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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 703 records · Page 39Linked to original sources

Recognition of ovarian cancer antigen CA125 by murine monoclonal antibody produced by immunization of lung cancer cells.

In studies aimed at developing monoclonal antibodies against lung adenocarcinomas, we produced a murine monoclonal antibody designated 130-22 by immunizing mice with lung cancer cells. Since in immunoperoxidase staining experiments this antibody was reactive not only with lung adenocarcinomas but also with ovarian carcinomas, we examined its relationship to the ovarian cancer marker CA125, an antigen recognized by monoclonal antibody OC125 produced by immunization of mice with ovarian carcinoma cells. Although CA125 antigen was adsorbed by 130-22 antibody, 125I-labeled 130-22 did not compete with OC125, indicating that although these two antibodies recognized CA125 antigen, they reacted with separate antigenic determinants. The antigen defined by both antibodies was thought to be heat-labile glycoprotein with a molecular weight of over 1,000,000. A series of immunoradiometric assays was developed using combinations of two monoclonal antibodies in a simultaneous forward sandwich mode. Mixed monoclonal antibodies may provide a more sensitive assay for the detection of CA125 than the homologous assay, in which OC125 was used both as a tracer and as a catcher. These results indicate that CA125 is an antigen with two separate epitopes present in both ovarian and lung adenocarcinomas and that combination use of monoclonal antibodies reactive with different antigenic determinants will give certain advantages to the immunoradiometric assay of cancer markers.

Adenocarcinoma↗

Stimulation of low density lipoprotein receptor activity by conditioned medium from a human cancer cell line.

Low density lipoprotein receptor activity in cultured rabbit aortic smooth muscle cells was enhanced by the addition of the conditioned medium derived from the serum-free culture of a human lung cancer cell line. By gel filtration, two peaks of low density lipoprotein receptor-enhancing fractions were obtained, and the molecular weights were 140,000 and greater than 850,000. These fractions also stimulated [3H]thymidine incorporation into DNA. Maximal stimulations of the low density lipoprotein receptor activity and [3H]thymidine incorporation were observed at 16 and 20 h after the addition of the conditioned medium, respectively. The apparent Km (about 10 micrograms/ml) was not changed by the addition of the conditioned medium. De novo cholesterol synthesis was also stimulated by the conditioned medium. It is speculated that certain factors released from the cancer cells affect cholesterol metabolism in normal cells.

Animals↗

A simple and efficient liposome method for transfection of DNA into mammalian cells grown in suspension.

For a highly efficient plasmid transfection into mammalian cells grown in suspension, DNA was entrapped in liposomes prepared by the phosphatidylserine calcium-induced fusion method. Employing this technique, a transfection efficiency of about 2% was achieved, with 22 tk+-transformants obtained from 10(3) of mouse mammary carcinoma FM3Atk- cells transfected with a plasmid carrying the thymidine kinase (tk+) gene of the Herpes simplex virus. As compared with a previous report [Ayusawa et al., J. Biol. Chem. 258 (1983) 48-53], this transfection method was more than four orders of magnitude higher than the calcium phosphate method used for FM3Atk- cells. It was shown that the tk+ gene was integrated into the chromosomal DNA and was expressed in all the tk+-transformant clones tested. The described method could be applied to various types of DNA and cells, including those grown as monolayers.

Animals↗

Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes.

We describe an interleukin, termed interleukin 5, that is the recombinant product previously referred to as T-cell-replacing factor (TRF), B-cell growth factor II (BCGF II), or killer-helper factor (KHF). TRF has been defined as a T-cell-derived lymphokine that acts on activated B cells as a B-cell differentiation factor. We have previously demonstrated that TRF is identical to BCGF II and induces expression of receptors for interleukin 2 (IL-2) on activated B cells. We also have reported that KHF can induce not only expression of IL-2 receptors on peanut agglutinin-binding (PNA+) thymocytes but also generation of cytotoxic T lymphocytes (CTL) in PNA+ thymocytes in the presence of IL-2. We show here that culture supernatants of T-cell hybridomas that produce TRF as well as TRF purified by high-pressure liquid chromatography (HPLC-TRF) have KHF activity and generate CTL in PNA+ thymocytes in the presence of stimulator cells and IL-2. Moreover, translation products (recombinant TRF) of Xenopus oocytes injected with cDNA encoding for murine TRF (BCGF II) also exert KHF activity. A rat monoclonal anti-TRF antibody TB13 can block generation of CTL by HPLC-TRF or recombinant TRF. These results indicate that TRF acts not only on B cells as BCGF II but also on PNA+ thymocytes as KHF. In view of the diverse activities and targets of TRF, we propose that TRF refers to a different interleukin, interleukin 5.

