Impairment of cliff avoidance reaction induced by subchronic methamphetamine administration and restraint stress: comparison between two inbred strains of rats

1. The effects of subchronic methamphetamine (MAP) treatment and restraint stress on the behavioral sensitization in stereotypy (stereotypy sensitization) and cliff avoidance reaction (CAR) were examined in two inbred strains of male rats; Fischer 344/N (F344), and Lewis/N (LEW). 2. In experiment 1, the animals received 4 mg/kg/day MAP for 30 days. LEW rats developed stereotypy sensitization earlier than F344 rats. However, both strains plateaued at the same stereotypy rating score. Furthermore, F344 rats were susceptible to CAR impairment as a result of MAP treatment, whereas LEW rats were not. 3. In experiment 2, the animals were exposed to daily restraint stress of 2hr for 4 weeks. MAP was administered (4mg/kg) 7 days after the last treatment day. Repeated restraint stress induced almost the same degree of stereotypy sensitization in both strains. F344 rats were susceptible to CAR impairment induced by repeated stress, whereas LEW rats were not. 4. The effects of psychostimulant and stressors appear to be similar not only with respect to stereotypy sensitization but also CAR impairment. Differences in MAP- or stress-induced CAR impairment between the two inbred strains may be genetically linked and may be involved in the development of psychotic behavior.     

Five steps to selling cosmetic dentistry

Fischer 344 (F344) and Lewis (LEW) rats show considerable neuroanatomical and neurophysiological differences within the mesolimbic dopamine system. The aim of our experiments was to study the functional correlates of such differences by examining open-field behavior and the sensitivity towards the psychostimulant and rewarding effects of amphetamine in male and female, F344 and LEW rats. In addition, the consequences of short versus extended habituation to open-field testing on amphetamine locomotion in these two rat strains was assessed. LEW but not F344 rats irrespective of gender showed between-session habituation of open-field activity. Amphetamine-induced locomotion was higher in F344 compared to LEW rats and in females compared to male rats. In addition, extended habituation increased the locomotor effects of amphetamine. The rewarding effects of amphetamine as measured by the conditioned place preference test were more pronounced in F344 than in LEW rats. Our results suggest that the two rat strains differed in their behavioral response to mild stress and to amphetamine and that these differences may depend upon differences within the mesolimbic dopamine system.     

Control of monocyte influx in glomerulonephritis in transplanted kidneys in the rat

Induction of anti-Thy-1 nephritis in different strains of inbred rats results in phenotypically different types of renal diseases. In Wistar and Lewis (LEW) rats, a transient influx of ED1+ macrophages occurs 24 hours after injection of anti-Thy-1 antibodies, whereas this does not occur in F344 rats. The present experiments were designed to investigate the role of the kidney in the regulation of the monocyte influx in this model. To dissociate the role of the immune system from local intrarenal factors in the control of monocyte influx, anti-Thy-1 nephritis was induced in LEW rats with an F344 kidney transplant and in F344 rats with a LEW kidney allograft. Acute rejection episodes were prevented by treatment with an anti-CD4 monoclonal antibody. Control rats received a syngeneic kidney graft. Monocyte influx after injection of anti-Thy-1 antibodies was found in the glomeruli of both LEW and F344 kidneys removed from LEW recipients, whereas there was no demonstrable monocyte influx after infusion of anti-Thy-1 antibodies in either LEW or F344 kidneys removed from F344 recipients. Monocyte infiltration correlated with the subsequent expansion of the mesangial extracellular matrix. The inability to attract monocytes was not due to the lack of glomerular expression of chemokines, because F344 and LEW glomeruli demonstrated a similar expression of monocyte chemoattractant protein-1 (MCP-1). Differences in the ability to activate the complement system were excluded. We conclude that the immune system controls the glomerular influx of monocytes and that the reaction of the mesangial cells is probably controlled by combinations of cytokines produced during the inflammatory process.     

