Search PubMed⌕ Search

Biomedical subjects

K Naito

Publications and source records attributed to K Naito.

At least 109 records · Page 6Linked to original sources

Endometrial expression of cellular protooncogene c-ski and its regulation by estradiol-17beta.

The expression of the cellular protooncogene c-ski was examined in the rat uterus. In situ hybridization revealed that c-ski mRNA was expressed in the uterus of the adult rat on the day of estrous and localized mainly in the luminal and glandular epithelia. To test the possibility that the expression of c-ski mRNA is induced by estrogen, rats were ovariectomized and estradiol-17beta (E2) was injected. The expression of c-ski mRNA was upregulated 3 h after E2 treatment, reaching the highest level at 6 h and this persisted until 24 h; the E2-induced expression of c-ski mRNA was restricted to the luminal and glandular epithelia. These results suggest that the c-ski gene plays a role in uterine epithelial cell proliferation and mediates the proliferative action of E2.

Animals↗

Effects of lesion of pontomedullary reticular formation on visually triggered vertical and oblique head orienting movements in alert cats.

The role of the nucleus reticularis pontis caudalis (NRPC) and the nucleus reticularis gigantocellularis (NRG) in control of vertical and oblique head orienting movements was investigated in alert cats by lesion of these nuclei with kainic acid. Cats were trained to orient the head vertically or obliquely to various targets. Following unilateral lesion of these nuclei, vertical orienting could be performed correctly with a slight decrease in velocity, while oblique orienting tended to exhibit zigzag course because of severe impairment of horizontal orienting. The horizontal and vertical components became coordinated in the course of experiments due to a significant decrease in vertical component velocity, resulting in smooth oblique trajectories. Results suggest that horizontal and vertical components of head orienting are controlled separately, but impairment of horizontal component causes adaptive change of vertical component velocity in oblique orienting.

Adaptation, Physiological↗

Novel, potent, and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives.

The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585.HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0. 85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the Ki value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).

3',5'-Cyclic-AMP Phosphodiesterases↗

Efficient selection of transgenic mouse embryos using EGFP as a marker gene.

We have established a reliable method that uses the EGFP (Enhanced Green Fluorescent Protein) gene as a marker for selecting transgenic embryos from preimplantation embryos. Embryos that were subjected to the pronuclear microinjection of the CMV/beta-actin/EGFP fusion gene were cultured in vitro until they developed into the morulae- or blastocyst-stage. The expression of EGFP was easily observed by a fluorescent microscopy. There appeared to be no damage to the in vivo developmental ability of the embryos in response to the EGFP excitation light, which utilized an IB filter for a period of 30 min. Modified PCR analysis using Dpn I and Bal 31 digestion of the embryonic DNA showed that all of the embryos expressing EGFP in all their cells were transgenic, while more than half with mosaic expression of EGFP were not transgenic. Approximately 77% of pups born from the embryos that uniformly expressed the EGFP gene were transgenic, while 21.4% of pups from the embryos with mosaic expression were transgenics. The results showed that the use of EGFP as a marker is very useful and reliable for selecting transgenic embryos, and that it is important to transfer the embryos expressing EGFP in all their cells to obtain truly transgenic animals.

Actins↗

Early valve failure after aortic valve-sparing root reconstruction.

Aortic valve-sparing root reconstructive surgery has been widely adopted to improve the patient's quality of life. We experienced a patient who required reoperation for progressive aortic regurgitation 17 months after the initial operation of valve-sparing root reconstruction with the reimplantation method in acute aortic dissection. In this study, we were concerned with valve durability because of the absence of sinuses of Valsalva in the new aortic root and the need for careful follow-up after this procedure.

Aortic Valve↗

Characterization of novel FcepsilonRII/CD23 isoforms lacking the transmembrane (TM) segment in human cell lines.

Human FcepsilonRII/CD23 is an approximately 45 kDa type II transmembrane glycoprotein belonging to the C-type animal-lectin family, and has two isoforms (a and b) that only differ in their intracytoplasmic tails. We previously found that in several human and mouse cell lines there were two additional CD23 transcripts (a' and b') lacking the exon 3 that encodes the entire transmembrane segment and a part of cytoplasmic tails. In this study, we analyzed the putative CD23a' and CD23b' products at protein levels and characterized with rabbit polyclonal antibodies against novel amino-acid sequences of the putative CD23a' and CD23b' molecules (anti-CD23a' Ab, anti-CD23b' Ab). Western blots in COS cells transfected with CD23a' or CD23b' cDNA as well as in vitro translation assays showed that the a' and b' CD23 transcripts were translated to about 40 kDa molecules. These 40 kDa molecules were also recognized by a polyclonal antibody against 25 kDa soluble fragment of human CD23. We also found that human cells having mRNAs for CD23a' and CD23b' expressed protein products recognized specifically by anti-CD23a' or anti-CD23b' Ab, respectively. In addition, the CD23a' and CD23b' molecules in transfected COS cells were resistant to Endo H(f) and PNGase F, although these truncated forms as well as the membrane-associated forms had an asparagine residue responsible for the N-linked glycosylation. Taken together, our results show that the a' and b' CD23 transcripts are expressed and translated in human lymphoid cells and that their translated products are retained in the cytoplasm where they might play an unique regulatory role in the expression of the full-length CD23 on the cell surface.

