Essential oils improved weight gain, growth and feed efficiency of young dairy calves fed 18 or 20% crude protein starter diets.

The objective was to evaluate interactions between starter protein (180 vs. 200 g/kg, DM basis) and a mixture of essential oils (EOs; containing thymol, eugenol, vanillin, limonene and guaiacol) on growth, metabolic and ruminal functions of Holstein dairy calves. In a completely randomized 2 × 2 factorial design, 48 calves, 3 days old (averaging BW 42.7 ± 1.9 kg), were allocated into groups fed the following diets: (i) 180 g/kg CP with no EO (180P-NEO); (ii) 180 g/kg CP with EO (180P-EO); (iii) 200 g/kg CP with no EO (200P-NEO); and (iv) 200 g/kg CP with EO (200P-EO). The EO was supplemented as 1 g/kg of starter DM. Calves were fed ad libitum starter diet and were weaned at day 59 of age, but diets continued until day 80. There were no interactive effects of CP and EO on intake and growth. Pre-weaning feed efficiency tended to be increased for 200P-EO (p = .09). Average daily gain and feed efficiency during pre-weaning period as well as weaning weight were increased (p < .05) by EO, whereas wither height was increased by EO (p = .03) and tended to be increased for 200P vs. 180P (p = .06). Post-weaning blood urea nitrogen concentration tended to be lower in 180P vs. 200P (p = .08). Ruminal short-chain fatty acids concentration was greatest in 200P-EO. The EO increased both butyrate (p = .02) and propionate proportions (p = .01) and reduced acetate proportional ratio (p < .01). Ruminal ammonia-N was tended to be lower in calves-fed EO (p = .05) and was lower in those fed 180P vs. 200P (p < .01). In conclusion, supplementation of the starter diet with essential oil improved weight gain, growth and feed efficiency of dairy calves, irrespective of dietary protein content.

Nutrient intake, rumen fermentation and growth performance of dairy calves fed extruded full-fat soybean as a replacement for soybean meal.

The objective of this study was to investigate the effects of extruded full-fat soybean (ESB) as a replacement for soybean meal (SBM) on nutrient intake, rumen fermentation, and growth performance of dairy calves. A total of 45 male Holstein dairy calves (42.0±0.5 kg of BW) were randomly assigned to one of three experimental diets: (1) 0% ESB (Control): 35.3% SBM no ESB; (2) 25% ESB: 27.0% SBM+9.0% ESB; and (3) 50% ESB: 19.0% SBM+19.0% ESB. All calves were weaned on day 56 of age and remained in the study until day 70 of age. During the pre-weaning and overall periods, substituting of SBM with ESB had no effect on intake of starter feed, metabolizable energy (ME), CP and non-fiber carbohydrate (NFC). Compared with the control, 50% ESB resulted in a decrease in starter feed intake, and intakes of other nutrients including CP, NFC and ME during the post-weaning period. Substituting SBM with ESB decreased intake of C16 : 0 and increased intakes of n-9 C18 : 1, n-6 C18 : 2 and n-3 C18 : 3 during the pre-weaning, post-weaning and overall periods. Using ESB as a replacement for SBM did not affect average daily gain, feed efficiency, rectal temperature and fecal score over the trial periods. Compared with control, the rumen concentration of NH3-N decreased for 50% ESB on days 35 and 56 of age but not when compared with 25% ESB. Rumen pH, total volatile fatty acids concentrations, and the molar proportions of ruminal acetate, propionate and butyrate were not different among treatments. Body measurements were not affected by the treatments. In conclusion, substitution of SBM with ESB may improve nitrogen utilization efficiency in dairy calves but slightly reduce post-weaning starter intake with no negative outcomes on growth performance and rumen fermentation.

Effects of forage offering method on performance, rumen fermentation, nutrient digestibility and nutritional behaviour in Holstein dairy calves.

