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Biomedical subjects

K H Lin

Publications and source records attributed to K H Lin.

At least 163 records · Page 9Linked to original sources
PubMed1990

Isolation and characterization of a rat liver epithelial cell line resistant to the antiproliferative effects of transforming growth factor beta (type 1).

Rat liver epithelial cells resistant to the growth-inhibitory effects of transforming growth factor beta 1 (TGF-beta 1) were isolated after 3 h exposure to 1.5 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine followed by continuous treatment with 1 ng/ml TGF-beta 1 for 6 weeks. In comparison to the parental or N-methyl-N'-nitro-N-nitrosoguanidine-exposed rat liver epithelial cells (concentration causing 50% inhibition of the rate of DNA synthesis, 0.25 ng/ml), these cells were 10-fold more resistant to the antiproliferative effects of TGF-beta 1 and exhibited resistance to growth inhibition by a highly purified liver-derived growth inhibitor, recombinant human tumor necrosis factor, and transforming growth factor beta 2. Single cell cloning of these resistant cells led to the isolation of a nontransformed clonal cell population (clone 11) which maintained stable resistance in the absence of TGF-beta 1 treatment. Binding of 125I-labeled TGF-beta 1 to rat liver epithelial cells and clone 11 cells was similar. Clone 11 cells exhibited a 5-10-fold resistance to the cytotoxins Adriamycin and vinblastine as assessed by a clonogenic assay. This drug resistance was accompanied by an increase in the steady state levels of the mRNAs for multidrug resistance gene (MDR-1), glutathione S-transferase-P, TGF-beta 1, and c-myc genes. The data presented here suggest an association between resistance to the growth-inhibitory effects of TGF-beta 1- and MDR-1-mediated multidrug resistance.

Animals↗
PubMed1990

Hormone and DNA binding activity of a purified human thyroid hormone nuclear receptor expressed in Escherichia coli.

Using a T7 expression system, large amounts of the human placental c-erbA protein (h-TR beta 1) were expressed. From 1 liter of Escherichia coli culture, approximately 50-100 micrograms of purified h-TR beta 1 were obtained. Analysis of the binding data indicated that the purified h-TR beta 1 binds to 3,3',5-triiodo-L-thyronine (T3) with a Ka = 2.8 x 10(9) M-1. It binds to 3,3',5-triiodo-L-thyropropionic acid, 3,3',5-triiodo-L-thyroacetic acid, D-T3, L-thyroxine (T4), and 3',5',3-triiodo-L-thyronine with 475, 120, 39, 7, and 0.1%, respectively, of the activity of L-T3. This order of binding activity to T3 analogs is similar to that reported for the T3 nuclear receptor identified in tissues or cultured cells. Furthermore, the purified h-TR beta 1 binds to the T3 response element of the rat growth hormone gene. Thus, the purified h-TR beta 1 is active. To identify the hormone binding domain, the purified h-TR beta 1 was affinity labeled with underivatized [3',5'-125I]T4. A partial digestion by trypsin yielded a 125I-labeled 25-kDa fragment which was identified to be the domain Phe240-Asp456 by amino acid sequencing. Thus, the purified h-TR beta 1 appears suitable for other structural and functional studies.

Base Sequence↗
PubMed1990

Infant leukemia: an analysis of nine Chinese patients.

