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Biomedical subjects

Y Tokunaga

Publications and source records attributed to Y Tokunaga.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hepatic undifferentiated (embryonal) sarcoma in an adult: a case report and review of the literature.

Undifferentiated (embryonal) sarcoma of the liver (USL) is a rare malignant tumour with a poor prognosis. The absence of specific symptoms, the rapid tumour growth, the normality of the common tumour markers, and the consequential delay in the diagnosis often result in significant enlargement of the tumour. To our knowledge, there have been only 42 reported cases of USL in adults worldwide during the 40 years since the clinicopathological entity of USL was defined. We report here a 27-year-old male with USL who has been treated successfully with surgical resection and adjuvant chemotherapy using ifosfamide, adriamycin and cisplatin. Although the prognosis of the disease remains generally poor, long-term survival has been achieved recently in patients with a combination of surgery and multi-agent chemotherapy.

Adult↗
PubMed2000

Novel rosette formation of murine spleen cells with autologous red blood cells.

Spleen cells of normal BALB/c mice formed rosettes with autologous red blood cells, and the formation was calcium ion dependent. Peritoneal exudate cells, bone marrow cells and thymocytes did not form such rosettes. Spleen cells were passed over a Sephadex G-10 column or incubated on a plastic surface in order to eliminate adherent cells from them. Cells obtained by both these methods were unable to form rosettes. B cell-, T cell- and natural killer cell-enriched fractions in spleen cells were unable to form rosettes either. Some of the mouse IgG subclasses suppressed rosette formation when added to its site. These are monoclonal antibodies whose specificities are directed against Aspergillus niger glucose oxidase. Moreover, Aspergillus niger glucose oxidase suppressed the rosette formation when spleen cells had been treated with it as well as when it had been added to the site of rosette formation. These findings suggest that some murine spleen cells have receptors to a structure on autologous red blood cells, which is recognized by an anti-Aspergillus niger glucose oxidase monoclonal antibody.

Animals↗
PubMed2000

Local distribution into brain tumor and pharmacokinetics of 4-pyridoxate diammine hydroxy platinum, a novel cisplatin derivative, after intracarotid administration in rats with 9L malignant glioma: simultaneous brain microdialysis study.

Local distribution into brain tumor and the pharmacokinetics of 4-pyridoxate diammine hydroxy platinum (PyPt), a novel cisplatin derivative, were examined using rats implanted with 9L glioma and compared with cisplatin. PyPt (5.0 mg/kg) and cisplatin (3.5 mg/kg) were administered as selective intracarotid infusions for 30 min to the rats. Dialysates from extracellular fluid (ECF) in tumor and non-tumor brain tissues were collected by simultaneous microdialysis. The amount of platinum was determined by atomic absorption spectrophotometry, as representative of the drug administered. Plasma concentration of total and protein unbound platinum, and urinary excretion amount and tissue distribution of total platinum were also determined. Unbound platinum was accumulated preferentially in the brain tumor tissue ECF after drug administration, while there was little distribution into normal tissue ECF of the brain. In the brain tumor, the values of the unbound platinum AUC and MRT, where AUC is the area under the concentration-time curve and MRT is the mean residence time, for PyPt were 1.7 and 1.3 times larger than with cisplatin, respectively. The brain tumor distribution coefficient (the ratio of brain tumor ECF platinum AUC to plasma protein unbound platinum AUC) for PyPt (0.85) was higher than that for cisplatin (0.69), indicating that the local amount of platinum distributed into the glioma is enhanced by PyPt rather than by cisplatin. The binding to plasma proteins of PyPt (23%) was lower than that of cisplatin (65%). The total platinum concentration in tissues after administration of PyPt was significantly lower than that of cisplatin in the kidney, liver and spleen. In addition, the urinary excretion amount of total platinum after the administration of PyPt was significantly larger than that of cisplatin. These results suggested that PyPt is easily eliminated by rapid urinary excretion because of its reduced interaction with plasma proteins and poor distribution to the kidney or reticuloendothelial tissues such as the liver and spleen. It is concluded that PyPt is an effective cisplatin derivative for the treatment of gliomas with the added advantage of enhancing local distribution of drug into the brain tumor and reducing its accumulation in the kidney, which has previously caused severe nephrotoxicity.

