[Respiratory implication of obesity].
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Diabetes Mellitus↗
Biomedical subjects
K Konno
Publications and source records attributed to K Konno.
Stimulation of tumor necrosis factor-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.
The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factor(s). When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemic cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 kD) exerted such a stimulating effect.
Animals↗
Induction of differentiation of human monoblastic and myeloblastic leukemia cell lines by TNF muteins.
The differentiation inducing activity of five recombinant human tumor necrosis factor (rHuTNF) muteins, prepared by protein engineering techniques, was compared by measuring the ability to reduce nitroblue tetrazolium dye of human myelogenous leukemia cells. TNF(C-Phe), in which the C-terminal leucine of TNF molecule was replaced by phenylalanine, was 20-times as potent in induction of differentiation of U-937 cells as the parent TNF(N-Met), in which methionine was added to N-terminal sequence of TNF. The differentiation inducing activity of TNF muteins was not always proportional to their binding activity to the receptors nor to their cytotoxicity on U-937 cells.
Amino Acid Sequence↗
Suppression of TNF-stimulated proliferation of diploid fibroblasts and TNF-induced cytotoxicity against transformed fibroblasts by TGF-beta.
Human transforming growth factor-beta (TGF-beta) dose-dependently inhibited proliferation of WI-38 cells, normal human diploid fibroblasts, stimulated by tumor necrosis factor (TNF). Inhibition occurred at 1 ng/ml concentration of TGF-beta. Also, TGF-beta dose-dependently suppressed cytotoxicity of TNF against L-929 cells, murine transformed fibroblasts. The concentration of TNF required for 50% cytolysis of L-929 cells was changed from 30 ng/ml to 350 ng/ml by 10 ng/ml TGF-beta. This suppression was abolished when L-929 cells were treated with actinomycin D or cycloheximide, suggesting that TGF-beta might inhibit the action of TNF via de novo protein synthesis. This response was not due to down regulation of TNF receptors nor to alteration of the affinity of TNF for its receptor.
Animals↗
Stimulation of granulocytic cell iodination by pine cone antitumor substances.
Antitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U-937, THP-1, K-562), human diploid fibroblast (UT20Lu), or mouse cell lines (L-929, J774.1). Iodination of HL-60 cells, which were induced to differentiate by treatment with either retinoic acid or tumor necrosis factor, were stimulated less than untreated cells. The stimulation of iodination of both PMN and HL-60 cells required the continuous presence of these fractions and was almost completely abolished by the presence of myeloperoxidase inhibitors. The stimulation activity of these fractions was generally higher than that of various other immunopotentiators. Possible mechanisms of extract stimulation of myeloperoxidase-containing cell iodination are discussed.
Adjuvants, Immunologic↗
Philanthotoxins. A mass spectrometric investigation.
A method employing liquid secondary-ion mass spectrometry (SIMS) in conjunction with metastable-ion measurements (linked scanning at constant B/E) to obtain sequence-specific information for three synthetic polyamine isomers was developed. The normal liquid SIMS spectra gave molecular weight information, but important sequence ions were of low intensity or obscured by the background. The metastable-ion spectra contained important fragment ions in particular due to cleavage along the polyamine chain. One of the three synthetic isomers was identical with a toxin present in the venom of the digger wasp. In conjunction with nuclear magnetic resonance spectroscopic studies, this should be a powerful method for the structural characterization of other closely related toxins present in the venom of this wasp.
Isomerism↗
Calcium binding and calcium-sensitivity of heavy meromyosin and subfragment-1 from squid (Todarodes pacificus) mantle and scallop (Patinopecten yessoensis) adductor muscles.
1. HMM and S-1 both bind one mol of calcium per mole of head, and a half of the calcium binding was diminished upon magnesium addition (10 mM) at the low affinity site. 2. The Mg-ATPase activity of HMM (without actin) was fully activated by the binding of one mol of calcium bound per mol of HMM. 3. The calcium binding profile to S-1 is the same as that to HMM, however, the Mg-ATPase activity of S-1 is independent of calcium binding. It is suggested that there are two kinds of myosin head (or S-1) in molluscan myosin, functionally different in calcium binding properties.
