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PubMed2006

Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.

Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained in a matching-to-place version of the water maze. After an acquisition phase, IL-6(+/+) mice injected intraperitoneally with lipopolysaccharide (LPS) exhibited deficits in working memory. However, IL-6(-/-) mice were refractory to the LPS-induced impairment in working memory. To determine the mechanism by which IL-6 deficiency conferred protection from disruption in working memory, plasma IL-1beta and tumor necrosis factor alpha (TNFalpha), c-Fos immunoreactivity in the nucleus of the solitary tract (NTS), and steady-state levels of IL-1beta and TNFalpha mRNA in neuronal layers of the hippocampus were determined in IL-6(+/+) and IL-6(-/-) mice after injection of LPS. Plasma IL-1beta and TNFalpha and c-Fos immunoreactivity in the NTS were increased similarly in IL-6(+/+) and IL-6(-/-) mice after LPS, indicating high circulating levels of IL-1beta and TNFalpha and activation of vagal afferent pathways were not sufficient to disrupt working memory in the absence of IL-6. However, the LPS-induced upregulation of IL-1beta and TNFalpha mRNA that was evident in hippocampal tissue of IL-6(+/+) mice was greatly attenuated or entirely absent in IL-6(-/-) mice. Collectively, these data suggest that humoral and neural immune-to-brain communication pathways are intact in IL-6-deficient mice but that, in the absence of IL-6, the central cytokine compartment is hyporesponsive.

Animals↗

PubMed2000

Immunity to equine influenza: relationship of vaccine-induced antibody in young Thoroughbred racehorses to protection against field infection with influenza A/equine-2 viruses (H3N8).

Field outbreaks of influenza that occurred in vaccinated Thoroughbred racehorses in Newmarket in 1995 and 1996 were investigated by nucleoprotein ELISA and serology. Investigations showed that serum levels of vaccine-induced single radial haemolysis (SRH) antibody correlated closely with protective immunity against equine influenza and were consistent with observations made in previous experimental studies using nebulised aerosol challenge. In the second part of this study, antibody levels stimulated by vaccination were investigated to examine probable protection in high risk groups, such as yearlings and horses in training. Results for yearlings correlated closely with experimentally derived antibody profiles described for several equine influenza vaccines. The horses in training had levels of antibody immediately prior to revaccination, which were higher than those measured in the yearlings. In conclusion, SRH antibody, used in the investigation of outbreaks and surveillance of post vaccination responses, was shown to correlate with and validate experimental vaccination and challenge models currently used in ponies in the licensing of modern vaccines. There may be benefit from serological monitoring of horses following vaccination through identification of susceptible periods to infection and demonstration of poor vaccine responders. This would allow appropriate and timely amendment of vaccination strategies to maximise protective immunity against influenza.

Animals↗

PubMed1991

Measuring the educational needs of doctors for training in child health surveillance.

The educational needs of general practitioners and other doctors wishing to provide child health surveillance are unknown. This study determines the needs of doctors prior to attending a course in child health surveillance by testing their knowledge of childhood immunization, and by self assessment of their skills and knowledge in different aspects of surveillance. A child health surveillance course must cover a core content to enable participants to reach a required standard. Assessment of educational needs allows greater emphasis and time to be given to certain aspects, thus making the course of greater educational value and more relevant to the participant.

Education, Medical, Continuing↗

PubMed2001

Nurse volunteers in school-based hepatitis B immunization programs.

School districts across the nation are implementing school-based hepatitis B virus vaccination programs. Because adolescents are at risk of contracting hepatitis B virus, these programs are important in preventing infections. Critical to the success of these programs is having qualified and cost-effective health professionals to administer the vaccine. This article describes the recruitment and training of professional nurse volunteers to administer vaccines in school-based clinics. During the 1998-1999 school year, approximately 60 nurses in Durham, North Carolina, volunteered 300 hours of time to the program. In the first year, the cost of recruiting and training volunteers exceeded the savings from salaried school nurse time. However, savings are expected in future years. Other benefits of recruiting volunteers to administer vaccine include allowing school nurses to remain in their usual assignments, increasing awareness of the health department's mission and school health in the community, and improving collaboration among local health agencies.