A study was made of the cellular and molecular characteristics of nine Chinese infants, consecutively presenting with acute leukemia. Five cases were acute lymphoblastic leukemia (ALL); four were acute nonlymphoblastic leukemia (ANLL). Hyperleukocytosis, hepatosplenomegaly, and poor response to conventional therapy were common features, and CNS involvement was detected at diagnosis in three cases. The blast cells from all five cases with ALL expressed early B-cell markers, i.e., HLA-DR+, CD19+, but CD10-. Terminal deoxynucleotidyl transferase (TdT) was present in blasts from four of the five cases and periodic acid-Schiff staining in blasts from two patients only. The leukemic cells of one patient also showed positive nonspecific esterase activity and expressed myeloid-associated antigens CD33 (My9), CD11 (OkM1), and CD14 (My4 and Mo2). Molecular analysis of leukemic cell DNA from this and two other patients showed rearrangement of the immunoglobulin (Ig) heavy-chain genes, but without any evidence of kappa light-chain gene rearrangement. T-cell receptor (TCR) genes remained in the germline configuration in these cases. Cytogenetic analysis showed translocation t(4;11) (q21;q23) in all four cases studied. In the group of ANLL, three cases belonged to the M4 and one to the M2 subtype. Chromosomal abnormality involving 11q23 was also detected in two patients: t(11;17)(q23;q11) and del(11)(q14q23) in each case respectively. Neither Ig nor TCR gene rearrangement was present in blast cells from patients with ANLL. The data indicate that chromosomal rearrangement of band 11q23 was quite common in Chinese infants with either form of leukemia, a finding that may have pathogenetic implications.

Antigens, CD↗
PubMed1990

Evolutionary study on the Coxsackievirus A 24 variant causing acute hemorrhagic conjunctivitis by oligonucleotide mapping analysis of RNA genome.

The evolution of the variant of Coxsackievirus A 24 (CA 24 v) which causes acute hemorrhagic conjunctivitis was explored. Using 15 isolates obtained from Southeast Asia during the period 1970-1986, the genetic distance between isolates was estimated from pairwise comparison of nucleotide changes deduced from common spots on oligonucleotide maps of the isolates. From regression analysis of the genetic distance and the time of isolation of the isolates, the evolutionary rate of CA 24 v was estimated to be 3.44 x 10(-4)/nucleotide/month. The phylogenetic relationship of these isolates was explored using the neighbor-joining method and the modified unweighted pair group method using arithmetic averages (UPGMA). The phylogenetic tree constructed indicates that CA 24 v appeared from one focal place in July 1968 +/- 25 months, very close to the time of the first world epidemic of, then newly recognized, acute hemorrhagic conjunctivitis.

Asia, Southeastern↗
PubMed1990

A subset of acute nonlymphocytic leukemia with expression of surface antigen CD7--morphologic, cytochemical, immunocytochemical and T cell receptor gene analysis on 13 patients.

An increasing number of acute leukemias coexpressed markers normally believed to be restricted to a single lineage have been found recently. This special subgroup of leukemias have drawn a lot of attention because of their biologic and clinical significance. In a study of 100 consecutive de novo ANLL patients diagnosed by FAB criteria, T-cell antigen CD7 was identified on the leukemic blasts of 13 patients, ten of whom had M1 subtype of leukemia, myeloblastic leukemia without maturation. All the patients showed positive staining with myeloperoxidase and expressed myeloid markers CD13 and/or CD33, but lacked CD11b, a marker of more mature myeloid cells. Combined staining with myeloperoxidase and CD7 of the cells from four patients revealed coexpression of both markers on the same cells. None of the patients expressed the two other T-cell antigens CD2 or CD5. All ten patients who had DNA analysis showed germline configuration of TCR beta and gamma chain genes. One patient had chromosomal translocation involving 11q23, t(11; 19) (q23; p13), which is the site frequently associated with both myeloid and lymphoid malignancies. The clinical implications of this subgroup of patients need further study on more patients, and need longer follow-up.

Adolescent↗
PubMed1990

Post-hepatitic aplastic anaemia in children in Taiwan, a hepatitis prevalent area.

Aplastic anaemia is a rare but serious complication of hepatitis, and hepatitis is an unusual cause of aplastic anaemia in children in the West. However, the relative frequencies of acquired aplastic anaemia in children in Taiwan, a hepatitis prevalent area, differ from those in the West, in the very high frequency of post-hepatitic aplastic anaemia (23.9% of all cases of aplastic anaemia). This may account for the higher incidence of aplastic anaemia in children in Taiwan. Although the prognosis of post-hepatitic severe aplastic anaemia was very poor, the present study using bone marrow transplantation, antithymocyte (or antilymphocyte) globulin, high-dose methylprednisolone and cyclosporin, etc., has improved the response rate and the survival.

