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Egg has ben documented as a rich source for the supply of biologically active peptides. This study characterizes the immunomodulatory effects of an egg white enzymatic hydrolysate (EWH) using a BALB/c mouse model of egg allergy. Mice were orally sensitized to egg white and subsequently gavaged with EWH. ELISA results indicated significant reductions of both serum histamine and specific IgE titers in EWH-fed mice, accompanied by a repression of both IL-4 and IFN-gamma production in spleen cell cultures. Similarly, real-time RT-PCR analyses highlighted decreased mRNA expression of IFN-gamma and IL-12 (Th1-biased), as well as lower ratios of IL-4 and IL-13 mRNA (Th2-biased). On the other hand, increased intestinal expressions of TGF-beta and FOXp3 mRNA were determined in EWH-fed mice, suggesting induction of local regulatory mechanisms. The presence of immunodominant epitopes was proposed to be responsible for the immunomodulatory effects observed.

Oryan, A., Mehrabani, D., Owji, S.M., Motazedian, M.H., Hatam, Gh. and Asgari, Q. 2008. Morphologic changes due to cutaneous leishmaniosis in BALB/c mice experimentally infected with Leishmania major. J. Appl. Anim. Res., 34: 87-92. BALB/c mice were injected subcutaneously in hind footpad with 10 6 promastigotes of Leishmania major. At various times, two mice each were euthenised and their skin, popliteal lymph nodes, spleen, liver and femoral bone marrow were removed and processed for histopathological and ultrastructural evaluation and for Specific PCR to confirm the presence of L. major infection. Diffuse infiltration by histiocytes, lymphocytes and plasma cells of the dermis and subcutaneous tissues of the infected skin was found along with small granulomas containing macrophages, lymphocytes and plasma cells. Follicular hyperplasia and sinus histiocytosis consisting of lymphocytes and plasma cells were evident in the lymph nodes and spleen. Sinusoid dilatation of liver and infiltration of lymphocytes, macrophages and plasma cells were demonstrated in the portal spaces of the liver. The amastigote form of the protozoa was clearly visible in the intracytoplasmic vacuoles of the femoral bone marrow macrophages. The PCR performed on tissues revealed infection by L. major. The results showed that, the femoral bone marrow was the tissue of choice for identification of amastigote form of L. major in experimentally infected BALB/c mice.

Lithium carbonate is used as a standard treatment for manic depression. While researchers have investigated the teratogenic effects of lithium carbonate on embryos of various animals in later stages of development, very limited work has been done on the probability of effects at early stages of development. In this study, the teratogenic effect of lithium carbonate was investigated at earlier preimplantation through implantation stages of development of Balb/C mouse embryos. A therapeutic dose (i.e., 300 mg/kg b.w.) was injected into mice intraperitoneally on days 3.5, 4.5, 5.5, and 6.5 of pregnancy. Then, on day 15.5 of gestation, embryos were collected from the pregnant animals. Among the embryos, 71.7% were healthy, 10.7% resorbed, 3.1% showed lordosis, 8.1% were underdeveloped and 8.4% had eye malformations. Significant increases (P < 0.05) in the number of hepatic megakaryocytes and nucleated red cells were also observed among experimental embryos. Analysis of maternal serum proteins prepared from dissected animals showed a significant increase or decrease (P < 0.05) in the levels of serum proteins albumin, α2 globulin, β globulin, and γ globulin. This research on early developmental stages suggests that pregnant mothers need to be aware of possible teratogenic effects at early stages of pregnancy, although it has been thought that the egg envelope can prevent teratogens from entering. In this case, mothers may need to stop lithium carbonate treatment before they make a decision to become pregnant. Anat Rec, 291:1088–1096, 2008. © 2008 Wiley-Liss, Inc.

Inbred BALB/c mouse implanted with murine tumors serves as an attractive model system for the studies of cancer biology in immuno-competent individuals. It is anticipated that tumor progression would induce notable pathophysiological consequences, some of which manifested as alteration in serum proteomic and glycomic profiles. Similar to sera derived from human cancer patients and immuno-compromised mice bearing human tumors, we show in this work that BALB/c mice of the same genetic background but bearing two distinct tumor origins both exhibited elevated expression levels of acute phase proteins including haptoglobin and serum amyloid P protein, in response to tumor progression. Such common traits are generally not informative nor qualifying as biomarkers. Additional mass spectrometry (MS)-based glycomic mapping nevertheless detected distinctive changes of sialylation pattern on the complex type N-glycans. MALDI MS/MS sequencing afforded a facile but definitive identification of an increase in internal Neu5Gcalpha2-6 sialylation on the GlcNAc of the Neu5Gc2-3Gal1-3GlcNAc terminal sequence as a common feature whereas a substitution of Neu5Gc by Neu5Ac was found to be induced by colonic but not breast tumor. A more pronounced change was similarly detected on N-glycans derived from ascitic fluids representing late tumor progression stages. We next demonstrated that such distinct change in glycotope expression can be localized to a particular protein carrier by LC-MS/MS analysis of glycopeptides. Serotransferrin was identified as one such abundant serum glycoprotein, which changed significantly not in protein expression level but in terminal glycosylation pattern.

The density of intestinal endocrine cells, in Balb/c mice with colon 26 (CT-26) carcinoma cells, were examined immunohistochemically at 28 days after implantation. After CT-26 cell administration there was a significant decrease in most of the intestinal endocrine cells (p ＜ 0.01) compared with the control group. The significant quantitative changes in the intestinal endocrine cell density might contribute to the development of the gastrointestinal symptoms commonly encountered in cancer patients.

In the present study, the initial developmental stage of Toxocara canis eggs and larvae, and number of recovered lar - vae from BALB/c mouse-infected organs are described. In vitro culture of T. canis detects the frequencies of interphasic, mitotic and embryonated eggs only within a 7-day period. Analysis by egg counting was carried out for 32 days. The results showed that at 7 days after cultivation, the frequency of larvae was 50.4% and that this frequency reached 52.8% in 32 days. In the experimental infection of BALB/c mice with T. canis, the number of recovered larvae statistically increased in the brain and liver, with doses of approximately 200 and 1000 eggs. After 7 days of infection, a larger number of larvae were obtained in the lung and liver, al - though a maximum amount was found in the brain after a 15- or 30-day post-infection period.

