We investigated whether liver transplantation affects endogeneous erythropoietin (EPO) synthesis. Serum EPO levels were measured before transplantation and during the peri-transplant period in ten consecutive paediatric patients who had received a liver allograft without recombinant EPO therapy. All patients were anaemic on post-operative day 1 (POD 1); however, the haemoglobin levels of three patients gradually increased and required phlebotomy on POD 5-9. The serum levels of EPO in all patients were within the normal range before surgery, but six of the ten patients had a transient increased level of EPO at 1248 h after transplantation. A transient increase of endogeneous EPO following paediatric liver transplantation may be associated with extramedullary erythropoiesis in human liver grafts.

Child↗

PubMed1998

Detection of Epstein-Barr virus and HTLV-I in T-cell lymphomas of skin in Taiwan.

Viral etiology has been associated with the pathogenesis of T-cell lymphomas of skin (TCLS). Therefore, we studied the presence of Epstein-Barr virus (EBV) and type I human T-cell lymphotropic virus (HTLV-I) in tumor cells of TCLS to determine the significance of these viruses with the disease. A retrospective study was conducted on the skin tissues from 28 Chinese patients with TCLS. We used in situ hybridization, immunohistochemistry, and polymerase chain reaction to determine the presence of viruses. Among the 28 cases, HTLV-I was only detected in two cases with adult T-cell leukemia/lymphoma, not in other cases of TCLS. This suggests that HTLV-I may not play a significant role in the oncogenesis of TCLS in Chinese patients. Conversely, EBV was detected in 12 cases (42.9%), including the secondary TCLS, large cell lymphoma, mycosis fungoides, adult T-cell leukemia/lymphoma, and angiocentric lymphoma. Nevertheless, latent membrane protein 1 was not detected in any of the EBV-positive cases. Neither was any correlation found between the presence of EBV in TCLS and the prognosis or the severity of the skin lesion. Although there is a close association of EBV with a portion of TCLS, its pathogenic role needs further investigation.

Adolescent↗

PubMed1998

Relatively low expression of multidrug resistance-1 (MDR-1) and its possible clinical implication in gastric cancers.

The mechanism of drug resistance of gastric cancer cells has rarely been investigated. We specifically examine the magnitude and the biologic significance of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All patients had previously been treated in prospective clinical trials for advanced gastric cancer in our institution. Patients with adequate prechemotherapy gastric cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were selected for the determination of the expression rate of MDR-1. The results were designated as negative or positive by the independent interpretation of two pathologists. A subgroup of patients who had been treated with doxorubicin- or etoposide-containing regimens were selected for further correlation with drug sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women with a median age of 55 years, were studied. Eight (13.3%; 95% confidence interval, 6%-25%) of them had MDR-1 expression. None of the pertinent clinicopathologic features, including the histopathologic types of the tumors and the extent of the diseases, correlated with the expression of MDR-1. Among the 30 patients who had received doxorubicin- or etoposide-containing combination chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas 19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer is relatively low. Its expression, however, is clinically relevant and is useful in predicting the chemoresistance of patients with gastric cancer receiving doxorubicin- or etoposide-containing combination chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

An automatic diagnostic system for CT liver image classification.

Computed tomography (CT) images have been widely used for liver disease diagnosis. Designing and developing computer-assisted image processing techniques to help doctors improve their diagnosis has received considerable interests over the past years. In this paper, a CT liver image diagnostic classification system is presented which will automatically find, extract the CT liver boundary and further classify liver diseases. The system comprises a detect-before-extract (DBE) system which automatically finds the liver boundary and a neural network liver classifier which uses specially designed feature descriptors to distinguish normal liver, two types of liver tumors, hepatoma and hemageoma. The DBE system applies the concept of the normalized fractional Brownian motion model to find an initial liver boundary and then uses a deformable contour model to precisely delineate the liver boundary. The neural network is included to classify liver tumors into hepatoma and hemageoma. It is implemented by a modified probabilistic neural network (PNN) [MPNN] in conjunction with feature descriptors which are generated by fractal feature information and the gray-level co-occurrence matrix. The proposed system was evaluated by 30 liver cases and shown to be efficient and very effective.

