SEARCH · PubMed Health

Results for “BALB/c mouse model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1997

Transmission of equine herpesvirus 2 to the mouse: characterization of a new laboratory infection model.

Intranasal inoculation of BALB/c mice with a recent clinical isolate of equine herpesvirus 2 (EHV-2 strain MR) produced a productive infection characterized by clinical signs, including weight-loss and conjunctivitis, but no mortality. Infectious virus was isolated from the lung, trachea and nasal turbinates with the highest titres present in lung tissue; EHV-2 neutralizing antibody was detected in the serum on day 21 post-inoculation. No infectious virus was detected in neural tissue, blood or lymphoid tissues. An EHV-2-specific nested PCR confirmed the presence of EHV-2 DNA in the respiratory tissues. In addition, EHV-2 DNA was detected in the trigeminal ganglia and olfactory bulbs from the first day after inoculation and these tissues remained positive for EHV-2 DNA for at least 30 days, by which time EHV-2 DNA had been cleared from all other tissues.

Animals↗

PubMed2005

Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma.

BACKGROUND: Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. OBJECTIVE: To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. METHODS: Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. RESULTS: Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. CONCLUSION: This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.

Animals↗

PubMed1998

Phospholipase A of Yersinia enterocolitica contributes to pathogenesis in a mouse model.

Some isolates of Yersinia enterocolitica exhibit phospholipase activity, which has been linked to lecithin-dependent hemolysis (M. Tsubokura, K. Otsoki, I. Shimohira, and H. Yamamoto, Infect. Immun. 25:939-942, 1979). A gene encoding Y. enterocolitica phospholipase was identified, and analysis of the nucleotide sequence revealed two tandemly transcribed open reading frames. The first, yplA, has 74% identity and 85% similarity to the phospholipase A found in Serratia liquefaciens. Though the other, yplB, was less similar to the downstream accessory protein found in S. liquefaciens, the organization in both species is similar. Subsequently, a yplA-null Y. enterocolitica strain, YEDS10, was constructed and demonstrated to be phospholipase negative by plate and spectrophotometric assays. To ascertain whether the phospholipase has a role in pathogenesis, YEDS10 was tested in the mouse model. In experiments with perorally infected BALB/c mice, fewer YEDS10 organisms were recovered from the mesenteric lymph nodes and Peyer's patches (PP) than the parental strain at 3 or 5 days postinfection. Furthermore, bowel tissue and PP infected with YEDS10 appeared to be less inflamed than those infected with the parental strain. When extremely high doses of both the parental and YEDS10 strains were given, similar numbers of viable bacteria were recovered from the PP and mesenteric lymph nodes on day 3. However, the numbers of foci and the extent of inflammation and necrosis within them were noticeably less for YEDS10 compared to the parental strain. Together these findings suggest that Y. enterocolitica produces a phospholipase A which has a role in pathogenesis.

Amino Acid Sequence↗

PubMed2005

Systemic administration of the chemokine macrophage inflammatory protein 1alpha exacerbates inflammatory bowel disease in a mouse model.

INTRODUCTION: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) exacerbates colitis in a mouse model. METHODS: Colitis was induced in Balb/c mice using trinitrobenzene sulfonic acid (TNBS). Starting four days later, animals received daily intraperitoneal injections of recombinant MIP-1alpha. On day 7, mice were killed and pieces of colon taken for immunohistology and polymerase chain reaction analysis. The direct effects of MIP-1alpha on mucosal T cells and fibroblasts in vitro were also investigated. RESULTS: Systemic administration of MIP-1alpha markedly enhanced colitis with mice developing large transmural ulcers filled with granulation tissue. Treatment resulted in increased numbers of CD4 cells infiltrating the colonic lamina propria, increased interferon gamma (IFN-gamma) levels, and increased transcripts for tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP3). Isolated lamina propria lymphocytes from mice with TNBS colitis contained increased numbers of IFN-gamma and TNF-alpha transcripts when stimulated with MIP-1alpha in vitro. Colonic lamina propria fibroblasts also responded to MIP-1alpha with increased proliferation and decreased collagen 1 synthesis but fibroblast proliferation was not seen in vivo. CONCLUSIONS: These experiments show that increasing serum concentrations of a chemokine, MIP-1alpha, exacerbates immune mediated colitis. The effect seems to be due to the ability of MIP-1alpha to boost Th1 responses in the gut wall. Our findings also suggest a potential pathway by which peripheral infections can exacerbate inflammatory bowel disease.

