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Biomedical subjects

H HogenEsch

Publications and source records attributed to H HogenEsch.

At least 37 records · Page 2Linked to original sources
PubMed1999

Absence of Peyer's patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice.

The chronic proliferative dermatitis (cpdm) mutation causes inflammation in multiple organs, most prominently in the skin. Examination of the immune system revealed severe abnormalities in the architecture of lymphoid tissues. Peyer's patches were absent. In contrast, the spleen, lymph nodes, and nasal-associated lymphoid tissues were present. The spleen had normal numbers of T and B cells, but the spleen, lymph nodes, and nasal-associated lymphoid tissues had poorly defined follicles and lacked germinal centers and follicular dendritic cells. The marginal zone in the spleen was absent. The total concentration of serum IgG, IgA, and IgE in cpdm/cpdm mice was significantly decreased, whereas serum IgM was normal. Fecal IgA was low to undetectable in mutant mice, and the concentration of fecal IgM was increased. The titer of DNP-specific Abs following immunization with DNP-keyhole limpet hemocyanin was significantly decreased for all IgG subclasses. In contrast, T cell function appeared normal as assessed by evaluation of the contact hypersensitivity response in cpdm/cpdm mice. The cpdm mutation causes a complex phenotype that is characterized by multiorgan inflammation and the defective development of lymphoid tissues. The cpdm/cpdm mouse may be a useful model to study the factors that control the development of lymphoid tissues, in particular the Peyer's patches, and the mechanisms that control the humoral immune response.

Animals↗
PubMed1999

Oral vaccination of animals with antigens encapsulated in alginate microspheres.

Most infectious diseases begin at a mucosal surface. Prevention of infection must therefore consider ways to enhance local immunity to prevent the attachment and invasion of microbes. Despite this understanding, most vaccines depend on parenterally administered vaccines that induce a circulating immune response that often does not cross to mucosal sites. Administration of vaccines to mucosal sites induces local immunity. To be effective requires that antigen be administered often. This is not always practical depending on the site where protection is needed, nor comfortable to the patient. Not all mucosal sites have inductive lymphoid tissue present as well. Oral administration is easy to do, is well accepted by humans and animals and targets the largest inductive lymphoid tissue in the body in the intestine. Oral administration of antigen requires protection of antigen from the enzymes and pH of the stomach. Polymeric delivery systems are under investigation to deliver vaccines to the intestine while protecting them from adverse conditions that could adversely affect the antigens. They also can enhance delivery of antigen specifically to the inductive lymphoid tissue. Sodium alginate is a readily available, inexpensive polymer that can be used to encapsulate a wide variety of antigens under mild conditions. Orally administered alginate microspheres containing antigen have successfully induced immunity in mice to enteric (rotavirus) pathogens and in the respiratory tract in cattle with a model antigen (ovalbumin). This delivery system offers a safe, effective means of orally vaccinating large numbers of animals (and perhaps humans) to a variety of infectious agents.

Administration, Oral↗
PubMed1999

Changes in keratin and filaggrin expression in the skin of chronic proliferative dermatitis (cpdm) mutant mice.

The expression of keratins and filaggrin by keratinocytes is a highly regulated process and depends on their state of differentiation and proliferation. As such, these proteins can be used as markers to determine if keratinocyte differentiation is normal. Mutant cpdm/cpdm mice develop a chronic skin disease characterized by epidermal hyperplasia and inflammation. Immunohistochemical staining for the basal keratins K5 and K14 revealed expression in the basal and suprabasal cell layers. The expression of K1 and K10 was reduced and limited to the outer layers of the stratum spinosum. Keratin 6 was expressed in the suprabasal layers of affected skin, and throughout all layers in severely affected skin. Filaggrin was present in the stratum granulosum which had variable thickness. These results indicate that the differentiation of keratinocytes in cpdm/cpdm mice was normal. The altered distribution and expression of keratins in comparison with the skin of control mice was the result of hyperproliferation.

Animals↗
PubMed1999

Biodegradable alginate microspheres as a delivery system for naked DNA.

Sodium alginate is a naturally occurring polysaccharide that can easily be polymerized into a solid matrix to form microspheres. These biodegradable microspheres were used to encapsulate plasmid DNA containing the bacterial beta-galactosidase (LacZ) gene under the control of either the cytomegalovirus (CMV) immediate-early promoter or the Rous sarcoma virus (RSV) early promoter. Mice inoculated orally with microspheres containing plasmid DNA expressed LacZ in the intestine, spleen and liver. Inoculation of mice with microspheres containing both the plasmid DNA and bovine adenovirus type 3 (BAd3) resulted in a significant increase in LacZ expression compared to those inoculated with microspheres containing only the plasmid DNA. Our results suggest that adenoviruses are capable of augumenting transgene expression by plasmid DNA both in vitro and in vivo.

