Reduced hexose transport by enterocytes associated with rapid, noninjurious rejection of Trichinella spiralis from immune rats

Rats immunized against Trichinella spiralis rejected larvae from a challenge infection within minutes. Infectivity of these once-rejected larvae for nonimmune rats following intestine-to-intestine transfer, infectivity for nonimmune mice following oral inoculation, and normal development in these mice indicated that the parasite did not sustain immediate or long term damage as a result of the host's immune response. Associated with rapid worm rejection was a change in host intestinal function - altered absorption. Uptake of a hexose, 14C-beta-methyl-D-glucoside, was studied in intestinal segments isolated from rats before and 30 min after primary and secondary infections. Larvae were administered intraintestinally. Absorption was measured using a tissue accumulation method, under conditions of substrate saturation (30 mMolar) and over a 5-min period. 3H-mannitol was used as a marker to measure extracellular water, hence, extracellular sugar. Following challenge infection of previously infected (immunized) hosts, there was a significant reduction (22%; P less than 0.05) in hexose absorption as compared to the uptake rate before challenge. In contrast, cellular uptake before and 30 min after primary infection was similar. These findings are presented in support of the hypothesis that the failure of T. spiralis larvae to infect immune hosts is the result, not of direct worm damage, but of functional changes in gut epithelium, the habitat of the parasite.     

Kinetics of immunological responses, resistance to reinfection, and pathological reactions to infection with Trichinella spiralis

Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.     

Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections

The objective of this study was to assess the normal range of cartilage volumes in the knee joints of healthy adults, the ratio between the patellar, femoral, and tibial cartilages, and the correlation of the volumes with age, body weight, height, body mass index (obesity), patellar bone size, and the diameter of the tibial head. We examined the knee joints of nine healthy volunteers and eleven normal post-mortem specimens with an age range of 24 to 82 years. The cartilage volumes of the patella, femur, medial tibia and the lateral tibia were quantified, using a fat-suppressed FLASH-3D sequence (resolution 2x0.31x0.31 mm3) and digital postprocessing, involving three-dimensional reconstruction. The mean total volume of the knee joint cartilage was 23,245 mm3, the relative standard deviation (CV%) 19%, and the range 16,341 to 33,988 mm3. In the patella, femur and tibia, the CV% amounted to between 22 and 25%. These joint surfaces occupied a relatively variable proportion of the total knee joint volume, the percentage of the patella being 11 to 22%, that of the femur 54 to 69%, that of the medial tibia 7 to 12%, and that of lateral tibia 11 to 16%. The volumes of the lateral tibia were systematically higher than those of the medial tibia (P<0.001). There was no significant correlation of the knee joint cartilage volume with age (r=+0.05), body weight (r=+0.38), height (r=+0.39) or body mass index (r=+0.29), but a relatively high correlation with the diameter of the tibial head (r=+0.78, P<0.001). After normalising the volumes to this diameter, the CV% of the total knee joint cartilage volume was reduced to 13%, its variation being 12 to 21% in the patella, femur and tibia. MRI is available for measuring cartilage volume during growth, functional adaptation, and tissue loss in degenerative joint disease. The study shows that a wide variation of cartilage volumes exists in the knee joints of normal adults. To reduce the variability between individuals, the cartilage volumes may be normalised to the head of the tibial diameter.     

The liver and immune responses. I. Regional lymph node response in rats to injection of semi-allogeneic adult liver cells

A 12-year-old Domestic Shorthair cat with a soft, fluctuant, subcutaneous mass, approximately 5 cm in diameter on the posterior aspect of the left tarsus was diagnosed as having protothecosis. Cultures, histopathology, and fluorescent antibody reagents were used to identify Prototheca wickerhamii as the etiologic agent. Protothecosis has not previously been recorded in cats.     