Amino Acid Sequence↗

Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives.

The intent of the work was to study the structure-activity relationships of AVP receptor antagonists bearing a chiral ring as a partial structure since such studies had been reported for only achiral compounds. In the present paper, we deal with compounds consisting of the chiral tricyclic hetero ring (1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoxaline and 1,2,3,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine) and 2-phenylbenzanilide analogues. These compounds exhibited a highly selective affinity for V2 receptor, and their stereochemical configuration had a great influence on V2 receptor binding. VP-343 (N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a] quinoxalin-5(1H)-yl]carbonyl]phenyl]-4'-methyl[1,1'-biphenyl]-2-ca rboxamide), VP-365 (N-[4-[[(11aS)-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benz odiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl-2-carboxamide) and VP-339 (N-[4-[[(11aS)-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]+ ++benzodiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl]-2-carboxami de) were the most potent compounds in vitro and in vivo. The IC50 values of VP-343, VP-365 and VP-339 against V2 receptor were 0.772, 1.18 and 0.216 nM, respectively. The ED300 values (dose required to increase three times the urine volume of the control rats; oral administration) of VP-343, VP-365 and VP-339 were 0.22, 0.31 and 0.78 mg/kg, respectively.

Animals↗

Phosphate exposure during the late 1-cell and early 2-cell stages induces a time-specific decrease in cyclin B and cdc25B mRNAs in AKR/N mouse embryos in vitro.

Phosphate induces 2-cell block in AKR/N mouse embryos in vitro. In an attempt to define the mechanism responsible for the inhibitory effect of phosphate, the critical period for this effect was determined. Then the amounts of the mRNAs for cyclin B and cdc25B, factors related to activation of M-phase promoting factor (MPF), were measured by quantitative reverse transcription-polymerase chain reaction. Exposure to phosphate during the late 1-cell (10-20 h after insemination) and early 2-cell stages (0-12 h after first cleavage) was found to induce 2-cell block in AKR/N mouse embryos. This period corresponds to the initiation of zygotic gene activation (ZGA). The presence of phosphate during second cleavage had no effect on 2-cell block of the embryos. The relative levels of cyclin B and cdc25B mRNAs did not change significantly during the 1-cell stage and decreased during the early 2-cell stage to almost half of the initial levels. When the amounts of mRNA in embryos cultured with and without phosphate were compared they were found to be almost identical even in the 2-cell block embryos, and a significant decrease in mRNA was observed only 33 h after insemination in embryos about to undergo phosphate block at the 2-cell stage. These results show that phosphate does not directly inhibit MPF activity and confirm the presence of cyclin B and cdc25B even in 2-cell block embryos. Furthermore, the fact that the decrease in mRNA levels corresponded to the critical period for the inhibitory effect of phosphate suggests that suppression of initial ZGA induction is involved in the 2-cell block of mouse embryos in vitro.

Animals↗

Inactivation of p34cdc2 kinase by the accumulation of its phosphorylated forms in porcine oocytes matured and aged in vitro.

Culturing of matured porcine oocytes in vitro results in the enhancement of their cytoplasmic ability for oocyte activation (so-called ageing), although they are arrested at metaphase II. The enhanced ability for oocyte activation is related to decreased activity of the maturation promoting factor (MPF). In the present study we clarified the molecular mechanism of MPF inactivation during ageing, especially the changes in the phosphorylation status of p34cdc2, a catalytic subunit of MPF, compared with that in fertilised oocytes. The MPF activity decreased gradually when maturation culture was prolonged from 36 to 72 h, confirming the decreasing MPF activity in aged oocytes. The activity of 48 h matured oocytes also decreased after in vitro fertilisation. Immunoblotting of p34cdc2 with anti-PSTAIRE antibody revealed that the culturing of matured oocytes induces a gradual increase in pre-MPF, which is a p34cdc2 and cyclin B complex inactivated by phosphorylation at the inhibitory phosphorylation site of p34cdc2. In contrast, pre-MPF decreased after fertilisation, indicating the degradation of cyclin B. These results suggest that the molecular mechanisms of inactivation of MPF are different between oocyte activation and ageing, and that the mechanism during ageing might be based on the inhibitory phosphorylation of p34cdc2, whereas that of oocyte activation is based on the degradation of cyclin B.

Amino Acid Sequence↗

Extensive cytogenetic studies of clonality following interferon-alpha therapy in chronic myeloid leukemia occurring in monosomic cells in a patient with Turner syndrome mosaic.

