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Biomedical subjects

A Uchida

Publications and source records attributed to A Uchida.

At least 289 records · Page 16Linked to original sources

Effect of vitamin D3 on proteoglycan degradation of growth cartilage.

Degradation of proteoglycans in growth cartilage plays an important role during endochondral ossification. Degradation is controlled by certain enzymes secreted by macrophages. Vitamin D3 metabolites markedly enhance the degradation of proteoglycans by macrophages in vitro. However, this enhancing activity of D3 metabolites is eliminated when the growth cartilage cells are lysed with 0.2N NH4OH. Puromycin (10 micrograms/ml) also inhibits the enhancement effect. These results suggest that D3 metabolites stimulate the synthesis of a D3-dependent substance by growth cartilage cells and that subsequently this substance enhances the enzymatic degradation of proteoglycans by macrophages.

Animals↗

Evaluation of skin biopsies from different body regions of onchocerciasis patients in Central Nigeria.

The diagnostic potential of skin snips from different body regions was evaluated in 97 onchocerciasis patients of Central Nigeria. Biopsies from the iliac crest had the greatest diagnostic potential followed by those of the calf and shoulder with 95% of Onchocerca volvulus carriers being diagnosed from these sites. However, 23.7% of microfilarial carriers in the skin of the outer canthus, shoulder, calf and ankle were negative in the iliac crest. The probability of diagnosing onchocerciasis in microfilarial positives from the 5 sites was, 0.76 for the iliac crest; 0.63 for the calf; 0.31 for the shoulder; 0.27 for the ankle; and 0.08 for the outer canthus. The concentrations of microfilariae in skin snips were significantly associated with the probability of a positive diagnosis especially with regard to those of the shoulder, iliac crest and calf.

Adolescent↗

[Limb salvage surgery for pelvic malignancies followed by reconstruction with hip endoprosthesis].

Between 1983 and 1987, nine patients with pelvic malignancy were treated with limb salvage surgery and preoperative chemotherapy. They were 6 males and 3 females, ranging in age from 13 to 73. There were 4 chondrosarcomas, 3 osteosarcomas and 2 Ewing's sarcomas. Seven patients received preoperative chemotherapy mainly consisting of adriamycin and cis-platinum. The remaining 2 patients with Ewing's sarcoma received T-11 protocol by Rosen. Surgical margins were wide but partially marginal in 6 patients and intra-lesional in 3 patients. Reconstruction with hip endoprosthesis fixed with screws and bone cement in the sacrum was performed after whole involved iliac bone was resected. Local recurrence was detected in one patient with osteosarcoma treated by marginal resection and 2 patients treated by intralesional resection. Complications occurred in 5 patients. Dislocation was observed in the first patient in this series. Other complications were infection in one patient, sciatic nerve palsy in one patient and leg length shortening in 2 patients. One patient walks without crutches, 5 patients with them. One patient uses a wheelchair and 2 patients are on bed rest. Four patients survived with no evidence of disease for 8-51 months (average 25 months). Two patients have survived with disease for 11-16 months (average 14 months). Three patients died from metastasis a 6-10 months (average 9 months).

Adolescent↗

Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. I. Proliferation of two distinct T-cell subsets.

In patients with carcinomatous pleural effusions blood T lymphocytes proliferated in vitro in response to autologous, freshly isolated effusion tumor cells in the autologous mixed lymphocyte-tumor culture (AMLTC) and to autologous blood non-T cells in the autologous mixed lymphocyte culture (AMLC). Treatment of the stimulator cells with the anti-HLA-DR monoclonal antibody (MAb) abrogated the stimulatory capacity in AMLC, but not in AMLTC. A subset of T cells that formed rosettes with autologous erythrocytes showed proliferative response to autologous non-malignant cells, whereas this subset did not respond to autologous tumor cells. Non-adherent lymphocytes were fractionated by centrifugation on discontinuous Percoll density gradients. Medium-sized T lymphocytes were excellent responders in AMLC, but were weak responders in AMLTC. Small T lymphocytes proliferated preferentially in AMLTC, but responded poorly in AMLC. Large granular lymphocytes (LGL) did not proliferate in mixed cultures of either type. Instead, LGL suppressed the T-cell proliferation in AMLTC. The same suppressor LGL, however, had no inhibitory effect on AMLC. Elimination of the CD4 subset reduced or abolished proliferative response in AMLC in all cases, whereas it was ineffective in diminishing the reaction in 6 of 8 AMLTC. In contrast, removal of the CD8 subset decreased or eliminated T-cell proliferation in 4 of 8 AMLTC, but in none of the AMLC. These results indicate that the autoreactive T lymphocytes detectable in response to tumor cells and non-malignant non-T cells differ in several characteristics. Thus, the reaction in the AMLTC is not due to contaminating non-malignant cells in the stimulator population and may be a tumor-induced proliferative response.

