Search PubMedSearch

Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 19 recordsLinked to original sources

Effect of eosinophil peroxidase on beta-adrenergic receptor density on guinea pig lung membrane.

We studied whether eosinophil peroxidase (EPO), an eosinophil granule basic protein, can alter beta-adrenergic receptor (BAR) density on the guinea pig lung membrane. Lung membrane was first preincubated with 1-10 U/ml EPO and then incubated with 10(-4) M NaI and 10(-4) or 10(-6) M H2O2 for 2 hours. BAR density was determined using (-)125I-cyanopindolol. EPO combined with 10(-4) M H2O2 and I decreased the BAR density in a concentration-dependent manner. When only 10(-4) M H2O2 was used, the decrease in BAR density was small but significant. When compared to I, bromide was less effective and chloride alone was not effective. These results suggest that EPO is one of the factors responsible for beta-adrenergic blockade in asthma.

Animals

Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor-channel complex in mice.

The role of the N-methyl-D-aspartate (NMDA) receptor-channel complex in ketamine-induced anesthesia was examined in mice. General anesthetic potencies were evaluated on a rating scale, which provided the data for anesthetic scores, loss of righting reflex, sleeping time and recovery time. All drugs were administered intraperitoneally. NMDA (60-300 mg/kg), an NMDA receptor agonist, dose-dependently antagonized the general anesthetic potencies of ketamine at a dose of 100 mg/kg which produced loss of righting reflex in more than 90% of the mice. On the other hand, a high dose of N-methyl-L-aspartate (400 mg/kg), a stereoisomer of NMDA, did not. A dose of 300 mg/kg of NMDA significantly shifted the dose-response curve of ketamine for loss of righting reflex to the right. A high dose of D-cycloserine (200 mg/kg), an agonist at the glycine site on the NMDA receptor complex, slightly but significantly shortened the sleeping time caused by ketamine (100 mg/kg). However, neither a critical subconvulsive dose of kainate (15 mg/kg), a kainate receptor agonist, nor a subconvulsive dose of quisqualate (120 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor agonist, reversed general anesthesia induced by 100 mg/kg of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Distribution of alkyl and alkenyl ether-linked phospholipids and platelet-activating factor-like lipid in various species of invertebrates.

The levels of alkenylacyl, alkylacyl and diacyl subclasses of choline glycerophospholipid (CGP) and ethanolamine glycerophospholipid (EGP) fractions in 28 species of various invertebrates were studied. We found that only small amounts of either 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) or 1-alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkenylacyl-GPE) are present in most species of insects. On the other hand, almost all species examined in various phyla other than Arthropoda were shown to contain large amounts of both alkylacyl-GPC and alkenylacyl-GPE. The highest proportion of alkylacyl subclass in CGP was noted in sponge, Halichondria japonica (81.8% of CGP) and the highest proportion of alkenylacyl subclass in EGP was found in clam worm, Marphysa sanguinea (88.7% of EGP). We next surveyed the presence of platelet-activating factor (PAF)-like lipid in 45 species of invertebrates. PAF-like lipid was widely distributed among various lower animals. The highest value was obtained for sea cucumber, Stichopus japonicus, in which PAF-like lipid was present throughout the body. We also confirmed the presence of acetyltransferase activity in several lower animals. These results suggest that alkyl and alkenyl ether-linked phospholipids including PAF are physiologically important molecules particularly for invertebrates belonging to lower phyla.

Animals

Induction of hepatic microsomal cytochrome P450 and drug-metabolizing enzymes by 4-benzylpyridine and its structurally related compounds in rats. Dose- and sex-related differential induction of cytochrome P450 species.

