Response of the chicken ovary to GH treatment during a pause in laying induced by fasting.

This study was undertaken to examine the effect of GH treatment during a pause in laying on (1) ovarian follicle formation, growth (folliculogenesis), and atresia; (2) follicle cell proliferation and apoptosis; and (3) mRNA expression of selected yolk-specific proteins in the chicken liver. A pause in egg laying was induced by food deprivation for 5 d, followed by feeding every other day, and then feeding daily from day 10 onward. Birds were divided into 3 groups: control (n = 18) fed ad libitum, subjected to a pause in laying (n = 18), and subjected to a pause in laying and injected every day with 200 µg/kg BW of chicken GH (chGH; n = 18). The liver, ovarian stroma, and follicles were isolated from the hens of each group on days 6 (ovary regression), 13 (ovary recrudescence), and 17 or 20 (ovary rejuvenated) of the experiment. The results showed that injection of chGH during fasting (1) increased the number of follicles <1 mm and proliferating cell nuclear antigen (PCNA)-positive (proliferating) cells in these follicles; (2) attenuated the expression of PCNA and survivin mRNA in the white follicles and the activity of caspases 3, 8, and 9 in the stroma and white follicles; (3) intensified the atresia of yellow hierarchical follicles; and (4) deepened the effect of starvation on egg yolk gene expression concomitantly with considerably increased IGF-1 transcription levels in the liver (P < 0.05 to P < 0.001). Prolongation of chGH injections into the refeeding period did not exert pronounced effects on the examined parameters. In summary, the results provide evidence that GH promotes the formation and development of prehierarchical follicles in the hen ovary during a pause in laying by regulating cell proliferation and apoptosis. Alterations in cell proliferation- and apoptosis-related gene expression or enzyme activity in ovarian follicles as well as the expression of egg yolk proteins in the liver after chGH treatment strongly suggest that this hormone is involved in determining the rate of regression and rejuvenation of the chicken ovary during a pause in laying.

Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Impact of an adaptive program for cognitive and emotional deficits (ADACOG program) in multiple sclerosis patients with cognitive impairments.

BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS), affecting approximately 40 to 70% of patients. We developed a psycho-educational program (ADACOG program) to allow patients to cope with cognitive deficits. The purpose of this exploratory study was to investigate the impact of the ADACOG program on subjective self-reported cognitive impairments, quality of life, anxiety, depression and self-esteem in MS patients. METHODS: ADACOG program is a psycho-educational program focusing on cognitive and emotional dysfunctions in MS consisting of three modules in small groups lasting two hours every two weeks. Forty-five MS patients with self-reported cognitive impairments and objective cognitive deficits were enrolled consecutively in two groups: (i) the ADACOG group (N=24) and (ii) the control group (N=21). Both groups of patients completed questionnaires evaluating self-reported cognitive impairments (Multiple Sclerosis Neuropsychological Screening Questionnaire), quality of life (Multiple Sclerosis Impact Scale), anxiety and depression (Hospital Anxiety and Depression Scale, HAD) and self-esteem (Rosenberg Scale) at inclusion (M0), one month later (M1) and seven months after inclusion (M7). The evolution of outcomes within ADACOG group and between both groups was analyzed. RESULTS: The analyses within the ADACOG group showed that patients reported better quality of life and fewer anxiety symptoms at M1 compared to M0 (respectively P=0.03 and P=0,04). Moreover, patients presented less subjective self-reported cognitive deficits at M7 compared to M0 (P=0.003). Score evolution for HAD depression and self-esteem were not significant within the ADACOG group. The change M1-M0 for MSIS-29 and HAD anxiety scores was significantly different between both groups (respectively P=0.04 and P=0.008), with improvement of quality of life and anxiety in the ADACOG group. The evolution of scores between groups was not significant for the other outcomes. DISCUSSION: This study showed a small effect of a psycho-educational program focusing on cognitive and emotional disorders in MS patients with subjective self-reported cognitive deficits and objective cognitive deficits. Interest of psycho-education focusing on cognition in MS patients is discussed.

