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Biomedical subjects

D C Liang

Publications and source records attributed to D C Liang.

At least 55 records · Page 3Linked to original sources

A clinicopathological study of Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis encompasses a wide clinical spectrum, from a benign localized disease to acute generalized disease with fatal outcome. Here the histological features and clinical data for thirteen patients are reviewed and compared. The antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis was also studied. METHODS: The antibodies used included S-100 protein, vimentin, peanut agglutinin, HLA-DR, leukocyte common antigen, UCHL-1, CD 20, lysozyme, alpha 1-antitrypsin and epithelial membrane antigen. RESULTS: Six patients had localized lesions affecting a bone or its surrounding soft tissue. Four patients had multifocal disease without organ dysfunction. All patients of these two categories survived, except for one adult who died of hypertensive cerebral hemorrhage. Three patients had multifocal disease with liver, lung or bone marrow dysfunction. One died and two were lost to follow up. CONCLUSIONS: There was no significant difference in pathological findings between localized disease and multifocal disease. Immunohistochemical examinations using a panel of antibodies, including S-100 protein, peanut agglutinin, HLA-DR and vimentin, were very helpful for diagnosis of Langerhans cell histiocytosis.

Adult↗

Cranial computed tomography in children with acute lymphoblastic leukemia after prophylactic treatment with cranial radiation therapy and intrathecal methotrexate.

BACKGROUND AND METHODS: Thirty-one children with acute lymphoblastic leukemia (ALL) who had received cranial radiation therapy (CrRT) and five concomitant doses of intrathecal methotrexate (IT MTX) for central nervous system prophylaxis (CNSP) and who had an event-free survival exceeding 5 years had cranial computed tomography (Cr CT) examination. The fractional dose for 21 of them was 1.5 Gy. The interval between the completion of CNSP and the time of Cr CT ranged from 5 to 8.5 years, with a median of 5 years 2 months. RESULTS: Unlike the previous reports in the literature that 9-77% of children with ALL who had received Cr RT 18 Gy and IT MTX as CNSP had CT scan abnormalities, in this study no patient had CT scan abnormalities. CONCLUSIONS: Our results might be attributable to the fractional dose of Cr RT being adequate, the IT chemotherapy being suitable, and the systemic chemotherapy not being intensive.

Brain↗

Computed tomography of spontaneous intracranial haemorrhage due to haemostatic disorders in children.

Intracranial haemorrhage is a serious problem in haemostatic disorders in children. Intracranial bleeding is sometimes more marked than suspected clinically. Computed tomography (CT) permits accurate, sensitive diagnosis of intracranial haemorrhage. We report 13 patients; 3 patients with hypoprothrombinaemia, 4 patients with thrombocytopenia or platelet dysfunction and 6 with haemophilia A, B or Von-Willebrand's disease. One patient with hypoprothrombinaemia had a subarachnoid hemorrhage (SAH), one a subdural haematoma (SDH) and the third a combination of SAH, SDH and intracerebral haematoma (ICH). One patient with thrombocytopenia or platelet dysfunction had a SDH, while the others had ICH. In the six patients with haemophilia A, B or Von-Willebrand's disease, there were four examples of ICH, five of SAH and six of SDH. A neurosurgical procedure was performed in only one patient. Three children died of serious intracranial complications with uncal herniation.

Adolescent↗

Health status of patients with childhood acute lymphoblastic leukemia in continuous complete remission for over five years. The Taiwan Children's Cancer Study Group.