3T3 Cells↗
PubMed1998

Evidence of reproductive failure and lack of perinatal transmission of Bartonella henselae in experimentally infected cats.

Five female specific pathogen-free (SPF) cats inoculated intradermally with B. henselae and bacteremic for 4 weeks, and one cat inoculated with 0.9% NaCl, were bred with uninfected SPF male cats. The uninfected female became pregnant with one breeding, while three infected cats became pregnant 1-12 weeks later, after repeated breedings. Two infected females either did not become pregnant or maintain pregnancies despite repeated breedings. Infected cats produced anti-B. henselae IgM and IgG antibodies. Fetuses and kittens of infected cats were not infected and did not produce anti-B. henselae antibodies. Male cats bred with infected females did not become infected or seroconvert. Maternal anti-B. henselae IgG antibodies detected in sera of kittens 2 weeks post-partum were no longer detectable 10 weeks post-partum. These findings suggest that B. henselae causes reproductive failure in female cats, but is not transmitted transplacentally, in colostrum or milk, or venereally. Infected cats immunosuppressed with methylprednisolone acetate after their kittens were weaned had no detectable bacteria in tissues, suggesting that they were no longer infected.

Animals↗
PubMed1998

The humoral immune response to Haemophilus influenzae type b: a mathematical model based on T-zone and germinal center B-cell dynamics.

Through careful mapping of the physiology of the T-zone and GC B-blast dynamics to a mathematical representation of the cell processes including proliferation, migration, differentiation, and cell death, a mathematical model is constructed to capture the dominant nominal primary, late follicular, and secondary humoral response to Haemophilus influenzae Type b. This model explicitly incorporates the dynamics of memory B-cells, T-zone and GC B-dynamics, IgM and IgG antibodies, avidity maturation, and IC presentation by FDCs into a coherent framework. This paper describes the relevant immunology, the pertinent physiological assumptions, the developed model, and the parameter identification procedure. The model parameters were found using a parameter identification procedure that capitalizes on the timing and interactions of certain dominant physiological attributes. Simulation results and validation tests indicate that the model reflects not only a nominal primary and secondary humoral immune response but also the tertiary and T-independent responses. The model shows robustness to variations in infection dosage, bacterial growth rate (virulence of the strain), and onset-timing of the secondary response. The utility of this model in studying the humoral immune response is demonstrated through suggested physiological assumptions, mechanisms, and rates to be eventually clinically evaluated as well as insights into vaccination design. The model and parameter identification techniques are easily adapted to other diseases which primarily evoke a humoral immune response.

Antibodies, Bacterial↗
PubMed1998

Induction of pulmonary immunity in cattle by oral administration of ovalbumin in alginate microspheres.

Respiratory infectious diseases are an important cause of economic losses to the cattle industry. There is a need for an effective, easy to administer vaccine to the critical bacterial pathogens that cause pneumonia in cattle. An orally administered vaccine could be given to a large number of animals without significant stress to the animals and with minimal labor. The purpose of this study was to determine whether the oral administration of a model antigen (ovalbumin) in alginate microspheres could induce pulmonary immunity in cattle. Calves were vaccinated orally with ovalbumin (OVA) following either a subcutaneous (s.c.) or oral priming dose of OVA. Calves primed and boostered by oral administration (oral/oral) of OVA encapsulated in alginate microparticles had increased numbers of antigen-specific IgA ASCs (ASCs) in bronchoalveolar lavage (BAL) fluids. Calves that received a s.c. priming followed by an oral booster inoculation (s.c./oral) of OVA in alginate microspheres had a greater number of anti-OVA IgA, IgG1 and IgG2 ASCs in BALF. S.c./oral calves also had increased numbers of anti-OVA IgG1 ASCs in peripheral blood whereas oral/oral calves had none. S.c./oral calves had increased anti-OVA IgG1, IgG2, and IgA titers in BALF, and IgG1 and IgG2 in serum compared to both oral/oral and sham vaccinated calves. These results indicate that oral administration of antigen encapsulated in alginate microspheres results in a mucosal immune response in the respiratory tract of cattle. Furthermore, s.c. priming both enhanced the IgA response and stimulated an IgG1 and IgG2 response not seen in oral/oral calves. The difference in antibody isotype results suggest that design of the vaccination protocol can direct antibody responses as needed for a specific immunization program.

