The role of FcRn includes the maintenance of serum IgG and albumin levels and the delivery of antigen in the form of immune complexes to degradative compartments within cells. The FcRn–IgG interaction is strictly pH-dependent, with a maximum at pH 6, and becomes undetectable as near neutral pH is approached, a feature that is essential for efficient transport. IgG transport between the blood and

Ku-0059436 manufacturer interstitial compartments may proceed by convection through paracellular pores in the vascular endothelium, or via FcRn-mediated transcytosis across vascular endosomal cells. Because of the redundancy of the transport systems, high-dose IVIG may help to block FcRn resulting in the enhanced clearance of pathogenic autoantibodies, but will never be able to block it completely, as

indicated in several experimental studies to date [42]. Although improving the binding of IgG to FcRn in vitro generally translates to an improved serum IgG half-life in vivo, this is not always the case. Recombinant therapeutics genetically engineered to contain IgG fragments with the CH2–CH3 domain that binds to FcRn can have significantly prolonged half-life due to protection of catabolism through FcRn binding. However, increased binding affinity to the FcRn does not appear to be proportional to the half-life extension. For example, when comparing variants of Herceptin antibody (an ERBB2-specific human IgG1 against mammary tumour cells) with a threefold selleck screening library increase in FcRn binding at acidic pH and another variant with a 12-fold increased binding at acidic pH and also enhanced binding at more neutral pH,

both antibodies exhibited similar half-lives when tested in a humanized FcRn transgenic mouse model [43]. Increased binding may enhance degradation of IgG under neutral 6-phosphogluconolactonase conditions. Clearly, there is an obvious need to have a better understanding of FcRn in the exact regulation of IgG-mediated responses and half-life in vivo. Research in immunoglobulin therapy with IVIG or SCIG has shown that therapy targets and treatment options evolve in parallel. Achieving good clinical outcomes to enable a state of health as found in immunocompetent individuals is achievable with the use of 0·4–0·6 g/kg/month for many patients with PI, although some patients may require higher doses. For patients with autoimmune neuropathies, an empirically derived starting dose of 2 g/kg is used frequently in the acute setting as in Guillain–Barré syndrome. For maintenance treatment, evidence from a recent randomized placebo-controlled trial in chronic inflammatory demyelinating neuropathy suggests that a dose of 1 g/kg every 3 weeks is sufficient to maintain strength [44]. Indications for review of immunoglobulin doses in patients with PI and autoimmune neuropathies are summarized in Table 5.

However, immunosuppressive therapy failed to improve her

condition. When her 17-year-old sister (patient 2) also developed epilepsy, an intensified search for metabolic diseases led to the diagnosis. On electron microscopy mitochondrial abnormalities mainly affecting neurons were detected in the brain biopsy of patient 1, including an increase in number and size, structural changes and globoid inclusions. In patient NVP-LDE225 ic50 2, light and electron microscopy on a muscle biopsy confirmed a mitochondrial myopathy, also revealing an increase in mitochondrial size and number, as well as globoid inclusions. Neurons may be the primary target of mitochondrial dysfunction in brains of patients with Alpers disease related to POLG1 mutations. During early disease stages, brain histopathology may be misleading,

showing reactive inflammatory changes. “
“S. Montori, S. Dos_Anjos, A. Poole, M. M. Regueiro-Purriños, I. L. Llorente, M. G. Darlison, A. Fernández-López and B. Martínez-Villayandre (2012) Neuropathology and Applied Neurobiology38, 710–722 Differential effect of transient global ischaemia on the levels of γ-aminobutyric acid type A (GABAA) receptor subunit mRNAs in young and older rats Aims: This study has investigated how global brain ischaemia/reperfusion (I/R) modifies levels of mRNAs encoding γ-aminobutyric acid type A (GABAA) receptor α1, β2 and γ2 subunits and glutamic acid decarboxylase 65 (GAD65) in an age- and structure-dependent manner. Gene expression in response to treatment with the anti-inflammatory agent meloxicam was also investigated. Methods: Global ischaemia was FK866 molecular weight induced in 3- and 18-month-old male Sprague–Dawley rats. CA1, CA3, and dentate gyrus (DG) hippocampal areas, cerebral cortex (CC) and caudate putamen (C-Pu) from sham-operated and I/R-injured animals were excised 48 h after the insult and prepared for quantitative click here polymerase chain reaction assays. Following I/R, meloxicam treatment was also carried out on young

