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Total respiratory support from swine lungs in primate recipients.

UNLABELLED: The use of nonhuman lung donors, such as swine, has the potential to provide an unlimited supply of organs. However, hyperacute rejection has prevented pulmonary xenotransplantation. OBJECTIVE: Our aim was to test the hypothesis that immunodepletion by pretransplantation swine lung perfusion will prevent hyperacute swine-to-primate pulmonary xenograft rejection and allow for a functional swine pulmonary xenograft. METHODS: Seven baboons underwent left pneumonectomy followed by orthotopic transplantation of the swine left lung. Four baboons received immunodepletion by perfusion with swine lungs before transplantation, and three received no treatment before transplantation. RESULTS: After transplantation, pulmonary xenografts from immunodepleted baboons had a low pulmonary vascular resistance and a high pulmonary blood flow compared with control animals, which had a high pulmonary vascular resistance and a low pulmonary blood flow. After 60 minutes of reperfusion, three of four immunodepleted animals also tolerated complete occlusion of the right pulmonary artery, with the baboon relying completely on the swine pulmonary xenograft for respiratory function for 11 hours. Pathologic analysis of peripheral lung biopsy specimens taken from control lungs displayed alveolar disruption and hemorrhage within small vessels, whereas swine lungs transplanted into immunodepleted baboons displayed little histologic evidence of injury. Furthermore, pulmonary xenografts transplanted into immunodepleted baboons demonstrated excellent respiratory function and adequate hemodynamics during occlusion of the right pulmonary artery. CONCLUSION: Hyperacute pulmonary xenograft rejection can be prevented by pretransplantation swine lung perfusion. Swine pulmonary xenografts can provide complete respiratory support in primates when rejection is prevented.

Animals↗

A novel virus in swine is closely related to the human hepatitis E virus.

A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine HEV is a ubiquitous agent and the majority of swine >/=3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3 were amplified by reverse transcription-PCR from sera of naturally infected pigs. The putative capsid gene (ORF2) of swine HEV shared about 79-80% sequence identity at the nucleotide level and 90-92% identity at the amino acid level with human HEV strains. The small ORF3 of swine HEV had 83-85% nucleotide sequence identity and 77-82% amino acid identity with human HEV strains. Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains. The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.

Amino Acid Sequence↗

Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta.

Aortic areas predisposed to early atherosclerosis in swine demarcated by Evans blue uptake (blue areas) show preferential intimal penetration by blood monocytes before and during lesion formation. These cells are thought to be the major source of foam cells in these early lesions. To examine mechanisms controlling monocyte migration into these areas, extracts of aortic tissue from both blue and white areas of hypercholesterolemic (H) and normal (N) swine were tested for chemotactic activity against monocytes from N and H swine and neutrophils from H swine. The data indicate that extracts of blue areas from H swine contained at least one, and possibly two, factors chemotactic only for monocytes from H swine, but not N swine. These factors were not present in similar extracts from white areas of H swine, or either blue or white area extracts from N swine. Gel filtration chromatography of crude blue area extracts separated two chemotactically active fractions of molecular weights 68,000 and 5000 that were not present in white area extracts and that elicited a positive chemotactic effect only for H swine monocytes. These findings provide a mechanism explaining our previous findings of preferential monocyte adhesion and intimal penetration in lesion-prone areas, and indicate that control of monocyte recruitment into the artery involves not only alteration of the arterial wall, but also functional changes in the circulating monocyte.

Animals↗

Insulin binding to liver microsomes from lean and obese swine during growth to market weight.

Insulin binding to liver microsomes from lean (Yorkshire) and obese (Ossabaw) swine was measured at four different times during growth to market weight. Over the physiological range of insulin, binding decreased during growth to market weight in Yorkshire swine. This was not observed for Ossabaw swine. When comparisons of insulin binding were made between lean and obese swine of a similar age, microsomes from lean swine bound more insulin over the physiological range of insulin than microsomes of obese swine. This difference was also observed when comparisons were made at similar live weights. The dissociation constant (Kd) for the high affinity receptor population increased with growth in both breeds indicating that binding affinity was decreasing. Over the physiological range of insulin, binding affinity was lower for liver microsomes of obese swine vs liver microsomes from lean swine when comparisons were made at a similar age. These results suggest that the liver of obese swine is moderately insensitive to insulin and that binding of insulin to liver from lean swine declines during growth to market weight.

