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Transmission dynamics of Echinococcus multilocularis; its reproduction number, persistence in an area of low rodent prevalence, and effectiveness of control.

On the basis of high prevalences of Echinococcus multilocularis in the growing fox populations in Central Europe, its total biomass may have increased significantly in the past 20 years. E. multilocularis is now also found in areas outside the known endemic area in Central Europe. Therefore, E. multilocularis, the causative agent of a serious parasitic zoonosis, might be of major concern for public health and a challenge to control. Some experimental field trials to control E. multilocularis using an anti-worm drug reduced parasite burden in a contaminated region during the control campaign, but failed to eradicate the parasite completely. It was our aim to develop a mathematical model describing the biomass of egg, larval, and adult worm stages of the E. multilocularis life-cycle, and simulate a hypothetical control campaign. Additionally, we derived the reproduction number of this parasite and explored conditions for the persistence of the parasite's life-cycle. Our model shows that while control campaigns rapidly reduce the worm burden in the definitive host, and consequently eggs in the environment, the pool of larvae in the intermediate host remains large. The parasite's life-cycle persists in a region where prevalence in the intermediate host is low (approximately 1%). Therefore, we conclude that the parasite is likely to re-emerge if control is discontinued on the basis of reduced worm population. Continued treatment of the definitive host is required to eradicate the larval stage of the parasite from the intermediate host population.

Animals↗

Differential effects of exercise and housing condition on murine natural killer cell activity and tumor growth.

Acute exercise and exercise conditioning have been shown to affect the activity of natural killer (NK) cells as well as the growth of experimentally induced tumors in animals. Since psychosocial factors are also known to alter NK activity and tumor growth, isolation, a known psychosocial stressor of mice, was also investigated to see if housing condition could alter exercise-induced changes in NK cell activity and tumor growth. NK cell activity and concentration of asialo GM1 (ASGM1) positive splenocytes were measured in male C3H mice inoculated i.v. with CIRAS 3 tumor cells. Mice were housed individually or in groups of four and trained to run for eight weeks on a rodent treadmill; controls remained sedentary throughout the experimental period. At four weeks into the training protocol, mice were injected with the tumor cells and continued to run for four weeks after tumor exposure. There was a significant effect of physical activity (p less than 0.019) but not of housing on splenic NK cytotoxicity against tumor targets in vitro. When the data were analyzed by presence or absence of lung metastases, only those animals without visible lung tumors had significantly higher NK activity as a function of exercise relative to sedentary controls. There were no significant differences in the frequency of ASGM1+ splenocytes between trained and untrained animals, irrespective of presence or absence of lung tumor colonies. There was a significant effect of housing (p less than 0.02), but not of physical activity, in mice with successful tumor takes with greater numbers of group housed animals (29/59) with tumor relative to individually housed animals (13/60).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Museum specimen data predict crop damage by tropical rodents.

Museum collections constitute a massive store of information on biological diversity. We used museum specimen data to generate ecological niche models that provide predictions of geographic distributions of native rodent pest species and agricultural census data that summarize the geographic distribution of nine crops in the state of Veracruz, Mexico, as well as crop losses between planting and harvest. Herein, we show that crop damage is related significantly to the predicted presence of rodent species for seven of nine crops. Museum collections may thus provide important baseline information for designing land-use and agricultural pest-management programs.

Animals↗

Cellular, molecular, and genetic characteristics of T cell reactivity to collagen in man.

Rheumatoid arthritis is significantly associated with the HLA determinant HLA-DRw4 and cell-mediated reactivity to collagen. To determine if genes linked to those coding for HLA-DRw4 constituted immune response genes for collagen reactivity, peripheral blood mononuclear cells from 20 individuals with rheumatoid arthritis, 13 individuals with other arthropathies, and 41 normal individuals were compared for their ability to synthesize the lymphokine leukocyte inhibition factor in response to denatured bovine collagen. All individuals were responsive to the control antigen Candida albicans. While 90% of the patients with rheumatoid arthritis responded to collagen, so did 30% of the individuals without rheumatoid arthritis. This included 15 normal individuals without any evidence of arthritis. Collagen responsiveness was dependent on interactions between T cells and macrophages was dependent on interactions between T cells and macrophages and was directed against determinants expressed by primary amino acid sequences in the synthetic polypeptide (Gly-Pro)n. HLA-DRw typing of 59 individuals revealed a highly significant relationship (P less than 0.0001, chi 2 = 33.7) between HLA-DRw4 and collagen responsiveness, irrespective of whether or not rheumatoid arthritis was present. All normal individuals who were HLA-DRw4-positive were collagen responders. These studies demonstrate that the cellular, molecular, and genetic characteristics of collagen reactivity in man parallel those documented for the T cell-dependent response to antigens under immune response gene control in rodents.