Ninety-seven patients with childhood acute lymphoblastic leukemia (ALL) have achieved complete continuous first remission for more than five years. They were treated by Taiwan Children's Cancer Study Group protocol 821 or protocol 842. Their present health status was evaluated using blood counts, immunology, a psychiatric analysis and growth parameters. Hemoglobin and platelet counts rose quickly to the normal range after complete remission was achieved, then remained at low normal throughout the course. The leukocyte counts responded immediately to chemotherapy, usually recovering to about 5,000/uL, then gradually increasing after completion of chemotherapy. The absolute neutrophil counts were at a low normal level during chemotherapy, then gradually recovered to the normal level after chemotherapy was completed. Immunologic investigation after completion of chemotherapy showed that the subsets of lymphocytes were nearly all in the normal range for the 38 patients tested. On the other hand, in 17 patients tested for T-cell function, it was found that 29.4% had low natural killer (NK) cell cytotoxicity, 11.8% had an abnormal phytohemagglutinin (PHA) test and all had abnormally low IL-2 production (in vitro). There were 29 patients who had psychiatric analyses; the full IQ was borderline in 10.3%. The primary or middle school academic scores of 55 patients were reported; 15% of them belonged to the lower one-third of the class. Height was assessed by the standard deviation score from the mean for 58 patients. The differences were statistically insignificant; however, there were six patients whose growth curves crossed over their initial percentile line.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Treatment of childhood acute lymphoblastic leukemia with protocol TCL-842 in Taiwan: the Taiwan Children's Cancer Study Group.

From March 1984 to May 1988, 212 children with acute lymphoblastic leukemia were enrolled on Protocol TCL-842. In all, 68 patients were classified as standard risk (SR), 56 as intermediate risk (IR), and 88 as high risk (HR) groups. Remission induction for all three groups consisted of vincristine (VCR), prednisolone (PRED) and L-asparaginase (L-Asp). One consolidation course with cyclophosphamide (CP) and cytarabine (AraC) was used for the SR and IR groups, and two courses were given to patients in the HR group. Central nervous system prophylaxis was randomized using either cranial irradiation 18 Gy + 5 intrathecal methotrexate (IT MTX) or triple IT with maintenance. Reinforcement cycles were employed periodically during maintenance therapy (basically 6-mercaptopurine+MTX) and varied among the three groups. Four-week oral PRED every 16 weeks was the sole reinforcement agent for SR. Two-week VCR+dexamethasone (DEX)+adriamycin CP cycles were used to reinforce IR and HR at different intervals. Five third-form cycles with VCR+DEX+AraC were used only for HR. Treatment was discontinued after three years in patients who achieved continuous complete remissions (CCR). Eight patients died during the induction phase and eight failed to achieve complete remission (CR). The CR rate for SR was 97%, for IR was 98% and for HR was 83.3%; the overall rate was 91.8%. As of 30 June 1991, 33 patients had dropped out, 12 had died during remission, and 52 had relapsed. Twenty-eight SR, 26 IR, and 29 HR patients remained in CCR with a median follow-up duration of 66 months (38-88 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Studies on the crystal structure of [L-Met]B0 bovine insulin at 3.0A resolution.

Based on the crystal symmetry of [L-Met]B0 bovine insulin (LMBBI) and the fundamental theory of the molecular packing method, the scheme for the determination of the position and orientation of the molecules by only using one-dimensional rotation and one-dimensional translation was chosen to be used, and therefore the calculation of the rotation function of the molecular replacement method and the refinement of the rotational and translational parameters by using the R-factor search method were simplified greatly. After the preliminary refinement by using the macromolecular rigid body refinement technique, the molecular model was further refined and adjusted by using the energy-minimizing stereochemical-restrained least squares refinement technique assisted by the manual revision on the difference Fourier maps. The L-Met residues on the N-terminus of the B-chain appeared clearly on the final electron density map.

Animals↗

Transient myeloproliferative disorder and acute myeloid leukemia: study of six neonatal cases with long-term follow-up.

