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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 397 records · Page 22Linked to original sources

[The effects of low-doses of fentanyl, buprenorphine and pentazocine on circulatory responses to endotracheal intubation].

This study evaluates the effects of low-doses i.v. fentanyl, buprenorphine and pentazocine on circulatory responses of endotracheal intubation in 70 scheduled surgical patients. Patients were allocated to 5 groups randomly and 2 (n = 11) or 4 (n = 13) micrograms.kg-1 of fentanyl, 0.5 mg.kg-1 of pentazocine (n = 13), 5 micrograms.kg-1 of buprenorphine (n = 10) and saline as a control (n = 23) were administered 5 minutes before the administration of thiopental, respectively. Then, patients were intubated with 0.1 mg.kg-1 of vecuronium. Blood pressure and heart rate were recorded. Only 4 micrograms.kg-1 of fentanyl diminished circulatory responses of systolic blood pressure on the stimuli of endotracheal intubation.

Adjuvants, Anesthesia↗

Mechanisms underlying apoptosis induced by combination of 5-fluorouracil and interferon-gamma.

Several investigators have reported on the clinical effects of 5-fluorouracil (5-FU) or the combination of 5-FU plus interferon-gamma (IFN-gamma) on patients with advanced colorectal carcinoma. It has also been reported that apoptosis induced by 5-FU is due to the effects on DNA synthesis and functional RNA synthesis. In the present study, we examine the biological mechanisms underlying 5-FU or the combination of 5-FU plus IFN-gamma, using the colorectal carcinoma cell line, COLO 201, 5-FU and IFN-gamma independently or additively induced apoptosis in COLO 201 in a dose- and time-dependent manner, which was correlated with the down-regulation of Bcl-2 and the up-regulation of Bax. An interleukin-1 beta-converting enzyme (ICE)-like protease inhibitor (but not an ICE-inhibitor) blocked apoptosis induced by only 5-FU. These results suggest that 5-FU has the capacity to induce apoptosis in COLO 201, resulting from the up-regulation of Bax; the apoptosis-inducing signal of 5-FU seems to be different from that of IFN-gamma. Thereby, 5-FU and IFN-gamma have additional effects on the induction of apoptosis. This finding provides an experimental basis for clinical therapy using 5-FU and/or IFN-gamma for colorectal cancer.

Adenocarcinoma↗

Presence of B cell progenitors in the thymus.

We characterize B cell progenitors in the thymus. Although mature thymic B cells are surface Ig+, B220(high), but CD43-, B cell progenitors in the thymus were found to be slg-, B220(med), and CD43+. Most progenitors showed rearranged Ig D-J and V-D-J patterns when DNA from sorted B cell progenitors was amplified by PCR, blotted, and probed. When B cell progenitors were purified from the thymus and injected intrathymically into Ig heavy chain (Igh) allotype-disparate recipients, B cells bearing donor-type Igh6 were detected in the thymus but not in the periphery. Thymic B cells generated from these progenitors were CD5+ cells, although there was a broad range of expression of CD5 molecules. Furthermore, B cells purified from thymus that had been inoculated with B cell progenitors were able to differentiate into Ab-forming cells under the influence of CD40 ligand plus IL-10, and secreted IgM with donor Igh6 allotype. We thus clarified the existence of B cell progenitors in the thymus and also characterized the surface markers and their developmental functions.

Animals↗

Renal effects of a nitric oxide donor, NOC 7, in anesthetized rabbits.

Intrarenal arterial infusion of angiotensin II (4 ng/kg per min) reduced glomerular filtration rate and urinary Na+ excretion without affecting fractional Na+ excretion. Infusion of norepinephrine (30 ng/kg per min) reduced both urinary Na+ excretion and fractional Na+ excretion with a slight hypofiltration. The angiotensin II- and the norepinephrine-induced renal responses were suppressed during simultaneous infusion of a spontaneous nitric oxide donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl 1-triazene (NOC 7, 30 ng/kg per min) which itself had little influence on the renal parameters. The results suggest that in the rabbit kidney in vivo NOC 7 can interfere with the angiotensin II-induced hypofiltration and norepinephrine-evoked tubular reabsorption and thereby suppresses their antinatriuretic actions.

Anesthesia↗

Monocytes express Fas ligand upon CD4 cross-linking and induce CD4+ T cells apoptosis: a possible mechanism of bystander cell death in HIV infection.

