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The striped snakeheadChanna striatais a highly nutritious and economically valuable food fish. Wild populations are declining due to habitat degradation and conversion as well as overexploitation. To promote sustainable use of this resource, a striped snakehead domestication program was initiated in 2013. Earlier research found that golden snail (Pomaceasp.) was suitable as a natural feed for the grow-out of striped snakehead juveniles. This study focused on the formulation of feed for fry, applying a fully randomised experimental method with 5 replicates. Each experimental unit (aquarium with aeration) contained four striped snakehead fry (total length 3.42 ± 0.21 mm). The feed treatments used commercial HI-PRO-VITE 782 feed, with golden snail flour added in 4 doses: A (0%), B (20%), C (25%), D (30%). Total length and weight were measured weekly; water quality and survival were monitored. Overall, the length-weight relation was allometric negative. In terms of both length and weight, growth was highest under treatment C and lowest under treatment A. Growth was significantly different between treatments: A and C for length and weight (analysis of variance with Tukey post-hoc test, α=0.05). Growth patterns and condition factor varied between treatments, with treatment C yielding better balanced growth compared to B (slower increase in length) and D (slower weight gain). Survival rate did not differ significantly between treatments. We conclude that enrichment of commercial feed (HI-PRO-VITE 782) with golden snail flour can improve striped snakehead fry growth, with 25% the most effective dose.

ResumeObjectif Evaluer le taux d’immunisation anti-erythrocytaire et anti-HLA dans les hemoglobinopathies. Patients et methodes Etude transversale (octobre 2009–mars 2010) concernant 83 patients suivis pour hemoglobinopathie. La recherche d’anticorps irreguliers est realisee par deux techniques : Coombs indirect et technique enzymatique sur carte gel. La recherche des anticorps anti-HLA de classe I est faite par la technique de lymphocytotoxicite complement dependante. Resultats L’âge moyen est de 30 ans (14–64 ans), le sex-ratio M/F est de 0,84. Il s’agit de 42 cas de syndromes drepanocytaires majeurs (29 drepanocytoses homozygotes et 13 drepano-thalassemies) et de 41 cas de syndromes thalassemiques (26 thalassemies majeures et 15 intermediaires). La frequence d’allo-immunisation anti-erythrocytaire est de 22,89 % sans difference entre les syndromes drepanocytaires et thalassemiques (7,31 %). La frequence d’auto-immunisation anti-erythrocytaire est de 24,8 %. Elle est plus elevee dans les syndromes thalassemiques (41,46 %) que dans les syndromes drepanocytaires (7,14 %) (p

As chemokines and adhesion molecules play major roles in the process by which leukocytes are recruited from the bloodstream into sites of inflammation, genetic variations in the production or activity of molecules may influence susceptibility to acute rejection episodes. This study sought to determine the impact of recipient monocyte chemoattractant protein-1 (MCP-1), chemokine receptor (CCR2, CCR5), and adhesion molecule (ICAM-1, PECAM-1 and L/E selectin) polymorphisms on acute rejection after renal transplantation. We selected 169 healthy blood donors and 173 renal transplant recipients for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. Using molecular methods DNA was genotyped for 11 polymorphisms of these inflammatory molecules genes. Results were stratified by the incidence of rejection episodes and by human leukocyte antigen (HLA) mismatching. No association was detected between adhesion molecule polymorphisms and the incidence of acute rejection episodes. However, a significant risk of acute renal loss was observed among HLA-identical recipients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence interval, 0.05 to 1.06; P = .035). In conclusion, the observed association of CCR2-64I with acute rejection episodes should be added to the spectrum of immunogenetic factors known to be involved in renal allograft rejection.

Allograft rejection is an immune response relying on the proliferation and the differentiation of T cells. CTLA-4 is a co-stimulatory molecule, expressed on activated T lymphocytes, which has been shown to play a crucial role in the down-regulation of T-cell activation. Herein, we have examined the impart of a genetic marker in the CTLA-4 gene on renal transplant outcomes. A cohort of 144 renal recipients and 100 healthy subjects were genotyped by the fragments analysis method using an automated sequencer. Patients were classified into two groups: Group I included 31 HLA-identical haplotype allograft recipients and Group II, 113 showing one or more HLA haplotype mismatches. Forty patients (27.78%) developed at least one acute rejection episode (ARE): 9 in Group I and 31 in Group II. Before transplantation, 20 patients were lymphocytotoxic antibodies (LCT) positive: 4 Group I, 2 of whom developed an ARE, and sixty in Group II, including 8 with an ARE. The occurrence of an ARE was associated with the presence of LCT before transplantation among the entire cohort of patients (P = .032) and among Group II (P = .037). The allelic frequencies of (AT)n polymorphism did not reveal significant differences between patients and controls. The most prevalent alleles were the 88 bp (51% in controls and 44.44% in patients) and the 106 bp (8% and 10.76%, respectively). We noticed an increase of the 120 bp allele frequency among patients who had undergone an ARE compared with those who did not display this complication (8.75% vs 3.85%). Likewise, among LCT-negative Group I, recipients the incidence of the 120 bp allele was higher in ARE than non-ARE patients. Although the differences were not statistically significant, we propose that the 120 bp allele of the CTLA-4 gene (AT)n microsatellite a predisposes to acute rejection episodes in renal transplantation.