A study of immunological responses of sheep clinically-affected with paratuberculosis (Johne's disease). The relationship of blood, mesenteric lymph node and intestinal lymphocyte responses to gross and microscopic pathology

Nineteen adult sheep diagnosed as having clinical paratuberculosis (Johne's disease) and 16 unaffected controls were examined in this study. Animals were tested for the presence of circulating antibodies of Mycobacterium avium ssp. paratuberculosis (M. a. paratuberculosis) and lymphocytes derived from the blood, mesenteric lymph nodes and intestines were examined for cell-mediated immune (CMI) responses to Johnin pure protein derivative (Johnin-PPD: J-PPD). Bacteriological examinations were carried out on faeces and tissues and any mycobacterial isolates identified as M. a. paratuberculosis (IS900+) or M. avium ssp. silvaticum (M. a. silvaticum) (IS901+) by polymerase chain reaction (PCR). Full necropsy and histopathological studies were performed and diseased animals were categorised on the basis of having a lepromatous or tuberculoid form of intestinal pathology. Unaffected control sheep were generally antibody-negative and demonstrated varying CMI responses to J-PPD. Clinically-affected animals were almost always antibody-positive with variable CMI responses. A correlation was observed between the histological lesion type in the intestine and the cellular immune response. Tuberculoid-type lesions were associated with strong CMI responses in lymphocytes derived from the peripheral blood, mesenteric lymph node and intestine, whereas lepromatous-type lesions were associated with weak CMI responses in all tissues examined.     

The influence of antibodies to TNF-alpha and IL-1beta on haemodynamic responses to the cytokines, and to lipopolysaccharide, in conscious rats

Male, Long Evans rats (350-450 g) were anaesthetized and had pulsed Doppler probes and intravascular catheters implanted to allow monitoring of regional (renal, mesenteric and hindquarters) haemodynamics in the conscious state. Our main objectives were to:- assess the effects of administering human recombinant tumour necrosis factor (TNF)-alpha and human recombinant interleukin-1 (IL-1)beta, alone and together; determine the influence of pretreatment with a mixture of antibodies to TNF-alpha and IL-1beta on responses to co-administration of the cytokines; ascertain if pretreatment with a mixture of the antibodies to TNF-alpha and IL-1beta had any influence on the responses to lipopolysaccharide (LPS). TNF-alpha (10, 100 and 250 microg kg(-1), in separate groups, n=3, 9 and 8, respectively) caused tachycardia (maximum delta, +101+/-9 beats min(-1)) and modest hypotension (maximum delta, -10+/-2 mmHg), accompanied by variable changes in renal and mesenteric vascular conductance, but clear increases in hindquarters vascular conductance; only the latter were dose-related (maximum delta, +6+/-6, +27+/-9, and +61+/-12% at 10, 100 and 250 microg kg(-1), respectively). IL-1beta (1, 10, and 100 microg kg(-1) in separate groups, n = 8, 8 and 9, respectively) evoked changes similar to those of TNF-alpha (maximum delta heart rate, +69+/-15 beats min(-1); maximum delta mean blood pressure, -14+/-2 mmHg; maximum delta hindquarters vascular conductance, +49+/-17%), but with no clear dose-dependency. TNF-alpha (250 microg kg(-1)) and IL-1beta (10 microg kg(-1)) together caused tachycardia (maximum delta, +76+/-15 beats min(-1)) and hypotension (maximum A, -24+/-2 mmHg) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (+52+/-6%, +23+/-8%, and +52+/-11%, respectively). Thereafter, blood pressure recovered, in association with marked reductions in mesenteric and hindquarters vascular conductances (maximum delta, -50+/-3% and -58+/-3%, respectively). Although bolus injection of LPS (3.5 mg kg(-1)) caused an initial hypotension (maximum delta, -27+/-11 mmHg) similar to that seen with co-administration of the cytokines, it did not cause mesenteric or hindquarters vasodilatation, and there was only a slow onset renal vasodilatation. The recovery in blood pressure following LPS was less than after the cytokines, and in the former condition there was no mesenteric vasoconstriction. By 24 h after co-administration of TNF-alpha and IL-1beta or after bolus injection of LPS, the secondary reduction in blood pressure was similar (-16+/-2 and -13+/-3 mmHg, respectively), but in the former group the tachycardia (+117+/-14 beats min(-1)) and increase in hindquarters vascular conductance (+99+/-21%) were greater than after bolus injection of LPS (+54+/-16 beats min ' and +439%, respectively). Pretreatment with antibodies to TNF-alpha and IL-1beta (300 mg kg(-1)) blocked the initial hypotensive and mesenteric and hindquarters vasodilator responses to co-administration of the cytokines subsequently. However, tachycardia and renal vasodilatation were still apparent. Premixing antibodies and cytokines before administration prevented most of the effects of the latter, but tachycardia was still present at 24 h. Pretreatment with antibodies to TNF-alpha and IL-1beta before infusion of LPS (150 microg kg(-1) h(-1) for 24 h) did not affect the initial fall in blood pressure, but suppressed the hindquarters vasodilatation and caused a slight improvement in the recovery of blood pressure. However, pretreatment with the antibodies had no effect on the subsequent cardiovascular sequelae of LPS infusion. the results indicate that although co-administration of TNF-alpha and IL-1beta can evoke cardiovascular responses which, in some respects, mimic those of LPS, and although antibodies to the cytokines can suppress most of the cardiovascular effects of the cytokines, the antibodies have little influence on the haemodynamic responses to LPS, possibly because, during infusion of LPS, the sites of production and local action of endogenous cytokines, are not accessible to exogenous antibodies.     

