Campylobacter and Salmonella are prevalent in broiler farms in Kyushu, Japan: results of a 2-year distribution and circulation dynamics audit.

AIM: To elucidate the distribution and circulation dynamics of Campylobacter and Salmonella in Japanese chicken broiler flocks. METHODS AND RESULTS: A 2-year investigation of the distribution of Campylobacter and Salmonella was conducted in 25 broiler flocks at nine farms in Japan from 2013 to 2014. Campylobacter and Salmonella tested positive in 11 (44·0%) and 24 (96·0%) broiler flocks respectively. One hundred and ninety-five Campylobacter and 184 Salmonella isolates were characterized into 12 Campylobacter (including two novel genotypes) and three Salmonella MLST genotypes. Only Salmonella isolation between caecal and environmental samples were significantly correlated. Further, one litter sample tested positive for Salmonella before new chicks were introduced. The Campylobacter strains rapidly lost culturability within 2-18 days; in contrast, the Salmonella strains survived from 64-211 days in artificially inoculated water samples. CONCLUSION: No persistent circulation-mediated Campylobacter contamination was observed. In contrast, circulation of Salmonella in broiler houses was seen, apparently due to the litter excreted from broiler flocks, as well as Salmonella-contaminated water and feed. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provides the distribution, genotypic data and circulation dynamics of Campylobacter and Salmonella as recently observed in Japanese chicken broiler farms.

An analysis of factors affecting production performance in broiler flocks on Japanese commercial farms.

1. The present study determined descriptive values of the main production measurements of flocks and assessed the relationship between these measurements and related management factors in Japanese commercial broiler farms. 2. The data set included 5060 flock records from 183 farms. The production index was calculated as follows: liveability × average daily gain/feed conversion ratio × 10. Management factors included in the analysis were broiler breeder age, the time interval between successive flocks, the season of placement and stocking density. 3. The mean (±SD) production index was 283.9 ± 28.83. Management factors significantly associated with a decreased production index were low broiler breeder age, flocks placed in summer and high stocking density (P < 0.05). 4. In regard to an interaction for the production index, flocks with high stocking density had a lower production index than those with low stocking density in flocks with a low broiler breeder age (P < 0.05). In summer, flocks with a short time interval between successive flocks had a lower production index than those with an intermediate or long time interval (P < 0.05). 5. The present study identified factors related to flock performance. The knowledge obtained from this analysis will contribute to improve flock performance by optimising management.

Quality of life and problems affecting recipients more than 10 years after living donor liver transplantation.

BACKGROUND: We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children. PATIENTS AND METHODS: We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL). RESULTS: The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition. CONCLUSION: The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.

The use of recipient superficial femoral vein as a venous graft for portal vein reconstruction in right lobe living donor liver transplantation.

In living donor liver transplantation (LDLT), portal vein thrombosis (PVT) in the recipient is frequently regarded as a contraindication. To reconstruct the PV of a right-lobe liver graft (RLG) using an interposition or jump graft from the splenomesenteric junction, various vein grafts and technical modifications have been introduced. The internal jugular, external iliac, or great saphenous veins have been utilized in such reconstructive procedures. However, the superficial femoral vein (SFV) is preferable to the autologous vein grafts in terms of caliber, wall thickness, and length. We employed the recipient SFV to reconstruct PVT among 40 adult LDLT using RLG. Thirty-three were reconstructed by single end-to-end anastomosis with the right or left recipient PV. Three patients were transplanted with a RLG using 2 separated PVs reconstructed by double anastomoses with both the right and left PVs of the recipient. The remaining 4 patients required venous grafting for portal reconstruction. We used the recipient SFV as an interposition or jump graft from the splenomesenteric junction to the graft PV. There were 2 cases of anastomotic PV stenosis; 1 in portal reconstruction without a venous graft and the other with a SFV graft. Both were treated successfully by balloon angioplasty. The recipient SFV is an excellent size match for the PV reconstruction as a long interposition or jump conduit when the venous system from the deceased donor is not available. The indication for LDLT in patients with complete PVT should be carefully decided before transplantation in terms of portal reconstruction.

