Microbial transglutaminase alters the immunogenic potential and cross-reactivity of horse and cow milk proteins.

Horse milk is a valuable raw material and a very attractive alternative for scientific research to address the issue of cow milk (CM) allergy due to its protein profile. A decrease in immunoreactive properties can be achieved by thermal, enzymatic, and hydrolytic processing. Therefore, the aim of this study was to explore the possibility of reducing the immunoreactivity of horse milk proteins by microbial transglutaminase (TG) polymerization. To determine how TG linking alters immunoreactivity under simulated digestion of the examined milk, analyses were performed before, during, and after digestion. The dose-dependent (1, 10, and 100 U) effects of microbial TG on horse and cow milk were analyzed. A consecutive 3-stage digestion was simulated with salivary, gastric, and intestinal fluids. The effects of digestion were analyzed by SDS-PAGE, particle size analysis, and size-exclusion chromatography. Immunoreactivity was assessed using competitive ELISA (ß-lactoglobulin and α-casein) and immunodot (sera from 7 patients aged 3 to 13 years who are allergic to CM proteins). Horse milk contained almost half of the amount of total proteins in CM. The dose 1 U/g of total milk protein changed the immunoreactivity of both cow and horse milk. With increasing TG doses, α-casein immunoreactivity increased, and ß-lactoglobulin decreased. After total digestion, horse milk was characterized by 2.4-fold lower average IgE and 4.8-fold lower IgG reactivity than CM. We found that TG alters the IgE and IgG reactivity of CM after in vitro digestion. Horse milk was less reactive to IgE and IgG than was CM, with animal and patient sera. The effect of TG on immunoreactivity depends on enzyme quantity and milk protein type. The diet based on modified horse milk proteins could be an alternative for some patients with CM protein allergy; however, confirmation through clinical trials is needed.

Yogurt starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus ameliorate symptoms and modulate the immune response in a mouse model of dextran sulfate sodium-induced colitis.

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis, lymphocyte profile, and regulatory T-cell response. Colitis was induced in BALB/c mice via the administration of 3.5% dextran sulfate sodium salt (DSS) in drinking water for 6 d. Next, the mice were gavaged intragastrically with an active yogurt cultures (YC) mixture (∼5 × 109 cfu/mouse per day) or saline (vehicle) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls, respectively. The length of the colon, disease activity index, histological scores, myeloperoxidase activity, epithelium-associated microbes, short-chain fatty acid profile, total IgA antibody-forming cells, CD3+CD8+, CD3+CD4+, CD3+CD4+CD25+, CD3+CD4+CD25+Foxp3+ T-cell subsets, and cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and tumor necrosis factor) were examined after termination of the mice. Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS. We observed limited weight loss and a decreased disease activity index score, lowered myeloperoxidase activity, and somewhat reduced damage of the intestine. The YC mixture upregulated the colon length, increased the amount and diversity of mucosa-associated microbes (enterobacteria, enterococci, and yeast), and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents. It downregulated the input of cytotoxic CD3+CD8+ T cells and CD3+CD4+CD25+FoxP3+ regulatory T cells in Peyer's patches and enhanced CD3+CD4+CD25+ T cells in spleens and CD3+CD4+CD25+FoxP3+ cells in peripheral blood mononuclear cells. Simultaneously, IgA antibody-forming cells were downregulated in mesenteric lymph nodes (MLN) and enhanced in spleens (SPL). The cultures mostly enhanced the production of cytokines tested in MLN and SPL, except for IL-6, which was downregulated in MLN. Interleukin-2 and IL-4 were the most upregulated in MLN, whereas IL-10, IL-4, IL-2, IFN-γ, and tumor necrosis factor were most upregulated in SPL. In serum, the YC mixture downregulated IFN-γ and clearly increased IL-2. Based on these results, we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set. The strains possess the ability to modulate the intestinal mucosal and systemic immune system toward both IgA production and induction of regulatory T cells, shifting Th1/Th2 balance.

Prostate Cancer in Deceased Organ Donors: Loss of Organ or Transplantation With Active Surveillance.

