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Biomedical subjects

K Yui

Publications and source records attributed to K Yui.

At least 37 records · Page 2Linked to original sources
PubMed1998

Unique molecular surface features of in vivo tolerized T cells.

Differential expression of surface markers can frequently be used to distinguish functional subsets of T cells, yet a surface phenotype unique to T cells induced into an anergic state has not been described. Here, we report that CD4 T cells rendered anergic in vivo by superantigen can be identified by loss of the 6C10 T cell marker. Inoculation of Vbeta8.1 T cell antigen receptor (TCR) transgenic mice with a Vbeta8.1-reactive minor lymphocyte-stimulating superantigen (Mls-1(a)) induces tolerance to Mls-1(a) by clonal anergy. CD4 lymph node T cells from Mls-1(a) inoculated transgenic mice enriched for the 6C10(-) phenotype neither proliferate nor produce interleukin-2 upon TCR engagement, whereas 6C10(+) CD4 T cells retain responsiveness. Analysis of T cell memory markers demonstrate that 6C10(-) T cells remain 3G11(hi) but express heterogeneous levels of CD45RB, CD62L, CD44, and the CD69 early activation marker, suggesting that T cells at various degrees of activation can be functionally anergic. These studies demonstrate that anergic T cells can be purified based on 6C10 expression permitting examination of issues concerning biochemical and biological features specific to T cell anergy.

Animals↗
PubMed1998

Factors affecting the development of spontaneous recurrence of methamphetamine psychosis.

The process triggering spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks) was studied in 41 flashbackers, along with 84 non-flashbackers with a history of MAP psychosis. Plasma monoamine metabolite levels were assayed in 25 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with persistent MAP psychosis and 28 control subjects. All flashbackers had experienced threatening events or frightening paranoid-hallucinatory states during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. Plasma norepinephrine levels were elevated during flashbacks. The results suggest that a mild fear of other people may have elicited memories of MAP psychosis associated with threatening experiences through increased sensitivity to psychosocial stressors. As a result the flashbacks occurred, including an increase in peripheral noradrenergic activity.

Adult↗
PubMed1998

Cytotoxic T-lymphocyte-mediated lysis of Toxoplasma gondii-infected target cells does not lead to death of intracellular parasites.

CD8(+) T cells play a crucial role in the control of infection with intracellular microbes. The mechanisms underlying the CD8(+) T-cell-mediated clearance of the intracellular pathogen Toxoplasma gondii are, however, not completely understood. The effect of CD8(+) cytotoxic T-lymphocyte (CTL)-mediated lysis of host cells on the viability of intracellular T. gondii was investigated. Quantitative competitive PCR of the gene encoding T. gondii major surface antigen (SAG-1) was combined with treatment of the parasites with DNase, which removed the DNA template of nonviable parasites. The induction by CD8(+) CTLs of apoptosis in cells infected with T. gondii did not result in the reduction of live parasites, indicating that intracellular T. gondii remains alive after lysis of host cells by CTLs.

Animals↗
PubMed1997

New assay for glycated lipoproteins by high-performance liquid chromatography.

We developed an automated analytic system for glycated lipoprotein using high-performance liquid chromatography (HPLC) with an affinity boronate column and a gel permeation column. This system can measure glycated lipoprotein (glycated LDL and glycated HDL) in a small (5 microliters) sample of serum in a short time (40 min/sample). Recovery with this system was 92.1%. Therefore a large number of samples can be measured in clinical use. The system should contribute to an elucidation of the role of glycated lipoprotein in atherosclerosis.

Chromatography, High Pressure Liquid↗
PubMed1997

Noradrenergic activity and spontaneous recurrence of methamphetamine psychosis.