We examined the abilities of 4-, 3- and 2-benzylpyridine and 4-tert-butylpyridine to induce hepatic microsomal cytochrome P450 and drug-metabolizing enzymes in male and female rats in order to define the effects of pyridine-containing compounds on drug metabolism. 4-Benzylpyridine (0.4 mmol/kg, for 2 consecutive days) induced total cytochrome P450 to about three times that of the controls at 24 hr, and its inducing effect was sustained for 120 hr after the treatment in male and female rats. 4-Benzylpyridine was a more potent inducer of cytochrome P450 than 3- and 2-benzylpyridine, which induced the cytochrome to 71.4 and 43.9%, respectively, of that produced by the 4-substituted isomer. 4-tert-Butylpyridine also induced cytochrome P450. Immunoblot analysis revealed that a single treatment of male rats with 4-benzylpyridine at doses ranging from 0.05 to 0.80 mmol/kg induced cytochrome P450b/e and caused a maximum increase in the level of the isozyme at the 0.2 mmol/kg dose. 4-Benzylpyridine at doses from 0.40 to 0.80 mmol/kg also induced cytochrome P450c/d in male rats. In female rats, 4-benzylpyridine induced cytochrome P450b at doses ranging from 0.1 to 0.80 mmol/kg and produced a maximum increase in the level of this isozyme at 0.40 to 0.60 mmol/kg. Induction of cytochrome P450c/d by 4-benzylpyridine in female rats was observed at a dose of 0.20 mmol/kg, and the magnitude of the induction of the isozyme was increased in a dose-dependent manner. Both 3- and 2-benzylpyridine induced cytochrome P450b/e and/or c/d depending on the increase of total cytochrome P450 without changing the induction patterns of the isozymes. 4-tert-Butylpyridine induced cytochrome P450b at doses ranging from 0.20 to 0.60 mmol/kg and slightly induced P450c/d at doses ranging from 0.10 to 0.40 mmol/kg in male rats. These results and our previous report (Matsuura et al., Biochem Pharmacol 41: 1949-1956, 1991) clearly show that the pyridine compounds having lipophilic groups at the 4- or 3-position of the ring could be inducers of cytochrome P450. The present results also revealed that 4-benzylpyridine shows dose- and sex-related differences in the induction of cytochrome P450b/e and c/d in rats.

Aminopyrine N-Demethylase

Transcriptional stimulation by thyroid hormone of a cytosolic thyroid hormone binding protein which is homologous to a subunit of pyruvate kinase M1.

We have recently shown that the monomer of rat pituitary pyruvate kinase subtype M1 (p58-M1) is a cytosolic binding protein for 3,3',5-triiodo-L-thyronine (T3). To understand the role p58-M1 plays in thyroid hormone action, we examined the regulation of p58-M1 by T3 in GH3 cells. Expression of p58-M1 was evaluated by metabolically labeling GH3 cells cultured in regular medium, thyroid hormone depleted medium (Td medium), or Td medium supplemented with T3 (Td + T3 medium) followed by immunoprecipitation. T3 stimulates the expression of p58-M1 by 2-fold. Analysis by pulse-chase experiments indicates that the increased expression is not due to the increase of stability of p58-M1. Northern analysis of mRNA prepared from cells cultured in regular, Td, or Td + T3 medium demonstrates that T3 increases the accumulation of cytoplasmic mRNA by 2-fold. Nuclei from cells cultured in the three conditions were prepared, and the rates of synthesis of nascent nuclear RNA were compared by an in vitro transcription assay. Addition of T3 stimulates the rate of transcription by 2-fold. The parallel and identical magnitude in the increase of transcription rate and the accumulation of mRNA indicates that T3 stimulates the synthesis of p58-M1 by increasing the transcriptional activity of its gene.

Animals

An exploration of the binding site of aldolase using alkyl glycolamido phosphoric esters and alkyl monoglycolate phosphoric esters.