Recent evidence indicates that death of uninfected lymphocytes by apoptosis plays an important role in the immunopathogenesis of HIV infection. We have previously demonstrated that CD4 cross-linking (CD4XL) performed in PBMC results in induction of T cell apoptosis in an accessory cell-dependent manner. In this study, we have investigated the roles of Fas interaction with its ligand (FasL) and of accessory cells in the CD4XL model of T cell apoptosis mediated by the anti-CD4 mAb Leu3a- or HIV-1 envelope protein g120. Here, we provide evidence that CD4XL-induced CD4+ T cell apoptosis is Fas-FasL interaction dependent and that monocytes play a critical role in inducing T cell apoptosis. We show that CD4XL-induced T cell apoptosis is blocked by the addition of soluble Fas or by anti-FasL mAb NOK-1; depletion of monocytes from PBMC, but not of CD19+ cells or CD8+ cells, abrogates CD4XL-induced T cell apoptosis. Conversely, addition of monocytes to purified CD4+ T cells augments CD4XL-induced apoptosis. In purified monocytes, CD4XL results in FasL expression; in purified CD4+ T cells, however, CD4XL upregulates Fas but not FasL expression. These findings underscore the important role of monocytes in HIV disease pathogenesis and firmly support the notion of CD4XL as a potent mechanism for inducing bystander cell death.

Antibodies, Blocking↗

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary anti-hapten response in mice.

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg-) B cells (centroblasts), and most of their progeny are sIg+ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg+ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg+ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg+ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg+ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.

Amino Acid Sequence↗

Induction of c-kit molecules on human CD34+/c-kit < low cells: evidence for CD34+/c-kit < low cells as primitive hematopoietic stem cells.

c-kit, a receptor for stem cell factor, has been widely accepted as a distinctive marker for hematopoietic stem cells. However, the level of c-kit expression on pluripotent hematopoietic stem cells is still controversial in mice and humans. We purified CD34+/c-kit < low cells (phenotypically c-kit-negative but only detectable at the message level) from human cord blood and examined their maturational steps in relation to the expression of c-kit molecules. When the CD34+/c-kit < low cells were cultured with cytokines (flt 3 ligand, interleukin 6 and interleukin 7) plus immobilized anti-CD34 monoclonal antibody (to crosslink CD34 molecules), c-kit molecules were clearly induced within 24 h. The c-kit expression gradually increased until day 8. When CD34+/c-kit(low) or CD34+/c-kit+ cells that had been induced from CD34+/c-kit < low cells were resorted and recultured using a methylcellulose culture system, they showed the same colony-forming ability as the freshly isolated CD34+/c-kit(low) or CD34+/c-kit+ cells, respectively. Furthermore, CD34+/c-kit < low cells have a similar hematopoietic potential to CD34+/c-kit(low) cells in assays for long-term culture initiating cell and colony-forming unit culture generated from long-term cultures. These findings suggest that CD34+/c-kit < low cells mature into CD34+/c-kit(low) and CD34+/c-kit+ cells, and acquire the reactivity to various humoral hematopoietic stimuli. Moreover, CD34+/c-kit < low cells showed a low level of rhodamine 123 retention, suggesting that CD34+/c-kit < low cells have multidrug resistance. Therefore, the CD34+/c-kit < low cells without colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte activity are also a pluripotent hematopoietic stem cell population, and the expression of c-kit on c-kit < low cells is the first maturational step of hematopoiesis.

Antigens, CD34↗

Tumor size as a simple prognostic indicator for gastric carcinoma.

BACKGROUND: Tumor size can be measured easily before or during operation with no special tools, but its prognostic use in patients with gastric carcinoma is still unclear. METHODS: Clinicopathologic data of 479 patients who underwent curative operation for gastric carcinoma were studies. The relationship between tumor size and survival of patients was investigated. RESULTS: The patients were divided into three groups: 182 with tumors measuring < 4 cm (group I), 252 with tumors of 4-10 cm (group II), and 45 with tumors of > or = 10 cm (group III). The 10-year survival rates for group I, II, and III patients were 92%, 66% and 33%, respectively (p < 0.01), and the three groups were significantly different with regard to depth of invasion (p < 0.01), number and level of lymph node metastasis (p < 0.01), and stage of disease (p < 0.01). Multivariate analysis indicated that tumor size independently influenced the survival of patients. CONCLUSIONS: Tumor size clinically serves as a simple predictor of tumor progression and survival of patients in gastric carcinoma.

