HGGs are a heterogeneous group of tumours, and the complexity of diverse mutations within common signalling pathways as well as the developmental and cell-type context of transformation contributes to the overall diversity of glioma phenotype. Enhanced understanding of the mutations and cell types giving rise to HGG, along with the ability to design increasingly complex mouse models that more closely simulate the process of human gliomagenesis will continue to provide improved experimental systems for dissecting mechanisms of disease pathogenesis and for preclinical testing. “
“Dying back’ axon degeneration

is a prominent feature of many age-related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease- and age-related losses may differ, both contribute to symptoms. Here, we review selleck chemicals recent advances in understanding axon pathology in age-related neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease,

amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and Ulixertinib in vitro conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age-related disease are inextricably linked and the term ‘healthy ageing’ downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age-related disease we must study both processes. “
“Human neurodegenrative diseases such as Parkinson’s

disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from almost stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generatioin of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients’ own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenrative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals.

The strains used for the study were collected from the current diagnostic material. Poziotinib API ZYM tests were used in diagnostic analysis. MICs of nicotinamide were determined by the macrodilution method in liquid medium. In the case of Candida strains, the presence of nicotinamide in the broth had a significant effect on the decrease of

enzymatic activity (P < 0.05) of esterase (C4), esterase lipase (C-8), valin-arylamidase, acid phosphatase and α-glycosydase. A considerably stronger effect of nicotinamide was observed in the case of dermatophytes (P < 0.005). Its action led to a decrease in the activity of all the enzymes under study except α-glucosidase produced by T. rubrum strains. Thus, nicotinamide exhibited biological activity towards C. albicans, T. rubrum and Trichophyton mentagrophytes, which resulted in a decrease in the activity of enzymes produced by the fungi. "
“Despite the generally excellent results achieved with fluconazole 150 mg weekly in recurrent vulvovaginal candidosis (RVVC), some patients with a long history of disease do not achieve complete resolution of symptoms following antimycotic treatment. It is thought that use of tight synthetic fabric underwear could be a significant factor in causing recurrence. We decided to compare underwear made of Dermasilk®, a pure fibroin fabric impregnated with a permanent antimicrobial protection,

with a cotton Ceritinib placebo to see whether it could be a useful adjunctive tool in the management of RVVC. We recruited 96 women who had a long-term history of RVVC and had not responded to oral antimycotics with complete satisfaction. The patients were Fossariinae randomly divided into two groups and instructed to use either white cotton placebo briefs or Dermasilk® briefs. Both groups were treated with fluconazole 150 mg once weekly for 6 months. After 6 months, the Dermasilk group showed a

statistically significant greater decrease of itching, burning, erythema and a smaller number of recurrences than the cotton group. Our work suggests that Dermasilk® briefs could be a useful adjunctive tool in addition to antimycotic treatment to help relieve the discomfort of recurrent vulvovaginitis. “
“Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients.

Overactivity of NK cells is not limited to cytotoxic function, whereas the increased IL-2-induced secretion of IFN-γ and TNF-α

from NK cells have also been reported in AD patients [34–36]. However, serum levels of IFN-γ and TNF-α were similar in AD patients and normal subjects [35, 36]. In contrast to cytokine release in NK cells, it has been shown that vascular endothelial growth factor (VEGF) secretion in AD patients was significantly decreased in AD patients compared to healthy individuals [37]. In addition to these reports that imply dysregulation of NK cells function, it is demonstrated that NK cells sensitivity to apoptosis is increased in AD patients and correlated with Bcl-2 anti-apoptotic expression [38]. However, it should be noted that there is a possibility that the involvement of NK cell in AD is not a defensive reaction, but it could be a result of progression of AD, which leads to the activation of this website immune system [39–41]. To approve this hypothesis, we should perform a long-time cohort study in which NK cell frequency and function has been considered in different times and in different stages of disease, particularly in the patients with stable disease that their disease shift to progressive phase. It is also suggested

