that he was basically retired from acting for good. "I don't like show business, I realized," he explained. "I like show, but I don't like the business." In 2010, Wilder released

4329-532: The Los Angeles Times , was inspired when he ate too much of the food at a London commercial shoot because "I am a nice Jewish kid from the Bronx, so I ate everything," and when he told his wife "I can't believe I ate the whole thing", she said, "There's your next Alka-Seltzer commercial." A 1971 commercial featured another catch-phrase from Cohen (along with Bob Pasqualina), "Try it, you'll like it!" It

4446-572: The bone marrow may result in abnormal or few leukocytes. Certain drugs or exogenous chemical compounds are known to affect inflammation. Vitamin A deficiency, for example, causes an increase in inflammatory responses, and anti-inflammatory drugs work specifically by inhibiting the enzymes that produce inflammatory eicosanoids . Additionally, certain illicit drugs such as cocaine and ecstasy may exert some of their detrimental effects by activating transcription factors intimately involved with inflammation (e.g. NF-κB ). Inflammation orchestrates

4563-424: The complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis (e.g., burn, trauma). Acute inflammation may be regarded as the first line of defense against injury. Acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators are short-lived and are quickly degraded in the tissue. Hence, acute inflammation begins to cease once

4680-521: The microenvironment around tumours, contributing to proliferation, survival and migration. Cancer cells use selectins , chemokines and their receptors for invasion, migration and metastasis. On the other hand, many cells of the immune system contribute to cancer immunology , suppressing cancer. Molecular intersection between receptors of steroid hormones, which have important effects on cellular development, and transcription factors that play key roles in inflammation, such as NF-κB , may mediate some of

4797-453: The "Plop, plop, fizz, fizz, oh what a relief it is" song in his iconic high, squeaky voice. In the early 1960s, a commercial showing two tablets dropping into a glass of water instead of the usual one caused sales to double. Alka-Seltzer TV ads from the 1960s and 1970s in the US were among the most popular of the 20th century, ranking number 13, according to Advertising Age . To increase sales in

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4914-452: The 14th century, which then comes from Latin inflammatio or inflammationem . Literally, the term relates to the word "flame", as the property of being "set on fire" or "to burn". The term inflammation is not a synonym for infection . Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together in discussion of infection, and

5031-420: The 1988 motion picture The In Crowd , immediately before the movie's first live broadcast of the fictitious "Perry Parker's Dance Party." In an Alka-Seltzer commercial from 1969, an actor named "Jack" (played by Jack Somack ) in a commercial for the fictional product "Magadini's Meatballs" has to eat a meatball and then say "Mamma mia, that's-a spicy meat-a ball-a!" in an ersatz Italian accent. Take after take

5148-667: The Actors Studio, he slowly began to be noticed in the off-Broadway scene, thanks to performances in Sir Arnold Wesker 's Roots and in Graham Greene 's The Complaisant Lover , for which Wilder received the Clarence Derwent Award for "Best Performance by an Actor in a Nonfeatured Role". One of Wilder's early stage credits was playing the socially awkward mental patient Billy Bibbit in

5265-470: The Chocolate Factory (1971). He collaborated with Mel Brooks on the films The Producers (1967), Blazing Saddles (1974) and Young Frankenstein (1974), and with Richard Pryor in the films Silver Streak (1976), Stir Crazy (1980), See No Evil, Hear No Evil (1989) and Another You (1991). He began his career on stage, and made his screen debut in an episode of the TV series The Play of

5382-479: The Chocolate Factory is strange yet comforting, full of narrative detours that don't always work but express the film's uniqueness." The three films Wilder appeared in following The Producers were box office failures: Start the Revolution and Quackser seemed to audiences poor copies of Mel Brooks films, while Willy Wonka & the Chocolate Factory was not a commercial success, although it later gained

5499-691: The Gilda Radner Ovarian Cancer Detection Center in Los Angeles and co-founding Gilda's Club . After his last acting performance in 2003—a guest role on Will & Grace , for which he received a Primetime Emmy Award for Outstanding Guest Actor in a Comedy Series —Wilder turned his attention to writing. He produced a memoir, Kiss Me Like a Stranger (2005) and five other books. Wilder was born Jerome Silberman on June 11, 1933, in Milwaukee , Wisconsin to

