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Biomedical subjects

T Chou

Publications and source records attributed to T Chou.

At least 37 records · Page 2Linked to original sources

Proportion of blasts with a clear halo around nucleoli at the end of induction therapy of acute myeloid leukemia correlates with achievement of complete remission, remission duration and relapse.

Bone marrow aspirates from 60 patients with acute myeloid leukemia (AML) were investigated using 95% ethanol fixation Papanicolaou stained preparations. The blasts were grouped into those with a clear halo around nucleoli (BCHN) and those without a clear halo. The patients were classified into three groups according to the degree of persistent BCHN at the end of induction therapy: group 1, no BCHN; group 2, less than 1% BCHN; and group 3, 1% or more BCHN. All patients in groups 1 (17 cases) and 2 (12 cases), and 12 of 31 cases in group 3 achieved complete remission (CR). Of 17 patients in group 1, two underwent bone marrow transplantation and two died from infection. Of the 37 patients who achieved CR, relapse was observed in two of 13 patients in group 1, and in all patients in groups 2 and 3. As to the patients treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine + daunorubicin + 6-mercaptopurine + prednisolone (BHAC-DMP) protocol, the percentages and number of BCHN at the diagnosis of AML in group 1 were significantly lower than those of groups 2 and 3. The percentage and number of BCHN at the diagnosis of AML were significant factors for the achievement of CR and for the prediction of long-term outcome. The reduction of BCHN to less than 1% at the end of induction therapy is a good indicator for the achievement of CR, and the disappearance of BCHN is a useful target for a long-lasting first CR; conversely, the persistence of BCHN is a major adverse factor for relapse.

Acute Disease↗

Electrostatics of lipid bilayer bending.

The electrostatic contribution to spontaneous membrane curvature is calculated within Poisson-Boltzmann theory under a variety of assumptions and emphasizing parameters in the physiological range. Asymmetrical surface charges can be fixed with respect to bilayer midplane area or with respect to the lipid-water area, but induce curvatures of opposite signs. Unequal screening layers on the two sides of a vesicle (e.g., multivalent cationic proteins on one side and monovalent salt on the other) also induce bending. For reasonable parameters, tubules formed by electrostatically induced bending can have radii in the 50-100-nm range, often seen in many intracellular organelles. Thus membrane associated proteins may induce curvature and subsequent budding, without themselves being intrinsically curved. Furthermore, we derive the previously unexplored effects of respecting the strict conservation of charge within the interior of a vesicle. The electrostatic component of the bending modulus is small under most of our conditions and is left as an experimental parameter. The large parameter space of conditions is surveyed in an array of graphs.

Biophysical Phenomena↗

Identification of drug-resistant myeloid leukemic cells by measurement of DNA content, nuclear area, and detection of P-glycoprotein.

BACKGROUND: This study was designed to evaluate the significance of aneuploidy in DNA ploidy, nuclear area, and expression of P-glycoprotein (P-GP) in differentiating drug-resistant myeloid leukemic cells (DRMLC) from drug-sensitive myeloid leukemic cells. METHODS: Bone marrow aspirates from 28 myeloid leukemic patients were fixed in 95% ethanol solution and stained using the Papanicolaou method. The nuclear area and DNA content were measured. An immunohistochemical study was performed using monoclonal antibody (JSB-1) directed against P-GP. RESULTS: Leukemic cell morphology changed once or twice after the diagnosis of acute myeloid leukemia (AML), blastic crisis (BC) of chronic myeloid leukemia, or chronic neutrophilic leukemia. DRMLC showed severe atypia and were morphologically distinguishable from normal myeloblasts, promyelocytes, and drug-sensitive leukemic cells at the diagnosis of AML or BC. The mean nuclear index (NI) and DNA index (DI) of DRMLC were significantly larger than those of drug-sensitive leukemic cells of AML or BC. The frequency of aneuploidy and P-GP expression was 9.1% and 4.5%, respectively, at the diagnosis of AML or BC, and 92.8% and 28.5%, respectively, for resistant disease. The incidence of heterogeneity in DNA ploidy was 86.3%. CONCLUSIONS: DI and NI values larger than 1.2 and the expression of P-GP are significant indications of DRMLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multiple myeloma-associated systemic vasculopathy due to crystalglobulin or polyarteritis nodosa.

