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Initiation/promotion versus complete carcinogenicity in the rodent liver.

4-N-Pyrrolidinylazobenzene (4N) is a close structural analog of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB). This structural similarity led us to evaluate it for genotoxic activity in vitro. We observed activity for 4N and DAB in the BHK cell transformation assay and subsequently in the Salmonella mutation assay of Ames. By a curious chance, Scribner, Miller and Miller, probably prompted by the same structural similarity, had synthesized 4N in the 1960s and found it to be noncarcinogenic to the rodent liver using a bioassay test protocol that detected DAB as carcinogenic. These findings were only described following the publication of our observations made in vitro. The conflict that apparently exists between these data can be interpreted in two separate ways. (a) Scribner et al. have suggested that 4N may be a carcinogenic initiator as opposed to a complete carcinogen like DAB. They also suggested that promotion of 4N-treated rodents with phenobarbitone might lead to the production of liver tumors. (b) We have evaluated the simpler concept that the activities observed for 4N in vitro define a carcinogenic potential that is not realized in vivo due to its rapid detoxification, at least in rodents. The first of these explanations implies that pure carcinogenic initiators may form a separate class of genotoxic agents from complete carcinogens, and perhaps of greater interest, that 4N might provide a valuable model compound for the study of carcinogenic promotion in the rodent liver. The second explanation regards potential carcinogenicity as a single property that can be defined in vitro and which may or may not be expressed in vivo depending on the enzymic environments encountered by the test chemical. It is clearly important to evaluate these different propositions in order to aid progress in the study of carcinogenic promotion, especially in the rodent liver. The presentation will describe our recent studies in vitro and in vivo in this connection.

Animals↗

Mammary gland neoplasia in long-term rodent studies.

Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation in cancer initiation. Comparative studies with the development of the human breast and the pathogenesis of breast cancer have contributed to validate rodent-to-human extrapolations. However, it has not been definitively established what type of information is necessary for human risk assessment, whether currently toxicity testing methodologies are sufficient for fulfilling those needs, or whether treatment-induced tumorigenic responses in rodents are predictive of potential human risk. An alternative to the traditional bioassays are mechanism-based toxicology and molecular and cellular approaches, combined with comparative in vitro systems. These approaches might allow the rapid screen of chemicals for setting priorities for further studies to determine the dose-response relationship for chemical effects at low doses, to assess effects other than mutagenesis and/or tumorigenesis, or to establish qualitative and quantitative relationships of biomarkers to toxic effects. Until there is enough information on the predictive value of mechanism-based toxicology for risk assessment, this approach should be used in conjunction with and validated by the traditional in vivo long-term bioassays.

Animals↗

Wild rodents as experimental intermediate hosts of Lagochilascaris minor Leiper, 1909.

A total of 25 specimens of Cavia porcellus (guinea pig), 5 Dasyprocta agouti (agouti), and 22 Calomys callosus (vesper mice) were inoculated with infective eggs of Lagochilascaris minor. The inoculum was prepared with embryonated eggs and orally administered to each individual animal through an esophagus probe. In parallel, 100 specimens of Felis catus domesticus were individually fed with 55-70 nodules containing 3rd-stage larvae encysted in tissues of infected rodents. Animals were examined and necropsied at different time intervals. The migration and encystment of L3 larva was observed in viscera, skeletal muscle, adipose and subcutaneous tissues from all rodents. Adult worms localized at abscesses in the cervical region, rhino, and oropharynx were recovered from domestic cats inoculated with infected rodent tissues. Through this study we can conclude that: (1) wild rodents act as intermediate hosts, characterizing this ascarid heteroxenic cycle; (2) in natural conditions rodents could possibly act as either intermediate hosts or paratenic hosts of Lagochilascaris minor; (3) despite the occurrence of an auto-infecting cycle, in prime-infection of felines (definite hosts) the cycle is only completed when intermediate hosts are provided; and (4) in the wild, rodents could serve as a source of infection for humans as they are frequently used as food in regions with the highest incidence of human lagochilascariasis.

Animals↗

Detection and characterization of Borrelia bissettii in rodents from the central California coast.