5616-650: The HB Studio in New York. Although the couple had not been together long, they married on July 22, 1960. They spent long periods of time apart, eventually divorcing in 1965. A few months later, Wilder began dating Mary Joan Schutz, a friend of his sister. Schutz had a daughter, Katharine, from a previous marriage. When Katharine started calling Wilder "Dad", he decided to do what he felt was "the right thing to do", marrying Schutz on October 27, 1967, and adopting Katharine that same year. Schutz and Wilder separated after seven years of marriage, with Katharine suspecting that Wilder

5733-902: The Marcus Center for the Performing Arts in Milwaukee, on April 9, 1991. In 1994, Wilder starred in the NBC sitcom Something Wilder . The show received poor reviews and lasted only one season. He went back to the small screen in 1999, appearing in three television movies, one of which was the NBC adaptation of Alice in Wonderland . The other two, Murder in a Small Town and The Lady in Question , were mystery movies for A&E TV that were cowritten by Wilder, in which he played

5850-465: The Week in 1961. His first film role was that of a hostage in the 1967 motion picture Bonnie and Clyde . His first major film role was as Leopold Bloom in the 1967 film The Producers , for which he was nominated for an Academy Award for Best Supporting Actor . It was the first in a series of collaborations with writer/director Mel Brooks, including Young Frankenstein , which Wilder co-wrote, garnering

5967-407: The actions of various inflammatory mediators. Vasodilation occurs first at the arteriole level, progressing to the capillary level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of plasma into the tissues, with resultant stasis due to the increase in the concentration of

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6084-461: The bedroom after the woman (played by Alice Playten ) has finished serving her husband (played by Terry Kiser ) a giant dumpling; the implication is that her cooking skills are severely lacking, despite her husband's lament, "I can't believe I ate that whole thing!", the commercial's catchphrase . She lies on the bed in delusional triumph. She offers her beleaguered husband a heart-shaped meatloaf; he disappears to take some Alka-Seltzer. When she hears

6201-909: The blood to the tissues through the blood vessels is known as extravasation and can be broadly divided up into a number of steps: Extravasated neutrophils in the cellular phase come into contact with microbes at the inflamed tissue. Phagocytes express cell-surface endocytic pattern recognition receptors (PRRs) that have affinity and efficacy against non-specific microbe-associated molecular patterns (PAMPs). Most PAMPs that bind to endocytic PRRs and initiate phagocytosis are cell wall components, including complex carbohydrates such as mannans and β- glucans , lipopolysaccharides (LPS), peptidoglycans , and surface proteins. Endocytic PRRs on phagocytes reflect these molecular patterns, with C-type lectin receptors binding to mannans and β-glucans, and scavenger receptors binding to LPS. Upon endocytic PRR binding, actin - myosin cytoskeletal rearrangement adjacent to

6318-419: The body to harmful stimuli, and is achieved by the increased movement of plasma and leukocytes (in particular granulocytes ) from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system , the immune system , and various cells in the injured tissue. Prolonged inflammation, known as chronic inflammation , leads to

6435-403: The book Gilda's Disease with oncologist Steven Piver, sharing personal experiences of Radner's struggle with ovarian cancer. Wilder himself was hospitalized with non-Hodgkin lymphoma in 1999, but confirmed in March 2005 that the cancer was in complete remission following chemotherapy and a stem cell transplant . In October 2001, he read from Charlie and the Chocolate Factory as part of

6552-598: The box office and was not well received by all critics; New York Times critic Renata Adler reviewed the film and described it as "black college humor". In 1969, Wilder relocated to Paris, accepting a leading role in Bud Yorkin 's Start the Revolution Without Me , a comedy that took place during the French Revolution . After shooting ended, Wilder returned to New York, where he read