Adipose Tissue↗

Respiratory tract inflammation in swine confinement workers studied using induced sputum and exhaled nitric oxide.

OBJECTIVE: To further define the asthma-like syndrome seen in swine confinement workers. DESIGN: A cross-sectional study was performed at a swine confinement facility in rural Nebraska and at the University of Nebraska Medical Center, Omaha, Nebraska. PARTICIPANTS: 24 swine confinement workers and 14 urban normal control subjects. All subjects completed a questionnaire concerning respiratory complaints. We performed hypertonic saline challenges on the swine confinement workers and control subjects in order to induce expectoration of sputum. Cell counts and cell differentials were determined in the induced sputum samples. Nasal, mean, and peak exhaled nitric oxide was measured in both groups. Spirometry was also done. RESULTS: Swine confinement workers were significantly more likely to report wheezing, cough, and sinusitis symptoms than controls (p = .003). Macrophages were significantly elevated in the induced sputum samples of the swine confinement workers vs the control subjects (0.59 macrophages/mL +/- 0.1 SEM vs 0.36 +/- .16; p = .006), while there was no difference in numbers of neutrophils. No eosinophils were observed. A small elevation in mean exhaled nitric oxide was seen in the swine confinement workers compared to normal controls (11.7 ppb +/- 0.6 SEM vs 10.2 +/- 1.6; p = 0.023). Spirometry values did not differ statistically between swine confinement workers and the control group. CONCLUSIONS: Swine confinement workers have signs and symptoms of lower respiratory tract inflammation when studied using induced sputum and exhaled nitric oxide. Findings in the swine confinement workers differ from those in asthmatics and chronic bronchitis.

Adult↗

Airway injury in swine confinement workers.

OBJECTIVE: To determine whether work-related respiratory symptoms are indicative of underlying lung disease among swine confinement workers and, if so, to identify whether respiratory changes were more indicative of airway or of interstitial lung injury. DESIGN: Nested case-control study within a population-based longitudinal study. SETTING: University hospital. PARTICIPANTS: Study participants were randomly selected from a group of 207 swine confinement workers followed longitudinally. Of these, 43 workers with respiratory symptoms were identified, and 31 were randomly selected for inclusion in this study. Three control groups (swine confinement workers, neighbor farmers, and blue collar workers) without work-related respiratory symptoms were frequency-matched by age, sex, and smoking status to the symptomatic swine confinement workers. MEASUREMENTS: Spirometry and lung volumes, diffusing capacity of carbon monoxide, chest radiograph, methacholine airway challenge, and bronchoalveolar lavage were done. An endobronchial biopsy was done in the last 27 participants evaluated. RESULTS: Although spirometric measures of airflow were similar between the symptomatic swine confinement workers and the three control groups, swine confinement cases were found to have significant elevations in residual volume (126.5 +/- 28.2 L) when compared to swine confinement controls (115.4 +/- 38.4 L; P less than or equal to 0.05), neighborhood farmer controls (101.1 +/- 29.4 L; P less than or equal to 0.005), and blue collar controls (106.4 +/- 30.4 L; P less than or equal to 0.05). Swine confinement cases also had an enhanced airway response to inhaled methacholine and had thickening of the epithelial basement membrane of the lobar bronchi. No parenchymal injury was observed in the swine confinement cases. CONCLUSIONS: Our findings suggest that swine confinement workers who have work-related respiratory symptoms are at risk for airway, but not parenchymal, lung injury, and that spirometry may not accurately reflect the extent of airway injury.

Adult↗

Detection of specific IgE as a screening tool for cow and swine breeders' occupational allergic dermatoses.