animals. Results: Data revealed significant decreases in the levels of all GABAA receptor subunit transcripts in the hippocampus of both young and older injured animals compared with sham-operated ones. In contrast, there was either an increase or no change in GAD65 mRNA levels. GABAA receptor subunit transcript decreases were also observed in the CC and C-Pu in young injured animals but not in the CC of the older injured ones; interestingly, significant increases were observed in the C-Pu of older injured animals compared with controls. Meloxicam treatment following the insult resulted in a diminution of the previously described I/R response. Conclusions: The data indicate that I/R results in the modification of the levels of several gene transcripts involved in GABAergic signalling in both the pre- and postsynaptic components, of this neurotransmitter system, in an age- and structure-dependent manner.

Many Māori will prefer to die at home and whānau often prefer to take their terminally ill relative home, although, as with other groups in Crizotinib society, the pressures of urbanization and geographical spread of modern whānau mean that this should not be assumed. When an individual prefers to die on their tūrangawaewae (tribal land) this may be geographically distant from their

current place of residence and/or rural. Good palliative care is likely to be facilitated by a heath care professional assisting the patient and whānau with finding appropriate health care services in their chosen place of death, for example identifying a local general practitioner and referring to local palliative care services. Community palliative care services may be more acceptable than inpatient hospice care to many Māori. In hospital or hospice, whānau and patients should

be offered a single room and access to appropriate spiritual and cultural support. As autopsy can be particularly distressing to Māori it is appropriate to prepare whānau in advance if referral to the coroner and/or autopsy is likely to be necessary and explain beta-catenin inhibitor why.[9] Care of the tūpāpaku (deceased) can be a particularly sensitive area as it is generally highly ritualized in Māori culture. Whānau may have specific cultural and spiritual practices they wish to observe around handling of the body, including washing and dressing and staying with the tūpāpaku as they progress from the ward, to the mortuary and to the funeral director then marae. The way in which the tūpāpaku is transported is also significant to many Māori, for example wrapped in allocated linen, feet first and following a pre-determined route away from public thoroughfares. Blessing the room the tūpāpaku died in with a karakia prior to cleaning may also be appropriate. Erastin research buy Again seeking advice from local kaumātua and specifically asking whānau is likely to be the best way to

avoid causing inadvertent offense by breaching protocol.[9] Individual patients and whānau may wish to use rongoā (traditional Maori methods of healing) to achieve their goals of care. Considering the Whare Tapa Whā model, rongoā may be valued for their contribution to aspects of well-being other than physical health. Local kaumātua (elders) can advise on local practice. The handling of food, taonga (valuables), the head and human waste are areas to be aware of. Generally, food and medicines for human consumption should be kept separate from items for general use, for example microwaves or refrigerators should be used for either food preparation/storage or non-food uses (e.g. heating wheat bags), not both, tea towels should only be used for drying dishes and tables should not be sat on.

Based on this data, it is surprising that the possibility that the entrance of mature cells into the thymus could be a common occurrence during the acute phase of an infectious/inflammatory process has not been generally addressed, since a large proportion of T and B cells acquire an activated phenotype in these situations. Moreover, thymocyte depletion observed in

several infectious disease models could even increase the possibility of peripheral cell migration into the thymus considering reports describing Pictilisib order that when the cellularity of this organ is compromised (neonatal, irradiation, SCID mice, atrophic aged thymi, etc.), peripheral cell infiltration into the thymus considerably increases [4, 6, 18, 19]. In this context, the aim of this work is to demonstrate selleck chemicals llc that migration of peripheral T and B cells

to the thymus occurs during the early phase of Th1 inflammatory/infectious processes triggered by different type of pathogens. In support of this hypothesis, we examine the entrance of B and T cells into the thymus in well-established Th1 infectious/inflammatory murine models. Furthermore, we demonstrate that peripheral T cells and B cells but not NK cells, macrophages, or DCs largely migrate to the thymus under inflammatory/infectious conditions but only when the cellularity of the organ is compromised. Moreover, the entrance of peripheral lymphocytes to the thymus necessarily requires monocyte chemoattractant protein-1 (MCP-1) production in this second organ and CCR2 expression