6669-527: The brand was featured in television commercials supporting the United States Ski Team that included alpine skier Lindsey Vonn and Nordic combined skier Bill Demong . Miniature figures of the Speedy mascot were shown with each. Alka-Seltzer products are sold in nighttime and daytime, or nondrowsy, formulas. The non-drowsy claims have recently been questioned. In 1951, the "Speedy" character

6786-504: The cancer returned and had metastasized. Radner died on May 20, 1989. Wilder later stated, "I always thought she'd pull through." Following Radner's death, Wilder became active in promoting cancer awareness and treatment, helping found the Gilda Radner Ovarian Cancer Detection Center in Los Angeles and co-founding Gilda's Club , a support group to raise awareness of cancer that began in New York City and now has branches throughout

6903-498: The cells within blood – a condition characterized by enlarged vessels packed with cells. Stasis allows leukocytes to marginate (move) along the endothelium , a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the shearing force along the periphery of the vessels moves cells in the blood into the middle of the vessel. * non-exhaustive list The cellular component involves leukocytes , which normally reside in blood and must move into

7020-765: The country. While preparing for his role as a deaf man in See No Evil, Hear No Evil , Wilder met Karen Webb (née Boyer), who was a clinical supervisor for the New York League for the Hard of Hearing. Webb coached him in lip reading . Following Gilda Radner's death, Wilder and Webb reconnected, and on September 8, 1991, they married. The two lived in Stamford, Connecticut , in the 1734 Colonial home that he had shared with Radner. The Wilders spent most of their time painting watercolors , writing, and participating in charitable efforts. In 1998, Wilder collaborated on

7137-454: The critics, nor was their next project, 1986's Haunted Honeymoon , which failed to attract audiences. The Woman in Red did win an Academy Award for Best Original Song for Stevie Wonder 's song " I Just Called to Say I Love You ". TriStar Pictures wanted to produce another film starring Wilder and Pryor, and Wilder agreed to do See No Evil, Hear No Evil only if he were allowed to rewrite

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7254-438: The development and propagation of inflammation, defects in leukocyte functionality often result in a decreased capacity for inflammatory defense with subsequent vulnerability to infection. Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations, digest bacteria ( Chédiak–Higashi syndrome ), or produce microbicides ( chronic granulomatous disease ). In addition, diseases affecting

7371-417: The efficacy of the phagocytic process, enhancing the lysosomal elimination of the infective agent. * non-exhaustive list Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved. Inflammatory abnormalities are a large group of disorders that underlie

7488-574: The end of recruit training , he was assigned to the medical corps and sent to Fort Sam Houston for training. He was then given the opportunity to choose any open post; wanting to stay near New York City to attend acting classes at the HB Studio, he chose to serve as paramedic in the Department of Psychiatry and Neurology at Valley Forge Army Hospital , in Phoenixville, Pennsylvania . In November 1957, his mother died from ovarian cancer . He

7605-430: The factors that promote chronic inflammation. A 2014 study reported that 60% of Americans had at least one chronic inflammatory condition, and 42% had more than one. Common signs and symptoms that develop during chronic inflammation are: As defined, acute inflammation is an immunovascular response to inflammatory stimuli, which can include infection or trauma. This means acute inflammation can be broadly divided into

7722-483: The film from being offensive was Richard Pryor . Pryor accepted the role in the film, which had been renamed Silver Streak , the first film to team Wilder and Pryor. They became Hollywood's first successful interracial movie comedy duo. While filming Silver Streak , Wilder began working on a script for The World's Greatest Lover , inspired by Fellini 's The White Sheik . Wilder wrote, produced, and directed The World's Greatest Lover , which premièred in 1977, but

7839-451: The filming of Hanky Panky ended, Wilder found himself missing Radner, so he called her. The relationship grew, and Radner eventually divorced Smith in 1982. She moved in with Wilder, and the couple married on September 14, 1984, in the south of France. The couple wanted to have children, but Radner suffered miscarriages , and doctors could not determine the problem. After experiencing severe fatigue and suffering from pain in her upper legs on