The process that triggers flashbacks due to previous methamphetamine (MAP) psychosis was studied in 28 flashbackers, along with 84 non-flashbackers with a history of MAP psychosis. We measured plasma monoamine metabolite levels in 12 of the flashbackers and eight of the non-flashbackers, along with 28 normal controls. Most flashbackers had undergone frightening experiences during previous MAP use. The dominant triggering factor was a mild fear of other people. Plasma norepinephrine (NE) levels in the 12 flashbackers were increased during flashbacks. Thus, MAP use associated with threatening experiences may have increased sensitivity to stressors, leading to the occurrence of flashbacks, including exaggerated noradrenergic activity.

Adult↗
PubMed1997

Precipitating factors in spontaneous recurrence of methamphetamine psychosis.

This paper examines noradrenergic hyperactivity in response to stress in the development of spontaneous recurrences of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks, in studies of psychedelic drug use. We studied predictors of flashbacks in 36 subjects with flashbacks, along with 80 subjects with a history of MAP psychosis who did not experience flashbacks. Plasma monoamine metabolite levels were assayed in 26 of the 36 subjects with flashbacks, 16 of the 80 subjects without flashbacks, nine subjects with persistent MAP psychosis, and 28 normal controls. None of the 28 controls became psychotic. A square root transformation was applied to all monoaminergic values, resulting in data nearly normally distributed. The subjects with flashbacks had been exposed to stressful events or threatening paranoid-hallucinatory states or both during previous MAP use. Most flashbacks occurred under conditions that provoked a mild fear of other people. Plasma norepinephrine levels were markedly increased during flashbacks. Thus, stressful experiences together with MAP use may have induced noradrenergic hyperreactivity to a mild stress, which in turn may elicit memories of MAP psychosis associated with stressful experiences. A mild fear of other people precipitated the flashbacks, including markedly increased noradrenergic activity. The results of this study suggest that noradrenergic hyperreactivity to a mild stress is a precipitating factor in spontaneous recurrences of MAP psychosis.

Adult↗
PubMed1997

Monoamine neurotransmitter metabolites and spontaneous recurrence of methamphetamine psychosis.

The present study was conducted to evaluate plasma levels of monoamine neurotransmitter metabolites in spontaneous recurrences of methamphetamine psychosis (i.e., flashbacks). The subjects were 50 physically healthy females comprised of 25 who experienced flashbacks (flashbackers), 18 who did not experienced methamphetamine psychosis, and 9 who were currently suffering from persistent methamphetamine psychosis. The control data were available from 28 normal healthy females, of whom 20 had previously abused methamphetamine (users) and 8 who had not (nonusers), none of whom had ever become psychotic. Plasma levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT), and their respective metabolites were assayed. Plasma NE levels were significantly higher in the 25 flashbackers during their flashbacks than during their periods of normalcy, and were significantly higher than those in the 20 user and 8 nonuser controls. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels during flashbacks were significantly higher than those in the 20 user controls. The nine subjects with persistent methamphetamine psychosis had significantly higher NE levels than the user and nonuser controls. The 16 nonflashbackers had significantly higher MHPG levels than the user controls. The present study suggests that an increase in peripheral noradrenergic activity is related to the occurrence of flashbacks.

Adult↗
PubMed1997

Oxidation of remnant-like particles from serum of diabetic patients, patients with ischemic heart disease and normal subjects.

Remnant-like particles (RLP) are reportedly involved in the pathogenesis of atherosclerosis, as are lipid peroxides. To assess the role of the oxidation of RLP in this disease, we compared the oxidation of RLP with that of total very low density lipoproteins (VLDL) obtained from the serum of 10 patients with ischemic heart disease (IHD), 10 patients with diabetes mellitus (DM) and 10 normal subjects by measuring the levels of thiobarbituric acid reactive substances (TBARS). Our results indicated that RLP were oxidized in vivo to a greater extent than total VLDL in all three groups of subjects. The serum levels of RLP were significantly higher in the patients than in the normal subjects. The oxidation of RLP may therefore be involved in the progression of atherosclerosis in patients with IHD or DM.

Adult↗
PubMed1997

Methamphetamine psychosis: spontaneous recurrence of paranoid-hallucinatory states and monoamine neurotransmitter function.