The potential effect of dietary forage supplementation on the performance and rumen development in dairy calves is well established. However, limited research has been directed to the comparative effects of forage offering methods on calf performance. The objective of the present study was to determine the effects of forage provision methods (total mixed ration or free choice) on the performance, nutrient digestibility, rumen fermentation and nutritional behaviour in newborn calves. Forty-five Holstein dairy calves (3 days of age and 41 ± 2 kg of body weight) were assigned to the following three groups (n = 15): (i) starter without forage provision (CON), (ii) starter supplemented with 10% alfalfa hay (AH) as a total mixed ration (AH-TMR) and (iii) starter and AH as a free-choice provision (AH-FC) for a period of 70 days. All the calves were offered 5 l of milk/day from day 3 to 50, and 2.5 l/day from day 50 until weaning on day 56. Dry matter intake (DMI) was greater (p < 0.01) in the AH-TMR and AH-FC treatments than in the CON during the pre- and post-weaning periods. Calves fed the AH-FC diet showed the highest post-weaning DMI among the treatments. The calves receiving ad libitum forage tended (p = 0.08) to increase crude protein digestibility and overall volatile fatty acids (VFA) concentrations in the rumen. No differences were observed among the treatments at the time spent on standing, lying, eating and performing non-nutritive oral behaviours. Compared to CON calves, animals in the AH-TMR treatment spent more time (p < 0.05) ruminating. In conclusion, our data suggest that forage supplementation in both forage offering methods increased total DMI, ruminal pH and ruminating time in dairy calves. Hence, there is no benefit in the free-choice provision of AH in dairy calves.

The effect of restricted milk feeding through conventional or step-down methods with or without forage provision in starter feed on performance of Holstein bull calves.

The objective of the current study was to examine whether step-down (STP) milk feeding method together with forage provision would improve performance, rumen fermentation, nutrient digestibility, blood metabolites, and structural growth of calves. Holstein bull calves ( = 40) were randomly assigned to 1 of 4 treatments in a completely randomized design with a 2 × 2 factorial arrangement. Treatments were 1) conventional (COV) milk feeding without forage provision (COV-NF), 2) COV milk feeding with forage provision, 3) STP milk feeding without forage provision, and 4) STP milk feeding with forage provision. Calves in the COV method ( = 20) received 5.5 L/d milk until d 56 of age followed by 2 L/d milk from d 56 to 59 of age. Calves in the STP method ( = 20) received 7 L/d milk until d 35, 4 L/d milk from d 35 to 48, and 2 L/d milk from d 50 to 59 of age. All the calves received the starter ration from d 3 of the study until d 74 of age. Forage-supplemented calves ( = 10/milk feeding method) received 15% alfalfa hay mixed with finely ground starter as a total mixed ration. All calves were weaned on d 60 of age and remained in the study until d 74. Regardless of the milk feeding method, the final BW (92.54 vs. 83.14 kg/d), starter intake (0.90 vs. 0.65 kg/d), total DMI (1.43 vs. 1.17 kg/d), and ADG (0.73 vs. 0.60 kg/d) were greater ( < 0.01) in forage-supplemented calves than those that received no forage during the preweaning, postweaning, and overall periods. Milk feeding method had no effect on ruminal pH, total VFA, acetate, or acetate:propionate ratio as well as body measurements. Ruminal pH and the molar proportions of acetate were greater ( < 0.05) in the forage-supplemented calves than those that received no forage during the pre- and postweaning periods. Regardless of forage provision, STP methods increased ( < 0.05) the postweaning numbers of monocytes and lymphocytes. Overall, there was no interaction between milk feeding methods and forage provision with respect to BW, DMI, G:F, apparent nutrient digestibility (DM, OM, and CP), and body measurements. The interaction of milk feeding method and forage provision was significant for the rumen concentration of butyrate ( < 0.05), with the highest concentration for the COV-NF treatment on d 35 of the study. In conclusion, independent of the milk feeding method, inclusion of 15% alfalfa hay in starter diets enhances the performance of dairy calves.

Effects of the step-up/step-down and step-down milk feeding procedures on the performance, structural growth, and blood metabolites of Holstein dairy calves.