Candesartan cilexetil reduces chronic renal allograft injury in Fisher-->Lewis rats

OBJECTIVES: To determine the effects of the angiotensin II receptor antagonist, candesartan cilexetil, on glomerular and systemic blood pressures and the development of renal injury in Lewis rat recipients of a single Fisher kidney (F334--> LEW transplantation), an established rat model of chronic renal allograft failure. DESIGN: Recent studies have shown that chronic injury of renal allografts in F334-->LEW rats may be virtually abrogated by supplying the Lewis recipients with two Fisher kidneys or, alternatively, by retaining a native kidney. These findings imply a major contribution from processes associated with nephron loss to the pathogenesis of chronic renal allograft failure, a notion supported by the observation that transplanting two kidneys also normalizes glomerular capillary pressure (PGC) in F344-->LEW rats. Thus, a pharmacological reduction in PGC, by blocking the effects of angiotensin II, should also lessen renal injury in F344-->LEW rats. MATERIALS AND METHODS: Bilaterally nephrectomized F344--> LEW rats were treated with the angiotensin II receptor blocker candesartan cilexetil (TCV-116) at 40 mg/l or with vehicle, administered in drinking water. Proteinuria and systolic blood pressure were assessed monthly, and histological studies were carried out after 24 weeks. The glomerular filtration rate and glomerular pressures were determined after 10 weeks in additional rats by clearance and micropuncture studies. RESULTS: Treatment with candesartan cilexetil lowered systemic blood pressure, normalized PGC at 10 weeks and greatly reduced proteinuria and allograft glomerulosclerosis at 24 weeks. CONCLUSIONS: These data indicate that the development of renal injury in F344-->LEW renal allografts can be prevented by the pharmacological blockade of angiotensin II receptors using candesartan cilexetil. This suggests that angiotensin-dependent processes contribute significantly to chronic injury in this model of late renal allograft failure.     

Strain differences in patterns of drug-intake during prolonged access to cocaine self-administration.

The current study examined possible interactions between genetic factors and prolonged drug access by testing the Fischer (F344), Lewis (LEW), and Wistar rat strains in a prolonged access cocaine self-administration (SA) procedure. Before prolonged access, the strains did not differ in breakpoints for food or cocaine with progressive ratio (PR) testing. The LEW and Wistar rats acquired cocaine SA faster than the F344s. With prolonged access to cocaine SA, the LEW and Wistar rats showed comparable within-session patterns that were higher at the outset of each session and decreased to a stable baseline. Alternatively, the F344 rats began sessions with lower intake and increased their rate of intake during the session. The F344 and Wistar rats took more drug per session than the LEW rats but did not differ from each other. Following prolonged access, the strains did not differ in breakpoints for food, but the Wistar rats had higher breakpoints for cocaine than the F344 rats. Possible underpinnings for the observed strain differences are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Practical aspects in the diagnosis and management of aplastic anemia

Groups of F344 rats and B6C3F1 mice were exposed to furfuryl alcohol vapor for 6 hours per day, 5 days per week for 14 days (0, 16, 31, 63, 125, 250 ppm) or 13 weeks (0, 2, 4, 8, 16, 32 ppm). Reduced survival was observed in the 14-day study at 250 ppm. Final mean body weights of rats and mice exposed to 125 ppm and of female mice exposed to 63 ppm were lower than controls at the end of the 14-day study; there were no significant differences in mean body weight among chemical-exposed and control groups in the 13-week study. Exposure to furfuryl alcohol had no toxicologically significant effect on organ weights in either rats or mice, and did not cause any adverse changes in hematology or serum chemistry parameters evaluated in rates in the 13-week study. Microscopic lesions associated with exposure to furfuryl alcohol were present in the nose of both rats and mice at all exposure concentrations in both the 14-day and 13-week studies. Lesions observed in the 14-day study consisted of inflammation of the nasal turbinates accompanied by necrosis and squamous metaplasia of the respiratory epithelium and necrosis and degeneration of the olfactory epithelium. Similar lesions were observed in both rats and mice in the 13-week study. In addition, squamous metaplasia and goblet cell hyperplasia of the respiratory epithelium, squamous metaplasia of the transitional epithelium and degeneration, hyperplasia and some respiratory metaplasia of the olfactory epithelium were also observed in rats in the 13-week study, and hyaline droplets in the respiratory epithelium and chronic inflammation and respiratory metaplasia in the olfactory epithelium were observed in mice in the 13-week study. In general the nasal passages of mice appeared less sensitive than those of rats at the concentrations used in the 13-week study; a no-observable-effect level was not achieved in either the 14-day or the 13-week study.     