INTRODUCTION: Prostate cancer has become an important clinical issue within deceased organ donors. There is still a considerable number of undiagnosed cancers, especially in early stage, despite frozen section analysis. The aim of the study was to evaluate outcomes of orthotopic liver transplants (OLTx) with organs from donors with prostate cancer. MATERIAL AND METHODS: A retrospective analysis was performed in deceased liver donors whose prostate glands were harvested for histologic examinations because of prostate cancer suspicion. The study group consisted of 72 men reported as potential liver donors between 2011 and November 2017. Prostate glands were primarily assessed by frozen sections and afterward in routine examination. Generally cancer diagnosed in frozen specimen was not considered for OLTx. Recipients who received an organ from the donor with prostate cancer were actively surveilled. RESULTS: There were 19 cases (26.40%) of prostate cancer diagnosed among the study group. In 12 cases diagnosis was made by frozen section assessment, of which 11 organs were disqualified from OLTx and 1 was transplanted. In 7 cases prostate cancer was diagnosed after OLTx in final routine histologic examination. Finally, 8 recipients (5 men and 3 women) received a new organ. Only 1 died during the perioperative period. In the remaining 7 patients the perioperative period was uneventful and no disease transmission was observed during follow-up. CONCLUSIONS: Diagnosis of prostate cancer in donors should not be treated as a contraindication for OLTx because the risk of disease transmission is low. Potential recipients must be fully informed and kept under oncological surveillance.

The effects of whey and soy proteins on growth performance, gastrointestinal digestion, and selected physiological responses in rats.

The objective of this work was to identify the nutritional and physiological effects of commercial soy and whey protein preparations. Wistar rats were fed with soy (S), whey (W), or casein (C) preparations as the sole dietary protein source. The nitrogen balance, body composition, changes in caecal microbiota, mucosal and bacterial enzyme activities, and allergenic potential of the preparations were analysed. The whey diet elicited greater skeletal muscle anabolism than the soy diet. Rats from the S group had the lowest values of body weight, fat, and lean mass gain. Compared to casein, soy and whey preparations decreased the protein efficiency ratio, increased N in the urine, and triggered the reduction of ammonia levels in the caecum. Changes in ß-glucuronidase and ß-galactosidase activities in the small intestine, caecum, and colon between experimental groups were observed. Significant differences were noted in the total counts of anaerobic bacteria and sulphite reducing bacteria during soy and whey treatments. This probably affected the short chain fatty acid level in caecal digesta resulting in the lowest propionic acid and total putrefactive short chain fatty acid levels during S treatment. Generally, whey preparations are a good choice for rapid bodybuilding (skeletal muscles), whereas soy preparations are more helpful during mass reduction.

Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity.

Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects.

Immune-modulating properties of horse milk administered to mice sensitized to cow milk.

The aim of this study was to examine immune adaptive changes, the expression of innate biomarkers and variations in intestinal microbiota composition after horse-milk administration in BALB/c mice, which were sensitized intraperitoneally using cow ß-lactoglobulin and α-casein with aluminum adjuvant. We measured serum antibody IgE levels and the expression of MCP-1, IL-4, and TNF-α in duodenal samples. Changes in immune cell populations in peripheral blood were quantified using flow cytometry, and intestinal microbiota composition was assessed using real-time PCR. We found that horse-milk administration decreased serum IgE levels in sensitized mice. The groups that received horse milk showed an increased population of regulatory T cells (CD4+Foxp3+). Horse-milk administration decreased the mRNA levels of IL-4 and resulted in higher transcripts of TLR-4 in all treatment groups; however, the levels of MCP-1, TNF-α, and TLR-2 were unaltered. After horse-milk treatment, we observed a positive effect, with increased numbers of intestinal Bifidobacterium spp. We observed immune-modulating properties of horse milk, but future studies should focus on testing horse-milk processing, such as fermentation and destroying most allergenic epitopes to continue research under clinical conditions.

Prostate Cancer in Deceased Liver Donors.