Management of living donor liver transplant patients using twice-daily 4-hour intravenous cyclosporine therapy.

Oral administration of cyclosporine (CsA) is the currently favored route in most liver transplant centers. From October 1998 to January 2008, 86 living donor liver transplantations (LDLTs) were performed in 85 patients (46 adults and 39 children) at our institution. Seventy-three patients received tacrolimus (Tac), and 12 intravenous CsA twice daily at a dose of 3 mg/kg/d as a 4-hour continuous infusion. Thirteen of 73 Tac-based patients were switched to CsA because of side effects. Five were switched to intravenous CsA because they were unable to take the drug orally because of severe Tac-related complications. The remaining eight patients switched to oral CsA. We evaluated patients (11 adults and three children), including 12 with induction therapy and two with conversion therapy within 2 weeks of LDLT. The patients were given a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d. Stable and adequate blood CsA concentrations were achieved by 4-hour intravenous CsA administration. Among several factors, only graft-to-recipient weight ratio (r = .743, P < .0001) showed significant correlations with initial blood CsA concentration. No adverse effects were observed after intravenous CsA. No patients developed biopsy-proven acute cellular rejection (ACR) during intravenous CsA administration, whereas two patients had histopathologically diagnosed episodes of ACR after conversion from intravenous to oral CsA. Our findings suggest that immediate administration of a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d is practical and effective for routine clinical use.

A free radical scavenger, edaravone, prevents ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

BACKGROUND: Due to the increase in liver transplantation, the donor shortage has become a serious problem, requiring marginal, non-heart-beating donors (NHBDs). The aims of this study were to evaluate the cytoprotective effect of edaravone, a free radical scavenger, on warm ischemia-reperfusion (I/R) injury of liver grafts from NHBDs. METHODS: Rat livers were harvested from heart-beating donors (HB group) or from NHBDs undergoing cardiac arrest for 30 minutes led by thoracotomy (NHB group), and reperfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. In another group (ED group), warm ischemic livers from NHBDs were reperfused with buffer containing edaravone (1 mg/L) after cold preservation. RESULTS: In the ED group, portal flow volume, bile production, and energy charge were significantly ameliorated. Lipid peroxidation, elevation of hepatic enzymes, and release of tumor necrosis factor-alpha and interleukin-1 beta were significantly alleviated, compared with the NHB group. CONCLUSIONS: These results suggested that edaravone has suppressive effects on warm I/R injury in liver grafts from NHBDs.

Microsurgical back wall support suture technique with double needle sutures on hepatic artery reconstruction in living donor liver transplantation.

OBJECTIVES: In living-donor-liver transplantation (LDLT), microsurgical reconstruction of the hepatic artery is an essential but challenging issue. Especially using a living donor graft, the hepatic artery is short, the intimal damage may be severe, and the usable vessel grafts are limited compared with cadaveric donors. Thus, sometimes it is difficult to use a conventional twist reconstruction technique in which one needs to turn over the hepatic artery. METHODS: To overcome these difficulties, we began to use a back wall support suture technique. From July 1991 to June 2007, we performed 110 LDLTs. In 87 cases, we used the conventional twist technique. In the most recent 23 cases, we used a back wall support suture technique. To put it briefly, we placed 2 sutures at the deepest, most difficult points in the artery for backside support. Each stitch was placed from the inner side of the arterial wall to the outer side with double needle sutures. The subsequent sutures were placed forward on either side adjacent to the previous suture. RESULTS: The total ratio of hepatic artery thrombosis (HAT) was 8.2% (9/110). In the conventional twist technique group, HAT occurred in 8 cases (9.2%). In the new technique group, it occurred in only 1 case that had an intimal dissection in the recipient artery (4.3%). Thus there was no HAT associated with the arterial anastomosis in the new technique group. CONCLUSION: Our technique allows for safe intimal adaptation without turning over the artery. In conclusion, this back wall support suture technique may contribute to more satisfactory results.