The crystal structures of two peptides containing 1-aminocyclohexanecarboxylic acid (Acc6) are described. Boc-Aib-Acc6-NHMe · H2O adopts a β-turn conformation in the solid state, stabilized by an intramolecular 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The backbone conformational angles (φAib = – 50.3°, ψAib = – 45.8°; φAcc6 = – 68.4°, ψAcc6 = – 15°) lie in between the values expected for ideal Type I or III β-turns. In Boc-Aib-Acc6-OMe, the Aib residue adopts a partially extended conformation (φAib = – 62.2°, ψAib = 143°) while the Acc6residue maintains a helical conformation (φAcc6 = 48°, ψAcc6= 42.6°). 1H n.m.r. studies in CDCl3 and (CD3)2SO suggest that Boc-Aib-Acc6-NHMe maintains the β-turn conformation in solution.

The HLA-A, B and DR phenotypes of 109 unrelated Tunisian individuals have been determined. The HLA-A and B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Tunisians and Kabyles from North Africa. A high frequency of HLA-A23 and HLA-Bw50 was observed in Tunisians and all Arab populations. A very close similarity in HLA-DR antigen frequencies exists between Tunisians and European Caucasoids. Linkage disequilibria between alleles of HLA loci were examined; many instances of previously reported antigen associations were seen in Tunisians, together with a number of associations which have not been described elsewhere. Aw34B8 and A2DRw14 are suggested as being common haplotypes in Tunisians.

Resume Propos Le but de notre etude etait de calculer l’incidence des syndromes lymphoproliferatifs (SLP) observes apres transplantation renale et d’etudier leurs particularites cliniques et leur impact sur la survie des malades et des greffons. Malades et methodes La population etudiee etait constituee de 316 transplantes de rein durant une periode de 20 ans. L’incidence etait calculee en rapportant le nombre des SLP sur la duree totale de suivi de tous les maladies ; la frequence cumulee est calculee selon la methode actuarielle. Resultats Sept cas de SLP ont ete diagnostiques durant un suivi cumule de 2202 ans, soit une incidence annuelle de 0,32 % (IC = 95 % : 0,30–0,34). Cette incidence etait de 0,81 %, (0,70–0,92), chez les receveurs de rein de cadavre et de 0,25 %, (0,23–0,27), chez les transplantes a partir de donneurs vivants (NS). Le diagnostic du SLP a ete porte apres un delai moyen de 3,22 ans (7,4 mois a 7,7 ans) et correspond a un lymphome B a grandes cellules dans six cas. Le traitement comportait toujours l’arret des immunosuppresseurs. Une remission complete a ete observee chez quatre malades ; trois malades sont decedes, soit un taux de mortalite de 6,1 % par an, contre 2,8 % chez les autres malades non atteints de SLP (NS). L’incidence annuelle de retour en dialyse etait de 6,1 % contre 3,1 % chez les autres malades (NS). Conclusion Chez nos malades, l’incidence annuelle des SLP est de 0,32 % par an. La survenue de cette complication tend a augmenter les taux de mortalite et de retour en dialyse d’ou l’interet des mesures preventives comportant, entre autres, la prevention des infections virales et l’adaptation du traitement immunosuppresseur.

The Gypsy is a ubiquitous figure in British literature, often functioning as a symbol of escape from the dominant social mores governing sex and gender roles and the ownership of capital. While in such nineteenth-century works as Jane Austen's Emma and Charlotte Bronte's Jane Eyre these associations are implicit, in the early twentieth century in the works of D. H. Lawrence (The Virgin and the Gypsy) and Virginia Woolf (Orlando), the functions of the Gypsy figures are comparatively overt and give considerable insight into British constructions of Romani identity. This paper examines the contrast between Victorian and Modernist representations of the Gypsy and the transformation in the way Gypsy identity is represented by non-Romani writers in the twentieth century.

Polymorphism of the gene encoding components of the renin-angiotensin-aldosterone synthase system (RAAS) represents an area of intense research of cardiovascular disease associations. Numerous studies have addressed the role of RAAS gene polymorphisms in the development and progression of renal disease. Also, it has been reported that patient with ACE (DD) and angiotensinogen AGT (TT) genotypes are associated with chronic allograft dysfunction (CAD). We investigated the effects of gene polymorphisms of the renin-angiotensin-aldosterone system in renal transplant patients (81 males and 50 females; mean age 29.6+/-10.2 years). Genotypes were determined using polymerase chain reaction sequence specific primers and PCR followed by RFLP analysis. Renal allograft recipients with chronic allograft dysfunction had significantly higher frequencies of the MM genotype than those without CAD (P0.05). The other genetic polymorphisms of the RAAS were not associated with CAD. This study proves that determination of AGT M235T genotype before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction.