Adolescent↗
PubMed1990

Acute abdomen in childhood leukemia.

With the continuing advancement in the treatment of childhood leukemia and the lengthened survival of these patients, an increased incidence of abdominal complications has been observed. A retrospective analysis of 364 patients with leukemia treated at the National Taiwan University Hospital from January 1977 through April 1988 was undertaken. Eleven patients (3.0%) developed abdominal complications during their course of disease, including acute appendicitis, intussusception, intestinal perforation, ovarian cyst rupture, etc. All of these patients had abdominal complications during the initial presentation or relapse of leukemia, and 9 (82%) of them had just received chemotherapy. Ten patients (91%) had thrombocytopenia and 7 (64%) had leukopenia. Blood cultures were positive in 5 patients (45%), and gram-negative enteric bacilli were isolated in 4 of them. All 5 septicemic patients had leukopenia or neutropenia. The clinical manifestations were nonspecific and were often masked. Most of the complications occurred in the right lower abdominal structures. Of the 7 children treated surgically, 3 had long term survival. Among the 4 patients who did not receive an operation, only 1 survived for more than 4 weeks. The mean length of survival tended to be longer in patients with additional surgical treatment. Prompt diagnosis and early aggressive treatment, under modern supportive facilities, appear to offer a more favorable outcome.

Abdomen, Acute↗
PubMed1990

Immunologic and virologic status of multitransfused thalassemic patients.

Viral markers of hepatitis B virus (HBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV), immunoglobulins and complements, T-cell subpopulation antibodies (OKT series) and mitogen responses have been investigated in 68 multitransfused thalassemic patients and in 46 age-matched children. Results showed (1) 56 patients (82.4%) had been exposed to HBV; 29 patients (42.6%) had been exposed to CMV and none were HIV infection. (2) Increased IgG, IgA, OKIal, and decreased C3, OKT3, OKT4, OKT4/OTK8 ratio showed in patients as compared to controls. (3) An apparent increase in lymphocyte proliferation was seen in patients' cultures with or without mitogen (PHA and ConA) stimulation. (4) No definite factors such as sex, age at first transfusion, number of transfusions or HBsAg carrier status correlated with the abnormal change of immunological tests. (5) Immunological investigation, done on 2 occasions six months apart, revealed no significant modifications except that 13 patients (19%) who were initially seronegative for CMV converted to seropositive. These investigations suggest that, although saline-washed RBC was used for the transfused patients, there was high prevalence of HBV and CMV infection. Further studies of lymphocyte function (i.e. lymphokines) are needed to understand the increased spontaneous proliferation in culture and PHA, ConA mitogen responses.

Adolescent↗
PubMed1989

Late onset hemorrhagic cystitis after allogeneic bone marrow transplantation.

Three patients with acute myeloblastic leukemia, thalassemia major and aplastic anemia experienced hemorrhagic cystitis on the 23rd, 35th and 36th day respectively after allogeneic bone marrow transplantation. The conditioning regimens before transplantation comprised cyclophosphamide with or without busulfan and total lymphoid irradiation. The hematuria lasted from 5 to 45 days and then subsided after treatment. Multiple factors including the toxicity of chemotherapeutic agents, viral infection and graft-versus-host reactions may contribute to late onset hemorrhagic cystitis after allogeneic bone marrow transplantation. Adequate treatment to minimize urothelial damage from chemotherapy, screening for viral infection and controlling graft-versus-host disease are mandatory in decreasing the complication of late-onset hemorrhagic cystitis after bone marrow transplantation.

Adolescent↗
PubMed1989

DNA polymorphism haplotype analysis of beta-thalassemia genes in Taiwan.