Systemic vasculopathy is a rare complication of multiple myeloma (MM). We describe a patient diagnosed with MM who developed clinical features of systemic vasculopathy including gangrene, livedo reticularis, hypertension, renal failure, and perforation of the small intestine. Histopathologic examination of the small intestine revealed necrotizing vasculitis in the small arteries, along with crystalline deposits in the small vessels. To our knowledge, previously reported cases of systemic vasculopathy associated with MM include at least 9 cases due to crystalglobulin deposition in vessels and 2 due to polyarteritis nodosa. Deposits of crystalglobulin may have induced systemic necrotizing vasculitis in our patient.

Adult↗

[Effect of the interaction of tannins with coexisting substances. VIII. Inhibitory effect of tannins on discoloration of natural pigments].

The discoloration of shikonin (1) and beta-carotene (2), occurring during storage of their ethanol solutions in the presence of oxygen in an illuminated room, was remarkably suppressed by hydrolyzable tannins, such as geraniin (4) and tannic acid JP (3) in the solution. The inhibitory effect of tannins was enhanced by the coexistence of metallic ion. The irradiation with ultraviolet lamp (254 and 365 nm) gave, at the first stage of the discoloration, two products, one of which was found to be 5,8-dihydroxy-2-(1-hydroxy-3-oxo-4-methyl-4-pentenyl)-1,4-naphthoquinone (7). The presence of hydrolyzable tannins induced higher accumulation of these two products in the solution, showing that the secondary structural transformations of these two products were strongly inhibited by these coexisting tannins. These results suggest that tannins could be efficient inhibitors of discoloration of natural pigments.

Carotenoids↗

Adoptive immunotherapy for primary lung cancer.

The data presented in the present clinical trial demonstrated that adoptive immunotherapy using IVS cells and alpha CD3-AT cells for primary lung cancer patients may have therapeutic efficacy in selected groups of patients. Further investigation, such as induction of cytokine genes into effector cells to maximize the in vivo anti-tumor activity, combination of active immunization (tumor vaccine) and adoptive immunotherapy (10) would be definitely required for utilization of adoptive immunotherapy for lung cancer.

Adult↗

[Mega-dose chemotherapy with peripheral blood stem cell transplantation (PBS-CT) for small cell lung cancer (SCLC)].

Feasibility and the efficacy of mega-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for small cell lung cancer (SCLC) were evaluated. Autologous peripheral blood stem cell (APBSC) was collected after induction chemotherapy (Extensive disease: CDDP+etoposide+ADM, Limited disease: CDDP+etoposide) followed by the administration of granulocyte colony stimulating factor (G-CSF). Five cases of ED and 2 cases of LD have been entered in the protocol so far. PBSC was harvested after the second course of induction chemotherapy, and a sufficient number of PBSC (CFU-GM > or = 1 x 10(5)/kg) could be harvested and cryopreserved in all 7 cases. After completion of 4 courses of induction chemotherapy, three patients who achieved CR or good PR were treated by the combination of CBDCA (1,600 mg/m2) plus etoposide (1,600 mg/m2) followed by APBSCT and G-CSF. Hematologic recovery after APBSCT was rapid (absolute granulocyte count > 500/microliters: 9-11 day, Plt > 3 x 10(4)/microliters:10-14 day) and no infectious episode nor bleeding tendency occurred throughout the treatment period. Although grade 3 gastrointestinal toxicity was seen in one patient, the mega-dose chemotherapy with APBSCT in SCLC was considered safe and feasible. Further clinical trials are needed to establish the role of mega-dose chemotherapy for the treatment of SCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia).

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.

AIDS-Related Opportunistic Infections↗

Phase II trial of recombinant interleukin-1 beta in patients with metastatic renal cell carcinoma.