Alkyl glycolamido phosphoric esters (P-O-CH2-CO-NH-(CH2)n-CH3) and alkyl monoglycolate phosphoric esters (P-O-CH2-CO-O-(CH2)n-CH3), which are analogs of the aldolase substrate fructose-1-phosphate, were synthesized and use for probing the active site of rabbit muscle aldolase. The inhibition constants (Ki) were affected by the length of the alkyl groups of these compounds and a maximum value of Ki was observed between the number of methylene groups 2 and 4, depending on the type of compound. In the previous investigation, N-(omega-hydroxyalkyl)-glycolamido bisphosphoric esters (P-O-CH2-CO-NH-(CH2)n-O-P) and alkanediol monoglyclolate bisphosphoric esters (P-O-CH2-CO-O-(CH2)n-O-P) have a minimum Ki value between the number of methylene groups 1 and 4. The difference spectra of aldolase caused by binding of alkyl glycoamido phosphoric esters or alkyl monophosphates resembled that of their analogous bisphosphoric esters, but the intensity of absorbance was smaller than that of the bisphosphoric ester analogs. These results suggest that rabbit muscle aldolase has two binding sites for the phosphate groups on the entrance end of the active site cavity, the singly wound beta-barrel of the parallel alpha/beta class structure. The distance between the phosphate binding site Lys-107 in the beta-sheet structure (c) and Arg-148 in the beta-sheet structure (d) may possibly be expanded or contracted by the forms of the bending structure of the biphosphate compounds. Also, the change of distance between the beta-sheet structure (c) and (d) containing Trp-147, may have an effect on the environment of the tryptophan and cause a change of the absorbance of aldolase especially at 295-299 nm. On the other hand, the synthetic monophosphate compounds bind at only one of the two phosphate binding sites and have very little effect on the absorbance of Trp-147, in a similar manner as orthophosphate. The alkyl groups of monophosphate may be repelled by the ionic amino acid side chains, Asp-33, Lys-146, Glu-187 and/or Lys-229 in the middle of the active site cavity. However, the end of the long alkyl group of some monophosphates may possibly contact the hydrophobic bottom of the active site cavity without effect on the environment of Trp-147.

Binding Sites

[Reevaluation of US and CT findings in adult intussusception].

Computed tomographic (CT) and ultrasonographic (US) findings of 10 adult patients with 11 intussusceptions were retrospectively analyzed. Through close scrutiny of wall structures of intussusceptums and mesenteric fat, new features of adult intussusceptions were found: 1. The returning walls were thicker than the entering walls in 10 of 11 intussusceptums. 2. The neck of the returning wall was thicker than its head in eight of nine intussusceptums. 3. Longitudinal compression of the wall and venous congestion resulting from an inside out turning of the wall structure were thought to be the cause of thickening of the returning wall. 4. Invaginated mesenteric fat tended to be located at the head (apex) in two of seven intussusceptions, making differentiation from intussusception caused by lipoma difficult. 5. The leading masses were detectable as apical soft tissue density masses in eight of 10 intussusceptions. These findings contradict those of previous reports on adult intussusceptions.

Adult

Liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric analysis of synthetic elastase inhibitor peptide.

A liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric method for the determination of tert-butyloxycarbonyl-Tyr-Leu-Val-CH2Cl (Boc-YLV-CH2Cl) was investigated. Boc-YLV-CH2Cl was eluted from a Cosmosil 5C8 column in a solvent system of 0.1% acetic acid-methanol (30: 70, v/v). The positive ion spectrum of Boc-YLV-CH2Cl showed a quasi-molecular ion at m/z 526 with fragment ions which provided structural information. Boc-YLV-CH2Cl was purified from blood and tissue samples with Sep-Pak C18 cartridges. The analysis in biological samples was performed by focusing the characteristic ion at m/z 526. The calibration graphs were linear over the concentration range studied (injected amounts of 9.5-190 pmol). The method was applied to the determination of Boc-YLV-CH2Cl in biological samples.

Amino Acid Sequence

CD7-positive acute myeloid leukemia: further evidence of cellular immaturity.