This is the first report of Borrelia burgdorferi sensu lato in rodents from San Luis Obispo county, with most isolates obtained from a previously unreported host, Neotoma lepida Thomas. B. burgdorferi sensu lato was identified in seven rodent species, including the California vole, Microtus californicus Peale; dusky-footed woodrat, Neotoma fuscipes Baird; desert woodrat, Neotoma lepida Thomas; brush mouse, Peromyscus boylii Baird; California mouse, Peromyscus californicus Gambel; deer mouse, Peromyscus maniculatus Wagner; and western harvest mouse, Reithrodontomys megalotis Baird. Ear punch biopsies were cultured in BSK-H medium from 179 rodents trapped at six different study sites. Overall, prevalence of rodent infection was 44/179 (24.6%), with 34 of these isolates from N. lepida. Spirochete isolates were obtained from rodents at all study sites, indicating widespread prevalence of B. burgdorferi sensu lato across rodent species and habitats. Nucleotide sequences for 14 of these isolates have been submitted to GenBank. Isolates from three N. lepida and one P. boylii had identical flagellin gene sequences, and phylogenetic analysis placed these spirochetes in B. burgdorferi sensu lato group DN127, now known as B. bissettii Postic, Marti Ras, Lane, Hendson & Baranton. Additional sequencing of the intergenic spacer regions between the 5S and 23S ribosomal genes was performed on three of these isolates. Phylogenetic analysis separated these isolates into two clusters that grouped with Colorado or California isolates. The role of B. bissettii and related species other than B. burgdorferi sensu stricto Johnson, Schmid, Hyde, Steigerwalt & Brenner as human pathogens in the United States warrants further investigation.

Animals↗

Culture condition-dependent senescence-like growth arrest and immortalization in rodent embryo cells.

Culture Condition-Dependent Senescence-Like Growth Arrest and Immortalization in Rodent Embryo Cells. We investigated the telomerase activity, telomere length, and replicative life span of cells from human embryos and rodent embryos (mouse, rat and Syrian hamster). We used two culture conditions for rodent embryo cells whereby the cells were plated at a density of 2 x 10(5) into a 25-cm(2) flask and subcultured every 3 days or every 10 days. We found that nearly 100% of the cultures of rodent embryo cells become immortal when they are subcultured using the 10-day culture protocol. These rodent embryo cells retain telomerase activity and long telomeres (19-50 kb) in the long-term cultures, whereas human embryo cells rapidly deplete telomerase activity associated with significant shortening of telomeres, and then they senesce. In contrast to the results from 10-day cultures, we found that some mouse cell cultures and most Syrian hamster cell cultures arrest cell growth after 13 and 29 population doublings, respectively, while retaining substantial levels of telomerase activity and experiencing no significant loss of telomeres when the cells were subcultured using the 3-day culture protocol. This growth arrest is phenotypically indistinguishable from cellular senescence. The present results suggest that in rodent cells the onset of senescence-like arrest can be activated without repression of telomerase, and that this activation pathway can be bypassed easily under certain culture conditions, such as the 10-day culture protocol.

Animals↗

Tilapia (Oreochromis niloticus) and rodents exhibit similar patterns of inhibited antibody production following exposure to immunotoxic chemicals.

The hemolytic plaque forming cell assay (PFC), a measure of ability to produce specific antibodies following challenge with antigen, is a powerful predictor of immunosuppression in chemical-exposed rodents. The efficacy of this assay for predicting humoral immunosuppression in non-rodent species remains unknown. In the present report, tilapia (Oreochromis niloticus) were exposed to 9 chemical agents known to inhibit antibody production in mice (benzo[a]pyrene, 7,12-dimethylbenzanthracene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dimethyl nitrosamine, cadmium chloride, azathioprine, hexachlorocyclohexane, T2 mycotoxin and toluene) and 5 chemical agents which do not inhibit this response (oxymethalone, acetonitrile, diethylstilbesterol, t-butylhydroquinone and formaldehyde). Eight of 9 agents which inhibit antibody production in rodents caused decreased PFC responses in fish. All 5 compounds with negative humoral effects in rodents were also negative in fish. Thus, 13/14 chemical agents tested gave similar results in tilapia as reported in rodents, suggesting a comparable pattern of humoral immunosuppression in chemical-exposed tilapia to that seen in laboratory rodent models.