The aim of this study was to determine the tissue colonization and pathogenicity of Arcobacter butzleri in BALB/c mice. For this purpose, 60 adult mice were distributed into three experimental groups consisting of 16 animals in each and into three control groups consisting of 4 animals in each. One ml of A. butzleri suspension containing 1x109 CFU/mL was inoculated by peroral (PO), intraperitoneal (IP) and intramammary (IMG) routes to BALB/c mice in experimental groups in order to determine the clinical and pathological findings. Animals in control groups received 1 mL of sterile saline solution. Duration of the experiment was limited for 15 days. The BALB/c mice were found to be susceptible to infection by the three ways of inoculation. In infected mice, diarrhea, weakness, decrease of body temperature (IP and IMG); hepatomegaly, splenomegaly (IP); swelling of mammary glands, exudation, abscess formation (IMG) were seen. Mortality was determined as 25% in PO inoculation group and as 95% in IP IMG inoculation groups. In histopathological examination, acute/chronic inflammation characterized with neutrophil and plasma cells and local necrosis or congestion (IP) were determined in the lungs, kidneys, regional lymph nodes, liver, spleen, stomach and colon. However, severe, diffuse and chronic pyogranulomatous and necrotizing inflammation and interstitial fibrosis were observed in mammary gland and its subcutaneous tissues (IMG). In all of inoculation groups, A. butzleri was reisolated until the 5th days of post inoculation. The results of this study have suggested that BALB/c mice might be an appropriate experimental animal model for studying A.butzleri infection. © 2016, Chartered Inst. of Building Services Engineers. All rights reserved.

Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina) and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena) were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea. This work was supported by the grants RTA 2013-00065-C02-01 from The National Institute for Agricultural and Food Research and Technology (INIA) and agrifood research in Spain (MPJdB) and SAF2014-54763-C2 from the European Social Fund (JP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Published

Our aim was to investigate the effects of intense pulsed light (IPL) on collagen expression in BALB/c mouse skin and confirm its relative molecular mechanisms. The dorsal skin of BALB/c mice was irradiated by IPL. Before treatment and from 1 day to 8 weeks (1 day, 3 days, 5 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks) after treatment, the irradiated skin specimens were examined. The histology showed dermis thickening, accompanied with increased collagen and better organization. After IPL irradiation from 2 W up to 8 W, the staining of collagen types I and III in the IPL-treated groups was stronger than in the sham groups (P0.05), and the mRNA expression levels of the procollagen types I and III had also increased (P0.05). The up-regulation effects of IPL irradiation were time-dependent. The mRNA expression levels of matrix metalloproteinase (MMP)-1 and MMP-2 decreased progressively after IPL irradiation at 2 W up to 8 W (P0.05), and this down-regulation effect of IPL was also time-dependent. However, the mRNA expression of vascular endothelial growth factor (VEGF) had shown no obvious change by the end of the experiment (P0.05). Taking these factors together, we can conclude that IPL irradiation can not only enhance new collagen production, but also decrease collagen degradation in photo-rejuvenation mechanisms in mouse skin.

The cause of influenza to the brain was investigated using the A/NWS/33 influenza virus infected BALB/c mouse model. NOS-2 mRNA levels in the infected mouse brain was greater than in control mice in all brain regions examined, particularly in the olfactory bulb and hippocampus by 1 day p.i. On the contrary, no differences in NOS-1 or NOS-3 mRNA levels were found between infected and control mice. There was also a marked increase in the levels of metabolites of nitric oxide in the olfactory bulb and hippocampus. Immunohistochemistry showed positive staining for anti-NOS-2 primarily in the hippocampus of infected mice. Further, anti-NOS-2 and GFAP staining was mostly found around capillary blood vessels of the hippocampus starting early in the course of the disease. These results indicate that the NWS enhances the activation of astrocytes and NOS-2 expression which in turn enhances NO production and the expansion of capillary blood vessels.

Anaplasmosis, caused by Anaplasma marginale, results in significant economic losses of cattle in tropical and subtropical regions worldwide. Six major surface proteins (MSPs) were well characterized and designated as MSP1, MSP2, MSP3, MSP4, and MSP5. The objective of this study was to evaluate the humoral immune response of BALB/c mice against the recombinant MSPs, incorporated into immunostimulating complex (ISCOM). The recombinant proteins purified by Ni-NTA columns were incorporated into ISCOM and ISCOMATRIX by the lipid film hydration method. BALB/c mice immunized with ISCOM/rMSPs and ISCOMATRIX/rMSPs vaccines produced whole IgG, IgG1, and IgG2a, in contrast to the negative groups (PBS and ISCOMATRIX adjuvant). All groups that received antigen responded specifically against the rMSPs by Western blotting, showing the rMSP1a (60-105kDa), rMSP1b (100kDa), rMSP4 (47kDa), and rMSP5 (29kDa). Additional studies will have to be performed in cattle to evaluate the humoral and cellular mechanisms of this subunit vaccine and their possible use as protective vaccines against homologous and heterologous strains of A. marginale.

