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At least 19 recordsLinked to original sources

Drug resistance in an immunological model of HIV-1 infection with impulsive drug effects.

We consider an SIR-type model of immunological behaviour for HIV dynamics, including the effects of reverse transcriptase inhibitors and other drugs which prevent cellular infection. We use impulsive differential equations to model drug behaviour. We classify different regimes according to whether the drug efficacy is negligible, intermediate or high. We consider two strains of the virus: a wild-type strain that can be controlled by both intermediate and high drug concentrations, and a mutant strain that can only be controlled by high drug concentrations. Drug regimes may take trajectories through one, two or all three regimes, depending on the dosage and the dosing schedule. We demonstrate that drug resistance arises at both intermediate and high drug levels. At low drug levels resistance does not emerge, but the total T cell count is proven to be significantly lower than in the disease-free state. At intermediate drug levels, drug resistance is guaranteed to emerge. At high drug levels, either the drug-resistant strain will dominate or, in the absence of longer-lived reservoirs of infected cells, both viral sub-populations will be cleared. In the latter case the immune system is maintained by a population of T cells which have absorbed sufficient quantities of the drug to prevent infection by even the drug-resistant strain. We provide estimates of a range of dosages and dosing schedules which would, if physiologically tolerable, theoretically eliminate free virus in this system. Our results predict that to control viral load, decreasing the interval between doses is more effective than increasing the dose.

Anti-HIV Agents↗

Distinct effects of protease and reverse transcriptase inhibition in an immunological model of HIV-1 infection with impulsive drug effects.

We present an immunological model that considers the dynamics of CD4+ T cells interacting with free virions, reverse transcriptase inhibiting drugs and protease inhibiting drugs. We divide the T cells into multiple classes and use impulsive differential equations to describe the drug activity. As expected, we find that insufficient dosing of either drug corresponds to high viral load and a large population of infectious T cells. The model further predicts that, in the absence of physiological limits on tolerable drug concentrations, sufficiently frequent dosing with the reverse transcriptase inhibitor alone could theoretically maintain the CD4+ T cell count arbitrarily close to the T cell count in the uninfected immune system. However, for frequent dosing of the protease inhibitor alone, the limiting T cell populations may not be enough to maintain the immune system. Furthermore, frequent dosing of both drugs has the same net effect on the T cell population as frequent dosing of the reverse transcriptase inhibitor only. Thus, the two drug classes can have fundamentally different effects on the long-term dynamics and the reverse transcriptase inhibitor, in particular, plays a crucial role in maintaining the immune system. We also provide estimates for the dosing intervals of each drug that could theoretically sustain the T cell population at a desired level.

CD4 Lymphocyte Count↗

Zebrafish as an immunological model system.

Two decades of research have established the zebrafish (Danio rerio) as a significant model system for studying vertebrate development and gene structure-function relationships. Recent advances in mutation screening, the creation of genomic resources, including the Zebrafish Genome Project and the development of efficient transgenesis procedures, make this model increasingly attractive for immunological study.

Animals↗

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms.

BACKGROUND: Cancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and depression, many of which co-occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms. METHODS: In November 2001, basic and clinical scientists met to consider evidence for a cytokine-immunologic model of symptom expression along with directions for future research. RESULTS: The characteristics of cytokine-induced sickness behavior in animal models have much in common with those of symptomatic cancer patients. Sickness behavior refers to a set of physiologic and behavioral responses observed in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines. In some cases, these responses can be prevented by cytokine antagonists. A combination of animal and human research suggests that several cancer-related symptoms may involve the actions of proinflammatory cytokines. CONCLUSIONS: Based on the similarities between cancer symptoms and sickness behavior, the authors discussed approaches to further test the implications of the relationship between inflammatory cytokines and symptoms for both symptom treatment and symptom prevention.

Animals↗

High-dimensional simulation of simple immunological models.

We propose a simple model for idiotypic-antiidiotypic immunological networks which represents a simplification of the model originally suggested by Stewart & Varela, and de Boer, van der Laan & Hogeweg. Window cellular automata enlarge the antibody concentration if the influence of the immediate neighborhood lies between 70 and 99% of its maximum value; in addition random recruitment is possible. We simulate the model on large square lattices as well as in higher dimensions. The results are in qualitative agreement with those of the earlier model. Moreover, in five to ten dimensions we find phase separation for not too large recruitment, which then leads to domains growing to "infinity" for infinite times.

Animals↗

Intracorneal bovine albumin: an immunologic model of corneal angiogenesis.

BACKGROUND: We characterized the neovascularization that follows the intracorneal injection of bovine albumin (BA) in rabbits as a model of corneal angiogenesis. METHODS: New Zealand white rabbits received intracorneal injections of phosphate-buffered saline with and without various amounts of BA. The rabbits were co-sensitized or pre-sensitized by intramuscular BA or were not sensitized. The corneal vascular response was quantified by ranking photographs taken periodically after the injection. RESULTS: In pre-sensitized animals, blood vessels were apparent within 4 days and reached maximum intensity 14 days after the intracorneal injection. Corneas also vascularized in non-sensitized rabbits, but a larger dose (> 0.2 mg BA) was required than in pre-sensitized animals (> 0.02 mg BA). Vascularization began later in non-sensitized animals and was less extensive than in pre-sensitized animals. CONCLUSION: The intracorneal injection of BA is a reproducible model of corneal angiogenesis in rabbits and should allow the involved immunological mechanisms to be elucidated.

