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Biomedical subjects

K M Chiu

Publications and source records attributed to K M Chiu.

29 records · Page 2Linked to original sources
PubMed1987

Immunologically mediated aplastic anemia in mice: effects of varying the source and composition of donor cells.

Experimental aplastic anemia (EAA) can be induced in CBA/J mice when they are sublethally irradiated and injected with lymph node cells (LNC) from C3H/He mice. Mice injected with LNC die of severe pancytopenia and marrow aplasia. In the present study, cells from other anatomical locations and subsets of LNC were examined for their ability to induce and to modulate EAA. Of peritoneal, splenic, and thymic cells, only cells from the thymus had EAA activity. C3H/He bone marrow cells did not induce any adverse effects in sublethally or lethally irradiated CBA/J mice. LNC, when depleted of B or phagocytic cells, retained EAA activity. In contrast, LNC depleted of T cells had significantly less EAA activity. Furthermore, when T cells of LNC were separated into peanut agglutinin (PNA)-receptor-positive and negative fractions, only the PNA- cells were able to induce EAA. EAA activity was lost when LNC were irradiated (1000 rad). The inability of splenic or bone marrow cells to induce EAA could have been due to the presence of cells that suppressed EAA activity. When splenic or bone marrow cells were coinjected with LNC, EAA was not induced. Coinjected irradiated splenic cells, but not bone marrow cells, were still able to inhibit EAA activity. Bone marrow cells seemed to inhibit EAA by replacing stem cells that were lost during the EAA process. On the other hand, splenic cells appeared to suppress EAA activity of LNC. Thus, radiosensitive PNA- T cells of lymph nodes or thymus were capable of inducing EAA, and their activity could be modulated by radioresistant splenic cells.

Anemia, Aplastic↗
PubMed1984

The separation of cytotoxic human peripheral blood monocytes into high and low phagocytic subsets by centrifugal elutriation.

Mononuclear cells (4 X 10(8) in a 5-ml volume) were loaded onto a Beckman JE-6B elutriator rotor spinning at 2,000 +/- 10 rpm with a flow rate of 10.0 ml/min. After lymphocytes were removed at flow rates between 10 and 11 ml/min with 500 ml of buffer, the flow rate was increased by 0.5 ml/min/fraction to collect 100-ml fractions. Highly enriched monocytes as judged by nonspecific esterase staining and morphology (70-95%) were found in each of eight fractions collected with flow rates between 11.5 to 15.0 ml/min. When stimulated with phorbol myristic acetate, these fractions mediated equivalent levels of cytotoxicity against 51Cr-labeled Chang liver cell line. Similarly, each monocyte-containing fraction was found to mediate the same level of cytotoxicity against antibody-sensitized 51Cr-labeled Chang liver cells. In contrast, cytotoxicity against the natural killer cell-sensitive K-562 cell line was found in only those fractions that contained a high percentage of lymphocytes. The fractions that were enriched in monocytes were found to differ in their ability to ingest latex. Those monocyte fractions that were collected between 11.0-12.0 ml/min consisted primarily of low numbers of latex-ingesting monocytes (less than 30%). Those monocyte fractions that were collected between 12.5 and 15.0 ml/min consisted primarily of latex-ingesting monocytes (50-70%). These data show that cytotoxic monocytes can be separated by centrifugal elutriation into at least two subsets that can be distinguished by their phagocytic activity.

Animals↗
PubMed1984

Susceptibility of Oncomelania hupensis subspecies to infection with geographic strains of Schistosoma japonicum.

Subspecies of Oncomelania hupensis were exposed to infection with zoophilic and anthropophilic strains of Schistosoma japonicum. The snails were Philippine O. h. quadrasi from the islands of Bohol, Leyte and Mindanao, O. h. formosana from Changhua and Ilan, and O. h. chiui from Taiwan, O. h. hupensis from China, O. h. nosophora from Japan and O. h. lindoensis from Indonesia. Anthropophilic strains of S. japonicum were from Bohol and Leyte in the Philippines, China, Japan and Indonesia. The zoophilic strains were from Changhua and Ilan, Taiwan. All geographic strains of the parasite developed exceptionally well and produced cercariae in 32-50% of O. h. chiui and 5-43% of the natural snail hosts. Development in other subspecies of snails with geographic strains of the parasite were variable. Only a few O. h. formosana (Changhua) could be infected with the parasites from other geographic areas and only one O. h. quadrasi each from Mindanao became infected with the Bohol and Changhua strains of S. japonicum.

Animals↗
PubMed1983

The immunological response of Wistar rats to the intracranially implanted C-6 glioma cell line.

The immune response of Wistar rats to the intracranial inoculum of 1 X 10(5) C-6 glioma cells was evaluated. The growth of these cells disrupted the blood-brain barrier by day 9. The rats with the implanted tumor cells died between three to four weeks following injection. No significant cell-mediated cytotoxicity against 51Cr labelled C-6 cells was seen in the short term (4 hours) cytotoxicity assay with spleen cells obtained from glioma-bearing rats at any stage of tumor growth. In the long term (18 hours) cytotoxicity assay, significant activity was detected using whole, adherent and nonadherent spleen cells from glioma-bearing rats at every assessment point during the growth of the tumor, but this cytotoxicity was also seen in normal rat splenocytes. The lack of cell mediated cytotoxicity above normal values was not due to a generalized immunosuppression since splenocytes from glioma bearers were found to have responses to Con A comparable to normal controls. However, normal or glioma-bearer splenocytes showed augmented cytotoxicity in the presence of serum obtained from rats bearing a glioma tumor starting by day 13 of tumor growth and rising in cytotoxic activity until death. This activity was not seen with normal serum. The glioma-bearer serum, though not cytotoxic to the C-6 cells alone, became cytotoxic with the addition of rabbit complement. These data indicate that the growth of intracranially implanted glioma cells in rats elicits primarily a humoral cytotoxic immunity without a significant cell-mediated immunity. This humoral immunity develops after the breakdown of the blood-brain barrier.