Adolescent↗

PubMed2003

Distribution and mitogen response of peripheral blood lymphocytes after exertional heat injury.

To determine whether immune disturbances during exertional heat injury (EHI) could be distinguished from those due to exercise (E), peripheral lymphocyte subset distributions and phytohemagglutinin-stimulated CD69 mitogen responses as discriminated by flow cytometry were studied in military recruits [18.7 +/- 0.3 (SE) yr old] training in warm weather. An E group (3 men and 3 women) ran 1.75-2 miles. During similar E, 11 recruits (10 men and 1 woman) presented with suspected EHI. EHI (40.4 +/- 0.3 degrees C) vs. E (38.6 +/- 0.2 degrees C) body temperature was significantly elevated (P < 0.05). Heat illness was largely classified as EHI, not heatstroke, because central nervous system manifestations were generally mild. Blood was collected at E completion or EHI onset (0 h) and 2 and 24 h later. At 0 h (EHI vs. E), suppressor, natural killer, and total lymphocyte counts were significantly elevated, helper and B lymphocyte counts remained similar, and the helper-to-suppressor ratio was significantly depressed. By 2 h, immune cell dynamics between groups were similar. From 0 to 24 h, T lymphocyte subsets revealed significantly reduced phytohemagglutinin responses (percent CD69 and mean CD69 fluorescent intensity) in EHI vs. E. Thus immune cell dynamics with EHI were distinguishable from E. Because heat stress as reported in exercise or heatstroke is associated with similar immune cell disturbances, these findings in EHI contributed to the suggestion that heat stress of varying severity shares a common pathophysiological process influencing the immune system.

Adolescent↗

PubMed1993

Granulocyte activation induced by intense interval running.

Activation of granulocytes has been associated with normal immune function, inflammation, and exercise-induced muscle damage. The effect of intense interval running on granulocyte activation was examined by use of flow cytometry, monoclonal antibodies, and spectrophotometric techniques. Eight trained males [maximal oxygen uptake VO2max, mean (SD) = 64.4 (3.6) ml/kg/min; age 30.1 (4.8) years] undertook an intense interval exercise (treadmill running) protocol to exhaustion. Subjects completed an average of 16.5 one-minute runs. Granulocyte expression of CR3 (CD11b), receptor for complement component C3bi (6 and 24 h post-test), and Fc gamma RIII (CD16) (24 h post-test) and the plasma concentration of elastase-inhibitor complex (1 h post-test) increased significantly (all P < .05). Subjects (8 of 8) exhibited a post-test decrease at either 1 or 6 h (P < .01) and a 24-h post-test significant increase (7 of 8; P < .05) in granulocyte 90 degrees light scattering (LS). Plasma lactoferrin (Lf) concentration, although increased by 17% at 6 h post-test, was not significantly different from resting values at any sampling point. Changes in plasma Lf and median channel 90 degrees LS were significantly correlated (r = -.43, P = .04), raising the possibility of monitoring exercise-induced granulocyte activation (degranulation) by flow cytometry. Intense interval exercise appears to induce granulocyte activation, as manifested by release of granule proteins and changes in 90 degrees LS and expression of both Fc and complement receptors.

Adult↗

PubMed2000

An algorithm for the prediction of proteasomal cleavages.