Mycobacterium bovis (BCG) infection of the lymph nodes of normal, immune, and cortisone-treated guinea pigs

Strain-2 inbred guinea pigs were infected intradermally with 10(5)-10(7) viable BCG (Pasteur) organisms by means of multiple scarifications of shaven midflank skin. The spread of the BCG to the draining lymph nodes and on to the spleen was followed quantitatively for 28 days. The population of bacilli at the inoculation site increased as much as tenfold the first 14 days. The number of viable BCG organisms recovered from the primary draining superficial dorsal axillary and inguinal lymph nodes varied from 0.1 to 1.0% of the inoculum, with a further tenfold to 100-fold drop in counts for the secondary subclavian and lumbar lymph nodes. The bacterial counts for the various nodes increased substantially the first 14 days. By 28 days, as many as 1,000 viable bacilli were recovered from the spleen. Increasing the inoculum size or the number of inoculation sites increased the primary node counts and promoted a more extensive and rapid spread by the BCG population to the secondary lymph nodes and spleen. Prior vaccination of the host with living BCG decreased the spread of the BCG inoculum from the scarification site to the various draining lymph nodes. Multiple injections of cortisone tended to reverse this effect.     

Ingestive responses to homeostatic challenges in rats with ablations of the anterolateral neocortex.

Because rats with either anterolateral neocortical (AN) or lateral hypothalamic (LH) damage initially display similar feeding and drinking deficits and recovery patterns, the present study examined the possibility that anterolateral neocortical ablations would also produce similar chronic ingestive impairments to glucoprivic and hydrational challenges. 73 male Sprague-Dawley rats received AN or dorsoposterior neocortical lesions or served as unoperated controls. Ss with AN ablations exhibited normal feeding responses to food deprivation and glucoprivation induced by insulin (4–26 U/kg, sc) or 2-deoxydextroglucose (2-DG [125 or 250 mg/kg, ip]), but their response to 500 mg/kg or 2-DG was impaired. These Ss also drank normally in response to hypertonic saline injections and following water deprivation but only if food was available during the test session. Results indicate that, although the anterolateral neocortex and LH are anatomically related, these brain regions appear to be functionally dissimilar in terms of the regulation of ingestion. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selectivity of IgE responses, mast cell sensitization, and cytokine expression in the immune response of Brown Norway rats to chemical allergens