Parkinsonism during cyclosporine treatment in liver transplantation: an unusual case report.

OBJECTIVES: Cyclosporine (CyA) has been associated with various neurological reactions but parkinsonism is not generally recognized as a nervous system side effect. We describe herein a rare case, in that the patient developed parkinsonism with rest tremor after receiving CyA following orthotopic liver transplantation (OLT). METHODS: The patient was a 42-year-old man who had liver cirrhosis with hepatitis C. We performed OLT because of liver failure and started immunosuppressive therapy with CyA + methylprednisolone + CD25 antibody. Ten days after OLT, he developed parkinsonism with a rest tremor. The patient did not have a pre-existent neurological disorder, and had not received significant amounts of dopamine-blocking drugs. RESULTS: We administered levodopa with marked improvement. Three days after that event, the neurologist suggested the possibility of drug-induced parkinsonism. We converted the immunosuppressive drug from CyA to tacrolimus. After that, the symptom disappeared. At 75 days after OLT, he was discharged with no neurological medication and now he is completely recovered. CONCLUSION: We think that parkinsonism may be an occasional consequence of CyA because of its relation to withdrawal of the drug and the lack of another evident cause.

Present status of pancreas transplantation in Japan--donation predominantly from marginal donors and modified surgical technique: report of Japan pancreas transplantation registry.

In Japan, organ donation has been still limited because of the strict donor criteria. The aim of this study was to show the effectiveness of pancreas transplantation (PTx) by analyzing the outcomes even under poor donor conditions. Thirty-six cases of PTx (32 simultaneous pancreas and kidney transplantations [SPK], 4 pancreas after kidney transplantations) performed during the last 8 years were examined especially for donor characteristics. Mean donor age of 41.4 +/- 11.9 years was considerably older compared with that in the United States and Europe; donors aged over 40 years comprised 67% of the total. According to the criteria described by Kapur, 29 cases (81%) in our series would be considered marginal. Thus, to increase blood supply into the pancreatic head, the gastroduodenal artery (GDA) was anastomosed using donor artery to common hepatic artery or iliac Y graft. These procedures were performed in 16 of the 24 cases in which there was liver procurement. Eventually, 34 cases (94%) preserved GDA continuity. Mean total cold ischemic time of pancreatic grafts was 12 hours 15 minutes. Of 214 registrants, 17 patients on the waiting list for SPK died of diabetic complications. To date, patient survival remains 100% with a mean follow-up period of 33 months. Pancreas graft survivals at 1, 3, and 5 years posttransplantation were 92%, 80%, and 80%, respectively. In contrast, kidney survivals were 91%, 91%, and 91%, respectively. The integrity of the pancreas head and duodenum by preservation of the GDA continuity might have decreased the risk associated with the marginal donors.

Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling.

Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures.

Molecular basis of CD36 deficiency. Evidence that a 478C-->T substitution (proline90-->serine) in CD36 cDNA accounts for CD36 deficiency.

CD36 deficiency is divided into two subgroups: neither platelets nor monocytes express CD36 (type I deficiency), and monocytes express CD36 in spite of the lack of platelet CD36 (type II deficiency). We have already demonstrated that a 478C-->T substitution (proline90-->serine) in platelet CD36 cDNA predominates in type II deficiency (Kashiwagi, H., S. Honda, Y. Tomiyama, H. Mizutani, H. Take, Y. Honda, S. Kosugi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1993. Thromb. Haemostasis. 69:481-484). In this study, we revealed that monocyte CD36 cDNA from two type II deficient subjects was heterozygous for C478 and T478 form, while platelet CD36 cDNA of these subjects consisted of only T478 form. In a type I deficient subject, both platelet and monocyte CD36 cDNA showed only T478 form. Expression assay using C478 or T478 form of CD36 cDNA transfected cells revealed that there was an 81-kD precursor form of CD36, and that the maturation of the 81-kD precursor form to the 88-kD mature form of CD36 was markedly impaired by the substitution. The mutated precursor form of CD36 was subsequently degraded in the cytoplasm. These results indicate that the 478C-->T substitution directly leads to CD36 deficiency via defects in posttranslational modification, and that this substitution is the major defects underlying CD36 deficiency.

