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Biomedical subjects

Takuya Osada

Publications and source records attributed to Takuya Osada.

35 records · Page 2Linked to original sources
PubMed2004

Noninvasive monitoring of deterioration in skeletal muscle function with forearm cast immobilization and the prevention of deterioration.

BACKGROUND: In this research inactivity was simulated by immobilizing the forearm region in a plaster cast. Changes in skeletal muscle oxidative function were measured using near-infrared spectroscopy (NIRS), and the preventative effect of the training protocol on deterioration of skeletal muscle and the clinical utility of NIRS were examined. METHODS: Fourteen healthy adult men underwent immobilization of the forearm of the non-dominant arm by plaster cast for 21 days. Eight healthy adult subjects were designated as the immobilization group (IMM) and six were designated as the immobilization + training group (IMM+TRN). Grip strength, forearm circumference and dynamic handgrip exercise endurance were measured before and after the 21-day immobilization period. Using NIRS, changes in oxidative function of skeletal muscles were also evaluated. Muscle oxygen consumption recovery was recorded after the completion of 60 seconds of 40% maximum voluntary contraction (MVC) dynamic handgrip exercise 1 repetition per 4 seconds and the recovery time constant (TcVO2mus) was calculated. RESULTS: TcVO2mus for the IMM was 59.7 +/- 5.5 seconds (average +/- standard error) before immobilization and lengthened significantly to 70.4 +/- 5.4 seconds after immobilization (p < 0.05). For the IMM+TRN, TcVO2mus was 78.3 +/- 6.2 seconds before immobilization and training and shortened significantly to 63.1 +/- 5.6 seconds after immobilization and training (p < 0.05). CONCLUSIONS: The training program used in this experiment was effective in preventing declines in muscle oxidative function and endurance due to immobilization. The experimental results suggest that non-invasive monitoring of skeletal muscle function by NIRS would be possible in a clinical setting.

Journal Article↗
PubMed2004

Muscle contraction-induced limb blood flow variability during dynamic knee extensor.

PURPOSE: To evaluate whether muscle contraction-induced variability of limb femoral arterial blood flow (FABF) can be reduced with longer sampling durations. This was assessed in relation to muscle contraction-relaxation cycles (CRcycles) during steady-state, one-legged, dynamic knee-extensor exercise (KEE) at varying "exercise intensities" and "contraction frequencies." METHODS: Eleven male subjects performed steady-state KEE at 10-40 W at 30 and 60 contractions per minute (cpm). FABF (Doppler ultrasound) and contraction-relaxation-induced variability in FABF was determined for 1-, 2-, 5-, 10-, 15-, 20-, and 30-CRcycles during approximately 4-min steady-state KEE. Variability was determined as coefficients of variation (CV). RESULTS: During KEE at 30 and 60 cpm CVFABF was significantly higher for 1-CRcycles (12.3% and 15.5%) and 2-CRcycles (9.6% and 11.8%) than for 30-CRcycles (4.0% and 5.2%), but similar for 10-CRcycles to 30-CRcycles at all work rates and contraction frequencies. The CVFABF between work rates at 30 and 60 cpm did not statistically differ (P = NS) for any of the CRcycle measurements. However, the single CRcycles-induced CVFABF at 60 cpm was significantly higher (P < 0.05) than that at 30 cpm at the lower exercise intensities of 10 and 20 W, but with no significant difference at 30 and 40W. CONCLUSION: Limb blood flow variability was markedly reduced with a longer sampling measurement of at least 10-CRcycles, which had a CVFABF of approximately 5%. Furthermore, the 1-CRcycle-induced FABF variability was similar at each exercise intensity, but significant variations were seen between contraction frequencies at lower exercise intensities. It is speculated the difference between the contraction frequencies at lower exercise intensities may be due to the muscle contraction-relaxation-induced variations in muscle force (intramuscular pressure), along with the superimposed blood pressure waves.

Adult↗
PubMed2004

Exercise-related time course of pulsatility index in brachial artery following forearm exercise assessed by Doppler ultrasound.