Animals↗
PubMed2000

Effect of thrombopoietin on acute myelogenous leukemia blasts.

It has been shown that the expression of c-mp1, which is a specific receptor for thrombopoietin (TPO), is restricted to the surface of megakaryocytes, platelets, human CD34+ progenitor cells and human erythroid/megakaryocytic leukemic cell lines. Recently, however, it has been reported that some acute myelogenous leukemia (AML) blasts expressed c-mp1 on their cell surface and proliferated in response to TPO. We therefore investigated the effect of thrombopoietin on the growth of leukemic blasts from patients with CD7-positive acute myelogenous leukemia (AML), which is a distinct biological and clinical subtype of AML. Significant growth responses of leukemic blasts to TPO were seen in 10/10 CD7+ and 7/20 CD7- AML cases using 3H-thymidine incorporation, while synergistic stimulatory effects of TPO with stem cell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were observed in both groups. In a leukemic blast colony assay, significant growth response to TPO was observed in 5/6 CD7+ and 4/17 CD7- AML cases examined. Furthermore, the expression of c-mp1 seemed to be higher in CD7+ AML cases than in CD7- cases, suggesting a relationship between the expression of c-mp1 and the proliferative response to TPO. These findings imply that CD7+ leukemic blasts express functional TPO receptors and proliferate in response to TPO. Thus CD7 expression on AML blasts may indicate the involvement of leukemic progenitors at an early stage of multipotent hemopoietic stem cells. In this review, we discuss the effect of TPO on AML blasts, especially in CD7+ AML cases.

Animals↗
PubMed2000

Vaccination of a refractory essential monoclonal cryoglobulinemia patient with cryoglobulin-pulsed dendritic cells.

We vaccinated a refractory essential monoclonal cryoglobulinemia patient with monocyte-derived DCs (Mo-DCs) pulsed with purified cryoglobulin as a tumor antigen. During the vaccinations, his acrocyanosis improved and we were able to reduce the number of hot baths used to treat his symptoms, with no side effects. Furthermore, cryoglobulin-specific proliferative responses were observed after the vaccination. As there was a recurrence of acrocyanosis after the final vaccination, vaccination with Mo-DCs pulsed with purified cryoglobulin would seem to be a useful treatment for refractory essential monoclonal cryoglobulinemia.

Antigens↗
PubMed2000

MLL gene rearrangement in t(9;11) acute myelogenous leukemia with minimal myeloid differentiation (FAB subtype M0).

A 25-year-old man was diagnosed with acute myelogenous leukemia (AML), French-American-British (FAB) subtype M0, based on cytochemical and flow cytometric findings. Cytogenetic analysis revealed the chromosome translocations t(9;11)(p22;q23), and MLL gene rearrangement was identified by Southern blotting. In adult AML, MLL gene rearrangement was initially reported in FAB M4 and M5 cases, and recently in M1 and M2 cases, but was rare in M0 or M3 cases. Because the sensitivity of detecting MLL gene rearrangement by cytogenetic analysis is extremely low compared with Southern blotting analysis, the MLL gene may be involved in substantial numbers of adult AML cases, regardless of FAB subtype.

Adult↗
PubMed2000

[A case of adenoid cystic carcinoma of the trachea resected surgically after Nd-YAG laser therapy].

A case of primary tracheal tumor ablated by endoscopic Nd-YAG laser prior to tracheal sleeve resection was reported. A 53-year-old man had dry cough, bloody sputum and dyspnea. Bronchoscopic examination revealed polypoid tumor which located 2 cm below the vocal cords and obstructed the airway almost completely. After tumor vaporized by Nd-YAG laser, bronchoscopy type 200 could pass through the tracheal lumen and the length of the lesion was diagnosed within 4 cm. Biopsy specimen was confirmed adenoid cystic carcinoma. Cervical trachea was resected of six tracheal cartilage (first to sixth cartilage) combined with left thyroid lobe under collar incision and median sternotomy. The neck was fixed for ten days by tying the jaw to the anterior chest wall in order to reduce excessive tension to the anastomosis. Pathological examination revealed the tumor residual microscopically, 60 Gy of radiotherapy was conducted.