Continuous low-dose human atrial natriuretic peptide promotes diuresis in oliguric patients after living donor liver transplantation.

Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute renal failure (ARF) after liver transplantation (OLT). We evaluated renal function in OLT patients with or without ARF, describing cases unresponsive to loop diuretics successfully treated with continuous low-dose ANP infusion without hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver transplantations (LDLTs) were performed in 26 patients. One case was excluded due to the need for continuous hemodialysis (HD) during the operation. Of the 26 cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other 20 were ARF-free (group 1). The median follow-up was 24 months. No patient required either continuous or intermittent HD. Only one patient died due to multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and intraoperative blood loss in group 2 were significantly higher than those in group 1. Three cases in group 2 failed to improve on high-dose loop diuretics with low-dose dopamine, exhibiting fluid overload. The remaining three cases in group 2 responded to conventional diuretic treatments. Continuous low-dose ANP was started 2, 4, or 5 days after LDLT, and urine output significantly increased after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1 month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss during the operation caused ARF, but did not affect renal function after LDLT. Continuous low-dose ANP improved renal function and diuresis for oliguric ARF patients, preventing the need for HD or continuous venovenous hemodialysis.

Localization of ubiquitin carboxyl-terminal hydrolase-L1 in cynomolgus monkey placentas.

Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) is a restrictedly expressed enzyme in neural and reproductive tissues, and it is considered to have a significant role in reproduction. In the present study, we investigated the localization of UCH-L1 in placenta of cynomolgus monkeys (Macaca fascicularis). UCH-L1 protein was detected in cytotrophoblasts of chorionic plate and villi, and decidual cells of decidua basalis in cynomolgus monkey placenta, and the amount of UCH-L1 protein in whole placenta increased as pregnancy progressed. These results supported that UCH-L1 is necessary for placental and fetal development in primate placenta. This is the first report to demonstrate the presence of UCH-L1 in primate placenta, and the cynomolgus monkey may be a useful model for the study of the functions of the ubiquitin-proteasome system in human pregnancy.

Stromal cell-independent differentiation of human cord blood CD34+CD38- lymphohematopoietic progenitors toward B cell lineage.

To study the cytokine regulation of early stages of human B-lymphopoiesis, we developed a stroma-free two-step culture system. Single human cord blood CD34+CD38- cells were individually cultured by micromanipulation with interleukin (IL)-3, stem cell factor (SCF), fIt3 ligand (FL), IL-6 and granulocyte colony-stimulating factor (G-CSF). About 10% of the cells formed primary colonies, which were individually tested for myeloid and B-lymphoid potentials by reculturing aliquots of the primary colony cells into secondary myeloid and B-lymphoid cultures. One third of the primary colonies proved capable of differentiation into CD19+IgM+ cells, as well as into myeloid lineage cells. RT-PCR analyses revealed that some cells in the primary culture had already matured to express B cell-specific transcripts. Thus, the combination of IL-3, SCF, FL, IL-6 and G-CSF supported the differentiation of CD34+CD38- lymphohematopoietic progenitors toward B cell lineage in addition to myeloid lineages. Screening of cytokines to identify the minimum requirement of cytokines in the primary culture revealed that IL-3 and SCF were essential and that the addition of FL, and to a lesser extent IL-6 or G-CSF, to the combination of IL3 and SCF remarkably enhanced the primary colony formation and the generation of CD19+ cells in the secondary B-lymphoid culture.