Algorithms↗

PubMed1998

The Quilty lesion enigma: focal apoptosis/necrosis and lymphocyte subsets in human cardiac allografts.

Quilty lesions, as first described by Billingham in 1981, or 'Quilty Effect' (QE) are distinct endomyocardial mononuclear cell infiltrates that have been observed in human heart transplant recipients, as well as in experimental models of heart transplantation. In the present investigations, the pattern and extent of apoptosis (programmed cell death) and myocyte necrosis, as well as specific lymphocyte subsets in Quilty lesions was assessed. Endomyocardial biopsies obtained from 13 patients at 10-3362 days post-transplant were examined. Apoptosis, as identified by DNA nick end-labeling, was found in myocytes at the periphery of Quilty lesions in 11 of 13 cases (85%), and 'early' stages of myocyte necrosis, as demonstrated by specific staining with alpha light chain myosin monoclonal antibodies (mAb), was observed at the same sites in 10 of 13 cases (77%) of both Quilty type A and type B lesions. Apoptosis was not identified in the lymphocyte infiltrates of any of the lesions examined. Lymphocyte subsets were characterized using mAb for T cell receptor (CD3), for helper/inducer T cells (CD4), for cytotoxic/suppressor T cells (CD8) and for mature B cells (CD20). Immunostaining revealed separate clusters of T lymphocytes with less prevalent B cells within the Quilty lesions. CD4+ cells were found in larger numbers than CD8+ cells in all cases. Non-B, non-T large lymphocytes were occasionally present. Except for the extent of the cellular infiltrate, no major cytochemical lymphocyte distribution differences were found between Quilty type A and B lesions. Myocyte apoptosis and early necrosis at the periphery of Quilty lesions suggest that early myocyte injury occurring in B lesions may represent initial or 'abortive stages' of cardiac allograft rejection. Why these lesions do not progress to overt rejection indeed warrant further detailed studies.

Actin Cytoskeleton↗

PubMed1998

Molecular cloning and characterization of fengycin synthetase gene fenB from Bacillus subtilis.

A fengycin synthetase gene, fenB, has been cloned and sequenced. The protein (FenB) encoded by this gene has a predicted molecular mass of 143.6 kDa. This protein was overexpressed in Escherichia coli and was purified to near homogeneity by affinity chromatography. Experimental results indicated that the recombinant FenB has a substrate specificity toward isoleucine with an optimum temperature of 25 degrees C, an optimum pH of 4.5, a Km value of 922 microM, and a turnover number of 236 s(-1). FenB also consists of a thioesterase domain, suggesting that this protein may be involved in the activation of the last amino acid of fengycin.

Amino Acid Sequence↗

PubMed1998

Testicular GATA-1 factor up-regulates the promoter activity of rat inhibin alpha-subunit gene in MA-10 Leydig tumor cells.

We have previously demonstrated that the basal transcription of rat inhibin alpha-subunit gene in a mouse testicular Leydig tumor cell line, MA-10, depends upon a 67-bp DNA fragment at the position of -163 to -97. Within this promoter region two GATA motifs were observed. In this study, we investigated the possible role of GATA-binding proteins in the regulation of inhibin alpha-subunit gene transcription in testicular cells. Northern blot and RT-PCR analyses showed that mRNAs encoding GATA-binding proteins, GATA-1 and GATA-4, were detected in mouse and rat testis and in MA-10 and rat Sertoli cells. Testis-specific GATA-1 mRNA, which is transcribed from a promoter 8 kb upstream to the erythroid exon I of mouse GATA-1 gene, was also identified in MA-10 cells. Mutations of GATA sequences in alpha-subunit promoter markedly decreased the transcriptional activity of alpha-subunit gene when measured by their ability of transient expression of a bacterial reporter gene, chloramphenicol acetyltransferase (CAT), in MA-10 cells. Cotransfection of alphaCAT chimeric construct with cDNA expression plasmid coding for mouse GATA-1 or GATA-4 protein revealed that GATA-1 but not GATA-4 can transactivate alpha-subunit promoter in a dose-dependent manner. The transactivation by GATA-1 was inhibited if GATA sequences in alpha-subunit promoter were mutated. Furthermore, electrophoretic mobility shift assay demonstrated that GATA-binding proteins present in nuclear extracts of MA-10 cells and rat testis interacted with the GATA motifs in alpha-subunit promoter, and the GATA-1 in these nuclear extracts formed a supershifted immunocomplex with antibody raised against mouse GATA-1 protein. We therefore concluded that the basal transcription of inhibin alpha-subunit gene in testicular MA-10 cells is up-regulated by testicular GATA-1 but not GATA-4 through its interaction with the GATA motifs in alpha-subunit promoter. In summary, we have provided the first evidence of the functional role of a GATA-binding protein in the regulation of testicular gene expression.