Effect of growth hormone on steroid concentrations and mRNA expression of their receptor, and selected egg-specific protein genes in the chicken oviduct during pause in laying induced by fasting.

This study was undertaken to examine the effect of growth hormone (GH) treatment during pause in laying on (1) the concentration of steroids in blood plasma and oviduct tissues, (2) the expression of mRNA of steroid receptors, and (3) the mRNA expression of selected egg-specific proteins in the chicken oviduct. A pause in egg laying was induced by food deprivation for 5 d, followed by feeding every other day, and then feeding daily from Day 10 onward. Birds were divided into three groups: control (n = 18) fed ad libitum, subjected to pause in laying (n = 18), and subjected to pause in laying and injected every day with 200 µg/kg BW of chicken GH (chGH; n = 18). The oviduct was isolated from hens of each group on Days 6 (when the oviduct was regressed), 13 (during oviduct recrudescence), and 17 or 20 (rejuvenated oviduct) of the experiment. Fasting caused a decrease in plasma concentrations of progesterone (P4), testosterone, and estradiol on Day 6 and a reduction in tissue concentrations of these steroids on Days 6 and 13. Fasting also caused an increased relative expression of estrogen receptor α and ß (ERα, ERß) and progesterone receptor (PR) in the magnum and shell gland on Day 6, increased ERα and PR in the magnum on Days 13 and 17 or 20, and increased androgen receptor (AR) mRNA in the magnum on Days 6 and 13 and in the shell gland on Day 13. A fasting-induced elevation in ovocalyxin-36 mRNA expression on Day 6 and a decrease in avidin mRNA on Days 6 and 13 and in ovocleidin-116 on Day 13 were also observed (P < 0.05 to P < 0.001). Administration of chGH abolished the fasting-induced decrease in the concentration of steroids in plasma and tissues. Furthermore, chGH enhanced the effect of fasting on mRNA expression of PR, ERα, and avidin in the magnum on Day 6, and ERα in the shell gland on Day 13. The gene expression of ovalbumin on Days 6 and 13, ovocalyxin-36 and ovocleidin-116 on Day 6 was decreased in chGH-treated chickens. In contrast, the expression of ovalbumin on Day 17 or 20 was increased (P < 0.05 to P < 0.001). The results obtained indicate that, by alterations in the concentration of steroid hormones and their receptor expression in the chicken oviduct, GH determines the rate of regression and rejuvenation of this organ during molting. Moreover, changes in the expression of selected egg proteins indicate that GH might be the regulator of the secretory activity of the hen oviduct.

Clinical target volume in postoperative radiotherapy for gastric cancer: identification of major difficulties and controversies

Purpose: To identify the main difficulties in postoperative clinical target volume (CTV) delineation in gastric cancer (GC). Methods: Before and after a training course, 20 radiation oncology residents were asked to delineate the CTV for the postoperative GC case on four computed tomography scans: dome of the diaphragm, anterior abdominal wall, duodenal stump and porta hepatis level, and to determine the lower CTV border. CTV volume was reconstructed from requested planar contours. Area of intersection (AI) for each requested scan and volume of intersection (VI), defined as the overlap of delineated area/volume with respective reference area (RA)/reference volume (RV) proposed by the senior radiation oncologist, were computed. The degree of agreement between the reference and participants’ contours was quantified using the Concordance Index (CI): AI/RA 9 100 % or VI/RV 9 100 %. The lower CTV border was analyzed separately. Pre- and post-training CIs were compared. A questionnaire investigated the difficulties with contouring. Results: Mean CI value was the lowest for the dome of the diaphragm (24 % pre-training, 35 % post-training) and for the duodenal stump (49 % pre-training, 61 % post-training). Mean CI for the CTV volume was 49 % pre-training and 59 % post-training, p = 0.39. Mean distance from the reference to the participants’ lower CTV borders was 2.73 cm pre-training and 2.0 cm post-training, p = 0.71. In a questionnaire, 75 % of respondents indicated the elective nodal area as the main difficulty. Conclusions: Delineation of the dome of the diaphragm and the duodenal stump, as yet not recognized as the source of variation, should be addressed in the international consensus guidelines and clarified (AU)

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Clinical target volume in postoperative radiotherapy for gastric cancer: identification of major difficulties and controversies.