that abnormalities in NK cells may lead to autoimmune diseases [42]. Thus, it may be possible that NK cell dysfunction has been Afatinib nmr supposed as an aetiological factor in AD patients. However, to prove this hypothesis, we should investigate in this field for a long-time on a large sample size. As both neuroprotective [43, 44] and neurodegenerative [45] effects of NK cells on neuron cells have been reported, it seems that understanding the precise role of NK cells in immunopathogenesis of AD needs to performance

of several in vivo studies on experimental models. However, it should be noted that study of NK cells in vivo is difficult which is in part due to the lack of mouse strains with selective NK cell deficiency. Surprisingly, in a limited number of studies with NK cell depletion in MS experimental models, it has been shown that NK cells are protective cells which inhibit autoreactive response of TH1 cell [46, 47]. Contrary to these reports, there is evidence that implies NK cells facilitate tuclazepam experimental MS induction [48, 49] so that NK cells were accumulated in the CNS of experimental autoimmune encephalomyelitis (EAE)-induced Lewis rats at the peak of disease. Moreover, antibody-mediated depletion of NK cells exacerbates disease after priming encephalitogenic T cells and enhances IFN-γ secreting TH1 cells [21]. The regulatory role of NK cells on TH1 responses in EAE not only in CNS but also in periphery is also demonstrated [50]. Interestingly, the studies on MS patients have shown that the frequency and function of NK cells are deficient [51], which are similar to AD reports.

3), the diverse gene usage observed in splenic B cells of dnRAG1 mice (Fig. 4), and the similar levels of heavy chain gene replacement observed in 56Rki and DTG mice (see Supplementary material, Fig. S4). Rather, several lines of evidence suggest that dnRAG1 expression PLX3397 impairs secondary V(D)J rearrangements that occur later in B-cell development associated with receptor editing. First, dnRAG1 mice exhibit impaired B-cell progression through the immature/T1-to-T2 B-cell transition, a stage that supports secondary V(D)J recombination.40 As a result, there is a significant loss of follicular B cells. Second, RAG1 is over-expressed in splenic B cells

in dnRAG1 mice relative to WT mice (Fig. 3c), suggesting that catalytically inactive RAG1 is expressed at sufficient levels to compete with endogenous RAG1 for binding to the recombination signal sequence. Third, dnRAG1 mice exhibit an expanded population of splenic B cells with a B1-like phenotype (Figs 1 and 2). This subset is known to harbour a high frequency of cells with poly-reactive

specificities,43 and might reasonably be expected to PD0325901 molecular weight increase under conditions of impaired receptor editing. Fourth, light chain rearrangements in sorted CD19+ B220lo B cells show evidence of skewing to Jκ1 (Fig. 5b). As the initial Vκ rearrangements tend to use the most proximal Jκ segment,44 this outcome is consistent with impaired initiation of secondary V(D)J rearrangement to replace a primary Vκ rearrangement to Jκ1. The B1 B cells normally constitute a small fraction of splenic B cells,

but are the most abundant B cells in the pleural and peritoneal cavities.27 B1 B cells are thought to be the primary source of natural antibodies capable of recognizing common microbial determinants, which, together with rapidly inducible antibodies generated by MZ B cells, play a critical role in early thymus-independent immune responses against encapsulated bacterial microorganisms such as Streptococcus pneumoniae.45,46 Expansion of B1 B cells has been observed in some strains of mice predisposed to autoimmune disease,47 mutant mice prone to developing a disease resembling chronic lymphocytic leukaemia,48 Olopatadine and mice deficient in certain regulators of B-cell signalling, such as SHP1,49 Lyn,50 or Siglec-G.51,52 We have not observed the onset of any obvious manifestations of autoimmune disease, such as the development of anti-nuclear antibody or glomerular nephritis, or chronic lymphocytic leukaemia-like syndromes in older dnRAG1 mice (data not shown). In this regard, the absence of B1 B-cell-associated pathological conditions in dnRAG1 mice is similar to that observed in Siglec-G-deficient mice.51,52 However, unlike Siglec-G-deficient mice, which exhibit elevated levels of serum IgM, dnRAG1 mice show a deficiency in circulating IgM and IgG antibodies (Fig. 6).