Animals↗
Wavelength regulation in iodopsin, a cone pigment.
The opsin shift, the difference in wavenumber between the absorption peak of a visual pigment and the protonated Schiff base of the chromophore, represents the influence of the opsin binding site on the chromophore. The opsin shift for the chicken cone pigment iodopsin is much larger than that for rhodopsin. To understand the origin of this opsin shift and the mechanism of wavelength regulation in iodopsin, a series of synthetic 9-cis and 11-cis dehydro- and dihydro-retinals was used to regenerate iodopsin-based pigments. The opsin shifts of these pigments are quite similar to those found in bacteriorhodopsin-based artificial pigments. On the basis of these studies, a tentative model of wavelength regulation in iodopsin is proposed.
Animals↗
Thermal stability as a probe of S-1 structure.
The stabilizing effect of nucleotides against thermal denaturation of subfragment-1(S-1) was studied quantitatively. We showed that ATP- (ADP.P1) and AMPPNP-bound species are very stable, while ADP- and PPi-bound species are much less so (after ligand affinities are accounted for); these two stability classes correspond to the two CD and UD spectral classes. We further showed that the result of PPi- and ADP-binding is a weakening of the affinity between S-1 heavy chain and light chains, resulting in turbidity due to formation of aggregates of naked S-1 heavy chain. We also showed that while PPi- and ADP-binding decrease the inactivation rate of S-1 ATPase by protecting the 50-kDa fragment, they actually increase the denaturation rate of the remaining moieties (27 and 20 kDa); the rate of decrease of the 27- and 20-kDa tryptic fragments is much slower than that of the 50-kDa fragment with ligand-free S-1; however, the rate of decrease of these two fragments is fast and equal to that of the 50-kDa fragment with ADP- and PPi-bound S-1. Therefore, nucleotide binding to S-1 strongly affects the structure of the light chain binding site on the heavy chain, and it seems that the domain structure of S-1 is maintained by light chain binding.
Adenine Nucleotides↗
Conversion of Lewis lung carcinoma into ascitic form.
Lewis lung carcinoma (3LL), which has been most frequently used for various investigations of cancer, was converted to an ascitic form designated 3LL-SA. Ascites tumor cells showed a mixed population of single cells and about 10% islands which were made up of 2 to about 50 cells. Transplantability was 100%. The biological and metastatic capacities were preserved in this line as shown by its ability to form hemorrhagic and necrotic tumors, and by its multiple lung metastases. Moreover, histological and ultrastructural characteristics of this tumor line were identical to those of the parental 3LL. Thus, it can be seen that 3LL-SA will be a useful tool for the study of cancer.
Animals↗
Establishment of the specific radioimmunoassay for serum thymic factor (STF).
Serum thymic factor is a humoral factor involved in the differentiation of T cells. In the present study, a radioimmunoassay system for STF was established using a specific antiserum and an iodinated synthetic STF as a tracer. Serum levels of STF-like immunoreactivities were around 30 pg/ml in human, but in contrast to previous reports serum STF levels did not show age-dependent decreases. STF-like immunoreactivities of the thymic gland were lower than those of the liver and kidney in rats. The livers of human and pig contained high STF-like immunoreactivities. The rat thymic gland extract showed three peaks of STF-like immunoreactivity by gel filtration of Sephadex G-25 which corresponded to the eluted position of authentic STF, a larger molecular size, and a smaller molecular size of STF, respectively, while the rat liver extract showed two peaks corresponding to the void volume fraction and to the position of authentic STF, respectively. When this void volume fraction was digested by trypsin, three peaks which corresponded to authentic STF, a larger molecular size, and a smaller molecular size of STF were observed. Present studies suggest that serum thymic factor is produced as a larger STF molecule in the liver and kidney.
Adult↗
Normal values for quantitative parameters for evaluation of mucociliary clearance in lungs.