Animals↗

PubMed1996

Pretreatment with allergen prevents immediate hypersensitivity and airway hyperresponsiveness.

The ability of subcutaneous pretreatment with an immunogenic peptide derived from Fel d I, the major cat protein, to suppress the development of allergic responses was examined in a mouse model of antigen-induced sensitization. BALB/c mice exposed to aerosolized Fel d I chain 1 peptide developed antigen-specific IgE responses, immediate cutaneous reactivity to the peptide, and increased airway responsiveness (AR). Both subcutaneous and intraperitoneal administration of the peptide prior to sensitization caused a 50% reduction in cutaneous reactivity which was associated with a decrease in serum anti-Fel d I chain 1 IgE and IgG1 antibody responses and an increase in specific IgG. Pretreatment with the peptide also suppressed spleen and lymph node proliferative responses to the peptide. However, only subcutaneous peptide injections could prevent the development of increased AR. Transfer of spleen cells from subcutaneously peptide-treated mice to sensitized recipients reduced serum antigen-specific IgE and IgG1 antibody responses and skin test reactivity, and prevented alterations in AR. These data suggest that IgE (and IgG1) responses and airway hyperresponsiveness induced by allergen sensitization via the airways can be modulated by subcutaneous administration of peptide. Further, the results define a model for investigating the modulatory effects of subcutaneous administration of immunogenic peptides or protein on an ongoing allergic response.

Aerosols↗

PubMed1999

Allergen-induced increase in airway responsiveness, airway eosinophilia, and bone-marrow eosinophil progenitors in mice.

Increases in bone-marrow (BM) inflammatory cell progenitors are associated with allergen-induced airway hyperresponsiveness and inflammation in asthmatics and dogs. Here, for the first time, we compare the time course of airway hyperresponsiveness, inflammation, and marrow progenitor responses in a mouse model of airway allergen challenge. Sensitized BALB/c mice were studied at 2, 12, 24, 48, and 72 h after intranasal ovalbumin or saline challenges. Outcome measurements included airway responsiveness, airway inflammation as assessed via bronchoalveolar lavage (BAL) and lung tissue sections, and BM eosinophil colony-forming units (Eo-CFU) as enumerated using a semisolid culture assay with optimal concentrations of interleukin-5. We observed significant increases in BAL fluid eosinophils, neutrophils, lymphocytes, and macrophages by 2 h after the second of two intranasal allergen challenges (P < 0.05). Significant increases in airway responsiveness or BM Eo-CFU were observed at 24 h and persisted until 48 h after the second challenge (P < 0.05). Airway inflammation, including eosinophils, persisted until at least 72 h (P < 0.05). We observed that allergen-induced airway eosinophilia is accompanied by increases in BM eosinophil progenitors, indicating that in this model, increased eosinophil production involves an expansion of the relevant stem-cell population. These findings support the use of this model to explore the mechanisms of increased eosinopoiesis observed in human asthma.

Allergens↗

PubMed2004

Effect of nitrogen dioxide exposure on allergic asthma in a murine model.

STUDY OBJECTIVES: The purpose of this study was to examine the effects of NO(2), a major component of air pollution, on airway eosinophilic inflammation and bronchial hyperreactivity, using a mouse model of asthma. SETTING AND SUBJECTS: BALB/c mice (eight mice per experimental group) were studied in a basic research laboratory at the University of Iowa. INTERVENTIONS: Using a standard murine model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal (IP) injections (days 1 and 7) and were challenged with aerosolized OVA (days 13 and 14). Some mice were exposed to NO(2) (2 ppm) in an exposure chamber for 24 h before undergoing OVA aerosol challenge. A control group was exposed to OVA alone. MEASUREMENTS AND RESULTS: The outcomes assessed included airway inflammation, bronchial hyperreactivity to inhaled methacholine, and goblet cell hyperplasia. We found that NO(2) exposure modestly increased airway neutrophilia but not airway eosinophilia in OVA-exposed mice. These mice exhibited epithelial damage and loss of epithelial mucin. Surprisingly, nonspecific bronchial hyperreactivity (ie, enhanced pause index) was not increased, although baseline smooth muscle tone was increased (p < 0.05) in the mice exposed to NO(2). CONCLUSIONS: These data indicate that relatively short-term (24 h) exposure to NO(2) causes epithelial damage, reduced mucin expression, and increased tone of respiratory smooth muscle. Reduced mucin production may be a mechanism of injury following long-term exposure to inhaled NO(2). Despite enhancing epithelial damage in OVA-exposed mice, NO(2) exposure does not otherwise alter the expression of allergen-induced airway responses.

