Cyclosporine A Impairs Nucleotide Binding Oligomerization Domain (Nod1)-Mediated Innate Antibacterial Renal Defenses in Mice and Human Transplant Recipients

Acute pyelonephritis (APN), which is mainly caused by uropathogenic Escherichia coli (UPEC), is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA), decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN. We show that CsA-treated mice exhibit impaired production of the chemoattractant chemokines CXCL2 and CXCL1, decreased intrarenal recruitment of neutrophils, and greater susceptibility to UPEC than vehicle-treated mice. Strikingly, renal expression of Toll-like receptor 4 (Tlr4) and nucleotide-binding oligomerization domain 1 (Nod1), neutrophil migration capacity, and phagocytic killing of E. coli were significantly reduced in CsA-treated mice. CsA inhibited lipopolysaccharide (LPS)-induced, Tlr4-mediated production of CXCL2 by epithelial collecting duct cells. In addition, CsA markedly inhibited Nod1 expression in neutrophils, macrophages, and renal dendritic cells. CsA, acting through inhibition of the nuclear factor of activated T-cells (NFATs), also markedly downregulated Nod1 in neutrophils and macrophages. Silencing the NFATc1 isoform mRNA, similar to CsA, downregulated Nod1 expression in macrophages, and administration of the 11R-VIVIT peptide inhibitor of NFATs to mice also reduced neutrophil bacterial phagocytosis and renal resistance to UPEC. Conversely, synthetic Nod1 stimulating agonists given to CsA-treated mice significantly increased renal resistance to UPEC. Renal transplant recipients receiving CsA exhibited similar decrease in NOD1 expression and neutrophil phagocytosis of E. coli. The findings suggest that such mechanism of NFATc1-dependent inhibition of Nod1-mediated innate immune response together with the decrease in Tlr4-mediated production of chemoattractant chemokines caused by CsA may contribute to sensitizing kidney grafts to APN.     

The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy‐seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy‐proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.     

更昔洛韦在D+/R+肾移植术后预防CMV 感染的疗效观察

目的:观察D+/R+肾移植术后人群应用更昔洛韦预防巨细胞病毒感染的疗效与安全性。方法:我院2003年5月至2011年11月期间D+/R+同种异体肾移植患者93例,肾移植术后预防性应用更昔洛韦,对移植后1年内巨细胞病毒的感染率、感染发生的时间及有症状的CMV发病率进行以及用药后不良事件进行分析。结果:在D+/R+肾移植人群中预防性使用更昔洛韦后的感染率为28%,有症状的CMV发病率4.3%,病毒血症的平均感染时间为231.3 d,严重不良事件发生率为45.1%。结论:在D+/R+肾移植术后患者中预防性更昔洛韦能够预防CMV感染并且延长CMV初次感染时间,使D+/R+肾移植患者获益。     

Importance of complement 3 and mannose receptors in phagocytosis of Paracoccidioides brasiliensis conidia by Nramp1 congenic macrophages lines

Genetic factors influence susceptibility to Paracoccidioidomycosis, a Latin American endemic mycosis. The pattern of susceptibility of congenic mouse strains infected with Paracoccidioides brasiliensis resembles the pattern of the Nramp1 gene. Thus, congenic murine bone-marrow-derived macrophage lines B10R (Nramp1rGly169) and B10S (null Nramp1 protein expression, Nramp1sAsp169) were infected with P. brasiliensis conidia and compared, under opsonic and nonopsonic conditions. Opsonization increased the percentage of phagocytosis by both cell lines. B10R macrophages exhibited a higher percentage of cells with associated conidia and higher number of conidia per macrophage than B10S. Heat-inactivation and EDTA treatment of serum used for opsonization, and treatment of macrophages with anti-complement receptor 3 (CR3) decreased phagocytosis by both cell lines. alpha-methyl-d-mannoside reduced phagocytosis by B10R macrophages, suggesting that the mannose receptor participates in phagocytosis by these cells. The CR3 expression was similar on both cell lines and B10R expressed more mannose receptors, but neither cell line expressed CR1. IFNgamma decreased the conversion of conidia to the yeast form of P. brasiliensis in B10R, but not in B10S macrophages.     