BACKGROUND: Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. METHODS: A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. RESULTS: In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. CONCLUSIONS: Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation.

Alveococcosis of the liver - strategy of surgical treatment with special focus on liver transplantation.

BACKGROUND: Echinococcosis is a zoonosis caused by infestation with any of 4 (of the 16) members of the Echinococcus genus, namely Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthus, and Echinococcus vogelii. The aim of this retrospective analysis was to present the outcomes of patients undergoing liver resection and liver transplantation (LT) for E. multilocularis infection. METHODS: A total of 44 patients who underwent surgical treatment of E. multilocularis infection in the period between 1989 and 2014 were included in the study cohort and retrospectively analyzed. RESULTS: LT was performed in 22 patients (50.0%), including 4 of 26 patients undergoing initial non-transplant management. Non-transplant procedures comprised liver resection in 23 patients (88.5%), diagnostic laparoscopy in 2 (7.7%), and left adrenalectomy in 1 patient (3.8%). Post-transplantation survival rates were 90%, 85%, and 75% at 1, 5, and 10 years, respectively. CONCLUSION: In conclusion, LT for E. multilocularis infection is a safe and effective treatment method.

Metabotropic glutamate receptor 1 acts as a dependence receptor creating a requirement for glutamate to sustain the viability and growth of human melanomas.

Metabotropic glutamate 1 (mGlu) receptor has been proposed as a target for the treatment of metastatic melanoma. Studies have demonstrated that inhibiting the release of glutamate (the natural ligand of mGlu1 receptors), results in a decrease of melanoma tumor growth in mGlu1 receptor-expressing melanomas. Here we demonstrate that mGlu1 receptors, which have been previously characterized as oncogenes, also behave like dependence receptors by creating a dependence on glutamate for sustained cell viability. In the mGlu1 receptor-expressing melanoma cell lines SK-MEL-2 (SK2) and SK-MEL-5 (SK5), we show that glutamate is both necessary and sufficient to maintain cell viability, regardless of underlying genetic mutations. Addition of glutamate increased DNA synthesis, whereas removal of glutamate not only suppressed DNA synthesis but also promoted cell death in SK2 and SK5 melanoma cells. Using genetic and pharmacological inhibitors, we established that this effect of glutamate is mediated by the activation of mGlu1 receptors. The stimulatory potential of mGlu1 receptors was further confirmed in vivo in a melanoma cell xenograft model. In this model, subcutaneous injection of SK5 cells with short hairpin RNA-targeted downregulation of mGlu1 receptors resulted in a decrease in the rate of tumor growth relative to control. We also demonstrate for the first time that a selective mGlu1 receptor antagonist JNJ16259685 ((3,4-Dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone) slows SK2 and SK5 melanoma tumor growth in vivo. Taken together, these data suggest that pharmacological inhibition of mGlu1 receptors may be a novel approach for the treatment of metastatic melanoma.

Reliability of frozen section in the assessment of allograft steatosis in liver transplantation.

BACKGROUND: Because liver allograft steatosis is an important risk factor of graft dysfunction after liver transplantation, it must be taken into consideration during graft acceptance. The aim of this study was to evaluate the reliability of frozen section in the assessment of liver steatosis before transplantation. METHODS: The retrospective analysis was based on data of 112 liver allograft procurements performed between 2003 and 2012. Hepatic steatosis was assessed in frozen and routine sections. Sensitivity, specificity, and positive and negative predictive values of the frozen section were evaluated with respect to detection of >30% and >50% steatosis. RESULTS: According to routine section assessment, there were 32 (28.6%) cases of steatosis >30% and 16 (14.3%) of >50%. The results of frozen section assessment were underestimated and overestimated in a similar low number of cases, both for the >30% (0.0% and 0.9%, respectively, P < 1.000) and the >50% (4.5% and 0.9%, respectively, P = .221) cutoff. Sensitivity, specificity, positive and negative predictive values of frozen section assessment were 100.0%, 98.8%, 97.0%, and 100.0%, respectively, for detection of >30% steatosis, and 68.8%, 99.0%, 91.7%, and 95.0%, respectively, for >50% steatosis. CONCLUSIONS: Considering high positive predictive value of frozen section assessment in detection of >50% steatosis, it may serve as a base to discard the use of graft for transplantation. However, according to the relatively moderate sensitivity of this method, decision of graft acceptance must also be made on consideration of other well-known factors for poor posttransplant function.

Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study.

Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.

Diet shapes the ability of human intestinal microbiota to degrade phytate--in vitro studies.

AIMS: Investigation of intestinal bacterial groups involved in phytate degradation and the impact of diets with different phytate contents on phytase activity. METHODS AND RESULTS: Faecal samples of adults on conventional (n = 8) or vegetarian (n = 8) diets and breastfed infants (n = 6) were used as an inoculum for modified media supplemented with phytate. Populations of Gram-positive anaerobes (GPA), lactic acid bacteria (LAB), Proteobacteria-Bacteroides (P-B), coliforms and anaerobes were studied. The PCR-DGGE analysis revealed a random distribution of DGGE profiles in the dendrograms of GPA, P-B and coliforms, and a partially diet-specific distribution in the DGGE dendrograms of LAB and anaerobes. The degradation of phytic acid (PA) was determined with HPLC method in supernatants of the cultures. Regardless of the diet, the Gram-positive anaerobes and LAB displayed the lowest ability to degrade phytate, whereas the coliforms and P-B cultures produced higher amounts of intermediate myo-inositol phosphates. Bacterial populations grown in a nonselective medium were the most effective ones in phytate degradation. It was the vegetarians' microbiota that particularly degraded up to 100% phytate to myo-inositol phosphate products lower than InsP3. CONCLUSIONS: A diet rich in phytate increases the potential of intestinal microbiota to degrade phytate. The co-operation of aerobic and anaerobic bacteria is essential for the complete phytate degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insights on the effect of diet on specific metabolic activity of human intestinal microbiota.

Microvesicular liver graft steatosis as a risk factor of initial poor function in relation to suboptimal donor parameters.

OBJECTIVE: We sought to examine the role of microvesicular graft steatosis in relation to donor parameters. MATERIALS AND METHODS: We performed 269 consecutive orthotopic liver transplantations (OLT) between 2004 and 2006. Donor parameters of age, body mass index (BMI), intensive care unit (ICU) stay, hypotension, cardiac arrest, pressors, sodium concentration, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), bilirubin, and activated partial thromboplastin time (APTT), as well as the degree of microvesicular graft steatosis were collected into the study. The endpoint of the study was liver graft dysfunction (AST or ALT > 2500 IU/L or prothrombin index < 50% during the first 7 days after OLT). RESULTS: The risk of initial poor function (IPF) at day 7 posttransplantation was significantly related to hepatic microvesicular steatosis (odds ratio [OR] = 1.38 per 1 SD = 9.3%; P < .021). Accounting for the influence of the other donor factors produced little change in the numerical values of relative risk: from 1.22 (following exclusion of GGT) to 1.46 (after elimination of the influence of bilirubin concentration). A 50% increased risk of IPF was equivalent to 12% of the extent of steatosis. CONCLUSION: Microvesicular steatosis is a risk factor for early hepatic dysfunction after OLT.

Impact of tumor characteristic on the outcome of liver transplantation in patients with hepatocellular carcinoma.

INTRODUCTION: Orthotopic liver transplantation (OLT) is a well-established treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. The aim of this study was to identify predictors of survival among 65 patients with HCC in cirrhotic livers who underwent liver transplantation (OLT). METHODS: From January 2001 to December 2008, we performed 655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by histological examination of the explanted livers; 74% of the patients met Milan criteria by histological examination. RESULTS: The median follow-up was 27 months (range = 1-96). We analyzed patient age and gender, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number/size, vascular invasion, and differentiation grade. There was no significant difference in survival among patients grouped according to the Model for End-stage Liver Disease staging system for HCC. The 5-year survival of patients with low differentiated (G3) HCC was significantly worse than that of those with moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86% respectively, (P < .01). Patients with microvascular invasion displayed a worse 5-year survival than those without vascular invasion (42% vs 80%; P < .01). CONCLUSIONS: The analysis indicated that the histological grade of the tumors and evidences of microscopic vascular invasion were the most useful predictive factors for overall survival among patients with cirrhosis after liver transplantation for HCC.