Culture system for extensive production of CD19+IgM+ cells by human cord blood CD34+ progenitors.

We established a co-culture system with a monolayer of the murine bone marrow (BM) stroma cell line, MS-5, in which human cord blood CD34+ cells differentiated to CD19+ cells. The addition of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) highly enhanced the production of CD19+ cells. The expansion of the cell numbers was over 10(3)-fold. Furthermore, a significant proportion (<45%) of the cells expressed surface IgM (sIgM) after 5 weeks of co-culture. CD34+CD19- cells also showed a similar development of CD19+ cells and CD19+sigM+ cells. Filter separation of MS-5 cells and CD34+ cells did not inhibit the growth of CD19+ cells. However, when further purified CD34+CD19-CD13- CD33- cells were cultured in the presence of MS-5 cells with or without a separation filter, CD19+ cells did not appear in the non-contact setting. This result suggested that the highly purified CD34+CD19-CD13-CD33- progenitors require the cell-cell contact for the development of CD19+ cells, whereas other CD34+ fractions contain progenitors that do not require the contact. This co-culture system should be useful for the study of early human B-lymphopoiesis.

New strategy for ABO-incompatible living donor liver transplantation with anti-CD20 antibody (rituximab) and plasma exchange.

It is more difficult to control humoral rejection in living donor liver transplantations (LDLT) across the ABO blood group barrier than in matched or compatible combinations. We achieved excellent results in ABO-incompatible transplantation with novel immunosuppressive regimens and plasma exchange (PE). Among 82 LDLT were 10 cases of ABO-incompatible recipients, including three who were administered rituximab for rescue or prophylactic therapy. Pretransplantation PE was performed as necessary to maintain hemagglutinin titers below 1:16 and posttransplantation PE was performed when there were signs of hyperacute rejection associated with high titers. Induction immunosuppression consisted of FK506, steroid, mycophenolate mofetil (MMF), and rituximab. The first patient was administered rituximab with deoxyspergualin (DSG), steroid pulse therapy, and PE on postoperative day (POD) 7, because of biopsy-proven humoral acute rejection. The titers and LFTs improved drastically. The second and third patients were administered rituximab just after the operation with other routine immunosuppressants for prophylaxis of hyperacute rejection. The second patient showed a slight deterioration in LFTs with an elevated titer, which normalized after steroid pulse therapy and PE. The third patient had no episodes of rejection. At present, that is 27, 17, and 6 months after the operations respectively, the 3 transplant recipients are in stable condition.

Experience with recipient's superficial femoral vein as conduit for middle hepatic vein reconstruction in a right-lobe living donor liver transplant procedure.

Middle hepatic vein reconstruction during the right-lobe living donor liver transplant procedure has been recognized to be a significant factor. We initially reconstructed only a single middle hepatic vein orifice draining into segment 8. In cases where the right-lobe liver graft has several major middle hepatic vein tributaries, including veins draining segment 5 that are remote from the right hepatic vein orifice, a long and thick interposition conduit is necessary for reconstruction. Among 11 consecutive adult patients who received a right-lobe liver graft without a middle hepatic vein at our institution, 8 underwent reconstruction of all major middle hepatic vein tributaries using a vein graft from the recipient's superficial femoral vein. The remaining 3 patients had no major middle hepatic vein tributaries. Posttransplant-computed tomography imagings showed increased liver mass with a patent superficial femoral vein graft in 8 patients. In the absence of a venous system from a deceased donor, a recipient superficial femoral vein offers an excellent size match to maintain the venous outflow of middle hepatic vein tributaries. Reconstruction with recipient superficial femoral vein plays an important role in maximizing liver function and minimizing morbidity in the early posttransplant period.

Beneficial effect of FR183998, a Na+/H+ exchanger inhibitor, on porcine pancreas allotransplantation retrieved from non-heart-beating donors.