At rest, vascular reactivity assessed by the changes in pulsatility index (PI) is one indicator of vessel stenosis in some clinical/basic science research. However, all types of vessel stenosis do not show an alteration in the PI, because flow perfusion may be maintained by the development of collateral vessels such as in severe arterial stenosis or non-severe arterial stenosis. Therefore at rest, changes in the PI may not always be a precise indicator of vessel stenosis. However, a few studies have used the PI following exercise, which may provide additional information on hemodynamics. The purpose of the present study was to examine the exercise-related time course of the PI in the brachial artery after ischemic or non-ischemic isometric handgrip exercise (IHE) using Doppler ultrasound, and to determine the potential use of this parameter as an indicator of vascular disease. Ten healthy young male subjects performed IHE at 10% and 30% of maximum voluntary contraction (MVC) for 2-minutes (min) with or without arterial occlusion (AO), or 2-min of AO alone. Following each 2-min session, PI was determined during the 5-min recovery period. A significant difference in the recovery PI was observed between IHE, ischemic IHE, as well as AO alone. Exercise with AO significantly increased the reduction in the PI compared to exercise alone, or AO alone, at both 10% and 30%MVC. These results suggest, exercise-induced changes in the time course of the PI during recovery may potentially be a useful diagnostic tool. Exercise-induced ischemic state may potentially be a useful indicator for detecting arteriovascular disease, even if it is not detected by AO alone.

Adult↗
PubMed2003

Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans.

The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of three groups receiving a high dose of recombinant human IL-6 (HiIL-6; n = 6), a low dose of IL-6 (LoIL-6; n = 6) or saline (Con; n = 6) infused into one femoral artery for 3 h. The stable isotope [6,6-2H2] glucose was infused into a forearm vein throughout the 3 h infusion period and for a further 3 h after the cessation of infusion (recovery) to determine endogenous glucose production and whole-body glucose disposal. Infusion with HiIL-6 and LoIL-6 resulted in a marked (P < 0.05) increase in systemic IL-6 concentration throughout the 3 h of infusion (mean arterial plasma [IL-6]s of 319 and 143 pg ml-1 for HiIL-6 and LoIL-6, respectively), followed by a rapid decline (P < 0.05) during the recovery period. Subjects experienced clinical symptoms such as shivering and discomfort during HiIL-6 administration, but were asymptomatic during LoIL-6 administration. In addition, only HiIL-6 elevated (P < 0.05) plasma adrenaline (epinephrine). IL-6 infusion, irrespective of dose, did not result in any changes to endogenous glucose production, whole-body glucose disposal or leg- glucose uptake. These data demonstrate that acute IL-6 administration does not impair whole-body glucose disposal, net leg-glucose uptake, or increase endogenous glucose production at rest in healthy young humans.

Adult↗
PubMed2003

Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans.

Previous studies show that exercise-induced hyperaemia is unaffected by systemic inhibition of nitric oxide synthase (NOS) and it has been proposed that this may be due to compensation by other vasodilators. We studied the involvement of cytochrome P450 2C9 (CYP 2C9) in the regulation of skeletal muscle blood flow in humans and the interaction between CYP 2C9 and NOS. Seven males performed knee extensor exercise. Blood flow was measured by thermodilution and blood samples were drawn frequently from the femoral artery and vein at rest, during exercise and in recovery. The protocol was repeated three times on the same day. The first and the third protocols were controls, and in the second protocol either the CYP 2C9 inhibitor sulfaphenazole alone, or sulfaphenazole in combination with the NOS inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) were infused. Compared with control there was no difference in blood flow at any time with sulfaphenazole infusion (P > 0.05) whereas with infusion of sulfaphenazole and L-NMMA, blood flow during exercise was 16 +/- 4 % lower than in control (9 min: 3.67 +/- 0.31 vs. 4.29 +/- 0.20 l min(-1); P < 0.05). Oxygen uptake during exercise was 12 +/- 3 % lower (9 min: 525 +/- 46 vs. 594 +/- 24 ml min(-1); P < 0.05) with co-infusion of sulfaphenazole and L-NMMA, whereas oxygen uptake during sulfaphenazole infusion alone was not different from that of control (P > 0.05). The results demonstrate that CYP 2C9 plays an important role in the regulation of hyperaemia and oxygen uptake during exercise. Since inhibition of neither NOS nor CYP 2C9 alone affect skeletal muscle blood flow, an interaction between CYP 2C9 and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over when NO production is compromised.