Evaluate the anti-erythrocyte and anti-HLA immunization rates in hemoglobinopathies.Cross-sectional study (October 2009-March 2010) on 83 patients followed for hemoglobinopathies. The irregular antibodies research is realized by two techniques: indirect Coombs and enzymatic technique on gel cards. The search for anti-HLA class I antibodies is done by complement dependent lymphocytotoxicity.The mean age was 30 years (14-64 years), the sex ratio M/F is 0.84. Our series included 42 cases of sickle cell disease (29 homozygous sickle cell anemia and 13 sickle-thalassemia) and 41 cases of thalassemia syndromes (26 major and 15 intermediate). The anti-erythrocyte alloimmunization rate is 10.84% without difference between thalassemia syndromes and sickle cell disease. The autoimmunization rate (22.89%) is higher in thalassemia syndromes (41.46%) than in the sickle cell disease (7.14%) (P0.001). The anti-HLA immunization rate is 31.6% without difference between thalassemia syndromes and sickle cell disease. The young age, transfusion at a young age and the total number of transfusions are the factors that increase the risk of anti-erythrocyte autoimmunization. No clinicobiological parameter does influence the anti-erythrocyte and anti-HLA alloimmunization. There is no significant association between anti-erythrocyte and anti-HLA immunization.The erythrocyte and anti-HLA anti-immunization rates are high in our series. Preventive strategy is needed to ensure optimal blood safety.

Despite initiatives to increase cadaveric donation, there is still a shortfall in donor organs. Kidneys from living donors now makes a significant contribution to increasing the number of organs available for transplantation in Tunisia. We performed a retrospective study of 405 kidney transplantations, including 321 (79.3%) from living donors performed from June 1986 to December 2007. We obtained information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%), whose mean age at the time of donation was 42.3 ± 12.2 years. Twelve (8.22%) perioperative complications occurred: wound infections (n = 4), pneumothorax (n = 4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean follow-up period was 117.4 ± 74.4 months. Hypertension occurred in 42 donors (25.9%) with mean values of 134 ± 20 for systolic and 79 ± 10 for diastolic blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria, 0.08 ± 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of whom developed chronic renal failure requiring dialysis at intervals of 36 and 84 months. In both cases, we diagnosed a familial form of focal segmental glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation due to senility. The relatively favorable outcomes suggest that living-donor kidney transplantation is an acceptable approach, in view of the superior results it yields in recipients. However, efforts to increase the number of cadaveric donors in Tunisia should be made. It is also important to develop a registry of long-term kidney function after kidney donation.

CTLA-4 and CD28 are T lymphocyte receptors involved in the regulation of T-cell activation. Allograft rejection is an alloimune response which is strongly dependent on T-cell proliferation. Thus, we examined the relationship between CTLA-4 and CD28 gene polymorphisms and renal transplant outcomes. We genotyped 141 renal recipients and 229 healthy controls using PCR-SSP methods for the (-318) C/T polymorphism in the promoter region of the CTLA-4 gene and IVS3 (+17) T/C on intron 3 of the CD28 gene, and by PCR-RFLP method for exon 1 (+49) A/G and CT60 G/A within the 3'-untranslated region (UTR) of the CTLA-4 gene. Patients were classified into two groups: Group I included 23 HLA-identical haplotype allograft recipients and group II, 118 recipients with one or more mismatches in HLA haplotypes. Thirty-six patients developed at least one acute rejection episode (ARE). No significant differences were observed between the genotypes or the allele distribution between ARE and non-ARE patients. However, in group I, (+49) A and CT60 (G) allele frequencies were lower in patients with ARE than those without ARE (0.100 and 0.400 vs 0.361 and 0.722 respectively). However, the difference was not significant. Our study suggested that these alleles may confer protection against renal allograft loss.

Studies looking at the type of pretransplantation renal replacement therapy on graft and patient survivals after kidney transplantation have produced conflicting results. Therefore, we studied the effect of pretransplantation dialysis modality (peritoneal dialysis [PD] or hemodialysis [HD]) on transplant outcomes. We performed a retrospective study of 78 patients (39 PD and 39 HD) who had their first renal transplantation between January 1986 and December 2004. Comparisons between groups were made using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Comparisons between actuarial curves of patient and technique survivals used log-rank tests. The percentages of recipient males, cadaveric donors, transplant-induced diabetes, mean period of dialysis, mean transplantation follow-up, mean duration of first hospital stay, first infection, acute tubular necrosis, and acute rejection episodes were not significantly different among PD versus HD patients, whereas recipient and donor mean ages were significantly higher in HD and PD patients, respectively. There were no differences in graft and recipient survivals among PD versus HD patients. After kidney transplantation, there was no difference between PD and HD patients concerning percentages of infection, acute tubular necrosis, acute rejection episodes or graft and recipient survivals.

Arterial hypertension often present after kidney transplantation is of multifactorial origin. The aim of this study was to determine the role of donor and recipient factors in the development of hypertension after renal transplantation. We retrospectively analyzed the data of 280 patients transplanted between 1985 and 2005, who still had functioning grafts at 1 year after transplantation. We recorded donor and recipient parameters. One hundred eighty-seven patients (66.8%) were hypertensive. Upon multivariate analysis of recipient factors, pretransplant hypertension (odds ratio) [OR]: 8.5, 95% confidence interval [CI]: 4.5 to 16.1); serum creatinine level130 micromol/L at 6 months (OR: 2.5, 95% CI: 1.3 to 4,7), male gender (OR: 2.02, 95% CI: 1.2 to 3.4), and chronic rejection (OR: 2.4, 95% CI: 1.2 to 4.7) were independent predisposing factors. Among donor factors, age was significantly associated with arterial hypertension upon univariate analysis. In conclusion, recipient factors, especially pretransplant hypertension, contribute to the disorder in renal transplant patients.