on migrating lymphocytes. Importantly, we demonstrate as a general mechanism that this phenomenon is triggered by IL-12 and IL-18 produced during the acute phase of Th1/inflammatory/infectious processes. Moreover, our data with OVA-specific TCR transgenic mice suggest that rather than being a TCR-dependent mechanism, any T cell has the potential to migrate to the thymus in response to inflammatory conditions. To address if migration into the thymus of mature peripheral lymphocytes is a common feature of Th1-driven inflammatory/infectious processes, we adoptively transferred CFSE-labeled splenocytes from mice either treated in vivo with LPS (a bacterial product) or infected with a fungus (Candida albicans) or a parasite (Trypanosoma cruzi) to recipient hosts that have received the same treatments. All these pathological conditions are characterized by a potent Th1 immune response, especially during the acute phase of the process [20-23]. Data presented in Fig. 1 demonstrate that after LPS treatment (Fig. 1A), C. albicans (Fig. 1B), or T. cruzi (Fig. 1C) infections, CD4+ and CD8+ T cells together with B cells entered the thymus in different proportions.

On average, infants were 12.5 months old at the conclusion of the study, but depending on how many sessions they contributed, infants ranged in age from 11.5 to 14 months when the study ended. All Daporinad cell line infants were born at full term and were in good health. All families but one were urban and of middle to upper-middle socio-economic status. Both mothers and fathers had on average 17 years of education. Mothers’ average age at the start of the study

was 33 years; fathers’ average age was 35 years. Families were recruited to participate in the study by posting fliers about the research around the university where the research was conducted and by leaving fliers at healthcare centers. Participants were also recruited via “snowball” technique where participants mentioned the research via word-of-mouth to friends or contacts. Families received disks with the movies from each observation session and a children’s book as thank you gifts. Based on prior studies of hand and reaching preference in infancy, we used a semi-structured reaching procedure

at each session to test one- or two-handed reaching preference (e.g., Corbetta & Bojczyk, 2002; Corbetta & Thelen, KU-60019 solubility dmso 1999; Corbetta et al., 2006; Fagard & Lemoine, 2006; Hinojosa et al., 2003; Michel, Ovrut, & Harkins, 1985; Michel et al., 2002, 2006; Morange-Majoux, Pezé, & Bloch, 2000; Rönnqvist & Domellöf, 2006). The items used in the reaching task were a Fisher Price® two-part car and doll (7.5 cm long × 3.5 cm wide × 7 cm high), a plastic toy block with ribbons on top (5 cm long × 5 cm wide × 5 cm high), a plastic rattle (14 cm long × 14 cm circumference at the widest part × 3 cm wide at the handle), and a cup with a plastic egg inside (5.5 cm long × 5.5 cm wide × 6.5 cm high; see Figure 1). Because there is evidence that large objects provoke bimanual task performance in comparison with smaller objects, we chose objects that could feasibly be grasped with one hand to assess changes in reaching preference (see Greaves, Imms, Krumlinde-Sundholm, Dodd, & Eliasson, 2012 for a review). Infants

sat in a baby chair with a plastic tray. Before each presentation, we performed a check to ensure symmetrical body alignment of the trunk and hands to prevent any biases in reaching and acquisition find more of the toys (e.g., slightly turned to one side, one hand beneath the tray, etc.). The experimenter sat out of camera range to the side of the baby chair facing the infant. The camera was placed on a tripod, opposite the infant, at a distance of approximately 2 m. An experimenter presented each toy five times, for a total of 20 presentations per session (Tronick et al., 2004). Using Michel et al.’s (1985) procedure, we presented the objects in two ways: (1) three of the four toys were presented at midline directly in line with the infant’s nose so that the objects were equally accessible to each hand (e.g.