The objective of this study was to compare the efficacy of the step-up/step-down (SUSD) and step-down (STP) methods of milk feeding on the performance, growth parameters, blood metabolites, and health of dairy calves. For this purpose, 45 Holstein male calves (3d of age and 41 ± 3 kg of body weight) were randomly assigned to one of the following milk feeding groups: (1) conventional (CONV; 4 L/d milk from d 1 to 52, and 2 L/d milk from d 53 to 56 of the study), (2) STP (6 L/d milk from d 1 to 29, and 4 L/d milk from d 30 to 45 of the study followed by feeding 2L/d milk from d 46 to 56 of the study), and (3) SUSD (6 L/d milk from d 1 to 5, 8 L/d milk from d 6 to 15, 10 L/d milk from d 16 to 35, 8L/d milk from d 36 to 42, 6 L/d milk from d 43 to 47, 4 L/d milk from d 48 to 52 of the study followed by feeding 2 L/d milk from d 53 to 56 of the study). Calves were weaned on d 56 and followed until d 70 of the study period. Animals had ad libitum access to the same starter ration during the entire study period (d 3 to 70). Starter intake, total dry matter intake, and average daily gain were greater in the SUSD calves than those in the CONV and STP treatments during the preweaning period. The SUSD procedure was found to increase body weight during the entire study and improved body length, wither height, heart girth, hip height, and hip width on d 56 and 70 of the study compared with the STP and CONV calves. The SUSD treatment increased blood glucose concentration on d 35 compared with CONV and STP procedures. The STP group had a higher starter intake than the CONV and SUSD animals. The STP animals exhibited a higher plasma concentration of total protein and BHBA than did the SUSD animals during the preweaning period. Neither the SUSD nor the STP procedure negatively affected the fecal score. In conclusion, the SUSD milk feeding procedure was found to improve the performance of dairy calves compared with the STP and CONV procedures. However, it appears that the STP procedure induces earlier reticulo-rumen developement in dairy calves than does the SUSD procedure.

Dose-responses of zinc-methionine supplements on growth, blood metabolites and gastrointestinal development in sheep.

The effects of zinc-methionine (Zn-Met) supplementation on growth, blood metabolites and gastrointestinal development were investigated in two experiments with sheep. The objective of Experiment 1 was to determine the effects of Zn-Met supplementation on hormones and metabolites involved in growth and energy balance regulation, while Experiment 2 aimed to determine the effects of Zn-Met on feed intake, body weight, gastrointestinal development and liver glycogen concentration in lamb. The animals were assigned to groups with different concentrations of dietary Zn-Met (0, 0.4, 0.8 and 1.2 g/day) in both experiments. In Experiment 1, feeding different doses of Zn-Met increased plasma insulin-like growth factor 1 (IGF-1) concentration, but it linearly decreased plasma growth hormone (GH). No differences were observed in blood cortisol, insulin and glucose concentrations among the treatments. In Experiment 2, addition of Zn-Met to the diets did not lead to changes in the body weights of the lambs. Both average daily gain and dry matter intake (DMI) increased linearly with increasing concentrations of dietary Zn-Met. Lambs receiving Zn-Met showed higher liver glycogen concentrations than the control. While significant increases were observed in the villus height and crypt depth in the duodenum and jejunum as a result of Zn-Met supplementation, no change was detected in blood glucose concentrations (p > 0.05). Our findings suggest that dietary Zn-Met may improve growth, energy balance and gastrointestinal development in sheep.

Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats.

Bariatric surgeries are hypothesized to produce weight loss and improve diabetes control by multiple mechanisms including gastric restriction and lower gut stimulation; the relative importance of these mechanisms remains poorly understood. We compared the effects of a typical foregut procedure, sleeve gastrectomy, (SG) with a primarily hindgut surgery, ileal transposition (IT), alone and together (SGIT), or sham manipulations, on food intake, body weight, gut hormones, glucose tolerance, and key markers of glucose homeostasis in peripheral tissues of adult male Sprague-Dawley rats (450-550 g, n = 7-9/group). SG, IT, and SGIT surgeries produced transient reduction in food intake and weight gain; the effects of SG and IT on intake and body weight were nonadditive. SG, IT, and SGIT surgeries resulted in increased tissue expression and plasma concentrations of the lower gut hormones glucagon-like peptide-1 and peptide YY and decreased plasma glucose-dependent insulinotropic peptide, insulin, and leptin concentrations. Despite transient effects on intake and weight gain, the SG, IT, and SGIT surgeries produced a significant improvement in glucose tolerance. In support of glycemic improvements, the protein abundance of key markers of glucose metabolism (e.g., GLUT4, PKA, IRS-1) in muscle and adipose tissue were increased, whereas the expression of key gluconeogenic enzyme in liver (G-6-Pase) were decreased following the surgeries. Therefore, our data suggest that enhanced lower gut stimulation following SG, IT, and SGIT surgeries leads to transient reduction in food intake and weight gain together with enhanced secretion of lower gut hormones and improved glucose clearance by peripheral tissues.

Genotyping of Echinococcus granulosus from domestic animals and humans from Ardabil Province, northwest Iran.