Adenocarcinoma↗

Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma.

BACKGROUND & AIMS: Matrix metalloproteinases have been implicated in invasion and metastasis of various human malignant tumors, but its role in human hepatocellular carcinoma has not been characterized in detail. The aim of the present study was to examine the secretion and activation of metalloproteinases in liver tissues from patients with hepatocellular carcinoma and evaluate its relationship with clinicopathologic characteristics. METHODS: Activity of metalloproteinases was measured in 30 surgical specimen pairs of human primary hepatocellular carcinoma and adjacent nontumoral liver and in five cultured human hepatoma cell lines using zymography. A comparison of this activity with clinicopathological features was made. RESULTS: In the liver tissues, enhanced secretion of active forms of gelatinase A and matrilysin was associated with portal venous invasion (P < 0.05, respectively), intrahepatic metastasis (P < 0.05, respectively), and recurrence within the first postoperative year (P < 0.01 and P < 0.05, respectively). Enhanced messenger RNA expression for membrane type 1-matrix metalloproteinase was observed in 22 of 30 cases and associated with capsule invasion and the activation of progelatinase A (P < 0.05, respectively). CONCLUSIONS: Active gelatinase A, active matrilysin, and membrane type 1-matrix metalloproteinase may play an important role in tumor spread of human hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Simultaneous injection of round spermatid nuclei from mice and hamster oscillogen can initiate the normal development of mouse embryos.

PURPOSE: In the mouse, mature oocytes that have been injected with spermatid nuclei failed to become activated. Additional stimulation is required to trigger activation of the oocytes that leads to embryo development. This study was performed to determine whether simultaneous injection of mouse round spermatids and hamster oscillogen can fertilize oocytes and contribute to normal embryo development. MATERIALS AND METHODS: We simultaneously injected mouse oocytes with mouse round spermatid nuclei and a preparation of oocyte-activating protein (oscillogen) from hamster spermatozoa and compared the results with those of injection of testicular spermatozoa. RESULTS: The incidence of normal fertilization and embryo development after simultaneous injection of round spermatid nuclei and hamster oscillogen was not significantly different from that after the injection of testicular spermatozoa. Moreover, the rate of development of two-cell embryos to term did not differ very much between the two groups of oocytes. CONCLUSIONS: Simultaneous injection of round spermatid nuclei and oscillogen appears to be an ideal method for successful activation of oocytes by spermatid nuclei in vitro.

Animals↗

The appearance of unusual phenotypic cells (CD4+ Mac-1+ class II+) in the liver of (NZW x BXSB)F1 mice is possibly an animal model for autoimmune hepatitis.

The male (NZW x BXSB)F1 (W/BF1) mouse, a murine model for autoimmune diseases, shows hepatosplenomegaly with lymphoid cell infiltration in the liver by 20 weeks of age. The majority of infiltrating cells are T cells, B cells and plasma cells, as seen in autoimmune hepatitis. Together with the increase in serum glutamate pyruvate transaminase (GPT) levels, anti-dsDNA antibody (Ab) and circulating immune complex (CIC) levels increase with age. These findings are compatible with those of autoimmune hepatitis in humans. In addition, a unique finding in this mouse is the accumulation of CD4+ Mac-1+ Class II+ cells in the sinusoidal space. The cells have the capacity to proliferate and differentiate into macrophages in vitro, indicating that they are the precursors of macrophages. This W/BF1 mouse provides a useful tool for not only analyzing the pathogenesis of autoimmune hepatitis but also establishing a new therapeutic strategy for it. In addition, we discuss the significance of the appearance of abnormal cells in autoimmune-prone mice.

Animals↗

Ectodomain interactions of leukocyte integrins and pro-inflammatory GPI-linked membrane proteins.