Carcinoma, Adenoid Cystic↗
PubMed2000

A discussion of anti-Aspergillus niger glucose oxidase monoclonal antibody reactivity to red blood cells of several species.

We observed that mouse spleen cells from rosettes with autologous red blood cells (RBCs) and that rosette-formation was suppressed by anti-Aspergillus niger glucose oxidase monoclonal antibody (mAb). In the present study, we investigated whether RBCs of species besides mice have the structure recognized by anti-A. niger glucose oxidase mAb by using rosette-formation and complement-mediated hemolysis. Lysates of monkey and human RBCs did not suppress rosette-formation whereas autologous (mouse), rat and sheep RBC lysates partially suppressed rosette-formation. Those lysates exerted their suppressive activity after they had been treated at 56 degrees C for 30 min. A. niger glucose oxidase also suppressed rosette-formation with or without treatment at 56 degrees C for 30 min. Alternatively, anti-A. niger glucose oxidase mAb lysed mouse, rat and sheep RBCs but not human RBCs with complement. These findings suggest that the cell surfaces of mouse, rat and sheep RBCs have a structure which can be recognized by anti-A. niger glucose oxidase mAb while the cell surfaces of monkey and human RBCs do not.

Animals↗
PubMed1999

Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.

Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.

Adult↗
PubMed1999

Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells.

Stimulation-regulated fusion of vesicles to the plasma membrane is an essential step for hormone secretion but may also serve for the recruitment of functional proteins to the plasma membrane. While studying the distribution of G protein-gated K+ (KG) channels in the anterior pituitary lobe, we found KG channel subunits Kir3.1 and Kir3.4 localized on the membranes of intracellular dense core vesicles that contained thyrotropin. Stimulation of these thyrotroph cells with thyrotropin-releasing hormone provoked fusion of vesicles to the plasma membrane, increased expression of Kir3.1 and Kir3.4 subunits in the plasma membrane, and markedly enhanced KG currents stimulated by dopamine and somatostatin. These data indicate a novel mechanism for the rapid insertion of functional ion channels into the plasma membrane, which could form a new type of negative feedback control loop for hormone secretion in the endocrine system.

Amino Acid Sequence↗
PubMed1999

Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra.

G-protein-gated K+ (KG) channels generate slow inhibitory postsynaptic potentials in the brain. Current opinion suggests that neuronal KG channels are heterotetramers of Kir3.1 and Kir3.2. In substantia nigra (SN), however, mRNA of Kir3.1 does not express, whereas that of Kir3.2 clearly does. Therefore, we have characterized the KG channels containing Kir3.2 subunits in SN using biochemical and immunological techniques. We found that they were composed of only Kir3.2 subunits and did not contain significant amounts of either Kir3.1 or Kir3.3. Furthermore, at least some of the KG channels in SN were assemblies of the splicing variants Kir3. 2a and Kir3.2c. The channels were localized specifically at the postsynaptic membrane on the dendrites of dopaminergic neurons. Kir3. 2c, but not Kir3.2a, could bind a PDZ domain-containing protein, PSD-95. The heterologously expressed KG channels composed of Kir3.2a plus Kir3.2c or Kir3.2a alone were activated by G-protein stimulation, but expression of Kir3.2c alone was not. This study reveals that the Kir3.2 splicing variants play distinct roles in the control of function and localization of some of the KG channels in dopaminergic neurons of SN.

Animals↗
PubMed1999

Effect of amino acid substitution in amphiphilic alpha-helical peptides on peptide-phospholipid membrane interaction.

It was previously found that a cationic amphiphilic peptide, Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4(3)), caused the destabilization of a phospholipid membrane and showed strong antibacterial activity [Lee et al. Biochim. Biophys. Acta 1986; 862: 211-219]. In order to investigate the effect of changing alpha-helix propensity, hydrophobicity and basicity in 4(3) on the peptide conformation and activity, the 4(3) analogs, [Gly (or Val)6]4(3), [Gly (or Val)2,6]4(3), [Gly (or Val)2,6,10]4(3), [Gln3]4(3), [Gln3,7]4(3) and [Gln3,7,11]4(3) were synthesized. Except for [Val2,6]4(3) and [Val2,6,10]4(3), which mainly formed a beta-structure, other peptides formed an alpha-helix and showed moderate membrane-perturbing activity toward neutral and acidic lipid vesicles. All the peptides other than [Val2,6,10]4(3) and [Gln3,7,10]4(3) had the antibacterial activity comparable with that of 4(3). The relationship between the membrane-perturbing activity and the antibacterial activity was not always parallel. Conclusively, the Ala-->Val substitution in 4(3) causes the change of peptide conformation and the presence of a cationic amino acid residue is necessary for the antibacterial activity.

