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Dendritic cells: regulators of alloimmunity and opportunities for tolerance induction.

Dendritic cells (DCs) are uniquely well-equipped antigen-presenting cells (APCs) regarded classically as sentinels of the immune response, which induce and regulate T-cell reactivity. They play critical roles in central tolerance and in the maintenance of peripheral tolerance in the normal steady state. Following cell or organ transplantation, DCs present antigen to T cells via the direct or indirect pathways of allorecognition. These functions of DCs set in train the rejection response, but they also serve as potential targets for suppression of alloimmune reactivity and promotion of tolerance induction. Much evidence from various model systems now indicates that DCs can induce specific T-cell tolerance. Although underlying mechanisms have not been fully elucidated, the capacity to induce T-regulatory cells may be an important property of tolerogenic or regulatory DCs. Efforts to generate "designer" DCs with tolerogenic properties in the laboratory using specific cytokines, immunologic or pharmacologic reagents, or genetic engineering approaches have already met with some success. Alternatively, targeting of DCs in vivo (e.g. by infusion of apoptotic allogeneic cells) to take advantage of their inherent tolerogenicity has also demonstrated exciting potential. The remarkable heterogeneity and plasticity of these important APCs present additional challenges to optimizing DC-based therapies that may lead to improved tolerance-enhancing strategies in the clinic.

Animals↗

[The humoral immunity indices of rhesus monkeys under the action of extreme factors in space flight].

Some features of nonspecific resistance of rhesus monkeys (G and A immunoglobulins and C3 complement component) are studied. Standards of IgG, IgA and C3 complement component in healthy rhesus monkeys are determined. The changes in the parameters of nonspecific resistance of the animals in all stages of their preflight training and shortly after flight experiment are examined. These alterations were appeared first of all as an increase in IgA level.

Animals↗

Survey on the current status of novel cancer drug therapies for gynecological cancers in Japan: a nationwide survey by the Japan Society of Obstetrics and Gynecology (JSOG).

OBJECTIVE: To characterize real-world implementation of novel therapies in gynecological oncology in Japan and identify actionable gaps through a nationwide survey. METHODS: A cross-sectional questionnaire was distributed to Japan Society of Obstetrics and Gynecology-affiliated institutions. The items covered institution characteristics; use of poly (ADP-ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors (ICIs), kinase inhibitors, and antibody-based agents; local adverse event (AE) manuals; availability of expert panels and immune-related adverse event (irAE) teams; and perceptions of educational sufficiency. RESULTS: Valid responses were obtained from 245 institutions, spanning universities, cancer centers, and general hospitals. Most institutions reported the routine use of PARP inhibitors, ICIs, kinase inhibitors, and antibody drugs. However, only 40.4% of institutions had an in-hospital irAE management team, 57.1% had an AE/irAE manual, and 31.0% and 12.2% considered prior educational opportunities sufficient for physicians and nurses/other medical staff, respectively. High-volume institutions and academic centers were significantly more likely to have medical oncology support, expert-panel access, irAE teams, manuals, and higher self-rated evidence-based management capacity. The majority favored e-learning and society-led case conferences, and 76.3% supported the development of drug therapy subspecialties in gynecologic oncology. CONCLUSION: Innovative drug modalities are widely implemented across Japanese gynecological oncology services. However, critical gaps persist in multidisciplinary irAE management, standardized manuals, and practical education. Coordinated society-led programs to expand irAE teams, streamline companion diagnostics, disseminate ready-to-use algorithms, and provide credential-targeted training may enhance safety, equity, and evidence-concordant care nationwide.

Immune Checkpoint Inhibitors↗

The effects of high-intensity intermittent exercise on the plasma concentrations of glutamine and organic acids.

Glutamine is an essential substrate for the proper functioning of cells of the immune system. Falls in plasma glutamine concentration after exercise may have deleterious consequences for immune cell function and render the individual more susceptible to infection. The purpose of the present study was to examine changes in plasma glutamine concentration (measured using a validated enzymatic spectrophotometric method) following an acute bout of intermittent high-intensity exercise. Eight well-trained male games players took part in the study. Subjects reported to the laboratory following an overnight fast and performed a 1-h cycle exercise task consisting of 20 1-min periods at 100% maximal O2 consumption (VO2max) each separated by 2 min of recovery at 30% VO2max. Venous blood samples were taken before exercise and at 5 min, 1 h, 2.5 h, 5 h and 24 h post-exercise. Glutamine was measured by enzymatic spectrophotometric determination of the ammonia concentration before and after treatment of the plasma with glutaminase (EC 3.5.1.2). Plasma glutamine concentration did not fall in the immediate post-exercise period [pre-exercise 681 (23) microM compared with 663 (46) microM at 5 min post-exercise, mean (SEM)], but fell to 572 (35) microM at 5 h post-exercise (P < 0.05 compared with pre-exercise). Plasma lactate concentration rose to 8.8 (1.0) mM at the end of exercise and fell to 1.8 (0.4) mM at 1 h post-exercise, but plasma concentrations of free fatty acids and beta-hydroxybutyrate both rose substantially in the post-exercise period (to 240% and 400% of pre-exercise levels, respectively). The circulating leucocyte count increased significantly during exercise (P < 0.01), continued to increase in the hours following exercise and peaked at 2.5 h post-exercise (mainly due to a neutrophilia). The fall in the plasma glutamine concentration at 5 h post-exercise could be due to increased renal uptake of glutamine, which generally occurs in conditions of metabolic acidosis or due to a greater removal of glutamine from the plasma resulting from the elevated circulating leucocyte count.

