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Biomedical subjects

A Yokoyama

Publications and source records attributed to A Yokoyama.

At least 19 recordsLinked to original sources
PubMed1992

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro.

Roles for interleukin-2 (IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8+ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4+ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4+ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.

Animals↗
PubMed1992

Preparation and biodistribution in mice of [11C]carfentanil: a radiopharmaceutical for studying brain mu-opioid receptors by positron emission tomography.

A potent mu-opioid agonist, [11C]carfentanil, was prepared by the methylation of carfentanil carboxylic acid with [11C]methyl iodide in order to study brain mu-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/mumol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of [11C]carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of [11C]carfentanil by the thalamus and striatum. These results indicate that [11C]carfentanil binds specifically to brain mu-opioid receptors.

Animals↗
PubMed1992

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports 123I-3-iodo-alpha-methyl-L-tyrosine.

123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

Amino Acids↗
PubMed1992

Accumulation of radioactivity in the pancreas after intravenous administration of [13N]ammonia.

A biodistribution study of [13N]ammonia in rats showed a high accumulation of radioactivity in the pancreas soon after the intravenous injection of this tracer. In humans, the pancreas was also clearly visualized by dynamic positron emission tomography soon after the intravenous injection of [13N]ammonia. To investigate the mechanism of the pancreatic accumulation of [13N]ammonia, in vitro studies with pancreatic slices and in vivo biodistribution and metabolism studies were carried out in rats. The results indicated that [13N]ammonia enters the pancreas from the blood by diffusion at a rate dependent on local blood flow, and then is rapidly incorporated into the amino acid fraction (mainly the glutamine fraction), followed by its incorporation into protein. These findings suggest that [13N]ammonia could be useful for diagnostic imaging of the pancreas.

Ammonia↗
PubMed1992

62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups.

Generator-produced positron emitting 62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups were synthesized and evaluated for their bifunctionality: the Cu chelating ability and the biochemical reactivity of the ester groups. In vitro studies showed high stability of the Cu chelate site (4,4-dimethyldithiosemicarbazone structure) and enzymatic hydrolysis of the ester site (ethylester or acetylester). The 62Cu-labeled compounds showed in vivo behavior which may be due to their ester hydrolysis.

Animals↗
PubMed1992

Application of the new zinc-62/copper-62 generator: an effective labeling method for 62Cu-PTSM.

A potential PET flow tracer, 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM), was prepared using a new 62Zn/62Cu generator. With this 62Cu-labeling method based on a ligand exchange reaction, 62Cu-PTSM was quantitatively obtained by simple mixing of the generator eluate, 62Cu-glycine and PTSM solution for a few seconds. The glycine contained in the 62Cu-PTSM injectate had no significant effect in mouse biodistribution studies. The PET studies of 62Cu-PTSM showed brain images that were not visualized by 62Cu-labeled albumin (a plasma pool tracer), in the dog cranium.

Animals↗
PubMed1992

Prolonged QT interval in alcoholic autonomic nervous dysfunction.

QT prolongation on electrocardiography is related to sudden cardiac death and is frequently found in alcoholics. We studied QT prolongation in relation to the function of cardiac autonomic nerves assessed by the coefficient of variation of the R-R interval (CVRR) in three age-matched groups of men: 32 alcoholics with autonomic nervous dysfunction (AN), 32 alcoholics without AN, and 32 healthy controls. The QTc interval and CVRR were measured at rest on the 30th day of abstinence, when electrolyte imbalance had disappeared. Subjects with arrhythmia, conduction abnormality, cardiomegaly, ischemic heart disease or diabetes mellitus were excluded. A CVRR of less than 80% of standard predicted value was judged to represent AN. In alcoholics, QTc correlated negatively with the ratio of CVRR to its standard value (r = -0.49, p < 0.0001). The incidence of QTc prolongation was higher in alcoholics with AN (46.9%) than in alcoholics without AN (21.9%, p < 0.05). QTc prolongation was not observed in healthy controls. The QTc interval was significantly (p < 0.01) longer in alcoholics with AN (444 +/- 20 msec) than in alcoholics without AN (426 +/- 17) and in healthy controls (398 +/- 18). These results suggest that alcoholism causes dysfunction of the autonomic nerves as well as worsening QT prolongation, and this may predispose such patients to sudden cardiac death.