Although glycosylphosphatidyl-inositol (GPI) linked membrane proteins do not possess transmembrane or cytosolic sequences they elicit transmembrane signals. Using microscopic fluorescence imaging and resonance energy transfer (RET) techniques we have shown that certain pro-inflammatory GPI-linked membrane proteins can interact with leukocyte beta 2 integrins (complement receptor type 3 (CR3) and 4 (CR4) and the leukocyte function-associated antigen-1 (LFA-1)). For example, physical associations between CR3 and Fc gamma RIIIB, CR3 and urokinase receptors, and CR3 and CD14 (lipopolysaccharide receptor) have been found. Although Fc gamma RIIIB appears to be constitutively associated with CR3, urokinase receptors and CD14 associations with CR3 are influenced by their ligation status and cell function (e.g. adherence and locomotion). CR3-to-urokinase receptor interactions have been confirmed by immunoprecipitation techniques. Immunoprecipitation of CR3 from Brij-58 lysates after biotinylation of neutrophil membranes revealed proteins of M(r) = 40,000, 50,000, 74,000 and 120,000, in addition to bands corresponding to the integrin alpha and beta chains. Cell functions such as transmembrane signaling and superoxide release/priming have been linked to these interactions. Importantly, reagents that affect the lectin-like site of CR3, such as N-acetyl-D-glucosamine, alpha-methyl-D-mannoside and beta-glucan alter these interactions and, in parallel, leukocyte functions. Thus, the interactions of GPI-linked proteins and integrins can be highly dynamic events linked to cell activities. Our studies suggest that it may be possible to develop new drugs directed at the lectin-like site of beta 2 integrins that block GPI-linked protein-to-integrin coupling thereby controlling inflammatory cell processes including cell adherence, locomotion and activation. Such drugs may be useful in clinical conditions such as ischemia-reperfusion injury, sepsis, arthritis and others.

CD18 Antigens↗

Classification of Setaria worms from calves and adult cattle into Setaria digitata and Setaria marshalli by polyacrylamide gel electrophoresis.

The protein profiles of solubilized whole worms of the species, Setaria digitata and Setaria marshalli were compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results showed that one band with a molecular size of 69 kDa was confirmed only in S. marshalli, while this band was not detected in S. digitata. There were no differences of the major bands between males and females of the respective worm species. As further investigation, two-dimensional gel electrophoresis was performed and at least one spot ranging from 64 to 73 kDa was confirmed in S. marshalli but not in S. digitata. Therefore, those worms could be classified into two species biochemically as well as by the morphological characteristics.

Animals↗

A globular complex formation by Nda1 and the other five members of the MCM protein family in fission yeast.

BACKGROUND: In the fission yeast Schizosaccharomyces pombe, Nda1, Nda4, Mis5 and Cdc21 proteins belong to the MCM (minichromosome maintenance) protein family which is thought to have six members. Each MCM member is required for the early stages of DNA replication, and has a well-conserved central 200-amino acid domain containing a putative ATP binding motif. However, the precise molecular functions of MCM proteins are not yet clear. RESULTS: We investigated the physical interaction of Nda1 protein with the other fission yeast MCM proteins using specific antibodies. Immunoprecipitation of Nda1 protein leads to the co-precipitation of all the other members of the fission yeast MCM protein family. We purified the MCM protein complex by a combination of column chromatography. The native molecular weight of the MCM complex was estimated by gel filtration to be 560 kDa. The purified fraction contained nearly equal quantities of the six MCM proteins. Electron microscope observation showed that the MCM complex has a globular shape with a central cavity. CONCLUSIONS: We have developed a procedure to purify fission yeast MCM proteins in a native hetero-oligomeric complex form for the first time, which opens an avenue to further biochemical analysis.

Amino Acid Sequence↗

Experimental uremia in male rats: effect of interval between partial nephrectomies on testicular function.

Testicular function in stepwise-nephrectomized rats, with a different interval between the two operations, was studied suing male Wistar rats. Serum levels of urea nitrogen and creatinine in stepwise-nephrectomized rats were significantly elevated compared to those in sham-operated rats (p < 0.001). With a 1-day interval between the two operations, these concentrations were considerably higher (p < 0.001) than those in 7-day interval rats. While serum LH levels were significantly reduced (p < 0.001) in 1-day interval rats, FSH levels in this group were considerably higher (p < 0.001) than in other groups. Serum concentrations of androstenedione in 1-day interval rats were significantly suppressed compared to other groups (p < 0.01). Serum testosterone levels in stepwise-nephrectomized rats were considerably lower (p < 0.001) than in sham-operated rats. It is assumed that testicular function in stepwise-nephrectomized rats is influenced by the interval between the two operations.

Androstenedione↗