Meissner effect and oscillatory penetration of a magnetic field from the pairing of valence and conduction electrons.
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Journal Article↗
Biomedical subjects
Y Takada
Publications and source records attributed to Y Takada.
Effects of N-terminal peptide of Glu-plasminogen on the activation of Glu-plasminogen and its conversion to Lys-plasminogen.
In order to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles, which results in its tight conformation, we synthesized peptides of the N-terminal portion of Glu-plg molecules and analyzed their effects on the activation of Glu-plg and its conversion to Lys-plasminogen (Lys-plg) by plasmin. Three peptides of Ala44-Lys50, Ala44-Glu51 and Ala44-Ser49 were synthesized in order to examine the effect of lysine residue in the peptide. Ala44-Lys50 and Ala44-Glu51 enhanced the activation of Glu-plg by urokinase, whereas the activation of Lys-plasminogen (Lys-plg) was slightly inhibited. The conversion of Glu-plg to Lys-plg by plasmin was also enhanced by these peptides. The results suggest that Ala44-Lys50 and Ala44-Glu51 worked on Glu-plg in a similar manner as lysine analogues by making its conformation looser. The third peptide Ala44-Ser49 did not have any effect on the activation of Glu-plg by urokinase or the conversion of Glu-plg to Lys-plg by plasmin. Ala44-Lys50 residue of Glu-plg is, therefore, strongly implicated as a candidate for the responsible site of the intramolecular binding in Glu-plg.
Alanine↗
Experimental study of color degree of freedom of gluons in e+e- annihilation at sqrt s around 60 GeV.
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Journal Article↗
Affinity of antineoplastic amino acid drugs for the large neutral amino acid transporter of the blood-brain barrier.
The relative affinity of six anticancer amino acid drugs for the neutral amino acid carrier of the blood-brain barrier was examined in rats using an in situ brain perfusion technique. Affinity was evaluated from the concentration-dependent inhibition of L-[14C]-leucine uptake into rat brain during perfusion at tracer leucine concentrations and in the absence of competing amino acids. Of the six drugs tested, five, including melphalan, azaserine, acivicin, 6-diazo-5-oxo-L-norleucine, and buthionine sulfoximine, exhibited only low affinity for the carrier, displaying transport inhibition constants (Ki, concentrations producing 50% inhibition) ranging from 0.09 to 4.7 mM. However, one agent - D,L-2-amino-7-bis[(2-chloroethyl)amino]- 1,2,3,4-tetrahydro-2-naphthoic acid (D,L-NAM) - demonstrated remarkably high affinity for the carrier, showing a Ki value of approximately 0.2 microM. The relative affinity (1/Ki) of D,L-NAM was greater than 100-fold that of the other drugs and greater than 10-fold that of any compound previously tested. As the blood-brain barrier penetrability of most endogenous neutral amino acids is related to their carrier affinity, the results suggest that D,L-NAM may be a promising agent which may show enhanced uptake and distribution to brain tumors.
2-Naphthylamine↗
Augmentation of antitumor effect on syngeneic murine solid tumors by an interleukin 2 slow delivery system, the IL-2 mini-pellet.
We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.
Animals↗
Insulinopenia as a risk factor in hepatectomy and its resolution by intraportal insulin administration.
Insulopenia is a possible risk factor in hepatectomy, especially since insulin has been recognized to have a significant hepatotrophic effect. In the current study, insulinopenic patients were defined as those who showed abnormally low insulinogenic indexes (less than 0.6) on the oral glucose tolerance test, compared with those in 22 normal volunteers (1.16 +/- 0.57, mean +/- SD). The insulinogenic index represents the ratio of the cumulative enhancement of immunoreactive insulin (IRI) to the glucose level (delta IRI/delta glucose). Surgical outcomes were studied retrospectively in 17 insulinopenic patients who underwent hepatic resections from January 1987 to July 1988. Six of 10 patients in the major hepatic resection group showed postoperative complications, 5 of whom experienced hepatic failure resulting in hospital death. By contrast, all seven patients in the minor resection group tolerated the operations. From August 1988, intraportal insulin was prospectively administered as a posthepatectomy management technique to nine patients, eight of whom were diagnosed as insulinopenic. These patients all tolerated major hepatic resections including four hepatic vascular exclusion procedures with veno-venous bypass. In conclusion, the current study indicates that insulinopenic patients are high-risk candidates for major hepatic resection and that intraportal insulin administration has a beneficial effect on the postoperative management of these patients.
3-Hydroxybutyric Acid↗
Effect of glucagon on hepatic energy charge and arterial ketone body ratio in normal rabbits.
