PubMed Health⌕ Search

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 163 records · Page 9Linked to original sources
PubMed2005

Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.

The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.

Animals↗
PubMed2006

DA-9601, Artemisia asiatica herbal extract, ameliorates airway inflammation of allergic asthma in mice.

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-KappaB by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-KappaB increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-KappaB pathway.

Administration, Oral↗
PubMedDate not supplied

Delayed-type hypersensitivity response in mice to Pneumocystis carinii.

Resistance to Pneumocystis carinii infection appears to be mediated by T lymphocytes but the mechanism and subsets of T cells involved are poorly understood. We used the BALB/c mouse model to study the delayed-type hypersensitivity (DTH) response to rat P. carinii. Mice were sensitized to P. carinii for seven days and then challenged with P. carinii antigens in the right rear footpads and normal rat lung antigens in the left rear footpads. A typical DTH response was observed in the right footpads as evidenced by significant swelling and substantial mononuclear cell infiltration at 24-h post-challenge. The DTH response could be transferred to naive syngeneic mice by adoptively transferring spleen cells from P. carinii-sensitized mice. In addition, by using anti-thy-1, anti-mouse Ig, anti-L3T4 and anti-Lyt-2.2 monoclonal antibodies in in vitro cytolysis experiments, we were able to demonstrate that the DTH response was dependent upon T lymphocytes. The response appeared to require cooperation between both L3T4+ and Lyt 2+ subsets of T lymphocytes.

Animals↗
PubMed1988

The sites of catabolism of murine monomeric IgA.

The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.

Animals↗
PubMed1986

Experimental nude mouse model of human colorectal cancer liver metastases.

A nude mouse model (BALB/c) was established for investigating the production of hepatic metastases by human colorectal carcinoma (HCC) cells. The malignant potentials of 3 different HCCs derived from a primary tumor (HCC-P4733), a lymph node metastasis (HCC-M14328), and a hepatic metastasis (HCC-M1410) were investigated following implantation into the spleens of athymic nude mice. Cells of the HCC-M1410 line produced extensive liver tumors in all mice by 30 days after injection. Cells of the HCC-M14328 and HCC-P4733 lines produced few liver tumors in the inoculated mice and then only after a 90-day period. Isozyme and karyotype analyses ascertained the human origin of all the tumors. Studies with [125I]IdUrd-labeled HT-29 carcinoma cells suggested that tumor cells reached the liver shortly after injection into the spleen. Thus the production of HCC tumors in livers of nude mice was determined by the ability of HCC cells to proliferate in the liver parenchyma rather than by the ability of the cells to reach the liver. The results suggest that the intrasplenic injection of HCC cells can provide a valuable model for the study of the biology and therapy of the liver metastases.

Animals↗
PubMed1985

Cold protection and heat enhancement of doxorubicin skin toxicity in the mouse.

A series of experiments were performed in a BALB/c mouse model to evaluate the efficacy of topical heating and cooling on doxorubicin (DOX) ulceration of the skin. Unanesthetized mice were administered a dose of 0.05 mg or 0.5 mg of DOX intradermally, followed by topical heating (43 degrees C-44 degrees C) or cooling (8 degrees C-10 degrees C) of the skin area for up to 1 hour. DOX disposition from skin and plasma was studied by high-pressure liquid chromatography in both cooled and uncooled groups of animals. Human tumor clonogenic cells were exposed to DOX for 1 hour at different temperatures to determine the direct effect of heat and cold on DOX-induced lethality in vitro. Skin temperature of 17 degrees C +/- 2.3 degrees C was achieved with cooling and skin temperature of 38.5 degrees C +/- 1.2 degree C was achieved with heating, compared to control intradermal skin temperature of 32 degrees C +/- 0.5 degree C. Local heating caused duration-dependent DOX lethality: 20% after 20 minutes, 40% after 45 minutes, and 80% after 1 hour. There were no deaths in the control groups. A 20% lethality rate was constant in the cooled groups. Skin lesions were approximately fourfold larger in the heated groups receiving 0.5 mg of DOX (P less than 0.05). In contrast, the application of cold significantly reduced intradermal DOX skin toxicity following the lower DOX dose of 0.05 mg (P less than 0.05). There was no consistent benefit for cooling beyond a 45-minute duration, which achieved maximal protection against ulceration. Pharmacokinetic studies of DOX disposition in skin and blood failed to show a significant difference for total tissue concentrations or plasma levels between cooled and uncooled animals. However, clonogenic human tumor cells (HEC-1A endometrial cells) did demonstrate significantly reduced DOX effects when exposed to the drug at reduced temperatures. These results confirm the biologic efficacy of local cooling and clearly contra-indicate the use of local heating to treat inadvertent DOX extravasations in the clinic. Instead, cold should be applied immediately and maintained for 45 minutes or longer to reduce or prevent serious DOX skin ulcerations in patients.

