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Dendritic leucocytes pulsed with monoclonal antibody-hapten conjugates elicit vigorous primary humoral responses in vivo.

Purified dendritic leucocytes (DL) were pulsed briefly in vitro with haptenated monoclonal antibodies (MoAb) to MHC class II and immediately injected i.v. into syngeneic recipients. Strong anti-hapten humoral responses were observed even though only a few picomoles of specific MoAb-hapten conjugates were injected with the DL. In contrast, DL pulsed with control conjugates, i.e. haptenated non-binding MoAbs, gave only weak responses. DL thus, can take up, process and present protein antigens even after brief exposure in vitro, and their immunogenicity is enhanced by pulsing with antigen conjugated to specific MoAbs. Furthermore, in the presence of fetal calf serum (FCS), but not normal rat serum, the control MoAb W6/32 (against human MHC class I) bound to DL. The vigorous primary humoral response achieved following this pulsing indicates that it is the binding and the corresponding increased uptake that enhances the immunogenicity of the DL.

Animals↗

Cardiovascular activity during mental stress following vigorous exercise in sportsmen and inactive men.

Thirty-six competitive sportsmen and 36 inactive men participated in a two-session experiment. Session 1 involved exercise to exhaustion so as to assess maximal oxygen consumption (VO2 max). In Session 2, both groups were randomized into three experimental conditions: 20 min of exercise at high intensity (70% VO2max) or moderate intensity (50% VO2max) or a light exercise control. Following 30 min of recovery, all subjects performed mental arithmetic and public speech tasks in a counterbalanced order. Cardiovascular, electrodermal, respiratory, and subjective variables were recorded. Sportsmen had higher VO2max, lower body fat, and lower resting heart rate (HR) than inactive men. A postexercise hypotensive response was observed among subjects in the 70% and 50% VO2max conditions, accompanied by baroreceptor reflex inhibition in the 70% condition. Systolic pressure was lower during mental arithmetic and during recovery from the speech task in the high-intensity than in the control group. Diastolic pressure was lower following mental arithmetic in the high-intensity group. No differences in HR reactivity, electrodermal, or respiratory parameters were observed, but baroreceptor reflex sensitivity was inhibited during mental arithmetic. The results are discussed in relation to previous reports of suppressed cardiovascular reactivity to mental stress tests following vigorous exercise and the role of stress-related processes in the antihypertensive response to physical training.

Adult↗

Vigorous response of cytotoxic T lymphocytes associated with systemic activation of CD8 T lymphocytes in fulminant hepatitis B.

BACKGROUND: Fulminant hepatitis is a clinical syndrome characterized by sudden and severe liver dysfunction. METHODS: We analyzed two patients with a superacute form of fulminant hepatitis B and compared findings with those of four patients with acute self-limited hepatitis B, two patients with acute exacerbation of chronic hepatitis B and four healthy individuals. RESULTS: In fulminant hepatitis, an increased population of human leukocyte antigen (HLA)-DR(+) CD8(+) lymphocytes was observed in peripheral blood by flow cytometry, which was accompanied by the presence of HLA-DR(hi) lymphocytes. The phenotype of CD8(+) T lymphocytes from patients with fulminant hepatitis was mostly that of the effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA(-) CCR7(-) phenotype dominated in the liver of these patients. A larger population of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) appeared in peripheral circulation of the fulminant hepatitis patients compared with that in a patient with acute hepatitis. HBV-specific CTLs were highly concentrated in the liver, although epitopes recognized by these CTLs in the peripheral blood and in the liver were similar. Peripheral CTLs were mostly functional as indicated by intracellular perforin and interferon-gamma. CONCLUSIONS: These results suggest the presence of vigorous activation of CD8(+) T cells in vivo in fulminant hepatitis and the necessity of extensive therapy in patients with this disease.

Adult↗

Pyomyositis caused by vigorous exercise in a boy.

We report on a 12-year-old boy who suffered from staphylococcal pyomyositis in both arms following vigorous exercise. No trauma or skin lesions were observed. In non-tropical areas, the etiology of pyomyositis can be related to muscle injury caused merely by exercise, without any other predisposing factors.

Abscess↗

Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.

Virus-specific CD4+ T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus-type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4+ T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta chemokines. In persons with chronic infection, HIV-1-specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1-specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1-specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development.