Anti-inflammatory effects of murine fetal liver (FL) cells were studied using BALB/c mouse contact hypersensitivity (paw edema) model. Paw weight differences, lymphatic organ weights, hematological and histological indices as well as proinflammatory (TNF-alpha) and anti-inflammatory (IL-10) cytokine levels in sera were evaluated. Immunophenotyping revealed that both murine FL homogenate cells (HC) and FL hematopoietic stem cells (HSC) express CD117 and CD38 surface markers. Single doses of 1x10(6) cells/mouse and 2x10(6) cells/mouse of FL HC as well as of FL HSC, when used separately, all statistically significantly (p

Toluene diisocyanate (TDI), a highly reactive industrial chemical, is one of the leading causes of occupation-related asthma in industrialized countries. The pathogenesis of TDI-induced asthma, however, remains not fully understood, in part due to lack of appropriate animal models. Twenty five female BALB/c mice (age: 8 weeks) were randomly divided into 5 groups: Ovabumin (OVA); OVA peptide amino acid residues No. 323–339 (Pep); TDI; alum and physiological saline. Mice were intraperitoneally injected with 25 lg OVA or pep absorbed on 300 lg alum, 300 lg alum or saline on days 0, 7 and 14. For the TDI group, mice were sensitized subcutaneously with 20 ll neat TDI on day 0; 20 ll of TDI in olive oil (1:10) on days 7 and 14; on days 21–23. Then each group was challenged intranasally with 20 ll of 1% OVA, 1% Pep, 1% TDI, 10% alum and saline respectively. On day 28, mice were killed under pentothal anesthesia. The results demonstrated that neutrophil-dominant inflammation with a few eosinophil infiltration occurred in the peri-bronchial and peri-vascular regions of the lungs. This was accompanied by hyperplasia/ hypertrophy of cells lining the airways and mucus production as shown by HE staining. Positive immunohistochemical MBP staining in parenchyma was also shown. Th2 cytokine IL-4 and IgE production were significant increased 5 days after last challenge while IFN-c level was below the detection limit. Conclusion: the clear elevation of IL-4 and IgE could allow to conclude a possible Th2-like dominated allergic response in TDI-exposed BALB/c mouse model. acceptedVersion

Pohanka M.: Evaluation of Immunoglobulin Production during Tularaemia Infection in BALB/ c Mouse Model. Acta Vet. Brno 2007, 76: 579-584. The chromatographic technique was used for assay of time-dependent content of antibodies in mice BALB/c infected by tularaemia. The assay was consequently performed on two types of chromatographic sorbents. The first was commercial CBind TM L specific for serum immunoglobulins IgM, IgG and IgA. The second was originally prepared sorbent including protein G covalently bound on EnzacrylRAH particles. This sorbent has specificity for immunoglobulin IgG and its subclasses only. Finally, mass concentration of immunoglobulins in serum was determined. Two curves expressing time behavior of immunoglobulin content (immunoglobulin mass concentration vs. days after immunization) were used for finding the proper mathematical function. The function found was sigmoid; subsequently, appropriate constants needed for function solution were evaluated.

With the mass production of fullerenes currently underway, and the mass production of carbon nanotubes soon to follow, only a few studies have examined the biological consequences of manmade nanoparticle exposure in the mammalian system. This study examines carbon nanoparticle (CNP) exposure in both in vitro (murine BALB/c alveolar macrophages) and in vivo (murine BALB/c intranasal instillations) systems. Three types of CNP were examined (single-walled nanotubes, multi-walled nanotubes, and C60 fullerenes). In vitro macrophage experiments included measurements of morphology changes, apoptosis, viability, and antigen-presenting cell function in response to CNP exposure. In vivo mouse experiments determined the inflammatory potential of CNP exposure in the lung using a BUXCO™ apparatus along with cell differentials and cell morphology. This study presents evidence that CNP, accumulated in the plasma membranes of cells (disrupting lipid rafts), increased alveolar macrophage function with regard to antigen-pr...

Cutaneous leishmaniasis (CL) is caused by several species of the protozoan parasite Leishmania and affects approximately 10 million people worldwide. Currently available drugs are not ideal due to high cost, toxicity, parenteral administration and suboptimal efficacy. Miltefosine is the only oral treatment (Impavido®) available to treat CL, given over a period of 28 days with common side effects such as vomiting and diarrhoea. Objective To explore the local application of miltefosine as a topical formulation to enhance activity and reduce the drug's adverse effects. Methods The antileishmanial activity of miltefosine was confirmed in vitro against several Leishmania species. The permeation of miltefosine, in different solvents and solvent combinations, through BALB/c mouse skin was evaluated in vitro using Franz diffusion cells. The topical formulations which enabled the highest drug permeation or skin disposition were tested in vivo in BALB/c mice infected with L. major. Key findings The overall permeation of miltefosine through skin was low regardless of the solvents used. This was reflected in limited antileishmanial activity of the drug formulations when applied topically in vivo. All topical formulations caused skin irritation. Conclusions We conclude that miltefosine is not an appropriate candidate for the topical treatment of CL.

Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae.

The chemopreventive effects of dead nano-sized Lactobacillus plantarum (nLp) on colon carcinogenesis, induced by dextran sulfate sodium and azoxymethane, were evaluated using Balb/c mice and compared with the effects of pure live L. plantarum (pLp). nLp is a dead shrunken form of L. plantarum derived from kimchi and has a particle size of 0.5-1.0 μm. Animals fed nLp showed less weight loss, longer colons, lower colon weight/length ratios, and fewer colonic tumors compared with pLp. In addition, the administration of nLp significantly reduced the expression of inflammatory markers, mediated the expression of cell cycle and apoptotic markers in colon tissues, and elevated fecal IgA levels more than pLp. Accordingly, the present study shows that the anticolorectal cancer activities of nLp are greater than those of pLp and suggests this is due to the suppression of inflammation, the induction of cell cycle arrest and apoptosis, and enhanced IgA secretion.

Background:: Leishmaniasis is now accounted as a worldwide disease, which is caused by different species of Leishmania parasite. This parasitic disease is now endemic in many areas including 16 developed and 72 developing countries. An estimated 12 million cases of leishmaniasis exist worldwide and a further 367 million are at the risk of acquiring the disease. A high rate of Leishmania and HIV co-infection has now been reported from 30 countries around the world. Th1 immune responses have the main role in eliciting immunity to Leishmania parasite. Many attempts have been made and different strategies have been approached to develop a potent vaccine against this parasite. Objectives:: The main objective of this study was to clone and detect the gene encoding Leishmania major gp63 in mouse CT26 cell line. Materials and Methods:: In this observational study, the Leishmania major gp63 gene segment was amplified using specific primers and then sub-cloned into pcDNA3 expression vector. The new construct was transfected into mouse CT26 cell line. Results:: The results clearly showed that pcDNA3 L. major gp63 was successfully constructed and transfected into CT26 mouse cell line and these cells have a high potency in accepting and expressing Leishmania genes. Conclusions:: A full length of L. major gp63 gene was cloned in to mouse CT26 cell line, which can be used in future vaccine studies for Leishmania.

