TCR-independent pathways mediate the effects of antigen dose and altered peptide ligands on Th cell polarization

We examined the role of the peptide/MHC ligand in CD4+ T cell differentiation into Th1 or Th2 cells using a TCR alphabeta transgenic mouse specific for hemoglobin (Hb)(64-76)/I-Ek. We identified two altered peptide ligands of Hb(64-76) that retain strong agonist activity but, at a given dose, induce cytokine patterns distinct from the Hb(64-76) peptide. The ability of these peptides to produce distinct cytokine patterns at identical doses is not due to an intrinsic qualitative property. Each peptide can induce Th2 cytokines at low concentrations and Th1 cytokines at high concentrations and has a unique range of concentrations at which these distinct effects occur. The pattern of cytokines produced from limiting dilution of naive T cells demonstrated that the potential to develop an individual Th1 or Th2 cell is stochastic, independent of Ag dose. We propose that the basis for the observed effects on the Th1/Th2 balance shown by the altered peptide ligands and the amount of Ag dose involves the modification of soluble factors in bulk cultures that are the driving force that polarize the population to either a Th1 or Th2 phenotype.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.     

Effect of sulfamethazine on sexual precocity and neuropeptide Y neurons within the tuberoinfundibular region of the chick brain

A hitherto ignored microvillous cell type, distinct from microvillous supporting cells and other microvillous cell types, was encountered in olfactory and respiratory epithelia of nasal turbinates of rat fetuses, near the transition between these two epithelia. The apex of the cell resembles the apices of vestibular hair cells. The cell has a cone-shaped bundle of microvilli, resembling the complex bundle of hair-cell stereocilia, accompanied by a cilium. Therefore we called this cell type the nasal hair cell. Cilium and microvilli seemed adhered. Cell numbers were very low, up to about 5 per turbinate. The cell's appearance is precocious compared to that of olfactory receptor and supporting cells. Also, while the apices of olfactory receptor and supporting cells and of ciliated respiratory cells underwent major morphological maturation during the developmental period from embryonic day 16 to day 21, the apical structures of the nasal hair cell only changed marginally from embryonic day 16, when they were first seen, through to at least embryonic day 21. The cell's location and precociously mature appearance suggests that it plays a special role in the development of nasal epithelia.     

Perioperative management of the pediatric patient

Children are not just small adults. Perioperative nurses working with pediatric patients plan nursing interventions based on established principles of perioperative practice as well as incorporating concepts of growth and development relating to the child. A thorough assessment of the pediatric patient prior to surgery enables the perioperative nurse to plan for the surgical procedure, modifying as need be for the individual patient's specific needs. With adequate preparation, communication, and emotional support, the pediatric surgical experience can be positive for the child, parents, and perioperative team.     

Vaccination for experimental gliomas using GM-CSF-transduced glioma cells

Within the pituitary, folliculostellate (FS) cells are considered to regulate the intercellular communication between endocrine cells by paracrine mechanisms. One of the possible paracrine factors involved, could be interleukin-6 (IL-6) which is produced by these cells. Since IL-6 has been shown to be a growth factor of pituitary cells, we have determined whether IL-6 can also influence FS cell proliferation. To test this, a FS cell-like mouse pituitary cell line (TtT/GF cells) was used that exhibits most characteristics of normal FS cells. Under serum-free conditions the proliferation of TtT/GF cells is critically dependent on the initial seeding density: cells seeded at low density do not grow at all whereas cells seeded at high density proliferate with maximal doubling times of 34 hrs. Mouse IL-6 (mIL-6) stimulated only low density cell cultures in a dose and time dependent manner. For cells seeded at high density, exogenously added IL-6 may have failed to stimulate growth because of endogenously produced mIL-6. Conditioned medium from TtT/GF cells, in which mIL-6 concentrations up to 1017 pg/ml were measured, stimulated the proliferation of TtT/GF cells, indicating an autocrine growth stimulatory mechanism. A neutralizing mIL-6 antibody partially suppressed the growth of TtT/GF cells seeded at high density and partially reduced the growth stimulatory activity of TtT/GF conditioned medium. Thus, IL-6 is one but not the only factor that is involved in the autocrine growth stimulatory loop. The relevance of this mechanism for normal FS cells and its physiological consequence needs to be elucidated.     

Flocking hip joint endoprosthesis

The author indicates the similarity of a human tooth and an endoprosthesis in their action, which is the basis for developing a procedure of endoprosthesis and designing an endoprosthesis with dumping elements. The procedure has been developed during a long-term surgical experiment by examining the results by the following techniques: X-ray, bed testing, light and scanning electron microscope. Experimental results are convincing. For coating the prostheses, polytetrafluoroethylene velour is used in the experiment, but cauflene, the material of the same kind polytetrafluoroethylene, is employed in the clinical setting. The experiments yielded two inventions patented in the Russian Federation. This direction in their development seems to be fruitful in preventing the aseptic endoprosthetic instability that is the most common and severe complication after endoprosthesis and requires most frequently resurgery.     

Healthy aging. A women''s issue

In this thesis, Korean prisoners' health behavior and the characteristics of their medical utilization were surveyed and analysed. Because prisoners are inclined to be mediators of communicable diseases or unhealthy behaviors between prison institution and the outside world, health care for prisoners is directly related to the national population. Data were collected through a self-administered survey of 5 Korean prisons out of a total of 38 correctional facilities and analysed in accordance with a causal model based on a path frame, by serial multiple regressions on health behavior, health status, and medical utilization, etc. According to the survey analysis, while prisoners were generally concerned with their health much more than they were before imprisonment, they perceived that their health status had deteriorated after imprisonment, and that their need for health services was increasing gradually during their time in prison. In the path analysis on the causal relations among variables related to the prisoners' health status and medical utilization, the prisoners' characteristics affected their health concern and health behavior, and subsequently affected their health status and medical utilization, respectively. To sum up these exploratory studies on prisoners' health behavior and health service utilization, some efforts to organize a health care system embracing the correctional institution and health care administration should be made on the level of establishing a health care delivery system for special social groups like prisoners.     

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry

BACKGROUND: As of May 1, 1995, the National Marrow Donor Program had a donor registry consisting of over 1.35 million HLA-typed volunteers recruited from most major cities and states in the United States. This registry represents the largest single HLA-typed pool of normal individuals in the world. METHODS: We analyzed the HLA-A, -B, -DR locus phenotypes of the National Marrow Donor Program donors in order to estimate gene and haplotype frequencies for major racial groups of the United States: Caucasian American, Asian American, African American, Latin American, and Native American. The large size of the database allowed us to calculate the frequencies of relatively rare antigens and haplotypes with more accuracy than previous studies. RESULTS: We observed 89,522 distinguishable HLA-A, -B phenotypes in 1,351,260 HLA-A, -B-typed donors and 302,867 distinguishable HLA-A, -B, -DR phenotypes in 406,503 HLA-A, -B, -DR-typed donors. Gene and haplotype frequencies differed remarkably among the five racial groups, with African Americans and Asian Americans having a large number of haplotypes that were specific to their racial groups, whereas Caucasian Americans, Latin Americans, and Native Americans shared a number of common haplotypes. CONCLUSIONS: These data represent an important resource for investigators in the fields of transplantation and population genetics. The gene and haplotype frequencies can be used to aid clinicians in advising patients about the probability of finding a match within a specific ethnic group, or to determine donor recruitment goals and strategies. The information is also a valuable resource for individuals who are interested in population genetics, selection and evolution of polymorphic human genes, and HLA-disease association.