Animals↗

Biperiden withdrawal in schizophrenic inpatients receiving long-term antipsychotic medication.

In a double-blind, 4 week study, 42 chronic schizophrenic inpatients receiving antipsychotic and antiparkinsonian (AP) drugs for greater than 3 months were either switched to placebo or maintained on biperiden. In the majority of the patients no clinically apparent discomfort was observed, and only two of 21 placebo patients developed extrapyramidal side effects (EPS) severe enough to require resumption of AP therapy. No significant increase was shown in most items on EPS. Our data suggest that for the majority of patients on long-term AP medication AP drugs should be prescribed only when EPS develop.

Adult↗

Morbidity risk of schizophrenia to parents and siblings of schizophrenic patients.

In order to estimate the familial morbidity risk of schizophrenia, parents and siblings of 1,691 inpatients meeting the DSM-III criteria for schizophrenia were investigated on the basis of a review of medical records, family history data and/or personal interviews. The morbidity risks of schizophrenia to parents and siblings of the schizophrenic probands were 4.0% and 4.1%, respectively, which were greater than the morbidity risk in the general population. Siblings of 118 probands whose parents suffered from schizophrenia were at a significantly greater risk of schizophrenia than siblings of 1,493 probands whose parents did not have schizophrenic illness. These findings support the notion of familial transmission of schizophrenia. A total of 16.4% of the schizophrenic probands had at least one first-degree relative with schizophrenia. This is significantly greater in the female probands than in the male probands.

Adult↗

Serum levels of maprotiline and its adverse effects on depressed patients.

The relationships between the side effects of maprotiline (MPT) and the serum concentration of MPT and desmethylmaprotiline (DMPT) were investigated with 27 blood samplings in 15 depressed inpatients. There were significant correlations between the side effects and serum levels of MPT and DMPT. Mild side effects frequently occurred at levels of more than 130 ng/ml of MPT and 70 ng/ml of DMPT. At more than 220 ng/ml of the MPT levels and 110 ng/ml of DMPT levels, severe side effects occurred. Nearly sigmoidal serum level/side effect response curves occurred with both compounds.

Adult↗

A comparison of maprotiline and its desmethylated metabolite serum concentrations in outpatients and inpatients.

An investigation was conducted on drug defaulting in 26 depressed patients (11 outpatients and 15 inpatients) treated with maprotiline (MPT), using the interrogation methods and measurements of drug serum levels. All the outpatients visited the clinic regularly and complied with taking the prescripted drugs as directed. The results were as follows: (1) The relationships between the MPT and desmethylmaprotiline (DMPT) serum levels and the daily MPT doses showed highly linear regressions in all the patients, and in the inpatients and outpatients separately. There were significant differences between the regression coefficients obtained in the outpatients and inpatients with respect to MPT (P less than 0.01) and DMPT (P less than 0.001). There was a discrepancy between the results from the patients' reports and measurements of the drug serum levels. This finding indicated noncompliance by the outpatients. (2) Comparing various factors of the outpatients to those of the inpatients, the DMPT/MPT ratio of the former was higher than that of the latter (P less than 0.05). This was also due to the patients' noncompliance, and this ratio, therefore, was considered to be a sensitive marker for checking the compliance of the patients treated with MPT.

Adult↗

A simultaneous analytical method for catecholamines, indoleamines, and related compounds in 11 rat brain regions.

A simple high-performance liquid chromatographic method that allows the determination of 10 biogenic amines and related compounds for crude brain extracts has been developed. The compounds that can be quantified comprise norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, dopamine, 5-hydroxyindole-3-acetic acid, homovanillic acid, 3-methoxytyramine, 5-hydroxytryptamine and tryptophan. The detection system involves a three electrode-coulometric determination followed by fluorometric determination. This method is highly selective and sensitive, and in the present study, the usefulness of this methodology was confirmed by applying it to the determination of the levels of these various substances in 11 rat brain regions.

Animals↗

Induction of c-Ha-ras transcription in rat cells by simian virus 40 large T antigen.

Rat 3Y1 cells expressing simian virus 40 large T antigen under the control of the mouse mammary tumor virus long terminal repeat were established. The amount of c-Ha-ras mRNA in those cells was elevated by about 20 times in parallel with large T antigen after exposure to dexamethasone for 48 h. In chloramphenicol acetyltransferase assays with a plasmid containing the c-Ha-ras-1 promoter the increase in c-Ha-ras mRNA was shown to occur at the transcriptional level.

