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H H Lee

Publications and source records attributed to H H Lee.

At least 37 records · Page 2Linked to original sources

Sustained release of vascular endothelial growth factor from calcium-induced alginate hydrogels reinforced by heparin and chitosan.

A possible alternative for immunosuppression is a microencapsulation technique using hydrogels, which have been utilized for cell immobilization and drug delivery systems. Angiogenesis is crucial for delivery of the metabolic products to the host tissues as well as to supply oxygen and nutrients to cells. The local delivery of angiogenic growth factors, such as VEGF and basic FGF, has been recently studied to enhance angiogenesis on peripheral tissue of graft. In this study, we evaluated sustained VEGF release with a model using hydrogels coated with chitosan and heparin in vitro. We fabricated calcium alginate gels and chitosan-coated calcium alginate gels. Heparinized chitosan-coated calcium-induced alginate hydrogel beads were prepared by soaking chitosan-coated calcium alginate gels in heparin solution. We compared the stability and VEGF release manner between three kinds of hydrogels. To compare the stability, 5 mL of each hydrogel was incubated with 20 mL PBS under the rotational culture. Compression forces were measured using a rheometer. The amount of VEGF released from the gels was measured by ELISA. The heparin-coated chitosan alginate hydrogels showed the highest surface stability among the three hydrogels. VEGF from the heparinized gel was released in sustained manner up to 10 days in vitro. Chitosan-coated alginate gels released 90% of loaded VEGF within 5 days. These results suggest that local delivery of VEGF using a heparinized hydrogel may provide a long-term supply of angiogenic growth factor that might induce new vessel formation in vivo.

Alginates↗

Interpostion vein graft in living donor liver transplantation.

UNLABELLED: In adult-to-adult living donor liver transplantation (LDLT), right lobe grafts without a middle hepatic vein can cause hepatic congestion and disturbance of venous drainage. To solve this problem, various types of interposition vein graft have been used. OBJECTIVES: We used various types of interposition vein grafts for drainage of the paramedian portion of the right lobe in living donor liver transplantation. METHODS: From June 1996 to June 2003, 37 of 176 patients (128 adults, 48 pediatric) who underwent LDLT received vein grafts for drainage of segments V, VIII, or the inferior portion of the right lobe. RESULTS: In 36 adult cases the reconstruction included the inferior mesenteric vein of the donor (n = 14); cadaveric iliac vein stored at cold (4 degrees C) temperature (n = 5); cryopreserved (-180 degrees C) cadaveric iliac vein (n = 10); cryopreserved cadaveric iliac artery (n = 1 case); donor ovarian vein (n = 1); recipient umbilical vein (n = 3); recipient saphenous vein (n = 1); recipient left portal vein (n = 1); recipient left hepatic vein (n = 1). In a pediatric case with malignant hemangioendothelioma that encased and compressed the inferior vena cava, we used an interposition vein graft to replace the inferior vena cava. CONCLUSION: Various types of interposition vein grafts can be used in living donor liver transplantation. Cryopreserved cadaveric iliac vein and artery are useful to solve these drainage problems.

Adult↗

Case of living donor liver transplantation in a patient with biliary atresia combined with situs inversus.

Until recently, situs inversus was considered to be an absolute contraindication for liver transplantation. However, recent reports have suggested that situs inversus should not be considered a contraindication. This study presents a successful living donor liver transplantation performed in a 4-month-old male infant with biliary atresia and situs inversus. The surgical findings revealed abdominal situs inversus with polysplenia and an absent retrohepatic inferior vena cava and intestinal malrotation.

Adult↗

Polymerase chain reaction for the diagnosis of human polyomavirus-associated nephropathy in renal transplant recipients.

Human polyomavirus type BK may be related to interstitial nephropathy or renal-allograft dysfunction. Patients with nephropathy due to infection with human polyomavirus may be identified early using the polymerase chain reaction(PCR). We attempted to evaluate whether the positive response in the PCR test of BK virus DNA in the plasma of renal transplant recipients affects the function of the renal allograft. Seventy-seven patients were prospectively analyzed according to the operative sex, age, sources of allograft, serum creatinine levels during PCR test for BK virus, postoperative type of immunosuppressant, and presence of graft rejection. Two groups were distinguished according to the PCR result for BK virus: group 1 (n = 12) positive PCR reaction and group 2 (n = 65) negative reaction. The mean follow-up was 32.6 weeks. The incidence of positive PCR tests for BK virus replication after renal transplantation was 15.6%. Decoy cells in the urine were detected in 20.7%. The incidence of BK virus nephropathy was 1.3%. The mean serum creatinine levels of group 1 and 2 at the time of the PCR tests were 1.34 and 1.22, respectively. The rejection rates in group 1 and 2 were 8% and 4.5%, respectively (P > .05). We consider that a PCR assay to detect BK virus in renal recipients blood may be useful to identify patients at risk for nephropathy. It may serve as a noninvasive indicator of BK virus replication, although this study is limited by the short follow-up and small numbers.