Adult↗
PubMed2003

Muscle reoxygenation rate after isometric exercise at various intensities in relation to muscle oxidative capacity.

The purpose of this study was to determine whether the reoxygenation rate (Reoxy-rate) immediately after static exercise at various submaximal intensities would be related to muscle oxidative capacity. Seven healthy male subjects performed isometric handgrip exercise for 10 sec at 30%, 60% and 90% of maximal voluntary contraction (MVC). The Reoxy-rate and muscle oxygen consumption during exercise (muscle VO2EX) were monitored by near infrared continuous wave spectroscopy (NIRcws). The muscle oxidative capacity was evaluated by the time constant for phosphocreatine resynthesis (PCrTc) using 31-phosphorus magnetic resonance spectroscopy (31P-MRS). The Peak blood flow of brachial artery after exercise (BABFpeak) was measured using Doppler ultrasound. There was no correlation between PCrTc and Reoxy-rate at 30% and 60% MVC. In contrast, Reoxy-rate at 90% MVC was positively correlated to PCrTC (r = 0.825, p < 0.05). The muscle VO2EX increased 5.9, 8.8 and 12.6-fold of the resting on average at 30%, 60% and 90% MVC, respectively, and the muscle VO2EX at 90% MVC was significantly higher than that at 30% and 60% MVC. On the other hand, BABFpeak increased only just 1.9, 2.4 and 2.7-fold of the resting on average at 30%, 60% and 90% MVC, respectively (Fig. 4). These results suggest that the higher oxidative capacity muscle shows slower muscle reoxygenation after 10 sec isometric exercise at 90% MVC because the Reoxy-rate after this type of exercise may be influenced more by muscle VO2 than by O2 supply. In contrast, 60% MVC and lower exercise intensities may not be severe enough to influence the muscle VO2 dependent Reoxy-rate.

Exercise↗
PubMed2003

Post-exercise hyperemia after ischemic and non-ischemic isometric handgrip exercise.

Post-exercise related time course of muscle oxygenation during recovery provides valuable information on peripheral vascular disease. The purpose of the present study was to examine post-exercise hyperemia (forearm blood flow; FBF, Doppler ultrasound) assessed by peak FBF, excess FBF and the time constant for FBF (FBF(Tc)) following isometric handgrip exercise (IHE). Post-exercise hyperemia was assessed in an ischemic and non-ischemic state at different exercise intensities and durations. Peak FBF and excess FBF were defined as the maximum FBF during recovery, and the total amount of FBF volume, respectively. FBF(Tc) represents the time to reach approximately 37% of the change in FBF between peak FBF and resting FBF (delta peak FBF). Ten subjects performed IHE at "10% and 30% maximum voluntary contraction (MVC)" for 2 min with or without arterial occlusion (AO), followed by 2 min of AO alone (Study I). In Study II, six subjects performed 30%MVC-IHE with AO for "100%, 66%, 33% and 10% of the exhausted exercise duration" (time to exhaustion). In Study I, although peak FBF and excess FBF were significantly higher in ischemic than non-ischemic IHE for both 10% and 30%MVC (p<0.05), FBF(Tc) was similar in the ischemic and non-ischemic conditions. The peak FBF, excess FBF and FBF(Tc) were all significantly higher at 30% than at 10%MVC (p<0.05). In Study II, the peak FBF and excess FBF increased linearly compared to the absolute and relative exercise durations for ischemic IHE. FBF(Tc) increased exponentially when compared to the absolute and relative exercise durations. These data suggest the ischemic exercise has a larger hyperemic response compared to the non-ischemic exercise. In conclusion, the peak FBF, excess FBF and FBF(Tc) seen during post-exercise hyperemia are closely correlated with exercise intensity and duration, not only in non-ischemic, but also in the ischemic exercise. In combination with the ischemic exercise, these parameters could potentially prove to be valuable indicators of peripheral vascular disease.

