Biomedical subjects

K J Young

Publications and source records attributed to K J Young.

18 recordsLinked to original sources

PubMed2003

Infusion of in vitro-generated DN T regulatory cells induces permanent cardiac allograft survival in mice.

Previously, we have demonstrated that pretransplant donor lymphocyte infusion (DLI) can activate recipient-derived CD3+CD4-CD8- double negative T regulatory (DN Tr) cells which have a potent immune regulatory function in vitro and in vivo. Here we studied the regulatory ability of DN T cell clones generated from the spleens of nai;ve anti-L(d) transgenic TCR+ (2C x dm2)F1 mice. We were able to identify subsets of DN T cell clones that were able to kill anti-Ld CD8+ T cells, and therefore had regulatory properties, and DN T cells with no regulatory properties. Next, we investigated the ability of these in vitro generated DN T cell clones to enhance cardiac allograft survival. (2C x dm2)F1 transgenic mice were infused with either regulatory or non-regulatory DN T cell clones, or left untreated one day before receiving an Ld-mismatched cardiac grafts from (C57BL/6 x Balb/c)F1 mice. Injection of non-regulatory DN T clone cells did not prolong cardiac graft survival in (2C x dm2)F1 mice when compare to untreated controls. In contrast, all of the cardiac grafts survived more than 100 days in mice that received DN Tr clone cells prior to transplantation. These results demonstrate that DN Tr cells can be generated in vitro and protect cardiac allograft from rejection when infused into recipients prior to transplantation. They also suggest that DN Tr cells may provide a novel therapy for the treatment of allograft rejection.

Animals↗

PubMed2000

Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression.

Despite increasing evidence for the existence of antigen-specific regulatory T cells, the mechanisms underlying suppression remain unclear. In this study we have identified and cloned a novel subset of antigen-specific regulatory T cells and demonstrated that these T cells possess a unique combination of cell surface markers and array of cytokines. The regulatory T cells are able to inhibit the function of T cells carrying the same T-cell receptor specificity and prevent skin allograft rejection in an antigen-specific, dose-dependent manner. The regulatory T cells are able to acquire alloantigen from antigen-presenting cells, present the alloantigen to activated syngeneic CD8+ T cells and then send death signals to CD8+ T cells. These findings provide a novel mechanism of regulatory T-cell-mediated, antigen-specific suppression.

Animals↗

PubMed2000

The legacy of the radiology residency of the Los Angeles College of chiropractic since 1978.

The radiology residence of the Los Angeles College of Chiropractic (LACC) has produced thirty-four graduates since being completely reworked in 1978 by Joseph W. Howe, D.C., D.A.C.B.R. A residency did exist before he arrived, having left the department chair position at National College of Chiropractic, but it was not very strong. Howe upgraded facilities, created opportunities for residents to study with some of the most eminent radiologists in the world and expanded the program to include up to six residents at any one time. The graduates of this program have had a profound effect on the profession, having taken positions in teaching, college administration, private clinical practice, private radiology, practice, and combinations thereof. Combined, they have published several books and book chapters and hundreds of papers in scholarly journals and trade publications

Chiropractic↗

PubMed1999

The role of essential pyrimidines in the hairpin ribozyme-catalysed reaction.

The hairpin ribozyme is an example of a small catalytic RNA that catalyses the endonucleolytic transesterification of RNA in a highly sequence-specific manner. We have utilised chemical synthesis of RNA to create mutants of the hairpin ribozyme in which a nucleoside analogue replaces one of the essential pyrimidines in the ribozyme. Individual pyrimidine nucleosides were substituted by 4-thiouridine, O4-methyluridine, O2-methyluridine or 2-pyrimidinone-1-beta-d-riboside. To facilitate the synthesis of oligoribonucleotides containing 4-thiouridine, we have devised a new synthetic route to the key intermediate 5'-O-(4, 4'-dimethoxytrityl)-2'-O-tert-butyldimethylsilyl-S-cyanoethyl-4-thiou ridine. The ability of the modified ribozymes to support catalysis was studied and the steady-state kinetic parameters were determined for each mutant. The range of analogues used in this study allows the important functional groups of the essential pyrimidines to be identified. The results demonstrate that each pyrimidine (U41, U42 and C25) plays an important role in hairpin ribozyme catalysis. The findings are discussed in terms of the various models that have been proposed for loop B of the hairpin ribozyme.