Adult↗

Growth of bone marrow cells on porous ceramics in vitro.

Following the transplantation of bone marrow cells to extra-osseous sites, bone formation occurs in those sites. This osteogenic potential of bone marrow cells might be utilized for filling defects in bone if they could be transported on porous ceramic materials. Before such an approach becomes feasible, it is important to know what happens to the cells in the presence of the ceramics that might be used. In order to investigate the interaction between bone marrow cells and ceramics, in vitro, a system for culturing bone marrow cells on ceramic materials has been developed. Bone marrow cells adhered well to the surface of calcium hydroxyapatite and tricalcium phosphate ceramics, and this was followed by the formation of fibrous tissue on and within the ceramics. These ceramics were compatible with bone marrow cells even in culture conditions in which there was a large surface area of ceramic interfacing with cells. The results support the proposal that calcium hydroxyapatite and tricalcium phosphate are appropriate as bone replacement materials. In contrast, calcium aluminate had an adverse effect on bone marrow cells when there was a high proportion of ceramic to culture medium. However, this effect was not present if the proportion of ceramic to culture medium was low. Therefore, a large amount of biodegradable porous calcium aluminate ceramic should not be used as an alternative to autogeneous bone grafting.

Aluminum↗

Is the sleeve anastomosis a risky technique?

We report 15 free flap transfers using sleeve vascular anastomoses with minor modifications of the original method. There was partial necrosis of one flap and one other required reoperation due to kinking of the feeding artery and not to the method of anastomosis. We believe that the sleeve anastomosis is reliable in clinical microvascular surgery if proper cases are selected. Indications for the method are discussed.

Adolescent↗

[Production and function of the monocyte cytotoxic factor (MCF)].

Monocytes lysing a variety of tumor cells were isolated by adhesion to autologous serum-coated plastic surfaces. When the blood monocytes were co-cultured with K562 cells for 3-24 h, the supernatants contained soluble factors, termed monocyte cytotoxic factors (MCF), capable of lysing K562 and other tumor cells in a 48-h microcytotoxicity assay. The production of MCF was mediated by typical monocytes expressing a surface phenotype of CD11 (+), CD16 (-), LeuM1 (+). When target cells were pretreated with actinomycin D, they showed an increase in their susceptibility to lysis by MCF. Addition of the drug to MCF assays also resulted in an enhancement of MCF-mediated lysis. Thus, the lytic activity of MCF was detectable in an 18-h assay. The presence of interferon (IFN)-alpha or -gamma augmented the biological activity of MCF, while pretreatment of target cells with IFN did not enhance MCF activity. The absorption of MCF activity was not elevated by actinomycin D or IFN. MCF lysed target cells that were resistant to tumor necrosis factor (TNF). One result of importance is that MCF lysed autologous and allogeneic freshly isolated human tumor cells. The lysis of fresh human tumor cells by MCF was not inhibited by monoclonal antibodies directed against TNF, lymphotoxin (LT), IFN-alpha, IFN-gamma, or interleukin 1 (IL-1). Furthermore, TNF, LT, IFNs, and IL-1 did not kill fresh human tumor cells. MCF activity was stable at low temperatures but was destroyed by heating. The biological activity of MCF was reduced or abolished by serum, trypsin, chymotrypsin and proteinase K, indicating the proteinaceous nature of MCF. The lytic activity was resistant to protease inhibitors. These data indicate that MCF is a noble cytokine that acts on human fresh tumor cells.

Cell Line↗

Lysis of autologous tumor cells by high-density lymphocytes is potentiated by the streptococcal preparation OK432 (Picibanil).