Adolescent↗

Comparison of survival probabilities for living-unrelated versus cadaveric renal transplant recipients.

UNLABELLED: Any attempt to improve organ donation would be of benefit due to the growing shortage of cadaveric sources for transplantation. OBJECTIVE: We compared the graft survivals and possible predictive variables among renal transplant recipients with organs from living unrelated (LURD) versus cadaveric donors (CD). METHOD: Among 104 consecutive renal transplants performed from July 1992 to February 2003, 41 were from LURD and 24 from CD. Immunosuppressive regimens were based on cyclosporine and steroids with mycophenolate mofetil added after 1998. Patient and graft survivals were estimated using the Kaplan-Meier method and compared using log-rank tests. The significance level of predictive variables was analyzed with the Cox proportional hazard model. The follow-up period was 2 to 127 months (median 46 months). RESULTS: Eight recipients lost their grafts (six from LURD and two from CD) due to four chronic rejections, one acute rejection, one recurrence of primary disease, and one death with a functioning graft. The graft survival rates at 1, 3, 5, and 7 years were 97.6%, 91.9%, 88.5%, and 82.2% for LURD transplants versus 95.5%, 90.9%, 90.9%, and 90.9% for CD transplants, respectively (P > .05). Delayed graft function and donor age (>55 years old) were statistically significant predictors of graft survival among LURD transplants. Donor age (>55 years old) and multiple preoperative transfusion history were significant in CD transplants. CONCLUSION: LURD transplant survival was similar to that of CD transplants in our series. LURDs are an excellent source of organs to expand the donor pool.

Actuarial Analysis↗

Changes in expression of T-cell activation-related molecules and cytokines during tolerance induction in an allogeneic skin transplantation murine model.

Bone marrow transplantation after treatment with busulfan and costimulatory blockade with monoclonal antibodies (mAb) cytotoxic T lymphocyte antigen 4 (CTLA4)-Ig and anti-CD154 mAb or two-signal blockade using anti-CD45RB and anti-CD154 mAb are nonmyeloablative treatment regimens for allogeneic transplantation. There may be differences in the mechanisms of donor cell engraftment and reactive cell deletion by which these regimens induce donor-specific tolerance. Therefore, this study was performed to investigate changes in T cells and cytokines during tolerance induction toward allogeneic skin grafts. BALB/c and C57BL/6 mice were used as donors and recipients, respectively. Skin and bone marrow transplantations were performed and busulfan was administered. Three groups were treated with mAb as follows: group 1, anti-CD154 mAb; group 2, anti-CD154 plus anti-CD45RB mAb; and group 3, anti-CD154 mAb plus CTLA4-Ig. The proportions of CD4+ or CD8+ T cells and the expression of CD45RB isoforms on splenocytes were measured using flow cytometry and the production of cytokines by CD4+ T cells using enzyme-linked immunosorbent assay. Group 2 showed a significant reduction in the proportions of CD8+ T cells and CD45RB high isoforms compared with groups 1 and 3. The levels of interleukin (IL)-2 and IL-4 in group 2 were lower and higher than those of groups 1 and 3, respectively. In conclusion, the combined use of anti-CD154 and anti-CD45RB mAb decreases the CD8+ T-cell population and the expression of CD45RB, resulting in a Th2 cytokine profile, which may be a characteristic mechanism leading to donor cell engraftment and reactive cell deletion for donor-specific tolerance.

Animals↗

Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation.