Increased tumor necrosis factor-alpha (TNF-alpha) gene expression in parainfluenza type 1 (Sendai) virus-induced bronchiolar fibrosis

Increased airway resistance and airway hyperresponsiveness induced in rats by infection with parainfluenza type I (Sendai) virus is associated with bronchiolar fibrosis. To determine whether increased tumor necrosis factor (TNF)-alpha gene expression is an important regulatory event in virus-induced bronchiolar fibrosis, pulmonary TNF-alpha mRNA and protein expression was assessed in rat strains that are susceptible (Brown Norway; BN) and resistant (Fischer 344; F344) to virus-induced bronchiolar fibrosis. Virus-inoculated BN rats had increased TNF-alpha pulmonary mRNA levels (P < 0.05) and increased numbers of bronchiolar macrophages and fibroblasts expressing TNF-alpha protein compared with virus-inoculated F344 rats (P < 0.05). Virus inoculation also induced elevated TNF-alpha mRNA and protein levels (P < 0.05) in cultured rat alveolar macrophages (NR8383 cells). A 55-kd soluble TNF receptor-immunoglobulin G fusion protein (sTNFR-IgG) was used to inhibit TNF-alpha bioactivity in virus-inoculated BN rats. Treated rats had fewer proliferating bronchiolar fibroblasts, as detected by bromodeoxyuridine incorporation, compared with virus-inoculated control rats (P < 0.05). There was also increased mortality in p55sTNFR-IgG-treated virus-inoculated rats associated with increased viral replication and decreased numbers of macrophages and lymphocytes in bronchoalveolar lavage fluid (P < 0.05). The results of this study indicate that 1) Sendai virus can directly up-regulate TNF-alpha mRNA and protein expression in macrophages, 2) TNF-alpha is an important mediator of virus-induced bronchiolar fibrosis, and 3) TNF-alpha has a critical role in the termination of Sendai viral replication in the lung.     

Glutathione S-transferase-pi is secreted as a monomer into human plasma by platelets and tumor cells

WY-14,643 (WY) and methylclofenapate (MCP) are peroxisome proliferators (PP) and hepatocarcinogens in rats. MCP causes hepatic polyploidization and preferentially induces replicative DNA synthesis in binucleate tetraploid hepatocytes (2 X 2N) in young Alpk:AP rats. To compare the effect of WY and MCP on hepatocyte ploidy and ploidy-specific DNA synthesis, male F344 rats were fed WY (0.1% in diet) or gavaged with MCP (25 mg/kg/day in corn oil) for 2, 5, or 10 days. Four rats per treatment group (including corn oil and diet control groups) were euthanized and the livers perfused at each time point. To identify cells undergoing DNA synthesis, all animals received BrdU by continuous infusion for 2 or 5 days prior to euthanasia. Hepatocyte ploidy and DNA synthesis were determined using one- or two-parameter flow cytometry. Averages +/- SEM for adult male F344 rats as a percentage of total hepatocytes for each ploidy subclass are 2N = 3.4 +/- 0.7%, 4N = 69.9 +/- 1.9%, 2 X 2N = 14.4 +/- 2.4%, 8N = 2.2 +/- 0.4%, and 2 X 4N = 9.6 +/- 0.9%. Significant alterations were not induced in the proportions of 2 X 2N or 4N ploidy subclasses by WY or MCP at any time point. However, WY caused increases in 8N hepatocytes at 2, 5, and 10 days (2 days, 5.2% vs 2.2% for controls; 5 days, 7.0% vs 3.1% for controls; 10 days, 6.4% vs 3.6% for controls) as did MCP at 5 and 10 days (5 days, 6.3% vs 2.5% for controls; 10 days, 5.3% vs 2.9% for controls). In addition, a majority of BrdU-containing hepatocytes were 4N following 5 and 10 days of WY and MCP [34.3% (WY) and 16.8% (MCP) vs 1.8% and 1.1% for controls, respectively, for 2 X 2N (5 days) as a percentage of total hepatocytes]. Hepatocytes with intermediary DNA content (between tetraploid and octaploid) from MCP- and WY-treated rats were predominantly mononuclear, the percentage of binucleate hepatocytes being similar to or less than the percentage of binucleate cells within the total tetraploid hepatocyte population. These data suggest that polyploidization is induced by PP and induction of S-phase by WY and MCP occurs primarily in 4N hepatocytes in mature F344 rats and not within 2 X 2N hepatocytes. Identification of a ploidy subpopulation at risk for tumor development in rodents is essential for clarifying the role of cell replication in risk assessment studies of PP.     

Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced relaxation of rat pulmonary and celiac artery rings

BN rats are well-known for their high capacity for IgE production and hyperresponsiveness to exposure to allergens or other chemicals. We examined the histological changes in the nasal cavity, trachea and lungs of BN and F344 rats after the inhalation of aerosol formaldehyde (HCHO), which exerts direct toxic effects on the respiratory system. The incidence of clinical signs such as sneezing and abnormal respiration in HCHO-treated F344 rats was higher than that in HCHO-treated BN rats. The mean body weight of HCHO-treated F344 rats apparently decreased in comparison with control F344 rats, but that of HCHO-treated BN rats was not significantly different from that of control BN rats. Changes such as squamous metaplasia, stratification, degeneration and desquamation were observed by light microscopy in nasal, tracheal and bronchial mucosa in the lungs of the HCHO-treated F344 rats. In the HCHO-treated BN rats, similar but milder lesions were restricted to the nasal mucosa. Scanning electron microscopic observation supported these light microscopic observations. These results suggest that BN rats have lower sensitivity to HCHO inhalation than F344 rats.     

Mucous cell metaplasia in rat nasal epithelium after a 20-month exposure to ozone: a morphometric study of epithelial differentiation

The present study was designed to examine the effects of long-term ozone exposure on nasal epithelia and intraepithelial mucosubstances (IM) throughout the nasal airways of F344/N rats. Animals were exposed to 0 (controls), 0.12, 0.5, or 1.0 ppm ozone, 6 h/day, 5 days/wk, for 20 mo. Rats were killed 1 wk after the end of the exposure, and nasal tissues were processed for light and electron microscopy. Standard morphometric techniques were used to determine epithelial cell densities and the amounts of IM in the surface epithelium lining the nasal airways. No mucous cells or IM were present in the epithelia lining the nasal lateral meatus and maxillary sinus of rats exposed to 0 or 0.12 ppm ozone. In contrast, rats exposed to 0.5 or 1.0 ppm ozone had marked mucous cell metaplasia (MCM) with numerous mucous cells and conspicuous amounts of IM in the surface epithelium lining these upper airways. Ozone-induced increases in total epithelial cells (i.e., epithelial hyperplasia) were present only in rats exposed to 1.0 ppm. The results of this study indicate that rats chronically exposed to 1.0 or 0.5 ppm, but not 0.12 ppm, ozone can develop marked MCM with significant increases in IM in both proximal and distal nasal airways. The epithelial changes observed throughout the nasal passages of ozone-exposed rats may be adaptive responses in an attempt to protect the upper and lower respiratory tract from further ozone-induced injury.     

Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.     

A non-randomized comparison of two radiotherapy protocols in inoperable squamous cell carcinoma of the oesophagus

Furosemide (F)-induced nephrocalcinosis (NC) has been traditionally described in low birth weight premature infants. To investigate the role of age on F-induced nephrocalcinosis we studied 24 Sprague-Dawley male rats grouped by age and F therapy vs. control as follows: A (4-week-old control), B (4-week-old + F), C (6-week-old control), D (6-week-old + F), E (10-week-old control), F (10-week-old + F). The rats were placed in metabolic cages for measurement of urine output, food and water intake. At day 14 they were anesthetized, exsanguinated and their kidneys harvested. Renal calcium deposition was assessed using NC score (scale 0-4) and quantitative calcium analysis in the contralateral kidney. Treated animals gained less weight and had higher urine output and fluid intake than the age-matched controls demonstrating the diuretic effect of furosemide. Control groups A, C, and E scored 0 histologically compared with B 2.75 +/- 0.50, D 2.00 +/- 0.58, and F 3.00 +/- 0.82 (p < 0.05 in all three paired groups). Kidney calcium content (micrograms/g dry weight) in B was 2,815.68 +/- 1,553.77 vs. A 202.58 +/- 32.02 (p = 0.04); D 1,574.05 +/- 540.21 vs. C 212.22 +/- 30.91 (p = 0.02); F 2,591.40 +/- 1,269.80 vs. E 210.38 +/- 26.79 (p = 0.02). There was no difference in the magnitude of NC among the three treated groups themselves. To determine the possible effect of age on timing of onset of NC additional 30 4-week-old and 30 10-week-old rats were studied. All 60 rats received furosemide. Six rats from each group were sacrificed on days 1, 3, 5, 7 and 11. In both groups, significant calcifications were seen already on day 3 and maximum calcification noted between days 3 and 5. We conclude that in this model the development of NC occurs within a few days of furosemide administration and that this phenomenon is not age dependent but rather reflects a property of the loop diuretic itself.     