Animals↗
PubMed1994

Induction of a MHC class I-restricted, CD8 positive cytolytic T-cell response by chimeric HIV-1 virus-like particles in vivo: implications on HIV vaccine development.

New insights into HIV-pathogenesis suggest that the cell mediated immune response might play a crucial role in controlling HIV infection by suppressing HIV-replication in CD4-positive cells by a lymphokine-like soluble factor and by killing HIV-infected cells via classical CTL mediated lysis. This type of a cellular immune response rather than an antibody response seems to be most promising to protect if not from infection, so at least from disease. Therefore rationally designed candidate vaccines should be capable of inducing a cell mediated immunity in addition to a humoral immune response. In order to avoid adverse side effects upon immunization, carefully selected antigens and epitopes should be presented in a favourable manner to the immune system. In previous experiments, we could demonstrate that the gag-polyprotein precursor, known to include a series of T-helper and CTL epitopes, assembles to highly immunogenic, complete noninfectious HIV-1 virus-like particles (VLP). Based on these VLP we developed a novel antigen presentation system, which allows the presentation of selected epitopes derived from HIV reading frames other than gag to the immune system. Alternatively complete derivatives of the HIV-1 external glycoprotein can be presented by the VLP. Immunological analysis of different VLP preparations in a BALB/c mouse model revealed the induction of a strong CTL response. The significance of these observations for future vaccine strategies is discussed.

AIDS Vaccines↗
PubMed1996

Protection of BALB/c mice against homologous and heterologous species of Brucella by rough strain vaccines derived from Brucella melitensis and Brucella suis biovar 4.

OBJECTIVE: To evaluate stable rough mutants derived from Brucella melitensis 16M and B suis 2579 (biovar 4) as vaccines against homologous and heterologous Brucella spp in the BALB/c mouse model. DESIGN, ANIMALS, AND PROCEDURE: Rough mutants VTRM1 and VTRS1 were obtained from B melitensis 16M and B suis 2579, respectively, by allelic exchange of rfbU gene encoding mannosyltransferase with a Tn5-disrupted rfbU gene. Mice were vaccinated with VTRM1 or VTRS1 and challenge exposed 8 weeks later. RESULTS: VTRM1 and VTRS1 replicated extensively in the spleen during the first 3 weeks of infection, then decreased rapidly. Antibodies specific for the O polysaccharide were not detected in sera of mice inoculated with either rough strain. Vaccination with VTRM1 or VTRS1 induced protection against virulent strains of B abortus (2308), B melitensis (16M), B suis biovar 1 (750), and B suis biovar 4 (2579). VTRM1 also protected against B ovis (PA) and against 4 field isolates of B abortus from bison or elk. VTRS1 conferred protection against 4 field isolates of B suis biovar 4 from reindeer. Vaccines prepared from live VTRM1 or VTRS1 provided significantly greater protection than that afforded by vaccines of killed cells in QS-21 adjuvant. Vaccination with VTRM1 containing VTRS1 gave minimal protection against the antigenically unrelated Listeria monocytogenes, thus demonstrating the immunologic specificity of protection against Brucella spp. CONCLUSIONS AND CLINICAL RELEVANCE: Results encourage evaluation, in primary host species, of VTRM1 and VTRS1, along with RB51, as alternative vaccines to strain 19, Rev 1, or other smooth phase vaccines.