Arthritis, Rheumatoid↗

Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane.

gamma-Carboxylation of vitamin K-dependent proteins requires a functional vitamin K cycle to produce the active vitamin K cofactor for the gamma-carboxylase which posttranslationally modifies precursors of these proteins to contain gamma-carboxyglutamic acid residues. The warfarin-sensitive enzyme vitamin K epoxide reductase (VKOR) of the cycle reduces vitamin K 2,3-epoxide to the active vitamin K hydroquinone cofactor. Because of the importance of warfarin as an anticoagulant in prophylactic medicine and as a poison in rodent pest control, numerous attempts have been made to understand the molecular mechanism underlying warfarin-sensitive vitamin K 2,3-epoxide reduction. In search for protein components that could be involved in this reaction we designed an in vitro gamma-carboxylation test system where the warfarin-sensitive VKOR produces the cofactor for the gamma-carboxylase. Dissection of this system by chromatographic techniques has identified a member(s) of the glutathione S-transferase gene family as one component of the VKOR enzyme complex in the endoplasmic reticulum membrane. The affinity-purified glutathione S-transferase(s) was sensitive to warfarin but lost its warfarin sensitivity and glutathione S-transferase activity upon association with lipids in the presence of Mn2+ or Ca2+. In the gamma-carboxylation test system, loss of warfarin-sensitive glutathione S-transferase activity coincided with formation of the VKOR enzyme complex. It is proposed that formation of VKOR in the endoplasmic reticulum membrane resembles formation of the lipoxygenase enzyme complex where the glutathione S-transferase-related FLAP protein binds cytosolic lipoxygenase to form a membrane enzyme complex.

Animals↗

LIM mineralization protein-1 potentiates bone morphogenetic protein responsiveness via a novel interaction with Smurf1 resulting in decreased ubiquitination of Smads.

Development and repair of the skeletal system and other organs is highly dependent on precise regulation of bone morphogenetic proteins (BMPs), their receptors, and their intracellular signaling proteins known as Smads. The use of BMPs clinically to induce bone formation has been limited in part by the requirement of much higher doses of recombinant proteins in primates than were needed in cell culture or rodents. Therefore, control of cellular responsiveness to BMPs is now a critical area that is poorly understood. We determined that LMP-1, a LIM domain protein capable of inducing de novo bone formation, interacts with Smurf1 (Smad ubiquitin regulatory factor 1) and prevents ubiquitination of Smads. In the region of LMP responsible for bone formation, there is a motif that directly interacts with the Smurf1 WW2 domain and can effectively compete with Smad1 and Smad5 for binding. We have shown that small peptides containing this motif can mimic the ability to block Smurf1 from binding Smads. This novel interaction of LMP-1 with the WW2 domain of Smurf1 to block Smad binding results in increased cellular responsiveness to exogenous BMP and demonstrates a novel regulatory mechanism for the BMP signaling pathway.

Adaptor Proteins, Signal Transducing↗

Variation in seropositivity for some respiratory disease agents in finishing pigs: epidemiological studies on some health parameters and farm and management conditions in the herds.

The relationship between the extent of seropositivity for Aujeszky's disease virus (ADV), Actinobacillus pleuropneumoniae (App.) serotype 2 and porcine influenza (PI) viruses serotype H1N1 and H3N2 in pigs on the one hand and the health status of the pigs and some farm and management conditions in the herds on the other hand was studied in 45 pig finishing herds, all members of one integration group. The health status was assessed by the extent of clinical signs, the use of veterinary drugs and the prevalence of pathological lesions in pigs at slaughter. There was no relationship between the extent of seropositivity on the one hand and clinical signs and use of veterinary drugs on the other hand. However, there was a positive relationship between the extent of seropositivity and the percentage of pigs with lesions of the respiratory tract at slaughter. Furthermore, the study indicates that the variation in seropositivity between pigs herds is associated with management related factors that particularly influence the possibility of the spreading of viruses. A sero-epidemiological investigation in 14 pig herds with recurrent pneumonia problems revealed a high percentage of seropositive pigs per herd. Furthermore, in a large number of herds, pigs were simultaneously seropositive for ADV and App. serotype 2, for ADV and PI serotype H1N1 or for ADV and PI serotype H3N2.

Actinobacillus Infections↗