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J N Mills

Publications and source records attributed to J N Mills.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of rodent-borne viruses in the natural host: implications for human disease.

Prevalence and transmission rates of rodent-borne viruses within host populations vary in time and space and among host-virus systems. Improving our understanding of the causes of these variations will lead to a better understanding of changes in disease risk to humans. The regulators of prevalence and transmission can be categorized into five major classes: (1) Environmental regulators such as weather and food supply affect transmission rates through their effect on reproductive success and population densities. (2) Anthropogenic factors, such as disturbance, may lead to ecosystem simplification and decreased diversity. These changes favor opportunistic species, which may serve as reservoirs for zoonotic viruses. (3) Genetic factors influence susceptibility of mice to infection or capacity for chronic shedding and may be related to population cycling. (4) Behavioral factors, such as fighting, increase risk of transmission of some viruses and result in different patterns of infection between male and female mice. Communal nesting may result in overwinter transmission in colder climates. (5) Physiologic factors control host response to infection and length of time the host remains infectious. Risk prediction is difficult because these regulators are numerous and often interact, and the relative importance of each varies according to the host species, season, year, and geographic location.

Animals↗
PubMed2003

Bartonella infection in sylvatic small mammals of central Sweden.

Sylvatic small mammals were captured in rural habitats near Uppsala, Sweden, to measure the prevalence of bartonella infections, characterize bacterial isolates and identify their host range, and increase our understanding of host-pathogen ecology. During 7 nights of trapping at 3 localities, 236 small mammals were captured (trap success 30%). Bartonella were isolated from bloods of Apodemus flavicollis (19 of 110 tested), Apodemus sylvaticus (6/25), Clethrionomys glareolus (9/60), Microtus agrestis (1/3), Mus musculus (1/18), and Sorex araneus (3/20). Nucleotide sequencing (a 338 bp fragment of the gltA gene) of 40 isolates yielded 6 unique genotypes. Five of the 6 genotypes were most similar to other known bartonella isolated from Old World small-mammal hosts. The most frequent genotype (83%) was isolated from A. flavicollis and M. musculus and was identical to Bartonella grahamii, a recently demonstrated human pathogen. These two hosts were most frequently captured in and around human structures and work places, thus providing conditions that could potentially lead to frequent human infections.

Animals↗
PubMed2001

Extreme genetic diversity among Pirital virus (Arenaviridae) isolates from western Venezuela.

Pirital-like virus isolates from rodents collected in a variety of habitats within a six-state area of central Venezuela were analyzed genetically by amplifying a portion of the nucleocapsid protein gene using RT-PCR. Comparisons of the sequences from 30 selected Pirital-like virus isolates demonstrated up to 26% divergence in nucleotide sequences and up to 16% divergence in deduced amino acid sequences. Within the Pirital monophyletic group, 14 distinct lineages or genotypes, differing by at least 6% in nucleotide sequences, were identified. Although sample sizes were small for some lineages, many of the different genotypes were sampled in only one region or locality, suggesting allopatric divergence. Complement fixation tests with representatives of the most divergent Pirital virus lineages failed to delineate multiple species or subtypes within the Pirital clade. These results indicate that the previously proposed 12% nucleocapsid protein amino acid sequence divergence cutoff value for delineating arenavirus species is not appropriate for the entire family. When individual clones were examined from PCR amplicons, a mean of 0.17% sequence diversity vs the consensus sequences was detected, suggesting diverse quasispecies populations within infected rodent hosts. Possible explanations for the extreme genetic diversity within and among Pirital virus populations in infected rodents are discussed.

Animals↗
PubMed2001

Hantavirus pulmonary syndrome in the State of São Paulo, Brazil, 1993-1998.