PURPOSE: To identify the main difficulties in postoperative clinical target volume (CTV) delineation in gastric cancer (GC). METHODS: Before and after a training course, 20 radiation oncology residents were asked to delineate the CTV for the postoperative GC case on four computed tomography scans: dome of the diaphragm, anterior abdominal wall, duodenal stump and porta hepatis level, and to determine the lower CTV border. CTV volume was reconstructed from requested planar contours. Area of intersection (AI) for each requested scan and volume of intersection (VI), defined as the overlap of delineated area/volume with respective reference area (RA)/reference volume (RV) proposed by the senior radiation oncologist, were computed. The degree of agreement between the reference and participants' contours was quantified using the Concordance Index (CI): AI/RA × 100% or VI/RV × 100%. The lower CTV border was analyzed separately. Pre- and post-training CIs were compared. A questionnaire investigated the difficulties with contouring. RESULTS: Mean CI value was the lowest for the dome of the diaphragm (24% pre-training, 35 % post-training) and for the duodenal stump (49% pre-training, 61% post-training). Mean CI for the CTV volume was 49% pre-training and 59% post-training, p = 0.39. Mean distance from the reference to the participants' lower CTV borders was 2.73 cm pre-training and 2.0 cm post-training, p = 0.71. In a questionnaire, 75% of respondents indicated the elective nodal area as the main difficulty. CONCLUSIONS: Delineation of the dome of the diaphragm and the duodenal stump, as yet not recognized as the source of variation, should be addressed in the international consensus guidelines and clarified.

Enfermedad renal poliquística en gatos: Revisión de la literatura / Polycystic kidney disease in cats: a literature review

La presente revisión se centra en la etiología, patogénesis, epidemiología, diagnóstico y tratamiento de la “enfermedad renal poliquística autosómica dominante” (ERPAD). La ERPAD es un trastorno genético heredable tradicionalmente asociado al gato persa y que afecta también al gato mestizo en todo el mundo. La enfermedad se presenta como una insuficiencia renal crónica generalmente en gatos mayores de tres años de edad y no posee un tratamiento específico. Sin embargo, el mayor uso de la ultrasonografía en tiempos recientes permite detectar la enfermedad de forma temprana, mejorar el pronóstico y llevar a cabo medidas de control basadas en la prevención de la cría de gatos afectados para evitar el nacimiento de progenie genéticamente susceptible(AU)

The present review focuses on the ethiology, pathogenesis, epidemiology, diagnosis and treatment of the “Autosomal Dominant Polycystic Kidney Disease” (ADPKD). It is an inheritable genetic disorder traditionally described in Persian cats and presently recognized in crossbreed cats worldwide. Affected animals develop chronic renal insufficiency and failure, and disease has a late onset, usually when cats are over three years old, and there is no specific treatment for it. However, the development in recent times of ultrasound imaging as the main diagnostic tool for ADPKD, is allowing early disease detection, improve prognosis and to implement control measures based on preventing breeding from affected cat to avoid genetically ADPKD susceptible progeny(AU)

Prevention of de novo hepatitis B virus infection by vaccination and high hepatitis B surface antibodies level in children receiving hepatitis B virus core antibody-positive living related donor liver: case reports.

Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.

Lipid, carbohydrate metabolism, and antioxidant status in children after liver transplantation.

Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.

Autoimmune hepatitis in transplanted liver.