Interleukin-1 (IL-1) plays a central role in the immune system, partly by stimulating the production of interleukin-2 (IL-2) and other cytokines by lymphocytes. In preclinical studies, recombinant interleukin-1 (rIL-1 beta) has shown antitumor activity. We conducted a phase II trial to evaluate the efficacy of rIL-1 in metastatic renal cell carcinoma (RCC). rIL-1 beta was given at a dose of 50 ng/kg i.v. daily for 5 days on a 28-day schedule. Nineteen patients were registered; 16 completed two cycles and were evaluable for response. There were no complete or partial responses to treatment. Toxicity was generally mild and typically involved grades I and II fever, rigors, hypotension, and weight gain. Severe neurologic toxicity was seen in two patients, grade IV seizures were seen in one, and grade III somnolence was seen in another. Analysis of soluble IL-2 receptor (sIL-2r) levels revealed an increase from a mean pretreatment level of 4,567 pg/ml to a mean of 6,124 pg/ml posttreatment (p < 0.001). The mean pretreatment IL-6 level was 51 pg/ml, increased to 84 pg/ml posttreatment (p < 0.05). Patients with bulky disease had higher sIL-2r levels, and patients with tumor fevers had higher IL-6 and sIL-2r levels than patients without fever did. A neutrophilic leukocytosis and a mild thrombocytosis were observed in response to rIL-1 beta administration. We conclude that rIL-1 beta in this dose and schedule is inactive in metastatic RCC.

Adult↗

Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph node cells.

The adoptive immunotherapy of cancer with sensitized T lymphocytes is well documented in several animal models. These studies indicate the existence of precursor lymphocytes, in the tumour-bearing animals, which can acquire therapeutic efficacy after in vitro manipulations. To generate immune effector cells, these precursor lymphocytes have to be antigenically stimulated in vitro by the tumour of origin. Using the weakly immunogenic MCA 205 and MCA 203 murine sarcomas, we demonstrate here that this in vitro antigenic stimulation can be achieved by sequential activation with anti-T-cell receptor (TCR) monoclonal antibody and interleukin-2 (IL-2). The culture of tumour-draining lymph node (TDLN) cells with anti-TCR/IL-2 resulted in an up to eightfold increase in cell numbers. The adoptive transfer of these activated cells mediated a significant reduction of 3-day established pulmonary metastases. Although this antibody could activate all of the TCR alpha beta-bearing T cells non-specifically, the therapeutic efficacy mediated by anti-TCR/IL-2-activated cells was tumour specific. Treatment of MCA 205 advanced pulmonary metastases resulted in prolongation of survival, and 30% of treated mice were tumour free for more than 90 days. These tumour-free mice rejected a challenge of MCA 205 but not MCA 203, indicating the development of long-lasting systemic tumour immunity. In spite of their in vivo anti-tumour efficacy, the anti-TCR/IL-2-activated TDLN cells did not exhibit detectable in vitro cytotoxicity. These results demonstrate that this activation method could be an alternative way to generating potent anti-tumour effector T cells.

Animals↗

Growth of the human optic disk and nerve during gestation, childhood, and early adulthood.

We measured vertical and horizontal diameters of the optic disk and retrobulbar optic nerve in eyes from 95 patients on whom autopsies were performed at the UCLA Medical Center over a 20-year period. Ages at death ranged from 4.8 months' gestation to 21.9 years. Optic disk surface area and nerve cross-sectional area were calculated for each subject by using the formula for an ellipse. Approximately 50% of the growth of the optic disk and nerve occurs by 20 weeks' gestation, and 75% by birth; 95% of the growth occurs before the age of 1 year. All optic disk and nerve measurements correlate strongly (correlations > .67; P < .0001) with subject height and globe anteroposterior diameter. We applied our results to the current understanding of optic disk and nerve development, and compared them to previous clinical and pathologic studies of optic nerve dimensions in adults and older children.

Adolescent↗

Transplacental immunity to varicella-zoster virus in extremely low birthweight infants.

Sixteen infants in our intensive care nursery (ICN) were inadvertently exposed to an adult who presented the next day with chickenpox. Since a majority of the patients were extremely premature, we were concerned that they might not have received transplacental varicella-zoster virus (VZV) antibody, and consequently would be at risk for contracting chickenpox. Serum samples were obtained from each infant and examined for the presence or absence of VZV antibody. Fourteen of the 16 infants had antibody levels equal to or in excess of 1:16 by indirect fluorescent antibody, including six of eight infants with birthweights equal to or less than 1000 gm, and eight of ten infants with gestational ages equal to or less than 28 weeks. Passive transfer of immunity to VZV appears to be common in infants as young as 24 to 28 weeks' gestation.

Antibodies, Viral↗