Hodgkin-like lymphoma, simulating anaplastic large cell lymphoma in the patient after renal transplantation--unusual case report and literature review.

UNLABELLED: We report the atypical case of posttransplant lymphoproliferative disorder (PTLD) diagnosed in 55-year men 9 years after renal transplantation. It was evaluated only by bone marrow biopsy, which showed its total involvement with malignant lymphoma. It was composed of two populations of lymphoid cells: large RS-like cells and small to medium ones, with slightly angular nuclei without visible nucleoli. Both cellpopulations did not show positive reaction for typical B cell markers (CD20, CD79a). Large RS-like cells were positive with CD30 and EBV-LMP. However, negative reaction with CD15 and positive reactions with UCHL1 and EMA were not consistent with classical type of Hodgkin lymphoma. Morphological picture and immunophenotype had suggested anaplastic T cell lymphoma. Because of negative reaction with ALK1, initial diagnosis was ALCL ALK-negative. Then, additional stains with BOB1 and Oct2 were performed, which were positive. Taking it into account the diagnosis was changed; finally Hodgkin-like B lymphoma was diagnosed. The patient was treated with CHOP regimen with good response. 5 years after primary diagnose of PTLD he is steel free of disease. CONCLUSIONS: 1. Apart from typical forms of PTLD, one may expect cases with nonspecific morphological picture and phenotype. 2. Negative reactions with typical immunohistochemical markers for lymphocytes of B cell line do not exclude the possibility of B-cell proliferation.

High light intensity protects photosynthetic apparatus of pea plants against exposure to lead.

The electron transport rates and coupling factor activity in the chloroplasts; adenylate contents, rates of photosynthesis and respiration in the leaves as well as activity of isolated mitochondria were investigated in Pisum sativum L. leaves of plants grown under low or high light intensity and exposed after detachment to 5 mM Pb(NO(3))(2). The presence of Pb(2+) reduced rate of photosynthesis in the leaves from plants grown under the high light (HL) and low light (LL) conditions, whereas the respiration was enhanced in the leaves from HL plants. Mitochondria from Pb(2+) treated HL-leaves oxidized glycine at a higher rate than those isolated from LL leaves. ATP content in the Pb-treated leaves increased to a greater extend in the HL than LL grown plants. Similarly ATP synthase activity increased markedly when chloroplasts isolated from control and Pb-treated leaves of HL and LL grown plants were subjected to high intensity light. The presence of Pb ions was found inhibit ATP synthase activity only in chloroplasts from LL grown plants or those illuminated with low intensity light. Low light intensity during growth also lowered PSI electron transport rates and the Pb(2+) induced changes in photochemical activity of this photosystem were visible only in the chloroplasts isolated from LL grown plants. The activity of PSII was influenced by Pb ions on similar manner in both light conditions. This study demonstrates that leaves from plants grown under HL conditions were more resistant to lead toxicity than those obtained from the LL grown plants. The data indicate that light conditions during growth might play a role in regulation of photosynthetic and respiratory energy conservation in heavy metal stressed plants by increasing the flexibility of the stoichiometry of ATP to ADP production.

Increased mRNA expression of transforming growth factor beta in the arterial wall of chronically rejected renal allografts in humans.