Among 63 cases of acute myeloid leukemia (AML), 14 were found to express the CD7 antigen, a cell surface marker usually found at an early stage during T lineage differentiation. The CD7-positive AML cases consisted of 5 cases of M1, 3 cases of M2, 3 cases of M4, 1 case of M5, 1 case of M6 and 1 case of M7. Among these 63 cases, the proportion of blast cells expressing the CD34 antigen was examined. The proportion of CD34-stained cells among the CD7-positive AML cases, although varying, was significantly larger than that among the CD7-negative AML cases (P less than 0.05). As the CD34 antigen was expressed on hematopoietic progenitor cells and was considered to reflect an early hematopoietic stage, the high proportion of cells expressing CD34 among the CD7-positive AML cases may support the notion that CD7-positive AML cells are immature.

Adolescent

Dedifferentiated leiomyosarcoma of the intestinal tract: histological, ultrastructural and immunohistochemical examinations.

Six cases of dedifferentiated leiomyosarcoma of the small and large bowel are presented with histological, ultrastructural and immunohistochemical examination. One case arose in the jejunum, two in the ileum, and the other three in the large intestine. The tumours were submucosal in four cases with large areas of ulceration; two were polypoid. Four tumours showed typical leiomyosarcomatous appearance with dedifferentiated components and two were typical leiomyosarcomas at the primary site with differentiated components only in metastatic foci. By immunohistochemistry, typical leiomyosarcomatous areas showed a positive reaction for muscle-specific actin (MSA), MB1, MB2 and myosin. In contrast, desmin-positive cells were scattered throughout the tumour or were not present. Tumour cells in dedifferentiated components were positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin in all cases but one; neuron specific enolase, MB1, MB2 and myosin were positive with variety. MSA was faintly positive in only a few tumour cells of two cases and desmin was not detected in any of the cases studied. Ultrastructurally, tumour cells in typical leiomyosarcomatous areas demonstrated evident smooth muscle features, although in dedifferentiated areas they lacked such features except in one case. Our results indicate that dedifferentiated elements may derive from ordinary leiomyosarcoma and loose muscle features due to dedifferentiation.

Aged

Microcytic variant of thymoma: histological and immunohistochemical findings in two cases.

Two cases of microcytic variant of thymoma are presented. Both tumours were well encapsulated with a yellow-whitish colour and soft consistency. Microscopically, they consisted of round cells, having ample vacuolated cytoplasm. Fat droplets were not detected in one case where fat staining was performed. Immunohistochemically, the tumour cells were strongly positive for AE1/AE3, MB1, MB2, and LN1 and faintly positive for epithelial membrane antigen. They lacked any other leucocyte antigens. Leu 7 showed a positive immunoreaction in a ring-like or homogeneous pattern, compatible with the cytoplasmic vacuoles or cytoplasm. Ultrastructurally, the vacuoles resembled cystically dilated rough-surfaced endoplasmic reticulum. Desmosome-like structures (case 1) and intermediate junctions (case 2) were identified between adjacent cells. These findings indicate that the present tumours belong to a category of microcystic thymoma. The vacuoles were attributed to excess accumulation of Leu-7-positive material, probably in the cystically dilated endoplasmic reticulum.

Antigens, Differentiation

Characterization of the transcallosal response in aged rats and its susceptibility to nootropic drugs.

The transcallosal response in aged rats was recorded and its susceptibility to certain nootropic drugs was compared with adult animals, under urethane-anesthesia. The transcallosal response in 24-month old rats was significantly reduced in the amplitude of both positive and negative waves, as compared with 5-month old animals. In adult rats, intravenous administration of 100 mg/kg of calcium hopantenate augmented the amplitude of both the positive and the negative waves. Intraperitoneal administration of 300 mg/kg of calcium hopantenate or 10-100 mg/kg of aniracetam increased the amplitude of the negative wave by 20-30% above the control level but had no effect on the positive one. In aged rats, these drugs, given intraperitoneally, also increased the negative wave without affecting the positive one and the degree of augmentation was more prominent; both drugs increased the amplitude of the negative wave by about 190% of the control. These results suggest that the susceptibility to the nootropic drugs became even more striking in older animals, the function in the brain of which are reduced by the natural ageing process.

