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James R. Leininger grew up in Indiana and Florida. He received a B.A. in 1965 and an M.D. in 1969, both from Indiana University. From 1969 to 1971, he did an internship at the University of Miami Medical School. In 1971-1972, he took post-graduate courses at the Center for Disease Control in Atlanta, Georgia, the Brooke Army Medical Center in San Antonio, Texas, the Walter Reed Army Institute of Research in Washington, D.C., and Fort Sam Houston, where he lectured. In 1972-1973, he taught at the University of Texas Medical School. He then settled in San Antonio.
In 1976, he founded Kinetic Concepts. He now served as Chairman Emeritus on the Board of Directors. In 1991, he formed MedCare Investment Funds, a private venture investment firm. He also co-founded the Renal Care Group. In 1994, he co-founded ATX Technologies, and has served on the Board of Directors since then. From 1975 to 1986, he also served as director of the Emergency Department of the Baptist Hospital System in San Antonio. He also sits on the Board of Directors of BioNumerik Pharmaceuticals and Spurs Sports & Entertainment. He has also invested in Texas real estate, and in food companies such as Promised Land Foods, Sunday House Foods, Seafood Wholesalers of Houston and Plantation Seafood Co. He also owns a direct mail firm, Focus Direct Inc., and a television station, Mission City Television Inc. A basketball fan, he is a part-owner of the San Antonio Spurs. From 1985 to 1991, he sat on the Board of Directors of the Texas Commerce Bank. He is a member of the American Medical Association, the Texas Medical Association, and the Institute of American Entrepreneurs. In 2007, he was inducted into the Texas Business Hall of Fame.
In 1988, he founded Texans for Justice, and he supported Thomas R. Phillips's campaign. He is the founder of the Texas Public Policy Foundation. He also controls Texans for Governmental Integrity. He also made donations to George W. Bush when he was Governor, and to the Republican Party of Texas. He has made significant donations to Texas Governor Rick Perry.
He is a devout Christian, and he has been described as an extremist, a label he himself describes as "sad". He sits on the Board of Trustees of Patrick Henry College. He is a proponent of school vouchers, and he started CEO San Antonio to give vouchers to children from modest backgrounds. He also sits on the Board of Directors of CEO America, another school voucher organization. He is a former Board member of the Carver Academy. He owns the copyright for The Beginner's Bible. In 1997, it was reported he had donated $1.5 million to Vanderbilt University, $3 million to the University of Miami, and $300,000 for diabetes research to the University of Texas Medical Center. He has also made donations to Boy Scouts of America, Habitat for Humanity, the American Red Cross, the Mental Health Association, the Young Men's Christian Association, The Miracle Foundation, as well as orphanages in India, Romania, Central America, Haiti, Ukraine, Russia, Myanmar, Thailand, and thirteen countries in Africa. He is married with four children and five grandchildren.