Twenty unrelated families of homozygous beta-thalassemia were collected for restriction polymorphism haplotype study of the beta-thalassemia (beta T) genes. DNA was extracted from WBC of the family members. With Southern blotting and DNA hybridization, restriction fragment length polymorphisms (RFLPs) were studied at 7 sites within the beta-globin gene cluster, including 5' epsilon-HincII, G gamma-HindIII, A gamma-HindIII, psi beta-HincII,3' psi beta-HincII, beta-AvaII,3' beta-BamHI. From RFLPs of the family members, restriction polymorphism haplotypes of the 40 beta T chromosomes and the 40 normal beta-globin gene (beta A)-bearing chromosomes were constructed. In beta T chromosomes. 26 (65%) belonged to haplotype I (+----++), 12 (30%) to haplotype II (+-----+), 1 (2.5%) to haplotype III (-++-+-+) and 1 (2.5%) to haplotype IV (++---++) which has not been reported in Chinese before. In beta A chromosomes, 12 different haplotypes were found. Seven (17.5%) belonged to haplotype I, 13 (32.5%) to haplotype II, and 6 (15%) to haplotype V (+----+-). The implications of RFLP and haplotyping of beta T genes in terms of molecular defects and prenatal diagnosis are discussed.

Asian People↗
PubMed1989

Extrahepatic biliary obstruction caused by cancer of non-liver origin in children: report of 5 cases.

Obstructive jaundice secondary to external compression of the extrahepatic bile duct caused by tumor of non-liver origin was found in 5 of 199 consecutive children with cancer between 1986 and 1988 at the Department of Pediatrics, National Taiwan University Hospital. Of the 5 patients, 2 had non-Hodgkin's lymphoma and the other 3 had acute promyelocytic leukemia, histiocytosis X and neuroblastoma, respectively. Extrahepatic biliary obstruction occurred as part of the initial presentation of malignancy in 3 cases, and later in the course of disease in the other 2 cases. In each instance, abdominal ultrasonography and computed tomography revealed dilatation of intrahepatic biliary trees due to mass compressing effects. A huge multilobulated tumor and multiple enlarged lymph nodes near the porta hepatis were found in all 3 patients who underwent an exploratory laparotomy. Wedge biopsy of the liver showed no cancer cell invasion. One case died before chemotherapy had commenced. The other 4 patients received chemotherapy and 3 of them received additional radiotherapy. Although jaundice and tumor regressed dramatically with this mode of treatments, subsequent recurrence of tumor without jaundice rapidly ensued in 3 patients. They all died, except 1 case, within 18 months from the occurrence of jaundice. This suggests that these patients were in an advanced stage of disease and should be diagnosed early and treated vigorously. Accordingly, cancer of non-liver origin, although rare, should be considered in the differential diagnosis of obstructive jaundice if survival is to be improved in these cancer children.

Adolescent↗
PubMed1989

Allogeneic bone marrow transplantation for thalassemia in Taiwan: factors associated with graft failure.

Fourteen thalassemia patients (aged 1.6-13.5 years; median age of 6 years) underwent allogeneic bone marrow transplantation (BMT) between March 1984 and May 1987. The preconditioning regimens consisted of oral busulfan, intravenous cyclophosphamide, with or without irradiation. Two of the patients, who received maternal transplants, failed to engraft but experienced autologous recovery. Of the 12 patients who received sibling marrow, two experienced autologous recovery and one developed marrow chimerism. Five patients died of complications of bone marrow transplantation: two died of intracranial hemorrhage, two died of sepsis, and one succumbed to acute graft-versus-host disease associated with cytomegalovirus infection. Six patients engrafted and have been followed for 1-4 years (median of 2.6 years) without intoward events. The overall survival rate was 64% (nine out of 14) with follow-up of 1-4 years. These results demonstrate that bone marrow transplantation can cure thalassemia but infection, graft-versus-host disease, and hemorrhage were major causes of morbidity and mortality in this group of patients. Other factors of importance include the unfavorable influence of engraftment of prior multiple transfusions and sex-mismatched transplantation. In patients who fail to engraft, autologous recovery usually occurs within 2 months of transplantation.

Adolescent↗
PubMed1989

A clinical study of intravenous immunoglobulin therapy for childhood idiopathic thrombocytopenic purpura.