Aging

Neoplastic basophil/mast cell precursors from chronic myelogenous leukemia display heterogeneous responses for a hematopoietic factor.

The response of neoplastic basophil/mast cell precursors to various hematopoietic factors was examined. Blastic or promyelocytic immature cells were obtained from six patients in basophilic crisis of chronic myelogenous leukemia. In all cases, after 14 days suspension culture more then 90% of the cells had basophilic features. 3H-thymidine uptake was markedly increased by the addition of GM-CSF in two cases, G-CSF in one, and IL-3 in two. In clonogenic cell assays, numerous colony formations were obtained when using the same growth factors as in the 3H-thymidine uptake assay. In addition, IL-3 induced colony formation in one case, despite a lack of thymidine uptake IL-4 had a synergistic effect on colony formation with IL-3 in one other case. None of the factors used showed any effect on differentiation. These findings indicate that the proliferation of neoplastic basophil/mast cell precursors may be regulated by various growth factors but response patterns are divergent.

Basophils

Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice.

The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.

Adjuvants, Immunologic

Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate.

OBJECTIVE: To determine coronary artery diameter change before and after an intracoronary infusion of isosorbide dinitrate in patients who have had Kawasaki disease, we performed coronary angiography in 188 such patients. PATIENTS AND METHODS: Four patient groups were studied. Groups 1 to 3 consisted of patients with Kawasaki disease: group 1 (the "normal" group; n = 65) had no coronary artery lesions; patients in group 2 had regression to normal of a coronary artery aneurysm after Kawasaki disease and were divided, according to the time since onset, into two subgroups, group 2-a (n = 20) being at an early stage after regression to normal (followed for 1.7 +/- 0.7 years) and group 2-b (n = 34) being at a later stage after regression (followed for 8.7 +/- 2.9 years); and group 3 (the "abnormal" group; n = 25) had persistent coronary artery aneurysm or stenosis or both. Group 4, the control group (n = 44), consisted of patients without Kawasaki disease who had congenital heart disease with normal coronary arteries. The coronary artery diameter change was calculated by the following formula: Percentage of change = (Diameter after infusion - Diameter before infusion)/Diameter before infusion x 100. RESULTS: The percentages of change in the coronary artery diameter after isosorbide dinitrate infusion were 16.2% +/- 13.4% (normal group), 11.3% +/- 7.2% (early-regression group), 7.8% +/- 8.3% (late-regression group), 6.8% +/- 7.8% (abnormal group), and 15.2% +/- 11.8% (control group). In the abnormal group, there was significantly poorer dilation than in the control and normal groups. The late-regression group also had significantly less change in diameter than did the control and normal groups (p < 0.05). CONCLUSIONS: These data suggest (1) that the coronary artery after Kawasaki disease becomes stiff not only in patients with persistent abnormal lesions but also in those with regressed aneurysms and (2) that stiffness of the coronary artery may be a risk factor for atherosclerosis.

Child

Arteriovenous differences of blood alcohol concentrations after celiac plexus block.

After a celiac plexus block with ethyl alcohol, patients sometimes complain of symptoms of alcohol intoxication. We studied the consecutive changes of arterial and venous blood alcohol concentrations in 11 patients and investigated whether an arteriovenous difference exists. We performed a celiac plexus block with 10 ml absolute ethyl alcohol. The sampling sites were radial artery and internal jugular vein. Blood samples were collected at 0, 5, 10, 15, 30, 60, 120, 240 and 480 minutes after the block. The maximum level was reached 15 minutes after injection in both arterial and venous blood, 29.9 +/- 19.4 and 27.7 +/- 21.8 mg/dl (means +/- SD), respectively. Arteriovenous differences were observed 5 and 10 minutes after ethyl alcohol injection (p less than 0.01). There was a significant negative correlation between the ratio of arteriovenous differences to venous sampling and the time elapsed after the block (r = 0.41, p less than 0.01).

Arm