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Biomedical subjects

I Suzuki

Publications and source records attributed to I Suzuki.

At least 37 records · Page 2Linked to original sources

Effects of oral administration of Echinacea purpurea (American herb) on incidence of spontaneous leukemia caused by recombinant leukemia viruses in AKR/J mice.

Four-week-old female AKR/J mice were given oral doses of powdered leaves from Echinacea purpurea three times weekly for 8 weeks (7.5 mg/mouse/week): controls received phosphate-buffered saline. Mean survival age of experimental AKR/J mice treated with the E. purpurea preparation was significantly prolonged and enlargement of thymic lymphoma in experimental mice was significantly suppressed compared with controls. In normal 3-week-old female AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection into the thymus of cell-free extract of thymus from the experimental 28-week-old female AKR/J mice that received the oral E. purpurea preparation was injected directly into the thymus. Proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the thymus was markedly inhibited after the first oral administration of the E. purpurea preparation as compared with untreated controls (final age, 28 weeks). Production of endogenous interferon (IFN)-gamma in AKR/J mice was also effectively augmented by the oral treatment with the E. purpurea preparation, however, the production of other cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 was minimal. These results suggest that this suppressive effects on spontaneously occurring leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on enhancement of nonspecific immune or cellular immune systems (or of both) by the E. purpurea preparation.

Animals↗

Directed forgetting with global forget instructions in an implicit and explicit memory test.

This study examined differences in directed forgetting effects between an implicit and an explicit memory test. 64 students (49 men, 15 women) were assigned to 4 (2 x 2) groups. In the middle of the study list, the group was given instruction to forget the presented item, whereas the control instruction group was not. Half of the subjects were given a Fragment Cued-recall test as an explicit memory test, and the other half were given a Fragment Completion test as an implicit memory test. Subjects learned an incidental learning task. Significant differences were found across conditions for instruction. The directed forgetting effect was observed on the explicit memory test (p<.05) but not on the implicit memory test. These results are discussed in terms of inhibition of retrieval theory.

Adolescent↗

Failure of low-dose radiosurgery to control temporal lobe epilepsy.

Radiosurgical treatment of intractable epilepsy has emerged as a noninvasive alternative to resection. Although gamma knife surgery (GKS) reportedly is effective when the radiation dose is sufficient to cause a destructive reaction in the targeted medial temporal lobe, the optimal target area and dose distribution are largely unknown. Some investigators have suggested that focused irradiation from a nondestructive dose is also effective. In this article the authors report two cases of medial temporal lobe epilepsy in which the patients underwent GKS performed using a 50% marginal dose of 18 Gy covering the amygdala. hippocampal head and body, and parahippocampal gyrus. In both cases this procedure failed to control seizures. Both patients became seizure free after undergoing anterior temporal lobectomy 30 and 16 months, respectively, after radiosurgery.

Adult↗

Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice.

The antidiabetic activity of Momordica charantia L. (Cucurbitaceae) was investigated in KK-Ay mice, an animal model with type 2 diabetes with hyperinsulinemia. The water extract of the fruit of Momordica charantia L. (MC) reduced the blood glucose of KK-Ay mice 3 weeks after oral administration (p<0.01) and also significantly lowered the serum insulin of KK-Ay mice under similar conditions (p<0.01). However, MC did not affect the blood glucose in normal mice. MC-treated KK-Ay mice blood glucose significantly decreased in an insulin tolerance test. Moreover, the muscle content of facilitative glucose transporter isoform 4 (GLUT4) protein content in the plasma membrane fraction from muscle significantly increased in the orally MC-treated mice when compared with that of the controls (p<0.01). These results suggest that the antidiabetic effect of MC is derived, at least in part, from a decrease in insulin resistance because of the increase of GLUT4 protein content in the plasma membrane of the muscle.

Administration, Oral↗

[A case of small cell lung cancer with paraneoplastic cerebellar degeneration and anti-voltage-gated calcium channel antibody].