Six neonates with hematological and clinical pictures indistinguishable from acute myeloid leukemia were studied. Two patients had Down syndrome and three others had either +21 or i(21q) chromosomal abnormalities in their blood cells at presentation. Granulocyte-macrophage colony-forming unit assays performed in bone marrow and peripheral blood mononuclear cells revealed abnormal growth patterns in two patients; both died of progressive disease of acute myeloid leukemia. All the other four neonates with normal in vitro cell growth pattern had spontaneous remission within 7 months. Of these four patients, one remains well and in remission for 8 years and the other three developed acute myeloid leukemia at the ages of 15, 32 and 19 months, respectively. We conclude that the in vitro cell growth pattern is helpful to distinguish transient myeloproliferative disorder from congenital acute myeloid leukemia and that patients with the former condition are at risk to develop acute myeloid leukemia subsequently.

Acute Disease↗

Molecular close-packing method and its application to crystal structure determination of deshexapeptide (B25-B30) insulin.

Based on the molecule-packing theory, we defined a molecule-packing function expressing the compatibility of packing among the symmetry-related molecules in a unit cell. A computer program imitating the close-packing of molecules in the objective crystal lattice and giving the function value of each rotation and translation of the molecule in the unit cell was performed, and it therefore made the close-packing of molecules express quantitatively. This method not only could judge a correct solution from several peaks of the rotation or translation function but it may also independently, quantitatively and quickly solve some specific problems of rotation and translation. Using known structure of despentapeptide (B26-B30) insulin as an example, the effectiveness of this method and its program was inspected, and this method was successfully applied to solving the translation problem of the unknown structure of deshexapeptide (B25-B30) insulin. The molecular close-packing method proved by the results of R-search and electron density maps is relatively independent of the molecular replacement method, though an effective complement of it.

Computers↗

The characteristics and motion model of insulin monomer.

The extensive conformational comparisons among the determined structures of the different species and crystal forms of insulin and the varied insulin derivatives were performed by using the least-squares superimposition technique and the graphics technique. The results of the investigation showed that the structure of molecule I in 2Zn insulin was closer to that of the natural monomer; the conformational difference between two molecules of a dimer came out during dimerization and it was further improved and stabilized during the hexamerization and packing of hexamers in crystal; through the hinge peptides, such as A10, B4, B8, B24, B20 and B23, there was a flexible relative motion among the structural segments in the insulin molecule, and the residues at the B-chain C-terminal might have a shift of more than 10A; the mobility for each residue side-chain was very different due to the different surroundings.

Insulin↗

The possible mechanism of binding interaction of insulin molecule with its receptor.

Detailed structural comparisons and investigation of DPI, 2 Zn insulin and some other derivatives of insulin were performed by the least-squares superimposition technique and the graphics technique. It is pointed out in this paper that the binding interaction with the receptor molecule should take place mainly on an amphipathic surface of the insulin molecule. In the middle, there is a hydrophobic surface with an area of about 150 A2 consisting of many hydrophobic residues; while the polar or charged groups distributing around the hydrophobic surface construct a hydrophilic zone. The hydrophobic surface is usually covered by the extended B-chain C-terminal peptides with great mobility and protected from the solvent molecules. The angle between the amphipathic surface and the surface of dimerization is about 20 degrees. The results from the detailed structural comparison between Al-(L-Trp) insulin and Al-(D-Trp) insulin have provided a very good explanation to their great difference in biological activity, and confirmed our proposed binding interaction model of the insulin molecule with its receptor as well.

Animals↗

Epirubicin and cytosine arabinoside for the induction therapy of childhood acute nonlymphocytic leukemia.

Epirubicin, a new anthracycline, was used in combination with cytosine arabinoside for the induction therapy of de novo acute nonlymphocytic leukemia in childhood. The treatment consisted of epirubicin 20 mg/m2/day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. The treatment could be repeated every 3 weeks. Remission induction rate was 80% (20/25). Moreover, in 13 patients, the remissions were obtained after a single course. In general, the side effects of epirubicin and cytosine arabinoside were tolerable. However, the main causes of all the three deaths were infections. Our study suggests that epirubicin is acceptable and effective for the induction therapy for de novo acute nonlymphocytic leukemia in childhood.