Liver transplantation is recognized as the appropriate treatment for end-stage liver disease. Four patients undergoing liver transplantation for classical end-stage liver disease developed de novo autoimmune hepatitis (AIH) in the graft. Recurrence of AIH after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in one other patient. Markedly elevated serum transaminases were observed, together with an elevated serum IgG and/or globulin fraction and histological feature typical of AIH on liver biopsy.

Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient.

We describe the case of successful delivery in a 21-year-old woman who became pregnant 3 years after liver transplantation and who received sirolimus during the first 6 weeks of gestation. Sirolimus was discontinued when ultrasonography revealed a pregnancy, she was switched to tacrolimus and prednisone was continued. The course of pregnancy was uneventful; there were no signs or symptoms of graft rejection. Due to fetal intrauterine threatening asphyxia the pregnancy was concluded by cesarean section in the 39th gestational week, delivering a healthy, 2950 g, Apgar 10, female infant.

Reduction of naive CD4/CD45RA+ T cells in children with biliary atresia before and after liver transplantation.

The aim of this study was to examine whether liver transplantation reverses the abnormal distribution of lymphocyte subsets previously observed in biliary atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell subset and an increase in the B and natural killer cell subpopulations. Eight biliary atresia children aged 1.08 to 6 years were studied before and 1 year after LTx for comparison with 15 age-matched healthy controls. The posttransplant immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor density were assessed by the use of double color flow cytometry (EPICS-XL MCL fluorocytometer). Biliary atresia patients were compared after LTx with subjects before LTx, essentially showing no statistically significant changes in lymphocyte subsets. We conclude that LTx of biliary atresia children does not reverse the abnormal lymphocyte subset distribution present before transplantation. Hence, these changes may reflect either their independence from the liver status or may result from immunosuppressive treatment that contributes to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+ naive T cells.

Effects of human growth hormone (hrGH) treatment on amine metabolism in rats subjected to extensive small bowel resection.

The effect of human recombinant growth hormone (hrGH) on intestinal adaptation in rats subjected to massive small bowel resection has been followed by monitoring changes in the tissue polyamine system and in red blood cell (RBC) polyamine levels. In parallel, the activities of monoamine oxidase A and B and diamine oxidase, the enzymes that catalyse one of the major routes of biogenic amine metabolism, oxidative deamination, were also examined. The results suggest that whilst hrGH treatment accelerates adaptive intestinal hyperplasia evoked by the resection, it has no significant effect on RBC polyamine level or gut mucosal DNA concentration as measured 3 weeks post surgery. hrGH treated operated rats exhibited significantly lower amine oxidase activities which implies that GH may alter biogenic amine systems.

The past and present of the Polish paediatric gastroenterology, hepatology and nutrition.

Gastroenterology has emerged from paediatrics as a separate discipline after 1978, due to the development of basic sciences, i.e., biochemistry, immunology, pathomorphology and introduction of miniaturized endoscopic and radiological equipment. This paper describes the most significant achievements in the areas of gastroenterology, hepatology, and nutrition in children in particular medical centres in Poland. It also discusses the role of the Polish Society for Paediatric Gastroenterology, Hepatology and Nutrition, the role of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and the role of other Scientific Societies and Foundations supporting the development of science and education. The emphasis has been placed upon utilitarian research and education with regard to the management of children with gastrointestinal and hepatic disease.

Trans fatty acids in human milk in Poland and their association with breastfeeding mothers' diets.

AIM: To determine the content of trans fatty acids in human milk in relation to breastfeeding mothers' diet. METHODS: Samples of milk were collected from 100 breastfeeding mothers and 7-d dietary records and anthropometry from 69 mothers were obtained. RESULTS: The following total trans fatty acids contents (median (lower-upper quartile); % wt/wt) in milk samples were determined: 1) data for Spring: colostrum--1.37 (1.00-2.00), mature milk at 5-6 wk of lactation--2.59 (1.49-3.34) and at 9-10 wk of lactation--2.36 (1.55-3.92); 2) data for Autumn: colostrum--1.80 (1.42-2.48), mature milk at 5-6 wk of lactation--2.41 (1.79-4.31) and at 9-10 wk of lactation--2.77 (1.53-4.18). The major sources of trans fatty acids in mothers' diets were bakery products, confectionery and snacks. Mothers who had high level of trans isomers in their milk consumed significantly higher amounts of these products. CONCLUSIONS: Bakery products, confectionery and snacks are a major source of trans fatty acids in maternal diet in Poland. The levels of trans fatty acids in human milk may reflect the current diet of the mother as well as the diet consumed early in pregnancy.