Animals↗

PubMed2000

Development of autosomal recessive polycystic kidney disease in BALB/c-cpk/cpk mice.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but devastating inherited disease in humans. Various strains of mice that are homozygous for the cpk gene display renal pathology similar to that seen in human ARPKD. The PKD progresses to renal insufficiency, azotemia, and ultimately a uremic death by approximately 3 wk of age. This study characterizes PKD in mice that are homozygous for the cpk gene on a BALB/c inbred mouse background. The BALB/c-cpk/cpk murine model displays renal as well as extrarenal pathology similar to that found in human ARPKD. The renal pathology includes the well-characterized early proximal tubule and, later, massive collecting duct cysts. The extrarenal defects in this murine model include common bile duct dilation, intrahepatic biliary duct cysts with periductal hyperplasia, and pancreatic dysplasia with cysts. Renal mRNA expression of c-myc, a proto-oncogene, and clusterin (SGP-2), a marker associated with immature collecting ducts, decreases during normal development but is upregulated in murine ARPKD. Expression of epidermal growth factor (EGF) mRNA is significantly diminished, whereas EGF receptor mRNA is upregulated in the BALB/c-cpk/cpk kidney compared with phenotypically normal littermates. To determine whether the altered EGF expression contributes to the development of PKD, neonatal mice were treated with exogenous EGF (1 microg/g body wt injected subcutaneously on postnatal days 3 through 9). EGF treatment reduced the relative kidney weight and common bile duct dilation and downregulated renal expression of clusterin and EGF receptor. However, exogenous EGF did not affect the degree of renal failure, the pancreatic pathology, or the misregulated renal expression of c-myc. In summary, the present study characterizes the renal and extrarenal pathology in the BALB/c-cpk/cpk murine model of ARPKD. Renal mRNA expression of EGF is diminished in this mouse model. EGF treatment did not prevent renal failure but ameliorated pathologic changes in the kidney and the biliary ducts of the BALB/c-cpk/cpk mouse.

Animals↗

PubMedDate not supplied

Inoculated mouse model of Pneumocystis carinii pneumonia.

A transtracheally inoculated mouse model of Pneumocystis carinii has been developed using BALB/c mice, a widely available strain free of latent P. carinii infection. The mean infectivity score of untreated inoculated mice was 4.1 compared to the mean infectivity score of 0.1 for trimethoprim/sulfamethoxazole (50/250 mg/kg) treated inoculated mice, approximately a four-log difference. An inoculated mouse model of P. carinii infection provides both a source of organisms from a different host and an animal model for study of drugs for therapy and prophylaxis which is less costly than rats and which requires less drug than required for rats.

Animals↗

PubMed1998

A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice.

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.

Animals↗

PubMed2005

[Establishment of a heterotopic heart transplantation model in mice].

OBJECTIVE: To establish a mouse model of heterotopic heart transplantation. METHODS: In isotransplantation,BALB/c mice were used as both donors and recipients. In allotransplantation, C57 mice were used as donors and BALB/c mice as recipients. The hearts of donor mice were transplanted into the abdominal cavity of recipient mice, connecting aortic ascent artery of donor mice and abdominal aortic artery of recipient mice, main pulmonary artery of donor mice and inferior vena cava of recipient mice. RESULTS: The mouse model of heterotopic heart transplantation was established successfully with a success rate of 90 %. The mean time of hot ischemia and cold ischemia were (0.9 +/-0.05) min and (34.8 +/-0.7) min, respectively. The survival time of isograft was more than 100 days and that of allograft was (7.7 +/- 0.3) days. CONCLUSION: The operational procedure of donor heart and the quality of blood vessel anastomosis are two key points for successful heterotopic heart transplantation.