Twenty-eight normal male subjects (13 nonsmokers and 15 smokers, 25 to 76 years of age) inhaled ultrasonically generated 99mTc-tagged human serum albumin aerosol (mass median diameter: 1.93 microns with geometric standard deviation of 1.52) and radioactivity from the thorax was measured continuously from anteriorly in 10 sec frame mode for 90 to 120 min to evaluate mucociliary clearance function in the lungs. Normal values for lung retention ratio (LRR), airway deposition ratio (ADR), airway retention ratio (ARR), airway clearance efficiency (ACE), alveolar deposition ratio (ALDR), and disappearance rate of radioactivity from the ciliated airways (DR) were presented. ALDR was significantly larger in nonsmokers than in smokers. LRR and ARR were significantly smaller and ACE, significantly larger in smokers at any time intervals than in nonsmokers, while ADR and DR were larger in smokers only in the initial 30 min following radioaerosol inhalation was completed. Thereafter there was little difference in ADR and DR between normal smokers and nonsmokers.
Adult↗
Isolation of cytomegalovirus from the lung tissue of patients with intrapulmonary neoplasma.
Cytomegalovirus in the lung tissue was detected by demonstrating cytopathic effects on culture of fibroblasts. Three clinical features were common to patients in whose lung tissue cytomegalovirus was identified: (1) They had lung cancer. (2) They were on a high dose of prednisolone. (3) There were diffuse shadows on their chest x-ray film.
Adult↗
Allosteric inhibition of nicotinic acetylcholine receptors of vertebrates and insects by philanthotoxin.
The effects of pure philanthotoxin (PhTX), a component of the venom of the wasp Philanthus triangulum, were studied on nicotinic acetylcholine receptors (nAChRs) of vertebrates and insects so as to compare their sensitivities and the mechanism of action of PhTX. Electrophysiological techniques were used on frog muscles and cockroach thoracic ganglia and biochemical techniques were applied to membranes from Torpedo electric organ and honeybee brain. PhTX (1-20 microM) inhibited reversibly the indirectly elicited muscle twitch and reduced the endplate current peak amplitude and its decay time constant in a concentration-dependent manner. In patch clamp studies, PhTX (1-5 microM) when combined with acetylcholine, induced a concentration-dependent decrease in frequency of channel openings and in channel open and burst times. The cockroach fast coxal depressor neuron was inhibited by PhTX in a time- and voltage-dependent manner. The initial rate of binding of [3H]perhydrohistrionicotoxin to Torpedo nAChR in the presence of carbamylcholine was inhibited competitively by PhTX. Binding of alpha-[125I] bungarotoxin to electric organ and honeybee brain membranes was inhibited by PhTX. Binding of [3H]acetylcholine to the electric organ receptor was potentiated by low concentrations of PhTX but inhibited by high concentrations. PhTX, therefore, inhibits both vertebrate and insect nAChRs, which may be important molecular targets for its toxicity. It is suggested that PhTX at high concentration may have some competitive action on nAChR, but it acts mainly as a blocker of the ion channel of the nAChR in its open conformation.
Acetylcholine↗
Mechanism of selective inhibition of varicella zoster virus replication by 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil.
To investigate the mechanism of action of 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BV-araU) on varicella zoster virus (VZV) replication, we examined the metabolism of the drug in VZV-infected cells using 14C-labeled BV-araU. [14C]BV-araU was taken up by the cells infected with thymidine kinase-positive (TK+)VZV, but not so much by TK- VZV-infected or mock infected cells. Most of the radioactivity in TK+ VZV-infected cells that were incubated with [14C]BV-araU was recovered from their acid-soluble fraction, and little from their acid-insoluble fraction. By high performance liquid chromatographic assay of the acid-soluble fraction, it was proved that BV-araU was metabolized to its 5'-monophosphate, diphosphate, and triphosphate only in TK+ VZV-infected cells. The radioactivity was not detected in VZV nucleocapsids or in VZV DNA and cellular DNA isolated from TK+ VZV-infected cells, even if BV-araU was added at a 1000 times higher concentration than the 50% inhibitory dose for VZV replication in vitro. Furthermore, it was enzymatically proved that [14C]BV-araU was selectively and effectively phosphorylated to BV-araU monophosphate by VZV TK and that affinity of BV-araU triphosphate for VZV DNA polymerase was the quite strong. From these results, it can be concluded that marked inhibition of VZV replication by BV-araU is due to selective phosphorylation of BV-araU in the TK+ VZV-infected cells and strong inhibition of VZV DNA synthesis by BV-araU triphosphate, without detectable incorporation into VZV DNA.