3-Hydroxybutyric Acid↗

A national program for control of acute respiratory tract infections: the Philippine experience.

Maturing programs on child immunization and diarrheal diseases, a community-based research project, and a rational drug-use program facilitated the launching in 1989 of a nationwide Philippine Control of Acute Respiratory Infections program (Phil-CARI). From 1990 to 1991 the Phil-CARI expanded rapidly, training >80% of its middle managers and frontline health care providers on the case-management protocols of the World Health Organization for acute respiratory infection. Multiple donors and good collaboration with various societies and medical schools assisted the program. However, by 1992, there were difficulties in maintaining training quality, follow-up, and supervision. Donor assistance dwindled and the health care delivery system decentralized. Government procurement systems were unable to meet the logistics demands of the program. The monitoring and evaluation system was inadequate to measure impact. The Phil-CARI provides lessons in searching for more sustainable approaches and systems to meet the various demands of a nationwide ARI control program and to create the desired impact.

Acute Disease↗

Cold chain status at immunisation centres in Ethiopia.

BACKGROUND: Child immunisation is among the most cost-effective ways of preventing premature child deaths, and the potency of vaccines, crucial for vaccine efficacy, is dependent on effective management of the cold chain at all levels of vaccine handling. OBJECTIVE: To assess the status of the cold chain at peripheral vaccine stores in Ethiopia. DESIGN: Institution based cross-sectional survey in two rural and one urban administrative areas were included in the study. Sixty seven health institutions providing static vaccination services were included in the study but cold chain system was assessed fully in only sixty four. Data were collected by interviewing health workers and by directly observing the cold chain equipment and records using structured forms. RESULTS: Conditions of the cold chain system were described based on 64 of the 67 centres visited, three were excluded because of non-functioning cold chain. Complete temperature record was observed in 37 (57.8%) of the centres. Thermometer was not available in four (6.3%) and thermometer reading was found to be outside the optimal range in another seven (10.9%) centres. Vaccine storage in the refrigerator was not proper in 47 (73.4%) centres. Majority of the centres had neither trained personnel nor budget for maintenance of the cold chain. CONCLUSION: There is a real danger of vaccines losing their potency at these centres even if they were potent on arrival. Relevant training for those handling the cold chain, improving the maintenance conditions of refrigerators and introduction of cold chain monitoring devises are recommended.

Drug Storage↗

Meeting the needs of people with AIDS: local initiatives and Federal support.

The Health Resources and Services Administration (HRSA), one of the seven agencies of the Public Health Service, is working to meet some of the resource and patient service needs engendered by the epidemic of acquired immune deficiency syndrome (AIDS). Those actions derived from, and support the continuation, expansion, and replication of, initiatives at the community and State levels. HRSA is carrying out many of the recommendations of the Intragovernmental Task Force on AIDS Health Care Delivery by enhancing the AIDS training of health care personnel in prevention, diagnosis, and care and by counseling and encouraging the expansion of facilities outside hospitals to care for AIDS patients. The agency, through its pediatric AIDS demonstration projects, is working on models for the care of children with HIV infections. The needs of AIDS patients are being addressed through a drug therapy reimbursement program; demonstration grants to 13 projects to promote coordinated, integrated systems of care in the community; and grants for the development of intermediate and long-term care facilities for patients. Ten regional education and training centers, funded in 1987 and 1988, will increase the supply of health care providers prepared to diagnose and treat persons with HIV infections. Programs will be conducted for several thousand providers over the next 3 years, using such modalities as televised programs and train-the-trainer courses. The centers will also offer support and referral services for providers.

Acquired Immunodeficiency Syndrome↗

Epidemic Salmonella enteritidis infection in Los Angeles County, California. The predominance of phage type 4.