We studied the process that triggers spontaneous recurrences of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks, in 28 female patients who experienced flashbacks, by comparing them with 92 female nonflashbackers with a history of previous MAP psychosis. The study evaluated plasma monoamine neurotransmitter function in 12 of the 28 flashbackers and in 8 of the 92 nonflashbackers. Control data were obtained from 28 normal, healthy females composed of 13 MAP users and 15 nonusers, none of whom became psychotic. The 28 flashbackers had experienced significantly greater frequencies of threatening events and frightening paranoid-hallucinatory states during previous MAP abuse than the 92 nonflashbackers. The dominant triggering factor was a mild fear of other persons. Plasma norepinephrine (NE) levels were significantly higher in the 12 flashbackers during flashbacks than during periods of normalcy and were significantly higher than those in the 13 user and 15 nonuser control subjects. Plasma NE levels in the 12 flashbackers during periods of normalcy were significantly higher than those in the 13 user control subjects. The eight nonflashbackers had significantly higher NE levels than the 13 user control subjects. This suggests that an increase in peripheral noradrenergic activity may be related to the occurrence of flashbacks. The present study suggests that repeated MAP use with frightening experiences may induce sensitivity to psychosocial stressors. A mild fear of other persons may have actualized the encoded frightening memories associated with the frightening experiences via increased sensitivity to psychosocial stressors. Thus, flashbacks may have been caused through an increase in peripheral noradrenergic activity.

Adult↗
PubMed1996

Monoamine neurotransmitter function and spontaneous recurrence of methamphetamine psychosis.

The process that triggered spontaneous recurrence of methamphetamine (MAP)-induced paranoid-hallucinatory psychosis, a phenomenon known as flashbacks, was studied in 41 subjects with flashbacks, along with 84 subjects with a history of previous MAP psychosis but no flashbacks. Plasma levels of norepinephrine (NE), dopamine, and 5-hydroxytryptamine, and their respective metabolites were assayed in 28 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with persistent MAP psychosis, and 28 healthy controls comprised of 20 MAP users and 8 non-users. None of the 28 controls had become psychotic. The 41 flashbackers had experienced significantly greater frequencies of threatening events and frightening paranoid-hallucinatory states during previous MAP use than the 84 non-flashbackers. The dominant factor that triggered flashbacks was a mild fear of other persons. The 41 flashbackers may have encoded threatening experiences as frightening images. Repeated MAP use with threatening experiences may induce sensitization to frightening images. Plasma NE levels during flashbacks were significantly higher than the levels during periods of normalcy, and the NE levels in the 20 user and 8 non-user controls. The 9 subjects with persistent MAP psychosis had significant higher levels of NE than the user and non-user controls. The 16 non-flashbackers had significantly higher MHPG levels than the user controls. The findings suggest that MAP use may induce changes at pharmacological levels in the process underlying sensitization to frightening images. We suggested that when the flashbackers experienced a mild fear of other persons, MAP-induced sensitization to frightening images may have been actualized. Thus, the flashbacks may have been caused through increased noradrenergic hyperactivity.

Adult↗
PubMed1996

Plasma monoamine metabolites and spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory psychosis: relation of noradrenergic activity to the occurrence of flashbacks.

The relationship between monoamine neurotransmitter function and spontaneous recurrence of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks, was studied in a group of incarcerated women. Plasma levels of norepinephrine (NE), dopamine, 5-hydroxytryptamine, and their respective metabolites were assayed in 28 flashbackers, 19 non-flashbackers with a history of previous MAP psychosis, and 9 subjects with persistent MAP psychosis. Control data were available from 61 physically healthy prisoners (41 MAP users and 20 non-users, none of whom became psychotic). The plasma NE levels of the 28 flashbackers during flashbacks were significantly higher than levels during periods of normality, and were significantly higher than those in the MAP user and non-user controls. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels during flashbacks were significantly higher than those in the user controls. The nine subjects with persistent MAP psychosis had significantly higher NE levels than the user and non-user controls. The 19 non-flashbackers had significantly higher MHPG levels than the user controls. Plasma levels of 3-methoxytyramine and dihydroxyphenylacetic acid contributed to the NE levels in the flashbackers, in contrast to the findings in the control group. Noradrenergic systems may be compromised in the flashbackers, suggesting increased vulnerability to psychotic decompensation. These findings suggest that aggravation in peripheral noradrenergic hyperactivity may be an important factor in the occurrence of flashbacks.