Adult↗
PubMed1992

[Effect of erythromycin on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide].

Recently, "low dose and long term" erythromycin (EM) treatment has been reported as effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). However the effective mechanism of EM is still obscure. In this study, we investigated the effect of EM on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS), and the following results were obtained. 1) The intrapulmonary influx of neutrophils was significantly suppressed (p less than 0.001) in mice intraperitoneally injected with EM at 5 mg per animal 2 hr before intratracheal injection of LPS (control group: 6.5 +/- 0.8 x 10(5) vs EM-treated group: 1.7 +/- 0.3 x 10(5)), but not 10 hr before lung challenge. This inhibition was observed at 6 hr after lung challenge, and became maximum with 84% suppression at 24 hr. 2) The intrapulmonary influx of neutrophils was not affected when EM was injected intraperitoneally daily for 3, 7, or 14 days, and lung challenge was performed 24 hr after the final administration of EM. 3) The number of neutrophils in the peripheral blood was not affected by EM. These results suggest that EM treatment impairs the capacity for pulmonary inflammation by reducing, at least in part, the migration of neutrophils to inflammatory sites.

Animals↗
PubMed1992

Investigation of radiopharmaceuticals for pancreatic imaging: accumulation of amines in the pancreas.

To develop radiopharmaceuticals for pancreatic imaging, radioiodinated ethyl benzene derivatives containing various functional groups (amino, carboxyl, and methyl groups) were synthesized and the effects of these functional groups were compared in vitro and in vivo. At 2 min after intravenous injection, the amino derivative, 2-(4-iodophenyl)-N,N-dimethyl ethylamine, displayed about twice the pancreatic uptake and a more than 8-fold higher pancreas/liver ratio than the carboxyl and methyl derivatives. This high and selective in vivo accumulation on the amino derivative in the pancreas was well supported by in vitro studies on the uptake by pancreatic tissue slices. The mechanism promoting pancreatic accumulation of radiopharmaceuticals with an amino group is also discussed.

Amines↗
PubMed1992

Evaluation of N-alkyl derivatives of radioiodinated spiperone as radioligands for in vivo dopamine D2 receptor studies: effects of lipophilicity and receptor affinity on the in vivo biodistribution.

A series of radioiodinated spiperone (2'-ISP) derivatives bearing amide N-alkyl substituents (N-methyl-2'-ISP, N-ethyl-2'-ISP, and N-propyl-2'-ISP) were synthesized and evaluated as potential singlet photon emission computed tomographic radiopharmaceuticals for visualizing dopaminergic receptors. The lipophilicity of these ligands (i.e., the partition coefficient for octanol-phosphate buffer) increased as the chain length increased. Investigation of blood-brain barrier permeability in rats showed a parabolic relationship between the brain uptake index and the partition coefficient. In vitro competitive binding studies showed that the relative affinity for the dopamine D2 receptor was in the order of N-propyl-2'-ISP greater than 2'-ISP greater than N-methyl-2'-ISP approximately N-ethyl-2'-ISP. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compounds. Thus, the in vivo behavior of these N-alkylated 2'-ISP derivatives involved a complex interplay between receptor affinity, lipophilicity, and blood-brain barrier permeability.

Animals↗
PubMed1992

Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors.

A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.

Animals↗
PubMed1992

Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography.

A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S)-[11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity.

Animals↗
PubMed1992

Interleukin 6 activity in pleural effusion. Its diagnostic value and thrombopoietic activity.