INTRODUCTION: Transforming growth factor beta (TGF-beta) has an established role in interstitial damage of renal transplants during chronic rejection (CR). However, its involvement in transplant vasculopathy is not clear. The aim of the study was to assess TGF-beta gene expression in the walls of large-caliber arteries within chronically rejecting renal allografts. We evaluated associations between gene expression of this factor and intimal thickness or clinical data. MATERIAL AND METHODS: Renal artery samples of kidney allografts were obtained from 20 hemodialysis patients with end-stage renal graft disease due to CR, who were undergoing graftectomy. The control group included 32 hemodialysis patients with end-stage renal disease, undergoing nephrectomy due to autosomal dominant polycystic kidney disease (n = 12), chronic pyelonephritis (n = 13), or kidney limited tumor (n = 7). Gene expression of TGF-beta was measured using real-time PCR. RESULTS: TGF-beta mRNA expression was 3.25-fold higher in CR than in control patients (P < .001). Expression of mRNA for this cytokine was not influenced by the following factors: intimal thickness; age; serum cholesterol, triglycerides and glucose; BMI; graft survival; time of dialysis before transplantation; total ischemic time; immunosuppressive regimen; incidence of acute rejection episode; panel reactive antibodies; and period of dialysis before graftectomy. TGF-beta is involved in neointimal formation in CR.

Posttransplant lymphoproliferative disorder: morphological picture and diagnostic difficulties.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of both solid organ and bone marrow transplantation. It includes a wide spectrum of proliferative changes ranging from reactive hyperplasia, borderline lesions to malignant lymphomas. PTLD develops in 1% to 10% of transplant recipients. We present 10 cases of PTLD. Five developed after renal, four after liver, and one after heart transplantation. Among the early lesions, we diagnosed two reactive plasmacytic hyperplasias; one infectious mononucleosis-like PTLD; one polymorphic lesion; and one "mixed" case of plasmacytic hyperplasia in one tonsil with a polymorphic PTLD in the second one. Among the lymphomas, we observed three diffuse large B-cell lymphoma (DLBCL); one mantle lymphoma; and one Hodgkin lymphoma-like PTLD. The morphological pictures of six PTLD cases were typical and posed no diagnostic problems. In the one case of plasmacytic hyperplasia, the lymph node morphology was atypical with atrophy of lymphoid components accompanying plasma cell proliferation. Contrary to a good prognosis of early, reactive PTLD, this patient experienced a rapid course and succumbed to sepsis. The most difficult case was a rare Hodgkin lymphoma-like PTLD, which was diagnosed only by a bone marrow biopsy. Because of its noncharacteristic immunophenotype, it was primarily diagnosed as an anaplastic lymphoma of the T-cell type. After additional immunohistochemical studies (BOB and OCT2), we established the final diagnosis of Hodgkin lymphoma-like PTLD. Due to the increasing number of organ transplantations, doctors of various specialties may encounter PTLD.

Two-stage transjugular intrahepatic porta-systemic shunt for patients with cirrhosis and a high risk of portal-systemic encephalopathy patients as a bridge to orthotopic liver transplantation: a preliminary report.

AIM: Placement of a transjugular intrahepatic porta-systemic shunt (TIPS) is a therapeutic option for the management of bleeding esophageal varices. However, the procedure is associated with an increased risk of portal-systemic encephalopathy (PSE). In this study, a two-stage modification of the standard TIPS technique was introduced for the management of variceal bleeding in cirrhotic patients with a high risk of PSE before liver transplantation. METHODS: The modified procedure was applied to four patients with cirrhosis, portal hypertension, and ascites. Two had a history of encephalopathy after variceal bleeding; the other two were encephalopathic at the time of the first stage of the modified procedure. In the first stage, a 6-mm diameter intrahepatic shunt was created using a Palmaz-Schatz stent. One month later, in the second stage, the lumen of the shunt was expanded to a diameter of 10 mm. RESULTS: Both stages of this TIPS procedure were undertaken without any associated adverse events. In particular, neither stage was followed by a deterioration of neurologic status. From completion of the second stage to undertaking orthotopic liver transplantation (a period of 2 to 6 months), no rebleeding from esophageal varices occurred. CONCLUSIONS: A two-stage TIPS procedure to reduce portal hypertension enables a more gradual adaptation to post-TIPS hemodynamic and metabolic changes than occurs after creation of a conventional TIPS. A two-stage TIPS procedure may be the method of choice for treating bleeding from esophageal varices in patients who have a high risk of developing PSE and give them a chance for liver transplantation.