7956-413: The fizzy noise coming from the bathroom, he quickly covers the glass of dissolving Alka-Seltzer as she wonders aloud if it is raining. Just when he has recovered his well-being, he hears her misreading recipes for dinner the next night: "Marshmallowed meatballs," "medium salad snails," and "pouched (actually poached) oysters". He returns to the bathroom for more Alka-Seltzer. The catchphrase, Howie Cohen told

8073-421: The harmful stimulus (e.g. bacteria) and compromise the survival of the organism. However inflammation can also have negative effects. Too much inflammation, in the form of chronic inflammation, is associated with various diseases, such as hay fever , periodontal disease , atherosclerosis , and osteoarthritis . Inflammation can be classified as acute or chronic . Acute inflammation is the initial response of

8190-505: The idea of one less smile in the world. According to his family, Wilder died while listening to one of his favorite songs, a rendition of " Over the Rainbow " sung by Ella Fitzgerald . Mel Brooks , as a guest on The Tonight Show with Jimmy Fallon , spoke about his grief, stating: "He was such a dear friend. I expected that he would go—but when it happens, it's still tremendous. It's a big shock. I'm still reeling. No more Gene? ... He

8307-400: The inflamed tissue via extravasation to aid in inflammation. Some act as phagocytes , ingesting bacteria, viruses, and cellular debris. Others release enzymatic granules that damage pathogenic invaders. Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response. In general, acute inflammation is mediated by granulocytes , whereas chronic inflammation

8424-483: The inflammation involves the parietal pleura , which does have pain-sensitive nerve endings . Heat and redness are due to increased blood flow at body core temperature to the inflamed site. Swelling is caused by accumulation of fluid. The fifth sign, loss of function , is believed to have been added later by Galen , Thomas Sydenham or Rudolf Virchow . Examples of loss of function include pain that inhibits mobility, severe swelling that prevents movement, having

8541-513: The local vasculature. Macrophages and endothelial cells release nitric oxide . These mediators vasodilate and permeabilize the blood vessels , which results in the net distribution of blood plasma from the vessel into the tissue space. The increased collection of fluid into the tissue causes it to swell ( edema ). This exuded tissue fluid contains various antimicrobial mediators from the plasma such as complement , lysozyme , antibodies , which can immediately deal damage to microbes, and opsonise

8658-511: The microbes in preparation for the cellular phase. If the inflammatory stimulus is a lacerating wound, exuded platelets , coagulants , plasmin and kinins can clot the wounded area using vitamin K-dependent mechanisms and provide haemostasis in the first instance. These clotting mediators also provide a structural staging framework at the inflammatory tissue site in the form of a fibrin lattice – as would construction scaffolding at

8775-453: The moon!" George Raft starred in the 1969 Alka-Seltzer commercial "The Unfinished Lunch". It consisted of Raft incarcerated in a prison lunchroom. He takes a bite of the prison food and recoils. Suddenly he bangs his cup on the steel table. It ripples throughout the room. He starts intoning "Alka-Seltzer, Alka-Seltzer..." Soon, the other hundreds of inmates do the same. The commercial became so popular that several weeks later, Raft appeared as

8892-406: The most critical effects of inflammatory stimuli on cancer cells. This capacity of a mediator of inflammation to influence the effects of steroid hormones in cells is very likely to affect carcinogenesis. On the other hand, due to the modular nature of many steroid hormone receptors, this interaction may offer ways to interfere with cancer progression, through targeting of a specific protein domain in

9009-422: The most successful co-starring vehicle for Mr. Pryor and Mr. Wilder", also acknowledging that "this is not elegant movie making, and not all of the gags are equally clever". After starring as a political cartoonist who falls in love in the 1990 film Funny About Love , Wilder performed in one final movie with Pryor, the 1991 feature Another You , in which Pryor's physical deterioration from multiple sclerosis

9126-488: The onset of an infection, burn, or other injuries, these cells undergo activation (one of the PRRs recognize a PAMP or DAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness ( rubor ) and increased heat ( calor ). Increased permeability of the blood vessels results in an exudation (leakage) of plasma proteins and fluid into