Between 1993 and 1998, 10 cases of clinical hantavirus infection were diagnosed in Brazil. Hantavirus-specific IgM, or positive immunohistochemical analysis for hantavirus antigen, or positive reverse transcription-polymerase chain reaction results for hantavirus RNA were used to confirm nine of these cases; eight were hantavirus pulmonary syndrome (HPS), and one was mild hantavirus disease. The remaining clinical case of hantavirus infection was fatal, and no tissue was available to confirm the diagnosis. During the first 7 months of 1998, five fatal HPS cases caused by a Sin Nombre-like virus were reported from three different regions in the State of São Paulo, Brazil: two in March (Presidente Prudente Region), two in May (Ribeirão Preto Region), and one in July (Itapecerica da Serra Region). Epidemiologic, ecologic, and serologic surveys were conducted among case contacts, area residents, and captured rodents in five locations within the State of São Paulo in June of 1998. Six (4.8%) of 125 case contacts and six (5.2%) of 116 area residents had IgG antibody to Sin Nombre virus (SNV) antigen. No case contacts had a history of HPS-compatible illness, and only one area resident reported a previous acute respiratory illness. A total of 403 rodents were captured during 9 nights of trapping (1969 trap nights). All 27 rodents that were found to be positive for IgG antibody to SNV antigen were captured in crop border and extensively deforested agricultural areas where four of the 1998 HPS case-patients had recently worked. The IgG antibody prevalence data for rodents suggest that Bolomys lasiurus and perhaps Akodon sp. are potential hantavirus reservoirs in this state of Brazil.

Adolescent↗
PubMed2001

Longitudinal studies of Sin Nombre virus in deer mouse-dominated ecosystems of Montana.

Sin Nombre virus (SNV), hosted by the deer mouse (Peromyscus maniculatus), is the primary etiologic agent of Hantavirus pulmonary syndrome (HPS) in North America. To improve our understanding of the epidemiology of HPS in the western United States, we conducted studies of population dynamics and SNV antibody prevalence in deer mouse populations for 6 years on 12 mark-recapture grids in Montana. Monthly numbers of deer mice ranged from zero to over 170 on 1-hectare grids. SNV antibody prevalence was higher than observed in studies in other parts of the United States, averaging 13% (0% to 50%), and peaking in May or June each year. Antibody-positive mice were older (heavier) (78% of positives were adults versus 52% of negatives) and more likely to be males (61% of positives versus 53.4% of negatives). A higher proportion of antibody-positive deer mice of all age-mass classes had scars than did antibody-negative mice. Month-to-month survivorship of antibody-positive adult mice was similar to that of antibody-negative mice, but survival of young antibody-positive deer mice was lower than antibody-negative deer mice. This is the first study to clearly suggest a detrimental effect of SNV infection on deer mice.

Age Factors↗
PubMed2001

Patterns of infection with Laguna Negra virus in wild populations of Calomys laucha in the central Paraguayan chaco.

In 1995, an outbreak of hantavirus pulmonary syndrome occurred in the central Paraguayan chaco. The primary reservoir of the virus, Laguna Negra virus, was identified as the vesper mouse, Calomys laucha. Over a 15-month period, we collected 1,090 small mammals at 12 locations representing 4 habitats common in the central Paraguayan chaco. Calomys laucha was common in agricultural habitats and uncommon in the native forest habitat. Populations of C. laucha were greater during the dry season months and declined during the wet season. A total of 643 small mammals were tested for antibodies cross-reactive to Sin Nombre virus. All of the antibody-positive animals were C. laucha (crude antibody prevalence ratio 12.1% [25 of 206]). Antibody prevalence ratio increased with body size and was more common among male (18%; n = 115) than among female (4%; n = 96) vesper mice. Antibody prevalence ratio was highest among animals from cropland habitats (18%; n = 72), followed by thorn scrub (13%; n = 46) and pastureland (7%; n = 81) and may be positively correlated to the proportion of C. laucha in the small mammal community. These data suggest that community-level dynamics, in addition to population-level dynamics, may be involved in the transmission of the virus through natural populations of vesper mice.

Animals↗
PubMed2001

Do unusual site-specific population dynamics of rodent reservoirs provide clues to the natural history of hantaviruses?

Between January 1995 and November 1997, longitudinal mark-recapture studies of rodent hosts of hantaviruses in a disturbed microhabitat within a shortgrass prairie ecosystem in southeastern Colorado (USA) were conducted. The site was distinguished by edaphic and floristic characteristics unique to this area and associated with historical land use patterns, as well as the year-around availability of water from a functioning windmill. Populations of two common rodent species that are hosts for hantaviruses, Peromyscus maniculatus and Reithrodontomys megalotis, had unusually rapid turnover, a younger age structure, and a much lower prevalence of antibody to Sin Nombre virus than did populations at nearby sites in more typical shortgrass prairie and canyon habitats. Based on these findings, we suggest that a stable resident population of the reservoir is critical to the maintenance of hantaviruses at a given site, and we hypothesize that long-lived, persistently infected rodents are the principal transseasonal reservoir of hantaviruses.

Animals↗
PubMed2000

Hantavirus pulmonary syndrome in Panama: identification of novel hantaviruses and their likely reservoirs.