Animals↗

PubMed1998

Lymphoproliferative disorder after liver transplantation.

Lymphoproliferative disorder (LPD) is a well recognized complication of solid organ transplantation. It is associated with Epstein-Barr virus (EBV) infection and is often a fatal complication of immunosuppression. We report a 2.5-year-old boy who developed LPD presenting as small bowel lymphoma after liver transplantation. The patient had intermittent fever after transplantation and reactivation of latent EBV infection was documented by pre- and posttransplant serologic tests. About 5 months after his liver transplantation, the patient had sudden onset of abdominal pain and emergency laparotomy was performed for peritonitis. He proved to have multiple small bowel perforations caused by B cell lymphoma and died of multiple organ failure 9 days after operation, despite aggressive treatment and stopping immunosuppressive agents. We conclude that prevention of overimmunosuppression in pediatric recipients after liver transplantation and early detection and treatment of LPD are important to decrease this often-fatal complication.

Child, Preschool↗

PubMed1998

Development and use of an enzyme-linked immunosorbent assay to monitor serum and urine acepromazine concentrations in thoroghbreds, and possible changes associated with exercise.

OBJECTIVES: To develop an ELISA that is sensitive and suitable for measurement of immunoreactive acepromazine (ACP) in horse serum and urine and to determine the acute effects of exercise on immunoreactive ACP values in Thoroughbreds. ANIMALS: 12 healthy Thoroughbreds (5 mares, 5 geldings, 2 stallions), aged 2 to 8 years. PROCEDURE: A commercially available antibody and a horseradish peroxidase-conjugated oxime derivative of immunoreactive ACP were used to develop a one-step ELISA. Horses were used in a crossover design study to evaluate possible effects of treadmill exercise on serum and urine ACP concentrations after a single (25 mg) IM injection of the drug. RESULTS: Immunoreactive ACP was detectable at concentrations as low as 50 pg/ml in serum and 100 pg/ml in urine, with intra- and interassay variabilities of 1.1 and 5.2%, respectively. The antibody had some cross-reactivity with a limited number of other phenothiazines. After drug administration, serum ACP immunoreactivity achieved a peak concentration (10.5 ng/ml) within 30 minutes and could be measured up to 48 hours in serum and 120 hours in urine. Although exercise had no significant effect on serum drug concentration, immunoreactive ACP disappeared more quickly (by 48 hours) from the urine of horses in the exercised group. CONCLUSIONS: This one-step ELISA provides a simple and sensitive means to measure immunoreactive ACP in equine serum and urine. The ability to detect drug several days after administration of a low dose of ACP should augment efforts to control illicit use of this drug in performance horses. Potential changes in ACP kinetics after exercise warrant further study.

Acepromazine↗

PubMed1998

Pregnancy after orthotopic liver transplantation in a Chinese patient: a case report.

A 28-year-old woman who had undergone orthotopic liver transplantation due to decompensated liver cirrhosis conceived 2 years after the operation. Immunosuppressive treatment was maintained during the pregnancy. The case was managed as high risk. Although intrauterine growth retardation arose in the third trimester, the patient finally gave birth to a healthy male baby. To our knowledge, the present case is the first successful pregnancy of an Asian woman after liver transplantation. The related problems are also discussed.

Adult↗

PubMed1998

Intraoperative Doppler ultrasound in liver transplantation.

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Adolescent↗

PubMed1998

Post-transplant changes of segment 4 after living related liver transplantation.