The study aimed at assessing whether detection of IgE specific to cow and swine allergens can be used as a screening tool for farmers' occupational eczema. Serum samples were taken from 51 farmers. The farmers were questioned about work-related skin symptoms using a nurse-administered questionnaire, verified by a dermatologist. Sera of 29 cow breeders were tested for IgE antibodies specific to cow dander and bovine serum albumin. Sera of 22 swine breeders were tested for IgE specific to swine epithelium, swine serum albumin, and swine urine proteins. Among cow breeders, IgE specific to cow dander was found in one farmer. Among swine breeders, IgE specific to swine epithelium was found also in one subject. On first examination, the cow breeder complained of slight itching of the conjunctivae while working in a cow barn and had no other allergic symptoms. One year later, however, he noticed episodes of hand eczema after contact with cows. In the IgE-positive swine breeder, only mild stationary psoriasis, and no work-related symptoms were found. Among the remaining 28 IgE-negative cow breeders, 11 complained of skin symptoms, but these were not related to working with cows; among 21 IgE-negative swine breeders, 7 subjects had skin diseases, none of which were related to working with swine. We conclude that detection of animal antigen-specific IgE may be an useful screening tool, although an exact assessment of sensitivity and specificity of the method in a larger population of exposed farmers will be required.

Adolescent↗

Technical feasibility and histopathologic studies of poly (N-isopropylacrylamide) as a non-adhesive embolic agent in swine rete mirabile.

BACKGROUND: Non-adhesive liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). We investigated the use of poly (N-isopropylacrylamide) (PNIPAM) as a non-adhesive embolic agent in swine rete mirabile. METHODS: The PNIPAM hydrogel was mixed with iohexol and embolization was performed in swine rete mirabile in 30 animals. The microcatheter was examined after embolization. Follow-up angiography was performed for embolic efficacy after embolization. Embolized retia were examined histopathologically, and the alterations of inside rete and surrounding tissue were observed. RESULTS: The copolymer hydrogel was used for rete embolization in 30 swine, 28 swine survived the procedure, 2 swine died, 1 swine died of cerebrum infarction and the other died of embolic agent reflux into the occipital artery. The inside wall of the microcatheter was smooth, without copolymer adhering to it. Follow-up angiography was performed in 22 swine, there was no rete recanalization in 20 swine and partial rete recanalization in 2 swine because of the trunk embolization of ascending pharyngeal arteries. Histopathologically, the copolymer was found diffused into vessels of 100 - 150 microm in diameter. In acute group, neutrophils scattered surrounding the copolymer and endothelial integrity was observed, without endothelial denuding and necrosis. In subacute and chronic groups, the copolymer was found inside retia, a few mononuclear cells and eosinocytes scattered inside and surrounding it. The muscular layer was loosened with most muscular nuclei degraded. CONCLUSION: Experimental rete embolization with PNIPAM, made radiopaque with iohexol, is technically feasible in swine. Because of its properties, PNIPAM has great potential as a therapeutic non-adhesive embolic agent.

Acrylic Resins↗

Protective immunity to Ascaris suum: analysis of swine peripheral blood cell subsets using monoclonal antibodies and flow cytometry.