Antiviral Agents↗
Inhibition of rat brain glutamate receptors by philanthotoxin.
The actions of philanthotoxin (PhTX) were studied on the function of glutamate receptors expressed in Xenopus oocytes injected with rat brain mRNA and on binding of radioligands to rat brain glutamate receptors. PhTX reversibly inhibited the oocyte responses to quisqualate, N-methyl-D-aspartate (NMDA) and kainate in a dose-dependent manner. The NMDA receptor was the most sensitive to PhTX action (10-fold more than the kainate receptor) and the least sensitive was the smooth current component of the quisqualate response. Recovery from PhTX block differed among the three amino acids. NMDA responses recovered completely within a few minutes whereas responses to kainate and quisqualate recovered more slowly. PhTX had no effect on equilibrium binding of [3H]glutamate to rat brain cortical membranes studied in buffer treated to eliminate microorganisms. Based on the drug specificity of this [3H]glutamate binding, it is suggested to be mostly to the NMDA receptor. Low concentrations of PhTX (1-10 microM) potentiated binding of [3H] MK-801, a specific noncompetitive inhibitor of the NMDA receptor. However, higher PhTX concentrations inhibited this binding with an IC50 of 20 microM, similar to its inhibition of the oocyte-expressed NMDA receptor. Inhibition of [3H]MK-801 binding by PhTX was noncompetitive. It is suggested that PhTX, like the more potent MK-801, binds to an allosteric site on the NMDA receptor and inhibits its function but its binding site is not identical with the MK-801 binding site.
Animals↗
[Detection of the occluded artery in cerebral infarction by MRI].
The appearance of flowing blood can be evaluated using magnetic resonance imaging (MRI). Depending on the velocity and direction of the flow, flowing blood has a variable appearance in MR images. Rapidly flowing blood which runs perpendicular to the imaging plane shows no signal (high velocity signal loss). Slow laminar flow has a stronger signal to the adjacent tissue when blood vessels run perpendicular to the imaging plane (flow related enhancement), and so when blood vessels course within the imaging plane (even echo rephasing). Considering these phenomena, we attempted to evaluate the occluded arteries in cases with cerebral infarctions. The occluded arteries showed high signal intensities both on T1 and T2 weighted images in all cases. A few cases whose occluded arteries had recanalized on angiography showed no signal in both images. It was found that the occluded site of internal carotid, middle cerebral or basilar artery could be identified on MRI. On the other hand, atherosclerotic middle cerebral arteries showed double linear high intensities along the arterial walls on both images. We speculated that these high intensities represented atherosclerotic plaque, slow laminar flow or thrombus along the artery. MR imaging could depict arterial occlusion, slow flow and thrombus.
Adult↗
Lignin inhibits (ADP-ribose)n glycohydrolase activity.
(ADP-ribose)n glycohydrolase activity was inhibited in vitro by lignin, a naturally occurring polymethoxyphenolic compound. However, coniferyl alcohol, which is a main component of lignin, was not inhibitory even at 100 micrograms/ml. Lignin caused competitive inhibition with respect to the substrate (ADP-ribose)n and its Ki value was 18 micrograms/ml. These results suggest that lignin with a polymerized structure has a functional domain that interacts with the (ADP-ribose)n glycohydrolase molecule at the same site as (ADP-ribose)n.
Binding, Competitive↗