Despite the numerous limitations of the translation

of animal observations into clinical implications for patients with type 1 diabetes [25], these data are in support of the possible use of ApoTf in subjects at high risk for developing type 1 diabetes [26]. Nevertheless, we cannot rule out the possibility that the prolonged use of recombinant human ApoTf might prove immunogenic in both the DP-BB rats and the NOD mouse with potential reduction of its immunomodulatory effects and this would probably strengthen the clinical anti-diabetogenic potential of ApoTf. In general terms, apoTf may be beneficial in the early stages of human type 1 diabetes, as suggested by its low plasma levels in newly diagnosed patients included in the present study. The reduced apoTf levels check details and defective iron-binding PLX4032 price capacity have been described previously in patients with long-standing type 1 diabetes [11]. While we can only speculate on the reasons for this discrepancy with this previous report [11], we note that the apoTf levels of newly diagnosed type 1 diabetes

patients included in our study manifested a correlation with HbA1C as a type 1 diabetes clinical marker [27] to suggest that the apoTf iron binding capacity may influence the glycaemic status of patients. Indeed, iron depletion improves insulin resistance in patients with non-alcoholic fatty liver disease and diabetes resulting in increased glucose uptake in vitro[28,29]. The use of the iron chelator

desferroxiamine on HepG2 cells induced the constitutive glucose transporter Glut1, while iron depletion increased insulin receptor activity, with an effect counteracted by iron supplementation [29]. A third observation is derived from the experimental data and is represented by the modulation of glucose homeostasis by endogenous apoTf deficiency that may indirectly amplify and accelerate type 1 diabetes onset. Indeed, it is well established that elevated glucose Rutecarpine levels contribute to beta cell destruction by inducing expression of autoantigens and fatty acid synthase (FAS), thus favouring the cell-mediated immune responses and apoptosis via FAS–FAS ligand interaction [30]. Based on the data from human sera we may further hypothesize that these mechanisms are limited to the early and possibly preclinical stages of type 1 diabetes, and we encourage a study aiming at measuring ApoTf blood levels in individuals who are at high risk for developing type 1 diabetes. Thus, if endogenous apoTf plays a protective role in type 1 diabetes, we suggest that the treatment with recombinant apoTf may also prove beneficial in prediabetic individuals or newly diagnosed type 1 diabetes patients. An additional mechanism for the apoTf qualitative involvement in type 1 diabetes is based on the defective apoTf secondary to the protein glycation that follows the prolonged hyperglycaemic conditions, and impairs the protein iron binding capacity [30].

Comparisons between clinical and histopathological data from induced (day 21) and spontaneous (week 29) diabetes are shown in Table 1. Previous vaccination in NOD mice, but not in the C57BL/6 strain, had blood glucose levels considered non-diabetic. This

protection was more pronounced when NOD mice were immunized with the prime-boost procedure. Analysis of diabetes incidence revealed the same pattern, i.e. protection in spontaneous but not in induced PD0332991 datasheet disease and superior efficacy of the prime-boost strategy compared to BCG alone. Vaccination increased insulitis in STZ-induced diabetes but decreased this process in NOD mice. The cytokine profile in NOD mice was investigated based on their production by cultured spleen cells stimulated with rhsp65. Mice immunized with BCG alone and the prime-boost BCG/DNAhsp6 presented a significantly higher production of IFN-γ in comparison to non-immunized NOD mice (Fig. 4a). As shown in Fig. 4b, this increased production by mice immunized with BCG followed by

pVAXhsp65 was also seen in TNF-α levels compared to the NOD group. The BCG/DNAhsp65 group showed a high production of IL-5 in comparison with the NOD and BCG–NOD groups, although there was no statistical difference (Fig. 4c). IL-10 levels seen in spleen cells stimulated LY2835219 with rhsp65 were similar among the groups; however, there was a small increase in the BCG/DNAhsp65–NOD group. CD4+CD25+FoxP3+ Treg cells were quantified in the spleen by using flow cytometry. As shown Glutathione peroxidase in Fig. 4e, the BCG- and BCG/DNAhsp65-immunized groups presented significantly lower percentages of Treg cells in the spleen than the non-immunized NOD mice. T1D is an autoimmune condition associated with T cell-mediated destruction of pancreatic beta-cells, resulting in loss of the ability

