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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 451 records · Page 25Linked to original sources
PubMed1989

[Thin-slice CT analysis of localized inflammatory pulmonary lesions--pathologic-CT correlation].

In order to evaluate thin-slice CT findings of localized inflammatory pulmonary lesions, 5 granulomatous lesions without preoperative pathological diagnosis were examined. On thin-slice CT, fifth order bronchi and vessels were detected, and inflammatory lesions were observed in margins of pulmonary veins. Of involved bronchi, thick walls were detected in 3 cases, central convergence in 2 cases, mucoid impaction in 3 cases. The characteristics of inflammatory nodules, strand-like shadow and concave margin of lesion contiguous to normal lung, were demonstrated on thin-slice CT. Thin-slice CT can be effective to differentiate localized inflammatory pulmonary lesion.

Aged↗
PubMed1989

Dose escalation study of recombinant human granulocyte-colony-stimulating factor (KRN8601) in patients with advanced malignancy.

To evaluate the toxicity and efficacy of recombinant human granulocyte-colony-stimulating factor (rh G-CSF) administered with intensive chemotherapy, 39 patients with advanced pulmonary cancers were enrolled in a dose escalation trial of rh G-CSF. Three days after initiation of chemotherapy rh G-CSF was administered i.v. for 14 consecutive days at five dose levels (50-800 micrograms/m2). Absolute neutrophil counts showed a dose-dependent increase with an increasing dose of rh G-CSF and the durations of neutropenia (less than 1000/mm3) shortened significantly at doses of 200, 400, and 800 micrograms/m2 compared to those at 50 micrograms/m2 (P less than 0.01). The duration of neutropenia was shortened significantly at all five dose levels following treatment with rh G-CSF compared to treatment without rh G-CSF (P less than 0.05). Adverse side effects associated with rh G-CSF administration were fever higher than 38 degrees C (21%), chest pain, and low back pain (13%). No intolerable side effects were experienced. It can be concluded that rh G-CSF is effective in shortening the duration of neutropenia following intensive chemotherapy at a dose level of 100 to 200 micrograms/m2 i.v. a 400-micrograms/m2 dose of rh G-CSF is recommended in patients with prior treatment because of the possibility of a lower bone marrow response.

Adult↗
PubMed1989

Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease.

The present study utilized the anti-Ta1 mAb to characterize the cell surface phenotypes of peripheral blood and intrathyroidal lymphocytes in patients with Graves' disease. We found an increase in PBL bearing the Ta1 Ag in untreated patients. The euthyroid patients in remission, induced by antithyroidal drugs, radioisotope therapy, and subtotal thyroidectomy, had lower percentages of Ta1+ cells than did untreated patients. An increased percentage of Ta1+ cells in untreated patients was found in both CD4+ cells and CD8+ cells. The ratio of CD4+Ta1+ cells to CD8+Ta1+ cells in untreated patients was significantly higher than that of normal subjects. There was a positive correlation between the percentage of Ta1+ cells and the level of anti-TSH receptor antibody. In this prospective study, the proportion of Ta1+ cells was decreased in parallel with the reduction in anti-TSH receptor antibody and free T3 levels. In the chronically treated patients, the proportion of Ta1+ cells in the thyroid tissue was, yet similar to that in the peripheral blood, markedly increased in comparison to that of normal subjects. In contrast to Ta1+ cells, the thyroid tissue had a significantly higher percentage of HLA-DR+ T cells than did the paired peripheral blood. The proliferative responses of the Ta1+ cell-enriched population isolated from untreated patients toward thyroglobulin and microsomal Ag were markedly higher than those in a Ta1+ cell-depleted population, but both populations were able to respond equally to PHA. These results suggest that the Ta1+ cells may include Ag-triggered memory cells that are reactive with thyroid-specific Ag. Furthermore, monitoring such cells may provide an objective measure of abnormal immunologic activity.

Adolescent↗
PubMed1989

Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy.

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.

Adult↗
PubMed1989

Detection of anionic sites and immunoglobulin A deposits in the glomerular capillary walls from patients with IgA nephropathy.