Adult↗
PubMed2002

IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle.

The aim of the present study was to examine whether IL-6 and TNF-alpha are expressed in, and released from, human skeletal muscle during exercise. We hypothesized that the skeletal muscle will release IL-6, but not TNF-alpha, during exercise because of previous observations that TNF-alpha negatively affects glucose uptake in skeletal muscle. Six healthy, male subjects performed 180 min of two-legged knee-extensor exercise. Muscle samples were obtained from the vastus lateralis of one limb. In addition, blood samples were obtained from a femoral artery and vein. Plasma was analyzed for IL-6 and TNF-alpha. We detected both IL-6 and TNF-alpha mRNA in resting muscle samples, and whereas IL-6 increased (P < 0.05) approximately 100-fold throughout exercise, no significant increase in TNF-alpha mRNA was observed. Arterial plasma TNF-alpha did not increase during exercise. Furthermore, there was no net release of TNF-alpha either before or during exercise. In contrast, IL-6 increased throughout exercise in arterial plasma, and a net IL-6 release from the contracting limb was observed after 120 min of exercise (P < 0.05).

Adult↗
PubMed2002

Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation.

There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycogen concentration influences glucose uptake during exercise, 13 healthy men were studied during two series of experiments. Seven men completed 4 h of two-legged knee extensor exercise 16 h after reducing of muscle glycogen by completing 60 min of single-legged cycling (Series 1). A further six men completed 3 h of two-legged knee extensor exercise on two occasions: one after 60 min of two-legged cycling (16 h prior to the experimental trial) followed by a high carbohydrate diet (HCHO) and the other after the same exercise followed by a low carbohydrate diet (LCHO) (Series 2). Muscle glycogen was decreased by 40 % when comparing the pre-exercised leg (EL) with the control leg (CL) prior to exercise in Series 1. In addition, muscle glycogen was decreased by the same magnitude when comparing LCHO with HCHO in Series 2. In Series 1, glucose uptake was 3-fold higher in the first 60 min of exercise, in the presence of unchanged pre-exercise GLUT4 protein in EL compared with CL, suggesting that the lower glycogen, and not the exercise the day before, might have provided the stimulus for increased glucose uptake. Despite the same magnitude of difference in pre-exercise glycogen concentration when comparing Series 1 with Series 2, neither direct-nor isotopic tracer-determined glucose uptake was higher in LCHO compared with HCHO in Series 2. However, arterial concentrations of insulin and glucose were lower, while free fatty acids and adrenaline were higher in LCHO compared with HCHO. These data suggest that pre-exercise glycogen content may influence glucose uptake during subsequent exercise. However, this is only the case when delivery of substrates and hormones remains constant. When delivery of substrates and hormones is altered, the potential effect of glycogen on glucose uptake is negated.

Adult↗
PubMed2002

Decreased synthesis of matrix metalloproteinase-7 and adhesion to the extracellular matrix proteins of human colon cancer cells treated with troglitazone.

PURPOSE: In the present study, we investigated the effect of troglitazone, a selective ligand and agonist of PPAR-gamma, on the metastatic potential of human colon cancer cells. METHODS: High- and low-PPAR-gamma expression clones of the colon cancer cell line, HT29, namely clones 21 and 3 respectively, were used. We investigated the effect of troglitazone on the proliferation, on the adhesion to extracellular matrix proteins and on the synthesis of matrix metalloproteinases (MMPs) of colon cancer cells. RESULTS: Troglitazone inhibited the proliferation of both subclones, in a dose-dependent manner, and the inhibitory effect correlated with the level of PPAR-gamma expression. Troglitazone strongly inhibited the production of MMP-7, an enzyme associated with invasiveness of cancer cells, by both subclones. In addition, troglitazone caused a strong decrease in the adhesion of clone 21 to extracellular matrix (ECM) proteins, laminin and type IV collagen. This effect was independent of beta1-integrins expression CONCLUSION: In addition to inhibition of cancer cell growth, troglitazone had an inhibitory effect on two important events associated with the metastatic potential of cancer cells, production of MMPs and adhesion to ECM proteins. Consequently, troglitazone is a promising agent for the treatment and prevention of colon cancer metastasis.