Kinetics↗

PubMed1999

Intervention studies on cancer.

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Clinical Trials as Topic↗

PubMed1999

Joseph W. Howe, D.C., D.A.C.B.R. and the development of modern chiropractic radiology.

Born in Galeton, Pennsylvania, on 27 May 1930, Joseph W. Howe has been extremely influential raising the educational standards for radiology in chiropractic. After receiving his D.C. from Palmer in 1952, he worked in private practice in Pennsylvania until being drafted into the Army, where he worked as a radiologic technician. After returning to civilian life and his practice, he attended many seminars and lectures on the subject, including one in 1958, taught by Roland Kissinger, D.C. at the National College of Chiropractic (NCC), the first postgraduate course in chiropractic roentgenology ever administered by a college. Howe then took and passed the second exam given by the American Board of Chiropractic Roentgenologists and was awarded certificate number eight in 1959. He helped to form the American Chiropractic College of Radiology and became its first Radiological Health Consultant. In 1968, he joined the Associates Diagnostic and Research Center (ADRC) in Tallmadge, Ohio, where he was able to concentrate on research and establish an off-campus facility for radiology residents of NCC. During this time Howe also lent his expertise to the Houston Conference on Spinal Manipulation. However, financial difficulties with the Center led Howe to leave, and accept a full time position teaching at NCC. Howe ultimately found himself too involved with administrative duties and not enough with the radiology that he loved, so he moved his family across the country in order to accept the radiology department chair at Los Angeles College of Chiropractic (LACC) in 1978. There he was given freedom to build the department to his high standards, and it retains the strongest residency in the profession, with up to six residents at any one time and links to prestigious radiologists like Donald Resnick, M.D. and Steve Rothman, M.D. Officially, Howe retired in 1998, but he still occasionally teaches residents and the Westwood-based radiology practice that he donated to LACC continues, run by the radiology faculty.

Chiropractic↗

PubMed1998

Michael A. Giammarino, D.C., D.A.C.B.R.: student, teacher, leader.

Born in Brooklyn in 1909, Michael A. Giammarino was one of the first chiropractic radiologists. After receiving his D.C. from Palmer in 1932, he worked in private practice in Brooklyn for six years. However, chiropractic was not licensed in New York so he moved to Coatesville, Pennsylvania, where he ran a successful private practice until his retirement in 1985. During that time, he became interested in radiology and attended many seminars and lectures on the subject, including one in 1946, taught by Waldo G. Poehner, D.C., the first postgraduate course in chiropractic roentgenology ever given. Poehner surprised him at the next convention of the National Chiropractic Association by nominating him for the position of vice-president of the Council on Roentgenology. Giammarino then became involved in the creation of the certification program in roentgenology, which evolved into today's Diplomate of the American Chiropractic Board of Radiology. Giammarino is a past-president of the Board as well as the Pennsylvania Licensed Chiropractors' Association. In addition to these activities, he taught many courses in radiology and undertook an extensive radiographic study of scoliosis in identical twins. He still lives in Coatesville and is very active in the community.

Chiropractic↗

PubMed1997

Metal ions play a passive role in the hairpin ribozyme catalysed reaction.

The hairpin ribozyme is an example of a small catalytic RNA which catalyses the endonucleolytic transesterification of RNA in a highly sequence-specific manner. The hairpin ribozyme, in common with all other small ribozymes such as the hammerhead, requires the presence of a divalent metal ion co-factor (typically magnesium) for the reaction to take place. To investigate the role of magnesium ions in the hairpin catalysed reaction we have synthesised two epimeric modified substrates in which a phosphorothioate replaces the scissile phosphodiester bond. Previously, Burke and co-workers have reported that no thio-effect is observed with the Rp-phosphorothioate isomer. We observe the absence of a thio-effect with both diastereomeric phosphorothioate hairpin substrates. Furthermore we report that inert cobalt (III) complexes are capable of supporting the hairpin ribozyme reaction, with a similar efficiency to Mg2+,even in the presence of EDTA. Variation of the net charge on the inert cobalt complex does not change the observed rate of reaction. These results suggest that metal ions play a passive role in the hairpin ribozyme catalysed reaction and are probably required for structural purposes only. This places the hairpin ribozyme in a different mechanistic class to other small ribozymes such as the hammerhead.

Base Sequence↗

PubMed1984