Administration, Oral↗
PubMed1998

Systematic method for determining intravenous drug treatment strategies aiding the humoral immune response.

This paper delineates a systematic method for determining "optimal" intravenous drug delivery strategies for patients having illnesses that primarily evoke a humoral immune response and are treatable by antibiotics. The method derives from a nonlinear, distributed predator-prey model that captures the dominant antigen and antibody interaction. This model is developed from relevant physiology, past predator-prey-type modeling work, available data, and pertinent parameter identification. Embedding this predator-prey model into a larger class of uncertain systems, by a finite dimensional approximation and a transformation to a linear fractional representation, enables the application of robust control based on linear matrix inequality optimization techniques. The optimization problem is solved by minimizing an upper bound on a measure of the total drug delivered subject to patient recovery (stability to healthy equilibrium state). Specifically, the paper addresses the treatment of Haemophilus influenzae through modeling, controller development, and simulations of infected adult patients subjected to typical and proposed intravenous antibiotic treatments. Through simulations the proposed intravenous drug strategy shortens patient recovery time, lowers peak drug concentrations and decreases the total drug administered when compared to standard antibiotic strategies.

AIDS-Related Opportunistic Infections↗
PubMed1998

Primary vascular neoplasms of lymph nodes in the dog.

Primary vascular neoplasms of lymph nodes are rare, and appear not to have previously been reported in domestic animals. This report describes hemangiomas and a lymphangioma in lymph nodes of aged Beagle dogs. Eight hemangiomas (4.8%) and one lymphangioma were present in 165 examined popliteal lymph nodes, and one hemangioma occurred in a hepatic lymph node. The hemangiomas were cavernous and benign.

Age Factors↗
PubMed1997

Experimental infection of young specific pathogen-free cats with Bartonella henselae.

Eighteen 12-week-old specific pathogen-free cats, blood culture- and serum antibody-negative for Bartonella henselae, were randomly allocated to groups and were intravenously inoculated with 10(10) (group 1), 10(8) (group 2), or 10(6) (group 3) B. henselae or with saline (group 4) or were not inoculated (group 5). Cats were humanely killed at 2, 4, 8, 16, and 32 weeks after inoculation. All B. henselae-inoculated cats were bacteremic by 2 weeks after infection. Bacteremia persisted until 32 weeks after infection in 1 cat. Cats in groups 1 and 2 had fever (>39.7 degrees C) and partial anorexia by 2 weeks after infection that lasted 2-7 days. All infected cats had Bartonella-specific IgM and IgG serum antibodies and lymphocyte blastogenic responses. Histopathologic lesions were observed in multiple organs of infected cats through 8 weeks after infection. Cats were readily infected with B. henselae by intravenous inoculation, developed histopathologic lesions that apparently resolved, and developed B and T lymphocyte responses to infection.

Animals↗
PubMed1996

Systemic and pulmonary immune response to intrabronchial administration of ovalbumin in calves.

Local immunization of the respiratory tract may be the best way to achieve protection against respiratory pathogens. In order to do so successfully, it is important to fully understand how the immune response to antigen administered via the respiratory route develops. We studied the respiratory and systemic immune response after subcutaneous (SC) and intrabronchial (IB) inoculation of calves with ovalbumin (OVA). Eight calves received two SC inoculations of OVA and eight other calves received two SC and three additional IB inoculations of OVA. The occurrence of OVA-specific antibodies and antibody-secreting cells (ASC) was measured over time using isotype-specific enzyme linked immunosorbent assay (ELISA) and ELISPOT. SC immunization of calves did not result in OVA-specific IgA in bronchoalveolar lavage (BAL) fluid. Subcutaneous priming followed by intrabronchial challenge caused an initial IgG1 response in the bronchoalveolar lavage fluid, followed by a large IgA response. The presence of IgG1-ASCs indicated that the IgG1 was at least partially locally produced. Most of the OVA-specific IgA in the BAL fluid was secreted by pulmonary ASCs as indicated by the large number of IgA-ASCs in BAL samples and the low serum level of OVA-specific IgA. Antigen-specific IgG1 ASCs were detectable among peripheral mononuclear cells after culture with OVA.

Animals↗
PubMed1996

Tenfold increased incidence of spontaneous multiple myeloma in long-term immunosuppressed aging C57BL/KaLwRij mice.