Amino Acid Sequence↗

VIGOROUS MOLD GROWTH IN SOILS AFTER ADDITION OF WATER-INSOLUBLE FATTY SUBSTANCES.

Various water-insoluble fatty compounds, when added to soil in finely divided form, will support as high-caloric nutrients a visible, vigorous growth of the molds, Fusarium solani Mart., F. diversisporum Sherb., and F. equiseti. n-Paraffins and olefins are most effective, because the effect of additives is reduced to the extent that oxygen atoms are introduced into the molecule. n-Fatty alcohols support growth in soil almost as well as the paraffins; however, growth is reduced when branched-chain compounds are added as nutrients. Compounds that will support mold growth when added to air-dried soil as finely powdered solids will not do so when incorporated at temperatures above their melting point, but will produce dense growth when applied to wet soil in this form. Mold growth is correlated with degradation of fatty matter. The rate of degradation is controlled by the availability of water, oxygen, and the basic inorganic nutrients.

Fatty Acids↗

Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland.

To better understand the immunological mechanisms that permit prolonged shedding of murine cytomegalovirus (MCMV) from the salivary gland, the phenotypic and functional characteristics of leukocytes infiltrating the submaxillary gland (SMG) were analyzed in infected BALB/c mice. A robust innate immune response, comprised of CD11c+ major histocompatibility complex class II+ CD11b- CD8alpha+ dendritic cells and gamma/delta T-cell receptor-bearing CD3+ T cells was prominent through at least 28 days postinfection. Concurrently, a dramatic increase in pan-NK (DX5+) CD3+ and CD8+ T cells was observed, while CD4+ T cells, known to be essential for viral clearance from this tissue, increased slightly. The expression particularly of gamma interferon but also of interleukin-10 and CC chemokines was extraordinarily high in the SMG in response to MCMV infection. The gamma interferon was produced primarily by CD4+ and CD8+ T lymphocytes and DX5+ CD3+ T cells. The SMG CD8+ T cells were highly cytolytic ex vivo, and a significant proportion of these cells were specific to an immunodominant MCMV peptide. These peptide-specific clones were not exhausted by the presence of high virus titers, which persisted in the SMG despite the strength of the cell-mediated responses. In contrast, MCMV replication was efficiently cleared from the draining cervical and periglandular lymph nodes, a tissue displaying a substantially weaker antiviral response. Our data indicated that vigorous innate and acquired immune responses are elicited, activated, and retained in response to mucosal inflammation from persistent MCMV infection of the submaxillary gland.

3T3 Cells↗

Mapping QTL for yield components, vigor, and resistance to Phytophthora palmivora in Theobroma cacao L.

Quantitative trait loci (QTL) mapping for agronomic traits was carried out in cocoa (Theobroma cacao L.). Regions of the genome involved in yield, vigor, and resistance to Phytophthora palmivora were identified. Three heterozygous clones, one upper Amazon Forastero (IMC78) and two Trinitario (DR1 and S52), were crossed with the same male parent, a lower Amazon Forastero (Catongo), known to be highly homozygous. Observations were made on progeny over nine consecutive years. One to three QTL related to yield were detected in each of the three populations, located on chromosomes 1, 2, 4, 5, 9, and 10. They explained between 8.1 and 19.3% of the phenotypic variation and showed various levels of repeatability. In IMC78, the QTL detected on chromosome 5 was the most repeatable over years. The QTL for the average individual pod weight on chromosome 4 was the most significant with an LOD of 17.3 and an R2 of 43.7. QTL related to these traits were identified in the same region of the genome in clones of different genetic groups. This suggests that molecular markers can be used to improve cocoa varieties.

Cacao↗

Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension.

The effectiveness of dobutamine (Dob) in preventing bone loss during 14 days of hindlimb suspension (Sus) was tested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats (age 155 days). One-half of each group was given Dob (2 mg . kg-1 . day-1) or saline (Sal). Histomorphometric measurements at midfemur revealed a 17% smaller cortical bone area (CBA) and a 32% lower periosteal mineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Sal rats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similar but nonsignificant effects on cross-sectional moment of inertia were observed. Nonsuspended Ex rats had no change in bone CBA when CBA is indexed to body weight. Sus appeared to uncouple the relationship between soleus weight and CBA. Dob attenuated the 43% decline in soleus weight after Sus in Ex but not in Sed rats. In summary, vigorous Ex before Sus does not affect loss of bone mass due to unloading; Dob effectively maintains CBA in Sed rats subjected to suspension.