to produce insulin [16]. As diabetes has no cure and the only available treatment consists in insulin administration, there is a great deal of interest to investigate immune-based interventions capable of protecting against the disease. Various studies have shown the potential of hsps to suppress immune responses in inflammatory diseases, such as rheumatoid arthritis, allergy and T1D [9, 17]. In this scenario, we hypothesized that a prime-boost approach with administration of BCG (a M. bovis that naturally expresses the mycobaterial hsp65) followed by the vaccine pVAXhsp65 (DNA vaccine encoding the hsp65 gene from M. leprae) could protect mice against the development of type 1 diabetes. These vaccines have already been tested separately and showed promising results not only in T1D, but also in other autoimmune diseases as arthritis and experimental autoimmune encephalomyelitis [12-15, 18, 19]. Thus, we expected an additive or synergistic effect from combining BCG and pVAXhsp65.

In-utero exposure to these autoantibodies due to placental crossing can also

result in permanent impairment to fetal development. These high-risk pregnancy conditions often result in poor outcomes such as preterm birth and low birth weight that also increase significantly the predisposition of a newborn to developmental disability and chronic Talazoparib clinical trial diseases later in life [7-10]. B cell depletion therapy has proven clinical benefits in the management of autoimmune conditions outside pregnancy. In this review, we will examine the available evidence of the possible contribution of B cells in shaping pregnancy outcomes and discuss the implication of B cell depletion in the clinical management of high-risk pregnancy. B cells, while known primarily for antibody production, also act as antigen-presenting cells and regulators of the Tamoxifen mouse innate and adaptive immune systems [4, 5]. The murine B cell compartment consists of two general populations, namely B1 and B2 cells. These cells have major differences in their phenotypes, anatomical location and functional characteristics [11,

12]. In humans, the existence of a human B1 subset is still a contentious subject, and the distinctions between B1 and B2 cells remain undefined [12]. Nevertheless, both murine B1 and human B1-like cells have been characterized as B cell subsets that spontaneously secret large amounts of polyreactive natural antibody IgM against double-stranded DNA (dsDNA), phosphorylcholine (PC) and low-density lipoproteins [11-14]. In the mouse, B1 cells have been characterized by a pattern of surface markers of B220low, immunoglobulin (Ig)Mhi, IgDlow, CD5+/–, CD43+ and CD23– expression, whereas B2 cells generally express B220hi, IgMhi/lo, IgDhi, CD43– and CD23+ markers but not CD5 markers, although B2 cells have been shown

to express low levels of CD5 following activation in vitro and in some studies Axenfeld syndrome CD5 expression has been shown on anergic B2 cells [12, 13]. In humans, CD5 expression has been described on both B1-like and activated B2 cells [12]. Recently, it has been suggested that the human B1-like cell population may include the circulating CD5+/–CD20+CD27+CD43+IgM+IgD+ B cell subset [14]. However, the definitive markers for the general human B1 cell population remain to be determined. B2 cells are known as conventional B cells, which make up the majority of the splenic B cell population. Unlike B1 cells, which appear in fetal liver tissue as early as mid-gestation and are regenerated by self-renewal processes in the peritoneal cavity, B2 cells emerge from bone marrow stem cells during the late neonatal period and their clones are selected by a stringent process of clonal deletion and expansion in the germinal centre of the spleen [12, 13].