We measured interleukin 6 (IL-6) concentrations in the pleural fluid of various patients to determine its role in pathophysiology and diagnosis by using specific functional bioassay. IL-6 levels were significantly higher in exudate than in transudate (79.3 +/- 176.2 U/ml [n = 55] vs 1.7 +/- 1.8 U/ml [n = 12]; p < 0.01). Tuberculous effusion contained a significantly higher amount of IL-6 than malignant effusion (181.3 +/- 176.2 U/ml [n = 13] vs 29.4 +/- 71.5 U/ml [n = 29]; p < 0.005). Pleural IL-6 levels were invariably higher than serum IL-6 levels, and both were significantly correlated (n = 21, r = 0.632; p < 0.02). Pleural IL-6 levels were significantly correlated with lactate dehydrogenase (LDH) in pleural fluid (r = 0.392; p < 0.01), ratio of pleural/serum LDH (r = 0.571; p < 0.01), pleural adenosine deaminase activity (r = 0.599; p < 0.01), and serum C-reactive protein (r = 0.494; p < 0.01). Furthermore, IL-6 levels were significantly correlated with peripheral blood platelet counts (r = 0.447; p < 0.001). These results suggest that (1) IL-6 is produced locally in pleural space, (2) pleural IL-6 level is helpful for differential diagnosis, and (3) locally produced IL-6 could leak to circulation and cause systemic effects such as the induction of C-reactive protein and thrombocytosis.

Adenosine Deaminase↗
PubMed1992

Diastolic mitral regurgitation in intact mitral valve detected by color Doppler echocardiography in a patient with acute aortic regurgitation.

A 38-year-old man was admitted with coingestive heart failure due to infective endocarditis. Echocardiography with color Doppler imaging revealed severe aortic regurgitation, mitral valve premature closure and diastolic mitral regurgitation. The flow of the diastolic mitral regurgitation was directed to the posterior wall of the left atrium through just behind the posterior mitral leaflet. The diastolic mitral regurgitation was observed only in the period of late diastole and no mitral regurgitation could be detected in the systolic phase. After successful aortic valve replacement, the diastolic mitral regurgitation disappeared completely.

Adult↗
PubMed1992

High myocardial accumulation of radioiodinated digoxin derivative: a possible Na,K-ATPase imaging agent.

In view of the high binding ability of cardiac glycosides to the myocardial Na,K-ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O-carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium.

Animals↗
PubMed1992

Partial structures and binding studies of maitotoxin, the most potent marine toxin.

Partial structures of maitotoxin (MTX) were deduced by extensive two-dimensional NMR measurements, showing that the toxin had carbon-carbon double bonds in both termini of the molecule, and a primary alcohol group at the end. These functionalities were used for preparation of a radioligand of MTX; [3H]H-MTX and [3H]benzoyl-MTX. Both radioligands had high levels of non-specific binding to tissues. The binding of [3H]MTX to rat glioma C6 cells was inhibited by a didesulfo-MTX, suggesting the presence of the specific site for MTX-binding on the external surface of the cell membrane.

Animals↗
PubMed1992

Influence on metastasis of the reduction of major histocompatibility complex (MHC) class I gene with an antisense oligonucleotide.

Cell surface MHC H-2K antigens expressed on various types of B16 melanoma cells of C57BL/6 mouse origin were stained by the avidin-biotinylated enzyme complex (ABC) technique. The low metastatic B16F1 cell line, which demonstrates high levels of H-2K antigen, stained strongly, while the high metastatic B16F10 cell line with no H-2K antigen was not stained. Metastatic colonies which developed in lungs after intravenous (i.v.) injection proved to be negative in both cases. Therefore, in consideration of decreased expression of H-2K antigen in the metastatic process both in vivo and in vitro, antisense oligonucleotides against the class I H-2K gene were transfected into B16F1 cells with H-2K antigens. Subsequent immunohistochemical assessment revealed lack of H-2K antigen expression in the cells, but nevertheless they still could not metastasize to lungs when i.v. injected. This may suggest that any link between the two is not directly causal.

Amino Acid Sequence↗