Outbred domestic swine or SLA inbred miniature swine were exposed to Ascaris suum either naturally on contaminated lots or by inoculation with UV-irradiated attenuated eggs. Both inbred and outbred swine developed virtually complete protection to a challenge of 10 000 eggs after natural exposure, but inbred swine were less resistant than outbred swine after UV-egg exposure. Flow cytometric analysis of peripheral blood mononuclear cells from these animals, performed to determine changes in cell subsets including helper T-cells, cytotoxic/suppressor T-cells, macrophages, and cells expressing class II major histocompatibility antigens, showed that both outbred and inbred swine had similar responses after parasite exposure. The levels of helper T-cells and cytotoxic/suppressor T-cells did not change after parasite exposure, while there was an appreciable but transient increase in macrophages only in those swine naturally exposed to A. suum. Swine exposed to A. suum, both naturally and by inoculation with UV-eggs, showed an increase in the amount of class II antigens detectable per cell. In a second set of experiments, outbred swine were exposed to A. suum naturally or by repeated experimental inoculation with different doses of normal eggs, and protective immunity and changes in blood cell subsets were determined. The greatest change in blood cell subsets was found at 3 and 5 weeks after initial parasite exposure, when macrophages were elevated moderately in a group of pigs inoculated every other day with 1000 eggs and markedly in a group that was naturally exposed; class II antigen expression was also increased during this period. These increases preceded peak serum antibody responses, which were lower in the naturally-exposed group relative to the experimentally-inoculated group. Both groups had high levels of protective immunity. This suggests than natural exposure to A. suum may activate cells and enhance specific immune responses to give high levels of protection.

Animals↗

[Viral carrier state and viral excretion in classical swine fever].

Studies on swine pest virus carrying and elimination on swine vaccinated by lapinizated vaccine strain "K" from rabbits were performed. Vaccinated swine were injected with the pathogenic virus on the 60th day post vaccination and to them were added not immunized swine with the aim to discover virus elimination. The experimental swine were decapitated on the 3, 5, 6 and 7th day post infection. Alternating passages were made by emulsion of the inner organs of these swine on not immunized swine as well as pathohistological investigation of the parenchymal organs and the brain. Presence of the virus and of pathohistological changes were not detected 7 days post injection of the virulent virus. Contact having swine which served as a indicator for virus elimination were observed for 21 days, but remained healthy. These swine, when infected with the virulent virus, suffered from pest.

Animals↗

Crossreactivity of Human versus Swine Platelet Surface Antigens Is Similar for Glycoproteins Ib and IIIa, but Not for the Glycoprotein IIb/IIIa Complex.

Swine platalets are very similar to those of humans and are therefore relevant to cardiovascular research. The swine coronary circulation mimics the human circulation and is large enough to obtain multiple blood samples in survival experiments. In swine regional ischemia similar to the human condition is easily obtainable, which makes the porcine model an ideal choice to study coronary artery disease. However, little is known about the similarity between swine and human platelet surface antigens. We tested the hypothesis that certain swine platelet antigens could crossreact with antihuman antibodies. Using FITC-conjugated monoclonal murine antihuman platelet antibodies, surface antigen expression was determined for human and Yorkshire swine platelets. Expression of CD9 (p24), CD42B (Ib), CD41b, (Ilb), CD61 (IIIa), CD41a (Ilb/IlIa), CD49b (VLA-2), CD62p, (P selectin), CD31 (PECAM-1D, and CD51/CD61 (vitronectin) was measured by flow cytometry. Significant crossreactivity with human platelets was observed consistently for swine platelet GP 1b and GP IIIa. Crossreactivity of the swine GPIb, and GP IIIa with the human receptors is evidence of receptor similarity between human and swine platelets. The implications of significant crossreactivity of these antigens and the lack of recognition of IIb/IIIa needs to be understood in cardiovascular research. Determining commercially available antihuman GP Ib and GP IIIa, rather than GP IIb/IIIa, would contribute to better elucidation of the effect of von Willebrand factor and the booming family of platelet inhibitors in the swine model of ischemia-reperfusion.

Journal Article↗

Likelihood of introducing selected exotic diseases to domestic swine in the continental United States of America through uncooked swill.

To help policy makers determine the need for current regulations (which require cooking of swill prior to feeding to swine), an assessment of the likelihood of exposing domestic swine in the continental United States of America (USA) to selected foreign animal disease agents by feeding uncooked swill was carried out. The hazard was assumed to originate from contraband food items entering the USA and subsequently being discarded in household waste. Such food waste may be collected by licensed waste feeders and fed to swine. This study showed that, of the four diseases studied, the probability of exposure was highest for the classical swine fever (hog cholera) virus. The median annual likelihood of one or more contaminated loads of swill being fed to swine in the continental USA was estimated as follows: classical swine fever virus: 0.063, foot and mouth disease virus: 0.043, swine vesicular disease virus: 0.005, African swine fever virus: 0.005.