The purpose of this study was to evaluate the outcome of the medial segment of the graft after living related liver transplantation (LRLT). Of the 12 pediatric recipients who underwent LRLT, 2 received whole left liver graft, 1 left lateral segment graft, and 9 extended left lateral segment grafts. The hepatic veins of the donor were reviewed and the volume of the medial segment and left lateral liver was measured before and 6 months after liver transplantation. The flow velocity and direction of the portal vein in the medial segment graft was also evaluated by Doppler ultrasound. The grafted livers of all recipients showed a substantial increase in volume of 9-120% 6 months after LRLT. For the left lateral segment, an increase in volume was found in all cases ranging from 21 to 245%. For the medial segment, volume increases of 5-48% were found in seven cases with normal hepatopetal flow detected inside the segment 4 intrahepatic portal vein. In four cases, the partial medial segment graft of the extended left lateral liver graft decreased in volume from 33 to 69%. Among these four cases, slow flow (n = 2) and hepatofugal flow (n = 1) were also detected in the intrahepatic portal vein of the medial segment. Mapping of the tributary of the hepatic veins of the graft revealed inadequate venous drainage of the partial segment 4 graft, which may be considered as the cause of the atrophic change of the partial segment 4 graft. In conclusion, different regenerative rates between the left lateral segment and the medial segment were noted, with a greater rate in the left lateral segment. The venous drainage of the medial segment is of primary concern in the determination of the outcome of the regeneration. Atrophic change occurs when inadequate hepatic venous drainage is encountered. Therefore, if an extended left lateral liver graft is required, the corresponding draining veins of the partial medial segment must be preserved. Otherwise, whole left liver or left lateral segment graft would be a better choice.

Blood Flow Velocity↗

PubMed1998

Effects of ondansetron on postoperative emesis in Chinese children.

BACKGROUND: Postoperative nausea together with vomiting (PONV) is a common adverse effect of general anesthesia. Ondansetron, a new serotonin (5-hydroxytryptamine) receptor antagonist of the subtype 3 is shown to be effective and safe in the prophylaxis and treatment of PONV. However, the clinical experiences of using ondansetron for prevention of PONV is lacking in Taiwan. The purpose of this study is to evaluate the efficacy and safety of ondansetron for prevention of PONV in Chinese children. METHODS: Eighty pediatric patients aged from 2 to 12 years undergoing herinorrhaphy were prospectively randomized to receive either ondansetron 0.1 mg/kg or saline placebo. All patients received general anesthesia with tracheal intubation. The parents of patients were educated how to record the episodes of postoperative emesis and other complications and answer questions in the form of questionnaire. The observation period lasted for 24 h postoperatively. RESULTS: The incidence of postoperative emesis was 55% and 10% in placebo and ondansetron group respectively. As to the severity of emetic symptoms it was milder in the ondansetron group. There was no difference in the incidence of other complications between the two groups. CONCLUSIONS: The intravenous administration of ondansetron 0.1 mg/kg is safe and effective in reducing postoperative emesis in Chinese children undergoing herinorrhaphy surgery.

Antiemetics↗

PubMed1997

Intracellular glutathione content of urothelial cancer in correlation to chemotherapy response.

We evaluated the possible correlation between intracellular glutathione (GSH) and drug sensitivity of urothelial cancer. Tissue GSH content of surgical specimens from 20 patients with urothelial cancer was assayed with high performance liquid chromatography (HPLC). GSH levels of cancer tissue (7.887 +/- 6.176 microM/mg protein) were significantly higher than GSH levels of normal mucosa (1.345 +/- 1.252 microM/mg). All patients having measurable lesions were then treated with methotrexate, epirubicin and cisplatin (MEC). These patients were classified into three groups according to clinical response criteria. GSH content in cancer tissue from four patients with complete response was 0.804 +/- 1.183 microM/mg protein. However, the cancer cells from patients with partial response and non-response contained a significantly higher level of GSH (6.295 +/- 2.459 (n = 8) and 12.955 +/- 6.141 microM/mg protein (n = 8), respectively). Intracellular glutathione content may play an important role in intrinsic resistance of urothelial cancer to MEC chemotherapy. It might be potentially used to predict drug sensitivity in urothelial cancer patients before starting chemotherapy.

Aged↗