A study of anionic sites in the glomerular basement membrane (GBM) from patients with immunoglobulin A (IgA) nephropathy is described. The relationship between the deposition of IgA and the detection of glomerular extracellular components, i.e., noncollagenous (NC-1) domain of Type IV collagen, in the glomerular capillary walls was examined by double immunofluorescence. Renal biopsy specimens from patients with IgA nephropathy were immersed in polyethyleneimine (PEI) as a cationic probe and then examined by electron microscopy. Renal specimens were also incubated with mouse monoclonal anti-NC-1 domain of Type IV collagen and then stained with fluorescein isothiocyanate (FITC)-labelled goat antimouse Ig antiserum. After these reactions, sections were stained with rhodamine-labelled rabbit antihuman IgA antiserum. GBM subepithelial anionic sites marked by PEI were altered by the deposition of electron-dense deposits (EDD) in patients with IgA nephropathy and there was a significant correlation between the levels of proteinuria and the incidence of EDD in the GBM in such patients. Marked proteinuria was observed in patients who showed loss of anionic sites in the GBM by electron microscopy. By double immunofluorescence, IgA was shown to be focally deposited outside the NC-1 domain of Type IV collagen-detected regions in the same patients. The authors concluded that high levels of proteinuria might be due to alterations of the size barrier and/or anionic sites of GBM in the moderate stage of IgA nephropathy.

Basement Membrane↗
PubMed1989

Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin.

The pharmacokinetics of (glycolato-0,0')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 micrograms/ml and 959 micrograms/min per ml for 254-S, 3.09 micrograms/ml and 208 micrograms/min per ml for cisplatin, and 19.90 micrograms/ml and 3446 micrograms/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.

Antineoplastic Agents↗
PubMed1989

Serial measurement of sister chromatid exchanges in the peripheral lymphocytes of patients with lung cancer receiving chemotherapy in relation to bone marrow toxicity.

The frequencies of sister chromatid exchanges (SCE) in the peripheral lymphocytes of patients with lung cancer before and after initial chemotherapy were serially measured and the correlation between SCE frequencies and bone marrow toxicity was evaluated. The addition of mitomycin C to vindesine plus cisplatin increased SCE frequencies significantly in patients with non-small cell lung cancer. A significant increase in frequencies of SCE was observed in patients treated with cyclophosphamide plus adriamycin plus vincristine as compared with those treated with cisplatin plus etoposide in small cell lung cancer. A significant inverse correlation was observed between SCE frequencies in the peripheral lymphocytes 7 days after treatment (x) and the nadir value/pretreatment value of platelets (y)(r = -0.685, P = 0.0007, y = 0.842-0.022x). The relation between SCE frequency and leukopenia showed the same trend as thrombocytopenia, but the correlation was not statistically significant (r = -0.444, P = 0.057). SCE assay may have potential clinical use for the prediction of chemotherapy-induced thrombocytopenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Computer imaging analysis of glomerular extracellular components in patients with IgA nephropathy.

Computer imaging analysis was used for quantitative evaluation of the extents, amounts and distributions of glomerular extracellular components, such as the 7S and NC-1 domains of type IV collagen, laminin (LN), fibronectin (FN) and IgA, in glomeruli from patients with IgA nephropathy. Renal biopsy specimens from 13 patients with IgA nephropathy were incubated with mouse monoclonal antibodies against the FN or non-collagenous (NC-1) domain of type IV collagen or polyclonal antiserum against the LN or 7S domain of human type IV collagen, and then stained with appropriate dilutions of FITC-labeled anti-mouse Ig antisera. Marked staining of the 7S or NC-1 domain of type IV collagen, LN or FN was detected in the glomerular capillary walls and/or mesangial areas in patients with IgA nephropathy. In particular, a prominent increase of FN was observed in the subendothelial regions of glomerular capillary walls, i.e. mesangial interposition, in the moderate or advanced stage of IgA nephropathy. Therefore, computer imaging analysis was shown to be useful for the quantitative determination of such components distributed in glomeruli from patients with IgA nephropathy.