Problem Many researchers have demonstrated that the expression of interleukin-17(IL-17) is higher in spontaneous abortion. However, whether Th17 cells are an independent factor in inducing abortion is not known. Method of study This study investigated the effect of exogenous recombinant IL-17 and an anti-IL-17 antibody in a normal and an abortion mouse model using flow cytometry, enzyme-linked immunosorbent assay, real-time PCR, and Western blot. Results Th17 cells and the related factors, IL-17 and RORγt, were significantly upregulated in abortion mice, and Treg cells and the related factor, Foxp3, were downregulated. Intraperitoneal injection of recombinant IL (rIL)-17 induced fetal loss in a normal mouse model, and an anti-IL-17 antibody prevented fetal loss in an abortion mouse model. Conclusion This study confirmed an imbalance of the Th17/Treg paradigm in abortion mice and IL-17 as a risk factor of fetal loss. An anti-IL-17 antibody may prevent abortion.

BALB/cJ mice housed under normal vivarium lighting conditions can exhibit profound retinal abnormalities, including retinal infoldings, autofluorescent inflammatory cells, and photoreceptor degeneration. To explore the sensitivity of the outer retina to cyclic lighting during aging, a cohort of BALB/cJ mice was evaluated with Scanning Laser Ophthalmoscopy (SLO), Spectral-Domain Optical Coherence Tomography (OCT) and conventional histopathology. Mice were bred and reared in a low-illuminance (extracage/intracage: 13 lx/1 lx) vivarium under cyclic light (14 h light: 10 h dark). Retinal imaging (around postnatal day 70) was performed to screen for any pre-existing abnormalities and to establish a baseline. Mice with normal retinas were separated into groups (A, B, C) and placed on bottom (Groups A & B) or top (Group C) of the cage racks where cage illumination was

Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.

The Balb/c mice were infected with Coxiella burnetii and samples of blood and major organs from the infected mice were collected on days 1 to 14 after infection. The DNAs extracted from the samples were detected by a developed real-time quantitative PCR specific for C. burnetii and high loads of C. burnetii were found in spleens, livers, and lungs, particularly in spleens. The Balb/c mice were immunized with whole cell antigen (WCA) of C. burnetii and coxiella loads in spleens of mice were assessed by the real-time quantitative PCR on day 7 after challenge with C. burnetii. The analysis suggested that phase I whole cells were excellent immunogen that elicited complete protection against coxiella infection by two-booster but not one-booster immunization. The results suggest that the combination of Balb/c model and the real-time quantitative PCR assay is a reliable and sensitive way to evaluate the efficiency of vaccines against Q fever.

PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.

Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated) or BALB/c (297 and 58 genes, respectively, up- and down-regulated) mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

Brucella abortus 2308 derivatives with mini-Tn 5 insertions in purE , purL , and purD display significant attenuation in the BALB/c mouse model, while isogenic mutants with mini-Tn 5 insertions in pheA , trpB , and dagA display little or no attenuation in cultured murine macrophages or mice. These experimental findings confirm the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages. In contrast to previous reports, however, these results indicate that exogenous tryptophan and phenylalanine are available for use by the brucellae in the phagosomal compartment.

SUMMARYNeonatal thymectomy induces autoimmune gastritis (AIG) in 40–70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H+/K+ ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-γ and tumour necrosis factor-α were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P

Although mice are amenable to gene knockout, they have not been exploited in the setting of seizure-induced neurodegeneration due to the resistance to injury of key mouse strains. We refined and developed models of seizure-induced neuronal death in the C57BL/6 and BALB/c strains by focally evoking seizures using intra-amygdala kainic acid. Seizures in adult male BALB/c mice, or C57BL/6 mice as reference, caused ipsilateral death of CA1 and CA3 neurons within the hippocampus. Termination of seizures by lorazepam was more effective than diazepam in both strains, largely restricting neuronal loss to the CA3 sector. Electroencephalography (EEG) recordings defined injurious and non-injurious seizure patterns, which could not be separated adequately by behavioral observation alone. Degenerating neurons in the hippocampus were positive for DNA fragmentation and approximately a third of these exhibited morphologic features of programmed cell death. Western blot analysis revealed the cleavage of caspase-8 after seizures in both strains. These data refine our C57BL/6 model and establish a companion model of focally evoked limbic seizures in the BALB/c mouse that provides further evidence for activation of programmed cell death after seizures.

Objective: Although cell density in cultured cells has demonstrated several alterations in the nature of cell kinetics, the changes in the metastatic aggressiveness of cancer lines under different cell densities have not yet been studied. Methods: In the current study, we investigated the influence of changing the cell density of cultured cancer cells (colon 26 and B16-F10) injected into the tail vein in BALB/c mice on the metastatic activity by evaluating the number of lung metastases, and the possible mechanisms of this phenomenon were discussed based on the basis of the results of an invasion assay and a cell adhesion assay. Results: The number of metastatic nodules was significantly higher in the high-density group than in the low one in colon 26 (p < 0.005), however, this phenomenon was not seen in B16-F10. Next, we performed the same experiment by changing the environment to the opposite conditions for the cells in the low- and high-density groups, and the results showed the metastatic activities to be always higher in the high-density group. Moreover, although no difference was seen regarding the invasive activity between the high- and low-density groups, an adhesion assay showed the difference in the adhesion cell rate to be significantly higher in the high-density group especially in early period after coculture with human umbilical vein endothelial cells (HUVEC) (p < 0.05). Conclusion: In some cell types, the metastatic activity could be altered and reversed by changing the environment, such as the cell density, during a relatively short period. As a result, the epigenetic changes of cancer cells are thus suggested to play a certain role in the malignant potentiality.

Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated) or BALB/c (297 and 58 genes, respectively, up- and down-regulated) mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

Background: Pramiracetam is being used, particularly by students, to increase cognitive function and enhance learning and memory. There are currently sparse data on the effect of pramiracetam, particularly in the brain. One recent study showed that there is an increased nitric oxide synthase (NOS) in systemically administered pramiracetam. Aims and Objectives: To determine if there would be a demyelinating effect in the hippocampus that is a sign of neurological damage due to increasing nitric oxide synthase. Materials and Methods: A total of fifteen mice were given 200 and 600 mg/kg dose of pramiracetam for qualitative histological comparison of their hippocampal myelination. After administration with food of the pramiracetam for 75 days, the mice were sacrificed and the brains were then extracted intact, and sagittal sections of the brain were made and stained with the Kluver-Barrera method. Hippocampi were analyzed using a compound microscope to observe for demyelination and neuronal degeneration. Results: Based on histological analysis, there were no signs of demyelination in the hippocampus of the Mus musculus brain. This may indicate that pramiracetam does not cause demyelination that may be due to increased NO production. Conclusion: Pramiracetam may be safe to take at doses of 200–600 mg/kg without any demyelinating effects in mouse.

This study investigated the therapeutic effects of combined local irradiation and anti-HER2/neu antibody in a mixed tumor mouse model comprised of a nonmetastatic neu-positive tumor and a metastatic neu-negative tumor. While local irradiation alone could control the primary tumor in a dose-dependent manner, it did not improve mouse survival. Combined treatment comprised of local irradiation and anti-neu antibody of tumor-bearing BALB/c mice significantly improved mouse survival (P < 0.5), even though the tumor growth was similar to that of the irradiated-alone group. The combined treatment significantly reduced metastatic tumor masses in the lung and increased immune cell infiltration in primary tumor tissues. However, immune deficient nude mice with tumors did not exhibit prolonged survival in response to the combined treatment. Collectively, these results show that combined local irradiation and anti-neu antibody can elicit an immune-mediated abscopal effect to extend survival. Although the mechanism for abscopal effects induced by the combined treatment of radiation and anti-HER2/neu antibody was not elucidated, to our knowledge this is the first published study to describe the abscopal effect induced by the combination of local irradiation and the anti-HER2/neu antibody.

In recent decades, accumulating evidence from both animal and clinical studies has suggested that a sufficiently activated immune system may strongly augment various types of cancer treatment, including photodynamic therapy (PDT). Through the generation of reactive oxygen species, PDT eradicates tumors by triggering localized tumor damage and inducing anti-tumor immunity. As the major component of anti-tumor immunity, the involvement of a cell-mediated immune response in PDT has been well investigated in the past decade, whereas the role of humoral immunity has remained relatively unexplored. In the present investigation, using the photosensitizer BAM-SiPc and the CT26 tumor-bearing BALB/c mouse model, it was demonstrated that both cell-mediated and humoral adaptive immune components could be involved in PDT. With a vascular PDT (VPDT) regimen, BAM-SiPc could eradicate the tumors of ∼70% of tumor-bearing mice and trigger an anti-tumor immune response that could last for more than 1 year. An elevation of Th2 cytokines was detected ex vivo after VPDT, indicating the potential involvement of a humoral response. An analysis of serum from the VPDT-cured mice also revealed elevated levels of tumor-specific antibodies. Moreover, this serum could effectively hinder tumor growth and protect the mice against further re-challenge in a T-cell-dependent manner. Taken together, these results show that the humoral components induced after BAM-SiPc-VPDT could assist the development of anti-tumor immunity.

Cultured rat cerebellar granule neurons (CGNs), which require a depolarizing agent in the medium for long-term survival, are widely used for the analysis of mechanisms underlying the activity-dependent survival of neurons. It was recently found that this is not the case for BALB/c mouse CGNs, which survive without a depolarizing agent. Co-culture experiments indicated that the mouse cells release a neurotrophic substance. However, the substance is apparently short-living in the medium, making its molecular identification difficult. Here a novel co-culture method was devised for estimating the relative molecular masses of biologically active substances, using a commercially available dialysis membrane filter unit to separate substance-donor from substance-recipient cells. By this simultaneous fractionation/bioassay, the molecular mass of the assumed neurotrophic substance was estimated to be3 kDa. Neurotrophic substances previously reported to be effective in rat CGNs, including neurotrophins, pituitary adenylate cyclase-activating polypeptide, parathyroid hormone-related polypeptide, glutamic acid, gamma-aminobutyric acid, and D-serine, were excluded as candidate molecules. Estrogen, however, remained a candidate. It should be stressed that the requirements for the activity-dependent survival of CGNs are species-dependent. Care should be taken in the analysis of activity-dependent neuronal survival using transgenic animals.

Objective: This study was eanied out to investigate the effects of Raphani Semen on immuno-response in the mouse model of allergic asthma. Methods: In this study, BALB/C mice were divided into 6 groups: Normal (Non-treated group), Control (Group with not treated after allergic sensitization and induction by ovalbumin), Treat I (Group with the oral administration of saline after allergic sensitization and induction by ovalbumin), Treat n (Allergic asthma group treated with acupuncture (BL 13)), Treat III (Allergic asthma group treated with the oral administration of Raphani Semen) and Treat lV (Allergic asthma group treated with the herbal-acupuncture of Raphani Semen (BL 13)). The effect on cytokine was assessed by measuring cytokine (lL-2, IL-4, IL-5, IL-10, IL-12, IFN-r) in bronchoalveoar lavage fluid(ELISA). ResuJts : The results obtained as follows: 1. The production of Interleukin-2 was decreased significantly in Treat I group, Treat n group and Treat IV group as compared with Control group. 2. The production of Interleukin-4 was decreased significantly in Treat I group, Treat II group and Treat IV group as compared with Control group. Among them. the production of Interleukin-4 was decreased remarkably in Treat IV group as compared with other groups. 3. The production of Interleukin-5 was decreased significantly in Treat I group and Treat IV group as compared with Control group. 4. The production of Interleukin-10 was decreased significantly in Treat I group and Treat III group as compared with Control group. 5. The production of Interleukin-12 was all decreased significantly in Treat I group, Treat n group, Treat m group and Treat IV group as compared with Control group. 6. The production of Intelferon- showed no significant changes in Treat I group, Treat n group. Treat m group and Treat Ⅳ group as compared with Control group. Conclusion: These results show that the production of Interleukin-4, 5 was decreased significantly in aJlergic asthma group treated with the herbal-acupuncture of Raph Semen (BL 13), It is known that inactivity of Th2 cell constrained the revelation and controlled hypersenstive action. As to this mechanism, it is suggested that the herbal-acupuncture of Raphani Semen(BL 13) constrained the revelation of allergic asthma.