[Magnesium status in children and adolescents with celiac disease]. / Stan odzywienia magnezem u dzieci i mlodziezy z celiakia.

UNLABELLED: Magnesium deficiency has been reported in patients with classical coeliac disease. Classical coeliac disease has been recently very rare, but the frequency of the silent or latent form has increased. The aim of the study was to evaluate the magnesium status in patients with coeliac disease diagnosed according to ESPGAN criteria. 41 GFD(+) patients aged 6-18 years, who were on a gluten-free diet (GFD) for 2.8 to 17.3 years (mean 11 years); with normal villous structure and IgAEmA(-), and 32 GFD(-) patients aged 5-17 years, with villous atrophy and IgAEmA(+): 8--after 7/12-13/12 of gluten challenge, 4--with late onset of coeliac disease, 20--with silent coeliac disease. All of the children did not have any other disorders. Magnesium status was examined by using: an i.v. Mg-loading test (30 mmol/1.73 m2); Mg urinary excretion and Mg concentration in serum, erythrocytes, and in hair. Abnormal values in GFD(+) and GFD(-) patients were found in: Mg i.v. loading test (retention > 40%) in 20 vs 34%, serum Mg (< 0.7 mmol/l) in 7 vs 3%, erythrocytes Mg (< 1.8 mmol/l) in 20 vs 25%. The reversed statistically significant correlation was found between Mg retention and Mg urinary excretion (R = -0.293, p = 0.009). No other statistically significant correlations were found. CONCLUSION: The magnesium deficiency was present in all patients with classical coeliac disease, but only in 1/5 of patients with coeliac disease on a gluten-free diet and in 1/5 of patients with silent coeliac disease.

Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea.

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events.

Deficiency of the expression of CD45RA isoform of CD45 common leukocyte antigen in CD4+ T lymphocytes in children with infantile cholestasis.

The immunological background of the pathological changes that appear in infantile cholestasis (infections, inflammatory process in the liver) is largely unknown. With the use of double color flow cytometry, we assessed the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 29 infants with extra and intra-hepatic cholestasis (12 and 17 patients, respectively), aged from 1 to 8.6 months. Control group consisted of 15 age-matched, healthy infants. We examined: (1) the expression of CD3, CD4, CD8, CD19 lymphocyte surface receptors; and (2) the distribution of lymphocyte subsets with distinctive surface Ag characteristics of 'naive' (CD45RA+) and 'memory' (CD45RO+) cells in both CD4+ and CD8+ cell populations. The surface markers expression was evaluated in terms of percentage of positive cells and receptor density. The following changes in the expression of lymphocyte surface markers are described: (1) a decrease in the percentage of total CD3+, CD4+ cells but normal percentage of CD8+ cells and elevated proportion of CD19+ B cells; (2) a reduction of the proportion of 'naive' CD4+ lymphocytes but normal percentage of 'naive' CD8+ as well as 'memory' CD4+ and CD8+ cell subsets; (3) a decrease in density of CD3, CD4+, CD8 receptors, and D45RA isoform in a subset of 'naive' CD4+ cells. We conclude that deficiency of 'naive' CD4+ T cell subset which possess important effector and immunoregulatory functions, and low expression of certain lymphocyte receptors known to be engaged in T cell activation, possibly reflect a defect of cell mediated immunity that may account for viral and bacterial infections, often observed in infants with cholestasis.