Complement C3↗
PubMed1989

Effects of booster HB vaccine in preventing hepatitis B virus infection from mother to child.

Hepatitis B immune serum 200 IU was injected intramuscularly to 127 infants born to hepatitis B e antigen positive mothers immediately after birth and at two months of age, and if necessary at four months. HB adjuvant vaccine 20 micrograms was injected subcutaneously at three, four, and six months. If antibodies to hepatitis B surface antigen were 2(2) or less, one to four doses of booster vaccine 20 micrograms were given. The first booster vaccination was given in 8.7% of cases by the age of one year, in 19.3% by 18 months, in 23.9% by 24 months, and in 36.2% by 30 months; thus 2-to-3-year-old infants were more frequently vaccinated than younger ones. This implies that 80%-90% of infants could be protected from vertical transmission of hepatitis B virus (HBV) up to the age of three years, if a booster vaccine was given to those born to HBeAg positive mothers not later than 24 months. Infants obtained enough antibody to prevent HBV infection by receiving one booster vaccination in 34 cases, by two in nine, by three in five, and by four in two.

Carrier State↗
PubMed1989

Association of IgA nephropathy and myasthenia gravis.

Three patients with IgA nephropathy associated with myasthenia gravis are described. In all 3 cases, myasthenia gravis emerged after the discovery of glomerulonephritis. Myasthenic symptoms were improved by thymectomy in 2 cases, but progression of the renal disease was not improved. Some systemic abnormalities, including immunological aberrations, were observed in these two disorders. It is postulated that T cell abnormalities in IgA nephropathy might be independent of the development of myasthenia gravis.

Adult↗
PubMed1989

Interleukin-1 production and action in thyroid tissue.

This study was undertaken to determine the effects of interleukin-1 (IL-1) on human thyroid epithelial cells (thyrocytes) and whether thyrocytes produce IL-1. The supernatants of cultured peripheral blood monocytes stimulated with lipopolysaccharide (LPS) increased [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Grave's disease. The IL-1 levels of cultured supernatants of monocytes were measured by a thymocyte costimulation assay and a solid phase sandwich immunoenzymometric assay. The supernatants of monocyte cultures stimulated with LPS contained significant amounts of IL-1 bioactivity and IL-1 alpha and IL-1 beta immunoactivity. Recombinant IL-1 beta (rIL-1 beta) also stimulated [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Graves' disease, and it increased the proportion of thyrocytes in the S phase of the cell cycle. Furthermore, thyrocytes stimulated with rIL-1 beta for 24 h produced significant amounts of prostaglandin E2. Indomethacin inhibited completely the rIL-1 beta-stimulated prostaglandin E2 production and increased markedly [3H]thymidine incorporation. IL-1-like activity also was detected in the cultured supernatants of lipopolysaccharide (LPS)-stimulated thyrocytes from Graves' and normal thyroid glands, but the amount of IL-1-like activity secreted by thyrocytes was significantly less than that secreted by circulating monocytes. The kinetics of the release of IL-1-like activity by thyrocytes were similar to those of its production by circulating monocytes. Pretreatment of thyrocytes with interferon-gamma failed to enhance the release of IL-1-like activity. Moreover, IL-1 alpha or IL-1 beta immunoreactivity could not be detected in the supernatants of LPS-stimulated thyrocytes, despite the presence of IL-1-like bioactivity. No IL-1 alpha mRNA was detected in unstimulated thyrocytes or thyrocytes stimulated with LPS and phorbol myristate acid. These findings demonstrate that thyrocytes produce an IL-1-like substance(s), but not IL-1, when stimulated by LPS. We conclude that IL-1 may regulate the proliferation of thyrocytes and that local production of IL-1 by infiltrating monocytes may contribute to the development of goiter in patients with autoimmune thyroid diseases.

Biological Availability↗
PubMed1989

Abnormal B lymphocyte function in thyroid glands from patients with Graves' disease.