Proteasomes, major proteolytic sites in eukaryotic cells, play an important part in major histocompatibility class I (MHC I) ligand generation and thus in the regulation of specific immune responses. Their cleavage specificity is of outstanding interest for this process. In order to generalize previously determined cleavage motifs of 20 S proteasomes, we developed network-based model proteasomes trained by an evolutionary algorithm with experimental cleavage data of yeast and human 20 S proteasomes. A window of ten flanking amino acid residues proved sufficient for the model proteasomes to reproduce the experimental results with 98-100 % accuracy. Actual experimental data were reproduced significantly better than randomly selected cleavage sites, suggesting that our model proteasomes were able to extract rules inherent to proteasomal cleavage data. The affinity parameters of the model, which decide for or against cleavage, correspond with the cleavage motifs determined experimentally. The predictive power of the model was verified for unknown (to the program) test conditions: the prediction of cleavage numbers in proteins and the generation of MHC I ligands from short peptides. In summary, our model proteasomes reproduce and predict proteasomal cleavages with high degree of accuracy. They present a promising approach for predicting proteasomal cleavage products in future attempts and, in combination with existing algorithms for MHC I ligand prediction, will be tested to improve cytotoxic T lymphocyte epitope prediction.

Algorithms↗

PubMed2026

Stratifying lung adenocarcinoma: a novel prognostic model based on mitochondrial outer membrane permeabilization activity.

UNLABELLED: Mitochondrial outer membrane permeabilization (MOMP) is a core apoptotic regulatory event that dictates mitochondrial integrity, where full activation drives cell death and sublethal dysregulation contributes to tumor genomic instability. We used the Cancer Genome Atlas lung adenocarcinoma cohort (TCGA-LUAD) as the training cohort and the Gene Expression Omnibus dataset GSE42127 as the validation cohort to identify prognostic genes related to MOMP activity in lung adenocarcinoma (LUAD) and to evaluate their potential biological significance. By intersecting MOMP-related genes with differentially expressed genes, combined with survival analysis, Mendelian randomization analysis, and 101 machine-learning algorithm combinations, seven prognostic genes, namely BIRC5, PSMD11, TNFRSF13C, YWHAZ, YWHAG, CYCS, and LTB, were identified. Next, an optimal prognostic model was constructed based on the gradient boosting machine (GBM) algorithm. Based on the risk score, LUAD patients were stratified into high- and low-risk groups, and patients in the high-risk group exhibited poorer overall survival in both the training and validation cohorts. Furthermore, a nomogram integrating the risk score and clinicopathological factors was developed and showed favorable predictive performance for 1-, 3-, and 5-year survival. Meanwhile, functional and immune analyses revealed that the high-risk group was enriched in DNA replication-related pathways and demonstrated a higher tumor mutation burden (TMB). Correlation analysis indicated that TNFRSF13C was positively correlated with activated B cells, whereas BIRC5 was negatively correlated with eosinophils, suggesting that MOMP-related genes might be involved in remodeling the immune microenvironment of LUAD. Drug sensitivity analysis showed differences in predicted half-maximal inhibitory concentration (IC50) values between the risk groups, suggesting the potential value of this model in assisting therapeutic stratification. Single-cell RNA sequencing (scRNA-seq) further identified T lymphocytes as a key cell type, with numerous prognostic genes exhibiting differential expression in T cells or dynamic changes during differentiation. We suggest that the MOMP-related signature established in this study may provide a reference for prognostic stratification in LUAD and offers candidate prognostic genes for subsequent experimental and clinical validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05058-6.

Lung adenocarcinoma↗

PubMed2005

Seroprevalence of hepatitis B virus and hepatitis C virus in Monte Negro in the Brazilian western Amazon region.

