MRI characteristics and oncological follow-up of patients with ISUP grade group 4 or 5 prostate cancer.

OBJECTIVES: To analyze multiparametric MRI (mpMRI) characteristics of patients with International Society of Urological Pathology (ISUP) grade group (GG) 4 or 5 prostate cancer (PC) and to correlate MRI parameters with the occurrence of biochemical recurrence (BCR) after radical prostatectomy (RPE). METHODS: In this single-center cohort study consecutive patients with mpMRI and ISUP GG 4 or 5 PC were retrospectively analyzed. Clinical, MR-guided biopsy, and diagnostic mpMRI parameter were assessed. A subcohort of patients with RPE and follow-up was analyzed separately. A univariate and multivariate analyses were performed to determine parameters that are associated to patients with BCR after RPE. RESULTS: 145 patients (mean age 70y, median PSA 10.9 ng/ml) were analyzed. 99% had a PI-RADS classification of 4 or 5, 48% revealed MRI T3 stage, and median diameter of the MRI index lesion (IL) was 15 mm. IL showed a median ADC value of 668 ×10-6 mm2/s and exhibited contrast enhancement in 94% of the cases. For patients with follow-up after RPE (n = 82; mean follow-up time 68 ± 27 m), MRI parameters were significantly different for contact length of the IL to the pseudocapsule (LCC), MRI T3 stage, and IL localization (p < 0.05). Higher PSAD and MRI T3 stage were independent parameters for the risk of BCR when incorporating clinical, biopsy, and MRI parameters. CONCLUSION: ISUP GG 4 or 5 PC has distinctive characteristics on mpMRI and were detected on MRI in all cases. In addition, higher PSAD and MRI T3 stage were significant predictors for BCR after RPE.

MRI grading for the prediction of prostate cancer aggressiveness.

OBJECTIVES: T o evaluate the value of multiparametric MRI (mpMRI) for the prediction of prostate cancer (PCA) aggressiveness. METHODS: In this single center cohort study, consecutive patients with histologically confirmed PCA were retrospectively enrolled. Four different ISUP grade groups (1, 2, 3, 4-5) were defined and fifty patients per group were included. Several clinical (age, PSA, PSAD, percentage of PCA infiltration) and mpMRI parameters (ADC value, signal increase on high b-value images, diameter, extraprostatic extension [EPE], cross-zonal growth) were evaluated and correlated within the four groups. Based on combined descriptors, MRI grading groups (mG1-mG3) were defined to predict PCA aggressiveness. RESULTS: In total, 200 patients (mean age 68 years, median PSA value 8.1 ng/ml) were analyzed. Between the four groups, statistically significant differences could be shown for age, PSA, PSAD, and for MRI parameters cross-zonal growth, high b-value signal increase, EPE, and ADC (p < 0.01). All examined parameters revealed a significant correlation with the histopathologic biopsy ISUP grade groups (p < 0.01), except PCA diameter (p = 0.09). A mixed linear model demonstrated the strongest prediction of the respective ISUP grade group for the MRI grading system (p < 0.01) compared to single parameters. CONCLUSIONS: MpMRI yields relevant pre-biopsy information about PCA aggressiveness. A combination of quantitative and qualitative parameters (MRI grading groups) provided the best prediction of the biopsy ISUP grade group and may improve clinical pathway and treatment planning, adding useful information beyond PI-RADS assessment category. Due to the high prevalence of higher grade PCA in patients within mG3, an early re-biopsy seems indicated in cases of negative or post-biopsy low-grade PCA. KEY POINTS: • MpMRI yields relevant pre-biopsy information about prostate cancer aggressiveness. • MRI grading in addition to PI-RADS classification seems to be helpful for a size independent early prediction of clinically significant PCA. • MRI grading groups may help urologists in clinical pathway and treatment planning, especially when to consider an early re-biopsy.

Imaging of exercise-induced spinal remodeling in elite rowers.