In BALB/c mice infected with Trichinella spiralis, changes in body temperature (Tb) were observed over 35 days after the infection. T. spiralis infection induced hypothermia two times at 7 and 28 days after infection. The initial decrease persisted for about one week with a peak (37.1 +/- 0.62 degrees C) around 10 days after the infection, while the later phase persisted for at least one week. Both 10 and 35 days after the infection, there were remarkable decreases in Tb. The serum glucose level of infected mice at 10 days was significantly (p < 0.01) decreased compared with that of control mice at the same number of days, while the level in infected mice at 35 days was not decreased. Moreover, the later phase of hypothermia was prevented by the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.), while the initial phase was not. We conclude that hypothermia was caused by two different mechanisms, involving the effects of hypoglycemia and prostaglandins.

Background There is an urgent need to develop and test novel compounds against malaria infection. Carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit Plasmodium falciparum in vitro. However, they are inflammatory and alter the permeability of the blood–brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (CM), a severe complication of the disease. In this work, the authors look into the effects of the administration of λ-carrageenan to the development and severity of CM in BALB/c mice, a relatively non-susceptible model, during infection with the ANKA strain of Plasmodium berghei. Methods Five-week-old female BALB/c mice were infected with P. berghei intraperitoneally. One group was treated with λ-carrageenan (PbCGN) following the 4-day suppressive test protocol, whereas the other group was not treated (PbN). Another group of healthy BALB/c mice was similarly given λ-carrageenan (CGN) for comparison. The following parameters were assessed: parasitaemia, clinical signs of CM, and mortality. Brain and other vital organs were collected and examined for gross and histopathological lesions. Evans blue dye assays were employed to assess blood–brain barrier integrity. Results Plasmodium berghei ANKA-infected BALB/c mice treated with λ-carrageenan died earlier than those that received no treatment. Histopathological examination revealed that intracerebral haemorrhages related to CM were present in both groups of infected BALB/c mice, but were more numerous in those treated with λ-carrageenan than in mock-treated animals. Inflammatory lesions were also observed only in the λ-carrageenan-treated mice. These observations are consistent with the clinical signs associated with CM, such as head tilt, convulsions, and coma, which were observed only in this group, and may account for the earlier death of the mice. Conclusion The results of this study indicate that the administration of λ-carrageenan exacerbates the severe brain lesions and clinical signs associated with CM in BALB/c mice infected with P. berghei ANKA.

We evaluated the protective efficacy of 94-kb virulence plasmid-cured, and phoP- or aroA-deficient strains of Salmonella enterica serovar Typhimurium (ΔphoP or ΔaroA S. Typhimurium) as oral vaccine candidates in BALB/c mice. Two weeks after the completion of 3 oral immunizations with 1 × 10(8) colony-forming units (CFU) of virulence plasmid-cured, and ΔphoP or ΔaroA S. Typhimurium at 10-day intervals, S. Typhimurium lipopolysaccharide (LPS)-specific mucosal secretory immunoglobulin A (s-IgA) antibody titers were detected in the cecal homogenate, bile and lung lavage fluid, but not in the intestinal lavage fluid. In addition, the increases in S. Typhimurium LPS-specific immunoglobulin G (IgG) and IgA antibody titers in the serum were also observed 2 weeks after completing 3 oral immunizations with virulence plasmid-cured, and ΔphoP or ΔaroA S. Typhimurium. The series of 3 oral immunizations protected the mice against an oral challenge with 5 × 10(8) CFU of the virulent strain of S. Typhimurium, suggesting that both the virulence plasmid-cured, and ΔphoP and ΔaroA S. Typhimurium strains are promising candidates for safe and effective live S. Typhimurium vaccines.

