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Biomedical subjects

S Koide

Publications and source records attributed to S Koide.

At least 127 records · Page 7Linked to original sources

Interactions between UFT and anticoagulants in lung cancer patients.

In order to study the interactions between UFT and anticoagulants, the plasma and tissue concentrations of 5-FU, uracil and FT-207 were examined in patients with lung cancer. Higher plasma concentrations of 5-FU and uracil were observed in the patients who were given warfarin and ticlopidine beforehand, whereas the concentrations of FT-207 were almost the same in the patients who were given anticoagulants as in those who were not. This may be interpreted as an inhibition of dihydrouracil dehydrogenase, the common metabolizing enzyme of 5-FU and uracil, by anticoagulants. With regard to the tissue concentrations, higher levels of 5-FU and uracil in the tumor and lymph nodes were obtained after anticoagulants were given beforehand. Concentrations of FT-207 in these tissues, however, were almost the same in the patients who were given anticoagulants as in those who were not. We thus concluded that an increase of 5-FU in tumor cells and lymph nodes can be achieved after elevating the plasma concentrations of ordinary oral doses of UFT by using anticoagulation therapy beforehand.

Aged↗

The sensitization phase of T-cell-mediated immunity.

Many cell-mediated immune responses appear to develop in two phases: A sensitization phase in which unprimed or memory T cells interact with dendritic cells to become active lymphoblasts, and an effector phase in which the T lymphoblasts and other presenting cells interact to eliminate the antigen. Antigen presentation is essential to both phases. Here we review several features that are pertinent to the special sensitization role of dendritic cells. First, dendritic cells from lymphoid tissues, blood, and lymph (lymphoid dendritic cells) express very high levels of class I and II MHC products, and these levels cannot be increased by exposure to cytokines such as immune interferon. Second, dendritic cells efficiently cluster antigen-specific T cells during primary responses. Other presenting cells, like macrophages and B lymphocytes, do not form clusters but do bind to sensitized T lymphoblasts. Dendritic-T-cell binding is not inhibited by mAb to CD4 and LFA-1 antigens. It is suggested that a dendritic-cell-specific molecule is required. Third, it is not yet clear if dendritic cells make a "lymphocyte activating factor." However, IL-1 is not produced, even when dendritic cells are in contact with responding T cells. Fourth, dendritic cells have the capacity to migrate from the tissues and move to T-dependent areas. Epidermal Langerhans cells represent a reservoir of tissue dendritic cells but seem to be immunologically immature. The viability and accessory function of the Langerhans cell greatly depend on a single cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), leading to the proposal that GM-CSF is critical in mobilizing active dendritic cells at the onset of a cell-mediated immune response.

Animals↗

[Experimental and clinical study of interactions between fluorinated pyrimidine derivatives and anticoagulants].

Interactions between fluorinated Pyrimidine derivatives and anticoagulants were studied experimentally and clinically, using transplanted tumor tissues of Donryu rats and tissues from lung cancer patients. In rats, which were given 5-FU, uracil, tegafur and UFT respectively, the higher tumor concentrations of 5-FU and uracil were observed when given warfarin and ticlopidine beforehand, on the other hand, the concentrations of tegafur were almost the same between rats with and without anticoagulants. In patients with lung cancer, who were given UFT and anticoagulants, the higher concentrations of 5-FU and uracil in plasma, tumor and lymph nodes were observed than those who were given UFT alone. The 5-FU concentrations in normal lung tissues were about a half of those in tumor. These results suggest a existence of the synergistic effects between fluorinated pyrimidine derivatives and anticoagulants in plasma and tissue concentrations of 5-FU.

Animals↗

[Clinical results of UFT plus anticoagulants as a postoperative adjuvant in lung cancer patients].

Warfarin, Ticlopidine and UFT as postoperative adjuvant have been administered patients with stage III and IV lung cancer who underwent surgical resection. In a controlled trial, 55 patients were divided into two groups, one with anticoagulants and UFT (27 cases), the other with UFT alone (28 cases). The prognoses of the two groups were followed for 6 years. The anticoagulant group demonstrated a statistically greater interval from operation to recurrence the control group, although the recurrence rates and the interval from recurrence to death were almost the same between the two groups. Survival rates of anticoagulant group were always superior to those of control group after 12 months postoperatively, and the median survival was about twice that of the control group. Although survival rates between the two groups revealed no statistical difference, in patients with adenocarcinoma, the difference between the two groups was statistically significant.

Anticoagulants↗

[Early detection of central nervous system dysfunction during cardiopulmonary bypass using EEG monitoring].

The EEG was monitored in fifty-four patients during and after various surgeries requiring cardiopulmonary bypass (CPB) to assist in the early detection of central nervous system dysfunction (CNSD). Bilateral frontopolar EEG signals were processed with a 2-channel, real-time Fast-Fourier-Transformer (FFT) analyser and Compressed Spectral Arrays (CSA) were obtained. The fifty-four patients were divided into 3 groups based upon clinical outcome; Group 1: patients without CNSD (83%); Group 2: patients with delayed recovery from anesthesia but without CNSD (4%); and Group 3: patients with apparent postoperative CNSD (13%). There was no difference in the CSA among these groups prior to rewarming, but after the rewarming phase, two distinct sets emerged. Groups 1 and 2 showed a shift of the CSA predominant peak from a low frequency to a higher frequency. On the other hand, Group 3 patients demonstrated either stable predominant peaks in the lower frequencies or gradual flattening of the CSA. We conclude that the intra-operative EEG monitoring is a useful tool for the early detection of CNSD during and after CPB.

Adult↗

Induction of murine interleukin 1: stimuli and responsive primary cells.