Animals↗
PubMed1983

Chronic intratumoral chemotherapy of a rat tumor with cisplatin and fluorouracil.

In order to demonstrate the feasibility and efficacy of intratumoral chemotherapy, brain tumors in rats were treated by direct infusion of cisplatin or fluorouracil. Each animal was initially implanted in the midline cerebellum with a chronic stainless-steel cannula, and 2 weeks later 1 X 10(5) 9L cells were injected through the cannula. 8 days after tumor cell transplantation, a small implantable pump containing drug, or saline as a control, was connected up to the same cannula, and the solution was pumped into the tumor region for 7 days. The results showed that both drugs produced statistically significant increases in survival as compared to the controls.

Animals↗
PubMed1982

Heterogeneity of cytolytic and suppressor clones of alloactivated cells generated from soft agar colonies.

Long-term cell cultures (or clones) were developed from soft agar colonies of lymphocytes alloactivated in mixed leukocyte culture reaction (MLR). Two types of colonies were identified: upper colonies that grew on the agar surface, and lower colonies found within the agar layer. Virtually all cytolytic clones originated exclusively from the upper colonies. Two groups of cytolytic clones could be distinguished, one with strong and the other with weak proliferation upon restimulation. Upper clones were capable of inhibiting primary MLR proliferation and this appeared to be related to their cytolytic effect on the stimulator. Many noncytolytic lower clones were found to suppress primary MLR cultures. Considerable heterogeneity was apparent from differences in the magnitude of suppression and the ability of the clones themselves to undergo stimulator-induced proliferation. Kinetic studies of MLR suppression were conducted to further analyze this heterogeneity. Two major kinetic patterns were observed. One showed a biphasic proliferation pattern of the MLR + clone culture. The first peak appeared to reflect an enhanced proliferation of the clone. The second phase seemed to represent diminished proliferation of the MLR responder. This type of suppression may be related to T cell growth factor depletion from MLR by the proliferating clone. The other kinetic pattern showed a consistently low proliferation of the MLR + clone culture throughout the 8-day assay period. Subsequent testing of these suppressor clones in third-party MLR cultures suggested that the specificity of suppression was unrelated to HLA-DR, MB, MT, and SB.

Cell Division↗
PubMed1980

Functional differences between cells from MLR colonies grown in soft agar cultures.

This report describes a method of growing soft agar colonies of human T lymphocytes activated in the MLR. Two types of colonies were demonstrated: lower colonies grew within the agar layer, and upper colonies grew on the surface of the agar layer. Three days of priming the lymphocytes in the MLR and the use of supernatants of day-3 MLR cultures to provide T cell colony growth factor were necessary for optimal colony formation. Lymphocytes obtained from colonies were grown in long-term (2 to 4 weeks) cultures to generate sufficient numbers of cells to be tested in different functional assays. Cells from both types of colonies exhibited PLT activity. Upper colony cells showed considerably higher CML activity than lower colony cells (mean percent cytotoxicity 37 +/- 5 vs 6 +/- 3). Cells from both types of colonies contained radiosensitive suppressor cell activity that inhibited the primary MLR. The suppressor cell effect of lower colony cells was specific for the original stimulator, but upper colony cells displayed nonspecific suppressive effects. For both types of colony cells, it appeared that suppressive effects were unrelated to the CML activity of these cells. These data suggest that the soft agar colony assay offers a promising approach to separate subpopulations of lymphocytes activated in the MLR.

Agar↗
PubMed1977

Interactions of alpha1-acid glycoprotein with the immune system. I. Purification and effects upon lymphocyte responsiveness.

Alpha1-acid glycoprotein (AAG) is a constituent of normal serum which is elevated in concentration in the acute phase of inflammation; its physical and chemical properties have been defined but its biological function is uncertain. In the present study, the effect of AAG on the proliferative response of lymphocytes to several different stimuli was determined. For this purpose AAG was prepared by precipitation of human ascites fluid with sulphosalicylic acid and passage of the supernate through SP-Sephadex; the eluted protein migrated as a single band during immunoelectrophoresis, polyacrylamide gel electrophoresis and chromatography on Bio-Gel-A-1-5 m in 6 M guanidine HCl. This AAG was found to markedly inhibit the proliferative response of human peripheral blood lymphocytes to PHA; it also inhibited blastogenesis induced by Con A and PWM, but to a lesser extent. AAG was not cytotoxic to lymphocytes, and its inhibitory effects were reversed at higher mitogen concentrations. Lymphocytes preincubated with AAG remained less reactive to PHA indicating that, although AAG appeared to react with PHA, its effect was directed predominantly to the cell. Further, AAG markedly inhibited the mixed lymphocyte response, and this effect was directed to the responder cells. Thus, AAG is another acute phase reactant with the ability to modulate lymphocyte responsiveness.

Cells, Cultured↗