Sensitizing chemicals can induce various types of allergic disease, including contact dermatitis and occupational asthma. In the present study we have examined the nature of the immune response induced in Brown Norway (BN) rats by oxazolone (OX), a potent contact allergen, and by trimellitic anhydride (TMA), a chemical known to cause sensitization of the respiratory tract and occupational asthma. BN rats were exposed topically to either OX or TMA at doses selected to achieve similar levels of proliferative activity by draining LNC. Both chemicals stimulated hapten-specific IgG antibody responses, but only TMA induced specific IgE antibody, an increase in total serum IgE and active sensitization of mast cells. Draining LNC from OX-treated rats expressed elevated IFN-gamma mRNA, whereas those from TMA-treated rats expressed elevated IL-5 mRNA compared to controls. Furthermore, Con A-activated draining LNC from rats exposed to TMA, but not OX, released significantly increased concentrations of IL-4. In conclusion, different chemical allergens can induce in the BN rat divergent patterns of IgE response and cytokine expression.     

Behavioral responses of juvenile rats (Rattus norvegicus) to neonates after infusion of maternal blood plasma.

Individual 18- or 30-day-old male and female Wistar rats (juveniles) were continuously exposed to 3–8-day-old pups for 5 days (sensitization) after intravenous (iv) infusion of maternal blood plasma (PL group) or 5% dextrose and water (IC group) through chronically implanted cannulas and were compared with nonhandled littermate controls (NHC group). Plasma from parturient females selectively increased retrieving behavior in 30-day-olds, and it was more powerful in females than in males. Prior to sensitization, both PL and IC 30-day-olds showed higher frequencies of retrieving, crouching, anogenital licking, and contact than did nonhandled juveniles. 30-day-olds that received maternal blood plasma continued to retrieve pups, with a latency peak for retrieving occurring at 72 hrs. 18-day-old subjects did not generally show effects of any of our manipulations. The iv cannulation and infusion procedures led to a persistent dissociation of retrieving behavior from play in older animals and an integration of retrieving with crouching and licking regardless of whether maternal plasma or control infusion was administered. Retrieving behavior was associated with play behaviors in younger juveniles and in older, nonhandled control animals irrespective of treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE)

The main mechanism causing catabolite repression in Escherichia coli is the dephosphorylation of enzyme IIAGlc, one of the enzymes of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). The PTS is involved in the uptake of a large number of carbohydrates that are phosphorylated during transport, phosphoenolpyruvate (PEP) being the phosphoryl donor. Dephosphorylation of enzyme IIAGlc causes inhibition of uptake of a number of non-PTS carbon sources, a process called inducer exclusion. In this paper, we show that dephosphorylation of enzyme IIAGlc is not only caused by the transport of PTS carbohydrates, as has always been thought, and that an additional mechanism causing dephosphorylation exists. Direct monitoring of the phosphorylation state of enzyme IIAGlc also showed that many carbohydrates that are not transported by the PTS caused dephosphorylation during growth. In the case of glucose 6-phosphate, it was shown that transport and the first metabolic step are not involved in the dephosphorylation of enzyme IIAGlc, but that later steps in the glycolysis are essential. Evidence is provided that the [PEP]-[pyruvate] ratio, the driving force for the phosphorylation of the PTS proteins, determines the phosphorylation state of enzyme IIAGlc. The implications of these new findings for our view on catabolite repression and inducer exclusion are discussed.     

Bacterial survival, lymph node pathology, and serological responses of bison (Bison bison) vaccinated with Brucella abortus strain RB51 or strain 19

From August 1993 to June 1994, 3 month-old bison (Bison bison) were vaccinated with Brucella abortus strain RB51 (SRB51, n = 6), strain 19 (S19, n = 3), or with saline (n = 1) and serologic responses and persistence of vaccine strains within lymph nodes were monitored. Bison vaccinated with S19 had granulomatous lymphadenitis and greater peak numbers of B. abortus than those vaccinated with SRB51. Bison vaccinated with RB51 had similar histological lesions and B. abortus were still present in lymph nodes at 16 weeks. Although antibodies against RB51 were produced, standard tube agglutination test responses of RB51-vaccinates remained negative. The histological lesions of B. abortus infections in bison were similar to those observed in cattle, but bison did not clear SRB51 as rapidly as cattle.     