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

To investigate the association between kidney transplant rejection and the polymorphisms of CTLA-4 gene exon 1(+49) and promoter (−318), genomic DNA of 70 renal transplant recipients and 110 healthy blood donors were genotyped by PCR-RFLP and PCR-SSP, respectively. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2, 37 one haplo-identical recipients. Thirty-one recipients experienced an acute rejection episode: 10 in G1 and 21 in G2. Ten G2 patients developed chronic allograft dysfunction (CAD). Allelic frequencies and genotype distribution were similar among patients and controls. CTLA-4 exon 1 genotype A/A and CTLA-4 promoter genotype C/C were significantly higher among G2 patients with CAD than without CAD (P < .01). The distribution of CTLA-4 exon 1-promoter genes did not reach significance between graft recipients and controls. The genotype frequency of (G/G-C/C) was increased among controls (42.72%) compared with graft recipients (G1 and G2; 35.71%). CTLA-4 polymorphisms gene were associated with susceptibility to chronic allograft dysfunction.

To investigate the relationship between the soluble HLA-G (sHLA-G) and the appearance of acute renal rejection (AR) episodes we have quantify in this study the level of sHLA-G by enzyme-linked immunosotrbent assay in 42 kidney transplant patients classified in two groups: G1: 17patients with acute rejection (AR+) and G2: 25 patients without AR (AR-). To establish our normal sHLA-G ranges, serum samples from 18 healthy controls were tested. Pre-transplantation sHLA-G levels were significantly increased in patients (mean +/- standard error of the mean, 60.48 +/- 12.18 units/ml) than healthy subjects (19.11 +/- 4.9 units/ml) (p = 0.001). Although the difference was not statistically significant, G1 patients (AR+) revealed lower levels of sHLA-G (mean +/- standard error of the mean, 31.25 +/- 6.71 units/ml) compared to G2 patients (AR-) (53.43 +/- 1721 units/ml). Nevertheless, the course of total sHLA-G levels was nearly identical in patients with and without rejection. Nonparametric analysis revealed that pre-transplantation levels of sHLA-G18.00 units/ ml (sensitivity: 87.8% and specificity of 72.2%) were not related to rejection. Also, multivariate analysis regarding anti-HLA antibody status, recipient age and gender showed that sHLA-G could not be an independent risk factor for renal graft rejection. However, a higher sera levels of sHLA-G seemed to contribute to better kidney allograft survival rate after 10 years of follow-up (significance tendency: p = 0.091) as shown by the survival analysis. Because of the small number of subjects studied, these results must be treated with caution. A much larger cohort of kidney transplant patients according to acute rejection would seem necessary to confirm these findings.

Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association, we analyzed polymorphisms of CCR5-∆32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518) in 173 renal transplant recipients and 169 healthy blood donors. The patients were classified in two groups: Group-1 (G-1) included 33 HLA-identical recipients and Group-2 (G-2) included 140 (one or more) mismatched graft recipients. Forty-two patients had developed acute rejection episodes (ARs): seven in G-1 and 35 in G-2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD). The genotypic and allelic frequencies of all polymorphisms studied did not reveal significant differences between patients and controls and among G-1 and G-2 recipients. However, a significant risk of acute renal transplant rejection was found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence inter-val [CI], 0.05-1.06; P = 0.035). There was no significant association of this polymorphism and CAD. In conclusion, the observed association of CCR2-64I with AR should be added to the spectrum of immunogenetic factors known to be involved in allograft renal loss.

The molecular and crystal structure of the synthetic, terminally blocked, model dipeptide t-Boc-L-Val-ΔAla-OMe (1) was determined by single-crystal X-ray diffraction. Crystal data for 1 are: C14H24N2O5, hexagonal, space group P65 (no. 170), a = 10.800(2) Å, c = 27.077(2) Å, and Z = 6. The crystal structure was solved by direct methods. The least-squares refinement led to R and Rw values of 0.077 and 0.075, respectively, for 1298 reflections with F ≥ 5 σ(F). The conformation of the Val residue is partially extended, while that of the ΔAla residue is trans, cis. The N-terminal protecting group is in the trans, trans disposition.

HLA-G is a particular non classical HLA class I molecule. Despite its tissue-restricted expression and low polymorphism, this molecule plays an important role in innate and adaptative immunity. The tolerogenic propriety of HLA-G makes it an immunomodulatory molecule acting in the early phases of conception, protecting fetal tissues from the maternal immune system. Immunomodulatory functions of HLA-G and the associations of this molecule with some pathological states are reported in this review. So, little amounts of soluble HLA-G or particular allelic expression of this molecule are associated with some pregnancy complications. HLA-G expression on tumor cells by preventing antitumor responses via a trogocytosis mechanism and regulatory T cells induction is associated with invasiveness and clinical evolution of some tumor types. HLA-G is also involved in the protection of the transplanted tissues from rejection. Revealing of new more functional homomultimeric isoforms of this molecule offers new insight in a better understanding of clinical and biological role of HLA-G.