Glucagon has been regarded as a hepatotrophic factor, although it is also known to stimulate energy-consuming reactions in the liver, such as gluconeogenesis and ureogenesis. To clarify the effect of glucagon on the hepatic energy metabolism, the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state [( NAD+]/[NADH]), as well as those in energy charge and mitochondrial oxidative phosphorylation of the liver after IV glucagon injection were studied in normal rabbits. Arterial ketone body ratio decreased significantly from 1.04 +/- 0.08 to 0.61 +/- 0.11 (mean +/- SEM; P less than 0.01) within 30 minutes after glucagon injection. Hepatic energy charge also decreased from 0.883 +/- 0.014 to 0.789 +/- 0.014 (P less than 0.01) at 30 minutes, whereas mitochondrial phosphorylation rate inversely increased from 38.4 +/- 9.5 to 87.3 +/- 9.7 (nanomoles adenosine triphosphate per milligram mitochondrial protein per minute; P less than 0.01) at 30 minutes. Arterial ketone body ratio and energy charge were subsequently restored to the initial values at 60 minutes and 2 hours, respectively. The present study suggests that glucagon causes an increase in energy expenditure in the liver that results in a transient decrease in hepatic energy charge accompanied by a decrease in arterial ketone body ratio.
Adenine Nucleotides↗
Effect of simvastatin on receptor mediated metabolism of low density lipoprotein in guinea pigs.
This study examined the effects of simvastatin, an inhibitor of HMG-CoA reductase, on the metabolism of labelled human low density lipoprotein (LDL) in animal models. Administration of 10 mg/kg per day simvastatin for 2 weeks reduced the levels of total cholesterol, LDL-cholesterol and triglycerides by 5.7 mg/dl (16%), 8.8 mg/dl (36%) and 4.9 mg/dl (13%), respectively in guinea pigs. High density lipoprotein-cholesterol levels rose 0.8 mg/dl (29%) by simvastatin treatment. Measurements of turnover of LDL were determined between simvastatin-treated guinea pigs and untreated guinea pigs using intravenous injection of 131I-labelled LDL and 125I-labelled galactose-treated LDL to quantify the LDL receptor pathway. Simvastatin significantly increased the fractional catabolic rate (FCR) of the LDL receptor-dependent pathway. In contrast, the FCR of the LDL receptor-independent pathway was not altered by simvastatin therapy. The FCR for LDL isolated from simvastatin-treated subjects compared to that from control subjects was very similar in both control and simvastatin-fed guinea pigs. These findings suggest that simvastatin mainly reduced serum cholesterol levels by accelerated FCR of LDL receptor mediated pathway.
Animals↗
Sperm immobilizing and fertilization-blocking monoclonal antibody 2C6 to human seminal plasma antigen and characterization of the antigen epitope corresponding to the monoclonal antibody.
A monoclonal antibody (Mab 2C6) with strong sperm immobilizing and agglutinating activities was generated by cell fusion between spleen cells from a mouse immunized with human seminal plasma (HSP) and mouse myeloma cells. It also showed a strong inhibitory effect on human sperm-egg interaction. The corresponding antigen was present on the whole surface of ejaculated spermatozoa. In male genital organs, immunostaining with Mab 2C6 was observed in epididymis and seminal vesicle but not in testis. By Western blotting, immunostaining with Mab 2C6 was detected around the 15-25 kDa region under both reducing and non-reducing conditions. The antigen corresponding to Mab 2C6 was susceptible to treatment with periodate or trifluoromethanesulfonic acid. The antigenic activities were slightly increased by treatment with neuraminidase but reduced by further treatment with glycosidases. Enzymatic digestions with pronase and papain also reduced the antigenic activities. The antigen molecules exhibited a strong binding affinity to RCA lectin. These results indicated that Mab 2C6 recognized one of the components which might be secreted from epididymis or seminal vesicle and bind to ejaculated spermatozoa as a sperm coating antigen. The corresponding antigen seems to be a glycoprotein and its carbohydrate moiety has an important role in the conformation of the antigen epitope.
Animals↗
Evidence that C4b-binding protein (proline-rich protein) is synthesized by hepatocytes.
C4b-binding protein (C4bp), a glycoprotein involved in regulating the classical pathway of the complement system, binds the activated form of C4b and accelerates the decay rate of the C4b, C2a complex. Recently, sequence analysis of the cDNA for proline-rich protein (PRP) demonstrated that PRP is identical with C4bp. We measured the concentration of C4bp in serum by single radial immunodiffusion in patients with various liver diseases. Concentration of C4bp was significantly lower in hepatic cirrhosis (P = 0.001) and higher in fatty liver (P = 0.0002) than the control values, after adjusting for age, sex, and concentration of total cholesterol, triglyceride, and C-reactive protein. Significant positive correlations were observed between the concentration of C4bp in serum and total protein, albumin, cholinesterase level, and lecithin-cholesterol acyltransferase activity. Immunohistochemical analysis of human liver with specific antiserum to human C4bp demonstrated reaction endproducts in the hepatocytes around the central veins. These observations provide evidence that C4bp is synthesized by hepatocytes.