Activating NK cell receptors frequently transmit activating signals via immunoreceptor tyrosine-based activation motifs (ITAMs) present in accessory proteins non-covalently associated with the intracellular region of the activating receptor [17]. Activating NK cell receptors employing this strategy typically express a short cytoplasmic tail lacking ITIMs or other tyrosine signalling motif and possess a basic residue within their transmembrane sequence for association with transmembrane accessory proteins [10, 18, 19]. LLT1 possesses these properties associated with an activating receptor. In the present study, we have examined the signalling pathways

associated with LLT1-stimulated OTX015 IFN-γ production. We determined that the human NK cell line NK92 expresses LLT1 on its surface, and upon ligation with CD161 expressing K562 target cells stimulates IFN-γ production. Using this LLT1:CD161 ligation system, we analysed IFN-γ production in the presence or absence of specific pharmacological inhibitors to determine what signalling pathways are required for LLT1-induced IFN-γ production. These results indicate that LLT1 downstream signalling is likely dependent upon Src-protein tyrosine kinase [Src-PTK], p38 and ERK signalling pathways, but not dependent upon PKC, PI3K or calcineurin. These results were followed up with phosphorylation analysis, which confirmed that the ERK signalling pathway

is associated with Apoptosis Compound Library chemical structure LLT1-mediated IFN-γ production. Finally, we analysed IFN-γ mRNA transcription associated with LLT1 ligation. We found that LLT1 ligation is not associated with any change selleck screening library in detectable IFN-γ mRNA levels, suggesting that LLT1 stimulates IFN-γ production by modulating post-transcriptional or translational events. Tissue culture.  NK92 cells were maintained using alpha-MEM

(Hyclone, Logan, UT, USA) with 25% defined Foetal Bovine Serum (Hyclone, Logan, UT, USA) and where appropriate 30 U/ml recombinant human IL-2 (Calbiochem, La Jolla, CA, USA). All other cells were maintained using 4+RPMI 1640 (GibcoBRL, Grand Island, NY, USA; with 10 mm MEM non-essential amino acids, 10 mm HEPES, 100 mm Sodium Pyruvate, 2 mm glutamine and penicillin/streptomycin) with 10% FetalPlex Animal Serum Complex (Gemini Bio-Products, Sacramento, CA, USA) at 37 °C, 5% CO2 in a water-jacketed tissue culture CO2 incubator. Flow cytometry.  To evaluate the surface expression of LLT1 on NK92, cells were stained with 5 μg of anti-human OCIL/LLT1 monoclonal antibody (R & D Systems, Minneapolis, MN, USA) and 10 μg of 4C7 mouse anti-human LLT1 monoclonal antibody (Abnova, Taipei, Taiwan) and a PE-conjugated goat anti-mouse IgG polyclonal secondary antibody. In order to confirm the lack of CD161 expression on NK92 cells, cells were stained with mouse anti-human CD161 (Clone DX12; BD Biosciences, San Diego, CA, USA) and an FITC-conjugated goat anti-mouse IgG polyclonal secondary antibody.

Between 10% and 20% of the transduced cell lines had these properties. They were then transplanted into sublethally irradiated CD45.2+Rag1−/− hosts in the continued in vivo presence of doxycycline through the drinking water. Four weeks

after transplantation BM, spleen, peritoneal cavity and thymus of these mice were analyzed by flow cytometry for the expression of CD45.2, for cells of host PCI-32765 price origin, and for the expression of CD45.1 and of GFP, for miRNA-expressing cells of donor origin, as well as for the expression of CD19+CD45.1+, further differentiated pre-B and B cells of donor origin. These mature B-cell compartments did not contain host-derived CD45.2+CD19+ cells, as expected in a RAG1−/− host. In the absence of miRNA expression, CD45.1+CD19+ pre-B cells transduced with either miR-221 or miR-222,

or both, did not migrate to BM. Hence, only host-derived CD45.2+, but no CD45.1+ donor-derived CD19+ precursor B cells could be found in BM. In the same hosts donor cells were found as CD45.1+GFP−CD19+sIgM+ B cells in spleen and peritoneum (Fig. 3A and B and Supporting Information Fig. 5). This reconfirms for the transduced pre-B-I-cell lines CHIR-99021 mouse used in our experiments the previous findings [14], that fetal liver-derived pre-B-I cells, upon transplantation, do not home to BM, but populate spleen and peritoneum with B1-type CD19+sIgM+CD5+ B cells. By contrast, transplantation of miR-221-expressing cells in the in vivo presence of doxycycline led, within 4 weeks, to an accumulation of approximately 3 × 105 donor-derived CD45.1+ cells in BM (Fig. 3A and B). Practically all of these donor-derived cells expressed GFP, hence miR-221. They had preserved their original CD19+GFP+IgM−IL-7R+AA4.1+ pre-B-I-cell-phenotype (Supporting Information Fig. 5, first panel). In the doxycycline-fed mice 40% of the IgM+IL-7R−AA4.1− cells in spleen (and 30% of the CD19+IgM+CD5+ in peritoneum) were GFP+CD45.1+ donor-derived mature B