Antineoplastic Agents↗
PubMed2002

Cholesterol granuloma of the breast mimicking carcinoma: report of a case.

Cholesterol granuloma of the breast is a rare benign condition which is often clinically and radiologically indistinguishable from breast carcinoma. We herein report the case of a 62-year-old asymptomatic woman who was found on a routine breast examination to have an elastic hard mass, measuring 0.9 cm in diameter, in the upper outer quadrant of the left breast. Physical examination and ultrasonography strongly suggested a carcinomatous lesion. A cytological examination of a fine-needle aspiration biopsy specimen was inconclusive because of the paucity of epithelial cells. A histological examination of excisional biopsy materials showed scattered cholesterol crystals arranged in irregular, parallel arrays, surrounded by histiocytes and giant cells, which were consistent with a diagnosis of cholesterol granuloma. This case report indicates the importance of performing a histological examination to establish the final diagnosis of cholesterol granuloma. We believe that a better awareness of this breast disease might help to prevent both a misdiagnosis and unnecessary surgery.

Aged↗
PubMed2002

Blood flow and oxygen uptake increase with total power during five different knee-extension contraction rates.

Controversies exist regarding quantification of internal power (IP) generated by the muscles to overcome energy changes of moving body segments when external power (EP) is performed. The aim was to 1) use a kinematic model for estimation of IP during knee extension, 2) validate the model by independent calculation of IP from metabolic variables (IP(met)), and 3) analyze the relationship between total power (TP = EP + IP) and physiological responses. IP increased in a curvilinear manner (5, 7, 13, 21, and 34 W) with contraction rate (45, 60, 75, 90, and 105 contractions/min), but it was independent of EP. Correspondingly, IP(met) was 5, 7, 10, 19, and 28 W, supporting the kinematic model. Heart rate, pulmonary oxygen uptake, and leg blood flow plotted vs. TP fell on the same line independent of contraction rate, and muscular mechanical efficiency as well as delta efficiency remained remarkably constant across contraction rates. It is concluded that the novel metabolic validation of the kinematic model supports the model assumptions, and physiological responses proved to be closely related to TP, supporting the legitimacy of IP estimates.

Adult↗
PubMed2002

Femoral artery inflow in relation to external and total work rate at different knee extensor contraction rates.

Whether limb blood flow is directly regulated to match the work rate, independent of the rate of contraction, remains elusive. This study therefore investigated the relationship between femoral arterial blood flow (FABF; Doppler ultrasound) and "external" (applied load) as well as "total" [external + "internal" (potential and kinetic energy changes of the moving lower leg)] work rate, during steady-state one-legged, dynamic, knee extensor exercise (1L-KEE) in the sitting position at different contraction rates. Ten subjects performed 1L-KEE at 30, 60, and 90 contractions/min (cpm) 1) at constant resistive loads of 0.2 and 0.5 kg inducing incremental external work rates (study I) and 2) at different relative resistive loads inducing constant external work rates of 9 and 18 W (study II). Moreover, 3) six subjects performed 1L-KEE at 60 and 100 cpm at incremental total work rates of 40, 50, 60, and 70 W (study III). In study I, FABF increased (P < 0.001) with increasing contraction frequency and external work rate, for each resistive load. In study II, FABF increased (P < 0.001) with increasing contraction frequency for each constant external work rate. Of major importance in study III, however, was that FABF, although increasing linearly with the total work rate, was not different (P = not significant) between contraction rates, at the total work rates of 40, 50, 60, and 70 W, respectively. Furthermore, FABF correlated linearly and positively with both the external and total work rate for each contraction frequency. In conclusion, the findings support the concept that leg blood flow during 1L-KEE in a normal knee extensor ergometer is matched directly in relation to the total work rate and metabolic activity, irrespective of the contraction frequency. The rate of contraction seems erroneously to influence the results only when it is related to the external work rate without taking into account the internal work component.

