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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 19 recordsLinked to original sources

Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer.

BACKGROUND: CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS: Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9-coated beads. RESULTS: The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS: Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.

Acrylic Resins

Miniature postsynaptic currents recorded from identified rat spinal dorsal horn projection neurons in thin-slice preparations.

Whole-cell voltage-clamp recordings were made from spinothalamic and spinomesencephalic tract neurons in thin-slice preparations of rat spinal cord. In the presence of tetrodotoxin, spontaneous inward and outward postsynaptic currents were observed near the resting membrane potential. These currents were divided into miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate, and miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine or gamma-aminobutyric acid (GABA). Glutamatergic mEPSCs had two components mediated by NMDA and non-NMDA receptors. Analyzing these miniature synaptic currents, valuable information concerning the pre- and postsynaptic mechanisms underlying modulation of synaptic transmission in the spinal dorsal horn could be obtained.

Action Potentials

Role of intracellular Ca2+ on histamine release from rat peritoneal mast cells.

The benzoic acid derivative 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) strongly inhibited histamine release from rat peritoneal mast cells induced by various secretagogues. TMB-8 also inhibited Ca2+ mobilization from intracellar Ca2+ stores. However, histamine release induced by compound 48/80 (condensation product of N-methyl-p-methoxy-phenethylamine and formaldehyde) was not affected by TMB-8. These results indicate that Ca2+ mobilization is necessary to elicit the release of histamine from mast cells.

Animals

Positive imaging of cardiomyopathy with 99mTc(V)-DMSA.

A case of histologically proven dilated cardiomyopathy and a case of clinically diagnosed cardiomyopathy (cardiac amyloidosis was strongly suspected but was not confirmed) were examined with 99mTc(V)-dimercaptosuccinic acid (DMSA). 99mTc(V)-DMSA accumulation in the damaged myocardium was clearly demonstrated. These results suggested the possibility that 99mTc(V)-DMSA could be used as a positive agent for cardiomyopathy.

Aged

Tactile agnosia and tactile aphasia: symptomatological and anatomical differences.

Two patients with tactile naming disorders are reported. Case 1 (right hand tactile agnosia due to bilateral cerebral infarction) differentiated tactile qualities of objects normally, but could neither name nor categorize the objects. Case 2 (bilateral tactile aphasia after operation of an epidural left parietal haematoma) had as severe a tactile naming disturbance as Case 1, but could categorize objects normally, demonstrating that tactile recognition was preserved. Case 1 may be the first case of tactile agnosia clearly differentiated from tactile aphasia. CT scans of Case 1 revealed lesions in the left angular gyrus, and in the right parietal, temporal, and occipital lobes. Case 2 had lesions in the left angular gyrus and of posterior callosal radiations. Our findings suggest that tactile agnosia appears when the somatosensory association cortex is disconnected by a subcortical lesion of the angular gyrus from the semantic memory store located in the inferior temporal lobe, while tactile aphasia represents a tactual-verbal disconnection.

Aged

Effect of chronic administration of phenobarbital on the hepatobiliary transport of phenol red: assessment by statistical moment analysis.

The effect of enzyme induction on the hepatobiliary transport of phenol red (PR) in rats was investigated by application of a new analytical system to determine local drug disposition based on statistical moment theory (T. Kakutani et al., J. Pharmacokin. Biopharm. 13:609-631, 1985). Employing the moment parameters obtained from the time courses of plasma and biliary concentrations of PR and its metabolite after intravenous injection, the hepatobiliary transport of PR was theoretically assessed by separating it into component subprocesses such as hepatic uptake, hepatobiliary transfer, and intrahepatic metabolism. The results demonstrated that the acceleration of plasma disappearance of PR caused by pretreatment with phenobarbital (PB), known to induce hepatic enzyme systems, could be attributed to elevation of both hepatic and extrahepatic clearances. While PB did cause bile flow elevation (choleresis) and increased metabolism, these effects were shown to make little contribution to accelerated plasma disappearance of PR, since it was shown that the hepatobiliary excretion of PR was rate-limited by the intrahepatic transfer process, which was unaffected by PB treatment. From the results of this study, this experimental/analysis methodology seems to be useful in obtaining detailed information about hepatobiliary transport of the drug from in vivo data.

Animals

Potent antitumour activity of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) against advanced L1210 leukaemia in mice.