INTRODUCTION: Because it is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have increased graft rejection rates, a serological crossmatch is routinely performed before kidney transplantation. But, the presence of these antibodies is not routinely monitored after transplantation. We investigated the panel-reactive antibody (PRA) response to know whether variations before or after kidney transplantation were associated with graft rejection. METHODS: We prospectively analyzed sera from 350 renal allograft recipients from September 1998 to March 2003. Pretransplantation and posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA. Recipients were stratified into 3 groups according to their PRA levels group I, PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%. RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33). Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326 pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA-positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326 posttransplantation PRA-negative subjects. Among the pretransplantation PRA stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in group II and 8.6% (28 of 326) in group I (P < .05). According to the postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16) in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection. CONCLUSION: Our study suggests that the PRA response pretransplantation and in the early posttransplantation period correlates with the kidney allograft rejection rate.

Adolescent↗

Posttransplantation lymphoproliferative disorder in pediatric liver transplantation.

INTRODUCTION: The aim of this study was to evaluate the clinical features of risk factors for posttransplantation lymphoproliferative disorder (PTLD) in pediatric liver transplantation. MATERIALS AND METHODS: Between June 1996 and June 2002, among 41 pediatric patients who underwent liver transplantation, 7 died in the postoperative period. Thirty-five patients, including 1 patient who died of PTLD, were reviewed. Based on the serology results, patients were divided into a high-risk group (EBV-naive recipients of EBV-positive grafts) and a low-risk group (patients other than those in the high-risk group). RESULTS: Five of 41 patients (12.2%) developed PTLD. All of them belonged to the high-risk group. The incidence of PTLD in the high-risk group was 31.3% (5 of 16). The mean duration between operation and diagnosis for PTLD was 9.8 months. Primary EBV infection developed at a median of 6 months after transplantation. Three of 5 patients developed rejection before the diagnosis of PTLD. One patient was diagnosed with laryngeal and gastrointestinal PTLD, whereas the other 4 had gastrointestinal PTLD. They experienced the following symptoms and signs: anemia (100%), hypoalbuminemia (100%), fever (80%), diarrhea (80%), gastrointestinal bleeding (80%), and anorexia (60%). CONCLUSION: The common features of PTLD development were as follows: (1) EBV-positive donors placed into EBV-naive recipients, (2) primary EBV infection approximately 6 months after transplantation, (3) young age, 1 year old at operation, and (4) requirement for intensive posttransplantation immunosuppression.

Child↗

Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.

Hepatitis B virus (HBV) prophylaxis is necessary to prevent de novo hepatitis B infection from HbcAb-positive donors. However, which protocol is more effective is somewhat controversial. Also, it is uncertain whether it is necessary to administer HBV prophylaxis for HbsAb-positive recipients. This study attempted to determine whether it is necessary to administer HBV prophylaxis for HbsAb-positive patients and to evaluate the efficacy of an HBIG monotherapy protocol. From May 1996 to July 2001, among 128 donors examined for HbcAb, 58 donors (45.3%) were HbcAb-positive. Eighteen HbcAb-positive grafts were transplanted to HbsAg-negative recipients. The 4 patients who died of unrelated causes were excluded from this study. Of 14 study cases, 12 recipients were HbsAb-positive, and 2 were HbsAb-naive. Prior to late 1998, we used HBV vaccination only for de novo infection prophylaxis. However, starting from December 1998, HBIG was administered from the time of the liver transplantation regardless of HBsAb positivity. The overall rate of de novo HBV infections from HbcAb-positive donors was 21.4% (3 of 14). All 3 recipients without HBIG prophylaxis presented with de novo HBV infections. Two were HbsAb-positive preoperatively. No de novo HBV infections occurred among recipients with HBIG prophylaxis. Therefore, it is essential to administer HBV prophylaxis even for vaccinated HbsAb-positive patients. HBIG monotherapy is effective to prevent de novo hepatitis B infections from HbcAb-positive donors in living donor liver transplantation.

Child↗

Can we expand the Milan criteria for hepatocellular carcinoma in living donor liver transplantation?

INTRODUCTION: The Milan criteria, namely, tumors 5 cm or less in diameter in patients with single hepatocellular carcinoma (HCC), no more than 3 tumor nodules, and each 3 cm or less in diameter in patients with multiple tumors, are accepted for cadaveric liver allocation. However, in living donor liver transplantation (LDLT), graft donation may only depend on the donor's intention. The aim of this study was to elucidate the feasibility of Milan criteria in LDLT. MATERIALS AND METHODS: From January 2001 to December 2002, 46 cases of liver transplantation (LT) for HCC included 5 hospital mortalities and 3 cadaveric transplantations, all of which were excluded. We classified the patients into Group I cases that met the Milan criteria and Group II cases that did not meet the Milan criteria. The analyses examined tumor-related risk factors affecting recurrence and survival, such as tumor size, number of tumor nodules, and presence of microvascular and macrovascular invasion. RESULTS: Twenty-one cases belonged to Group I and 17 to Group II. There was no significant difference in the recurrence or survival rates between Groups I and II. The risk factors affecting recurrence were macrovascular invasion and tumor size (5 cm). The number of tumor nodules and microvascular invasion did not appear to affect recurrence. The risk factor affecting survival was macrovascular invasion. CONCLUSION: We suggest that in selected cases the Milan criteria could be extended to increase the number of tumor nodules as long as the HCC were small and did not macrovascular invasion.