9243-491: The origin of cancer was at sites of chronic inflammation. As of 2012, chronic inflammation was estimated to contribute to approximately 15% to 25% of human cancers. Gene Wilder Gene Wilder (born Jerome Silberman ; June 11, 1933 – August 29, 2016) was an American actor, comedian, writer and filmmaker. He was mainly known for his comedic roles, but also for his portrayal of Willy Wonka in Willy Wonka &

9360-598: The original 1963–64 Broadway adaptation of Ken Kesey 's novel One Flew Over the Cuckoo's Nest opposite star Kirk Douglas . In 1963, Wilder was cast in a leading role in Mother Courage and Her Children , a production starring Anne Bancroft , who introduced Wilder to her boyfriend (and later husband) Mel Brooks . A few months later, Brooks mentioned that he was working on a screenplay called Springtime for Hitler , for which he thought Wilder would be perfect in

9477-672: The original jingle. Speedy was again revived in 2008 when Alka-Seltzer began a series of new commercials featuring him (using a CGI character created by animation director David Hulin to recreate the stop-motion puppetry of the 1950s and 1960s); in these ads, he was voiced by Debi Derryberry . Inflammation Inflammation (from Latin : inflammatio ) is part of the biological response of body tissues to harmful stimuli, such as pathogens , damaged cells, or irritants . The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin calor , dolor , rubor , tumor , and functio laesa ). Inflammation

9594-420: The overall effect of the medication, the aspirin ( acetylsalicylic acid ) is not required to produce the effervescent action of Alka-Seltzer; the effervescence is produced by the baking soda ( sodium bicarbonate ) and citric acid reacting to form sodium citrate and carbon dioxide gas. The product has been extensively advertised since its launch in the United States. It was originally marketed by Mikey Wiseman,

9711-572: The pair an Academy Award nomination for Best Adapted Screenplay . He also starred in Woody Allen 's Everything You Always Wanted to Know About Sex* (*But Were Afraid to Ask) (1972). Wilder directed and wrote several of his own films, including The Woman in Red (1984). With his third wife, Gilda Radner , he starred in three films, the last two of which he also directed. Her 1989 death from ovarian cancer led to his active involvement in promoting cancer awareness and treatment, helping found

9828-410: The pair working together on a script called Traces —which became 1982's Hanky Panky , the film where Wilder met comedian Gilda Radner . Through the remainder of the decade, Wilder and Radner worked on several projects together. After Hanky Panky , Wilder directed his third film, 1984's The Woman in Red , which starred Wilder, Radner, and Kelly LeBrock . The Woman in Red was not well received by

9945-501: The phagolysosomes then kill microbes inside the phagocyte. Phagocytic efficacy can be enhanced by opsonization . Plasma derived complement C3b and antibodies that exude into the inflamed tissue during the vascular phase bind to and coat the microbial antigens. As well as endocytic PRRs, phagocytes also express opsonin receptors Fc receptor and complement receptor 1 (CR1), which bind to antibodies and C3b, respectively. The co-stimulation of endocytic PRR and opsonin receptor increases

10062-492: The plasma membrane occurs in a way that endocytoses the plasma membrane containing the PRR-PAMP complex, and the microbe. Phosphatidylinositol and Vps34 - Vps15 - Beclin1 signalling pathways have been implicated to traffic the endocytosed phagosome to intracellular lysosomes , where fusion of the phagosome and the lysosome produces a phagolysosome. The reactive oxygen species , superoxides and hypochlorite bleach within

10179-503: The role of Leo Bloom . Brooks elicited a promise from Wilder that he would check with him before making any long-term commitments. Months went by, and Wilder toured the country with different theater productions, participated in a televised CBS presentation of Death of a Salesman , and was cast for his first role in a film—a minor role in Arthur Penn 's 1967 Bonnie and Clyde . After three years of not hearing from Brooks, Wilder

10296-399: The script for Quackser Fortune Has a Cousin in the Bronx and immediately called Sidney Glazier , who produced The Producers . Both men began searching for the perfect director for the film. Jean Renoir was the first candidate, but he would not be able to do the film for at least a year, so British-Indian director Waris Hussein was hired. With Margot Kidder co-starring with Wilder, it