Adult↗
PubMedDate not supplied

Dendritic cell-based immunotherapy.

Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publication of the first clinical data of DC-based vaccines, and through this and subsequent studies, a number of important developmental insights have been gleaned. These include the ideal source and type of DCs, the discovery of novel antigens and methods of loading DCs, the role of DC maturation, and the most efficient route of immunization. The generation of immune responses against tumor antigens after DC immunization has been demonstrated, and favorable clinical responses have been reported in some patients; however, it is difficult to pool the results as a whole, and thus the body of data remains inconclusive, in part because of varying DC preparation and vaccination protocols, the use of different forms of antigens, and, most importantly, a lack of rigorous criteria for defining clinical responses. As such, the standardization of clinical and immunologic criteria utilized, as well as DC preparations employed, will allow for the comparison of results across multiple clinical studies and is required in order for future trials to measure the true value and role of this treatment modality. In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions.

Antigen Presentation↗
PubMedDate not supplied

Dendritic cells cultured in anti-CD40 antibody-immobilized plates elicit a highly efficient peptide-specific T-cell response.

The function of dendritic cells (DCs), antigen-presenting cells that can initiate and regulate cellular and humoral responses, is highly influenced by their level of maturation. Immature DCs may be harmful in anti-tumor immunotherapy, because they can induce immunotolerance rather than immunostimulation. In this study, the authors sought to determine the optimal culture conditions for obtaining fully mature DCs. When DCs were cultured in agonistic anti-CD40 monoclonal antibody-immobilized plates, they showed a higher expression of the maturation marker CD83 than DCs cultured without CD40 ligation or those cultured in medium supplemented with anti-CD40 monoclonal antibody. In addition, when interferon-gamma (IFN-gamma) was added to the medium, additive up-regulation of CD83 expression was observed. These DCs treated with both maturation signals showed a higher secretion of interleukin-12. To evaluate the capacity of antigen presentation, specific cytotoxic T lymphocytes were generated using autologous DC pulsed with a human lymphocyte antigen-A24-restricted peptide epitope derived from carcinoembryonic antigen. Interferon-gamma-secreting CD8+ T cells were analyzed by flow cytometry using the cellular affinity matrix technology. Dendritic cells, matured with CD40 ligation and IFN-gamma, were more efficient at eliciting an antigen-specific T-cell response in vitro than DCs stimulated with anti-CD40 monoclonal antibody or IFN-gamma alone. A cytotoxicity assay using carcinoembryonic antigen-expressing tumor cell lines also showed that DCs matured with both signals were more efficient at inducing cytotoxic T lymphocytes. These results demonstrate that DC culture in an anti-CD40 monoclonal antibody-immobilized plate in medium supplemented with IFN-gamma has a positive impact on DC maturation and may be optimal for eliciting an antigen-specific T-cell response without the need for CD4+ T-helper epitopes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Enumerating antigen-specific T-cell responses in peripheral blood: a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis.

Detection of the circulating antigen-specific T-cell response to immunization is an important biologic end point in clinical trials of cancer vaccines. Typically employed assays are peptide MHC tetramer, ELISpot, and intracellular cytokine analysis. Although there is no agreement on the definition of a positive response in these assays, many groups have chosen a number of T cells greater than 2 standard deviations above the mean of the negative controls. The authors wished to determine how well this cutoff performed for each of these assays in detecting positive and negative T-cell responses to a model antigen, the immunodominant HLA-A*0201-restricted epitope of cytomegalovirus (CMV) pp65. For each assay, the mean + 2 standard deviations of the response for CMV seronegatives was the point that best separated the two groups. Using this value, each assay had a sensitivity of 87.5% and specificity of 95% to 100% and exhibited a high degree of concordance (kappa 0.76-0.9) with the other two. The authors conclude that currently available immunologic assays perform well in detecting biologically relevant levels of antigen-specific T cells. These assays will better define the quantity and quality of protective immune responses to viral disease and offer insight into the requirements for protective anti-cancer immunity.

Antigens↗