Hantavirus pulmonary syndrome (HPS), a severe respiratory disease with high mortality caused by rodent-borne hantaviruses, has previously been identified in the United States and Canada as well as central and southern South America. In late 1999 and early 2000, an outbreak of acute illness compatible with HPS was reported in Los Santos, Panama, with the death of 3 of the 12 (25%) suspected cases. Hantavirus-specific antibodies were detected in patient sera, and virus RNA was detected by reverse transcriptase-polymerase chain reaction. Sequence analysis of virus genome N-, G1-, and G2-encoding fragments showed this to be a novel hantavirus, Choclo virus. Serologic and virus genetic analyses of rodents trapped in the area showed Oligoryzomys fulvescens to be the likely reservoir for the HPS-associated Choclo virus. In addition, Zygodontomys brevicauda rodents were shown to harbor another genetically unique hantavirus, Calabazo virus.

Animals↗
PubMed2000

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↗
PubMed2000

Criteria used by employers to select new graduate employees.

OBJECTIVE: To find out what criteria and methods are used by Australian employers to select new graduates to work in their practices. DESIGN: Questionnaires were completed by 258 employers and the responses were analysed using the SAS system. RESULTS: During selection, employers placed most reliance on formal interviews or visits to the practice. These occasions were used to assess the applicant's personal qualities including their ability to interact effectively with clients and colleagues. Employers used resumes mainly in selection of applicants to interview and many discounted nominated referees as being insufficiently critical. Academic knowledge was regarded as less important than personal qualities and very few employers reported using gender as a basis for selection. CONCLUSIONS: Senior veterinary students need to be aware of the importance placed by employers on interpersonal skills and personal qualities and should make every effort to engage in practical work, paid work and other activities that will help develop these attributes. They should be conscious that practitioners with whom they work may be contacted by potential employers and they should learn to present themselves realistically in a resume.

Australia↗
PubMed1999

Oncostatin M induces leukocyte infiltration and cartilage proteoglycan degradation in vivo in goat joints.

OBJECTIVE: To evaluate the effect of intraarticular injections of recombinant human oncostatin M (rHuOSM) in the goat joint. METHODS: One milliliter of endotoxin-free normal saline (vehicle) containing either 40 ng, 200 ng, or 1,000 ng of rHuOSM was injected into the right radiocarpal joints (RCJs) of 12 male angora goats, while the left RCJs were injected with an equivalent volume of vehicle alone. In subsequent studies, the right and left RCJs of 8 male angora goats were injected with 200 ng of rHuOSM, and 1 hour later, the right RCJs were injected with either 5 microg of recombinant murine leukemia inhibitory factor binding protein (rMuLBP) or 1 mg of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in 1 ml of vehicle, while the left RCJs received 1 ml of vehicle alone. Goat joints were examined for clinical features of inflammation, and synovial fluid (SF) was aspirated on day 0 (before injection) and at days 2 and 6 postinjection. RESULTS: Injections of rHuOSM stimulated dose-dependent increases in the carpal:metacarpal ratio, SF volume, and SF leukocyte numbers, and stimulated dose-dependent decreases in the cartilage proteoglycan (PG) content ex vivo and PG synthesis. No significant changes were observed in the control joints that received saline alone, or between RCJs that were injected with 200 ng rHuOSM followed by 5 microg rMuLBP and RCJs that were injected with 200 ng of rHuOSM alone, except in respect to synovial fluid keratan sulfate concentrations, where a modest statistically significant reduction was observed in the joints injected with the combination of rHuOSM and rMuLPB. In contrast, RCJs injected with 200 ng rHuOSM followed by 1 mg of rHuIL-1Ra had significantly lower SF volumes (P<0.0001) and a significantly higher rate of ex vivo PG synthesis (P<0.0001). CONCLUSION: These results indicate that rHuOSM stimulates inflammation and modulates cartilage PG metabolism in vivo. Some of the effects of rHuOSM in vivo appear to be due, in part, to elaboration of IL-1. Even at very high doses, however, the rHuIL-1Ra did not attenuate OSM-mediated cartilage PG resorption. Thus, OSM has the potential to contribute to synovitis in vivo and can stimulate cartilage PG resorption in vivo, independent of IL-1.

Animals↗
PubMed1999

Search for the Ebola virus reservoir in Kikwit, Democratic Republic of the Congo: reflections on a vertebrate collection.