Adolescent↗

Oxygen tension is a major determinant of hepatotoxicity due to 2-ethylhexanol in isolated tissue cylinders from periportal and pericentral regions of the liver lobule from phenobarbital-treated rats.

2-Ethylhexanol, a metabolite of the commonly used plasticizer di(ethylhexyl)phthalate, was shown to cause toxicity exclusively to periportal regions of the perfused liver (Keller et al., 1990, J. Pharmacol. Exp. Ther. 252, 1355-1360.) To determine whether this toxicity was due to local oxygen tension or to drug delivery, isolated cylinders (plugs) of periportal and pericentral regions of the liver lobule from rats pretreated with phenobarbital were collected with a micropunch following brief perfusion of the organ. Plugs were 0.2 mm wide and 0.5 mm long and weighed between 0.5 and 1 mg each. Following incubation for at least 2 hr in Eagle's medium, they were judged viable based on production of urea at high rates and minimal leakage of lactate dehydrogenase (LDH). Plugs could be cultured for up to 24 hr with minimal loss of activity. Urea synthesis from ammonium chloride (3 mM) by plugs incubated in Krebs-Henseleit buffer equilibrated with 95% O2:5% CO2 was proportional to protein concentration and was linear with time for up to one hour at rates around 75 mumol/g/hr. Incubation of plugs with 2-ethylhexanol (0.1 to 3 mM) diminished urea synthesis in a dose-related manner (half-maximal effect = 0.5 mM). Ethylhexanol also caused extensive cell damage assessed from LDH leakage in incubations at 800 microM O2 but significantly less injury at 200 microM O2. Concomitantly, urea synthesis was inhibited by ethylhexanol by over 80% at 800 microM O2 but less than 50% at 200 microM O2. Plugs isolated from both regions of the liver lobule were affected similarly by ethylhexanol and O2. Taken together, these data indicate that ethylhexanol toxicity is dependent on oxygen tension in isolated sublobular regions of the liver lobule, and therefore it is unlikely that drug delivery can explain the selective injury to periportal regions in studies with the perfused liver.

Animals↗

A subset of acute lymphoblastic leukemia with co-expression of myeloid antigens: prevalence and clinical significance.

In order to evaluate the biological features and clinical significance of myeloid antigen expression in acute lymphoblastic leukemia (ALL), immunophenotype analysis was performed on leukemic cells from 160 patients diagnosed as ALL by the French, American and British (FAB) criteria using a comprehensive panel of monoclonal antibodies to lymphoid and myeloid associated antigens. Expression of myeloid antigens was found in 32 cases (20%), including 11 out of 49 adults (22.4%) and 21 out of 111 children (18.9%). CD33 was positive in 18 patients (11.3% of the total cases), CD13 in 15 patients (9.4%), CD 11b in 12 patients (7.5%) and CD14 in 1 patient (0.6%). Nine patients expressed two or more myeloid antigens. There were no significant differences in clinical manifestations and hematological pictures between the ALL patients with myeloid antigen expression (My+ ALL) and those without (My- ALL). No consistent chromosomal abnormality was found in My+ ALL. Eighty percent of the childhood and 44.4% of the adult My+ ALL patients achieved complete remission, compared with 87% and 80%, respectively, for childhood and adult My- ALL, but the differences were not statistically significant. After a median follow-up of 2.1 years, there were also no statistically significant associations between myeloid antigen expression and shorter duration of remission or poorer survival rate for patients with both adult and childhood ALL.

Adult↗

Non-Hodgkin's lymphomas in Asia.