Heterosis and reselection for pyrethroid resistance trait maintenance in the lady beetle Eriopis connexa (Germar)

Exposure of Eriopis connexa (Germar) to pyrethroid residues in agroecosystems has resulted in selection for resistance (R). Pyrethroid resistance allows E. connexa to survive lambda-cyhalothrin applications. Following a field release of E. connexa, development of resistance in an incipient population may depend on three major factors such as the maintenance of: (i) selection pressure, (ii) frequency of mating with susceptible phenotypes (S) and (iii) differential reproductive performance due to the fitness costs associated with resistance. To investigate the potential effects of these three factors on the development of pyrethroid resistance by progeny of field released E. connexa, our experiments included panmictic mating between R and S phenotypes, followed by descendant rearing with and without insecticide selection pressure, reselection and determination of resistance levels. In addition, we measured the reproductive performance of the parental R and S phenotypes and their descendants to assess the cost of resistance after crossing and reselection. Survival of R × S descendants exposed to lambda-cyhalothrin was reduced across successive generations in the absence of selection pressure, but still enhanced after four generations indicating the persistent presence of resistant phenotypes in the population. Under selection pressure with exposure to lambda-cyhalothrin applied at label rates, descendant survival was >50%. Fecundity and survival were higher in the first-generation of crossed R × S females, but higher fecundity was not sustained after reselection. Adults of the R population exhibited a fitness cost, reduced longevity, when compared to S phenotypes and R × S crossed populations. Therefore, resistance maintenance in E. connexa after release will depend on selection pressures imposed by insecticide exposure. In the absence of selection pressure, the phenotype for resistance was reduced, but not completely lost. Further, resistant phenotypes can be reselected following insecticide exposure and this can explain, in part, the high frequency of field-evolved resistance to lambda-cyhalothrin in E. connexa.     

Surface phagocytosis of Staphylococcus epidermidis and Escherichia coli by human neutrophils: serum requirements for opsonization and chemiluminescence

We examined the serum requirements for surface phagocytosis of Staphylococcus epidermidis and Escherichia coli and for the subsequent chemiluminescent response of human neutrophils. Substantial surface phagocytosis of S. epidermidis occurred in the absence of opsonins, although the presence of 10% pooled or heat-inactivated serum significantly increased phagocytosis. There was no significant difference between these opsonins, indicating that surface phagocytosis of S. epidermidis did not require complement. Unopsonized E. coli were not as readily phagocytized as S. epidermidis (33% versus 57%). In contrast to S. epidermidis optimal phagocytosis of E. coli required complement as 10% heat inactivated donor serum (HHS) was significantly less effective as an opsonin than 10% pooled healthy donor serum (PHS). The time kinetics for phagocytosis of each organism were similar, with most of the phagocytosis occurring in the first 10 min. The chemiluminescent response of neutrophils produced discrepant results. Maximal chemiluminescence was observed when neutrophils were stimulated with bacteria opsonized in PHS. The response to HHS-opsonized bacteria was less, and chemiluminescence to unopsonized bacteria was only marginally higher than the control, even though there was relatively good phagocytosis. These results define the opsonic requirements for surface phagocytosis of S. epidermidis and E. coli and indicate that although complement may not be required for phagocytosis, it is necessary for generation of a maximal oxidative burst, and thus may be essential for efficient intracellular killing.     

Surface phagocytosis of Staphylococcus epidermidis and Escherichia coli by human neutrophils: serum requirements for opsonization and chemiluminescence

Abstract We examined the serum requirements for surface phagocytosis of Staphylococcus epidermidis and Eschericia coli and for the subsequent chemiluminescent response of human neutrophils. Substantial surface phagocytosis of S. epidermidis occured in the absence of opsonins, although the presence of 10% pooled or heat-inactivated serum significantly increased phagocytosis. There was no significant difference between these opsonins, indicating that surface phagocytosis of S. epidermidis did not require complement, Unopsonized E. coli were not as readily phagocytized as S. epidermidis (33% versus 57%). In contrast to S. epidermidis optimal phagocytosis of E. coli required complement as 10% heat inactivated donor serum (HHS) was significantly less effective as an opsonin than 10% pooled healthy donor serum (PHS). The time kinetics for phagocytosis of each organism were similar, with most of the phagocytosis iluminescent response of neutrophils produced discrepant results. Maximal chemiluminescence was observed when neutrophils were stimulated with bacteria opsonized in PHS. The response to HHS-opsonized bacteria was less, and chemiluminescence to unopsonized bacteria was only marginally higher than the control, even though there was relatively good phagocytosis. These results define the opsonic requirements for surface phagocytosis of S. epidermidis and E. coli and indicate that although complement may not be required for phagocytosis, it is necessary for generation of a maximal oxidative burst, and thus may be essential for efficient intracellular killing.     