Investigations with 3H-thymidine and electron microscopical studies in rat livers following thermocoagulation of the thoracic duct at the base of the neck (author's transl)

Autoradiographic studies with 3H-thymidine were done in 90 male and female white Sprague Dawley rats following thermocoagulation of the thoracic duct at the base of the neck. In the acute stages of these experiments we were unable to find any significant influence of a lymphedema on the hepatocytes and Kupffer cells. In the longterm experiments the labelling indices of the hepatocytes were slightly above those of healthy controls of the same age. In another 14 male and female white Sprague Dawley rats we did electron microscopical investigations of the liver. In the acute phase of the experiment we found an intra- and extrahepatic edema as well as damages of the hepatocytes at the periphery of the liver acini. After 12-15 days these findings have regressed. It seems therefore that an intrahepatic lymphedema does not influence the regenerative capacity of the liver to a marked extent.     

Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE)

The optic nerve of rats with EAE was examined at various times to determine the integrity of the blood-brain barrier (BBB) and to assess monocyte-macrophage, T cell, and microglial responses. In naive control animals, leakage of horseradish peroxidase (HRP) and the presence of cells expressing major histocompatibility complex (MHC) class II antigen were evident in the meninges of the retrobulbar optic nerve. In rats with EAE, microglia in the region of the lamina cribrosa and in the regions adjacent to the meninges became activated from day 7 to 8 postinduction (pi). HRP leakage was also evident in the region of the lamina cribrosa from day 7 to 8 pi. On day 8 pi, infiltration of inflammatory cells and Monastral blue leakage were apparent in the myelinated region of the optic nerve. The intensity of these cellular and vascular changes peaked at day 12 pi, when signs of clinical disease became manifest. Monocytes-macrophages expressing MHC class II and the ED1 antigen, together with lymphocytes expressing the alphabetaT cell receptor, constituted the major proportion of cells associated with inflammatory lesions. Thus: (i) the inherent weakness of the BBB as well as the presence of both antigen (myelin) and MHC class II+ cells in the retrobulbar optic nerve are likely susceptibility factors for the frequent involvement of this region in EAE and multiple sclerosis; and (ii) activation of microglia occurs early in the pathogenesis of experimental optic neuritis.     

Kinetics, localization and cytokine profile of T cell responses to immune stimulating complexes (iscoms) containing human influenza virus envelope glycoproteins

Immune stimulating complexes (iscoms) are 40 nm particles combining adjuvant-active Quillaja saponins and multimeric presentation of antigens. The distribution in mice of influenza virus iscoms and the resulting T cell responses in the lymph nodes (LN) and spleen were characterized. After a single subcutaneous injection, iscoms were delivered to the draining LN where they induced a transient population of LN cells which responded with proliferation and secretion of interleukin-2 (IL-2), gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) after restimulation. The response in the spleen developed more slowly, sustained for 12 weeks and was characterized by cells producing in particular IL-2 and IFN-gamma but also IL-4. A booster resulted in a dramatic enhancement of the production of IFN-gamma, indicating that iscoms efficiently recruit cells with Th1 properties. Comparisons of T cell responses to iscoms and to influenza virus antigen in Freund's complete adjuvant demonstrate that these adjuvants affect both the localization and cytokine profile of T cell responses.     