10413-644: The script. The studio agreed, and See No Evil, Hear No Evil premiered in May 1989 to mostly negative reviews. Many critics praised Wilder and Pryor, as well as Kevin Spacey 's performance, but they mostly agreed that the script was terrible. Roger Ebert called it "a real dud "; the Deseret Morning News described the film as "stupid", with an "idiotic script" that had a "contrived story" and too many "juvenile gags", while Vincent Canby called it "by far

10530-471: The set of Haunted Honeymoon , Radner sought medical treatment. Following a number of false diagnoses, she was found to have ovarian cancer in October 1986. Over the next year and a half, Radner battled the disease, receiving chemotherapy and radiotherapy treatments. The disease finally went into remission, giving the couple a respite, during which time Wilder filmed See No Evil, Hear No Evil . By May 1989,

10647-399: The sister brand. Alka-Seltzer is a combination of sodium bicarbonate , aspirin , and anhydrous citric acid used for the relief of heartburn, acid indigestion, and stomach aches. Alka-Seltzer is sold in foil packets, each containing two tablets. Prior to 1984, it was also available stacked in cylindrical glass bottles. It is available in many different flavors. It was once marketed as

10764-482: The stimulus has been removed. Chronic inflammation is inflammation that lasts for months or years. Macrophages, lymphocytes , and plasma cells predominate in chronic inflammation, in contrast to the neutrophils that predominate in acute inflammation. Diabetes , cardiovascular disease , allergies , and chronic obstructive pulmonary disease (COPD) are examples of diseases mediated by chronic inflammation. Obesity , smoking, stress and insufficient diet are some of

10881-428: The stomach saying to the man: "Well, I'll try — if you will." Alka-Seltzer had a series of commercials during the mid-1960s that used a song called " No Matter What Shape (Your Stomach's In) ". A different version was recorded by The T-Bones and was released as a single, which became a hit in 1966. The ads featured only the midsections (no faces) of people of all shapes and sizes. A clip of the ad can be seen briefly in

10998-556: The teacher said that if he was still interested at age 13, he would take Wilder on as a student. The day after Wilder turned 13, he called the teacher, who accepted him; Wilder studied with him for two years. When Jeanne Silberman felt that her son's potential was not being fully realized in Wisconsin, she sent him to Black-Foxe , a military institute in Hollywood, where he was bullied and sexually assaulted , primarily because he

11115-410: The tissue ( edema ), which manifests itself as swelling ( tumor ). Some of the released mediators such as bradykinin increase the sensitivity to pain ( hyperalgesia , dolor ). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly neutrophils and macrophages , to flow out of the blood vessels (extravasation) and into the tissue. The neutrophils migrate along

11232-771: The treatment of atherosclerosis have focused on addressing inflammation directly. New anti-inflammatory drugs, such as monoclonal antibodies targeting IL-1β, have been studied in large clinical trials, showing promising results in reducing cardiovascular events. These drugs offer a potential new avenue for treatment, particularly for patients who do not respond adequately to statins. However, concerns about long-term safety and cost remain significant barriers to widespread adoption. Inflammatory processes can be triggered by negative cognition or their consequences, such as stress, violence, or deprivation. Negative cognition may therefore contribute to inflammation, which in turn can lead to depression. A 2019 meta-analysis found that chronic inflammation

11349-1042: The underlying mechanisms of atherogenesis . Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to people. For instance, elevation in markers of inflammation predicts outcomes of people with acute coronary syndromes , independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein , prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors, such as LDL levels. Moreover, certain treatments that reduce coronary risk also limit inflammation. Notably, lipid-lowering medications such as statins have shown anti-inflammatory effects, which may contribute to their efficacy beyond just lowering LDL levels. This emerging understanding of inflammation’s role in atherosclerosis has had significant clinical implications, influencing both risk stratification and therapeutic strategies. Recent developments in

11466-519: The word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation , on the other hand, describes just the body's immunovascular response, regardless of cause. But, because the two are often correlated , words ending in the suffix -itis (which means inflammation) are sometimes informally described as referring to infection: for example, the word urethritis strictly means only "urethral inflammation", but clinical health care providers usually discuss urethritis as