Adult↗
PubMed1996

Inhibition of apoptosis and augmentation of lymphoproliferation in bcl-2 transgenic Fas/Fas ligand-defective mice.

Mice defective in Fas (CD95 or APO-1) or its ligand (lpr or gld mice) develop age-dependent lymphadenopathy and systemic autoimmune disease. T cells accumulating in the lymph nodes of these mice express reduced levels of Bcl-2 protein and are susceptible to spontaneous and glucocorticoid-induced apoptosis. We backcrossed bcl-2 transgenic mice to lpr and gld mice to homozygosity to determine the effects of Bcl-2 overexpression. T cells in these mice were resistant to spontaneous and glucocorticoid-induced apoptosis in vitro. Moreover, the accumulation of CD4(-)CD8(-) T cells in the lymph nodes and the spleens was augmented, suggesting that a Bcl-2-dependent mechanism regulating the number of T cells residing in the peripheral lymphoid organs in addition to the Fas-mediated pathway exists.

Animals↗
PubMed1996

Effects of repeated treatment with methamphetamine plus scopolamine and methamphetamine on behavioral sensitization and conditioning.

This study compared repeated treatment with methamphetamine (4.0 mg/kg, i.p.) plus scopolamine (0.5 mg/kg, i.p.) and methamphetamine alone in behavioral sensitization and drug conditioning with respect to a reciprocal balance between the dopaminergic and cholinergic systems. Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of stereotyped behavior than repeated methamphetamine treatment. Methamphetamine plus scopolamine-induced stereotyped behavior was reproduced by challenge injections of not only methamphetamine plus scopolamine and methamphetamine, but also, to a lesser extent, by scopolamine challenges. The methamphetamine plus scopolamine-sensitized rats were conditioned to a low-frequency tone (300 Hz, 100 dB) as conditioned stimulus associated with the drug state. They responded to pairings of the tone and placebo injections, but not to the tone alone or the placebo alone. The methamphetamine-sensitized rats failed to exhibit conditioning. These results suggest that methamphetamine plus scopolamine-induced pronounced behavioral sensitization may produce an enhanced conditioning. Exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for drug conditioning. We concluded that behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems, in favor of a dopaminergic dominance. Conditioning to the drug-associated tone may operate via a reciprocal balance between the dopaminergic and cholinergic systems.

Animals↗
PubMed1996

Behavioral responses induced by repeated treatment with methamphetamine alone and in combination with scopolamine in rats.

Repeated amphetamine (A) or methamphetamine (M) treatment induces behavioral sensitization and drug conditioning. The present study compared behavioral sensitization and drug conditioning between treatments with M combined with scopolamine (S) and M alone with respect to a reciprocal balance between the dopaminergic and inhibitory cholinergic systems in rats. Repeated treatment with M (4.0 mg/kg i.p.) combined with S (0.5 mg/kg i.p.) (MS) produced progressive enhancement of stereotyped behavior, compared with repeated M treatment alone. Repeated MS treatment induced focussed stereotyped behavior that was elicited by every challenge injection of not only MS and M, but also partially by S. MS- but not M-sensitized rats exhibited conditioned responses to a tone (300 Hz, 100 dB) associated with drug state, suggesting that MS-induced pronounced behavioral sensitization may lead to an enhanced conditioned response to the conditioned stimulus (CS) of a tone. It is suggested that MS-induced behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems in favor of a dopaminergic dominance, and that such a balance may be involved in the conditioning to the drug-associated tone CS.