In experiments performed with tumor cells isolated from surgical specimens and lymphocytes collected at the time of surgery, tumor cells are often lysed by blood lymphocytes. Some of the effectors are present in the high-density T-cell subset. This population has little or no anti-K562 activity. For the auto-tumor lysis of T cells with high density, CD8-positive cells are mainly responsible. OK432 pretreatment of the effectors potentiates the existing lytic function or induces it in cases in which the cells have no such function. In general, the potentiating effect reflects inherent patterns of cytotoxicity. In contrast to the lysis of autologous tumor cells, cells with low but not high density were induced to lyse K562.

Antigens, Differentiation, T-Lymphocyte↗

Suppression of T-cell response in autologous mixed lymphocyte-tumor culture by large granular lymphocytes.

The role of large granular lymphocytes (LGL) in the autologous mixed lymphocyte-tumor culture (MLTC) was studied in cancer patients with malignant pleural effusions. When blood lymphocytes were cocultured in vitro with autologous tumor cells freshly isolated from carcinomatous pleural effusions, [3H]thymidine incorporation was weakly stimulated on day 6 in 6 of 30 samples. Removal of LGL from the responder population by treatment with the Leu-7 or Leu-11b monoclonal antibody plus complement (C') induced or augmented the proliferative response. LGL and small T-lymphocytes were isolated by discontinuous Percoll gradient centrifugation and tested separately for the proliferative response to autologous tumor. T-cells proliferated in 24 of 30 cases, while LGL showed no proliferation. Addition of LGL to autologous mixed T-cell-tumor cultures suppressed the proliferation of T-cells. LGL, however, did not inhibit T-cell proliferation induced by alloantigens and lectins. The suppressive activity of Percoll-purified LGL was not reduced by OKT3 plus C' treatment, but it was totally abrogated by Leu-11b plus C'. Supernatants produced by 24-hour culture of LGL with autologous tumor contained soluble factors that suppressed the autologous MLTC without killing the autologous tumor or T-blasts. The LGL-mediated suppression was not abolished by anti-interferon-alpha or anti-interferon-gamma antibody. Activation of T-cells in the autologous MLTC induced lytic potential restricted to autologous tumor. In the presence of LGL, T-cells failed to develop autotumor killing activity. Once autotumor killer T-cells were generated in autologous MLTC, their cytotoxicity was no longer inhibited by LGL. These results indicate that LGL from patients with carcinomatous pleural effusions suppress the capacity of autotumor-recognizing T-lymphocytes to proliferate and develop autotumor cytotoxicity in the autologous MLTC. This could explain why fresh T-cells have no cytolytic activity to autologous tumor.

Adenocarcinoma↗

Augmentation of autologous tumor killing activity of tumor-associated large granular lymphocytes by the streptococcal preparation OK432.

In vitro overnight exposure to the streptococcal preparation OK432 of blood and tumor-associated lymphocytes enhanced their lytic activity against autologous, freshly isolated tumor cells from malignant pleural effusions of cancer patients. This enhancement was mediated through factors that were distinct from interferon (IFN) and interleukin 2 (IL 2). Treatment with IFN-alpha, -beta, or -gamma, or IL 2 failed to augment autologous tumor killing (ATK) activity, although the treatment enhanced natural killer (NK) activity. Intrapleural (i.pl.) injection of OK432 induced or enhanced ATK and NK activities of effusion large granular lymphocytes (LGL) in patients who showed a reduction or disappearance of effusion tumor cells. No such increase in ATK and NK activities was seen with effusion LGL of patients who had no clinical benefit from i.pl. OK432 therapy. Blood ATK and NK activities were not consistently modified by the therapy. These results indicate that i.pl. administration of OK432 induces an augmentation of ATK activity of effusion LGL, which may be involved in the elimination of effusion tumor cells. The data also suggest that the host immune defense against tumor may be better represented by tumor-associated lymphocytes than by blood lymphocytes, and that it is important to examine the effect of biological response modifiers on ATK activity of tumor-associated effector cells.

Biological Products↗

[Effective mechanisms of BRM, with special reference to induction of autologous tumor cell-killing (ATK) activity by OK-432].