Molecular basis of proteolytic activation of Sendai virus infection and the defensive compounds for infection

It has been proposed that the pathogenicity of Sendai virus is primarily determined by a host cellular protease(s) that activates viral infectivity by proteolytic cleavage of envelope fusion glycoproteins. We isolated a trypsin-like serine protease, tryptase Clara, localized in and secreted from Clara cells of the bronchial epithelium of rats. The enzyme specifically cleaved the precursor of fusion glycoprotein F0 of Sendai virus at residue Arg116 in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the presentation of the membrane fusion domain in the amino-terminus of the F1 subunit. Administration of an antibody against tryptase Clara in the airway significantly inhibited the activation of progeny virus and multiple cycles of viral replication, thus reducing the mortality rate. These findings indicate that tryptase Clara in the airway is a primary determinant of Sendai virus infection and that proteolytic activation occurs extracellularly. We identified two cellular inhibitory compounds against tryptase Clara in bronchial lavage. One was a mucus protease inhibitor, a major serine protease inhibitor of granulocyte elastase in the lining fluids of the human respiratory tract, and the other was a pulmonary surfactant which may adsorb the enzyme, resulting in its inactivation. These compounds inhibited virus activation by tryptase Clara in vitro and in vivo, but did not themselves affect the hemagglutination and the infectivity of the virus. The functional domain of the mucus protease inhibitor against the enzyme, which is organized in two homologous N- and C-terminal domains, is located in the C-terminal. Administration of these compounds in the airway may be useful for preventing infection with Sendai virus.     

A diallel cross analysis of genetic determinants of copulatory behavior in rats.

Conducted a diallel cross analysis aimed at obtaining information regarding genetic influences on the copulatory behavior of rats, and permitting considerations of adaptive significance. A total of 1,073 rats of 4 inbred strains-ACI, F344, LEW, and WF-and all possible F1 crosses were used. Of 385 males tested, 73 failed to mate. The F1 Ss were more likely to mate than were Ss with inbred genotypes. Overdominance was generally apparent for low frequencies of mounts and intromissions preceding ejaculation across 5 series and 3 tests. A trend for directional dominance toward low scores on various latency measures of copulatory behavior also was apparent. According to the theory relating directional dominance to adaptation, it would appear generally adaptive for rats to copulate rapidly and to ejaculate after relatively few mounts and intromissions. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pathogenicity studies of an Arkansas variant infectious bursal disease virus

A variant infectious bursal disease virus (IBDV), IBDV-s977, was blind passaged in cell culture, plaque purified, and attenuated by serial passage at a high multiplicity of infection (MOI) in chick embryo fibroblasts (CEF). Cell culture passages of virus caused less bursal atrophy and splenomegaly than did the original isolate and retained immunogenicity; however, virus tended to persist for a longer time in the bursa and spleen of birds infected with the highest CEF passages. Antibody to both low MOI and high MOI passages of IBDV-s977 poorly neutralized virus that was isolated from bursal tissue 28 days postinfection (PI). The spleens of chickens infected with the eighteenth CEF passage were negative for virus at 3 and 7 days PI but had high titers of virus at 14 and 28 days PI. There was also more virus in the bursa of birds infected with the fifteenth and eighteenth CEF passages at 28 days PI than at 7 or 14 days PI. Defective interference (DI) was demonstrated when cell cultures were coinfected with a constant amount of low MOI virus and serial dilutions of high MOI virus. There was an increase in interference score with increased passage number in CEF, and there was more interference in virus passaged at a high MOI. There was an inverse relationship between interference score and bursal lesion score and splenomegaly at 7 days PI, indicating that DI particles may be involved in virus attenuation. There was a positive relationship between interference and viral persistence in the bursa and spleen at 28 days PI. Antiserum to s977 was shown to enhance the nonlytic replication of s977 in CEF, presumably within macrophages, providing a possible mechanism for the pathotypic variation seen in emerging strains of IBDV.     