PURPOSE: This study was carried out in Monte Negro (state of Rondônia), a village in the Brazilian western Amazon region, where a University of São Paulo Medical School program for medical student training in rural assistance took place. It aimed to determine the prevalence of hepatitis B virus and hepatitis C virus, to investigate risk factors for infection, and to evaluate the State immunization program against hepatitis B virus in the region. METHODS: The study is a cross-sectional seroprevalence survey, comprising 267 volunteers who answered a comprehensive questionnaire and had blood samples collected, which were analyzed in São Paulo for the presence of antibodies against hepatitis B virus (Hbs Ag, anti-Hbs, and anti-Hbc) and hepatitis C virus using commercial kits. Data were stored in a specific data bank, and the association between seropositivity and potential risk factors was analyzed by means of uni-, bi-, and multi-variate analysis, considering +/- 5%. RESULTS: The seroprevalence of hepatitis B virus was 61.79% and of hepatitis C virus was 0.38%. Statistical analysis on the data bank showed that the prevalence of hepatitis B virus rose significantly with age, especially after adolescence. Infection was higher in those coming from outside the state of Rondônia. Exposure to vaccination against hepatitis B virus was higher in younger individuals and in those who were born in Rondônia. CONCLUSION: Monte Negro is a highly endemic region for hepatitis B virus but not for hepatitis C virus. Our results also provide indirect evidence indicating a significant improvement in the immunization program in Rondônia in recent years.

Adolescent↗

PubMed1999

Potential of the Executive Order Increasing the Participation of Asian Americans and Pacific Islanders in Federal Programs.

OBJECTIVES. This study evaluated the effectiveness of a program designed to reduce primary care treatment barriers for Asian Americans and Pacific Islanders (AAPIs). Interpreters, home health visits, prevention education, cultural sensitivity trainings, and an AAPI phone line were provided to increase the utilization of primary care services at a rural community health center. METHODS. The number of primary care patients and infant immunization rates were measured from 1993& shy;1996. Emergency room visits were measured to assess the impact of primary care increases upon reducing inappropriate emergency room visits. Baseline frequencies and data from other ethnic populations were used as control measures. RESULTS. AAPI primary care patients increased by 87 percent, compared to a total population increases of less than 8 percent. Timely immunization rates for infants rose from 36 percent to 93 percent. Emergency room visits declined by 20 percent. CONCLUSIONS. Treatment barriers for primary care may be reduced for AAPIs if appropriate cultural considerations are addressed. Support for a link between primary care interventions and reduced emergency room utilization is suggested.

Journal Article↗

PubMed1992

[Body immunocorrection when vaccination is contraindicated (a clinico-epidemiological validation)].

The article summarizes the results of epidemiological observation which was performed in one of the training units. The goals of this observation were to estimate the prophylactic efficiency of the selected application of Natrii nucleinas in persons with the lowered immunoresistance on the background of antigrip immunization. A high clinico-epidemiological effectiveness ws approved for 10-days administration of the Natrii nucleinas in persons with clinic manifestations of grip and other respiratory infections at the moment of vaccination. It is resulted in the diminishing of the morbidity index, duration and gravity of this pathology in the postvaccinal period. The administration of Natrii nucleinas was experimentally substantiated during this epidemiological observation.

Acute Disease↗

PubMed1993

Epidemiological factors associated with neonatal tetanus mortality: observations from a cluster survey in Nigeria.

A cluster survey on neonatal tetanus (NNT) mortality was conducted in Kano Metropolis, Northern Nigeria, to investigate epidemiological factors associated with NNT mortality. The survey was a two-stage cluster sampling technique and lasted for two weeks. A total of 2,623 live-births were recorded over a 12-month period. Less than 40% of the births followed two or more antenatal visits and tetanus toxoid coverage was 32.0%. Over 60% of births were outside hospitals and related facilities. Of the epidemiological factors investigated, only antenatal care, tetanus toxoid coverage, hospital delivery, poor cord management and traditional surgery showed significant association with NNT death. It is suggested that an appropriate community-specific prevention strategy for the region should include health education to improve utilisation of antenatal and hospital-delivery facilities, discourage traditional surgery and improve tetanus toxoid coverage. A case is also made for training and involvement of traditional birth attendants (TBAs) since most deliveries occurred outside hospitals and related facilities.

Cluster Analysis↗

PubMed2004

Cancer, infection and immunity: a personal homage to Jan Svoboda.