Cystic echinococcosis is endemic in Iran, particularly in Ardabil Province, where it causes health and economic problems. The genetic pattern of Echinococcus granulosus has been determined in most parts of Iran, except in this area. In the present investigation, 55 larval isolates were collected from humans (11), sheep (19), goats (4) and cattle (21). For analysis of the genetic characteristics of E. granulosus isolates, DNA sequencing of mitochondrial cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes was applied. Fifty isolates were successfully analysed, with 92% (46) and 8% (4) identified as G1 and G3 genotypes, respectively. The sequence analyses of the isolates displayed nine characteristic profiles in cox1 sequences and eight characteristic profiles in nad1 sequences. Based on these results, the sheep strain (G1 genotype) was the most prevalent in humans, sheep, goats and cattle. The buffalo strain (G3 genotype) was not only demonstrated in sheep (1 isolate) and cattle (1 isolate), but also for the first time in two human isolates. These findings will provide information for local control of echinococcosis.

Short communication: expression of peptide YY, proglucagon, neuropeptide Y receptor Y2, and glucagon-like peptide-1 receptor in bovine peripheral tissues.

The role of distal gut signals in control of feed intake and metabolism in cattle has received scant attention. Peptide YY (PYY) and glucagon-like peptide-1, which are secreted from enteroendocrine cells of the distal gut in monogastrics have several functions, including regulation of energy balance. However, little is known of the tissue expression of these peptides and their receptors in cattle. The aim of the current study was to characterize the tissue distribution of PYY, neuropeptide Y receptor Y2 (Y2), proglucagon (GCG), and glucagon-like peptide-1 receptor (GLP1R) in various peripheral tissues of cattle. Four male 7-wk-old dairy calves were euthanized and 16 peripheral tissues were collected. Conventional PCR and quantitative real-time PCR were performed to confirm tissue expression and quantify the transcript abundance in various tissues. The results of conventional PCR revealed that mRNA for both PYY and Y2 was detectable in the rumen, abomasum, duodenum, jejunum, ileum, and colon but not in other tissues. Quantitative real-time PCR data demonstrated that PYY mRNA was 2- to 3-fold greater in the pancreas, kidney, and heart relative to the liver. By conventional PCR, GCG mRNA was detected in the abomasum, duodenum, jejunum, ileum, and colon and GLP1R mRNA was expressed in all gut segments, pancreas, spleen, and kidney. Quantitative real-time PCR data demonstrated that, relative to transcript abundance in the liver, GCG mRNA was 4- to 40-fold higher from abomasum to colon, and GLP1R mRNA was 50- to 300-fold higher from the rumen to colon, 14-fold greater in the pancreas, 18-fold higher in the spleen, and 166-fold greater in the kidney. The tissue distribution of PYY, GCG, and their receptors observed in the current study is, in general, consistent with expression patterns in monogastrics. The predominant expression of PYY, Y2, and GCG in the gut, and the presence of GLP1R in multiple peripheral tissues suggest a role for PYY in controlling gut functions and for GLP-1 in regulating multiple physiological functions in cattle.

Effects of continuous lactation and short dry periods on mammary function and animal health.

The dry period is required to facilitate cell turnover in the bovine mammary gland in order to optimize milk yield in the next lactation. Traditionally, an 8-week dry period has been a standard management practice for dairy cows based on retrospective analyses of milk yields following various dry period lengths. However, as milk production per cow has increased, transitioning cows from the nonlactating state to peak milk yield has grown more problematic. This has prompted new studies on dry period requirements for dairy cows. These studies indicate a clear parity effect on dry period requirement. First parity animals require a 60-day dry period, whereas lactations following later parities demonstrate no negative impact with 30-day dry period or even eliminating the dry period when somatotropin (ST) is also used to maintain milk yields. Shortened dry periods in first parity animals were associated with reduced mammary cell turnover during the dry period and early lactation and increased numbers of senescent cells and reduced functionality of lactating alveolar mammary cells postpartum. Use of ST and increased milking frequency postpartum reduced the impact of shortened dry periods. The majority of new intramammary infections occur during the dry period and persist into the following lactation. There is therefore the possibility of altering mastitis incidence by modifying or eliminating the dry period in older parity animals. As the composition of mammary secretions including immunoglobulins may be reduced when the dry period is reduced or eliminated, there is the possibility that the immune status of cows during the peripartum period is influenced by the length of the dry period.

Differential gene expression of the toll-like receptor-4 cascade and neutrophil function in early- and mid-lactating dairy cows.