Animals↗

Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: similarities and differences compared with rodents.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNAs are expressed in developing and adult rodent tongue and are important for the proper development of lingual gustatory and somatosensory innervation in rodents. Here, we wished to determine whether the findings in rodents apply to humans. By using in situ hybridization histochemistry, distinct, specific, and in some instances overlapping patterns of BDNF and NT-3 mRNA expression were found in the developing and adult human tongue, gustatory papillae, and taste buds. BDNF mRNA was expressed in the superior surface epithelium of the developing fungiform papillae (i.e., developing taste buds), in the epithelium covering the circumvallate papillae, and in the subepithelial mesenchyme. Interestingly, BDNF mRNA was expressed in the lingual epithelium before nerve fibers reached the epithelium, indicating a prespecialization of the gustatory epithelium before the arrival of nerves. In the adult fungiform papillae, BDNF mRNA labeling was found in taste buds and in restricted areas in the non-gustatory lingual epithelium. NT-3 mRNA was found in the developing lingual epithelium and gustatory papillae. NT-3 mRNA labeling was observed in the adult fungiform taste buds, overlapping with BDNF mRNA labeling, in contrast to what was seen in rodents. NT-3 mRNA was additionally found in restricted areas in filiform papillae. Protein gene product 9.5 (PGP) antibodies were used to investigate a possible correlation between lingual innervation and sites of neurotrophin gene activity. Adult human tongue innervation differed from that of rodents, possibly in part due to a different neurotrophin expression pattern in the human tongue. Based on these findings, we suggest that BDNF and NT-3 are important for the initiation and maintenance of the gustatory and somatosensory innervation also in humans. The broader and somewhat overlapping expression patterns of BDNF and NT-3 mRNAs, compared with rodents, suggest additional and possibly somewhat overlapping roles for BDNF and NT-3 in the human tongue and also indicate differences between species. It is important that interspecies differences be taken into consideration.

Adult↗

Handheld digital equipment for weight composite distress paradigms: new considerations and for rapid documentation and intervention of rodent populations.

Animal care in the third millennium will require a melding of scientific and humane interests to achieve optimal care of genetically engineered mice and to expedite scientific and medical advances by using these mammals. Undoubtedly, rodent patients present certain difficulties for those who wish to assess their daily well-being and to contribute to efficient and successful scientific discovery. High-density housing, large experimental groups, and low-lux room lighting makes the application of large-animal care standards to rodents seem daunting to researchers and veterinary care programs. In addition, great variability in training and experience among those responsible for the direct application of humane care to rodents exists. Most of the direct animal care in small animal facilities occurs in decentralized locales by personnel who have completed obligatory but relatively minimal animal care training. Examples of personnel in this category include postdoctoral fellows, junior-level scientists, summer students, and assistant laboratory animal technologists. Some programs even use the husbandry staff to perform health checks of high-risk populations on a daily basis. For this reason, the extrapolation of performance-based intervention in rodent care is difficult to apply practically. Early efforts to enhance humane outcome in rodents have been published by scientists and veterinarians and are largely directed at singular endpoints, such as weight loss and declining temperatures, in specific models. Scientists often are reluctant to accept such standards because of concern about premature intervention or variability between scorers and to reservations regarding a lack of procedural likeness with their proposed study. This paper highlights a digital method for melding current advanced animal scoring standards using palm pilot user-friendly methods that account for composite weight scoring, behavioral or physiologic attributes, and interventions. Information is rapidly downloaded and results in quick storage of large rodent population monitoring. This minimizes interpretative variability between caregivers and greater standardization of procedures. These considerations facilitate the rapid diagnosis of outliers and make possible intervention that streamlines the delivery of humane care to large experimental populations.

Animal Technicians↗

Isolation and characterization of flagellates from rodents and canids in Masinga, Machakos District, Kenya.