Disseminated strongyloidiasis

It is known that the susceptibility of experimental autoimmune uveitis (EAU) is controlled by both major histocompatibility antigen complex (MHC) and non-MHC genes. In this report, we studied the role of non-MHC gene in the induction of EAU. LEW, WKAH, (LEW x WKAH) F1 and (LEW x WKAH) F2 rats were examined for their incidence and severity to develop EAU by immunization with bovine S-antigen (S-Ag). We found that all LEW rats developed severe EAU within 2 weeks after immunization, but no WKAH rat did. Most F1 rats developed mild inflammation in 3-4 weeks after immunization. A quarter of F2 rats developed EAU within 2 weeks, half of them developed it in 3-6 weeks after immunization, and the others did not. These findings suggest that only one non-MHC gene controls the susceptibility to S-Ag induced EAU in rats.     

Engraftment characteristics of peripheral blood stem cells mobilised with cyclophosphamide and the delayed addition of G-CSF

Avridine is a potent synthetic adjuvant that can induce arthritis is most rat strains. The clinical appearance and histopathology of avridine-induced arthritis show great similarity to other arthritis models such as collagen-induced arthritis. In LEW and DA rats the avridine-induced arthritis is severe and long lasting. To investigate a possible genetic influence on the disease we compared LEW, DA and E3 rats, which are of different genetic origins, for their ability to develop arthritis after injection of a low dose of avridine (1.5 mg/rat). The E3 rat was shown to be resistant, whereas all of the DA rats developed arthritis. Recombinant inbred strains derived from DA and E3 parentals varied in susceptibility to avridine. Only strains sharing RT1av1 with DA developed arthritis, indicating a role for the MHC genes. The MHC association was further analysed in a series of Lewis congenic strains using the 1.5 mg avridine dose. All strains developed arthritis. LEW.1C and LEW.1W developed only acute arthritis, whereas LEW.1A, LEW, LEW.1D, LEW.1N and LEW.1F developed chronic arthritis. In particular, the LEW.1F rats developed a chronic severe arthritis of high incidence. The chronic arthritis showed an active, erosive joint inflammation several months after induction. Nude rats are resistant to avridine-induced arthritis, indicating a T cell dependence of the disease which supports the importance of MHC. However, non-MHC genes are also crucial to arthritis development. Recombinants between DA and E3, sharing RT1av1 with DA, showed either a lower incidence or a lower severity of disease than the DA rats. The E3 rat and the recombinants with RT1u were completely resistant, whereas LEW.1W, also RT1u, were highly susceptible.     

The role of environmental ammonia in respiratory mycoplasmosis of rats

Young adult, pathogen-free rats of Sherman and Fischer (F344) substrains were inoculated intranasally with 10(8) colony-forming units (GFU) of M. pulmonis and housed for 4 to 6 weeks in environments with ammonia maintained at specific concentrations from 25 to 250 ppm. All levels of NH3--whether produced naturally from soiled bedding or derived from a purified source--significantly increased the severity of the rhinitis, otitis media, tracheitis, and pneumonia (including bronchiectasis) characteristic of murine respiratory mycoplasmosis (MRM). The prevalence of pneumonia, but not that of other respiratory lesions of MRM, showed a strong tendency to increase directly with environmental NH3 concentration. In contrast, NH3 exposure of rats not infected with M. pulmonis caused anatomic lesions that were unlike those of MRM and were limited to the nasal passages. It was concluded that environmental NH3, at concentrations commonly encountered in present day cage environments for rats, plays an important role in pathogenesis of MRM.