Alleles↗
PubMed1997

Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo.

Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response that potentiates antitumor immunity but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood but are likely to involve mediation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10 but not tumor necrosis factor alpha. IL-6 mRNA and protein are strongly enhanced in the PDT-treated EMT6 tumor. PDT also increased IL-6 mRNA in exposed spleen and skin. These data suggest that the general inflammatory response to PDT may be mediated at least in part by IL-6. In addition, IL-6 may modulate the local antitumor immune response. In contrast, IL-10 mRNA in the tumor decreases following PDT. Most importantly, IL-10 is markedly induced in the skin of mice exposed to a PDT regime that strongly inhibits the CHS response, and the kinetics of IL-10 induction coincide with the known kinetics of CHS inhibition. We propose that the enhanced IL-10 expression plays a role in the observed suppression of cell-mediated responses seen following PDT.

Animals↗
PubMedDate not supplied

[Model of coxsackievirus B3 persistent infection in orally-inoculated BALB/c mouse].

Many mouse models of human enterovirus disease have been pro- posed, concerning both acute and persistent infection. However, rather paradoxically since the usual way of contamination is fecal-oral, most of them used a systemic route of infection. The aim of the present work was to follow the development of an experimental enterovirus infection and to study the viral persistence at the organ level. Twenty-eight female 3-week old BALB/c mice were infected with 5 x 10(4) TCID(50) of coxsackievirus B3 (CV-B3), Nancy strain, by oral route using a rigid cannula introduced into the stomach. The kinetics of infection was studied by sacrificing 2 animals at different times post infection (from 1 hour to 90 days). The presence of the virus in various organs (small intestine, heart, pancreas, lung, spleen, kidney, liver) was studied by cell culture and RT-PCR. As soon as one hour post infection, the virus was detected in the small intestine. In the heart, the virus was present at 24 and 48 hours post infection by RT-PCR and culture, respectively. At 5 days post infection, all the organs but the liver were found infected. The virus was detected up to 15 days in kidney, 21 days in pancreas, 30 days in lung and spleen, and 45 days in intestine, by both culture and PCR. The heart was still found infected 90 days post infection by both techniques. These results show the dramatic cardiotropism of CV-B3 inoculated by oral route, with a detection of the virus very soon in the course of infection (24 hours) and a persistence of the virus for more than 3 months. The intestine, the initial target of enterovirus infection, can also be considered as a site of viral persistence.

Animals↗
PubMed1998

The BALB/c mouse as an animal model for progressive sensorineural hearing loss.

To develop the BALB/c mouse strain as an animal model for the study of progressive sensorineural hearing loss, mice ranging in age from young adult through middle age were studied. Auditory brainstem response thresholds, histopathology [cytocochleograms for hair cells, the packing density of spiral ganglion cells (SGCs), the number of neurons and overall size of the anterior ventral cochlear nucleus (AVCN)], and behavioral paradigms (prepulse inhibition, fear-potentiated startle) were compared with previous data from C57BL/6J (C57) and DBA/2J (DBA) mouse strains. Progressive high frequency hearing loss in BALB/c mice was generally more rapid than C57 and slower than DBA (e.g. mean thresholds for 16 kHz: 10-month-old BALB/c mice = 71 dB SPL; 55-day-old DBA mice = 79 dB SPL; 12-month-old C57 mice = 50 dB SPL). Like the other strains, BALB/c exhibited a progressive loss of hair cells and SGCs that was most severe in the cochlear base and least severe in the middle turns; however, BALB/c mice had relatively more SGC loss in the apex. Unlike C57 and DBA, no loss of neurons was observed in the AVCN following cochlear pathology (although AVCN volume was reduced). Like the other strains, successful fear conditioning was obtained with a 12 kHz conditioned stimulus. Prepulse inhibition showed that middle and low frequency tones (4-12 kHz) became more salient as high frequency hearing declined. Similar results had been previously obtained with C57 and DBA mice and were interpreted as reflecting hearing-loss-induced plasticity in the central auditory system.

