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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 343 records · Page 19Linked to original sources
PubMed1994

Expression of adhesion molecule ICAM-1 (CD54) in thyroid papillary adenocarcinoma.

The expression of adhesion molecules in thyroid specimens from 10 cases of papillary adenocarcinoma, 5 cases of follicular adenoma and 3 normal thyroid specimens was examined by an immunohistochemical method. Thyroid epithelial cells from all cases of papillary adenocarcinoma expressed the intercellular adhesion molecule 1 (ICAM-1, CD54). The ICAM-1-positive staining in these was detected predominantly on the apical site of malignant thyroid epithelial cells. However, no ICAM-1 expression was detected on thyrocytes of adenoma, and normal thyroid tissues. Furthermore, thyroid epithelial cells in patients with thyroid tumor and normal thyroid tissue did not react with anti-LFA-1, anti-VLA-4, anti-VCAM-1 and anti-ELAM-1 monoclonal antibodies. It is speculated that ICAM-1 expression in thyroid papillary adenocarcinoma may have a functional significance.

Adenocarcinoma, Follicular↗
PubMed1994

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Antibodies, Monoclonal↗
PubMed1994

A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer.

A dose escalation study of teniposide (VM-26) plus cisplatin (CDDP) was carried out using recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 46 previously untreated patients with advanced small cell lung cancer (SCLC). The dose of CDDP was 80 mg/m2/day intravenously (i.v.) (day 1) and VM-26 was escalated from 60 mg/m2/day to 80, 100 and 120 mg/m2/day i.v. x 5 days for four cycles. The dose of rhG-CSF was 90 micrograms/m2/day subcutaneously for 13 days. The feasibility of the regimen at the starting dose level of VM-26 with or without rhG-CSF was initially examined in 10 patients chosen through random allocation. WHO grade 4 neutropenia was observed in 17% (three out of 18 courses) of patients in the rhG-CSF group and in 63% (12 out of 19 courses) of the control group (P < 0.01). The number of patients with febrile episodes (> 38 degrees C) over the four courses of chemotherapy was 1 in the rhG-CSF group and 4 in the control group. According to these results, all 36 patients received rhG-CSF in the dose escalation stage. The incidence of WHO grade 4 neutropenia at the dose levels of 60, 80, 100 and 120 mg/m2/day of VM-26 was 66, 57, 76 and 85%, respectively (P > 0.1). The incidence of grade 4 thrombocytopenia was 19, 31, 18 and 46%, respectively (P > 0.1). The overall response rate was 100% in patients with limited stage SCLC and 83% in patients with extensive stage SCLC. The actual administered VM-26 dose per week at the dose level of 100 mg/m2/day was 1.6-fold higher than the planned starting dose (60 mg/m2/day) per week. At the dose level of 120 mg/m2/day, 50% of patients developed WHO grade 4 leucopenia, which lasted longer than 1 week and 67% of the patients had WHO grade 3 or 4 diarrhoea. At this same dose, all patients had at least one febrile episode (> 38 degrees C), and 1 patient died of cerebral bleeding with severe thrombocytopenia. The median survival time of all patients was 451 days (411 days, extensive disease; 497 days, limited disease). VM-26 plus CDDP with rhG-CSF was active in previously untreated patients with SCLC. The recommended dose of VM-26 in combination with CDDP for a phase II study is 100 mg/m2/day for 5 days with rhG-CSF support.

Adult↗
PubMed1994

The expression of adhesion molecules in thyroid glands from patients with Graves' disease.