Persons undergoing maintenance immunosuppressive treatment (MIST) were shown to be at increased risk for the development of early malignancies, often of cells of the immune system. Very little is known about the late effects of MIST. Some clinical studies indicated an age-related increase in the incidence of plasma-cell disorders, in particular in that of multiple myeloma (MM). In the present study the influence of MIST on the development of monoclonal B-cell proliferative disorders, monoclonal gammopathies (MG), was studied in an animal model, the C57BL/KaLwRij mouse. This strain is known for its susceptibility to develop with aging MG similar to those in humans. Two widely used treatment protocols (azathioprine/prednisolone and Cyclosporin A/prednisolone) were tested in young and adult mice. Both regiments were shown to increase 10-fold the incidence of spontaneous multiple myeloma. Unexpectedly, the same high incidence of MM and in addition the development of a life-shortening lymphoblastic lymphoma were found in a high frequency in the control group that received Cremophor EL only, i.e., the solvent of Cyclosporin A. Repeated experiments with another lot of Cremophor showed a 6-fold increased frequency of NM but no lymphoblastic lymphoma. With respect to the life-span and the incidence of hemopoietic neoplasms the least harmful drugs for MIST appeared to be azathioprine/prednisolone. The results of the experiments in this C57BL/KaLwRij mouse model give a warning for increased incidence of MM in susceptible aging individuals and address a question whether Cremophor EL is a safe solvent for Cyclosporin A.

Aging↗
PubMed1996

Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm).

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To further elucidate its pathogenesis, organs of 1-, 2-, 3-, 4-, 5-, and 6-week-old cpdm/cpdm mice were examined. At 4 weeks, the epidermal thickness was increased, whereas already at 3 weeks, the bromodeoxyuridine incorporation was increased in the basal keratinocytes. However, already at the age of 1 week, skin, lungs, and lymph nodes were infiltrated by eosinophils although no macroscopic lesions were present. Compared with control animals, 6-week-old cpdm/cpdm mice had decreased serum IgE levels and increased numbers of mast cells. From the age of 1 week these mast cells became increasingly IgE positive. In contrast, the mast cells of the control animals remained IgE negative. Mast cells of control and cpdm/cpdm mice were interleukin-4 and tumor necrosis factor-alpha positive. A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis factor-alpha from activated mast cells. Tumor necrosis factor-alpha may lead to the expression of E-selectin on endothelial cells, facilitating interleukin-4-mediated eosinophil transendothelial migration. Although various pathogenetic aspects of the cpdm/cpdm mouse need further elucidation, this model can be a tool to study eosinophil infiltration, leukocyte-endothelial cell interactions, and mast cell proliferation. Furthermore, the cpdm/cpdm mouse can be used to study chronic inflammatory skin disease because of the severe epidermal proliferation.

Animals↗
PubMed1995

Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect.

Animals↗
PubMed1995

Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.

Amyloidosis↗
PubMed1994

Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice.

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been used to study the effect of different cholesterol-containing diets on the remnant lipoprotein levels and composition and on the possible concurrent development of atherosclerotic plaques. On high fat/cholesterol (HFC) diet, the high expressing lines 2 and 181 developed severe hypercholesterolemia (up to 40 and 60 mmol/liter, respectively), whereas triglyceride levels remained almost normal when compared with regular mouse diet. The addition of cholate increased the hypercholesterolemic effect of this diet. In lines 2 and 181, serum levels of apo E3-Leiden also increased dramatically upon cholesterol feeding (up to 107 and 300 mg/dl, respectively). In these high expressing APOE*3-Leiden transgenic mice, the increase in both serum cholesterol and apo E3-Leiden occurred mainly in the VLDL/LDL-sized fractions, whereas a considerable increase in large, apo E-rich HDL particles also occurred. In contrast to the high expressing lines, the low expressing line 195 reacted only mildly upon HFC diet. On HFC diets, the high expresser APOE*3-Leiden mice developed atherosclerotic lesions in the aortic arch, the descending aorta, and the carotid arteries, varying from fatty streaks containing foam cells to severe atherosclerotic plaques containing cholesterol crystals, fibrosis, and necrotic calcified tissue. Quantitative evaluation revealed that the atherogenesis is positively correlated with the serum level of cholesterol-rich VLDL/LDL particles. In conclusion, with APOE*3-Leiden transgenic mice, factors can be studied that influence the metabolism of remnant VLDL and the development of atherosclerosis.

Animals↗