A 3-month ecologic investigation was done to identify the reservoir of Ebola virus following the 1995 outbreak in Kikwit, Democratic Republic of the Congo. Efforts focused on the fields where the putative primary case had worked but included other habitats near Kikwit. Samples were collected from 3066 vertebrates and tested for the presence of antibodies to Ebola (subtype Zaire) virus: All tests were negative, and attempts to isolate Ebola virus were unsuccessful. The investigation was hampered by a lack of information beyond the daily activities of the primary case, a lack of information on Ebola virus ecology, which precluded the detailed study of select groups of animals, and sample-size limitations for rare species. The epidemiology of Ebola hemorrhagic fever suggests that humans have only intermittent contact with the virus, which complicates selection of target species. Further study of the epidemiology of human outbreaks to further define the environmental contact of primary cases would be of great value.

Animals↗
PubMed1999

The proinflammatory and chondral activities of leukemia inhibitory factor in goat joints are partially a function of interleukin-1.

We wished to determine if the effects of injected recombinant human leukemia inhibitory factor (LIF) are a function of endogenous goat interleukin-1 (IL-1) production and, conversely, if the effects of injected recombinant human IL-1 are a function of endogenous LIF production in goat radiocarpal joints (RCJ). In preliminary experiments, murine LIF binding protein (MuLBP) and recombinant HuIL-1RA were found to independently attenuate the cartilage proteoglycan resorbing activity of goat synovial membrane-conditioned medium (GSMCM), implying activity against goat LIF and goat IL-1, respectively. The present study shows that the proinflammatory and chondral actions of rHuLIF in goat RCJ are partially attenuated by rHuIL-1RA. This implies that a small but important component of the in vivo activity of rHuLIF is a result of IL-1 production in the synovial joint. With the exception of proteoglycan synthesis, the absence of significant effects by MuLBP on the actions of rHuIL-1alpha in goat RCJ suggests that the proinflammatory and chondral effects of IL-1alpha in vivo are probably not mediated by LIF.

Animals↗
PubMed1999

Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins.

beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two beta-defensins have been identified. Here, we report the identification of two genes encoding beta-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human beta-defensin-1 (HBD-1) gene and mouse beta-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat beta-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of beta-defensins. The beta-defensin genes mapped closely on rat chromosome 16 and were closely linked to the alpha-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were approximately 0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel beta-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of beta-defensins to host defense in the lung, kidney, and other tissues.

Amino Acid Sequence↗
PubMed1998

Epidemiology of rodent bites and prediction of rat infestation in New York City.

The authors examined the epidemiology of rodent bites occurring in New York City from 1986 through 1994 to identify factors contributing to increased probability of rodent bite and rat infestation. City blocks on which a rodent bite case had been reported (n=415) and three control blocks per bite block, matched by borough and randomly selected, were compared according to demographic characteristics obtained from US Census data. Environmental variables were defined using a geographic information system to extract distances to areas potentially providing food or refuge for rats, such as parks. Borough-specific models of bite risk were generated by logistic regression using data collected from 1991 to 1994; risk values were then generated for all city blocks. Field surveys for signs of rat infestation conducted on 31 randomly selected blocks indicated a significant association between degree of infestation and predicted risk. Spatial analyses comparing neighboring blocks showed that blocks with bite cases were significantly clustered. The models based on data from previous years correctly predicted 72 percent of 53 block addresses of rodent bite cases from 1995 as being locations of high or intermediate risk. A combination of geographic and epidemiologic analyses could help investigators identify the spatial occurrence of rat infestation over a large area and might help to focus control activities.

Adolescent↗
PubMed1998

Venezuelan hemorrhagic fever: clinical and epidemiological studies of 165 cases.

Epidemiological and clinical data are presented on 165 cases of Venezuelan hemorrhagic fever (VHF), a newly emerging viral zoonosis caused by Guanarito virus (of the family Arenaviridae). The disease is endemic in a relatively circumscribed area of central Venezuela. Since its first recognition in 1989, the incidence of VHF has peaked each year between November and January, during the period of major agricultural activity in the region of endemicity. The majority of cases have involved male agricultural workers. Principal symptoms among the patients with VHF included fever, malaise, headache, arthralgia, sore throat, vomiting, abdominal pain, diarrhea, convulsions, and a variety of hemorrhagic manifestations. The majority of patients also had leukopenia and thrombocytopenia. The overall fatality rate among the 165 cases was 33.3%, despite hospitalization and vigorous supportive care.

Hemorrhagic Fevers, Viral↗