We studied the potential role of adhesion molecules in the pathogenesis of Graves' disease. Thyroid specimens of Graves' thyroid glands and control thyroid glands were stained with monoclonal antibodies against adhesion molecules by an immunohistologic method. Thyroid tissues obtained from patients with Graves' disease had an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on capillary endothelial cells around the thyroid follicles and on postcapillary endothelial cells in lesions with aggregates of mononuclear cells. Positive staining for ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4) was found on the infiltrating mononuclear cells. The postcapillary vascular endothelial cells expressed increased endothelial-leukocyte adhesion molecule-1 (ELAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 and ELAM-1 were detected on the dendritic-like cells in the germinal centers of lymphoid follicle-like areas. No significant expression of these adhesion molecules was detected on normal thyroid glands. These results suggest that the LFA-1/ICAM-1 and ELAM-1 pathways may be responsible for the migration of mononuclear cells into the thyroid glands of patients with Graves' disease, and that the VLA-4/VCAM-1 pathway plays a critical role in the cellular interactions that lead to the formation of B-memory cells and the excess production of antibodies.

Adult↗
PubMed1994

In vitro and in vivo cytogenetic effects of recombinant interleukin-2 on human lymphocytes.

To determine the cytogenetic effects of rIL-2, we investigated the rIL-2-induced sister chromatid exchange (SCE) and chromosomal aberrations in human peripheral lymphocytes in vitro and in patients given rIL-2 as a 24-hour infusion for 28 consecutive days. No significant increase in SCE frequency and chromosomal aberrations was observed after in vitro incubation of lymphocytes with 100 U/ml of rIL-2. A daily rIL-2 dose of 6.6 x 10(5) U/m2 did not induce any significant effect on SCE frequency and chromosomal aberrations while a marked increase was observed in the percentage of IL-2 receptor positive cells and HLA-DR positive cells. Although IL-2 therapy is only in developmental stage, our results suggest there is little or no potential mutagenic and/or carcinogenic hazard with this agent.

Aged↗
PubMed1994

A randomized prospective study of imipenem-cilastatin with or without amikacin as an empirical antibiotic treatment for febrile neutropenic patients.

To evaluate the effect of adding amikacin (AMK) to imipenem-cilastatin (IPM/CS), we conducted a randomized controlled trial in patients who experienced neutropenia (< 1,000/mm3) and fever (> 38 degrees C) induced by cancer chemotherapy. There were 70 patients who entered the trial; 34 and 36 patients received IPM/CS plus AMK (arm A) and IPM/CS (arm B), respectively. There was no significant difference in patient characteristics between the two groups. Among 67 evaluable patients, 29 of 32 (91%) and 25 of 35 (71%) responded to the antibiotics therapy in arm A and B, respectively, with EORTC criteria (p < .047). Median days of antibiotics administration and of febrile episode over 38 degrees C were not statistically significantly different between arm A and B. There was no patient with severe side effects, such as seizure, and 17 patients (30%) experienced emesis in both groups. These data suggest IPM/CS plus AMK is therapeutically superior to IPM/CS alone in patients with neutropenic fever induced by cancer chemotherapy.

Adult↗
PubMed1994

Characterisation of the external surfaces of Pseudomonas aeruginosa isolated from human blood and respiratory tract.

The surface structures of the cell envelopes of 16 clinical isolates of Pseudomonas aeruginosa were examined by electronmicroscopy with the new fixation technique of freeze-substitution. Two types of structures were observed among the organisms. In one group of strains, mostly isolated from blood, a dense fibrous layer c. 30 nm thick was found around the outer-membrane surface, whereas no such structure was observed in the other group of isolates, most of which were from sputum. Lipopolysaccharides extracted from the isolates with a dense fibrous layer were found by SDS-PAGE to have long O-polysaccharide chains, whereas strains without such a layer mostly had lipopolysaccharides that lacked high mol. wt. O-polysaccharide chains.

Bacteremia↗
PubMed1994

Phase I and pharmacokinetic study of paclitaxel by 24-hour intravenous infusion.