Animals↗
Molecular cloning and expression of the cDNA for alpha 3 subunit of human alpha 3 beta 1 (VLA-3), an integrin receptor for fibronectin, laminin, and collagen.
alpha 3 beta 1 (VLA-3), a member of the integrin family of cell adhesion receptors, may function as a receptor for fibronectin, laminin, and collagen. A partial cDNA clone (2.4 kb) for the human alpha 3 subunit was selected from an endothelial cell lambda gt11 cDNA library by specific antibody screening. Several overlapping cDNA clones were subsequently obtained, of a total length of 4.6 kb from various cDNA libraries. The reconstructed alpha 3 cDNA was expressed on the surface of chinese hamster ovary cells as detected by an alpha 3-specific mAb after transfection, suggesting that the cDNA is authentic. Within this sequence was an open reading frame, encoding for 1,051 amino acids, including a signal peptide of 32 residues, a long extracellular domain (959 residues), a transmembrane domain (28 residues), and a short cytoplasmic segment (32 residues). Overall, the alpha 3 amino acid sequence was 25-37% similar to the other integrin alpha subunits that are cleaved, with most similarity to the alpha 6 sequence (37%), and less similarity to those alpha subunits that have I domains (15-20%, excluding the I domain sequence itself). Features most like those in other alpha subunits are (a) the positions of 18/19 cysteine residues, (b) three potential metal binding domains of the general structure DX(D/N)X(D/N)GXXD, and (c) the predicted transmembrane domain. The mass of alpha 3 calculated from its amino acid sequence is 113,505. The human alpha 3 sequence was 89% identical to hamster galactoprotein b3, and 70% similar to the chicken CSAT antigen band 2 protein partial sequence, suggesting that these two polypeptides are homologues of human alpha 3.
Amino Acid Sequence↗
Cloning and expression of cDNAs for the alpha subunit of the murine lymphocyte-Peyer's patch adhesion molecule.
cDNA clones encoding the alpha chain of the murine lymphocyte-Peyer's patch adhesion molecule (LPAM), which is associated with lymphocyte homing, have been isolated by screening with the human VLA-4 (alpha 4h) probe. Several alpha 4 antigenic determinants were identified on COS-7 cells after transfection. From overlapping clones, approximately 5 kb of contiguous nucleotide sequence have been determined, encoding a protein sequence of 1039 amino acids for the LPAM alpha chain (alpha 4m). LPAM is a member of the integrin family of cell-surface heterodimers, and alpha 4m is the murine homologue of the human alpha 4 h chain. The two proteins have a total sequence similarity of 84%, with an almost perfect conservation (31/32 amino acids) in the cytoplasmic domain. Like alpha 4h, alpha 4m is distinct from other integrin alpha chains because it has neither an I-domain nor a COOH-terminal cleavage site. The positions of the characteristic Cysteine residues are conserved, and a putative protease cleavage site is located near the middle of the protein sequence. The NH2-terminal part of the protein contains seven homologous repeats, and three of them include putative divalent cation-binding sites. These sites are among the most conserved between the alpha 4m sequence and other alpha chains, and may therefore be involved in the binding of integrin alpha and beta chains. An additional cDNA clone was isolated which shares a sequence of perfect homology with the alpha 4m encoding cDNAs, but has a unique 3' poly-A end. This observation correlates with the fact that three discrete murine RNA bands are observed in Northern blot experiments using alpha 4m as a probe, whereas only two human RNA species are described for alpha 4h, indicating a higher complexity for murine than for human sequences.
Amino Acid Sequence↗
Alcohol-induced depression: involvement of serotonin.
We examined tryptophan and serotonin (5-hydroxytryptamine) levels in the blood after consumption of alcohol. Forty-five minutes after drinking, whole blood serotonin concentration was significantly reduced, whereas no changes were observed in tryptophan level. The diurnal rhythm of 5-HT in subjects who the day before had drunk alcohol was quite different from the control group, but very similar to that of patients with depression. The results strongly suggest that the mechanism of depression after alcohol drinking may be related to serotonin.
Adult↗
Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism.