C20H35N3O6 (Boc-Aib-DL-Pip-Aib-OMe, Boc = tert-butyloxycarbonyl, Aib = alpha-aminoisobutyric acid, Pip = pipecolic acid, OMe = methoxy), M(r) = 413.5, monoclinic, P2(1)/c, a = 18.055 (3), b = 15.048 (3), c = 17.173 (3) angstrom, beta = 91.7 (1)-degrees, V = 4663.8 (9) angstrom3, Z = 8, D(m) = 1.16, D(x) = 1.178 Mg m-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 0.081 mm-1, F(000) = 1792, T = 297 K. The final R value for 4925 [I greater-than-or-equal-to 3sigma(I)] reflections is 0.065 (wR = 0.067). The peptide backbone of the two independent molecules in the asymmetric unit is folded at the -Aib-Pip- sequence to form a type-I (I') beta-bend stabilized by a 1

The polymorphism of C4A and C4B genes was investigated in Tunisian patients with insulin dependent diabetes (IDDM) and compared to family members (sibs) and to healthy controls. Multiplex families were analysed. A significant increase in C4AQO (26.86% vs 6.90%) and C4BQO (40.29% vs 8.28%) phenotypes was noted in IDDM patients compared with controls. Using RFLP analysis, we confirmed the high frequency of C4 null alleles. We also observed that most of these alleles were genes deleted in IDDM patients (72.23% vs 20% for CA4QO and 74.07% vs 16.70% for C4BQO). A significant decrease in the C4B long (14.92% vs 67.12%) form of the gene was also demonstrated by RFLP analysis compared with controls. Two haplotypes were frequently associated with IDDM patients in whom the C4A and C4B were deleted genes.

To investigate the association between kidney transplant rejection and PTPN22 (protein tyrosine phosphatase non-receptor 22) polymorphism, genomic DNA of 175 renal transplant recipients and 100 healthy blood donors were genotyped by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2 included 142 with one or more HLA mismatches. Forty-nine patients developed an acute rejection episode (ARE): 8 in G1 and 41 in G2. The allelic frequencies of PTPN22 R620W revealed a significant difference between patients and controls. In fact, the W-allele was significantly more frequent in graft recipients than in blood donors (0.05 vs 0.01, P < .05). Furthermore, the frequency of this allele was increased in G1 patients with an ARE (0.188) compared with those without an ARE (0.040), but the difference was not statistically significant. Thus, we concluded that the PTPN22 W-variant allele could be involved in the susceptibility to acute allograft rejection in Tunisian kidney transplant patients.

This study examined the impact of graft function at the end of the first year after kidney transplantation on long-term graft survival. We analyzed the roles of serum creatinine (Scr) and other variables as predictors of graft survival among 235 adult kidney transplant patients. The subjects were divided into 3 groups according to their Scr at the end of the first year: group 1, Scr100 micromol/L; group 2, 100 micromol/Lor = Scror = 150 micromol/L; and group 3, Scr150 micromol/L. The annual rate of graft loss of 0.7% (95% confidence interval [CI], 0.63-0.77) in group 1, was lower than those in group 2 (2.1%; 95% CI, 2.02-2.18; P.0001) and group 3 (6%; 5.74-6.26; P.0001). Regression analysis showed the role of recipient age at the time of operation, and Scr level at the end of the first year to be independent predictors of graft loss. Graft survival was not influenced by any other studied parameter, including donor age, year of procedure, warm ischemia time, history of acute tubular necrosis, and occurrence of an acute rejection episode. We conclude that the 1-year Scr value predicts long-term renal graft survival, representing a simple, practical tool to identify recipients with an high risk for late graft failure.

Mannose-binding lectin (MBL), a collagen-like serum protein, is a key component of innate immunity. MBL binding to carbohydrates present on pathogens mediates lectin-dependent activation of the complement pathway. There is growing interest in the importance of innate immunity in host defense, particularly when adaptive immunity is compromised. Three single nucleotide polymorphisms (SNPs) of the MBL gene have been described in the first exon to be associated with low MBL serum concentrations as well as impaired MBL structure and function. Clinical studies have shown that these MBL SNPs are associated with increased susceptibility to infections, especially in immunocompromised patients. To investigate the association between acute kidney transplant rejection and polymorphism at codon 54 of the MBL gene, the DNA genomic of 133 renal transplant recipients and 117 healthy blood donors was analyzed by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified into two groups: group 1 included 32 HLA-identical recipients and group 2, 101 one haplo-identical recipients. Forty-eight (36.1%) subjects had developed one or more acute rejection episodes (AREs) within the first 6 months after transplantation: 9 in group 1 (28.12%) and 39 in group 2 (38.61%). The genotype and allele frequencies of (+54) MBL gene polymorphism among patients and controls did not reveal a significant difference. However, the frequency of MBL-B mutant allele was increased among patients with AREs compared with those without AREs: group 1 (0.167 vs 0.065) versus group 2 (0.205 vs 0.105). Although the difference was not significant, perhaps because of the small number of patients, the MBL at codon (+54) polymorphism could be involved in the susceptibility of Tunisian kidney transplant recipients to acute allograft rejection episodes.