Paclitaxel, a new antitubular agent, appears to be one of the most promising single agents for the chemotherapy of various solid tumors. The primary objectives of this phase I study of paclitaxel using 24-h continuous intravenous infusions were to determine the maximum tolerated dose of paclitaxel administered by this schedule to Japanese patients with solid tumors and to evaluate the pharmacokinetics of paclitaxel. Eighteen patients received one of five doses of paclitaxel, 49.5, 75, 105, 135 or 180 mg/m2. Premedication with diphenhydramine, dexamethasone, and ranitidine was used to prevent acute hypersensitivity reactions. Pharmacokinetic data were obtained from all 18 patients. Dose-limiting toxicities observed at 180 mg/m2 consisted of grade 4 granulocytopenia associated with grade 3 infection. No severe HSRs or cardiac toxicity were detected. Reversible toxicities observed included liver dysfunction, alopecia, peripheral neuropathy and myalgias. Pharmacokinetic studies performed using high-performance liquid chromatography demonstrated that plasma concentrations of paclitaxel increased during the 24-h infusion and declined immediately upon cessation of the infusion with a half life of 13.1-24.6 h (75-180 mg/m2). Less than 10% of paclitaxel was excreted in the urine within 72 h. The peak plasma concentrations and the areas under the concentration-versus-time curves increased linearly with the dose administered. Antitumor activity was observed in one patient with pulmonary metastasis from pharyngeal cancer. Based on these studies a phase II trial dose of 135 mg/m2 administered over 24 h was chosen.

Adolescent↗
PubMed1994

A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin.

We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP+Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD = 4.3) and 0.1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2-5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP+Dx. In the HDMP+Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and 18 patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.

Adult↗
PubMed1994

CPT-11: population pharmacokinetic model and estimation of pharmacokinetics using the Bayesian method in patients with lung cancer.

In this study, we aimed to develop a population pharmacokinetic model for CPT-11 and to use the Bayesian method to estimate CPT-11 pharmacokinetic parameters in each of 43 patients who received combined therapy consisting of CPT-11 and etoposide. The group was divided into first and second data sets of 30 and 13 patients, respectively. We developed a population pharmacokinetic model of CPT-11 based on the first data set. The individual pharmacokinetic parameters [area under the concentration curve (AUC) and clearance (CL)] were subsequently estimated by using the Bayesian method on the second data set. Plasma CPT-11 concentrations were measured by high-performance liquid chromatography, and compartmental pharmacokinetic models were fitted by the Bayesian method. The population pharmacokinetic model was developed by using the nonlinear mixed effect model. We selected the volume of the central compartment (Vc), CL, and distribution rate constants (K12, K21) as population pharmacokinetic parameters. The population mean values (CV%) of Vc, CL, K12, and K21 were, respectively, 31.8 (15.7%) liter/m2, 14.1 (27.8%) liter/h/m2, 1.1 (8.4%)/h, and 0.41 (30.3%)/h. Residual intraindividual variability was 22.9%. The optimal sampling regime for estimation of the AUC and CL in using the Bayesian method was the two time points of 1 and 8 h post infusion. The mean predictive error, the mean absolute predictive error, and the root mean squared error were -3.3, 9.4, 3.2% (AUC) and 6.3, 10.0, 3.5% (CL), respectively. We concluded that the AUC and CL of CPT-11 could be estimated from plasma concentrations at two times by using the Bayesian method.

Bayes Theorem↗
PubMed1994

Granulocyte colony-stimulating factor does not enhance phagocytosis or microbicidal activity of human mature polymorphonuclear neutrophils in vitro.

The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to chemotaxis, superoxide production, and phagocytosis and microbicidal activity against the following viable microorganisms: Staphylococcus aureus, serum-resistant Pseudomonas aeruginosa, and Candida albicans. Recombinant hG-CSF (rhG-CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner. The chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not enhanced by rhG-CSF at any of the concentrations used. rhG-CSF did not induce the generation of superoxide by itself. However, rhG-CSF was able to prime human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent manner. rhg-CSF did not enhance phagocytosis or killing of the three species of microorganisms by normal PMNs. With PMNs obtained from patients who had hematological disorders or solid tumors, no enhancement of the microbicidal activity was observed in most cases. Microbial killing mediated by PMNs depended on the ratio of PMNs to target organisms. We concluded from these facts that the most important effect of rhG-CSF was to increase the number of the peripheral PMNs and not to enhance the functions of mature PMNs.