Between April and July 1994, 501 cases of Salmonella enteritidis infection were reported in Los Angeles County, California, nearly 5 times the number reported between April and July 1993; of these, 422 (84%) were sporadic (not related to known outbreaks). A case-control study was done to determine risk factors for sporadic illness; the distribution of S enteritidis phage types was evaluated. Case-patients (n = 58) were county residents older than 1 year with culture-confirmed S enteritidis infection in August 1994. One to two acquaintance controls (n = 98) were matched to each case by age, sex, and race. Two risk factors-eating raw or undercooked eggs (matched odds ratio [MOR] = 6.6; 95% confidence interval [CI] = 1.9, 23.0) and eating in restaurants (MOR = 4.9; 95% CI = 1.2, 19.4) in the 3 days before the onset of illness-remained significant in the conditional logistic regression model. Of 16 randomly selected S enteritidis case-isolates, 15 (94%) were phage type 4. The reasons for the regional predominance of phage type 4, an S enteritidis subtype recently associated with large and destructive increases in salmonellosis among poultry and humans in Britain and much of Europe, are unclear. To minimize human S enteritidis infection, food service workers need frequent training in the proper handling of raw foods, eggs should be kept refrigerated during distribution and storage, and eggs should be cooked until the yolk is firm, particularly for persons at the greatest risk for serious illness: pregnant women, elderly persons, and those with compromised immune systems. Clinicians should obtain stool specimens for culture from patients who present with diarrhea and fever or bloody diarrhea or who are possibly part of an outbreak.

Adolescent↗

Influence of exercise on the immune function of rats of various ages.

The purpose of this study was to determine whether exercise could prevent the age-related decline in mitogenesis, which has been well documented in rats, mice, and humans. At 1, 6, 12, and 18 mo of age, male Fischer F344 rats were subjected daily to swimming exercise for 6 mo. At the end of the 6-mo training period, spleen lymphocytes were isolated from the exercised rats and from age-matched sedentary controls. The induction of lymphocyte proliferation was measured with the mitogens concanavalin A (ConA) and lipopolysaccharide (LPS). In addition, the ability of the lymphocytes to produce interleukin 2 (IL 2) in response to ConA induction was measured. ConA- and LPS-induced proliferation decreased 41-63% between 7 and 25 mo of age in both exercised and sedentary control rats. ConA-induced IL 2 production decreased 42 and 62% between 7 and 25 mo of age for exercised and sedentary control rats, respectively. Although the age-related decline in mitogen-induced proliferation and IL 2 production was smaller in exercised rats, this was due to a lower level of mitogenesis and IL 2 production in lymphocytes from young exercised rats. Exercise resulted in a significant decrease (23-32%) in mitogen-induced lymphocyte proliferation and IL-2 production in 7-mo-old exercised rats compared with 7-mo-old sedentary rats. However, in the 18- and 24-mo-old rats, mitogen-induced lymphocyte proliferation and IL 2 production was not significantly different between exercised and sedentary control rats.

Aging↗

Physiological changes associated with the pre-event taper in athletes.

Some of the physiological changes associated with the taper and their relationship with athletic performance are now known. Since the 1980s a number of studies have examined various physiological responses associated with the cardiorespiratory, metabolic, hormonal, neuromuscular and immunological systems during the pre-event taper across a number of sports. Changes in the cardiorespiratory system may include an increase in maximal oxygen uptake, but this is not a necessary prerequisite for taper-induced gains in performance. Oxygen uptake at a given submaximal exercise intensity can decrease during the taper, but this response is more likely to occur in less-skilled athletes. Resting, maximal and submaximal heart rates do not change, unless athletes show clear signs of overreaching before the taper. Blood pressure, cardiac dimensions and ventilatory function are generally stable, but submaximal ventilation may decrease. Possible haematological changes include increased blood and red cell volume, haemoglobin, haematocrit, reticulocytes and haptoglobin, and decreased red cell distribution width. These changes in the taper suggest a positive balance between haemolysis and erythropoiesis, likely to contribute to performance gains. Metabolic changes during the taper include: a reduced daily energy expenditure; slightly reduced or stable respiratory exchange ratio; increased peak blood lactate concentration; and decreased or unchanged blood lactate at submaximal intensities. Blood ammonia concentrations show inconsistent trends, muscle glycogen concentration increases progressively and calcium retention mechanisms seem to be triggered during the taper. Reduced blood creatine kinase concentrations suggest recovery from training stress and muscle damage, but other biochemical markers of training stress and performance capacity are largely unaffected by the taper. Hormonal markers such as testosterone, cortisol, testosterone : cortisol ratio, 24-hour urinary cortisol : cortisone ratio, plasma and urinary catecholamines, growth hormone and insulin-like growth factor-1 are sometimes affected and changes can correlate with changes in an athlete's performance capacity. From a neuromuscular perspective, the taper usually results in markedly increased muscular strength and power, often associated with performance gains at the muscular and whole body level. Oxidative enzyme activities can increase, along with positive changes in single muscle fibre size, metabolic properties and contractile properties. Limited research on the influence of the taper on athletes' immune status indicates that small changes in immune cells, immunoglobulins and cytokines are unlikely to compromise overall immunological protection. The pre-event taper may also be characterised by psychological changes in the athlete, including a reduction in total mood disturbance and somatic complaints, improved somatic relaxation and self-assessed physical conditioning scores, reduced perception of effort and improved quality of sleep. These changes are often associated with improved post-taper performances. Mathematical models indicate that the physiological changes associated with the taper are the result of a restoration of previously impaired physiological capacities (fatigue and adaptation model), and the capacity to tolerate training and respond effectively to training undertaken during the taper (variable dose-response model). Finally, it is important to note that some or all of the described physiological and psychological changes associated with the taper occur simultaneously, which underpins the integrative nature of relationships between these changes and performance enhancement.