The molecular structures of four protected isovaline- (Iva-)containing peptides to the pentamer level have been determined by x-ray diffraction. The peptides are t-Boc-Ala(S)-Iva-Ala-OMe (t-Boc : tert-butyloxycarbonyl; OMe : methoxy) and its (R)-Iva diastereomer, and t-Boc-[Ala-(R)-Iva]2-Ala-OH and its (S)-Iva diastereomeric methyl ester analogue. The two tripeptides are folded in an open type II beta-bend conformation. The fully developed right-handed 3(10)-helix formed by the (R) -Iva pentapeptide, which includes an unusual intramolecular (acid) O-H ... O = C (peptide) H bond, is partially unfolded (near the C-terminus) in the (S)-Iva pentapeptide. H-1-nmr and Fourier transform ir absorption studies suggest that in CDCl3 solution (a) the two tripeptides maintain a type II beta-bend conformation of comparable stability and (b) both diastereomeric pentapeptide sequences adopt a fully developed 3(10)-helix. A comparison with the preferred conformation of other extensively investigated C-alpha,alpha-disubstituted glycines is made and the implications for the use of the Iva residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.

HLA class II antigens are transmembrane glycosylated heterodimers composed of an α and a β chain. Several of these chains are highly polymorphic. The structural bases of the polymorphism are nucleotide acid substitutions which are situated in the first domain (exon II) of α and β genes. Specific sequences of these domains can be obtained by amplification of genomic DNA using the polymerase chain reaction. Polymorphic sites are recognized by restriction endonuclease treatment and separation of the DNA fragments by polyacrylamide gel electrophoresis. The resulting fragments of different lengths are used to identify different alleles. We used the above technique for typing the HLA-DQA1 alleles in 41 Tunisian diabetic patients. The frequency of DQA1 ∗ 0301 was greatly increased compared with the control group. This was in agreement with previously published data in Caucasian and Japanese insulin-dependent diabetes mellitus (IDDM) patients, while the significant increase in the frequency of the DQA1 ∗ 0501 allele was comparable with that of Caucasian IDDM patients but contrasted with a decrease in this allele in Japanese IDDM patients. Our results provide confirmation of the contribution of the DQA1 ∗ 0301 allele to disease susceptibility in a Tunisian population.

Cutaneous manifestations in renal transplant recipients are frequently represented by infections and cancerous lesions. However, dermatologic lesions secondary to autoimmune diseases are rare. We report a case of pustular psoriasis occurring after renal transplantation in a 31-year-old woman with a history of vitiligo. The patient was on hemodialysis for 2 years for undetermined chronic nephropathy. She received an HLA identical live related transplant from her brother. She was maintained on an immunosuppressive regimen of corticosteroids, azathioprine, and cyclosporine, which was replaced with mycophenolate mofetil because of neurotoxicity and azathioprine was stopped. Thirty-one months after renal transplantation, she developed pustular psoriasis which was treated with retinoids; she experienced a relapse and resistance to treatment despite the reintroduction of cyclosporine.

The aim of this study was to determine the epidemiological and the clinical characteristics of post-transplant lymphoproliferative disease (PTLD) and to evaluate its impact on patients' and grafts' survival.Three hundred and sixteen adult kidney recipients, transplanted between June 1986 and May 2006, were included. The incidence rates were calculated by dividing the number of different events (PTLD, death and graft-loss) by the total duration of follow-up. The survival rates and the cumulated frequency of PTLD were calculated according to the actuarial method.Seven recipients developed PTLD during a cumulated follow-up of 2202 years. The annual incidence was of 0.32% (95% CI : 0.30-0.34). It was of 0.81% (0.70-0.92) in recipients of kidneys from deceased donors, and of 0.25% (0.23-0.27) in patients transplanted from living donors (NS). The delay after transplantation for the diagnosis of PTLD ranged from 7.4 months to 7.7 years. PTLD was a B cell lymphoma in six cases and affected extra nodal sites in most of the cases. The treatment, comprising the cessation of immunosuppressive therapy in all cases, resulted in complete remission in four patients. Three patients died, representing an annual death rate of 6.1%, versus 2.8% in patients without PTLD (NS). The annual incidence of graft loss was 6.1% versus 3.2% among patients without PTLD (NS).PTLD was observed in 2.2% of our patients, with an annual incidence of 0.32%. It resulted in a decrease of both patients' and grafts' survivals. Preventive measures, including the improvement of the monitoring of immunosuppressive drugs and the prevention of viral infections, should be considered to reduce the risk of PTLD.

Late loss of kidney allograft, caused by immunological and non-immunological factors, remains a major problem in the field of transplantation. The aim of this study was to analyze the risk factors affecting long-term kidney graft survival more than 15 years. In a retro-spective analysis, clinical and laboratory variables and outcome of 330 patients who received a kidney transplant from living or cadaveric ABO-compatible donors at the Charles Nicolle Hospital, Tunis between 1986 and 2005 were recorded. A total of 58 patients who had follow-up data longer than 15 years constituted the subjects of this study. Patients were classified into two groups: Group I (Gp I), those who had kidney graft survival more than 15 years and Group II (Gp II), those who had kidney graft survival less than 15 years. There were 27 patients in Gp I (46.5%) and 31 in Gp II (53.5%). Graft loss in Gp II patients occurred in the first year in 15.1%, at three years in 35.5 %, at five years in 71 % and at 10 years in 83.9 %. The cause of graft loss was chronic graft dysfunction in 24 cases (77.4%), recurrence of the original kidney disease in three and graft versus host disease, urinary fistula, vascular rejection and graft rupture in one case each. There was no statistically significant difference between recipient and donor age or sex, duration on dialysis, number of acute rejections and infections between the two groups. Eleven of 27 patients (40.7 %) in Gp I and eight of 31 patients (25.8 %) in Gp II received total mismatched kidneys while the others received kidneys with varying degrees of match. The HLA DR2 matching was higher in Gp I (44.4 %) than in Gp II (29 %), whereas DR3 matching was higher in Gp II (45.2 %) in comparison with Gp I (11.1 %). Cross-match was negative in all our patients. Thirteen patients (48.1%) in Gp I and 17 (54.8 %) in Gp II.had a history of having episode(s) of acute rejection The number of acute rejection episodes did not contribute significantly to long-term graft survival in our series. Delayed graft function significantly lowered long-term graft survival; it was seen in seven cases in Gp I (25.9 %) versus 23 cases in Gp II (74.2 %) (X2=13.46). In our study, the long-term graft survival was similar to what is reported from developed countries. The main risk factors were HLA DR matching and delayed graft function.