The relative frequencies of the various histopathologic types of lymphomas are generally similar among Asian countries. Hodgkin's disease and follicular lymphomas are relatively rare in Asia. Among NHL, the Asians have a higher rate of aggressive NHL, as compared with the NCI data. Immunologic analysis revealed that PTCL is common in Asia. The relative frequency of PTCL is comparable among Chinese in Taiwan, the east coast of China, and Hong Kong, as well as in adult T-cell leukemia/lymphoma (ATLL) nonendemic areas in Japan. The increased rate of T-cell lymphomas in Asia is attributed to the low incidence of follicular lymphomas. The similar patterns of distribution in histopathologic and immunologic subtypes of NHL in Asia suggest that a common ethnic or geographic factor exists. To elucidate it, further detailed epidemiologic studies are needed. Primary extranodal NHL is slightly more prevalent in Asia than in the United States; the most frequent primary site is Waldeyer's ring in Japanese patients and the GI tract in Chinese patients. Primary small intestinal lymphoma in Asia showed the pattern of the Western type. Primary cutaneous lymphomas are rare in Asia. The clinical features of PTCL in Asia are comparable with those described in the United States, except for a predilection for the nasal/paranasal region. In Asia, outside Japan, ATLL has been reported only in Taiwan. The seroepidemiologic survey of carriers of ATLL showed the rate of seropositivity for HTLV-I in Taiwan was similar to that in nonendemic areas in Japan. The clinicopathologic features of ATLL in Taiwan and Japan are essentially identical. In children in Japan and Taiwan, Hodgkin's disease is much less frequent than in the West. However, the relative frequencies of the histopathologic and immunologic subtypes of childhood NHL in Japan and Taiwan do not differ significantly from those of the West. Although Burkitt's lymphoma in Japan and Taiwan is of nonendemic type, in India it may comprise both endemic and nonendemic types in almost equal number.

Adult↗

Hepatotoxicity due to clofibrate is oxygen-dependent in the perfused rat liver.

Toxicity of clofibrate, a hypolipidemic drug, was assessed in livers from fasted rats perfused in both the anterograde and the retrograde directions. Oxygen uptake decreased steadily following infusion of clofibrate (15 mM) and was diminished by about 40% in 15 min. Cell damage, assessed by the appearance of lactate dehydrogenase (LDH) in the effluent perfusate, began within 20 min. Maximal values for LDH release into perfusate were around 250 U/g/hr after perfusion with clofibrate for 40 min. Inhibition of oxygen uptake and release of LDH into the perfusate was dose-dependent (half-maximal effect = ca. 12 mM clofibrate). Nearly 90% of hepatocytes in oxygen-rich, periportal regions but only about 30% in oxygen-poor, pericentral areas took up trypan blue, an indicator of irreversible cell death, following perfusion with clofibrate in the anterograde direction. In contrast, when livers were perfused in the retrograde direction, 85% of cells in upstream, oxygen-rich pericentral regions were damaged whereas only about 30% in downstream areas were stained. When local oxygen tension was lowered by reducing the flow rate to one-quarter of normal, trypan blue uptake in periportal areas was diminished nearly completely (ca. 5% of cells were stained). Incubation in vitro of isolated cylinders of periportal and pericentral tissue with clofibrate at 800 or 200 microM oxygen led to about three times greater LDH release in incubations carried out at high than at low oxygen tension. This experiment led us to rule out the involvement of clofibrate delivery in the mechanism of zone-specific toxicity. Subsequently, local rates of oxygen uptake were measured using miniature oxygen electrodes placed on the liver surface. Clofibrate decreased oxygen uptake about 30% in oxygen-rich, periportal regions of the liver lobule, yet had no effect on respiration in downstream, pericentral areas. These phenomena can best be explained by a direct effect of clofibrate on active mitochondria in periportal regions of the liver lobule where oxygen uptake predominates, since state 3 but not state 4 rates of respiration were inhibited by clofibrate in isolated mitochondria (half-maximal effect = ca. 1.8 mM clofibrate). Thus, toxicity of clofibrate in upstream, periportal areas of the liver lobule is dependent on local oxygen tension and affects actively respiring mitochondria. This may lead to local cell death and be responsible for initiating a sequence of events leading to the well-known carcinogenic effects of this compound.

Animals↗

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↗