Thyroid-infiltrating B lymphocytes from patients with Graves' disease were investigated in regard to their phenotypic profiles, cell size, cell cycle status, proliferative response to Staphylococcus aureus Cowan 1 (SAC), and spontaneous production of immunoglobulin G (IgG) and antithyroidal autoantibodies. Thyroid tissues and peripheral blood were obtained at the time of subtotal thyroidectomy of 27 Graves' patients who had been treated with thionamide drugs and iodide before operation. Two intrathyroidal mononuclear cell populations were obtained from these thyroid tissues. One cell population was isolated from the supernatants after mechanical disaggregation of the tissues and was defined as TG-1 cells. Another cell population, defined as TG-2 cells, was isolated from the supernatants of overnight cultures of the thyroid debris after enzymatic digestion. The percentages of B lymphocytes bearing activated markers and plasma cells (CD20+CD21-, IgM+IgD-, CD20+ transferrin receptor+, PCA-1+) were significantly higher in the TG-1 and TG-2 cell populations than in peripheral blood from Graves' disease patients and normal subjects. These phenotypic changes were accompanied by increased thyroid gland B lymphocyte cell size from patients with Graves' disease. The proliferative response of B lymphocytes to SAC was markedly lower in TG-1 and TG-2 cell populations than in peripheral blood cells from Graves' disease patients and normal subjects. B lymphocytes isolated from thyroid glands secreted significantly more IgG and antithyroidal autoantibodies than those from peripheral blood. Based on the findings of abnormalities in thyroid-infiltrating B lymphocytes, we suggest that activated B lymphocytes may induce the excessive production of antithyroidal autoantibodies in thyroid glands from patients with Graves' disease.

Adult↗
PubMed1989

Cytotoxic activity of interleukin-2 (IL-2) activated killer cells toward thyroid epithelial cells.

We investigated the sensitivity of thyroid epithelial cells (thyrocytes) to IL-2 activated killer cells. The thyrocytes were lysed by autologous and allogeneic IL-2-activated killer cells; there were no differences in sensitivity to the killer cells between normal thyrocytes and thyrocytes from patients with Graves' disease. When thyrocytes were pretreated with recombinant interferon (rIFN) gamma or alpha, the IL-2-activated killer cell-mediated cytotoxicity was depressed and varied inversely with the cell surface expression of class I HLA gene products. The rIFN-gamma pretreatment did not alter the kinetics of thyrocytes lysis by IL-2-activated killer cells. Using cold target competition analysis, rIFN-gamma-pretreated thyrocytes clearly competed less effectively than did untreated cells for lysis of untreated target cells. These results suggest that rIFN-gamma or IFN-alpha pretreatment of thyrocytes may reduce their ability to be recognized by effector cells. These findings suggest that destruction of thyrocytes in autoimmune thyroiditis may be, in part, due to IL-2-activated killer cells and may be regulated by IFN.

Cells, Cultured↗
PubMed1989

Phase II study of carboplatin in non-small cell lung cancer.

Forty four patients with advanced non-small cell lung cancer (NSCLC) were treated with carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylate platinum II) at a dose of 400-450 mg/m2 intravenously every four weeks in a phase II study. Forty three patients were evaluated for response and toxicity. Two patients achieved responses resulting in an overall response rate of 4.7% (95% confidence limits: 0.6-15.8%); one of these had not been treated previously and the other had been treated previously with vinblastine. The durations of their responses were 5 and 7 months, respectively. The response rate in 28 previously untreated patients was 3.6% (1/28; 95% confidence limits: 0.1-18.3%). Myelosuppression was the most commonly found toxicity, and thrombocytopenia especially was dose-limiting. Thrombocytopenia (less than 75,000/mm3) was observed in 12 patients (28%). Leukopenia (less than 3,000/mm3) was observed in 14 patients (33%). No serious infection or bleeding occurred, however. Treatment with 400-450 mg CBDCA/m2 was well tolerated in the good risk patients in this study. Mild to moderate emesis was observed in 28 patients (65%). No renal toxicity, neurotoxicity or ototoxicity was seen. It was demonstrated that CBDCA had little efficacy in NSCLC at the dose and schedule given in the present study.

Adult↗