11583-399: Was Roald Dahl's original choice to play Willy Wonka. Peter Sellers even begged Dahl for the role. The film was not a big success on its opening weekend, although it received positive reviews from critics such as Roger Ebert , who compared it to The Wizard of Oz . The film currently holds a 92% "Fresh" rating on Rotten Tomatoes with the critical consensus stating " Willy Wonka &

11700-573: Was a critical failure. The Frisco Kid (1979) was Wilder's next project. The film was to star John Wayne , but he dropped out and was replaced by Harrison Ford , then an up-and-coming actor. For some reason when you pair him [Pryor] with Gene Wilder, they make a particular kind of magic together. And, together, they are probably the funniest pair that's ever been on screen. —Sidney Poitier In 1980, Wilder teamed up again with Richard Pryor in Stir Crazy , directed by Sidney Poitier . Pryor

11817-800: Was accepted at the Bristol Old Vic Theatre School in Bristol, England. After six months of studying fencing, Wilder became the first freshman to win the All-School Fencing Championship. Desiring to study Stanislavski's system , he returned to the US, living with his sister and her family in Queens , New York City. He enrolled at the HB Studio . Wilder was drafted into the Army on September 10, 1956. At

11934-515: Was called for a reading with Zero Mostel , who was to be the star of Springtime for Hitler and had approval of his co-star. Mostel approved, and Wilder was cast for his first leading role in a feature film, 1967's The Producers . The Producers eventually became a cult comedy classic , with Mel Brooks winning an Academy Award for Best Original Screenplay and Wilder being nominated for an Academy Award for Best Supporting Actor . Nevertheless, Brooks' first directorial effort did not do well at

12051-485: Was clearly noticeable. It was Pryor's last starring role in a film (he appeared in a few cameos before he died in 2005) and also marked Wilder's last appearance in a feature film. His last two movies were not financially successful. Wilder's remaining work consisted of television movies and guest appearances in TV shows. Wilder was inducted into the Wisconsin Performing Arts Hall of Fame, at

12168-602: Was composed by Tom Dawes, a former member of The Cyrkle . The slogan was altered to "Plink, plink, fizz" in the United Kingdom. Speedy was revived for a "Plop, plop, fizz, fizz" song spot in 1976. Sammy Davis Jr. , recorded two versions of the "Plop Plop Fizz Fizz" jingle in 1978, one of which (the "big band" version) was featured on a television commercial. Both the big band and rock versions had additional lyrics (with at least one verse unique to each song) written by Tom Dawes, former lead singer of The Cyrkle who wrote

12285-665: Was discharged from the army a year later and returned to New York. A scholarship to the HB Studio allowed him to become a full-time student. At first living on unemployment insurance and some savings, he later supported himself with odd jobs such as a limousine driver and fencing instructor. Wilder's first professional acting job was in Cambridge, Massachusetts , where he played the Second Officer in Herbert Berghof 's production of Twelfth Night . He also served as

12402-442: Was done to not sadden fans of Willy Wonka & the Chocolate Factory , stating: The decision to wait until this time to disclose his condition wasn't vanity, but more so that the countless young children that would smile or call out to him 'there's Willy Wonka ,' would not have to be then exposed to an adult referencing illness or trouble and causing delight to travel to worry, disappointment, or confusion. He simply couldn't bear

12519-638: Was filmed on location in Dublin, and at the nearby Ardmore Studios , in August and September 1969. In 1971, Wilder auditioned to play Willy Wonka in Mel Stuart 's film adaptation of Roald Dahl 's Charlie and the Chocolate Factory . After reciting some lines, director Mel Stuart immediately offered him the role. Before Wilder was officially cast for the role, Fred Astaire , Joel Grey , Ron Moody , and Jon Pertwee were all considered. Spike Milligan