OBJECTIVES: As in-vivo knowledge of training-induced remodeling of intervertebral discs (IVD) is scarce, this study assessed how lumbar IVDs change as a function of long-term training in elite athletes and age-matched controls using compositional Magnetic Resonance Imaging (MRI). DESIGN: Prospective case-control study. METHODS: Prospectively, lumbar spines of 17 elite rowers (ERs) of the German national rowing team (mean age: 23.9 ±â€¯3.3 years) were imaged on a clinical 3.0 T MRI scanner. ERs were imaged twice during the annual training cycle, i.e., at training intensive preseason preparations (t0) and 6 months later during post-competition recovery (t1). Controls (n = 22, mean age: 26.3 ±â€¯1.9 years) were imaged once at corresponding time points (t0: n = 11; t1: n = 11). Segment-wise, the glycosaminoglycan (GAG) content of lumbar IVDs (n = 195) was determined using glycosaminoglycan chemical exchange saturation transfer (gagCEST). Linear mixed models were set up to assess the influence of cohort and other variables on GAG content. RESULTS: During preseason, IVD GAG values of ERs were significantly higher than those of controls (ERs(t0): 2.58 ±â€¯0.27% (mean ±â€¯standard deviations); controls(t0): 1.43 ±â€¯0.36%; p ≤ 0.001), while during post-competition recovery, such differences were not present anymore (ERs(t1): 2.11 ±â€¯0.18%; controls(t1): 1.89 ±â€¯0.24%; p = 0.362). CONCLUSIONS: Professional elite-level rowing is transiently associated with significantly higher gagCEST values, which indicate increased lumbar IVD-GAG content and strong remodeling effects in response to training. Beyond professional rowing, core-strengthening full-body exercise may help to enhance the resilience of the lumbar spine as a potential therapeutic target in treating back pain.

Cartilage Degradation in Psoriatic Arthritis Is Associated With Increased Synovial Perfusion as Detected by Magnetic Resonance Imaging.

Objective: Even though cartilage loss is a known feature of psoriatic arthritis (PsA), research is sparse on its role in the pathogenesis of PsA and its potential use for disease detection and monitoring. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and dynamic contrast-enhanced MRI (DCE MRI), research has shown that early cartilage loss is strongly associated with synovial inflammation in rheumatoid arthritis (RA). The aim of this study was to determine if acute inflammation is associated with early cartilage loss in small finger joints of patients with PsA. Methods: Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution 3 Tesla dGEMRIC and DCE MRI using a dedicated 16-channel hand coil. Semi-quantitative and quantitative perfusion parameters were calculated. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), total cartilage thickness (TCT), and joint space width (JSW). Results: We found significant negative correlations between perfusion parameters (except Kep) and dGEMRIC indices, with the highest value at the MCP joints (KTrans: τ = -0.54, p = 0.01; Kep: τ = -0.02, p = 0.90; IAUC: τ = -0.51, p = 0.015; Initial Slope: τ = -0.54, p = 0.01; Peak: τ = -0.67, p = 0.002). Heterogeneous correlations were detected between perfusion parameters and both, total PsAMRIS and PsAMRIS synovitis sub-scores. No significant correlation was seen between any perfusion parameter and JSW and/or TCT. Conclusion: As examined by DCE MRI and dGEMRIC, there is a potential association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.

[Post-dural puncture headache]. / Postpunktioneller Kopfschmerz.

Headache following dural puncture is a typical complication of neuraxial analgesia and can impair the ability to perform activities of daily living up to incapacitation. The use of thin, atraumatic needles and special puncture techniques (e.g. reinsertion of the stylet) can prevent the majority of post-dural puncture headaches (PDPH). One of the most effective measures to prevent headache after accidental dural puncture is the intrathecal or epidural administration of morphine. When the diagnosis of PDPH is confirmed after excluding relevant differential diagnoses, some of which are potentially life-threatening, caffeine, theophylline and non-opioid analgesics are effective agents to reduce the severity of the symptoms. Traditional measures, such as strict bed rest and hyperhydration can no longer be recommended. If invasive treatment of the headache is warranted an epidural blood patch is still the method of choice with a high rate of success.

Seasonal variation in haemodynamics and blood pressure-regulating hormones.