C 13 H 14 N 4 O 3 , M r =274.3, orthorhombic, Pna2 1 , a=19.048 (6), b=10.507 (4), c=6.691 (4) A, V=1339. 1 A 3 , Z=4, D m =1.36 (flotation), D x =1.360 Mg m -3 , λ(Mo Kα)=0.7107 A, μ=0.933 cm -1 , F(000)=576, T=298 K, R=0.0839, wR=0.0643 for 773 observed reflections. The whole molecule is approximately planar, which can be seen from the values of the torsion angles about the non-rigid bonds; the molecular dimensions are in agreement with those found in analogous compounds

Orthorhombic, P2 1 2 1 2 1 , a=26.529, b=11.337, c=4.971A, Z=4, R=0.053. The torsion angles at the N-C β , C β -C α , and C α -C' bonds of β-Ala are close to the skew (+) trans, and skew(-) conformations, respectively. This is a common observation for linear peptides and derivatives of β-Ala, whereas the L-Ala residue is quasi-extended. No intramolecular hydrogen bonds are present

years, 56.5%; 31 to #45 years, 33.5%; and .45 years, 4%. Primary renal disease was chronic glomerulonephritis in 85 cases (42.5%), chronic pyelonephritis in 43 (21.5%), nephroangiosclerosis in 17 (8.5%), hereditary nephropathy in 11 (5.5%), and unknown in 44 (22%). Initial renal replacement therapy (RRT) was hemodialysis (HD) in 155 cases (77.5%), continuous ambulatory peritoneal dialysis (CAPD) in 24 (12%) and the two techniques combined in 21 (10.5%). For LRD, only first-degree relatives who gave their informed consent were accepted. All patients received ABO compatible and cross-match negative kidneys. At least 3 units of blood transfusions were given to 161 patients (80.5%) and cytotoxic antibodies were screened. All patients received a combination of prednisolone: 2 mg/kg/d on day 0, tapered to 0.2 mg/kg/d on day 90 and azathioprine at 125 mg/d. Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) was used as prophylactic treatment of graft rejection in 98 cases (48%) during the first 15 days. Cyclosporine was administered in 112 patients (56%) twice daily orally at 5 mg/d beginning on day 3 to 15 days in LRD transplants with one identical haplotype and after corticoresistant acute rejection episodes. The dosages were adjusted to clinical state and cyclosporine blood level (radioimmunoassay). Acute rejection episodes were treated with a combination of pulses of methylprednisolone and ALG/ATG in 75 cases. OKT3 was introduced in six cases when ALG/ATG failed to reverse the rejection. Mycophenolate mofetil was used in 11 cases with cyclosporine nephrotoxicity. The results were expressed as mean 6 standard deviation (SD). Comparisons were made with chi squared test for categorical variables and PLSD Fisher’ test for continuous variables. The survival rates were computed using the actuarial method. P , .05 was considered statistically significant. RESULTS The waiting time on dialysis was 28 6 22 months (1 to 119 months). For LRD, the donors were 96 (52.7%) siblings, 84 (46.2%) parents, and 2 children. HLA matching was 0 mismatches (MM) in 48 cases (26.4%) and 3 MM in 134 (73.6%). Their mean age was 38.6 6 13.4 (16 to 65) years. For CAD, HLA matching was 1 to 6 MM. The cytotoxic antibodies were positive in 27% of cases. Acute tubular necrosis (ATN) occurred in 26 cases (14.3%) of LRD and in 3 (16.7%) CAD. All those patients were hemodialyzed requiring 1 to 10 sessions, but all recovered. The difference between the two groups was not statistically significant (P 5 .07). The mean time of warm ischemia was 44 6 13 minutes for patients who have expressed ATN and 41.9 6 10.9 for those without ATN. The mean time of cold ischemia for CAD was 26.8 6 6 hours. Acute rejection was encountered in 16 (33.3%) cases of LRD with 0 MM, 80 (59.7%) cases of LRD with 3 MM, and 14 (77.8%) cases in the CAD group. The differences between the three groups were statistically significant (P , .0009). Complications Infectious complications were very common (86% of cases). Viral infections occurred in 40% of cases, mostly CMV (21%) and herpes (14%). No HIV infection was seen. Bacterial infections occurred in 60% of cases, mostly urinary tract infections (49%), septicemia (11.5%), and bronchopulmonary infections (5%). Six patients had scabies. Urologic complications occurred in 31 cases: 14 (7%) urinary leaks, 6 (3%) urinary stenosis, 2 ureteral compressions, 4 lymphoceles, 3 urinary lithiasis, and 2 urinary tuberculosis. Vascular complications were seen in eight cases: two arterial thrombosis, two venous thrombosis, three arteriovenous fistulae, and one perirenal hematoma. We noted recurrence of focal segmental glomerulosclerosis in six cases and glomerulonephritis de novo in two cases.