A 55-year-old man presenting with 4 weeks of progressive dysarthria, gait ataxia and vertigo was admitted to our hospital. Chest X-ray films revealed a mass shadow in the right upper lobe of the lung, and transbronchial brushing specimens showed small-cell carcinoma. Extensive examination revealed metastatic lesions in the mediastinal lymph nodes and liver, but brain MRI showed no findings suggestive of metastasis or atrophy. A diagnosis of PCD associated with SCLC was made, and the patient had a high titer of anti-P/Q-type VGCC antibody. He was treated by chemotherapy and radiation therapy, which resulted in a transient improvement in the PCD symptoms.

Autoantibodies↗

Mechanism of oxidation of inorganic sulfur compounds by thiosulfate-grown Thiobacillus thiooxidans.

Thiobacillus thiooxidans was grown at pH 5 on thiosulfate as an energy source, and the mechanism of oxidation of inorganic sulfur compounds was studied by the effect of inhibitors, stoichiometries of oxygen consumption and sulfur, sulfite, or tetrathionate accumulation, and cytochrome reduction by substrates. Both intact cells and cell-free extracts were used in the study. The results are consistent with the pathway with sulfur and sulfite as the key intermediates. Thiosulfate was oxidized after cleavage to sulfur and sulfite as intermediates at pH 5, the optimal growth pH on thiosulfate, but after initial condensation to tetrathionate at pH 2.3 where the organism failed to grow. N-Ethylmaleimide (NEM) inhibited sulfur oxidation directly and the oxidation of thiosulfate or tetrathionate indirectly. It did not inhibit the sulfite oxidation by cells, but inhibited any reduction of cell cytochromes by sulfur, thiosulfate, tetrathionate, and sulfite. NEM probably binds sulfhydryl groups, which are possibly essential in supplying electrons to initiate sulfur oxidation. 2-Heptyl-4-hydroxy-quinoline N-oxide (HQNO) inhibited the oxidation of sulfite directly and that of sulfur, thiosulfate, and tetrathionate indirectly. Uncouplers, carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and 2,4-dinitrophenol (DNP), inhibited sulfite oxidation by cells, but not the oxidation by extracts, while HQNO inhibited both. It is proposed that HQNO inhibits the oxidation of sulfite at the cytochrome b site both in cells and extracts, but uncouplers inhibit the oxidation in cells only by collapsing the energized state of cells, delta muH+, required either for electron transfer from cytochrome c to b or for sulfite binding.

2,4-Dinitrophenol↗

Sulfite oxidation by iron-grown cells of Thiobacillus ferrooxidans at pH 3 possibly involves free radicals, iron, and cytochrome oxidase.

Thiobacillus ferrooxidans cells grown on ferrous iron oxidized sulfite to sulfate at pH 3, possibly by a free radical mechanism involving iron and cytochrome oxidase. A purely chemical system with low concentrations of Fe3+ simulated the T. ferrooxidans system. Metal chelators, ethylenediamine tetraacetic acid (EDTA), 4,5-dihydroxy-1-3-benzene disulfonic acid (Tiron), o-phenanthroline, and 2,2'-dipyridyl, inhibited both sulfite oxidation systems, but the T. ferrooxidans system was inhibited only after the initial brief oxygen consumption. EDTA and Tiron, strong chelators of Fe3+, inhibited the oxidation at lower concentrations than o-phenanthroline and 2,2'-dipyridyl, strong chelators of Fe2+. Inhibition of Fe3+-catalyzed sulfite oxidation by EDTA and Tiron was instant, but the inhibition by o-phenanthroline and dipyridyl was briefly delayed, presumably for the reduction of Fe3+ to Fe2+. Mannitol, a free radical scavenger, inhibited both systems to the same extent. Cyanide and azide inhibited only the T. ferrooxidans system, suggesting a role of cytochrome oxidase. It is proposed that sulfite is oxidized by a free radical mechanism initiated by Fe3+ on the cell surface of T. ferrooxidans. Cytochrome oxidase is possibly involved in the regeneration of Fe3+ from Fe2+ by the normal Fe2+-oxidizing system of T. ferrooxidans.