Animals↗

PubMed1997

Antiinterleukin-5 antibody prevents airway hyperresponsiveness in a murine model of airway sensitization.

Eosinophils play a central role in the inflammatory response associated with bronchial asthma. We studied the involvement of eosinophils in the development of airway hyperresponsiveness (AHR) in a mouse model of allergic airway sensitization. Sensitization of BALB/c mice to OVA via the airways induced allergen-specific T-cell responses, IgE production, immediate cutaneous hypersensitivity (ICH), and increased airway reactivity. Airway sensitization was associated with eosinophil infiltration of the airways and increased production of interleukin-5 (IL-5) in cultures of peribronchial lymph node cells. Treatment of OVA-challenged animals with anti-IL-5 antibody during the sensitization protocol completely abolished the infiltration of eosinophils into the lung tissue and prevented the development of AHR without affecting levels of allergen-specific IgE, cutaneous hypersensitivity and allergen-specific T cell responses. These findings demonstrate that infiltration of lung tissue by eosinophils, triggered by increased IL-5 production, is a major factor in the development of AHR in this mouse model of airway sensitization.

Animals↗

PubMed2005

Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression.

Polymorphism of tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of brain serotonin (5-HT), is associated with less synthesis of brain 5-HT in DBA/2J and BALB/c than in C57BL/6J and 129/Sv mice. We selected the forced swimming test, a mouse model used to assess the antidepressant potential of drugs, and neurochemical techniques to study strain differences in the response to citalopram, a selective 5-HT reuptake inhibitor. Citalopram reduced immobility time in C57BL/6J and 129/Sv mice but had no such effect in DBA/2J and BALB/c mice. The drug reduced accumulation of 5-hydroxytryptophan (5-HTP), an indicator of 5-HT synthesis, in C57BL/6J and 129/Sv mice but much less in DBA/2J and BALB/c mice. Pretreatment with tryptophan raised 5-HTP accumulation and reinstated the antidepressant-like effect of citalopram in DBA/2J and BALB/c mice, whereas pharmacological inhibition of 5-HT synthesis prevented the effect of citalopram in C57BL/6J and 129/Sv mice. Because there were no strain differences in catecholamine synthesis, locomotor activity, and brain levels of citalopram at the end of the behavioral test, the results suggest that the failure of citalopram to reduce immobility time in DBA/2J and BALB/c mice is attributable to genotype-dependent impairment of 5-HT synthesis. Interstrain comparisons could probably be a useful strategy for understanding the mechanisms underlying the response to selective serotonin reuptake inhibitors.

Animals↗

PubMed2001

Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis.

Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice deficient in both pfp and IFN-gamma were significantly less proficient than pfp- or IFN-gamma-deficient mice in preventing metastasis of tumor cells to the lung. Pfp and IFN-gamma-deficient mice were as susceptible as mice depleted of natural killer (NK) cells in both tumor metastasis models, and IFN-gamma appeared to play an early role in protection from metastasis. Previous experiments in a model of fibrosarcoma induced by the chemical carcinogen methylcholanthrene indicated an important role for NK1.1(+) T cells. Herein, both pfp and IFN-gamma played critical and independent roles in providing the host with protection equivalent to that mediated by NK1.1(+) T cells. Further analysis demonstrated that IFN-gamma, but not pfp, controlled the growth rate of sarcomas arising in these mice. Thus, this is the first study to demonstrate that host IFN-gamma and direct cytotoxicity mediated by cytotoxic lymphocytes expressing pfp independently contribute antitumor effector functions that together control the initiation, growth, and spread of tumors in mice.

Animals↗

PubMed2006

[Effects of glucocorticoid on airway mucus secretion in asthma: experiment with asthmatic mouse model].