Jan Svoboda has had an extraordinary influence on my research. Following our first meeting in 1967, he encouraged me to pursue my tentative evidence for the existence of endogenous retroviruses latent in normal cells. He introduced me to the Czech scientists, Pavel Veselý and Jan Závada, with whom I collaborated fruitfully on the transformed cell phenotype and on virus pseudotypes, respectively. Through my brief training in his laboratory in Prague I gained a breadth and depth of analysis in virology, immunology and oncology that helped me subsequently to tackle problems in AIDS and AIDS-associated malignancy at the levels of both cell biology and epidemiology.

Animals↗

PubMed1999

Integrated management of childhood illness: a summary of first experiences.

The strategy of Integrated Management of Childhood Illness (IMCI) aims to reduce child mortality and morbidity in developing countries by combining improved management of common childhood illnesses with proper nutrition and immunization. The strategy includes interventions to improve the skills of health workers, the health system, and family and community practices. This article describes the experience of the first countries to adopt and implement the IMCI interventions, the clinical guidelines dealing with the major causes of morbidity and mortality in children, and the training package on these guidelines for health workers in first-level health facilities. The most relevant lessons learned and how these lessons have served as a basis for developing a broader IMCI strategy are described.

Child↗

PubMed1996

Technical and ethical problems associated with patch testing.

When relevant allergens are identified by patch testing, and patients can avoid them in their environment, improvement of dermatitis is the rule. Some forms of chronic dermatitis may not clear completely, but patients are usually satisfied with modification of their previously more severe problem. In 1981 when asked what he felt were the five most important advances in clinical dermatology during the 20th century, Dr. Marion B. Sulzburger, an icon in American dermatology, said that, "The increased use and usefulness of the patch test and the international standardization of test concentrations and methods" was number one. Those of us who are enthusiastic patch testers and fascinated by the evaluation of patients with irritant and allergic contact dermatitis would agree. It is a thrilling clinical experience to be able to tell a machinist that he need not stop his lifelong occupation, but instead will do fine if he will simply avoid the waterless hand cleanser he has been using which is preserved with glutaraldehyde. The woman whose facial dermatitis has embarrassed her for years and clears when she stops using the Quaternium-15 preserved moisturizer that you have identified in your patch testing is grateful to you forever, and again happy in her own life. In 1991, my research assistants, Patricia Norris and Mary Lou Belozer, and I studied 30 university hospital workers who answered our advertisement asking for individuals who believed they were troubled by their rubber gloves (unreported study). By evaluating these people through history, physical examination, and patch testing, we were able to prove glove relatedness in 14 of them. Nine of the 14 had contact urticaria to latex, and only 5 had allergic contact dermatitis to rubber glove ingredients. Fifteen of our patients had irritant dermatitis. In this study, none of the patients with allergic contact dermatitis to glove ingredients had contact urticaria. However, since that time, we have observed a number of patients who had both forms of allergic reaction. Three of our patients who presented with nummular (patchy) hand dermatitis also had contact urticaria to latex, but no positive patch tests. With latex glove avoidance, their dermatitis resolved; an example of how scratching urticaria can eventuate in longer lasting dermatitis in some people ("the itch that rashes"). The patients presented to their dermatologist with dermatitis, but their true initiating event was urticaria which lasted only hours. The gratifying part of this study was that patch testing and contact urticaria testing allowed us to discover the 5 patients with allergic contact dermatitis and the 9 patients with contact urticaria who could benefit from glove alternatives. We were also able to assure patients in the remainder of the group that their hand eczema was not glove induced, but rather was related to their wet work. In most instances, therapeutic intervention helped, but in several cases job changes were required. Patch testing, when done properly, produces exciting results. When done improperly, it confuses and misleads patients and results in embarrassment to physicians who cannot properly interpret their results. Should a physician choose to include patch testing in his or her evaluation of patients with contact dermatitis it is essential, in my view, that he or she have highly developed skills in the diagnosis and treatment of skin diseases, and that these physicians be elaborately trained in the techniques of application and the methods of interpretation of patch tests.