Animals↗
PubMed1996

TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation.

All T cells of TCR-beta transgenic mice bear a single TCR-beta chain and consequently the diversity of the TCR may be reduced by as much as one million-fold. Despite this limited diversity, many measures of lymphocyte function in these mice are normal. We have previously demonstrated that lymphoid cells from TCR-beta mice are unable to mediate an intense graft-versus-host response (GVHR). In order to investigate the mechanism of this hyporesponsiveness, we studied in vivo allorecognition in diverse strains of TCR-beta mice. All tested strains of TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barriers. In addition, mixtures of cells from several strains of TCR-beta mice only generated mild GVHRs. Sensitive tests of in vitro allorecognition show that lymphoid cells from TCR-beta mice respond less vigorously to alloantigen as measured both by decreased proliferation and decreased IL-2 production in a MLR. In addition, cells from TCR-beta mice fail to use exogenous IL-2 appropriately in their response to alloantigen. We conclude that the fixed TCR-beta chain causes a defective response to alloantigen, which is measured as decreased IL-2 generation and utilization, and that this abnormality results in a decreased GVHR.

Animals↗
PubMed1995

Age-dependent reduction of Bcl-2 expression in peripheral T cells of lpr and gld mutant mice.

Autoimmune-prone lpr and gld mice carry defects in the apoptosis-mediating cell surface molecule Fas and its ligand, respectively. These mice develop lymphadenopathy because of an age-related accumulation of nonmalignant CD4- CD8- T cells in the peripheral lymphoid organs, suggesting a role for Fas-mediated apoptosis in peripheral T cell homeostasis. However, these accumulating cells are more susceptible to apoptosis ex vivo than peripheral T cells from control mice. To investigate the influence of additional regulatory elements on defects in the Fas-mediated apoptosis pathway, we analyzed the expression of Bcl-2 protein, a repressor of apoptosis, in T cells of lpr and gld mice. The expression levels of Bcl-2 in peripheral T cells of aged lpr and gld mice were significantly reduced when compared with their normal counterparts. Bcl-2 expression decreased with age in peripheral T cells, but not in thymocytes, suggesting that down-regulation of Bcl-2 protein occurs in the periphery. Analysis of T cell subsets indicated that CD4+ and CD4- CD8- T cells expressed significantly reduced levels of Bcl-2, whereas CD8+ cells maintain high levels of Bcl-2 expression. However, all peripheral T cell subsets including CD8+ cells were susceptible to glucocorticoid-induced apoptosis, indicating that there is no direct correlation between the levels of Bcl-2 expression and susceptibility to glucocorticoid-induced apoptosis. These studies suggest the presence of complex regulatory mechanisms for lymphocyte apoptosis and survival.

Age Factors↗
PubMed1995

Methamphetamine plus scopolamine potentiates behavioral sensitization and conditioning.

The effects of repeated methamphetamine (4.0 mg/kg) plus scopolamine (0.5 mg/kg) treatment on behavioral sensitization and drug conditioning in rats were compared with the effects of repeated methamphetamine treatment. Behavioral sensitization induced by repeated methamphetamine plus scopolamine treatment was more vigorous than that induced by repeated methamphetamine treatment. Repeated methamphetamine plus scopolamine treatment produced sensitized responses, not only to methamphetamine plus scopolamine and methamphetamine but also, to a lesser extent, to scopolamine. Methamphetamine plus scopolamine-sensitized rats but not methamphetamine-sensitized rats exhibited conditioned responses to a low-frequency tone (300 Hz, 100 dB) associated with the drug state, suggesting that robust methamphetamine plus scopolamine-induced behavioral sensitization may lead to enhanced conditioning. It is plausible that robust behavioral sensitization might operate via a reciprocal balance between the dopaminergic and cholinergic systems in favor of dopaminergic dominance. Conditioning to the drug-associated tone may be mediated via a reciprocal balance between the two transmitter systems.

Acoustic Stimulation↗