OBJECTIVE: To study the effects of glucocorticoid on airway mucus secretion in asthma. METHODS: Twenty-four BALB/c mice were randomly divided into 3 equal groups: asthma group [ovalbumin (OVA) and aluminum hydroxide were injected intraperitoneally on day 0 and day 14 so as to establish mouse asthma model and aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24], asthma + dexamethasone group (OVA and aluminum hydroxide were injected intraperitoneally on days 0 and 14, aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24, and dexamethasone was injected intraperitoneally 1 hour before the aerosol inhalation), and control group (aerosol inhalation of PBS was conducted instead). Twenty-fours hours after the last exposure the mice were anesthetized deeply and their left lungs were excised to collect the bronchoalveolar lavage fluid (BALF) to calculate the numbers of total cells and eosinophils, then Alcian blue/periodic acid-Schiff staining and immunohistochemistry of the air passage were conducted to measure the expression levels of MUC5AC mRNA and protein and interleukin-4 (IL-4) mRNA. RESULTS: The numbers of total cells in the BALF of the asthma group were (12.50 +/- 0.14) x 10(9)/L and (1.12 +/- 0.10) x 10(9)/L respectively, both significantly higher than those of the control group, (6.49 +/- 0.05) x 10(9)/L and (0.05 +/- 0.02) x 10(9)/L respectively (both P < 0.01), and were significantly higher than those of the asthma + dexamethasone group, (6.68 +/- 0.03) x 10(9)/L and (0.06 +/- 0.01) x 10(9)/L respectively too (both P < 0.01). The levels of MUC5AC mRNA, MUC5AC protein, and IL-4 mRNA of the asthma group were 0.5341 +/- 0.303, 0.1906 +/- 0.0008, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1994 +/- 0.0128, 0.1194 +/- 0.0007, and 0.2389 +/- 0.0289 respectively, all P < 0.01), and those of the asthma + dexamethasone group (0.2729 +/- 0.0345, 0.1456 +/- 0.0003, and 0.2424 +/- 0.0260, all P < 0.05). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma group were 0.1906 +/- 0.0008, 0.5341 +/- 0.0303, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1194 +/- 0.0007, 0.1994 +/- 0.0128, and 0.2398 +/- 0.0289 respectively, all P < 0.01). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma + dexamethasone group were 0.1456 +/- 0.0003, 0.2729 +/- 0.0345, and 0.2424 +/- 0.0260 respectively, all significantly lower than those of the asthma group (all P < 0.01). The MUC5AC protein expression and mRNA expression of the asthma + dexamethasone group were still significantly higher than those of the control group (both P < 0.01), however, the IL-4 mRNA expression of the asthma + dexamethasone group was not significantly different from that of the control group (P > 0.05). CONCLUSION: Relieving the inflammation, glucocorticoid may play a role in the treatment of excessive mucus production through down-regulating the expression of MUC5AC and of IL-4.

Aluminum Hydroxide↗

PubMed2004

Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments.

BACKGROUND/AIMS: Pathogenesis of atopic dermatitis (AD) has been studied in animal models such as the NC/Nga mouse strain or Balb/C mice that are repeatedly treated with 2,4,6-trinitro-1-chrolobenzene (TNCB). These mice exhibit features of chronic contact dermatitis, including an intensified early type skin reaction, increased number of mast cells and elevated serum IgE levels with a shift of cutaneous cytokine expression from a type 1 to type 2 profile. However, it is difficult to investigate the unique skin changes of AD such as dry skin, barrier dysfunction, and increased turnover of the stratum corneum (SC) in these animals with biophysical instruments because of the presence of their fur coats. In this study, we succeeded in establishing a mouse model of AD in hairless mice that are suitable for various functional analyses of the SC as well as for examining the immunological characteristics of human AD by treating TNCB-contact sensitized hairless mice with 1% TNCB every other day for 36 days. METHODS: In hairless animals treated with TNCB every 2 days for 36 days, we measured time courses of skin swelling induced by contact hypersensitivity reaction on days 0, 6, 20 and 36. During the time course, non-invasive measurements for skin surface condition with biophysical instruments were conducted, and the area size and the rear surface villi of corneocytes obtained were measured. Also skin samples and blood samples were taken at each time point for histology and measurement of serum IgE level. RESULTS: A gradual intensification of an early type contact hypersensitivity reaction was observed over the treatment period. These mice exhibited reduced SC hydration, heightened trans-epidermal water loss, and increased skin thickness. These mice also showed a decrease in the surface area size of each corneocytes and marked villus formation on their rear surface. Histologically, there was an increase in the number of CD4 and CD8 positive T cells in the epidermis. Also observed was a marked increase in the number of dermal mast cells and eosinophils, which correlated with elevated serum IgE levels induced by TNCB treatments. CONCLUSIONS: From the results obtained we conclude that repeated treatments of TNCB-sensitized hairless mice with TNCB provides a useful means by which to study the pathological characteristics of AD skin lesions as well as their immunological characteristics.