Adrenergic beta-Agonists↗

Self-efficacy and participation in vigorous physical activity by high school students.

The relationship between physical activity self-efficacy and participation in vigorous physical activity by high school students is examined in this article. Self-efficacy is hypothesized to be positively related to participation in three settings (physical education class, other school-related activities, and outside of school). The effects of age, gender, perceived barriers, and actual barriers are also examined. The sample consists of 1,041 grade 9 and 11 students from a large Metropolitan Toronto school board. Factors derived from a previous (factor) analysis were used to examine the effects of self-efficacy, perceived barriers, and life strain (an actual barrier). The results of multiple regression analysis indicate that physical activity self-efficacy, despite external barriers (but not internal barriers), is predictive of physical activity participation in the hypothesized direction. Other results show consistent age and gender effects on physical activity participation and some support for the hypothesized relationship between perceived barriers and participation.

Adolescent↗

Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo.

Dendritic cells (DCs) genetically engineered to overexpress CD95 (Fas) ligand (CD95L-DC) were proposed as tools to induce peripheral tolerance to alloantigens. Herein, we observed that CD95L-DC obtained after retroviral gene transfer in bone marrow (BM) precursors derived from CD95-deficient (lpr/lpr) mice elicit much stronger allospecific type 1 helper T-cell and cytotoxic T-cell activities than control DCs upon injection in vivo, although they induce lower T-cell responses in vitro. Indeed, a single injection of CD95L-DC prepared from C57BL/6 mice was sufficient to prime bm13 recipients for acute rejection of C57BL/6 skin allografts that were otherwise tolerated in the context of this single weak major histocompatibility complex (MHC) class I incompatibility. Massive neutrophil infiltrates depending on interleukin (IL)-1 signaling were observed at sites of CD95L-DC injection. Experiments in IL-1 receptor-deficient mice or in animals injected with depleting anti-Gr1 monoclonal antibody (mAb) established that neutrophil recruitment is required for the development of vigorous T-cell responses after injection of CD95L-DC in vivo.

Animals↗

Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses.

A great variety of in vitro culture protocols for human monocyte-derived dendritic cells (mo-DCs) has been used to generate DCs suitable for use in immunotherapy. It is thought that activated DCs undergo one-way differentiation into "exhausted" DCs. In the present study, we contrived an in vitro method for facilitating expression of CD70 by mature DCs. This was achieved by vigorous washing of mo-DCs before exposure to lipopolysaccharide (LPS). Unexpectedly, these mature DCs retain expression of some interleukin (IL)-12 family members after extended periods and maintain their ability to stimulate type 1 T cell responses. In contrast, DCs exposed to IL-4 before LPS stimulation or LPS-stimulated DCs not exposed to washing stress before activation failed to express CD70 and did differentiate into exhausted DCs. It is interesting that DCs expressing CD70 (CD70+ DCs) induced interferon-gamma production from purified, allogeneic CD8+ T cells through a direct CD27-CD70 interaction. This is evidence for a pathway resulting in generation of CD8 T effectors by B7-independent mechanisms. These data suggest that exposure of immature DCs to LPS stimulation contributes to their terminal differentiation into CD70+ DCs, which have potent ability to prolong type 1 T cell responses through alternative pathways.

Adoptive Transfer↗

What changes are needed to keep vascular surgery alive and vigorous?

To keep vascular surgery alive and vigorous, we need to regain our preeminence as the principal therapists for patients with aneurysms, carotids, and occlusive disease of the lower extremities. We must regain the sense of excitement about our specialty and refocus training for residents and practicing surgeons toward those skills necessary to provide the full range of therapies at the highest level. Attaining these goals will require embracing, obtaining, and applying endovascular expertise throughout the vascular workforce. We can no longer moan and whine over encroachments into our turf by nonsurgeons. We must make our own opportunities. Changes in our attitude, our identity, and our structure will be necessary to do so. Our ability to make change will depend upon our values, defined as the judgment as to whether we remain a derivative of our general surgical roots (with continued emphasis on improved quality from traditional operations) or embrace the disruptive technology of endoluminal therapy as the next iteration of vascular surgical practice. We cannot do both because the preparation for the latter precludes the former. We are at a crossroads because if we accept endovascular technologies as critical to our future, our path is clear.