Ethics, Medical↗

PubMed2005

Differential response of plasma and immune cell's vitamin E levels to physical activity and antioxidant vitamin supplementation.

OBJECTIVE: To assess the differential response of plasma, lymphocyte and neutrophil vitamin E levels to high-intensity physical activity and to vitamin C and E supplementation. SUBJECTS: In all, 14 male trained amateur runners (32-36 y old) were randomly divided in two groups (supplemented and placebo), and participated in a half marathon race. The subjects did not take any other supplements than the ones provided for this study. INTERVENTION: Vitamin C (152 mg/day) and E (50 mg/day) supplementation was administrated to athletes for a month, using a new almond-based isotonic and energetic beverage (supplemented group). The usual dietary habits of participants were assessed using a self-reported 7-day 24-h recall before the day of the study. To avoid the beverage influence, nonenriched vitamin C and E almond-based isotonic and energetic beverage was given to the placebo group. After 1 month, subjects participated in a half marathon race (21 km run). Vitamin E concentration was determined in plasma, neutrophils and lymphocytes before and immediately after the race, and 3 h after finishing the race. RESULTS: Daily energy intake and caloric profile of supplemented and placebo group were not different except for vitamin C and E supplementation. Vitamin supplementation and exercise had no effect on vitamins E levels in plasma. The exercise significantly (P<0.05) increased the lymphocyte vitamin E concentration both in the placebo (+119%) and supplemented groups (+128%), and neutrophil vitamin E content in the supplemented group (+88%). These levels remained significantly (P<0.05) high after the short recovery. After exercise, vitamin E levels in lymphocytes and neutrophils of supplemented subjects were practically twice the levels before exercise, whereas neutrophil vitamin E content of the placebo group was close to those in plasma. CONCLUSION: After endurance exercise, lymphocytes increased their vitamin E content in the supplemented and placebo subjects whereas this trend in neutrophils was just observed in the supplemented group. The determination of vitamin E content in lymphocytes and neutrophils after exercise is a useful tool to assess the functional status of vitamin E.

Adult↗

PubMed1977

Response of immunosympathectomized rats to training.

The influence of chronic exercise was investigated with male rats assigned to normal (N) and sympathectomized (IS) groups. Animals in the latter group were injected daily for 5 days with the antiserum to the nerve growth factor beginning 24 h after birth. Training was introduced when the animals were 35--45 days old and lasted for 12 wk. The exercise program used by both groups was progressive in nature and modified in accordance with the performance capability of the IS animals. When IS and N rats performed a standardized treadmill test, the IS rats had significantly higher rectal temperatures than normal animals. Significant training differences were observed in resting heart rate and in mean blood pressures, but only in the N animals. However, both trained groups exhibited significantly less vasoconstricting ability to conditions of lower body negative pressure than their nontrained controls. Varied doses of epinephrine and norepinephrine were injected into both groups and training per se had no significant influence on the responses recorded. However, both IS group had changes which indicated that a supersensitivity to catecholamines had occurred. Although selective training adaptations can occur without sympathetic nerves, it was concluded that an intact nervous system was essential for maximal training effects to occur.

Animals↗

PubMed1979

[Structural changes of synaptic membranes under the action of specific antisera using the spin probe technique].

The spin probing technique was used to study the interaction of preparations of rat cerebral cortex synaptic membranes with specific antisera. It was found that the fluidity of membrane matrix largely depended on the nature of physiological processes involving synaptic membranes in vivo. The supramolecular structure of synaptic membranes isolated from the brain of trained animals differed from that of controls. Differences in the properties of synaptic membranes were also revealed during their incubation with specific antisera. The data obtained are interpreted in terms of immunochemical theory of memory and training.

Animals↗