Adaptation, Physiological↗

The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system.

This study examines the effect of methylprednisolone on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass (CPB) system. This isolated CPB system is an in vitro model which simulates the pro-inflammatory immune response. Whole blood from 10 volunteers was obtained in two equal amounts. Heparin and saline were added to the control group while heparin and methylprednisolone were added to the methylprednisolone group. The blood was added to two identical CPB circuits and bypass commenced by a trained perfusionist. Samples were taken at blood donation (Sample 0), 10 min after the addition of drugs (Sample 1) and after 30, 60 and 90 min of CPB (Samples 2, 3 and 4, respectively). Cytokines interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor soluble receptor 2 (TNFsr2) and the leucocyte adhesion molecules L-selectin, HLA DR, CD18 and CD11b were determined. IL-8 increased in both groups. This increase was significantly less in the methylprednisolone group. Increases in granulocyte CD11b and CD18 expression were less in the methylprednisolone group than in the control group but did not reach statistical significance. These results indicate that methylprednisolone significantly reduces the production of IL-8 in an isolated CPB system. This effect occurs in the absence of IL-10.

Antigens, CD↗

Bloodborne pathogens.

Worker exposure to bloodborne diseases can be minimized through: . training and education programs; . use of personal protective equipment such as gloves, gowns, face masks and eye protection; . work practices such as thorough hand washing after each patient contact; . proper handling of sharps; . engineering controls such as biological safety cabinets and puncture-resistant sharps containers; . immunization programs; . proper disposal of contaminated waste; . use of disinfectants; . labeling and signs.

Accidents, Occupational↗

Immunisation of children by a nurse without a doctor present.

Over 16 months 148 children were referred by health visitors and general practitioners to a specially trained nurse for failing to complete courses of immunisation. A further 91 children of travellers' families were identified as needing immunisation. The nurse carried out 810 immunisations on 237 of these children in their homes without a doctor being present. There were only two refusals, and one child suffered a mild anaphylactic shock. The cost per immunisation, in nurse's salary and travel expenses, was pounds 8. This is an effective and fairly inexpensive way of achieving uptake of immunisation in such groups of children, and there seems no reason why trained nurses should not give immunisations either in a child health clinic or at home, without a doctor present.

Child↗

The design and use of appropriate health technologies for developing countries.

Health care in developing countries is discussed in terms of the administrative systems, medical manpower and technologies which are most appropriate to the economic and cultural environment in which they will be used. Appropriate technology must be preceded by appropriate research and development and those involved in the training of overseas students should critically examine the relevance of the course to the needs of the students.

Biomedical Engineering↗

Exercise enhances survival rate in mice infected with Salmonella typhimurium.

Mice voluntarily trained on exercise wheels for 16-18 days and were then infected with an approximate LD50 dose of Salmonella typhimurium. These trained mice exhibited a small, but statistically significant (P = 0.037) increase in survival rate (34/77) compared to sedentary control mice (23/79) after 7 days.

Animals↗

Should you vaccinate patients in your ED? Check out these unique protocols.

Although controversial, ED vaccination programs can successfully target minority, low-income, and uninsured populations. Without access to vaccination registries, only single-shot immunizations such as influenza and pneumococcal are feasible in the ED. For a vaccine program to be financially feasible, an ED needs a significant Medicaid population and low immunization rates in the community. Protocols for vaccine programs should delegate the responsibility to nursing with standing orders.

Bacterial Vaccines↗

Odour learning and immunity costs in mice.

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.

Animals↗