Acids↗

A new one-Pot method for the synthesis of alpha-siloxyamides from aldehydes or ketones and its application to the synthesis of (-)-bestatin

A new one-pot method for the synthesis of alpha-siloxyamides is described. The three substrates, H-C(CN)(2)O-SiMe(2)t-Bu, aldehydes or ketones, and primary or secondary amines, are simply mixed in one portion in acetonitrile or ether; the alpha-siloxyamides are obtained within short peroids in excellent yields in many cases. As a demonstration of our method, the synthesis of (-)-bestatin was carried out.

Journal Article↗

Fas ligand costimulates the in vivo proliferation of CD8+ T cells.

Fas ligand (FasL/CD95L/APO-1L) is one of a growing number of TNF family members whose triggering costimulates maximal proliferation of activated T cells. In this study we show that maximal Ag-dependent accumulation of transferred TCR-transgenic CD8(+) T cells requires Fas (CD95/APO-1) expression by the adoptive hosts. Additionally, adoptively transferred FasL(+) CD8(+) T cells demonstrate a 2-fold advantage in Ag-driven expansion over their FasL(-)counterparts. This study illustrates the in vivo role of TCR-dependent FasL costimulation in the Ag-specific proliferation of both heterogeneous and homogeneous populations of primary CD8(+) T cells and long-term CTL lines. Thus, cross-linking FasL on naive and Ag-experienced CD8(+) T cells whose Ag-specific TCRs are engaged is required to drive maximal cellular proliferation in vivo.

Adoptive Transfer↗

Effect of anions on selective solubilization of zinc and copper in bacterial leaching of sulfide ores.

Bacterial leaching of sulfide ores using Thiobacillus ferrooxidans, Thiobacillus thiooxidans, or a combination of the two was studied at various concentrations of specific anions. Selective zinc and copper solubilization was obtained by inhibiting iron oxidation without affecting sulfur/sulfide oxidation. Phosphate reduced iron solubilization from a pyrite (FeS(2))-sphalerite (ZnS) mixture without significantly affecting zinc solubilization. Copper leaching from a chalcopyrite (CuFeS(2))-sphalerite mixture was stimulated by phosphate, whereas chloride accelerated zinc extraction. In a complex sulfide ore containing pyrite, chalcopyrite, and sphalerite, both phosphate and chloride reduced iron solubilization and increased copper extraction, whereas only chloride stimulated zinc extraction. Maximum leaching obtained was 100% zinc and 50% copper. Time-course studies of copper and zinc solubilization suggest the possibility of selective metal recovery following treatment with specific anions.

Acidithiobacillus thiooxidans↗

A conformationally reliable spacer for molecular tweezers

[figure: see text] A reliable and rigid spacer, trans,trans,trans-perhydronaphthacene, for molecular tweezers was designed. A synthesis and molecular recognition study of its 1,14-disubstituted derivatives was carried out.

Journal Article↗

The pathway for perception and transduction of low-temperature signals in Synechocystis.

Low temperature is an important environmental factor that has effects on all living organisms. Various low-temperature-inducible genes encode products that are essential for acclimation to low temperature, but low-temperature sensors and signal transducers have not been identified. However, systematic disruption of putative genes for histidine kinases and random mutagenesis of almost all the genes in the genome of the cyanobacterium Synechocystis sp. PCC 6803 have allowed us to identify two histidine kinases and a response regulator as components of the pathway for perception and transduction of low-temperature signals. Inactivation, by targeted mutagenesis, of the gene for each of the two histidine kinases and inactivation of the gene for the response regulator depressed the transcription of several lowtemperature-inducible genes.

Bacterial Proteins↗

The dual functions of fas ligand in the regulation of peripheral CD8+ and CD4+ T cells.