During early lactation, neutrophils display several reduced immune functions. Particularly, a delayed recruitment of neutrophils into the infected udder seems to be one of the underlying events involved in the severity of postpartum Escherichia coli intramammary infections. The purpose of this study was to analyze the effect of in vitro chemotaxis and diapedesis on the expression of toll-like receptor-4 (TLR4)-related genes in bovine blood neutrophils isolated from 10 early-lactating (EL) and 10 mid-lactating (ML) cows. Functional characterization of the neutrophil population was performed by measuring phagocytosis and production of reactive oxygen species (chemiluminescence). Messenger RNA was extracted from neutrophils, and the expression of TLR4 and associated genes in EL and ML cows was analyzed by reverse-transcription quantitative PCR. To study the effect of chemotaxis and diapedesis on the expression of genes of the TLR4 cascade, neutrophils were stimulated to (trans)migrate in response to C5a using in vitro models. Our salient findings were that both neutrophil migration in vitro and lactation stage induced significant changes in the expression of several genes of the TLR4 signaling cascade. Before migration, expression of TRAF6, ATF3, RELA, IL8, and C5aR were lower in EL than in ML cows. Diapedesis and chemotaxis induced an increase in expression of TLR4, ATF3, and IL8 in both EL and ML cows. Diapedesis resulted in a downregulation of Syk, a TLR4-associated gene, in ML cows. This study shows that the perturbations in neutrophil functions during EL are accompanied by modulation of TLR4 pathway genes. These data can contribute to the understanding of the mechanisms explaining the relationship between stage of lactation and risk of severe E. coli mastitis.

An integrated view on how the management of the dry period length of lactating cows could affect mammary biology and defence.

The dry period is necessary to facilitate cell turnover in the bovine mammary gland and to optimize milk production in the next lactation. An 8-week dry period has long been the golden standard of management for dairy cows. Genetic improvements and new management technologies have led to higher milk production and a need for re-evaluation of the dry period length. Over the last decade, dry period length has been proposed to be shortened or eliminated mainly from an economic point of view. However, the influence of modified dry period length on the immune defence of the bovine mammary gland and the occurrence of new intramammary infections has not yet been appreciated. The objective of this review is to discuss the bovine mammary gland biology, defence and systemic health when the dry period length is modified. Shortening or eliminating the dry period may minimize or remove the impact of milk accumulation at dry off, thereby lessening the immunodeficiency of the dam that is characteristic of this period. Composition of mammary secretions may change and the extent of tissue remodelling may be reduced when the dry period is reduced or eliminated. Additionally, impact of the dry period length on energy and nutritional status, and on hormonal and local regulatory factors, lead us to hypothesize that changing the dry period length might also affect the response to intramammary infection. It is concluded that there is a need to integrate mammary gland biology and defence mechanisms in studies dealing with modified dry period lengths.

Effects of short dry periods on performance and metabolic status in Holstein dairy cows.

To evaluate effects of different dry period lengths on milk yield, milk composition, and energy balance of dairy cows, 122 multiparous and primiparous Holstein dairy cows were used in a completely randomized experimental design with 56-, 42-, and 35-d dry period lengths. Actual dry period lengths for respective treatments (TRT) were 56 +/- 5.1 d, 42 +/- 2.1 d, and 35 +/- 2.7 d. Overall, cows in the 42- and 56-d TRT gained more body condition than those in 35-d TRT during the dry period; however, postpartum body condition score did not change substantially among the TRT. Although from 3 to 210 DIM, differences were not detected in the milk yield of multiparous cows between the 35- and 56-d TRT, primiparous cows in the 35-d TRT produced less milk than those in 56-d TRT. In primiparous cows, the milk production at wk 9, 10, and 11 of lactation was lower in the 35-d compared with the 56-d TRT. Primiparous cows in the 35-d compared with the 56-d TRT produced less milk protein. In the 35-d TRT, serum triglyceride concentration was greater in primiparous cows than in multiparous cows during the peripartum period. Among primiparous cows, those in the 56-d TRT had greater concentrations of nonesterified fatty acids than those in the 35-d TRT during the peripartum period. No significant differences were observed in concentrations of serum glucose, insulin, and insulin-like growth factor-I during early lactation among TRT. There was also no difference among TRT for incidence of metabolic disorders. Thus, this study indicates that shortening the dry period to 35 d may be beneficial in multiparous and overconditioned cows, but not in primiparous cows.

Cytotoxic T lymphocyte antigen-4 promoter variants in breast cancer.