Host response to initial and challenge infections, following treatment, of Gyrodactylus bullatarudis and G. turnbulli (Monogenea) on the guppy (Poecilia reticulata)

Patients homozygous for the Z allele of alpha-1-antitrypsin (alpha 1AT) have very low serum levels and are predisposed to emphysema. There have also been reports of emphysema being associated with the heterozygous phenotype FZ. To investigate whether F alpha 1AT was dysfunctional, the inhibitory activity of F alpha 1AT against human neutrophil elastase (HNE) was compared with that of common alpha 1AT phenotypes. Time-dependent inhibition of HNE by alpha 1AT was used to calculate the association rate constant (k assoc) for M, MZ, FM, FZ, F (partially purified from FZ or FS), Z and S alpha 1AT phenotypes in human sera. The results for k assoc at 25 degrees C were 9.1 (SD 0.9), 9.7 (SD 0.9), 8.0 (SD 0.8), 4.0 (SD 0.4), 4.2 (SD 0.8), 5.1 (SD 0.6) and 8.6 (SD 0.6) x 10(6) M-1s-1 respectively. F was found to have reduced activity much like that of Z, the alpha 1AT most commonly associated with emphysema. MZ (low risk for disease) and FZ heterozygotes had similar intermediate alpha 1AT levels. However the in vivo inhibition time for FZ was almost three times longer than for MZ, indicating greater exposure to proteolytic damage from free elastase for FZ than MZ individuals. In conclusion, F alpha 1AT is expressed in serum at low normal levels but is dysfunctional in its ability to inhibit HNE. Individuals who coinherit the F and a deficiency allele such as Z or Null, are likely to have a high risk for the development of emphysema. The disease risk for F homozygotes remains to be determined.     

Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation

BACKGROUND/AIMS: In rats with cholestasis due to bile duct ligation, the expression of the Na+-dependent taurocholate co-transporting polypeptide, the major uptake system for conjugated bile acids in hepatocytes, is down-regulated. Our purpose was to examine the expression of the organic anion transporting polypeptide, a Na+-independent uptake system for bile acids and organic anions, in rats with bile duct ligation, and to compare the expression of organic anion transporting polypeptide to that of Na+-dependent taurocholate co-transporting polypeptide. METHODS: Rats with bile duct ligation were studied after 1, 3 or 7 days. The expression of organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide proteins was examined by Western blot analysis and steady-state mRNA levels were determined by Northern blot analysis using cDNAs encoding organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide. Sham-operated animals were used as controls. RESULTS: The expression of organic anion transporting polypeptide protein was slightly, but not significantly, decreased 1 day after ligation (10.3%); it was markedly decreased after 3 days (56.9%; p<0.03) and 7 days (46.8%; p<0.05) compared to sham-operated animals. Steady-state mRNA levels of organic anion transporting polypeptide were decreased by 79.7% (p<0.04), 48.8% (p<0.02) and 57.4% (p<0.02) after 1, 3 and 7 days respectively. For comparison, Na+-dependent taurocholate co-transporting polypeptide protein and mRNA levels were decreased by 73.8% (p<0.03) and 70.0% (p<0.05) at 1 day and remained low after 3 and 7 days. CONCLUSIONS: In rats with bile duct ligation, the expression of organic anion transporting polypeptide protein and mRNA is down-regulated. Down-regulation of organic anion transporting polypeptide seems less pronounced than that of Na+-dependent taurocholate co-transporting polypeptide. Nevertheless, it could contribute to a decreased uptake of potentially toxic bile acids or organic anions in this situation.     

Responses of observer rats (Rattus norvegicus) to complex, diet-related signals emitted by demonstrator rats.

We explored the effects of complex, food-identifying signals emitted by demonstrator Long-Evans rats (Rattus norvegicus) on food preferences of their observers. In Experiments 1 and 2, observers identified each of 2 or 3 foods their demonstrators had eaten before interacting with observers. In Experiment 3, individual observers interacted with groups of demonstrators. Some of these demonstrators had eaten one food, some another. Observers then chose between the 2 foods. The greater the proportion of demonstrators in a group that had eaten a diet, the greater the proportion of that diet the observers ate. In Experiment 4, each observer interacted over several weeks with a series of demonstrators and preferred each of the foods its demonstrators had eaten. In sum, the food preferences of observers were affected by several different types of complex, food-identifying signals like those one might expect rats to encounter outside the laboratory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)