cells (Supporting Information Fig. 5, second and third panel). This suggests that only pre-B-I cells expressing the transduced miR-221 migrate to and reside in the BM, while those not expressing miR-221 mature directly into IgM+ B cells, without migrating to BM. Furthermore, IMP dehydrogenase it indicated that continued miR-221 expression does not inhibit the in vivo differentiation to mature B cells. The transplanted, thereafter ex vivo FACS-sorted CD45.1+GFP+sIgM− BM cells were capable to develop to GFP+CD19+MHCII+sIgM+ B cells within 3 days in vitro (Supporting Information Fig. 6). Hence, again, overexpression of miR-221 had no detectable inhibitory effect on this development to immature and mature B cells. When CD45.1+ donor-derived cells from the spleen of untreated mice were sorted and cultured in vitro for 3 days, the cells became GFP+ within 3 days.

Seven months after implantation in October 2001, the knee prosthesis was finally removed after consent of the patient. Fungal and

bacterial cultures taken at this time remained negative. The patient showed a fast clinical improvement with a reduction of ESR and CRP to 23 and 16, respectively. Itraconazole therapy was continued with 400 mg day−1 for another 6 months. Serum levels were not measured during ITZ treatment. One Gefitinib month after the termination of ITZ administration, the patient developed a recurrence of infection with a draining fistula close to the knee. Therefore, in March 2002, the patient was referred for a second opinion to a tertiary care orthopaedic reference centre. The consultant advised to amputate the leg just above the knee to allow the proper fitting of a limb prosthesis. The patient refused to follow the advice of limb amputation. But in September 2002 he agreed to an arthrodesis of the knee with an external fixation devise. Cultures taken during the arthrodesis were negative. Four months after placement, the external fixation devise was removed but in January 2003 (only 1 month after removal) the patient presented again with

pain, mild swelling, skin lesions and one pus-producing fistula in a scar above the proximal left tibia (Fig. 3). Magnetic resonance imaging YAP-TEAD Inhibitor 1 manufacturer (MRI) showed a multi-loculated abscess on the anteromedial side of the left tibia and infiltration of the local tissue (Fig. 4a,b), while MRI of the upper leg was without pathological findings. During surgical exploration of the lower leg, several subcutaneous collections of fluid were excised and again P. apiosperma was cultured. In vitro next susceptibility testing according to CLSI 38A2 broth microdilution15 after almost 1 year of ITZ therapy showed that the causative P. apiosperma strain had high minimal inhibitory concentrations (MIC) of amphotericin B (16 mg l−1), ITZ (>16 mg l−1), and isavuconazole

(16 mg l−1). The lowest MICs/MECs (minimal effective concentrations) were found for voriconazole (VORI; 1 mg l−1), posaconazole (1 mg l−1), caspofungin (1 mg l−1), anidulafungin (0.5 mg l−1) and micafungin (0.125 mg l−1). Because VORI was just registered in the European Union in 2003, with the label to treat Scedosporium and Pseudallescheria infections and based on our in vitro susceptibility results, previous case reports with favourable outcome,16–18in vitro studies19,20 and in vivo results21,22 with Scedosporium strains, the antifungal therapy was changed from ITZ to oral VORI (loading dose: 2 dd 400 mg for two days, followed by 1 dd 400 mg). As the patient was not clinically improving and ulcerous skin lesions persisted, suggesting progression and spreading of the Scedosporium infection, an above knee amputation was carried out in April 2003, six weeks after initiation of VORI therapy.

Indeed, morphological examination of the mucosa shows epithelial cells in various states of degradation in the vicinity of the schistosome egg (56). Alternatively, the diminished secretion could result from adaptation of the ileal mucosa to the infection. Such an adaptive response has been described for N. brasiliensis-infected rats RGFP966 and is directed by a neurally mediated mechanism possibly aimed at preventing excessive fluid loss (57). Likewise, in T. spiralis infected ferrets,

basal and stimulated jejunal secretions were attenuated during the enteric stage of infection (58). In these models, the reduced secretion was accompanied by a shift from cholinergic to noncholinergic regulation of secretion, which was associated with an increase in substance P immunoreactivity within