Activation of Na(+)/H(+) exchanger (NHE) may have an important role in the ischemia/reperfusion injury by producing intracellular calcium overload. Recent studies have shown a beneficial effect of an NHE inhibitor on the ischemia/reperfusion injury in the heart. In this study, we examined the effect of FR183998, a potent NHE inhibitor, in porcine pancreas allotransplantation from non-heart-beating Landrace pig donors (NHBDs). The four experimental groups included: untreated with no preservation (group 1; n = 3), treated with no preservation (group 2; n = 5), untreated with preservation (group 3; n = 6), and treated with preservation (group 4; n = 4). The preservation was made in ice-cold University of Wisconsin (UW) solution for 24 hours. The groups treated received 1 mg/kg FR183998 before donor cardiac arrest and 10 mg in the UW solution flush in situ. Serum blood glucose, insulin, and amylase were measured daily. An intravenous glucose tolerance test (IVGTT) was performed on the postoperative day (POD) 7 when pigs were sacrificed for histological examination. Graft survival rates on that day in groups 1,2,3, and 4 were 3 of 3; 5 of 5; 3 of 6; and 4 of 4, respectively. The mean K values of IVGTT in groups 3 and 4 were 0.78 +/- 0.10 and 1.27 +/- 0.16, respectively, which were significantly different (P < .05). Upon histological examination, pancreatic tissue in group 3 showed more severe edema and necrosis than other groups. FR183998 may be considered beneficial for ischemia/reperfusion injury to pancreatic grafts from NHBDs.

Excessive portal flow causes graft nonfunction in small size liver transplantation: an experimental study in pigs.

We investigated the effects of portocaval shunt (PCS) on excessive portal flow in producing sinusoidal microcirculatory injury in small-for-size liver transplants in pigs. The posterior segment of a whole liver (25%) was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS (n = 11), and group B, graft without PCS (n = 11). The PCS was a side-to-side anastomosis of the portal vein and the inferior vena cava. In group A, eight pigs survived for more than 4 days; all pigs except for one died of graft nonfunction within 24 hours in group B. The portal flow after reperfusion decreased in group A, but increased about three times greater in group B than that before the operation (P < .01). In group B, destruction of the sinusoidal lining and bleeding in the periportal areas were observed after reperfusion, findings that were not recognized in group A. These results suggest that graft nonfunction after small-for-size liver transplantation may be attributable to excessive portal flow producing sinusoidal microcirculatory injury.

Synergistic enhancement of class I major histocompatibility complex antigen expression in K562 cells induced by recombinant human interferon-gamma and tumor necrosis factor in combination.

The effects of recombinant preparations of human interferon-gamma (rIFN-gamma) and tumor necrosis factor (rTNF), alone or in combination, on class I or class II major histocompatibility complex (MHC) antigen induction were studied using K562, a multipotent hematopoietic precursor cell line. Class I antigens were weakly induced by rIFN-gamma; however, rTNF at any concentration examined (1-1000 U/ml) showed no effect on the induction of class I or class II antigens in the cells. rIFN-gamma (600 U/ml) induced approximately 20% of the cells to express class I antigens after 72-h exposure, whereas 81% of the cells demonstrated class I antigens on their cell surfaces when the cells were simultaneously exposed to 600 U/ml of rIFN-gamma and 1000 U/ml of rTNF. The class II MHC antigens were not induced by the treatments with rIFN-gamma or rTNF, alone or in combination. A synergistic increase of mRNA for class I MHC molecules was demonstrated by treatments of the cells with rIFN-gamma and rTNF in combination. rTNF, but not rIFN-gamma, weakly induced granulocyte-monocyte antigens on the cell surface; however, no synergism was observed on the induction of these antigens by the combined treatments with rIFN-gamma and rTNF. These results indicate that class I MHC antigen expression on K562 cells can be induced by IFN-gamma in cooperation with TNF in a manner different from myeloid antigen expression.