Sebum Excretion in Acromegaly

The sebum excretion rate (S.E.R.) was measured in 20 patients with acromegaly. Eleven were untreated at the time of the measurement and nine had previously undergone surgical hypophysectomy or had received pituitary irradiation by yttrium-90 or radiotherapy. In five patients the S.E.R. was measured before and after such treatment. The mean S.E.R. in the untreated acromegalics was much greater than in a normal population and decreased significantly after successful pituitary ablation. No significant decrease in mean S.E.R. occurred in the group of patients with a poor clinical response to ablation. The correlations between S.E.R. and log serum growth hormone, plasma 11-hydroxycorticosteroid levels, and heel-pad thickness were significant, but there was no significant correlation between S.E.R. and serum protein-bound iodine levels. This suggests that the changes in S.E.R. were due to pituitary ablation but could not necessarily be attributed solely to changes in growth hormone, thyroid-stimulating hormone, or adrenocorticotrophic hormone. The association between the clinical state of the acromegaly and the S.E.R. was better than the association between acromegaly and serum growth hormone. We conclude that the S.E.R. is a useful addition to the clinical and endocrinological data used in assessing acromegaly.     

A novel pleiotropic mutation in Escherichia coli K12 which affects transduction, transformation and rates of mutation.

A mutant strain of Escherichia coli K12, R2721, has been shown to differ from its parent strain, S491, in four associated phenotypic characters as a result of a single mutation. This strain did not give recombinants with DNA transduced by bacteriophage PI or bacteriophage Mu, nor transformats after exposure to R factor DNA: lysates of bacteriophage PI grown on this strain did not appear to contain any transducing particles when tested on normal recipients. Moreover, the reversion rates, both spontaneous and ultraviolet-induced, for two auxotrophic markers were reduced. The frequency of revertants was at least two orders of magnitude lower in cultures of R2721 than in cultures of S491I. Many of the rare revertants for one or other of the auxotrophic markers were found to have regained normal reversion frequencies for the other marker and for the capacity to be transduced. In all other respects, recombination in R2721 appeared normal, the frequency of chromosomal mobilization by and F' factor was unaffected and normal yields of recombinants were obtained from matings with Hfr strains. The only circumstance in which transduction of R2721 was observed was when the capacity to ferment galactose was selected and PI had been grown on a strain carrying lambdadgal when, presumably, integration was effected by the phage-coded gene products. The mutation has been located on the E. coli chromosone map between tonA and pro and has been given the symbol tdi (transduction inhibition). Double mutants, (tdi recA) and (tdi recB), have been isolated and show no unexpected properties.     

Phagocytosis of E. coli by renal tubular epithelia

Despite significant advances in our understanding or renal tubular cell function, the in vivo handling of E. coli by renal tubules has not been previously investigated. The present studies were, therefore, designed to study this aspect of nephron function. Live and dead E. coli and vehicle alone were microinjected into the proximal tubular lumen of a single nephron of rats, and the microinjected tubules were morphologically studied at one-half, two, four, and six hours after. The bacteria initially contacted the luminal cell membrane. The luminal cell membrane adjacent to the bacteria subsequently invaginated, and both live and dead E. coli eventually became internalized into the tubular epithelial cytoplasm. Since dead E. coli are unlikely to invade the cells, their intracytoplasmic localization is a result of tubular epithelial phagocytosis. Similar microinjections of dead E. coli together with rat erythrocytes revealed a preferential phagocytosis of dead E. coli. Examination of the microinjected nephron with dead E. coli 48 hours after also demonstrated a development of microscopic interstitial nephritis surrounding the microinjected tubule. In conclusion, the renal tubular epithelia of the proximal and distal segments of rat nephron have phagocytic potential for E. coli which are further capable of inducing an inflammatory reaction around the microinjected tubule.     

Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.     

Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats

The effects of high-sodium (HS) and normal-sodium (NS) diets on ovarian hormone modulation of mean arterial pressure (MAP) were examined in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Ovariectomy increased MAP (OVX-Sham) to a greater extent in DS rats maintained for 2 wk on a HS (22 mmHg) compared with a NS (6 mmHg) diet. Ovariectomy had no effect on MAP in DR rats on NS but did increase MAP in rats on HS (10 mmHg) diets. On HS diets, glomerular filtration rate (GFR) was 36% less in the DS-Sham than DR-Sham animals; ovariectomy increased GFR in both strains by 1.4-1.5-fold; glomerular angiotensin II type 1 receptor (AT(1)R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT(1)R densities by 1.3-fold in DR rats but had no effect in DS rats; 17beta-estradiol (E(2)) downregulated adrenal AT(1)R densities in both strains on either diet; ovariectomy reduced estrogen receptor-alpha (ER-alpha) protein expression in the renal cortex by 40-50% although renal ER-alpha expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E(2) treatment, suggesting that E(2) deficiency mediates the effects of ovariectomy on MAP, GFR, AT(1)R densities, and renal ER-alpha protein expression. In conclusion, ovariectomy-induced increases in MAP are augmented by HS diet in both strains, and this effect is not mediated by a reduction in GFR. Aberrant renal AT(1)R regulation and reduced renal ER-alpha expression are potential contributors to the hypertensive effects of E(2) deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E(2) deficient, such as postmenopausal women.     

Fabry disease: twenty novel alpha-galactosidase A mutations and genotype-phenotype correlations in classical and variant phenotypes

BACKGROUND: Fabry disease (OMIM 301500) is an X-linked inborn error of glycosphingolipid metabolism resulting from mutations in the alpha-galactosidase A (alpha-Gal A) gene. The disease is phenotypically heterogeneous with classic and variant phenotypes. To assess the molecular heterogeneity, define genotype/phenotype correlations, and for precise carrier identification, the nature of the molecular lesions in the alpha-Gal A gene was determined in 40 unrelated families with Fabry disease. MATERIALS AND METHODS: Genomic DNA was isolated from affected males or obligate carrier females and the entire alpha-Gal A coding region and flanking sequences were amplified by PCR and analyzed by automated sequencing. Haplotype analyses were performed with polymorphisms within and flanking the alpha-Gal A gene. RESULTS: Twenty new mutations were identified (G43R, R49G, M72I, G138E, W236X, L243F, W245X, S247C, D266E, W287C, S297C, N355K, E358G, P409S, g1237del15, g10274insG, g10679insG, g10702delA, g11018insA, g11185-delT), each in a single family. In the remaining 20 Fabry families, 18 previously reported mutations were detected (R49P, D92N, C94Y, R112C [two families], F113S, W162X, G183D, R220X, R227X, R227Q, Q250X, R301X, R301Q, G328R, R342Q, E358K, P409A, g10208delAA [two families]). Haplotype analyses indicated that the families with the R112C or g10208delAA mutations were not related. The proband with the D266E lesion had a severe classic phenotype, having developed renal failure at 15 years. In contrast, the patient with the S247C mutation had a variant phenotype, lacking the classic manifestations and having mild renal involvement at 64 years. CONCLUSIONS: These results further define the heterogeneity of alpha-Gal A mutations causing Fabry disease, permit precise heterozygote detection and prenatal diagnosis in these families, and provide additional genotype/phenotype correlations in this lysosomal storage disease.     

Transforming activity of R- and Lac-plasmids of clinical strains of Gram-negative bacteria]

The isolated plasmid DNA of clinical strains of Gram-negative bacteria were shown to have transforming activity when E. coli strain 0600 and S. typhimurium strain LT-2 were used as recipients. The frequency of transformation depended on the recipient strain and the character of the plasmids. The presence of deletion mutants was revealed among the transformants. Such mutants occurred with varying frequency, most often in S. typhimurium strain LT-20; the reason for this phenomenon is at present under discussion. The transformation of plasmids controlling lactose splitting and their conjugation transfer into recipient S. typhimurium strain LT-2 is possible only under condition of using recipient (R+). The possibility of the formation of the cointegrate (R and lac plasmids) in recipient S. typhimurium strain LT-2 is discussed.     

Differences in adhesion, phagocytosis and virulence of clones from Entamoeba histolytica, strain HM1: IMSS

Orozco E., Suárez M. E. and Sánchez T. Differences in adhesion, phagocytosis and virulence of clones from Entamoeba histolytica, strain HM1: IMSS. International Journal for Parasitology15: 655–660. Clones isolated from Entamoeba histolytica, strain HM1: IMSS were tested for adhesion, phagocytosis and virulence after subculturing in liquid medium. Other clones were isolated from a subpopulation of strain HM1: IMSS, and highly phagocytic trophozoites were eliminated by irradiation, after incorporating bromodeoxiuridine into their DNA by phagocytosis of labelled bacteria. We thus obtained several clones from strain HM1: IMSS showing a different degree of phagocytosis. Some phagocytosis-deficient clones showed impairment in red blood cell adherence, while others showed a reduced intake of particles into their cytoplasm. The degree of phagocytosis always was associated with the virulence of the clone.     