104 Beyond HCV core protein and

NS3, NS4 also suppressed T-cell responses as a result of the effect on monocytes or DC. The DCs produce high levels of type I IFN in response to double-stranded RNA generated upon viral replication.105 However, HCV suppresses this response via the NS3–NS4A viral protein, which blocks IFN regulatory factor 3-mediated induction of type I IFN.106 In Brady et al.’s study,107 supernatants from NS4-stimulated monocytes inhibited LPS-induced maturation of DC and suppressed their capacity to stimulate proliferation and IFN-γ production by allospecific T cells. Their data suggested that HCV subverts cellular immunity by inducing IL-10 and inhibiting IL-12 production by monocytes, which in turn inhibits the activation of DC that drive the differentiation of Th1 cells. Takaki et al.108 also found that HCV non-structural proteins, particularly NS4, change the iDC MAPK inhibitor phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions. HCV NS5 was also shown to impair PDC function with

several other in vivo studies indicating decreased numbers and impaired function of PDC in chronically HCV-infected patients.109 BGJ398 supplier Over-expression of HCV core, NS3, NS5A or NS5B proteins induced apoptosis in mature DC.110 Likewise, individual HCV proteins, Core, NS3, NS4, NS5 as well as fused polyprotein (Core–NS3–NS4) were found to impair functions of both iDC and mDC by regulating the expression of co-stimulatory and antigen presentation molecules, strikingly reducing IL-12 secretion, inducing

the expression of FasL to mediate apoptosis, interfering with allo-stimulatory capacity, inhibiting TLR signalling and inhibiting nuclear translocation of nuclear factor-κB in DC.111 It is reported that increased PD-L1 expression and PD-L1/CD86 ratio on DC was associated with impaired DC function in HCV infection.112 Further indications that HCV affects DC function came directly from studies using the cell culture-produced HCV (HCVcc). Culture with HCVcc demonstrated inhibition of maturation of MDDC induced by a cocktail of cytokines (IL-1β, TNF, IL-6, prostaglandin E2) Uroporphyrinogen III synthase while enhancing the production of IL-10. In addition, DC exposed to HCVcc were impaired in their ability to stimulate antigen-specific T-cell responses.71 Similar experiments performed by Shiina and Rehermann113 proved that HCVcc inhibited TLR-9 mediated IFN-α production by PBMC and PDC. In contrast to its effect on PDC, HCVcc did not inhibit TLR3-mediated and TLR4-mediated maturation and IL-12, IL-6, IL-10, IFN-γ and TNF-α production by MDCs and MDDCs. Likewise, HCVcc altered the capacity of neither MDCs nor MDDCs to induce CD4 T-cell proliferation. Gondois-Rey et al.

Several EM techniques have been used to investigate Cilomilast price biofilms, with scanning electron microscopy (SEM) as the predominant choice (Sutton et al., 1994; Priester et al., 2007; Sangetha et al., 2009). Conventional SEM methods are far from optimal for investigation of water-containing specimens such as biofilms, because the technique requires dehydration

of the sample. In most cases, the choice of microscope is based on availability and not the suitability. We here present a micrograph survey of P. aeruginosa biofilm development with four different SEM techniques: standard SEM, cryo-SEM and environmental-SEM as well as focused ion beam (FIB)-SEM. All bacteria were grown in ABtrace minimal medium containing 0.3 mM glucose for continuous cultures and 0.5% glucose for batch cultures, as previously described (Bjarnsholt et al., 2005). Planktonic cultures were grown in shake flasks at 37 °C. Continuous biofilms were cultivated in once-through flow chambers, perfused with sterile media, as previously described (Bjarnsholt et al., 2005). The biofilms were imaged by SEM as previously described (Qvortrup et al., 1995). Briefly, bacteria were harvested and fixed in 2% glutaraldehyde, postfixed in 1% OsO4, critical point–dried using CO2 and

sputter-coated with gold according to standard procedures. Specimens for SEM were investigated with a Philips XL Feg30 SEM operated at 2–5 kV accelerating high throughput screening tension. Glass-pieces from the flow cell were broken and plunge-frozen in slushed liquid nitrogen at −210 °C and transferred in a special transfer container, which is under continuous vacuum to the cryo-preparation chamber attached to the Quanta 3D FEG (FEI). The sample temperature was raised to −95 °C for approximately 3 min to sublime any condensed ice from the surface