12636-451: Was having an affair with his Young Frankenstein co-star, Madeline Kahn . After the divorce, he briefly dated his other Frankenstein co-star, Teri Garr . Wilder eventually became estranged from Katharine. Wilder met Saturday Night Live actress Gilda Radner on August 13, 1981, while filming Sidney Poitier's Hanky Panky . Radner was married to guitarist G. E. Smith at the time, but she and Wilder became inseparable friends. When

12753-481: Was inspired to write a scene that takes place at Transylvania Station, where Igor and Frederick meet for the first time. The scene was later included in the film almost verbatim. Medavoy liked the idea and called Brooks, asking him to direct. Brooks was not convinced, but having spent four years working on two box-office failures, he decided to accept. While working on the Young Frankenstein script, Wilder

12870-516: Was introduced. The character was conceived by creative directors Bob Watkins and Chuck Tennant of the Wade Advertising agency and designed by illustrator Wally Wood . Originally named Sparky, the name was changed to Speedy by sales manager Perry L. Shupert to align with that year's promotional theme, "Speedy Relief". Speedy appeared in over 200 TV commercials between 1954 and 1964. His body was one Alka-Seltzer tablet, while he wore another as

12987-626: Was offered the part of the Fox in the musical film adaptation of Antoine de Saint-Exupéry 's classic book, The Little Prince . When filming was about to begin in London, Wilder received an urgent call from Brooks, who was filming Blazing Saddles , offering Wilder the role of the "Waco Kid" after Dan Dailey dropped out at the last minute, while Gig Young became too ill to continue. Wilder shot his scenes for Blazing Saddles and immediately afterwards filmed The Little Prince . After Young Frankenstein

13104-679: Was raised Jewish, but he held only the Golden Rule as his philosophy. In a book published in 2005, he stated, "I have no other religion. I feel very Jewish and I feel very grateful to be Jewish. But I don't believe in God or anything to do with the Jewish religion." Wilder studied Communication and Theatre Arts at the University of Iowa , where he was a member of the Alpha Epsilon Pi fraternity. Following his 1955 graduation from Iowa, he

13221-402: Was remade with Kathy Griffin in 2006. In 1972, an actor (Milt Moss) spent the commercial moaning, "I can't believe I ate that who-o-o-o-o-ole thing" while his wife (Lynn Whinic) made sarcastic comments and finally advised him to take some Alka-Seltzer. In 2005, this ad was also remade, featuring Peter Boyle and Doris Roberts from the 1996–2005 TV sitcom Everybody Loves Raymond . In 2009,

13338-504: Was struggling with a severe cocaine addiction , and filming became difficult, but once the film premiered, it became an international success. New York magazine listed "Skip Donahue" (Wilder) and "Harry Monroe" (Pryor) as number nine on their 2007 list of "The Fifteen Most Dynamic Duos in Pop Culture History", and the film has often appeared in "best comedy" lists and rankings. Poitier and Wilder became friends, with

13455-416: Was such a wonderful part of my life." Various celebrities shared their grief for Wilder on Twitter such as Carl Reiner , Albert Brooks , Billy Crystal , Julia Louis-Dreyfus , and Russell Crowe . James Corden gave a tribute to Wilder on his show The Late Late Show with James Corden saying "He was just a magical person, and he made everybody around him feel this incredible feeling of joy." Wilder

13572-455: Was the only Jewish boy in the school, according to his own account. After an unsuccessful short stay at Black-Foxe, Wilder returned home and became increasingly involved with the local theater community. He performed for the first time in front of a paying audience at age 15, as Balthasar ( Romeo 's servant) in a production of Shakespeare 's Romeo and Juliet . Gene Wilder graduated from Washington High School in Milwaukee in 1951. Wilder

13689-549: Was written, the rights were to be sold to Columbia Pictures , but after having trouble agreeing on the budget, Wilder, Brooks, and producer Michael Gruskoff went with 20th Century Fox , where both Brooks and Wilder had to sign five-year contracts. Young Frankenstein was a commercial success, with Wilder and Brooks receiving Best Adapted Screenplay nominations at the 1975 Oscars , losing to Francis Coppola and Mario Puzo for their adaptation of The Godfather Part II . While filming Young Frankenstein , Wilder had an idea for

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