Administration, Topical↗

PubMed2006

Oncolytic murine autonomous parvovirus, a candidate vector for glioma gene therapy, is innocuous to normal and immunocompetent mouse glial cells.

The sensitivity of brain tumour cells to wild-type or recombinant parvoviruses H1-PV and MVMp makes these agents promising candidates for gene therapy of astrocytoma. This application raises the question of whether parvoviruses exert deleterious or bystander effects on normal glial cells surrounding tumours. We addressed this question in the mouse model by using cell cultures derived from BALB/c, C57BL/6 and VM/Dk strains. Astrocytes and a large proportion of microglia cultures were competent for MVMp uptake. Infection was, however, abortive as replication-associated viral proteins synthesis took place in less than 10% of astrocytes and no progeny virions were produced. This restriction was even more pronounced for microglia in which no viral protein expression could be detected, save for a minute fraction of VM/Dk-derived cells. Infection with MVMp had no significant effect on glial cell survival and did not interfere with their immune potential. Indeed, neither the lipopolysaccharide (LPS)/interferon (IFN-gamma)-induced cytotoxicity of VM/Dk-derived microglia towards the mouse glioma (MT539MG) cell line, nor the glial cells capacity for tumour necrosis factor alpha production upon LPS stimulation or LPS/IFN-gamma stimulation were affected by infection with MVMp. Moreover, stimulation with LPS and/or IFN-gamma resulted in a decreased expression of the viral replicative and cytotoxic protein NS1. Together, our data indicate that, in the natural host, a majority of normal glial cells are not competent for MVMp replication and that the abortive infection taking place in a minor fraction of these cells fails to impede their survival and immunocompetence, giving credit to the consideration of autonomous parvoviruses for glioma therapy.

Animals↗

PubMed2006

Combination effect of mycophenolate mofetil with mizoribine on cell proliferation assays and in a mouse heart transplantation model.

BACKGROUND: Mycophenolate mofetil (MMF) is a highly potent immunosuppressant that suppresses the proliferation of T and B cells by the uncompetitive inhibition of inosine monophosphate dehydrogenase (IMPDH). Consequently, under MMF immunosuppression, good graft survival has been achieved in clinical organ transplantation, although MMF shows adverse gastrointestinal effects. Mizoribine (MZ) also inhibits IMPDH in a competitive manner and is used clinically for organ transplantation in Japan as an immunosuppressant with fewer adverse gastrointestinal effects. Therefore, in this study we investigated the synergistic effects on in vitro and in vivo assays of mice of a combination of MMF with MZ immunosuppression. METHODS: Mixed lymphocyte reaction (MLR) assay and a mouse heart transplantation model were used to evaluate the immunosuppressive effect of MMF with MZ. The median-effect principle and a combination index (CI) were employed to determine synergism, an additive effect, or antagonism. RESULTS: Combination of MMF with MZ resulted in mild synergistic effects in the inhibition of MLR (CI = 0.854-1.143). In the mouse heart transplantation model, C57BL/6 recipients who received a BALB/c heart under the combination of MMF and MZ at 40 + 40 or 80 + 80 mg/kg/day showed a strong synergistic prolongation of graft survival with 19.7 +/- 18.9 (P = 0.0012, CI = 0.438) and 78.4 +/- 36.9 days (P = 0.0002, CI = 0.317), respectively, compared with recipients treated with MMF or MZ monotherapy. CONCLUSIONS.: The combination of MMF and MZ showed mild synergistic effects in the inhibition of MLR and strong synergistic effects in a mouse heart transplantation model.

Animals↗