gained during transfer. The temperature of the sample was then reduced to −125 °C. BCKDHA Essentially, to avoid charging problems while searching for a suitable site, the sample was sputter-coated with platinum for 160 s, giving a thickness of approximately 15 nm. The sample was then passed through the transfer lock to the FIB-SEM cryo-stage, which was maintained at −125 °C. Imaging was performed using an accelerating voltage of 3–10 kV. Biofilm containing glass-pieces from the flow cell were broken of and were mounted onto double-sided carbon tape on a small, circular metal stub, and samples were imaged with a Quanta 3D FEG SEM (FEI) operated in ESEM mode. The biofilm samples were viewed with a gaseous secondary electron detector in a humidified environment. The system was operated under high accelerating voltages (5–15.0 kV), and the low chamber pressures were gained with a special ESEM final lens insert, so a maximum pressure of 2700 Pa could be obtained. The biofilms were fixed with 2% glutaraldehyde in 0.05 phosphate buffer (pH = 7.2) and postfixed in 1% osmium tetroxide with 1.

4a). IL-12p40 mRNA levels (Fig. 4b) were increased significantly in both lymph nodes (P < 0·005) and spleen (P < 0·01) after TNF-α injection. In contrast, the levels of IFN-γ (Fig. 4c) and IL-10 (Fig. 4d) mRNA expression remained unchanged after TNF-α injection compared to the BSA-injected group. The magnitude of the IFN-γ response was much higher compared to the low levels of IL-10 mRNA in both lymph nodes and spleen, indicating that Th1 cytokines predominate in guinea pigs 6 weeks after BCG vaccination. Peritoneal cells were stimulated with PPD or live M. tuberculosis for assessing the effect of TNF-α injection on mRNA

expression. In the learn more TNF-α-injected guinea pigs, stimulation of peritoneal cells in vitro Selleckchem AP24534 with live M. tuberculosis caused a significant increase (P < 0·01) in the mRNA response at 12 h (Fig. 5a), and a further increase at 24 h (Fig. 5b) compared to the BSA-treated guinea pigs. Similarly, PPD caused a significant increase (P < 0·01) in the TNF-α mRNA at 12 h

(Fig. 5a) but a decrease (P < 0·05) at 24 h (Fig. 5b). Both M. tuberculosis and PPD stimulation induced similar levels of TNF-α mRNA in the peritoneal cells from BSA-injected guinea pigs (Fig. 5a,b). Peritoneal cells showed a high level of IL-12p40 mRNA expression after stimulation with M. tuberculosis (P < 0·005) compared to PPD in both TNF-α- and BSA-injected guinea pigs (Fig. 5c) but there was no difference in the response between the two groups. Although PPD induced a lower level of IL-12p40 mRNA expression in the peritoneal cells of both TNF-α- and BSA-injected guinea pigs compared to M. tuberculosis stimulation, the response was significantly lower (P < 0·05) in the TNF-α-injected guinea pigs (Fig. 5c). The IL-10 mRNA expression was significantly lower (P < 0·05) when peritoneal cells from TNF-α-injected guinea pigs

were stimulated with either M. tuberculosis or PPD (Fig. 5d) compared to the BSA-injected group. In the BSA-injected guinea pigs, peritoneal cells stimulated with PPD had four times higher levels of IL-10 mRNA than the M. tuberculosis-stimulated cells. Lymph node, spleen and lung tissues from TNF-α- and BSA-injected animals were processed for histological studies to determine whether Acetophenone TNF-α altered the cellular response to BCG vaccination. The H&E staining of the lymph nodes indicated that there was an increase in the infiltration of mononuclear cells in the lymph nodes of TNF-α injected animals (Fig. 6). As clear from the figure, this was seen throughout the lymph nodes in the TNF-α-injected guinea pigs, while in the BSA-injected animals they were mainly in the cortical areas (indicated by arrows). There were no significant histological changes in the lung or spleen tissues between the TNF-α- or BSA-injected guinea pigs.