African Swine Fever↗

Human and swine hepatitis E viruses from Western India belong to different genotypes.

BACKGROUND/AIMS: Hepatitis E is endemic in India. Earlier, we showed prevalence of IgG antibodies to hepatitis E virus (IgG-anti-HEV) in different animal species and inability of at least one human hepatitis E virus (HEV) strain to infect pigs. In the US where hepatitis E is not endemic in humans, zoonotic spread of HEV was suspected as swine and human HEV were closely related and cross-species infection was documented. The present study attempts to identify and partially characterize swine HEV from India. METHODS: Serum samples from 284 pigs were screened for the presence of HEV-RNA (nested polymerase chain reaction; PCR) and IgG-anti-HEV (enzyme-linked immunosorbent assay; ELISA). PCR products (Open Reading Frame-2 region) were sequenced and subjected to phylogenetic analysis. Two sero-negative pigs were inoculated with swine HEV-positive serum pool. RESULTS: ELISA and PCR positivity were 42.9 and 4.6%, respectively. All Indian swine HEV sequences clustered with genotype IV. Pigs could be experimentally infected with swine HEV. CONCLUSIONS: Swine HEV circulates in Indian pigs. In contrast to US and Taiwan wherein both human and swine HEV isolates belong to same genotype, Indian human HEV isolates belong to genotype I whereas genotype IV circulates in swine. Though experimental infection with Indian swine HEV was possible, at least one human HEV strain could not infect pigs.

Amino Acid Sequence↗

Antigenic and molecular heterogeneity in recent swine influenza A(H1N1) virus isolates with possible implications for vaccination policy.

In order to explore the occurrence of antigenic drift in swine influenza A(H1N1) viruses and the match between epidemic and vaccine strains, 26 virus isolates from outbreaks of respiratory disease among finishing pigs in the Netherlands in the 1995/1996 season and reference strains from earlier outbreaks were examined using serological and molecular methods. In contrast to swine H3N2 viruses, no significant antigenic drift was observed in swine H1N1 viruses isolated from the late 1980s up to 1996 inclusive. However, a marked antigenic and genetic heterogeneity in haemagglutination inhibition tests and nucleotide sequence analyses was detected among the 26 recent swine H1N1 virus strains. Interestingly, the observed antigenic and molecular variants were not randomly distributed over the farms. This finding indicates independent introductions of different swine H1N1 virus variants at the various farms of the study and points to a marked difference between the epidemiologies of human and swine influenza viruses. The observed heterogeneity may hamper the control of swine influenza by vaccination and indicates that the efficacy of current swine influenza vaccines requires re-evaluation and that the antigenic reactivity of swine influenza viruses should be monitored on a regular basis.

Animals↗

Isolation of H3N2 swine influenza virus in South Korea.

Swine influenza is a significant respiratory disease causing occasional reproductive problems in naïve swine herds. Although different subtypes of swine influenza virus (SIV) have been implicated in clinical outbreaks of swine influenza in Asian countries, no virus isolation has been made to identify SIV of subtypes other than the H1N1 subtype in the Korean swine population. In December 1998, an outbreak of acute respiratory disease was identified in a commercial swine farm located in the Kyunggi province of South Korea. A causative agent, which agglutinated rooster red blood cells, was detected from the lungs of 3 piglets from the index herd and was determined to be type A influenza virus using a commercial influenza virus typing kit. Hemagglutination activity (HA) of the isolates was completely inhibited by a swine antiserum against a recent US H3N2 SIV isolate (A/Sw/IA/41305/1998) but not by H1N1 swine antiserum (A/Sw/IA/1979). Reverse transcription-polymerase chain reaction (RT-PCR) revealed all 3 isolates were H3 SIV subtypes. Sequence analysis of hemagglutinin gene PCR products supported the belief that the Korean H3 SIV isolates were genetically similar to the known mammalian H3 influenza viruses. This is the first report on a clinical outbreak of swine influenza caused by the H3N2 virus in Korea.