Seasonal variation in blood pressure (BP) has been described in some people, although the variation is small for both systolic and diastolic BPs. The aim of this study was to elucidate underlying haemodynamic and hormonal mechanisms that may occur to defend seasonal changes in BP. Participants were 27 men and 7 women with either normal BP or early hypertension. Measurements of haemodynamics (cardiac output by dual-gas rebreathing) and hormones (resting catecholamines, renin activity, and aldosterone by radioenzymatic assay or radioimmunoassay) were performed during the summer, fall, winter, and spring seasons. Student's paired t-test with Bonferroni modification and regression analyses were used to examine the data with a significance level of P<0.05. Systolic and diastolic BP remained relatively constant across seasons. Cardiac output and stroke volume significantly decreased 10 and 15%, respectively, from summer to winter, whereas heart rate and systemic vascular resistance significantly increased 5 and 11%, respectively. Plasma aldosterone (PA) significantly increased 59% from summer to winter, whereas plasma norepinephrine (PNE), plasma epinephrine, and plasma renin activity (PRA) increased 19, 2, and 17%, respectively (pNS for each). Across the four seasons, mean arterial pressure significantly correlated with PRA and PA, whereas systemic vascular resistance significantly correlated with PNE and PRA. There are dramatic counterregulatory haemodynamic and hormonal adaptations to maintain a relatively constant BP. Norepinephrine, PRA, and aldosterone have a function in mediating the changes in haemodynamics.

Dissemination of bovine leukemia virus-infected cells from a newly infected sheep lymph node.

To investigate the early establishment of bovine leukemia virus (BLV) infection, we injected BLV-infected or mock-infected allogeneic cells into the shoulder of sheep in which an efferent lymphatic duct of the draining prescapular lymph node had been cannulated. Rare mononuclear cells acting as centers of BLV infection in culture were present within 4 to 6 days in efferent lymph and within 6 to 10 days in blood. Soon after BLV injection, immunoglobulin M+ (IgM+) and CD8+ cells increased in efferent lymph and oscillated reciprocally in frequency. CD8+ blasts increased on days 4 to 6, when infectious centers increased 100-fold in lymph. On days 6 and 7, both lymph and blood were enriched with CD8+ cells that were labeled late on day 5 with an intravenous pulse of 5-bromo-2'-deoxyuridine (BrdU). Lymph, but not blood, was enriched with BrdU+ B cells on day 7. Capsid-specific antibodies became detectable in efferent lymph on days 6 to 8 and surface glycoprotein-specific antibodies on day 9, preceding their detection in serum by 9 to 14 days. Systemic dissemination of BLV-infected cells was thus accompanied by an increase in proliferating CD8+ cells and the onset of BLV-specific antibodies in lymph. Infectious centers reached maximum frequencies of 0.2% in lymph by days 11 to 13, and then their frequencies increased by 5- to 40-fold in blood cells, suggesting that many infected blood cells do not recirculate back into lymph. Beginning on days 10 to 13, a subpopulation of B cells having high levels of surface IgM increased sharply in peripheral blood. Such cells were not present in lymph. After a day 16 pulse of BrdU, recently proliferated cells that stained intensely for surface IgM appeared in blood within 15 h. Predominantly B lymphocytes contained the viral capsid protein when lymph and blood cells were cultured briefly to allow BLV expression. However, both early in lymph and later in blood, BrdU+ B cells greatly exceeded productively infected cells, indicating that new BLV infections stimulate proliferation of two different populations of B cells.

Drosophila-raf acts to elaborate dorsoventral pattern in the ectoderm of developing embryos.

In the early Drosophila embryo the activity of the EGF-receptor (Egfr) is required to instruct cells to adopt a ventral neuroectodermal fate. Using a gain-of-function mutation we showed that D-raf acts to transmit this and other late-acting embryonic Egfr signals. A novel role for D-raf was also identified in lateral cell development using partial loss-of-function D-raf mutations. Thus, we provide evidence that zygotic D-raf acts to specify cell fates in two distinct pathways that generate dorsoventral pattern within the ectoderm. These functional requirements for D-raf activity occur subsequent to its maternal role in organizing the anterioposterior axis. The consequences of eliminating key D-raf regulatory domains and specific serine residues in the transmission of Egfr and lateral epidermal signals were also addressed here.

Blood flow velocities in the basal vein after subarachnoid haemorrhage. A prospective study using transcranial duplex sonography.