U kliničkoj praksi velike povrede, bolesti ili nasledne malformacije često dovode do stvaranja velikih koštanih defekata, koji ne mogu spontano da zarastu. Popravka ovakvih koštanih defekata predstavlja već dugo vremena izazov za regenerativnu medicinu i tkivno inženjerstvo. Proces zarastanja fraktura prolazi kroz tri faze: inflamacije, obnove i remodeliranja. Dakle, popravka koštanih defekata (fraktura) je okarakterisana inicijalnom inflamatornom reakcijom čiji su glavni akteri makrofagi. U odnosu na obilje literaturnih podataka o ulozi makrofaga u procesima zarastanja mekih tkiva, malo je podataka o njihovoj ulozi u procesima reparacije kosti. Predmet ove doktorske disertacije je ispitivanje modulatornog efekta različito tretiranih makrofaga na ektopični osteogeni proces in vivo, kao i delovanja makrofaga različitog porekla i posle različitih tretmana na in vitro diferencijaciju preostablastnih ćelija. Istraživanje je izvedeno na singenim miševima Balb/c soja, muškog pola, starosti 10-12 nedelja. Implanti su formirani od nosača za makrofage koji su imali i funkciju skafolda, a to su bili mineralni matriks kosti (MMK) i krvni ugrušak. Implanti su se međusobno razlikovali po tretmanu unetih peritonealnih makrofaga (PM). Kontrolni implanti nisu sadržavali makrofage, već samo nosače. Ispitivano je sedam tipova implanata koji su bili formirani od: nosača i rezidentnih (nestimulisanih) PM; nosača i tioglikolatom elicitiranih PM; nosača i PM tretiranih lipopolisaharidom u koncentraciji 5 ng/ml; nosača i PM tretiranih lipopolisaharidom u koncentraciji 500 ng/ml; nosača i PM tretiranih sa 5 x 10-6 M deksametazona; nosača MMK i krvnog ugruška; nosača MMK i fiziološkog rastvora. Pokazano je da osteogeni proces zavisi od načina tretmana makrofaga, pa je tako najizraženiji u implantima sa rezidentnim, kao i deksametazonom tretiranim makrofagima, dok je u implantima sa makrofagima tretiranim lipopolisaharidom u koncentraciji 500 ng/ml osteogeni proces inhibiran... In clinical practice, major injuries, diseases or congenital malformations often lead to the formation of large bone defects, which can not heal spontaneously. Repair of these bone defects has long been a challenge for regenerative medicine and tissue engineering. The process of fracture healing passes through three phases: inflammation, reparation and remodeling. So repair of bone defects (fractures) is characterized by an initial inflammatory response, whose main participants are macrophages. Compared to the abundance of literature data about the role of macrophages in the healing process of soft tissues, there is lack of information on their role in the process of bone repair. The subject of this doctoral thesis was to investigate the modulatory effect of differently treated macrophages on ectopic osteogenic process, as well as effects of macrophages of different origin and after different treatments on osteogenic differentiation of preosteoblasts in vitro. The study was performed on male Balb/c mice 10-12 weeks of age. Implants were formed from the carriers which served as scaffolds for macrophages and these were bone mineral matrix (BMM) and blood clot. Experimental implants contained differently treated peritoneal macrophages (PM). Control implants did not contain macrophages, but only cell carriers. We examined seven types of implants, which have been formed from: carriers and resident (non-stimulated) PM; carriers and thioglycollate elicited PM; carriers and PM treated with 5 ng/ml of lipopolysaccharide; carriers and PM treated with 500 ng/ml of lipopolysaccharide; carriers and PM treated with 5 x 10-6 M dexamethasone; BMM and blood clot; BMM and saline. The results of in vivo investigation showed that the osteogenic process depends on previous treatment of macrophages, and is the most pronounced in implants which contained resident PM or PM treated with dexamethasone...

Introduction Allergic contact dermatitis (ACD) is a skin disease characterized by eczema and itching. A considerable proportion of chemicals induce ACD in humans. More than 10,000 substances should be tested for skin sensitization potential under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for sensitization testing by REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred mouse strain recommended in the regulatory guidelines. However, the availability of CBA/JN mouse in China is only limited to a few animal suppliers, which makes the mouse difficult to obtain. BALB/c mouse, which is widely commercially available, is considered for alternative use but it can only be used in the assay after it has been evaluated by formal validation study. Thus, a validation study was conducted in our laboratory to determine if BALB/c mouse could also be used in the LLNA:BrdU-ELISA. Methods Forty-three test substances including 32 LLNA sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration used were the same as that used in the formal validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Female BALB/c mice of 8–10 weeks old were randomly allocated to groups (four mice per group). The test substance (25 μl) or the vehicle alone was applied to the dorsum of both ears daily for 3 consecutive days. A single intraperitoneal injection of 0.5 ml of BrdU (10 mg/ml) solution was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, weighed and stored at − 20 °C until BrdU-ELISA was conducted. Results This validation study for the LLNA:BrdU-ELISA using BALB/c mouse correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The accuracy, sensitivity, specificity, false positive rate, false negative rate, positive predictivity values and negative predictivity values in this study, which could indicate the performance of the LLNA:BrdU-ELISA using BALB/c mouse, were not different statistically from that of the validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Discussion This validation study indicates that BALB/c mouse could be used alternatively in the LLNA:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

The aim of this study was to examine whether the RT-PCR method for various Th1/Th2 cytokines is appropriate for determination of response to allergens using C57BL/6 and Balb/c mice, which are known to preferentially demonstrate Th1 and Th2 responses, respectively. To this end, both strains of mice were sensitized by skin painting with the contact allergen dinitrochlorobenzene (DNCB) or the respiratory allergen trimellitic anhydride (TMA). We used the sensitizing protocol adopted by Kimber and coworkers (Toxicology 103, 63-73, 1995). At various time points after the last application, the levels of mRNA expression for Th1-type cytokines IFN-gamma, IL-18, and IL-12p40, as well as receptor IL-18R, and the Th2-type cytokine IL-4 and the receptor ST2L, in lymph nodes were measured. The results suggest that differential expression of IL-12p40 and IL-4 mRNA after 24 h allows clear discrimination between DNCB and TMA in C57BL/6 mice, more obviously than in Balb/c mice. Furthermore, to examine this method, C57BL/6 mice were exposed to OXA, DNFB, and TNCB (Th1-predominant allergens) or PA, TDI, and MDI (Th2-predominant allergens). Elevation of IL-12p40 expression was significant with the Th1 inducers, while the level of IL-4 was higher with Th2-predominant allergens. The results of the present study demonstrate, for the first time, that differential expression of IL-12p40 and IL-4 in C57BL/6 mice may be useful as a parameter for assessing influence of contact and respiratory allergens.

The ‘classical’ myelin basic protein (MBP) exons belong to a much larger unit, termed the ‘Golli-MBP’ gene. Here we have examined the T-cell determinant structure of the Golli protein region in the BALB/c mouse. Golli p10-24, which was shown to have the strongest affinity for I-A d , could not induce T-cell activation. Paradoxically, the poorer binding, overlapping p5–19 was effective at inducing T-cell proliferation. Thus, immunogenicity is not necessarily related to the MHC-binding affinity of self-peptides. In addition, MBP: p151–168-specific T cell clones responded only poorly to J37, a Golli-MBP protein, while MBP: 59–76-specific clones responded well to J37.