Blood Bactericidal Activity↗
PubMed1994

Expression of basic fibroblast growth factor in synovial tissues from patients with rheumatoid arthritis: detection by immunohistological staining and in situ hybridisation.

OBJECTIVE: The distribution and production of basic fibroblast growth factor (bFGF) was examined on the synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The localisation of bFGF was determined by an immunohistochemical staining procedure using anti-bFGF monoclonal antibody. The expression of bFGF mRNA was detected by nonradioactive in situ hybridisation using bFGF antisense oligo DNA. RESULTS: The bFGF was found in the synovial lining cell, sublining stromal fibroblast-like cells, and vascular endothelial cells from patients with RA and OA. Little or no bFGF was found in non-inflamed synovium. Immunostaining of bFGF in the synovial cells was more extensive and intense in synovium of patients with RA than that of patients with OA. The nuclei of the synovial lining cell layer were also immunostained. These nuclear staining were more intense in the lining cell layer from RA patients with moderate or severe proliferation of synovial cells than in RA patients with mild proliferation. The bFGF mRNA was also detected in the synovial lining cell layer of the inflamed synovium. CONCLUSION: The synovial lining cells produced bFGF. The proliferation of synovial cells in the inflamed joints may be the results of stimulation by the bFGF in autocrine manner.

Aged↗
PubMed1994

Increment of CD8S6F1 cells in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the role of CD8 cell subsets in the pathogenesis of rheumatoid arthritis (RA) and the phenotypes of T cells adherent or non-adherent to the target cells (endothelial cells and synovial cells) pre-treated with IL-1 beta. METHODS: The expression of S6F1 on CD8 cells and that of an activation marker on CD8 cells and CD8 cell subsets was evaluated in specimens of peripheral blood and synovial fluid obtained from 15 patients with RA and 10 with osteoarthritis (OA) using a two- or three-colour immunofluorescence method for analysis. RESULTS: The percentage of CD8S6F1 cells among CD8 cells in synovial fluid was significantly greater than that of peripheral blood. Synovial fluid from RA patients had a greater percentage of CD8S6F1 cells compared with either peripheral blood of matched patients or synovial fluid of OA patients. The percentage of CD8HLA-DR cells in synovial fluid was markedly greater than that in paired samples of peripheral blood in patients with RA. In the CD8S6F1 cells from both groups of patients, synovial fluid showed an increased percentage of HLA-DR cells compared with peripheral blood. Similar results were observed in CD8 cells lacking S6F1 expression (CD8S6F1-) from both groups of patients. There was no significant difference in the percentage of HLA-DR cells between CD8S6F1 and CD8S6F1- cell populations in peripheral blood. In contrast with peripheral blood, in synovial fluid of RA patients the percentage of HLA-DR cells in the CD8S6F1 cell population was markedly greater than that in the CD8S6F1- population. However, the percentage of HLA-DR cells in both cell populations was similar in synovial fluid of OA patients. In both the endothelial and the synovial cell adhesion assays, the percentage of CD8S6F1 among CD8 cells and the mean fluorescence intensity of S6F1 antigen on CD8S6F1 cells were significantly greater in the adherent T cell population than that in the non-adherent T cell population. CONCLUSION: These results suggest that increased expression of S6F1 antigen and the increased percentage of HLA-DR cells on CD8 cells in synovial fluid may be responsible for the migration of these cells into inflamed synovial tissues, and for cellular interactions between these cells and synovial cells or the extracellular matrix.

Adult↗
PubMed1994

Interleukin 4 increases human synovial cell expression of VCAM-1 and T cell binding.

OBJECTIVE: The effects were studied of interleukin 4 (IL-4) on T cell-synovial cell adhesion and on the expression of adhesion molecules on the surface of synovial fibroblast-like cells. METHODS: The adhesion of T cells toward the synovial cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on synovial cells were analysed by flowcytometry. RESULTS: Stimulation of synovial cells with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of synovial cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells. The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial cells. CONCLUSIONS: These results suggest that the increased adhesion of T cells to IL-4-stimulated synovial cells is mediated by VLA-4/VCAM-1 pathway.