A total of 728 animals comprising of 633 rodents and 95 canids were examined for leishmanial parasites. Flagellates were isolated from 67 out of 111 (60.4%) Acomys subspinosus (spiny mouse), 12 out of 143 (8.4% ) Mastomys natalensis (multimammate rat), 2 out of 50 (4.0%) Lemniscomys striatus (striped mouse), 2 out of 6 (33.3%) Herpestes sanguineus (slender mongoose), 1 of 1 Helogale parvula (dwarf mongoose) and 1 out of 84 Canis familiaris (domestic dog). All isolates were characterized by Isoenzyme analysis using nine enzymes, namely, malate dehydrogenase (MDH), phosphoglucomutase (PGM), glucose phosphate isomerase (GPI), isocitrate dehydrogenase (ICD), nucleoside hydrolase (NH), glucose 6-phosphate dehydrogenase (G6PD), malic enzyme (ME), 6-phosphogluconate dehydrogenase (GPGD) and mannose phosphate isomerase (MPI). Enzyme profiles of these isolates were compared with those of five WHO Leishmania reference strains and five well characterized rodent trypanosomes of the subgenus Herpetosoma. The profiles of the isolates were found to be different from those of the Leishmania and Trypanosoma reference strains but the parasites were morphologically similar to rodent trypanosomes. These results suggest that Leishmania parasites were not among the isolates. The enzymes profiles of the three mongoose isolates were identical but differed from profiles of isolates from rodents and dog. This is the first time in Kenya that a high prevalence of nonpathogenic trypanosomes is reported in rodents and canids. From the epidemiological point of view, these trypanosomes must be differentiated from the pathogenic species of trypanosomes and Leishmania that infect man and other animals. The results of this study suggest that rodents do not seem to play a role as reservoirs of Leishmania parasites in Masinga Location, Kenya.

Journal Article↗

Field efficacy of deltamethrin for rodent flea control in San Bernardino County, California, USA.

A study was conducted to determine the initial and residual activity of deltamethrin (0.05% dust) applied to rodent burrows (at approximately 14 g/burrow) against fleas in the Silverwood Lake area of San Bernardino County. In initial toxicity (2-d post-treatment), deltamethrin provided 97% flea control and in residual toxicity it resulted in 68% control of the rodent fleas at 15-d post-treatment. The flea fauna consisted of Oropsylla montana (89.9%) and Hoplopsylls anomalus (10.1%). All rodents captured in this study were California ground squirrels, Spermophilus beecheyi. In mark-release-recapture trials, using the microchip identification implant method at the treatment site, the recapture rate of rodents was 29% from 2- to 58-d post-treatment, declining to 21% after 98 d. In the tail-clip method at the treatment site, the recapture rate of 40% at 15-d post-treatment rose to 87% and 73% at 56- and 58-d post-treatment, respectively. At the control site, the recapture rate of 100% at 15-d post-post-treatment dropped to 20% after 98 d. In another trial at Camp Cedar Crest in the Running Springs area, deltamethrin applied to rodent burrows resulted in 70% control of fleas infesting S. beecheyi. Based on the two trials, deltamethrin showed a good initial control of rodent fleas in enzootic or epizootic plague control.

Animals↗

[The in vitro model of inhalation anesthesia using rodent ventilator].

OBJECTIVE: To set up a method of applying inhalation anesthesia in rodent using rodent ventilator and to study the dynamic procedure of the in vitro model. METHODS: The output port of the anesthesia machine was connected to the input port of the rodent ventilator, which was connected to a syringe simulating the lung. After supply of anesthetic gas, the gas samples from the input port of the ventilator and the syringe in the end-expiratory phase were collected at 10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds respectively and were determined using the gas chromatography(GC). The ratios of the anesthetic concentrations of the syringe to that of the input port were calculated (CE/CI). In elimination phase, the gas samples from the syringe were collected at 0,10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds respectively and were determined by GC. The ratios of the anesthetic concentrations of the gas at 10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds to that at 0 second were calculated(C'E/C0). RESULTS: CE/CI increased in the inhalation phase, there was an inverse relationship between CE/CI and time, the correlation coefficients were 0.90, 0.95 and 0.93 respectively (P < 0.01). The mathematical fitting equations were y = -0.19 + 0.19x(-1), y = -7.75 + 0.99x(-1), and y = -7.21 + 0.97x(-1) respectively. C'E/C0 decreased in the elimination phase,the correlation coefficients were 0.90, 0.94 and 0.95 respectively (P < 0.01). The mathematic fitting eqations were y = 5.65-0.02x(-1), y = 7.82-0.01x(-1),and y = 8.20-0.01x(-1), respectively. CONCLUSION: The in vitro model of rodent inhalation anesthesia using the rodent ventilator was set up. The establishment of this model has provided a basis for studies on inhalation anesthesia in rodents.

Anesthesia, Inhalation↗

The interaction of human and rodent IgE with the human basophil IgE receptor.