OK-432, a streptococcal preparation, is known to have strong BRM functions and is expected to produce clinical improvement and prolongation of survival in treated cancer patients. In order to clarify the immunopharmacological mechanisms involved with its clinical effectiveness, intrapleural injection of OK-432 was attempted in patients with malignant pleural effusion due to metastasis from lung cancer. About 70-80% of patients thus treated showed clinical improvements with reduction or disappearance of effusion and effusion tumor cells within a week after the therapy. The clinical response was accompanied by an abrogation or reduction of suppressor macrophages and a stimulatory increase of effective cytotoxic cells resulting in an increase of NK and ATK activity. These in vivo effects observed in the OK-432-treated patients were reproducible in vitro by incubating normal or effusion lymphocytes with tumor-associated macrophages. OK-432 was also shown to reduce the locomotor inhibitory activity of macrophages toward LGL, and to augment the production of various sorts of cytokines, such as IL-1 and MCF by macrophages and IL-2 and NKCF by lymphocytes, all of them being exerted upon activation of the anti-tumor immunological mechanism.

Biological Products↗

Natural cytotoxicity of human blood monocytes and natural killer cells and their cytotoxic factors: discriminating effects of actinomycin D.

The effect of actinomycin D on target susceptibility to human blood natural killer (NK) cells and monocytes was analysed in direct cell-mediated and their cytotoxic factor-mediated cytotoxicity assays. Treatment of K562 cells with actinomycin D reduced their susceptibility to lysis by non-adherent lymphocytes and Percoll-purified large granular lymphocytes (LGL) in a 4-hr 51Cr-release assay, without affecting their sensitivity to monocytes purified by adherence to autologous serum-coated plastic surfaces. The drug treatment caused no shift in the kinetics of cytotoxicity. In the target binding assay LGL formed fewer conjugates with actinomycin-D-treated K562 cells than with untreated ones, while the binding of monocytes to targets was not reduced by the drug treatment of K562 cells. The cold target competition assay revealed that actinomycin-D-treated cold K562 cells showed less successful inhibition than untreated cold K562 cells. Lymphocytes and monocytes could be induced to release soluble cytotoxic factors, termed natural killer cytotoxic factors (NKCF) and monocyte cytotoxic factors (MCF), respectively, when co-cultured with K562 cells. Both cytotoxic factors lysed NK-sensitive target cells in a 48-hr assay. Actinomycin-D-treated K562 cells reduced or abolished the ability to stimulate the release of NKCF from lymphocytes, whereas they induced MCF secretion from monocytes as effectively as untreated ones. On the other hand, actinomycin D treatment of K562 cells enhanced their susceptibility to NKCF and MCF. This actinomycin-D-induced augmentation of target sensitivity to the cytotoxic factors was restricted to NK-sensitive target cells (K562 and Molt-4). NK-resistant target cells (Raji, YAC-I, EL4 and T blasts) were not lysed by NKCF and MCF even after they were treated with actinomycin D. The capacity of K562 cells to bind NKCF and MCF was not altered by actinomycin D. Treatment of the adherent cell population with OKMI or Leu-MI plus complement abrogated both cell-mediated cytotoxicity and MCF production, while Leu-IIb plus complement was ineffective. These results suggest that the effect of actinomycin-D treatment can be used to distinguish the two distinct types of blood mononuclear cells with natural cytotoxicity, NK cells and monocytes, and that each effector type recognizes different plasma membrane moieties of NK target cells, although the cytotoxic factors released from each effector cell similarly bind to and lyse the target cells.

Animals↗

Bone ingrowth into three different porous ceramics implanted into the tibia of rats and rabbits.

Three different porous ceramics--calcium aluminate, calcium hydroxyapatite, and tricalcium phosphate--were implanted into the proximal tibia in rats and rabbits to study the interactions between these ceramics and a bony site that is abundant in bone marrow. New bone was consistently formed within the bone marrow surrounding and adjacent to all three types of ceramics. Calcium hydroxyapatite and tricalcium phosphate ceramics permitted bone ingrowth into their pores. The newly formed bone was found only in the part of the ceramic intruding into the bone, not in the portion protruding in the soft tissues outside the tibia. Partial replacement of the new bone opposite the medullary portion by new hemopoietic marrow occurred with longer implantation times. In contrast, no bone was seen within the pores of any of the calcium aluminate implants.

Aluminum↗