An interleukin 1 alpha (IL-1 alpha) cDNA probe and an IL-1 responsive T-cell clone (D10.G4; half-maximal stimulation, 0.1-1 pM) have been used to study the production of IL-1 by primary murine cell populations, particularly macrophages and dendritic cells. Spleen and peritoneal macrophages produced IL-1 mRNA and released biologically active IL-1 when challenged with lipopolysaccharide (LPS). Induction of IL-1 was evident over a dose range of 0.01-10 micrograms of LPS per ml, and maximal mRNA levels were maintained from 4 to 20 hr. Several other stimuli did not induce IL-1 in cultured macrophages, including phorbol 12-myristate 13-acetate, gamma-interferon, Con A, macrophage colony-stimulating factor, IL-3, cachectin, and activated T cells. Activated T cells could markedly reduce the response of peritoneal macrophages to LPS. When other cell types were compared with macrophages, keratinocytes had high levels of IL-1 mRNA, apparently in response to endogenous LPS. However B and T lymphocytes did not yield detectable IL-1 during proliferative responses to LPS and Con A, respectively, while dendritic cells produced little or no IL-1 when challenged with a battery of stimuli. Therefore, IL-1 may not be required for the potent accessory function of dendritic cells in lymphocyte mitogenesis. The results indicate that macrophages and dendritic cells have different secretory capacities. The macrophage is the principal leukocyte that synthesizes IL-1, and select stimuli increase and decrease the levels of macrophage IL-1 mRNA.

Animals↗

Relation of ABH blood group antigen expression to prognosis in lung carcinoma.

The ABH blood group antigens were studied in resected specimens from patients with lung cancer employing monoclonal antibodies against A, B and H antigens by the immunoperoxidase technique. There were no differences between paraffin-processed and fresh-frozen materials in detectability of ABH antigens. Comparing specimens at operation with those at autopsy from the same patient, the loss of A and B antigens in the latter was demonstrated more frequently than H antigen. Concerning the relation between the prognoses and the expression of ABH antigens, the group with good prognosis preserved more ABH antigens than that with poor prognosis. In contrast, the group with poor prognosis showed less ABH antigens. There were also statistical differences in antigen detectability and prognosis, particularly in stage 1 patients, adenocarcinomas and well-differentiated lung cancers.

ABO Blood-Group System↗

[Abnormalities of blood coagulation and effect of anticoagulant therapy in postoperative patients with lung cancer].

To evaluate coagulable state, beta-thromboglobulin (beta-TG) levels have been followed sequentially in 70 postoperative patients with lung cancer. Nineteen out of them were treated with warfarin plus ticlopidine at a dosage enough to prolong the thrombo-test time to approximately 20% of normal value. There was a significant rise in beta-TG compared with control subjects and beta-TG was correlated with stages of disease. Serial beta-TG determinations revealed that beta-TG and CEA levels fairly paralleled with each other which suggested beta-TG might be useful in following tumor progression or response to therapy in postoperative period. As to the relation between beta-TG levels and five-year survivals, patients whose beta-TG were under 50 ng/ml showed more favorable prognoses than those who had higher levels. Long term anticoagulation with warfarin plus ticlopidine reduced the beta-TG levels of 19 stage 3 or 4 patients, especially in stage 4 the rate of reduction was marked. Nineteen patients with anticoagulant-treated group demonstrated a more prolonged time from beginning of treatment to first evidence of disease progression than 18 non-treated patients. Also anticoagulant-treated group had a more prolonged clinical course than non-treated group after disease progression. These results might be associated with disease stabilization which achieved with anticoagulant therapy. Survival at 30 months after initiation of treatment was 74% in the treated group and 64% in the nontreated group. Although there was no statistical difference in two groups, survival of treated group exceeded that of the non-treated group throughout the observation period. In stage 4 patients, however, the difference between two groups was statistically significant.

Adult↗

Nonsurgical retrieval of an accidentally dislodged vent catheter retention ring.

During open mitral commissurotomy in a patient with mitral stenosis, a vent catheter retention ring was accidentally slipped off into the left atrium and lodged near the orifice of the right renal artery. Nonsurgical retrieval of this intraarterial foreign body was performed successfully under fluoroscopic guidance in the operating room using a combined approach of angiographic catheters and guidewire, these being inserted via the arteriotomy site of the right femoral artery created for cardiopulmonary bypass.

Catheterization↗

Properties of memory T lymphocytes isolated from the mixed leukocyte reaction.

During the primary mixed leukocyte reaction, T lymphocytes of the lyt-2- helper subclass proliferate in response to transplantation antigens on allogeneic dendritic cells. We have isolated populations of antigen-specific proliferating lymphoblasts and recultured them in fresh medium. Within 2 days, the blasts become smaller in size, lose responsiveness to T-cell growth factor or interleukin 2, but retain vigorous reactivity to the original alloantigen. Two new biologic properties of these "memory" lymphocytes have been noted. First, they primarily respond to alloantigen on dendritic cells, whereas freshly sensitized lymphoblasts react to allogeneic dendritic cells, macrophages, and B lymphocytes. Second, the memory lymphocytes quickly aggregate with dendritic cells that are either syngeneic or allogeneic, but not with B cells. The aggregates that form with syngeneic dendritic cells disassemble within hours and do not release interleukin 2 or proliferate. The aggregates that form with allogeneic dendritic cells remain intact, release large amounts of interleukin 2 on the first day of culture, and synthesize DNA on the second day. Therefore, dendritic cells actively cluster memory lymphocytes by an antigen-independent mechanism, and this may underlie the heightened functional activity of each cell type.

Antigen-Presenting Cells↗