The cross-reactivity of the human IgE receptor with mouse and rat IgE was studied. Using leukocytes from a patient with chronic myelogenous leukemia, in which the mononuclear fraction contained up to 75% basophils, both rat and mouse IgE were found to inhibit the binding of 125I-human IgE to the human basophilic leukemia (HBL cells). About 15-fold more rodent IgE was required for 50% inhibition of binding than unlabeled human IgE (hIgE). Dose-response studies using increasing amounts of rodent vs human 125I-IgE indicated that the HBL cells had about 8000 receptors per cell for hIgE and 5500 receptors per cell for rodent IgE. When the HBL cells were surface labeled with 125I and subsequently solubilized with non-ionic detergent, the labeled hIgE receptor could be isolated by either affinity chromatography on IgE-Sepharose (either human or rodent) or by immunoprecipitation with hIgE and anti-IgE. By SDS-PAGE on 10% gels, the receptor had a m.w. of 58,000 daltons. The solubilized receptors exhibited some rebinding to hIgE-Sepharose, and this rebinding could be inhibited by either human or rodent IgE but not by human IgG. Both the HBL cells and normal human basophils could be passively sensitized with murine IgE anti-DNP for antigen-induced histamine release. The minimum concentration of the mouse IgE antibody for sensitizing normal basophils was 20 to 200 ng/ml. Pretreatment of basophils with human IgE, but not human IgG, abrogated the capacity of the murine IgE antibody to sensitize the cells for histamine release, which indicated that the human and rodent IgE were interacting with the same receptor.

Animals↗

Nutritional adequacy and quality control of rodent diets.

One of the most often neglected variables in experimental investigations using rodents is the diet. Recent observations that diets can influence the response of a rodent to the drug, chemical or other factors under study, with biased interpretation of results, have drawn great interest. In order to be assured that the biologic response observed is a reflection of the material or condition under study, it is imperative that the diet provide essential nutrients in the proper proportions and that contaminants be kept to a minimum. Quality control is the key to these requirements; rodent diets can provide adequate nutrition, free of significant contamination. The diets which can be provided vary according to the degree of refinements; the three major types are (1) natural product, (2) semipurified and (3) chemically defined diets. Natural product diets may be open or closed formula, depending on the amount of information that the label reveals. Guaranteed analyses of proximate nutrients are provided but are of little use in assessing the nutrient value of the formulation. The National Academy of Sciences, National Research Council publications on laboratory animal nutrient requirements should be available to all investigators using experimental animals to help them evaluate the nutritional adequacy of the diets they use. Rats and mice may be considered together under some circumstances relative to crude dietary needs, but the Syrian golden hamster should be treated separately for purposes of diet. This species appears to digest foods more like a ruminant. An ideal diet for rodents is not on the horizon because of variable needs relative to different types of research and holding. Storage and shelf life of rodent diets also play important roles in providing adequate nutrition. Variations in moisture, temperature and exposure to other chemicals can affect the quality of the feed and research results. In addition, a number of chemical and biological contaminants have been found in rodent diets, and surveillance over such variables must be a part of all laboratory animal diet quality control. Federal regulatory mandates now require that investigators assure that nutrient requirements of animals are met and that diets are reasonably free from contamination. Accepted practices in good management, formulation, shipping and storage will help achieve these commendable goals.

Animal Feed↗

[Zoo-anthroponoses involving rodents: epidemiologic considerations].

A large number of zoo-anthroponoses is known, in the natural cycle of which are involved rodents or lagomorphs. This is mainly related to the numerical importance of rodents, their ecological plasticity, their relationships with man. Thus, it is important, for the epidemiologist, to differentiate synanthropic rodents living in close contact with man and often spread by him, which are at the origine of frequently urban diseases, from wild rodents usually having only few contacts with man in rural areas only. The events allowing the passage of an infectious agent from rodent to man appear varied, as are epidemiological schemes in which these animals can play different roles: they can act, alone or together with other animals, as natural reservoirs, or, on the contrary, they are only occasionally infected, and the transmission can occur by direct contact, by bite, through the environment, or with the help of an arthropod vector. It is particularly interesting to follow the evolution of some of these epidemiological systems, in order to evaluate the impact of human activities, such as deforestations, new technics for agriculture and cattle breeding, urbanization, increasing transportation, development of leisure activities. In order to reduce this infectious risk, we should look for the means of a correct balance between rodent and human populations, by joining the control of epidemiologically dangerous species, modification of some of our behaviours, a relevant health information, together with the care of the protection of natural ecosystems.

Animals↗

Coexistence of several novel hantaviruses in rodents indigenous to North America.