Animals↗

Effects of pair housing on diurnal rhythms of heart rate and heart rate variability in miniature swine.

This study investigated the effects of pair housing on diurnal rhythms of heart rate and autonomic nervous activity in miniature swine. For this purpose, six adult Göttingen miniature swine were initially housed individually in an animal cage. Then, two of each swine were housed in a large cage together for 3 weeks. After that swine were separated into individual cages again. During this experimental procedure, electrocardiogram (ECG) was recorded with a Holter ECG recorder. Autonomic nervous activity was evaluated by power spectral analysis of heart rate variability. Heart rate and autonomic nervous activity clearly showed a diurnal rhythm in miniature swine housed in individual cages. When two swine were housed together, heart rate was significantly increased throughout the day and diurnal rhythm disappeared. Although these changes gradually recovered to basal levels, these parameters had not completely returned to basal levels even after 2 weeks. Heart rate was still higher than the initial level just after swine were re-housed in their own individual cages. Heart rate and autonomic nervous activity returned to basal levels about 2 weeks after re-housing. Further, heart rate in some swine decreased below their initial levels. These results suggest that it takes miniature swine at least 2 weeks to adapt to different circumstances. Furthermore, the power spectral analysis of heart rate variability can be used as a useful method in a study for answering controversial issues related to stress response.

Animals↗

Age-dependent seroprevalence of antibodies against a Helicobacter pylori-like organism and Helicobacter pylori in commercially reared swine.

OBJECTIVE: To determine the prevalence of antibodies against a swine-origin Helicobacter pylori-like organism (HPLO) and H pylori in conventionally reared swine. ANIMALS: 640 conventionally reared swine of various ages from 16 high-health farms in Canada, 20 sows from Ohio, and 35 gnotobiotic swine. PROCEDURES: Blood was collected from the cranial vena cava. Sera were collected and tested via ELISA for antibodies against antigen prepared from a swine-origin HPLO and human H pylori strain 26695. RESULTS: Antibodies reactive with a swine HPLO, H pylori, or both were detected in 483 of 640 swine from all 16 farms in western Canada. Seroprevalence varied with age and was low (5.6%) in suckling ( 4 weeks old to adulthood. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that colonization by a swine-origin HPLO, H pylori, or both and resultant seroconversion, like that of H pylori infection in humans, were common in commercial swine operations. Furthermore, data indicated that gastric infection was acquired at an early age. The relationships to gastric colonization by HPLOs and clinical manifestations of disease such as gastritis and gastroesophageal ulceration remain to be determined.

Age Factors↗

Comparative response of swine and rats to high-fiber or high-protein diets.

Twenty-four growing swine and 24 growing rats were fed high-protein (34%) diets on an ad libitum basis to determine their effects on body weight, carcass characteristics, intestinal microbiological profile and visceral organ weights. High dietary fiber reduced body weight gain and gain:feed ratio in both swine and rats and decreased body fatness in swine; it increased relative kidney weight (percentage of body weight) in both swine and rats and decreased relative liver weight in rats but increased it in swine. Absolute weights of stomach and large intestine were unaffected by high fiber in either species, but relative weight of small and large intestine was increased in swine and relative weight of stomach was increased in rats. High dietary protein increased absolute and relative weights of kidneys in both species and increased relative liver in swine but not in rats. Absolute weight of large intestine was increased by high dietary protein in rats and tended to be increased in swine; relative large intestine weight was increased in both species. The microbial profile of large intestinal contents of rats showed no effect of diet on Enterobacteriaceae, Campylobacter, Salmonella or total anaerobes and cellulolytic organisms, but coliforms were higher in rats fed high fiber or high protein than in controls. We conclude that dietary levels of fiber and protein influence growth of specific segments of the gastrointestinal tract of growing rats and swine, probably by different mechanisms of action.

Animal Feed↗