Acoustic Stimulation↗
PubMed1990

The BALB/c mouse as a model for immunological studies of microfilariae-induced pulmonary eosinophilia.

Tropical pulmonary eosinophilia (TPE) is believed to result from extreme immediate hypersensitivity to microfilariae localized in the pulmonary vasculature of some persons with lymphatic filariasis. Female BALB/c mice repeatedly immunized by ip injection of Brugia malayi microfilariae become amicrofilaremic within 24 hr of iv parasite challenge, whereas non-sensitized control animals remain patent for greater than 72 hr. Immunized, but not control mice, develop peripheral blood and pulmonary eosinophilia (2,000 cells/mm3 and 65,000 cells/bronchoalveolar lavage, respectively). Serum and bronchoalveolar lavage filarial-specific IgG antibodies are greater in sensitized mice than in controls (ELISA absorbance values 20- and 10-fold higher, respectively). Serum IgE antibody levels are also greater (P less than 0.01) in immunized parasite-challenged mice than in controls (mean cpm 125I-labeled anti-mouse IgE bound to B. malayi antigen-coated Sepharose beads: 7,852 vs. 1,741, respectively). This model exhibits several of the major features of human TPE: amicrofilaremia, elevated levels of serum IgG and IgE antibodies to microfilariae, and blood and pulmonary eosinophilia. This model may be useful in the examination of the role of filarial antigen-specific lymphoid cells and antibodies in regulating the pathologic responses to microfilariae trapped in the lung.

Animals↗
PubMed2006

Poxvirus CD8+ T-cell determinants and cross-reactivity in BALB/c mice.

Mouse models of orthopoxvirus disease provide great promise for probing basic questions regarding host responses to this group of pathogens, which includes the causative agents of monkeypox and smallpox. However, some essential tools for their study that are taken for granted with other mouse models are not available for these viruses. Here we map and characterize the initial CD8+ T-cell determinants for poxviruses in H-2d-haplotype mice. CD8+ T cells recognizing these three determinants make up around 40% of the total responses to vaccinia virus during and after resolution of infection. We then use these determinants to test if predicted conservation across orthopoxvirus species matches experimental observation and find an unexpectedly cross-reactive variant peptide encoded by ectromelia (mousepox) virus.

Animals↗
PubMed2003

[Induction of lymphangiogenesis by mouse ascites hepatoma cell H22 in vitro].

OBJECTIVE: To construct lymphangiogenesis model of Balb/c mouse in vitro to observe the impact of mouse ascites hepatoma cell H22 on the lymphangiogenesis and lymphatic endothelial proliferation. METHODS: Intraperitoneal benign lymphangioma induced by incomplete Freund's adjuvant in Balb/c mouse was harvested and embedded in fibrin gel to culture in vitro with conditioned medium (CM) of H22 cell. The gels, observed by inverted microscope and transmission electron microscope, were then digested to separate the cells. The expression of Flt-4, c-fos and iNOS in the cell and the content of NO in medium were studied by immunohistochemical and histochemical method. RESULTS: Lymphatic capillary generating from lymphangioma specimen in the gels was observed by inverted microscope and transmission electron microscope. H22 CM was observed to enhance growth of the vessels, induce expressions of Flt-4, c-fos and iNOS in the separated cells and increase content of NO in the medium. CONCLUSION: The model is convenient for in vitro study of lymphangiogenesis. H22 cell can accelerate lymphangiogenesis, which warrants further study for the understanding of the role of lymphangiogenesis in metastasis.

Animals↗
PubMed2004

A comparison of murine and human alveolar macrophage responses to urban particulate matter.