CTLA4 is a coinhibitory molecule expressed mainly on activated T lymphocytes. To test the putative involvement of CTLA-4 in inhibitory state of immunity to breast cancer, we genotyped 283 patients and 245 healthy control subjects for -1722 T/C, -1661 A/G, and -318 C/T single nucleotide polymorphisms in the promoter region of the CTLA4 gene. There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Moreover, the incidence of the most frequent haplotype combination (TAC/TAC, T -1722, A -1661, C -318) was only slightly higher among healthy controls than patients (68.4 vs. 64.8%, P = 0.2). This haplotype combination was associated with lower stages of the disease (P = 0.0007), however, and higher estrogen receptor (ER) expression in patients (P = 0.006). Association with tumor prognostic or predictive factors was also observed with certain genotypes: the -1661 AA genotype was associated with lesser lymph node (LN) involvement (P = 0.017) and higher ER expression (P = 0.004), and the -318 CC genotype with lesser LN involvement (P = 0.007). These results suggest that CTLA4 promoter variants participate in the progression of breast cancer rather than in its initial development.

Heterozygosity in CTLA-4 gene and severe preeclampsia.

OBJECTIVE: One of the major complications of pregnancy, preeclampsia makes pregnancy termination inevitable in most cases. Similarities exist between the mechanisms that maintain normal pregnancy, allograft transplants, and, it is postulated, peripheral self-tolerance. In addition, the critical role of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) molecule in maintaining self-tolerance has been established. Therefore, the frequency of CTLA-4 A49G polymorphism was investigated in severe preeclampsia. PATIENTS AND METHODS: Genomic DNA extracted from mononuclear cells of the peripheral blood of 36 pregnant women with severe preeclampsia and 151 healthy women was analyzed. A49G polymorphism in position 49 of exon-1 of the CTLA-4 gene was studied by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method. RESULTS: The frequency of the GG genotype was 2 (5.6%) in patients and 19 (12.6%) in controls, while the frequency of the AA genotype was 4 (11.1%) and 60 (39.7%). Interestingly, the frequency of the AG genotype was significantly higher in preeclamptic than in healthy women from the general population (83.3% vs. 47.7%; P=0.0005). CONCLUSION: These data suggest that heterozygosity in the CTLA-4 A49G allele might be a predisposing factor for severe preeclampsia. Whether the observed association results from linkage imbalance with other loci on chromosome 2 or other polymorphisms of the CTLA-4 gene or even from a preferential transfer and/or expression of one allele from a heterozygous mother to the fetus will be the subject of future investigations.

Exon-1 polymorphism of ctla-4 gene in Iranian patients with Graves' disease.

Polymorphisms in ctla-4 gene have been shown to be associated with the Graves' disease (GD) susceptibility in different populations in the world. This study was undertaken to disclose the probable association of exon-1 polymorphism of ctla-4 with GD in Iranian patients. A49G polymorphism was investigated in 90 patients and 90 age/sex matched normal healthy controls, using PCR-SSCP and PCR-RFLP methods. Frequencies of AA, AG and GG genotypes among patients were found to be 21 (23.3%), 49 (54.5%) and 20 (22.2%) while these frequencies among healthy controls were 30 (33.3%), 53 (58.9%) and 7(7.8%), respectively. A significant increase of GG genotype and G allele was observed in patients (p = 0.012 and p = 0.025). In conclusion, consistent with the results of most other studies, the presence of a G allele in position 49 of ctla-4 exon-1 is associated with susceptibility to GD in Iranian population.

p53 gene alteration and protein expression in Iranian women with infiltrative ductal breast carcinoma.

Genetic alterations in the p53 tumor suppressor gene with or without protein overexpression have been reported to be associated with sporadic breast cancer. To assess the role of p53 in infiltrative ductal breast carcinoma among Iranian patients, p53 protein expression and p53 gene mutations were studied by immunohistochemical analysis and single-strand conformation polymorphism, respectively. The p53 protein was expressed in 25 out of 51 (49%) tumors and p53 gene mutations were detected in 17 out of 37 (46%) tested tumors. No significant correlation was observed between p53 gene mutations and p53 protein expression. There was no significant correlation between p53 abnormalities (mutation and expression) and tumor size, histological grade, nodal status, and progesterone receptor expression. However, a non-statistically significant trend of association (P=0.07) was observed between p53 gene mutations and lack of estrogen receptor. The high percentage of alterations both in p53 gene and protein among southern Iranian breast cancer patients suggests that p53 is probably one of the genes involved in sporadic breast cancer in this area.