BACKGROUND: Early recognition of emerging delayed neurological deficits (DND) in patients after subarachnoid haemorrhage (SAH) is not always possible by transcranial Doppler sonography. Aim of this study was to investigate a) whether determination of blood flow velocities in deep cerebral basal veins can predict DND in these patients b) the correlation of venous flow velocity to cerebral blood flow (CBF). METHODS: a) We prospectively investigated the mean flow velocity in the basal vein (VBVR), in the middle cerebral artery (VMCA) and in the extracranial internal carotid artery (VICA) in 66 patients after spontaneous SAH. Examinations were performed daily during the first 10 days, using transcranial duplex sonography. Thirty-seven patients had VMCA exceeding 120 cm/s. They were categorised in three groups: 1: no delayed neurological deficit; II: transient DND; III: permanent DND or death associated with vasospasm. b) In another group of 14 patients, interdiane variations in global cerebral blood flow (CBF) measured by the Kety-Schmidt-method were correlated with variations in VBVR, VMCA, and VICA. FINDINGS: a) In patients without deficit, VBVR was significantly elevated above normal values the first day (p < 0.05), and days 5 and 6 (p < 0.1) after VMCA exceeding 120 cm/s. In group III (permanent deficit), flow velocities in the BVR were significantly below normal on day 5 (p < 0.05) and 9 (p < 0.1). b) The correlation between changes in VBVR to changes in CBF (r = 0.78, p < 0.001) was closer than between changes in VMCA to the changes in CBF (r = 0.54, p < 0.05). INTERPRETATION: In case of elevated VMCA, patients with higher VBVR seem to have a better outcome. Changes in CBF correlate better with VBVR than with arterial flow velocities.

The SU and TM envelope protein subunits of bovine leukemia virus are linked by disulfide bonds, both in cells and in virions.

After the polyprotein precursor of retroviral envelope proteins is proteolytically cleaved, the surface (SU) and transmembrane (TM) subunits remain associated with each other by noncovalent interactions or by disulfide bonds. Disulfide linkages confer a relatively stable association between the SU and TM envelope protein subunits of Rous sarcoma virus and murine leukemia virus. In contrast, the noncovalent association between SU and TM of human immunodeficiency virus leads to significant shedding of SU from the surface of infected cells. The SU and TM proteins of bovine leukemia virus (BLV) initially were reported to be disulfide linked but later were concluded not to be, since TM is often lost during purification of SU protein. Here, we show that SU and TM of BLV do, indeed, associate through disulfide bonds, whether the envelope proteins are overexpressed in transfected cells, are produced in virus-infected cells, or are present in newly produced virions.

Nutritional assessment, intervention, and evaluation of weight loss in patients with non-small cell lung cancer.

PURPOSE/OBJECTIVES: To describe weight change in patients from the time of cancer diagnosis to the last healthcare encounter before death, to describe reported nutritional assessment, intervention, and evaluation; and to determine the relationship of weight change and cancer-related symptoms to nutritional assessment, intervention, and evaluation. DESIGN: Descriptive, correlational. SETTING: A National Cancer Institute-designated cancer center and its associated university medical center in the northeastern United States. SAMPLE: Medical records of 93 individuals with non-small cell lung cancer. METHODS: Retrospective chart review. MAIN RESEARCH VARIABLES: Weight change; nutritional assessment, intervention, and evaluation; and cancer-related symptoms. FINDINGS: Mean weight change from cancer diagnosis to last healthcare encounter was -4.75 kg (SD = 6.05 kg). The mean regression slope of weight change was -3.69 kg/healthcare encounter (SD = 6.49 kg). The results of content analysis indicated that 90 subjects had nutritional assessments, 54 subjects had interventions, and 24 subjects had evaluations of intervention effectiveness. No association existed between weight change or cancer-related symptoms and nutritional assessment. Nutritional intervention was positively associated with dysphagia and depression, and evaluation of intervention effectiveness was positively associated with weight loss and dysphagia. CONCLUSIONS: Assessments of weight change and appetite usually were reported and appeared to be a routine part of patient care. However, assessments of weight loss and anorexia led to interventions only 60% of the time. When interventions were recommended, only 44% were evaluated for effectiveness. IMPLICATIONS FOR NURSING PRACTICE: Assessment of nutritional status needs to be broadened, interventions need to be initiated more often, and creative solutions to nutritional problems need to be sought. Regular evaluation of interventions is essential.

Sex, age, height, and weight as predictors of selected physiologic outcomes.

The purpose of this study was to determine the extent to which sex, age, height, and weight predict selected physiologic outcomes, namely, forced expiratory volume in one second (FEV1), hemoglobin concentration, food intake, serum glucose concentration, total serum cholesterol concentration, and cancer-related weight change. Secondary analysis was performed on four datasets with sample sizes ranging from 60 to 8,489. FEV1 (R2 = .56), hemoglobin (R2 = .40), food intake (R2 = .25), glucose (R2 = .24), cholesterol (R2 = .21 and .15), and cancer-related weight change (R2 = .16 and .06) were predictable to varying extents. Moreover, the use of sex, age, height, and weight as covariates and in sample size determination was shown to be relevant when testing the effects of interventions or other variables on these physiologic outcomes.