Eight children with idiopathic thrombocytopenic purpura, who responded poorly to the conventional therapy or who already had severe side-effects, were treated with high dose intravenous immunoglobulin. Six of the 8 patients already had chronic diseases (disease duration longer than 6 months) when they entered into this study. Six patients had elevated platelet counts greater than 30 x 10(9)/L (the responders) after immunoglobulin induction therapy (2 g/kg immunoglobulin), and the average peak platelet counts were 231 x 10(9)/L. Two short-term pretreated patients were cured, 2 patients were in a drug-free state (platelet counts ranging from 50 to 150 x 10(9)/L), but another 2 responders did not benefit from the maintenance immunoglobulin therapy (0.5 g/kg/dose). From our preliminary results, high dose intravenous immunoglobulin seemed effective in all short-term pretreated and some chronic cases. It is worth trying immunoglobulin therapy when conventional therapies are not satisfactory.

Age Factors↗
PubMed1989

Acute graft-versus-host disease: a clinical report and analysis of risk factors.

Of the 31 cases of allogeneic bone marrow transplantation performed in the past 4 years at the National Taiwan University Hospital, 25 evaluable cases were retrospectively studied for incidence, severity, and risk factors of acute graft-versus-host disease (GVHD). The incidence was 60% (15/25) with the proportion of severe form (greater than or equal to grade II) being 53% (8/15). Skin involvement was the most common (13/15), gut the second (5/15), and liver the third (4/15). Most of the diagnosis of skin disease were confirmed by biopsy. Acute GVHD accounted for 3 deaths directly and was the next most common cause of death in post-transplant patients. The long-term survival rate for cases with grade 0-I disease was 65%, and that for those with grade II-III disease was 38%. Multivariate linear regression analysis of risk factors associated with severe form GVHD showed that the diagnosis of aplastic anemia was the most significant factor. Total lymphoid irradiation with or without plasmapheresis in aplastic anemia might contribute to the occurrence of severe acute GVHD.

Acute Disease↗
PubMed1988

Expression of tumor-associated aldehyde dehydrogenase gene in rat hepatoma cell lines.

Significant changes in aldehyde dehydrogenase (ALDH) activity occur during rat hepatocarcinogenesis in vivo. To compare the structure and expression of the tumor aldehyde dehydrogenase gene in rat hepatoma cell lines and normal rat liver, several rat hepatoma cell lines, including HTC, H4-II-EC3, JM2, McA-RH7777, and four lines established in this laboratory have been examined for T-ALDH gene expression using a tumor ALDH complementary DNA. Northern blot analysis of polyadenylate-containing RNA from log-phase cells and normal rat liver with T-ALDH complementary DNA indicates production of a single major 1.7-kilobase transcript in the high activity lines HTC, JM2, RLT-2M, RLT-3C, RLT-9F, and intermediate activity line RLT-5G. There is a direct correlation between expression of T-ALDH enzyme activity and the amount of 1.7-kilobase transcript. S1 nuclease protection experiments confirm that there is only one major T-ALDH transcript in the high activity lines. Thus, cell line differences in T-ALDH activity are reflected in the level of a single T-ALDH transcript. Southern analysis was used to identify the T-ALDH gene in genomic DNA. The results indicate that no significant amplification or rearrangement of the T-ALDH gene has occurred in these hepatoma cells. DNA methylation has been proposed to play an important role in gene expression. Genomic DNA from HTC, JM2, McA-RH7777, H4-II-EC3, RLT-2M, RLT-9F, RLT-3C, RLT-5G, rat embryo and normal rat liver were digested with MspI and HpaII to examine methylation patterns. A digestion pattern consistent with hypomethylation was detected only in DNA from the high T-ALDH activity cell lines HTC, JM2, RLT-2M, and RLT-9F. This suggests that constitutive expression of T-ALDH in the hepatoma cells is related to changes in DNA methylation patterns.

Aldehyde Dehydrogenase↗