Timing, conditions, and complications of post-operative conception and pregnancy in female renal transplant recipients

The aim of this study was to explore the timing, conditions, and complications of post-operative conception and pregnancy among female renal transplant recipients in China. A cohort of 25 female renal transplant recipients who subsequently had successful pregnancies was randomly selected from eight organ transplantation centers in China. In this cohort, there were 38 post-transplant conceptions and 25 live births. The effects of conception and pregnancy on renal function as well as any effects of transplantation on delivery, prematurity, and maternal and infant health were investigated. Out of 38 conceptions after transplantation, seven ended in spontaneous abortion, six in artificial abortion, and 25 in single births, seven of which were premature (28%). The growth and development of all of the infants were normal. All the 25 received artificial (formula) feeding. Six patients had to return to hemodialysis therapy at 1–41 months after conception due to reduced function of the transplanted kidney. It appears best for female renal transplant recipients to wait at least for 2 years post-transplant before pregnancy. We found no significant effect on fetal growth and development. The incidence of premature births among female renal transplant recipients was high which might have an effect on transplant renal function and maternal health. Breast feeding is not considered suitable for these patients and was therefore not studied.     

Interactions between oxidative stress and inflammation in salt-sensitive hypertension

The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.     

Schistosoma mansoni modulation of phagocytosis in Biomphalaria glabrata

Both short-term (3 hr) exposure of Biomphalaria glabrata snails (M-line and 13-16-R1) to Schistosoma mansoni (PR1) miracidia and in vitro incubation of parasite sporocysts with host hemolymph components altered host phagocytic ability. Hemocytes obtained from susceptible (M-line) snails that had been exposed to parasite miracidia for 3 hr showed reduced levels of phagocytosis of yeast cells in vitro compared to hemocytes from unexposed individuals. Incubation of whole hemolymph with sporocysts in vitro also reduced yeast phagocytosis in this susceptible strain. In contrast, resistant (13-16-R1) hemocytes showed increased levels of yeast phagocytosis after in vitro incubation with the parasite, and the opsonic properties of 13-16-R1 plasma were greater after exposure of snails to miracidia. These strain-specific effects of S. mansoni on host hemocyte phagocytosis and plasma opsonization were seen only when both plasma and hemocytes were present at the time of exposure to the parasite.     

Haematology and Biochemistry of Ankylosing Spondylitis

Forty men with ankylosing spondylitis have been reviewed clinically, radiologically, haematologically, and biochemically, and the results of the last two compared with a male group of rheumatoid patients and a control group. In the patients with ankylosing spondylitis the haemoglobin levels were much higher and the E.S.R. significantly lower than in the rheumatoid group, and the E.S.R. in the patients with ankylosing spondylitis was unrelated to disease activity as evidenced by pain. The alkaline phosphatase level was raised in 19 cases and in most was derived from bone. Though 10 patients had abnormal globulin levels, the albumin levels were normal, as was renal function in all cases.     

Effects of feeding endophyte-infected fescue seed on reproductive traits of male mice divergently selected for resistance or susceptibility to fescue toxicosis

Our objective was to determine whether consumption of endophyte-infected fescue seed affected male reproduction differently in a mouse line previously selected for susceptibility (S) to fescue toxicosis than in a line previously selected for fescue toxicosis resistance (R). For 8 weeks following weaning, 48 males per line were provided diets containing 50% of either endophyte-infected (E+) or endophyte-free (E-) fescue seed. Each male was then paired with a female for 1 week, with litter size and weight recorded from subsequent births. Males were then killed, testes and seminal vesicles were weighed, cauda epididymal sperm were collected and testis cross-sections were fixed. The E+ diet reduced litter size by 0.5 in mates of S males but increased it by 1.0 in mates of R males (line by diet interaction P=0.05). Testis traits were not affected by diet or the line by diet interaction. Sperm integrity was adversely affected by the E+ diet (P<0.01) but did not differ significantly between lines, nor were line by diet interactions important. In earlier work, the E+ diet reduced long-term reproduction by a larger amount in S- than in R-line mated pairs. Because the E+ diet had similar effects on reproductive traits in R and S males in the current experiment, we infer that the differential impact previously reported acted primarily through traits expressed in females.