Although Fas ligand (FasL) is well characterized for its capacity to deliver a death signal through its receptor Fas, recent work demonstrates that FasL also can receive signals facilitating antigen (Ag)-specific proliferation of CD8(+) T cells. The fact that the gld mutation differentially influences the proliferative capacity of CD8(+) and CD4(+) T cells presented the intriguing possibility that a single molecule may play opposing roles in these two subpopulations. The present study focuses on how these positive and negative regulatory roles are balanced. We show that naive CD4(+) T cells are responsive to FasL-mediated costimulation on encounter with Ag when Fas-mediated death is prevented. Thus, the machinery responsible for transducing the FasL positive reverse signal operates in both CD4(+) and CD8(+) T cells. Instead, differential control of FasL expression distinguishes the role of FasL in these two T cell subpopulations. FasL costimulation occurs immediately on T cell receptor ligation and correlates with the up-regulation of FasL expression on CD8(+) and naive CD4(+) T cells, both of which are sensitive to the FasL costimulatory signal. Conversely, FasL-initiated death occurs late in an immune response when high levels of FasL expression are maintained on CD4(+) T cells that are sensitive to Fas-mediated death, but not on CD8(+) T cells that are relatively insensitive to this signal. This careful orchestration of FasL expression during times of susceptibility to costimulation and conversely, to death, endows FasL with the capacity to both positively and negatively regulate the peripheral T cell compartment.

Antigens↗

Gene polymorphism for microsomal epoxide hydrolase and susceptibility to emphysema in a Japanese population.

Recently, it was reported that gene polymorphism for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the first-pass metabolism of epoxide intermediates, was associated with susceptibility to emphysema. This association was examined in a Japanese population, performing polymerase chain reaction (PCR)-based direct sequencing and restriction fragment length polymorphism assays for variant forms of mEPHX. The subjects consisted of 79 smokers with moderate to severe emphysema diagnosed by lung computed tomography scans, 58 smokers without emphysema, with a comparable smoking history, and 114 consecutive subjects who undertook annual health checkups. The allele frequency of exon 3 Tyr113 to His113, which was reported to confer slow mEPHX activity, was substantially higher in the population control group compared with that of the Caucasian control subjects in a previous study. However, neither the genotype distribution of exon 3, nor that of exon 4 His139 to Arg139, was significantly different between the two groups of smokers. These data indicate that the gene polymorphism for mEPHX is not associated with susceptibility to emphysema in the Japanese population. The discrepancy between the two studies may be explained either by racial difference or by the selection bias of subjects in the previous study, which examined those who had only mild to moderate emphysema with lung cancer or those who were clinically diagnosed as having chronic obstructive pulmonary disease.

Disease Susceptibility↗

The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation.

The cloning and characterization of the human melanocortin-1 receptor (MC1R) and the demonstration that normal human melanocytes respond to the melanocortins, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotrophic hormone (ACTH), with increased proliferation and eumelanogenesis had put an end to a long-standing controversy about the role of melanocortins in regulating human cutaneous pigmentation. We have shown that alpha-MSH and ACTH bind the human MC1R with equal affinity, and are equipotent in their mitogenic and melanogenic effects on human melanocytes. We also showed that the activation of the MC1R is important for the melanogenic response of human melanocytes to ultraviolet radiation (UVR). The MC1R is also the principal mediator of the inhibitory effects of agouti signaling protein (ASP) on melanogenesis. Expression of the MC1R is subject to regulation by its own ligands alpha-MSH and ACTH, as well as by UVR and endothelin-1. Recent studies that we conducted on the expression of MC1R variants by human melanocytes and the implications of these variants on the function of the MC1R revealed the following. Human melanocytes homozygous for Arg160Trp mutation in the MC1R demonstrated a significantly reduced response to alpha-MSH. Also, this culture responded poorly to ASP and exhibited an exaggerated cytotoxic response to UVR. Another culture, which was homozygous for Val92Met mutation in the MC1R, demonstrated a normal response to alpha-MSH. Heterozygous mutations that are frequently expressed in various melanocyte cultures did not disrupt MC1R function. These results begin to elucidate the significance of MC1R variants in the function of the receptor. Our data emphasize the significance of a normally functioning MC1R in the response of melanocytes to melanocortins, ASP, and UVR.

Agouti Signaling Protein↗