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Biomedical subjects

M Yoshimoto

Publications and source records attributed to M Yoshimoto.

At least 289 records · Page 16Linked to original sources
PubMed1979

Quantitative structure-activity relationships in 2,5-bis(1-aziridinyl)-p-benzoquinone derivatives against leukemia L-1210.

Antileukemic activities of more than 30 2,5-bis(1-aziridinyl)-p-benzoquinones (4) were correlated against well-defined physicochemical constants. These compounds were evaluated against lymphoid leukemia L1210 in BDF1 mice. The best equations obtained exhibited a linear dependence on the hydrophobic constant, pi. Characteristic aspects of the equations are that the larger the relative hydrophilicity of the drugs the stronger the antileukemic activity will be and that the more hydrophilic compounds have a greater chemotherapeutic index. Steric and electronic effects were also determined to be important. Based on the correlations, three compounds (11, 15 and 19) were designed, synthesized, and biologically evaluated.

Animals↗
PubMed1978

Disseminated atypical mycobacteriosis in a child--a case of Mycobacterium sculoflaseum.

A case of disseminated mycobacterial disease caused by mycobacterium sculoflaceum is presented in a three-year-old female. Atypical acid-fast organisms were found in cultures from the tissue of lymph node and bone marrow, gastric juice and feces. Histologically the mesenteric lymph nodes contained numerous large macrophages which had large numbers of acid-fast bacilli. Caseation necrosis was absent. Distinguishing features are the extensive involvement of lymph nodes and bones and the preference for intracellular presence of acid-fast bacilli. Up to the present in Japan there are only 17 reported cases of atypical mycobacteriosis in children.

Child, Preschool↗
PubMed1976

Correlation analysis of Baker's studies on enzyme inhibition. 2. Chymotrypsin, trypsin, thymidine phosphorylase, uridine phosphorylase, thymidylate synthetase, cytosine nucleoside deaminase, dihydrofolate reductase, malate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, and glyceraldehyde-phosphate dehydrogenase.

The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to suggest special enzyme-ligand interactions. Several examples are given of the use of correlation equations in comparing structural features of different systems.

Animals↗
PubMed1975

Structure-activity relationship in synthetic fibrinolytics. 2-Phenethynylcyclopropanecarboxylates.

The fibrinolytic activity of nine 2-phenethynylcyclopropanecarboxylates was measured in the hanging clot test. The structure-activity relationship is given by log 1/C equals 0.54 log P + 2.01 where P is the octanol-water partition coefficient of the carboxylate ion pair and C is the molar concentration of the drug. The equation obtained for the cyclopropanecarboxylates is compared with similar equations for benzoates, salicylates, and N-phenylanthranilates.

Alkynes↗
PubMedDate not supplied

Model system for heat-induced translocation of cytoplasmic beta-galactosidase across phospholipid bilayer membrane.

The possibility of the translocation of the enzyme across the phospholipid bilayer membrane was investigated by using the liposomes prepared by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in which beta-galactosidase (beta-gal) was entrapped. Exposing the POPC liposomes entrapping beta-gal inside to heat treatment (40-50 degrees C, 1-60 min) was found to induce its translocation across the liposome membrane. The translocated activity of beta-gal from inner to outer aqueous phase of liposomes indicated the maximal value when the liposomes entrapping beta-gal were heated at 45 degrees C for 30 min. The gel permeation profiles of the liposomes before and after heat treatment (45 degrees C, 30 min) also supported the translocation of beta-gal across the liposome membrane. The membrane fluidity of liposomes was found to be increased with increasing temperature, so that the hydrophobicity of liposome membrane was also increased. The local hydrophobicity of beta-gal was maximized at the temperature of 40-50 degrees C. The mechanisms of beta-gal translocation have been suggested to be triggered by the enhancement of hydrophobic interaction between the liposome surface and beta-gal molecules. Finally, a minimal scheme of possible mechanism on the heat-induced translocation of beta-gal has been presented on the basis of the hydrophobic interaction between the liposome and the proteins. The experimental data on the heat-induced translocation of beta-gal were well corresponding to those from model calculation.

Chromatography, Gel↗
PubMedDate not supplied

Conformationally changed cytochrome c-mediated fusion of enzyme- and substrate-containing liposomes.

The fusion between enzyme-containing liposomes and substrate-containing liposomes was studied, utilizing conformationally altered cytochrome c as fusion mediator under stress conditions. The liposomes were composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and liposome aggregation and subsequent liposome fusion were induced by the addition of cytochrome c, which was partially denatured by 0.5 M guanidinium hydrochloride (GuHCl). In the presence of 0.5 M GuHCl, cytochrome c was found to have a significantly large local hydrophobicity which was determined with the aqueous two-phase partitioning method. Under these conditions, cytochrome c could efficiently bind to POPC bilayer membranes as quantitatively evaluated by immobilized liposome chromatography (ILC). The retardation of cytochrome c treated with 0, 0.5, and 1 M GuHCl on ILC could be correlated with the corresponding local hydrophobicity of cytochrome c. The enzymatic reaction triggered by liposome fusion involved the proteolytic enzyme alpha-chymotrypsin and its substrate succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (Suc-AAPF-pNA), which were separately trapped in POPC liposomes. Addition of partially denatured cytochrome c (most likely in the molten globule state) to the mixture of enzyme- and substrate-containing liposomes resulted in the release of one of the hydrolysis products, p-nitroaniline, to the outer phase of the fused liposomes, indicating that the enzymatic reaction occurred during the liposome fusion process. Such a coupled fusion-reaction system may have specific advantages over the conventional fusion analysis and may find application as drug delivery system.

Cell Membrane Permeability↗
PubMedDate not supplied

Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography.

To investigate age-related changes in cerebral energy production, we compared senescence-accelerated prone mice (SAMP8) as an animal model of accelerated aging and senescence-accelerated resistant mice (SAMR1) as a control. Considering that the cerebral glucose metabolic rate (CMRglc) at the time of O(2) deprivation and 2,4-dinitrophenol (DNP) loading would reflect anaerobic glycolytic capacity and mitochondrial function, respectively, we investigated dynamic changes in CMRglc before and after loading with these perturbations. Fresh brain slices were incubated with [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [(18)F]FDG uptake in these slices were obtained on the imaging plates. The fractional rate constant (=k(3)*) of [(18)F]FDG proportional to the CMRglc was evaluated by applying the Gjedde-Patlak graphical method to the image data. The k(3)* value before the hypoxic perturbation in all of the brain sites analyzed was higher in SAMP8 than SAMR1 in both the 2- and 10-month-old groups. With O(2) deprivation, k(3)* values were higher without site specificity in the 2-month-old SAMP8 than in 2-month-old SAMR1, whereas in 10-month-old mice, there was no significant difference between the two groups. In contrast, with DNP loading, while no significant difference was noted between 2-month-old SAMP8 and 2-month-old SAMR1, in 10-month-old mice, the SAMP8 group showed lower values in certain regions than SAMR1 mice. These results suggest that in the brain tissue of SAMP8, a marked transient enhancement of anaerobic glycolytic capacity in the 2-month-olds and a decrease in mitochondrial function in the subsequent period occur, as a result of which glucose metabolism appears to be enhanced in both the 2- and 10-month-old groups compared to SAMR1 mice.

Age Factors↗