Linear IgA bullous dermatosis (LABD) of childhood is one of the chronic, non-hereditary blistering diseases of childhood in which clinical, histologic and therapeutic findings are similar to those associated with bullous pemphigoid (BP) and dermatitis herpetiformis (DH). LABD, however, can be distinguished from BP of DH by direct immunofluorescence (IF) demonstration of linear IgA deposits along the basement membrane zone (BMZ).During the period 1984-1993, 12 children with LABD were studied. Their ages ranged from 2 years to 15 years with a mean of 8.5 years. There were 7 males and 5 females. All children had a generalized eruption consisting of large tense blisters arising on normal skin. The blisters were more profuse on the lower trunk, pelvic region and limbs. Face and scalp were also affected. Occasionally, annular blister formation producing a "rosette" or "cluster of jewels" was found. Pruritus was frequent. Histological features of BP and DH were seen. Direct IF showed linear deposits of IgA at the BMZ in all cases. IgM, IgG, and complement were also seen in 8 cases. Four patients showed IgA BMZ antibodies by indirect IF. There were no symptoms of malabsorption and 3 patients had a mild bowel lesions. HLA studies showed the B8DR3 antigen in 7 of the 10 patients studied. Nine patients were treated with dapsone associated in 3 patients with prednisone. Three patients were controlled on oxacillin.LABD of childhood is a definite clinical entity. It is the most frequent chronic, non hereditary bullous disease of childhood in Tunisia. It is characterized by a self limiting blistering eruption which resembles BP or DH histologically and has a characteristic linear deposits of IgA at the BMZ of the skin. The treatment consisted on dapsone therapy, but 3 patients in our study were well controlled on oxacillin.

The frequency of HLA-DR antigens, as well as the prevelence of islet cell insulin autoantibodies and other autoimmunity disorders, were investigated in Tunisian patients with insulin-dependent diabetes mellitus (IDDM) and were compared with family members (sibs) and healthy control subjects. Cytoplasmic islet cell autoantibodies (ICA) were found in 79 of 175 (45.1%) patients with IDDM, in 23 of 126 (18.25%) unaffected first degree relatives of type I diabetes patients and in only two of 146 (1.3%) control subjects. In 79 ICA positive patients with IDDM, 46.8% presented other evidence of autoimmunity by testing for specific autoantibodies. Insulin autoantibodies were found in 86.9% of healthy ICA-positive sibs. A good correlation between HLA-DR3/DR4 heterozygous phenotypes and the presence of ICA in patients with IDDM and their unaffected sibs was observed in the Tunisian population. In fact, this heterozygous phenotype is found in 63.3% of ICA-positive diabetic patients and in 44.4% of ICA-positive unaffected sibs, whereas, HLA-DR3/DR4 antigens were noted in only 22.9% of ICA-negative diabetic patients and in no ICA-negative unaffected sibs. In these studies, we also summarized the distribution of HLA-DR antigens in patients with IDDM who presented autoimmune disorders other than ICA.

Kaposi’s sarcoma (KS) is a rare tumor but its incidence is higher following renal transplantation and especially among people of Arab, Jewish and Mediterranean ancestry. We report 3 cases among 120 recipients of renal transplants followed-up for at least 3 years.

Until June 1986 renal transplants for Tunisian patients were performed in Europe (2), but since then, a renal transplantation program has started at the Charles Nicolle University Hospital in Tunis. The responsibility for transplantation is shared between nephrologists, urologists and immunologists.

We report 4 cases of gelatin drop dystrophy corneal amyloidosis in two brothers and two sisters of the same family. The age of onset is between 1 and 10 years. The corneal signs are described at different stages of development. Lesions are initially asymmetrical. The typical is a subepithelial nodule starting in the center and then expanding to involve the whole cornea. There is no relationship between extension and outcome of the disease. Diagnostic is confirmed by histological examination. There was no consanguinity between parents and no other cases were found in the family. An immunological study with HLA typing was performed. All patients were treated with lamellar or transfixing keratoplasty with a follow-up of 2 to 5 years.

Haplotypes including HLA A, B, C, DR, and DQ were compared in a study population comprising 18 Tunisian multiplex families with diabetic children. Eighty haplotypes found in IDDM patients were compared with 148 haplotypes present in healthy family members. RFLP analysis showed that two DR subtypes were significantly more common in the diabetic haplotypes (DR4-DQw8: 82 per cent in IDDM members compared to 0 per cent in healthy members, p less than 0.001 and DR-Dw25: 56 per cent in IDDM patients compared to 16.7 per cent in healthy members, p less than 0.001) and these were in most cases found in haplotype combinations with HLA A2 B44 DR4 DRw53 and HLA A 24 B18 DR3 genes, respectively.