Characterization of maternal and zygotic D-raf proteins: dominant negative effects on Torso signal transduction.

The maternal D-raf serine/threonine kinase acts downstream of Torso (Tor) for specification of cell fates at the embryonic termini. D-raf activity is also required in other signal transduction pathways and consistent with its pleiotropic role, we find accumulation of a 90-kD D-raf protein throughout embryonic development. We also characterize the accumulation of maternal D-raf proteins in 0-2-hr embryos derived from females with germ cells lacking D-raf activity. Accumulation of a 90-kD or truncated mutant D-raf protein is observed for some of these embryos, while others lack the maternal D-raf protein. Then to determine whether rescue of the Tor pathway is influenced by pools of nonfunctional maternal D raf. wild-type D-raf mRNA was injected into embryos that inherit maternal stores of inactive 90-kD of truncated D-raf protein. For embryos lacking the maternal D-raf protein, a high level of terminal rescue is obtained. In contrast, rescue is reduced or not observed for embryos that accumulate mutant maternal D-raf proteins. These findings suggest that mutant forms of D-raf may deplete the embryo of a positive activator and/or form inactive protein complexes that affect rescue of the Tor pathway.

Lack of checkpoint control at the metaphase/anaphase transition: a mechanism of meiotic nondisjunction in mammalian females.

A checkpoint mechanism operates at the metaphase/anaphase transition to ensure that a bipolar spindle is formed and that all the chromosomes are aligned at the spindle equator before anaphase is initiated. Since mistakes in the segregation of chromosomes during meiosis have particularly disastrous consequences, it seems likely that the meiotic cell division would be characterized by a stringent metaphase/ anaphase checkpoint. To determine if the presence of an unaligned chromosome activates the checkpoint and delays anaphase onset during mammalian female meiosis, we investigated meiotic cell cycle progression in murine oocytes from XO females and control siblings. Despite the fact that the X chromosome failed to align at metaphase in a significant proportion of cells, we were unable to detect a delay in anaphase onset. Based on studies of cell cycle kinetics, the behavior and segregation of the X chromosome, and the aberrant behavior and segregation of autosomal chromosomes in oocytes from XO females, we conclude that mammalian female meiosis lacks chromosome-mediated checkpoint control. The lack of this control mechanism provides a biological explanation for the high incidence of meiotic nondisjunction in the human female. Furthermore, since available evidence suggests that a stringent checkpoint mechanism operates during male meiosis, the lack of a comparable checkpoint in females provides a reason for the difference in the error rate between oogenesis and spermatogenesis.

Beta 1 integrins regulate axon outgrowth and glial cell spreading on a glial-derived extracellular matrix during development and regeneration.

In the present study we have investigated functional roles for beta 1 integrin receptors in regulating axon outgrowth, and glial cell adhesion and spreading in the Xenopus retina. The XR1 glial cell line, isolated from Xenopus retinal neuroepithelium, deposits a proteinaceous extracellular matrix (ECM) with potent neurite outgrowth promoting activity. To investigate a potential role of the integrins as cellular receptors for these glial cell-derived ECM components, embryonic and regenerating retinal explants were cultured in the presence of polyclonal antibodies directed against the beta 1 integrin receptor complex. The IgGs and Fabs of the anti-beta 1 integrin antibody strongly inhibited ganglion cell axon outgrowth on the glial cell-derived ECM, although axons grew freely across the surfaces of glial cells surrounding the explants. The antibodies also inhibited outgrowth on purified laminin containing substrates in a dose-dependent fashion. In addition, the anti-beta 1 antibodies were effective at inhibiting the spreading of glial cells that migrated out from the embryonic explants, and also inhibited attachment and spreading of Xenopus XR1 glial cells on ECM substrates. These results show that the beta 1 integrins play important functional roles in axon outgrowth during development and regeneration, and also serve in regulating retinal glial cell attachment and spreading in vitro, and thus are likely to play similar roles in vivo.

Peripheral blood mononuclear cells from sheep infected with a variant of bovine leukemia virus synthesize envelope glycoproteins but fail to induce syncytia in culture.