the mucosa. Interestingly, in this context, S. mansoni infection in the mouse results in increased immunoreactivity for the neuropeptide CGRP in close apposition to MMC within the ileum (6,7). Although the role of CGRP in S. mansoni infection remains to be elucidated it is likely that CGRP is involved in neuro-immune interactions between local primary afferent nerve fibres and mast cells (7). Extrapolation of these murine data to man involves a large number of uncertain assumptions, partly arising out of the lack of adequate human data [for reviews see (59,60)] but also since schistosome infection in mice differs in many respects

from that in humans (60). In both human and murine, however, the majority of pathology develops FK506 in vitro at the sites of maximal accumulation of eggs: the intestine and the liver (59,60). Gastrointestinal schistosomiasis is characterized by chronic abdominal pain and discomfort, loss of appetite and diarrhoea that commonly contains occult blood (60). The present results show that in mice, in addition to the previously described impairment of sugar and fluid transport (61), the basal secretion and the maximal secretory capacity of the ileal epithelium are severely reduced 8 weeks after schistosome infection. next If and how this finding relates to the patient symptoms cannot be inferred at present, but a derangement of fluid transport may explain some of these. The reported impairment of the mucosal barrier in the murine ileum suggests that translocation of bacteria from the gut lumen to extra-intestinal sites (62) might be increased during schistosomiasis. At present, only limited information is available on the effects of schistosomiasis on murine intestinal function (63). The present results suggest, however, that use of murine models may be of importance for the dissection of the intestinal pathologies. In summary, in S. mansoni-infected mice, the intestinal barrier is severely impaired both in WT and in Mcpt-1−/− mice and egg excretion takes place independently of mMCP-1.

Counts of eosinophils and globule leucocytes were not normally distributed, were transformed as ln(count + 1), and were analysed using the general linear models procedure of SAS. The model included fixed effects of breed, group (infection status by day of sacrifice, with two infected and three control groups) and breed by group interaction. Results are presented as back-transformed means and SE. Serum

immunoglobulin concentrations were analysed within infection status using the model used for the repeat-measures analysis of variance of FEC and PCV. RGFP966 nmr Lymph node IgE concentrations at sacrifice were analysed using the model applied to the abomasal cell counts. Simple correlations (r) were calculated between measurements taken in infected animals at sacrifice at 3 and 27 days p.i. (i.e. in the presence of larvae and adult worms respectively). Reported correlation coefficients differed from zero (P < 0·05) unless stated otherwise. No parasite eggs were seen in the

faeces of control animals throughout the study, but all experimentally infected lambs had measurable FEC by 16 days p.i. (Figure 2). The mean FEC of wool sheep was similar to that of hair sheep on day 16, but was 2·8-fold higher at day 21 (3647 ± 770 vs. 1280 ± 867 respectively), and 2·5-fold higher at day 27 (3136 ± 1599 selleck screening library vs. 1267 ± 837) than that of wool sheep (P = 0·12 when mean FEC were averaged across days 21 and 27). Abomasa of control sheep were free of adult H. contortus, whereas worms were present in all challenged sheep. On day 27 p.i., the mean number of adult H. contortus in infected hair sheep (2491 ± 753) was lower (P = 0·07) than

that in wool sheep (4535 ± 690). Lower worm counts were correlated with higher PCV (r = −0·53, P = 0·08) and lower FEC (r = 0·71, P = 0·01). The average PCV of control hair (36·3 ± 0·7) and wool (35·5 ± 0·5) sheep were similar and did not differ between days. However, infection was associated with lower PCV in both breeds at days 16 and 21, followed by an increase in PCV in both breeds at day 27 (Figure 2). In infected animals, PCV were next higher in hair compared with wool sheep; this difference approached significance (P < 0·10) at day 21 p.i. The day of peak FEC corresponded to the time of lowest PCV and FEC and PCV were negatively correlated (r = −0·78, P = 0·07). Breed differences in abomasal lymph node weight were not observed in control animals, but lymph nodes from infected hair sheep were heavier than those of infected wool sheep (P = 0·04, Table 1). Lymph nodes of infected animals of both breeds were likewise heavier (P < 0·001) than those of corresponding control animals. Lymph node weights at sacrifice were favourably associated with PCV on days 0 (r = 0·58), 16 (r = 0·61) and 21 p.i. (r = 0·56).