Adult↗
PubMed1994

Expression of intercellular adhesion molecule-1 and infiltration of lymphocytes in glomeruli of patients with IgA nephropathy.

Using immunofluorescence, we studied 19 patients with IgA nephropathy to determine whether the expression of intercellular adhesion molecule (ICAM)-1 in glomeruli might reflect the disease activity. The relationship between the expression of ICAM-1 and the infiltration of lymphocytes, monocytes and polymorphonuclear leukocytes (PMN) in glomeruli of IgA nephropathy cases was examined. The expression of ICAM-1 in patients in the advanced stage was significantly higher than that in patients in the mild stage. In double immunofluorescence, the distribution of ICAM-1 expression in glomeruli was different from that of IgA deposition in patients in both stages. Glomeruli which showed increases of ICAM-1 expression had marked infiltration of lymphocytes (OKT4+, OKT8+ T cells), and monocytes (OKM1+ cells). Increase of urinary protein and decreases in renal function were observed in patients in the advanced stage. It appears that the expression of ICAM-1 is closely linked to glomerular cell proliferation, and infiltration of lymphocytes and monocytes in patients with IgA nephropathy. However, the expression of ICAM-1 in glomeruli might not be correlated with IgA-dominant immune complexes in this disease.

Antibodies, Monoclonal↗
PubMed1994

Pituitary function in patients with Rathke's cleft cyst: significance of surgical management.

The pituitary function of patients with Rathke's cleft cyst before and after surgery was investigated to clarify the significance of surgery and operative indications. The authors have treated 19 patients with Rathke's cleft cyst. There were panhypopituitarism in 2 patients (11%), amenorrhea and/or galactorrhea in 3 (16%), diabetes insipidus in 4 (21%), and visual disturbance in 9 (47%). All the patients underwent systematic endocrinological examination and were found to have various degrees of pituitary dysfunction. Panhypopituitarism was endocrinologically confirmed in 2 patients. Hyperprolactinemia was observed in 4. These patients underwent aspiration of the cyst contents and biopsy of the cyst wall. Postoperative follow-up endocrinologic evaluation performed more than 3 months after surgery showed improvement in pituitary function in 9 out of 13 patients (69%). Amenorrhea and/or galactorrhea recovered or improved in 100% of patients and visual disturbance improved in 89%. However, diabetes insipidus and panhypopituitarism did not improve postoperatively, in any patient. The results of the present study indicate that the incidence of pituitary dysfunction in patients with Rathke's cleft cyst is higher than suspected and in most cases surgical intervention improves pituitary function and the clinical status of the patient. Therefore, surgical treatment is recommended even when the patient has only mild symptoms or signs, including pituitary dysfunction, to prevent irreversible panhypopituitarism.

Adolescent↗
PubMed1994

Successful treatment of metastatic pulmonary tumors by bronchial arterial infusion chemotherapy in two patients with locally well controlled uterine cancer.

Pulmonary metastatic tumors in two patients with locally well controlled uterine cancer were treated with bronchial arterial infusion chemotherapy. The first patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage IIb cervical cancer. Fifteen months after the operation, pulmonary metastasis was identified. Clinical evidence of tumor was negative after bronchial arterial infusion chemotherapy, systemic chemotherapy and radiotherapy. The patient continues to be healthy without recurrent signs six years after bronchial arterial infusion chemotherapy. The second patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage II endometrial cancer. Fifteen months after the operation, pulmonary metastasis was identified. After bronchial arterial infusion chemotherapy and systemic chemotherapy, regression of the tumors was observed. This patient has also survived for two years since the lung metastases. These results indicate that bronchial arterial infusion chemotherapy is a potent treatment for pulmonary metastases of uterine cancer.

Adult↗