Peripheral blood mononuclear cells (PBMCs) infected with the oncogenic retrovirus bovine leukemia virus (BLV) produce virus when cultured briefly. BLV can be transmitted in cocultures to adherent susceptible cells, which become infected, express viral proteins, and fuse into multinucleated syncytia several days later. PBMCs from 3 of 10 BLV-infected sheep displayed a lifelong deficiency in induction of syncytium formation among indicator cells in culture, although large numbers of PBMCs synthesized viral transcripts or capsid protein. Since the infected, syncytium-deficient PBMCs were > or = 97% B cells, the deficiency could not be attributed to altered host cell tropism. The syncytium-deficient phenotype was recapitulated in newly infected sheep, demonstrating that this property is regulated by the viral genotype. The alteration in the BLV genome delayed but did not prohibit the establishment of BLV infection in vivo. Envelope glycoproteins were synthesized in syncytium-deficient PBMCs, translocated to the cell surface, and incorporated into virions. However, monoclonal antibodies specific for the BLV surface glycoprotein did not stain fixed PBMCs of the syncytium-deficient phenotype. Moreover, an animal with syncytium-deficient PBMCs had lower titers of neutralizing antibodies throughout the first 5 years of infection than an animal with similar numbers of infected PBMCs of the syncytium-inducing phenotype. The syncytium-deficient variant productively infected indicator cells at greatly reduced efficiency, showing that the alteration affects an early step in viral entry or replication. These results suggest that the alteration maps in the env gene or in a gene whose product affects the maturation or conformation, and consequently the function, of the envelope protein complex.

Effect of aldosterone on renal potassium conservation in the rat.

The importance of reduced plasma aldosterone concentration (PAC) in renal potassium (K) conservation is unclear. Thus we examined the effect of aldosterone on incipient, developing, and established renal K conservation. Adrenalectomized (ADX) dexamethasone-replaced rats were continuously treated with high, normal, or low dosages of aldosterone during 4 days of dietary K restriction and were compared with rats without aldosterone replacement. High and normal aldosterone replacement reduced the fall in urinary K excretion and led to significantly lower plasma [K], skeletal muscle tissue K content, renal tissue K content, and greater negative cumulative balance of K compared with low aldosterone replacement. Likewise, plasma [K] and skeletal muscle tissue K content were significantly less in intact rats after 3 days of K deprivation and chronic treatment with aldosterone. Acute aldosterone treatment significantly increased urinary K excretion by isolated perfused kidneys. We conclude that incipient, developing, and established renal K conservation is not independent of mineralocorticoid activity and that the rapid fall in PAC during K depletion is necessary for maximal renal K conservation.

Lymphocyte activators elicit bovine leukemia virus expression differently as asymptomatic infection progresses.

Since bovine leukemia virus (BLV) replicates in B-lymphocytes, viral expression and production should respond to agents activating these cells. We asked whether synthesis of BLV capsid (CA) protein and production of infectious virus would increase when peripheral blood mononuclear cells (PBMCs) from infected sheep were stimulated in short-term culture with lipopolysaccharide (LPS), a polyclonal activator of B-cells, and compared its effects with those of phytohemagglutinin (PHA), a lymphocyte activator known to increase BLV expression. LPS treatment of PBMCs from asymptomatic sheep that had been infected for 1-4 years increased the number of cells synthesizing CA protein, the amount of CA protein per cell, and the number of PBMCs acting as infectious centers. LPS derived from several different microbes was effective. During the ensuing 4 years of asymptomatic infection, the number of PBMCs expressing virus under minimal stimulation increased for each animal. The ability of LPS to recruit additional cells to express CA protein remained constant or decreased in magnitude, yet at the same time, lower concentrations of LPS were required to elicit a maximal effect. This suggests that the cellular pathways affected by LPS are endogenously more activated as infection progresses. PHA initially stimulated fewer cells to synthesize BLV CA protein than LPS did although the amount of CA protein synthesized per cell was greater with PHA. As infection progressed, PHA surpassed LPS in the numbers of PBMCs induced to express CA protein. This suggests that the cellular pathways affected by PHA become more responsive to its effects as infection progresses. LPS increased CA expression early and transiently during culture whereas the PHA-mediated increase continued to develop for several days. Thus, LPS increases BLV expression but does so differently than PHA. Moreover, these longitudinal results show that the activation state of BLV-infected cells changes as asymptomatic infection progresses.