Animals↗

Effects of yohimbine and desipramine on cardiac noradrenaline release and ventricular arrhythmias during acute coronary artery occlusion and reperfusion in anesthetized dogs.

Effects of yohimbine (YHMB, an alpha 2-antagonist) and desipramine (DMI, a neuronal uptake inhibitor) were compared on cardiac noradrenaline (NA) release either upon left ansa subclavia nerve stimulation during acute occlusion of the left anterior descending coronary artery (LAD) or upon subsequent LAD reperfusion without stimulation in anesthetized dogs. In control dogs, before LAD occlusion, coronary sinus (CS) NA output increased from 5.4 +/- 1.0 to 26.8 +/- 4.0 ng/min (p less than 0.05) upon stimulation (2 Hz, 30 s). The response to stimulation remained unchanged 25 min after LAD occlusion. During reperfusion 60 min after occlusion, the output of CS-NA and lactate increased from 6.1 +/- 0.8 to 51.3 +/- 19.4 ng/min (p less than 0.05) and from 2.7 +/- 0.5 to 6.7 +/- 1.3 mg/min (p less than 0.05), respectively. In dogs treated with YHMB, the stimulation-induced increase in NA output was potentiated at least fourfold (p less than 0.05) either before or during LAD occlusion, but not during reperfusion. In dogs receiving DMI, stimulation-induced CS-NA output was enhanced to a similar extent (approximately twofold, p less than 0.05) either before or during occlusion, while reperfusion-induced NA output was markedly potentiated by approximately ninefold (p less than 0.05). Maximum dP/dt of left ventricular pressure remained unchanged upon reperfusion in all groups. The total arrhythmic ratio in the drug-treated groups did not significantly differ from the ratio in control dogs upon either stimulation or reperfusion. The data suggest that an abrupt increase in NA output upon reperfusion may result from a washout of NA locally accumulated in the ischemic and (or) peri-ischemic region during the preceding occlusion period, and that NA thus released does not have substantial hemodynamic effects. The results indicate that in the presence of YHMB or DMI, the potentiated increase in NA release in response to either nerve stimulation during LAD occlusion or to reperfusion without stimulation did not aggravate ventricular arrhythmia, most probably owing to the antiarrhythmic properties of these substances.

Anesthesia↗

Distinct effects of Na+ and Li+ on the induction of morphological changes in A431 cells mediated by epidermal growth factor.

Epidermal growth factor (EGF) induced the formation of thin sheetlike extensions (lamellipodia) and filamentous extensions at the edges of colonies of A431 cells. To determine the necessary processes for the induction of the morphological changes mediated by EGF, the effects of a variety of ions on these changes were examined. In a NaCl solution supplemented with CaCl2, MgCl2 and glucose, no EGF-induced morphological changes were observed. However, when the NaCl was replaced with LiCl, fingerlike extensions were formed, but sheetlike extensions were not. Addition of vanadate to the NaCl solution also induced fingerlike extensions in cells treated with EGF. In contrast, sheetlike lamellipodia were formed in EGF-treated cells by the addition of K+ or PO4(3-) to the NaCl solution or by the addition of PO4(3-) to the LiCl solution. These findings indicate that Li+, K+, PO4(3-) and vanadate are involved in the processes of EGF-induced morphological changes. Since vanadate and Li+ have been shown to inhibit phosphatases, an EGF-dependent phosphorylation step may play an important role in the induction of the morphological changes observed.

Carcinoma, Squamous Cell↗

Correlation of positive syphilis serology with invasive amebiasis in Japan.

Approximately 20% of 52 Japanese males with invasive amebiasis confirmed by gel diffusion precipitin test (GDP) were positive by both Treponema pallidum hemagglutination test (TPHA) and nontreponemal antigen tests, and an additional 20% were positive by TPHA alone. However, none of 109 GDP-negative Japanese males without invasive amebiasis were positive on these serologic tests for syphilis. At least 2 bisexuals and 4 homosexuals were among those with invasive amebiasis. All of these biased males were positive on both TPHA and nontreponemal antigen tests. Four of the biased males had liver abscess and 2 had amebic dysentery or colitis. Bisexual or homosexual males were not found in the negative GDP group. These observations suggest that sexually transmitted amebiasis due to Entamoeba histolytica occurs among sexually biased males in Japan.

Adolescent↗