Animals↗

An immunological model of epilepsy: seizures induced by antibodies to GM1 ganglioside.

Following observations that the intracerebral injection into rats of antiserum to brain gangliosides resulted in recurrent epileptiform activity and that seizure activity was not seen if antibodies were removed by absorption of the antiserum with pure GM1 ganglioside, a study was undertaken to establish characteristics of the immunological agents used to produce this model of epilepsy. It was determined that the potencies (antibody titers with GM1 ganglioside) of antiganglioside sera can be correlated with the intensities of epileptiform activity they induce; that immunoglobulin fractions from antiganglioside sera are even more effective biologically than the antisera; and that antibodies to GM1 ganglioside purified by affinity chromatography can also induce recurrent epileptiform discharges but are not as effective as either native antiserum or immunoglobulin fractions.

Animals↗

[Cervix carcinoma as an immunological model. Part 2. In vitro studies and HLA system typing].

Carcinoma of the cervix uteri is one of the most important tumors in women. The tumor induces an immunological defense reaction against itself in the tumor host. The round cell infiltrate at the tumor invasion line, which predominantly consists of small lymphocytes is the morphological equivalent of this interrelationship. In the lymph-nodes of the drainage area of the tumor certain patterns of reaction can be differentiated, which may be interpreted as humoral or cellular immune reactions. Cellular immune reactions in lymph-nodes of patients operated according to the method of Wertheim-Meigs were correlated with a better prognosis of the tumor disease. The hypothesis of an involvement of the HSV-type II in the genesis of the cervical carcinoma is supported by the increased incidence of antibodies against the virus. Therewith, relations between the stage of disease and the age of the patient were found as a possible basis for the virus hypothesis and the immune reaction to the tumor associated antigens an altered genetic situation may be presumed. Typing in the HLA-system demonstrates an accumulation of the frequency of the antigen B12 in patients with carcinoma of the cervix. These investigations may lead to a differentiated outlook with regard to the detection of risk groups and therapeutical consequences for cervical cancer.

Antibodies, Viral↗

Toxocara canis infections in a pig model: immunological, haematological and blood biochemistry responses.

The immunological, haematological and enzymatic responses to the inoculation in pigs of 100,000 embryonated eggs of Toxocara canis were studied. Fifteen females were inoculated and three remained as controls. Haematological values were analysed from day 7 p.i. until day 126 p.i. In the inoculated group, white blood cells were raised on day 14 p.i. and eosinophil values on days 7, 14, 21, 35 and 49 p.i. showing significant differences compared with controls (P < 0.05). Absolute eosinophil counts (per ml) presented two rises, the first on days 7, 14 and 21 p.i. and the second on days 35 and 49 p.i. Blood biochemistry was maintained within normal values. Serological examination by ELISA to determine antibody levels against Toxocara canis L2/L3 excretory-secretory (ES) antigens showed values higher than the positive cut-off (1:32) from day 7 p.i. and until the end of the study on day 126 p.i., presenting two peaks: one on day 28 p.i. and the second covering days 49 to 56 p.i. Western blots of sera of inoculated animals presented, from day 7 p.i., two polypeptide bands of 55 and 70 kDa MW and, from day 56 p.i., an additional band of 120 kDa MW, all of which persisted until the end of the study. Immunological responses were sustained over time. No direct correlation was observed between the rise in eosinophils and antibody titres. To validate the conclusions, more studies are required on the polypeptide bands.

Animals↗

Inability to establish ectopic endometrium in a natural killer cell-deficient murine model. Immunologic, histologic and histochemical assessment.

OBJECTIVE: To investigate what effect natural killer (NK) cells have on the implantation of heterologous endometrial scrapings. STUDY DESIGN: Anti-asialo GM1 (AA-GM1) anti-sera have been shown to eliminate NK cell activity in various strains of rats and mice. Either AA-GM1 antibodies (+) or rabbit antiglobulin (-) was administered to beige mice (NK cell deficient) or beige control mice (not NK cell deficient of the same strain). The heterologous endometrial scrapings were prepared by scraping seven pairs of uterine horns from normal mice of the same strain. Beige and normal mice were then injected intraperitoneally every 3 days with the heterologous endometrial scraping and antibodies for a period of 50 days. The four experimental groups (n = 10 per group) can be summarized as being beige (+), beige (-), normal (+) and normal (-). RESULTS: There was no evidence of ectopic endometrial tissue in any of the four test groups by histologic examination or by using immunohistochemical staining techniques. Histologic evidence of an impaired immune response was clearly demonstrated in the beige mice receiving AA-GM1 antibodies. CONCLUSION: Using this model, a deficiency of NK cell activity did not appear to enhance the implantation of endometrial tissue on the abdominal peritoneum of mice.

Animals↗