Three genetically distinct members of the Hantavirus genus have been detected in Nevada rodents by RT-PCR and nucleotide sequence analysis. These include Sin Nombre (SN), El Moro Canyon (ELMC), and Prospect Hill (PH)-like viruses which are primarily associated with Peromyscus maniculatus (deer mouse), Reithrodontomys megalotis (western harvest mouse), and Microtus spp. (voles), respectively. Although this region of the United States is ecologically diverse, rodents infected with different hantaviruses appear to coexist in several different geographical and ecological zones. In two widely separated states, Nevada and North Dakota, PH-like viruses are present in three different species of vole. In addition, ELMC-like virus has been detected in both R. megalotis and M. montanus (mountain vole). SN virus is a cause of hantavirus pulmonary syndrome throughout much of the United States. SN virus RNA is found in 12.5% of P. maniculatus in Nevada and eastern California. Two lineages of SN virus coexist in this region and differ from SN viruses originally found in infected rodents in New Mexico, Arizona, and Colorado. These data show the complexity of hantavirus maintenance in rodents. Distinct hantaviruses or virus lineages can coexist either in different or the same rodent species and in either different or the same geographic or ecological zones.

Animals↗

Guanarito virus (Arenaviridae) isolates from endemic and outlying localities in Venezuela: sequence comparisons among and within strains isolated from Venezuelan hemorrhagic fever patients and rodents.

Despite intensive surveillance, Venezuelan hemorrhagic fever (VHF), caused by Guanarito (GTO) virus, has been detected in only a small region of western Venezuela. To determine whether VHF is associated with a particular regional GTO virus strain(s), 29 isolates from rodents and humans throughout the surrounding regions were analyzed by partial sequencing of the nucleocapsid protein gene. Phylogenetic trees delineated nine distinct GTO genotypes that differ by 4-17% in nucleotides and up to 9% in amino acid sequences; most appeared to be restricted to discrete geographic regions, although a few genotypes were isolated in several locations. Each genotype included at least one strain recovered from a rodent, but only two genotypes were isolated from VHF cases. The presence outside of the endemic/epidemic region of two genotypes isolated also from VHF cases suggests that human pathogenic viruses occur outside of the endemic zone, but do not frequently infect people and/or cause apparent disease there. VHF does not appear to be associated with a GTO virus genotype that is restricted to a certain rodent species. When quasispecies diversity was examined, rodent isolates had higher sequence variation than human isolates. One rodent isolate included a mixture of two phylogenetically distinct genotypes, suggesting a dual infection.

Animals↗

Diffusion and home range parameters from rodent population measurements in Panama.

Simple random walk considerations are used to interpret rodent population data collected in Hantavirus-related investigations in Panama regarding the short-tailed cane mouse, Zygodontomys brevicauda. The diffusion constant of mice is evaluated to be of the order of (and larger than) 200 meters squared per day. The investigation also shows that the rodent mean square displacement saturates in time, indicating the existence of a spatial scale which could, in principle, be the home range of the rodents. This home range is concluded to be of the order of 70 meters. Theoretical analysis is provided for interpreting animal movement data in terms of an interplay of the home ranges, the diffusion constant, and the size of the grid used to monitor the movement. The study gives impetus to a substantial modification of existing theory of the spread of the Hantavirus epidemic which has been based on simple diffusive motion of the rodents, and additionally emphasizes the importance for developing more accurate techniques for the measurement of rodent movement.

Animals↗

Human and rodent humoral immune responses to Andes virus structural proteins.

In the present work we identified B-cell epitopes recognized by sera of humans and rodents naturally infected with Andes virus, a hantavirus present in Chile and Argentina. Analysis of patient and rodent sera with overlapping peptides revealed 21 human and rodent epitopes on the three structural proteins. Whereas in the nucleoprotein the region comprising aa 248-260 was shown to be the key determinant of human sera, the major antigenic site of rodent antibody reactivity is located at aa 326-338. In G1, the main epitope recognized by human sera was mapped to aa 14-26, while rodent antibodies bound predominantly to aa 599-611. In contrast, humans and mice had strong responses to three regions in G2 (aa 691-703, aa 918-930, aa 955-967), of which the last two are associated with neutralization of Hantaan virus. This insight affords important information for the development of immunotherapies for the acute phase of hantavirus cardiopulmonary syndrome.

Adolescent↗