The time dependency of the antitumour activity of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) was examined in mice inoculated i.p. with 10(5) mouse L1210 leukaemia cells. The increase in life span was greater in mice treated with 72 mg kg-1 DWA2114R on the 6th day following tumour inoculation than in mice treated at earlier times. Such superior effects against advanced L1210 were also seen with cis-diammine (1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) but not seen with the parent compound, cis-diamminedichloroplatinum(II) (CDDP) or other antitumour agents devoid of platinum. After the injection of DWA2114R on day 6, most of the ascites tumour cells accumulated in the S and G2/M phases of the cell cycle and the total cell number markedly decreased from 10(8) to less than 10(6). On the other hand, only a temporary G1 arrest and a less than 50% reduction of the cell number were induced after a similar treatment on day 3. Interestingly, the superiority of DWA2114R for advanced L1210 was lost in athymic nude mice and mice depleted of T cells by anti-thymocyte antisera. In addition, mice cured of advanced L1210 specifically rejected re-inoculated L1210 cells. These results indicate that the superior antitumour activity against advanced L1210 is unique to DWA2114R among the agents tested (except for CBDCA) and is caused by both an increased drug susceptibility of tumour cells and a drug-induced antitumour effect mediated by T cells of the host mice.

Animals

Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA).

Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human/mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fc portion and/or CH1 or CL region of murine IgG, and (2) human/mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients.

Aged

Hepatocyte response to continuous low dose-rate radiation in radioimmunotherapy assessed by micronucleus assay.

The response of hepatocytes to low dose-rate irradiation was examined in mice following the injection of radiolabelled monoclonal antibody. Mice were injected intravenously with an 131I-labelled monoclonal antibody 196-14 which recognizes CA125 antigen, and the effect of continuous low dose-rate irradiation on hepatocytes was assessed using the micronucleus assay. The frequency of micronuclei increased in a dose-dependent fashion, but it was lower than the frequency induced by conventional external X-rays which was determined immediately after the irradiation. A linear quadratic model (micronucleus frequency = aD+bD2+c) showed that the value of b decreased with low dose-rate irradiation from the radiolabelled antibody. It is concluded that the micronucleus assay is useful for the evaluation of the response of hepatocytes to irradiation in radioimmunotherapy.

Animals

Transient unilateral reverse ventilation/perfusion mismatch in a patient with lung cancer.

The authors report a transient, unilateral reverse ventilation/perfusion (V/P) mismatch in a patient with squamous cell lung cancer. The right lung was well perfused but not ventilated (unilateral reverse V/P mismatch). However, lung imaging performed 3 days later demonstrated the absence of both perfusion and ventilation (V/P match). Reverse V/P mismatch may be a transient process.

Carcinoma, Squamous Cell

Production of multiple growth factors by a newly established human thyroid carcinoma cell line.

A multiple growth factor-producing tumor cell line (NIM-1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM-1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM-1-conditioned medium (NIM-1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony-stimulating factor (CSF)-dependent cell lines, NFS60-KX and TF-1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and interleukin(IL)-6 mRNAs in NIM-1 cells. Enzyme-linked immunosorbent assays (ELISA) using NIM-1CM also confirmed the production of IL-1 alpha and a small amount of IL-1 beta besides G-CSF, GM-CSF and IL-6 in NIM-1 cells. In addition, unexpected production of IL-11 in NIM-1 cells was detected by northern blot hybridization analysis and by bioassay using an IL-11-dependent cell line. Therefore, NIM-1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM-CSF, IL-6 and IL-11.

Adenocarcinoma, Papillary

Mechanism of action of MY-1250, an active metabolite of Repirinast, in inhibiting histamine release from rat mast cells.

1. When MY-1250 (3.6 x 10(-5) M) was added to mast cells, it caused a rapid increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP) and decrease in adenosine 5'-triphosphate (ATP), both of which recovered to their original levels within 2 min. The accumulation of cyclic AMP was maximal at 20 s after challenge with MY-1250. The minimum level of ATP was observed at 20 s after addition of MY-1250. 2. The initial rise in [Ca2+]i and the histamine release induced by DNP-AS antigen (40 micrograms ml-1) was most strongly inhibited at 20 s after incubation of the mast cells with MY-1250. 3. MY-1250 strongly and dose-dependently inhibited the histamine release from rat mast cells induced by antigen. Moreover, MY-125 strongly inhibited calcium ion mobilization from the intracellular Ca(2+)-store. 4. These results suggested that the inhibitory mechanism of MY-1250 on the initial rise in [Ca2+]i and histamine release induced by antigen was due to the inhibition of ATP-dependent Ca(2+)-release from the intracellular Ca(2+)-stores.

Adenosine Triphosphate

Effect of ryanodine on histamine release from rat peritoneal mast cells induced by anti-IgE.

Ryanodine strongly inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Ryanodine also inhibited Ca(2+)-mobilization from the intracellular Ca(2+)-store as well as histamine release in mast cells activated by anti-IgE. These results suggest that the effect of ryanodine on histamine release from rat mast cells might be due to the inhibition of Ca2+ release from the intracellular Ca2+ store.

Animals