Amino Acid Sequence↗
PubMed1999

Jejunal pouch to avoid stricture after esophagojejunostomy with circular stapler.

BACKGROUND: Anastomotic stricture is one of the most common problems in esophagojejunostomy using the end-to-end anastomosing (EEA) instrument (Auto Suture Co, Norwalk, CT) after total gastrectomy. To alleviate the stricture, several methods, such as incision to the scar, balloon dilatation, and steroid injection are available. To avoid stricture, the jejunal pouch may allow use of a larger EEA than Roux-en-Y (ReY) reconstruction does. STUDY DESIGN: A total of 45 patients underwent curative total gastrectomy and esophagojejunostomy with jejunal pouch construction (27 patients) or ReY (18 patients), using the EEA. The effects of jejunal pouch construction with a large EEA on avoidance of stricture and benefit to nutritional status were investigated by comparing it with the ReY in terms of postoperative morbidity, postprandial symptoms, and nutritional parameters (serum protein, serum albumin, body weight). RESULTS: EEA28 or larger could be used in 25 patients in the pouch group and 8 patients in the ReY group (p < 0.05). Stricture developed in one patient in the pouch group and in four patients in the ReY group (p < 0.05). Postprandial symptoms were experienced less frequently (p < 0.05) in the pouch group than in the ReY group. When stricture and symptoms were analyzed according to the size of EEA, they occurred more frequently (p < 0.05) in the patients with EEA25 than those with EEA28 or EEA31. No significant differences were evident in nutritional parameters. CONCLUSIONS: The choice of jejunal pouch technique allowed the use of a larger EEA than that of ReY reconstruction, resulting in avoidance of anastomotic stricture and postprandial symptoms, though little benefit in nutritional status was evident to the patients after total gastrectomy.

Anastomosis, Roux-en-Y↗
PubMed1999

Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist.

The present study has demonstrated that the sleep-promoting potency of 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A2A receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep-wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pons and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non-rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680-inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep-promoting effect.

Adenosine↗
PubMed1999

Cytoplasmic liberation of protein gene product 9.5 during the seasonal regulation of spermatogenesis in the monkey (Macaca fuscata).

Primate spermatogenesis is distinguished by yet unidentified mechanisms to regulate its spermatogenetic activity. In contrast to the well documented hormonal regulators, the cellular events responsible for the regulation of the spermatogenesis has not been addressed. By using PGP 9.5-immunohistochemistry, our previous study demonstrated that the monkey spermatogonia are divided into two distinct sub-populations, i.e. cytoplasmic PGP 9.5-positive and cytoplasmic PGP 9.5-negative spermatogonia. By comparing the cytoplasmic expression of PGP 9.5 between the breeding and nonbreeding seasons of the Japanese monkey (Macaca fuscata) in association with PCNA labeling, the present study demonstrates that the cytoplasmic PGP 9.5-positive Ap spermatogonia significantly increases when the spermatogenetic activity declines in the nonbreeding season. An ultrastructural subcellular localization of PGP 9.5 suggests that the increase of the cytoplasmic PGP 9.5 expression is due to a liberation of PGP 9.5 molecule from the nucleus into the cytoplasm. The results provide a theoretical basis by which PGP 9.5 serves as a novel marker for spermatogonial subtypes, which will have further implications for future studies on spermatogenesis. The analysis using this novel marker suggests that the Ap spermatogonia is a key stage to regulate the amount of the sperm produced in response to the hormonal regulators, and the cytoplasmic liberation of PGP 9.5 may serve as a pivotal phenomenon that enables the fully restorable, transient suppression of spermatogenesis in primate.

Animals↗