Cadaver↗

Small-for-size graft in adult living-donor liver transplantation.

In the era of living donor liver transplantation (LDLT), graft size is related to recipient prognosis. This study was performed to compare the clinical outcomes according to the graft-to-recipient weight ratio (GRWR) in adult LDLT. Seventy-nine adult patients who had undergone LDLT between June 1997 and June 2002 were retrospectively analyzed. The patients were divided into two groups according to the GRWR (group I, GRWR < 0.8%, n = 11; group II, GRWR > or = 0.8%, n = 68). The mean follow-up period was 19.4 (range 1 to 48) months. The recipients were 62 men (78.5%) and 17 women (21.5%) of mean age 45.2 (range 18 to 63) years. The overall patient survival rates were 74.7% at 1 year and 70.7% at 2 years. The patient survival rate in group I was 54.6% at 1 year and 40.9% at 2 years, whereas that in group II was 77.9% at 1 year and 75.3% at 2 years, showing a significant difference (P = .03). There were no significant differences in postoperative total bilirubin, transaminase enzyme level, prothrombin time (INR), portal vein flow on Doppler sonography, amount of ascites through the drain, complications, or acute rejection rates between the two groups. In conclusion, the minimum acceptable graft size in an adult-to-adult LDLT is GRWR of 0.8%. This study suggests that careful postoperative management and/or technical modifications during surgery are necessary, because small-for-size grafts (GRWR < 0.8%) result in lower patient survival rates.

Adult↗

Risk factors on graft survival of living donor kidney transplantation.

UNLABELLED: Living donors have always been the basic resources of transplantation in our country, where cadaveric harvesting is still hampered for various reasons. OBJECTIVE: The aim of this study was to compare graft survival rates between living unrelated donor (LURD) and living related donor (LRD), to assess the potential risk factors for the graft survival, and to discuss the role of LURD. METHOD: From October 1991 to February 2003, 77 living donor renal transplants were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables were donor relationship, recipient age and sex, donor age and sex, HLA-DR mismatching, nonspecific blood transfusion history of donor, acute rejection episodes, repeated rejection episode (more than 3 times), delayed graft function, recurred primary disease, and immunosuppressive regimen. Graft survival rate was assessed with the Kaplan-Meier method and the significance of possible variables with the Cox proportional hazard model. RESULTS: Eleven recipients lost their grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%, and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%, and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05). Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1) and preoperative multiple transfusion history (RR = 4.2) were significant factors on graft survival in our series. CONCLUSION: Acute rejection episodes markedly decreased the long-term graft survival in live donor renal transplants. The use of LURD transplants provides graft survival comparable with LRD transplants and proper management to acute rejection is essential for long-term graft survival.

Adult↗

Induced eosinophilia and proliferation in Angiostrongylus cantonensis-infected mouse brain are associated with the induction of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK signals.

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we show that A. cantonensis-induced eosinophilia and inflammation might lead to the induction of IAP/NF-kappaB, JAK/STAT1 and MEKK1/JNK signals. The phosphorylation levels of JAK and JNK, STAT1, IAP, NF-kappaB and MEKK1 protein products were significantly increased after 12 days or 15 days of A. cantonensis infection. However, no significant differences in MAPKs such as Raf, MEK-1, ERK1/2 and p38 expression were found between control and infected mice. The activation potency of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK started increasing on day 3, with significant induction on day 12 or day 15 after A. cantonensis infection. Consistent results were noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in the brain tissues of infected mice. These data suggest that the development of brain injury by eosinophilia of A. cantonensis infection is associated with activation of JAK/STAT1 signals by cytokines, and/or activation of MEKK1/JNK by oxidant stress, and/or activation of NF-kappaB by increasing IAP expression.