There is increasing evidence linking mortality, increased asthma morbidity, and other respiratory disorders to increases in fine airborne particulate matter (PM) concentrations. However, there are only limited data dealing with the biological mechanisms that ultimately lead to the reported health effects. Rodents are frequently used as an animal model to help elucidate the mechanisms of toxicity that may provide clues for the understanding of PM toxicity in humans; however, the relationships between murine and human PM toxicity have not been established. PM is known to target the pulmonary epithelium and resident alveolar macrophages (AM). PM can initiate cytotoxic effects on the AM including apoptosis and necrosis, depending on the particle concentration, which may be central to the pathological effects just described. This study examined AM apoptosis and necrosis initiated by PM in AM from humans and BALB/c mice in an in vitro exposure model. Freshly isolated AM from human volunteers were incubated with seven different residual fractions of PM1648 derived from organic solvent extractions, high-temperature heating and acid digestions that change the surface characteristics of the original PM. These results were compared to the analogous murine experiments. The results suggested that, at the same concentration of PM, the trend of toxicity and the posttreatment effects observed in BALB/c and human AM have a similar pattern. Altering the surface chemistry by removal of one or more PM components, such as through the various treatments conducted in this study, is sufficient to alter PM bioactivity in both human and murine AM in a similar manner. In addition, the human and murine models were compared with regard to in vitro cytotoxicity using PM(2.5) particles. The cytotoxic PM(2.5) effects were identical in both human and mouse models. Regression analysis revealed that the BALB/c mouse is a suitable model for PM cytotoxicity of AM as it is a good predictive model for the human AM responses.

Air Pollutants↗
PubMed1997

Catalase, a novel antigen for Helicobacter pylori vaccination.

The efficacy of an orogastric vaccine comprised of purified Helicobacter pylori catalase plus the mucosal adjuvant cholera toxin (CT) was examined with both the Helicobacter felis and H. pylori mouse models with BALB/c mice. Native H. pylori catalase (200 microg) plus CT was initially used as a vaccine antigen in the H. felis mouse model and protected 80% (8 of 10) of the challenged animals, while all control animals were infected (20 of 20). In a follow-up experiment, recombinant H. pylori catalase plus CT was used for immunization, and groups of mice were challenged with the Sydney strain of H. pylori. Immunization with recombinant catalase protected a significant proportion (9 of 10) of the mice from H. pylori challenge, indicating that this enzyme should be considered as a candidate for a future vaccine. This study provides the first available data on the efficacy of protective immunization with the new Sydney strain of H. pylori in a mouse model. These data also provide indirect evidence that proteins which are normally intracellular, such as catalase, may be present on the surface of H. pylori and thus may provide targets for immunization.

Animals↗
PubMed1979

Immune-mediated arrest and reversal of established visceral metastases in athymic mice.

The metastasizing MDAY-D2 tumor of DBA/2 mice disseminates in BALB/c allogeneic athymic nude (nu/nu) mice in a manner identical to that observed in the syngeneic host. Both the kinetics and organ distribution pattern of metastases from s.c. implants of MDAY-D2 are routinely predictable at any given tumor dose. BALB/c heterozygote (nu/+) litter-mates reject MDAY-D2 grafts on the basis of the multiple minor histocompatibility differences that exist between DBA/2 and BALB/c mice. The in vitro cell-mediated cytotoxic response detected in tumor-bearing BALB/c nu/+ mice is "low grade" (isotope release is approximately 40 to 50% by 24-hr 111-indium-8-hydroxyquinoline assay and approximately 6 to 8% by 6-hr 51Cr assay) and yet correlates directly with tumor rejection. BALB/c nu/nu mice can be protected against MDAY-D2 by previous reconstitution with lymphoid cells from normal or MDAY-D2-sensitized BALB/c nu/+ mice. In addition, surgically documented, established visceral metastases in BALB/c nu/nu mice can be arrested and regressed by the adoptive transfer of MDAY-D2-sensitized BALB/c nu/+ spleen cells. This represents one of the few models where established metastases have been immunotherapeutically regressed. As such, the MDAY-D2 BALB/c nu/nu mouse model offers unique advantages for studying the role of the immune system in regulating the metastatic process.

Abdominal Neoplasms↗