The potential of the antibiotics chloramphenicol succinate (CAPS) and thiamphenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was investigated. CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, daily by gavage, for 17 days. At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for haematological examination and haematopoietic stem cell assays. Both CAPS and TAP induced significant reductions in red blood cell count, haematocrit and haemoglobin values at day 1 post dosing; counts of colony-forming units-erythroid and colony-forming units-granulocyte-macrophage, were similarly significantly decreased at this time. All these reduced parameters returned towards normal at days 13 and 22. At days 41, 98 and 179, results for all haematological values and stem cell assays in both CAPS- and TAP-treated mice compared with the controls; there was no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as would be expected in a developing or overt bone marrow aplasia. We therefore consider that the administration of CAPS and TAP, which have been associated with the development of aplastic anaemia in man, induce a reversible anaemia, but not a chronic bone marrow aplasia, when given at haemotoxic dose levels for 17 days in the BALB/c mouse.

The active role of chemokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. In this study the expression pattern of several chemokines and cytokines was elucidated using reverse transcription-PCR and immunohistochemistry in a recently established EAE model of the BALB/c mouse that is characterized by CNS infiltration of polymorphonuclear neutrophils. Elevated mRNA levels of the chemokines MIP-1alpha, MIP-2 and MCP-1 were detected in the CNS of diseased mice, whereas no chemokine expression could be measured in asymptomatic mice. Activated astrocytes were shown to be the main source of MIP-1alpha and MIP-2 before and during cellular CNS infiltration. Among the infiltrating immune cells the neutrophils secreted MIP-1alpha and MCP-1. These results suggest involvement of ordered chemokine expression during the process of neutrophil attraction into the CNS, which may play an important role in the initiation and perpetuation of autoimmune CNS inflammation in the BALB/c mouse. This is the first EAE model to describe CNS expression of the C-X-C chemokine MIP-2, corresponding to an observed neutrophil accumulation in the CNS.

Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytokines are thought to play a substantial role in the control of H. pylori infection. To determine the importance of T helper (Th) cytokines and background genes we investigated the natural course of H. pylori infection in BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)-4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H. pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/-) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4 deficiency had no detectable effect on H. pylori recovery rates from either strain of mice. Our data suggest a protective role of IFN-gamma by mediating inflammation in murine H. pylori infection. In addition, our data emphasize that background genes which differ between BALB/c and C57BL/6 mice regulate the clearance of H. pylori.

Objectives.—To determine the morphologic changes and disease progression of aerosolized cowpox virus infection in BALB/c mice and to ascertain the suitability of cowpox virus–infected BALB/c mice as a model of aerosol-transmitted, orthopoxviral respiratory disease. Methods.—BALB/c mice were inoculated with cowpox virus, Brighton strain, by aerosol or intranasal route. Mice were killed at specified times after inoculation, necropsied, and tissues were collected for routine histology, immunohistochemistry, and electron microscopy. Results.—Inoculation by both routes resulted in disease and death. Immunolabeled viral antigen and lesions predominated in the tissues associated with the inoculation route, that is, lungs, airways, trachea, and nasal passages and sinuses. Tracheitis was evident in the intranasally infected group only. Lesions were generally necrotizing and hemorrhagic, neutrophilic, and increased in extent and severity in a time-dependent fashion. Viral intracytoplasmic inclusion bodies, immunolabeled viral antigen, or virions were readily seen in epithelial tissues, smooth muscle cells of airways and vessels, fibroblasts, periosteal cells, perineural cells, and macrophages. Although the extension of infection appeared to be primarily direct, lesions suggesting hematogenous dissemination were occasionally noted in bone marrow and skin. Transmission electron microscopy demonstrated features of cell injury or death, virion assembly and maturation, and both A-type and B-type inclusions. Conclusions.—Aerosol inoculation of BALB/c mice with cowpox virus provides a reliable and facilitative model of aerosol-transmitted, orthopoxviral respiratory disease.

To assess the relationship between mouse sperm head morphology and karyotype, sperm heads with either a normal or an abnormal morphology were injected individually into enucleated mouse oocytes that were karyotyped at the metaphase of the first cleavage. BALB/c male mice that produce an unusually high proportion of morphologically abnormal spermatozoa were used as sperm donors. Abnormal karyotypes were found in a significantly higher proportion of eggs injected with severely misshapen sperm heads (36-38%) as compared to those injected with normal and quasi-normal heads (15-21%) (p < 0.01). Most karyotype abnormalities were structural rather than numerical, the most common being breaks and exchanges of chromosome type in both normal and abnormal spermatozoa.

Objectives Considering the geographic differences in the prevalence of virulence factors such as CagA or VacA of H. pylori isolated from Korean adults compared with those from western countries, the establishment of a mouse model infected with H. pylori isolated from Korean adults is needed to investigate the pathogenesis and to develop vaccines against H. pylori infection in Korea. The aim of this study was to establish the BALB/c mouse model infected with H. pylori isolated from Korean. Methods Six-week-old BALB/c mice were inoculated intragastrically with 10(9) CFU of H. pylori. Loss of glandular architecture, erosions and infiltration of inflammatory cells within the lamina propria compared with normal gastric mucosa were scrutinized. Evidence for H. pylori infection was assessed by rapid urease test of gastric mucosa and by microscopic examination using the H & E stain and Warthin-Starry silver stain. Results Rapid urease test was positive in 55% of all inoculated mice. Definite histologic changes and the evidence of H. pylori colonization were observed in the H. pylori infected group. Significant infiltration of inflammatory cells was observed 6 weeks after the last inoculation and the level of serum IgG against H. pylori was increased from 2 weeks after the last inoculation. Conclusions The H. pylori isolated freshly from Korean adults could colonize the stomach of BALB/c mice and induce pathologic alterations that mimics human gastric diseases. This model would facilitate the investigations for the pathogenetic mechanisms of H. pylori infection.