Angiostrongylus cantonensis↗

Induction of matrix metalloproteinase-9 in murine eosinophilic meningitis caused by Angiostrongylus cantonensis.

Matrix metalloproteinases (MMP) have been implicated in the pathogenesis of various inflammatory diseases of the central nervous system. In the present study, a gelatinase was found to be induced in parasitic meningitis caused, in mice, by Angiostrongylus cantonensis. The enzyme had a molecular weight of about 94 kDa, showed maximal activity between pH 6 and pH 8, and was clearly inhibited by EDTA and 1,10-phenanthroline but not by leupeptin or phenylmethanesulphonyl fluoride. When samples of cerebrospinal fluid from the mice with meningitis were blotted with specific antiserum against gelatinase B (MMP-9), a 94-kDa immunopositive band was observed, indicating that the induced gelatinase was MMP-9. In the A. cantonensis-infected mice, immuno-histochemistry demonstrated MMP-9 within the endothelial cells lining the vascular spaces of the brain and in the leucocytes that were found, in aggregates, in the subarachnoid space. Leucocytes may play an important role in the pathogenesis of inflammatory disorders of the central nervous system.

Angiostrongylus cantonensis↗

Ultrastructural localization of matrix metalloproteinase-9 in eosinophils from the cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis.

Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of eosinophilic meningitis caused by Angiostrongylus cantonensis. In the present study, such meningitis in mice was found to be associated with elevated expression of MMP-9 mRNA, elevated MMP-9 concentrations and enhanced MMP-9 activity in the cerebrospinal fluid (CSF). Immunocytochemistry showed that an anti-MMP-9 antibody reacted with macrophages, neutrophils and eosinophils from the CSF. As eosinophils are generally considered to be effector cells in host defence against A. cantonensis infection, high-resolution immuno-electron microscopy was then used to confirm the localization of MMP-9 in the eosinophils from the CSF. The method used, which was based on immunogold, indicated that the eosinophilic MMP-9 was mostly localized in the 'small' granules in the cytoplasm and along the cell membrane, and not in the crystalloid-containing secretory granules observed. It therefore appears that MMP-9 is synthesised and/or stored in the small granules of the eosinophils, and is released into the subarachnoid space of the host's brain by secretion or cell rupture.

Angiostrongylus cantonensis↗

Identification and characterization of mutations underlying Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA).

Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA; MPS IIIA) is caused by a deficiency of the lysosomal enzyme haparan N-sulphatase (NS). The genomic DNA segments of the NS gene from two Chinese patients with MPS IIIA were amplified by polymerase chain reaction, followed by DNA sequencing to study the molecular lesions. Four mutations (i.e. N42K, D235N, P293S and R377C) and five polymorphisms (i.e. IVS2-72A --> G, IVS2-26T --> C, IVS5+17C --> T, IVS5-37GC --> CTGT and R456H) were identified. Transfection of COS-7 cells with cDNA mutagenized to the corresponding mutations did not yield active enzyme, demonstrating the deleterious nature of the mutations. Western blot analysis revealed a 62-kDa precursor and 56-kDa mature forms for cells transfected with wild-type and polymorphic R456H enzymes. For cells transfected with mutant enzymes, the reduction in precursor and mature forms suggests an increased degradation of the mutant enzymes. The polymorphic DNA haplotype of the NS gene was analysed in 52 unrelated subjects. All five polymorphisms were in Hardy-Weinberg equilibrium. The strong non-random association among the five polymorphisms suggests little or no recombination in the NS gene.

Adolescent↗

Cardiogenesis in the Drosophila model: control mechanisms during early induction and diversification of cardiac progenitors.

The dorsal vessel of Drosophila displays developmental, functional, and morphological similarities to the primitive linear heart tube of early vertebrate embryos. Because these similarities extend to the genetic and molecular level, Drosophila has become a fruitful model to study control mechanisms of early heart development. Herein we summarize recently obtained insights into control mechanisms during early induction and diversification of cardiac progenitors in Drosophila. We also show that induction of tinman, a key cardiogenic gene, in the dorsal mesoderm by Dpp (Drosophila BMP) involves protein/protein interactions between Tinman and the Smad proteins Mad and Medea, in addition to their DNA-binding activities to specific tinman enhancer sequences. Furthermore, we present evidence that binding of a high-mobility-group protein, HMG-D, to the Dpp-responsive enhancer of tinman as well as to the Tinman protein may be involved in the formation of a fully active enhancer complex.

Animals↗