Attitude of Health Personnel↗

Determination of the intensity dimension in vigorous exercise programmes with particular reference to the use of the rating of perceived exertion.

The nature and magnitude of the training effect is a function of the frequency, duration and intensity with which vigorous exercise is undertaken. The intensity dimension is a key element in producing changes in central cardiovascular haemodynamics, but because of a 'self-awareness' factor implicated in both the reporting and regulating the intensity level, the determination of this parameter is difficult. Contemporary research with psychophysical ratings of effort sense has led to the recommendation by the American College of Sports Medicine that the rating of perceived exertion is a useful device in the determination of exercise intensity. This paper presents a review of research related to the setting of exercise intensity from a psychophysiological standpoint, and includes a set of observations from research which has examined the influence of perceptual, cognitive and affective variables on the reporting of the rating of perceived exertion.

Exercise↗

Cardiorespiratory fitness and vigorous leisure-time physical activity modify the association of small size at birth with the metabolic syndrome.

OBJECTIVE: Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome. RESEARCH DESIGN AND METHODS: Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and VO(2max) were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study. RESULTS: Men with a ponderal index (kg/m(3)) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in <25 min/wk of vigorous LTPA and in men with a VO(2max) <28.6 ml x kg(-1) x min(-1) or <2.44 l/min. In active and fit men, however, the association was absent. CONCLUSIONS: Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.

Body Mass Index↗

Vigorous neuronal differentiation of amplified and grafted basic fibroblast growth factor-responsive neurospheres derived from neuroepithelial stem cells.

Neuroepithelial stem cells (NESCs) have emerged as a possible donor material aimed at neural transplantation for the repair of damaged neural circuitry, particularly because of their propensity to differentiate into neurons. We previously ascertained in vitro that NESCs derived from rat early embryos could be amplified in culture containing basic fibroblast growth factors (bFGF), and that neurospheres grown for 7 days in the culture had a strong tendency to differentiate into neurons. In this report, we analyze immunohistochemically the biological nature of bFGF-responsive neurospheres derived from NESCs. We first succeeded in amplifying the number of NESCs from the mesencephalic neural plate of embryonic day 10 Wistar rats with the addition of bFGF. Grown neurospheres were labeled with bromodeoxyuridine (BrdU) in vitro and were stereotactically transplanted into the right striatum of the normal adult Wistar rat. Two weeks after transplantation, a viable graft in the host brain was observed. While many BrdU/Hu double positive cells were seen in the graft, and a few BrdU/nestin double positive cells were also seen, no BrdU/GFAP double positive cells could be identified. These results suggested that bFGF-responsive neurospheres derived from NESCs demonstrated a propensity to differentiate into neurons in the adult brain environment. Furthermore, following in vitro amplification of the original stem cell number with bFGF, the grown neurospheres preserved their propensity to differentiate vigorously into neurons. NESCs are thus suggested as a feasible candidate for intracerebral grafting donor materials aimed at reconstruction of damaged neural circuits.

Animals↗

Vigorous allograft rejection in the absence of danger.

Tolerance to self is a necessary attribute of the immune system. It is thought that most autoreactive T cells are deleted in the thymus during the process of negative selection. However, peripheral tolerance mechanisms also exist to prevent development of autoimmune diseases against peripheral self-Ags. It has been proposed that T cells develop tolerance to peripheral self-Ags encountered in the absence of inflammation or "danger" signals. We have used immunodeficient Rag 1-/- mice to study the response of T cells to neo-self peripheral Ags in the form of well-healed skin and vascularized cardiac allografts. In this paper we report that skin and cardiac allografts without evidence of inflammation are vigorously rejected by transferred T cells or when recipients are reconstituted with T cells at a physiologic rate by nude bone graft transplantation. These results provide new insights into the role of inflammation or "danger" in the initiation of T cell-dependent immune responses. These findings also have profound implications in organ transplantation and suggest that in the absence of central deletional tolerance, peripheral tolerance mechanisms are not sufficient to inhibit alloimmune responses even in the absence of inflammation or danger.

Adoptive Transfer↗

Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.

Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.

Animals↗