To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood-brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L-kynurenine (L-KYN), 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital-anesthetized rats using an in situ brain perfusion technique. L-KYN was found to be taken up into brain at a significant rate [permeability-surface area product (PA) = 2-3 x 10(-3) ml/s/g] by the large neutral amino acid carrier (L-system) of the blood-brain barrier. Best-fit estimates of the Vmax and Km of saturable L-KYN transfer equalled 4.5 x 10(-4) mumol/s/g and 0.16 mumol/ml, respectively. The same carrier may also mediate the brain uptake of 3-HKYN as D,L-3-HKYN competitively inhibited the brain transfer of the large neutral amino acid L-leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7-1.6 x 10(-3) ml/s/g), and at far lower rates (PA, 2-7 x 10(-5) ml/s/g) for 3-HANA, KYNA, and QUIN. Transfer for KYNA, 3-HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L-KYN across the blood-brain barrier and suggest that circulating L-KYN, 3-HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3-HANA cross the blood-brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions.
Animals↗
Effect of mental stress on platelet aggregation: possible link to catecholamine levels.
The present study was aimed at testing the hypothesis about the relation between mental stress and platelet function. Plasma samples were obtained from 100 students immediately before, and 30 min and 7 h after undergoing a bleeding time test, which was used as mental stressor. Platelet responses to serotonin, ADP and collagen, as well as plasma catecholamine levels were assayed. Plasma serotonin levels had a high negative correlation with the bleeding time. Stress resulted in an increase in platelet responses to serotonin, ADP and to the elevation of catecholamine levels. Furthermore, a significant negative correlation between the platelet aggregation induced by ADP and collagen and the bleeding time was demonstrated. It is concluded that mental stress had a significant effect on platelet aggregation. This study provides evidence of increased platelet aggregability in association with elevated plasma catecholamine levels.
Adenosine Diphosphate↗
MCI-9042: high affinity for serotonergic receptors as assessed by radioligand binding assay.
This study assessed the specificity of displacement potencies of MCI-9042 [+/-)-1-[o-[2-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)- 2-propyl hydrogen succinate hydrochloride), a new antiplatelet agent, in [3H]4-bromo-2,5-dimethoxyphenylisopropylamine [( 3H]DOB) and [3H]ketanserin binding to 5HT2-serotonergic receptors in the rat brain using the radioligand binding method. The assessment of the displacement potencies of MCI-9042 and its derivative, M-1 [(+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)- 2-propanol)hydrochloride), on alpha 1-, alpha 2-, beta-adrenergic, 5HT1-, 5HT2- and muscarinic receptors were also studied. MCI-9042 and M-1 showed strong displacement effects to 5HT2-receptors using [3H]DOB binding and [3H]ketanserin binding sites, and weak displacement effects for [3H]serotonin, [3H]prazosin, [3H]p-aminoclonidine, [3H]CGP12177 and [3H]QNB binding to 5HT1-, alpha 1-, alpha 2-, beta-adrenergic receptors and muscarinic receptors. Thus, the present study suggests that MCI-9042 is specific for 5HT2-receptor.
Adrenergic alpha-Agonists↗
Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men.
The GHRH test and L-dopa test were performed in 12 normal young men (24.1 +/- 1.1 years) and 12 normal elderly men (77.8 +/- 1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0 +/- 11.7 vs 86.7 +/- 11.6 micrograms/l). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 +/- 5.9 vs 11.2 +/- 2.1 micrograms.h-1.l-1, p less than 0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0 +/- 2.7 vs 20.3 +/- 1.8 ng.h-1.l-1 (p less than 0.001), and 21.8 +/- 4.6 vs 5.4 +/- 1.1 micrograms.h-1.l-1 (p less than 0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.
Adult↗
Actual characteristics of the glands distributed in the lamina propria mucosae of the fowl esophagus.
We performed histological and histochemical investigations on the glands distributed in the lamina propria mucosae of the fowl esophagus and demonstrated their actual characteristics. 1. Glandular cells of the compound tubular glands located in the lamina propria mucosae contained a number of fine pepsinogen granules. 2. Reactions to neutral, weak and strong acid mucopolysaccharides, neutral mucus type II and III and sialomucin were evidently positive in these cells. 3. Based on the facts in 1) and 2), we consider that the glands located in the fowl esophagus are undifferentiated gastric glands. 4. The same glands possessed no parietal cells. 5. We demonstrated that the esophageal cardiac glands in the lamina propria mucosae of human esophagus were undifferentiated gastric glands, and they possessed parietal cells. These glands were confirmed in humans alone among the mammalia. 6. The significance of the existence of the same kind of gland in human and fowl esophagus is extremely important. 7. PAS-positive substance in the above-mentioned glands in the fowl esophagus contains sulfuric, acid, neutral mucopolysaccaride and neutral mucus of type II and III but no glycogen. The compound tubular glands distributed in the lamina propria mucosae of the fowl esophagus have been described as mucous glands. We performed histochemical investigation and demonstrated that these glands were undifferentiated gastric glands.
Animals↗