In a 27-year-old female with Turner syndrome mosaic, Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) occurred only in the monosomic cells (45, Xc). Extensive cytogenetic studies, including triple-color fluorescence in situ hybridization (FISH), revealed that Ph-positive monosomic cells (45, Xc), Ph-negative monosomic cells and normal diploid cells (46, XX) were present in her bone marrow at diagnosis. After successful interferon therapy, the non-leukemia cells expanded and reconstituted normal hematopoiesis resulting in complete cytogenetic response, following the selective suppression of the monosomic Ph-positive leukemia clone. The ratio of Xc to XX cells in bone marrow cells was significantly increased to that in skin fibroblasts. Moreover, the ratio of Ph-positive cells to Ph-negative cells was found to be significantly different between karyotyping and FISH. Studies of this quite unique case not only confirmed the clonality of CML, effectiveness of interferon-alpha and X chromosome imbalance among different tissues, but also demonstrated a discrepant increase of the BCR/ABL-positive clone in CML. The latter supports the hypothesis that reduced programmed cell death may be the primary mechanism responsible for the expansion of the leukemia clone in CML. Our study verifies the importance of extensive analysis of a neoplastic disease in patients with a constitutional chromosomal abnormality.

Adult↗

Mesoblastic nephroma in adulthood: a case report.

BACKGROUND: Mesoblastic nephroma is an uncommon renal tumor of infancy and rarely occurs in adults. We report an adult case of mesoblastic nephroma. METHODS: A 50-year-old woman was found incidentally to have a right renal mass by abdominal ultrasonography. Computed tomography and magnetic resonance imaging revealed a heterogeneous tumor and angiography showed a mixture of hypervascularity and hypovascularity. Right radical nephrectomy was performed. RESULTS: The tumor was an encapsulated yellowish solid mass. Microscopically, the tumor was composed of spindle cell proliferation. Atypia and mitoses were not identified. Among the tumor cells, there were tubular arranged epithelial elements. CONCLUSION: The patient was free of recurrence 14 months postoperatively. Mesoblastic nephroma is classified as a benign tumor but recurrence and malignant formation of this tumor have been reported so regular postoperative follow up is required.

Age of Onset↗

Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis.

OBJECTIVES: To compare plasma levels of matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) between patients with knee osteoarthritis and normal subjects, to investigate whether the degree of knee joint involvement is related to those measurements, and to compare patients with and without generalized osteoarthritis. METHODS: Eighty-three women with knee osteoarthritis (OA patients) were studied. Plasma levels of MMP-3, MMP-9 and TIMP-1 were measured by enzyme immunoassays. Knee and hand radiographs were taken of all patients. The joints of the knee and hand were graded from 0 to 4 according to Kellgren and Lawrence criteria. All OA patients were divided into a generalized OA (GOA) group (n = 37) and a knee OA (KOA) group (n = 46) according to Doherty's criteria. MMPs and TIMP were also measured in 19 normal subjects. RESULTS: Plasma levels of MMP-3 and TIMP-1 were significantly higher in OA patients than in normal subjects. In contrast, MMP-9 was lower in OA patients than in normal subjects. Plasma levels of MMP-3 and MMP-9 were not influenced by the grade of knee OA. TIMP-1 was influenced by the grade of knee OA. Plasma levels of MMP-3 were significantly elevated in GOA compared to KOA. In contrast, there were no significant differences in plasma levels of MMP-9 and TIMP-1 between GOA and KOA. CONCLUSION: Since the plasma level of MMP-3 in GOA was higher than that in KOA patients, it may be a superior indicator for whole-joint degeneration.

Aged↗

A case of primary adrenal lymphoma diagnosed from percutaneous needle biopsy.

A case of bilateral lymphoma of the adrenal glands is reported. A 72-year-old woman was admitted to our hospital for evaluation of bilateral adrenal masses. A 20-gauge core needle biopsy of the left adrenal tumor was performed under ultrasonographic guidance. The pathological specimen revealed a malignant lymphoma. The diagnostic procedure for adrenal lymphoma is discussed.

Adrenal Gland Neoplasms↗

Idiopathic clitoral hypertrophy.

We report a case of clitoral hypertrophy of unknown origin. A 3-year-old girl showed clitoral hypertrophy at birth. Biochemical analysis of peripheral blood and endocrinological examinations were normal. Other virilizing symptoms were not recognized. Clitoroplasty was carried out, and the clitoris has not enlarged 20 months after the operation. Her mother was administered cefotiam and terbutaline (beta-stimulant) during pregnancy because of threatened abortion. No virilizing agents such as progesterone were used during pregnancy.

Abortion, Threatened↗

Bandage distraction technique for ankle arthroscopy.

In ankle arthroscopy, the joint space of the talocrural joint is often too narrow for insertion of the scope and instruments. Various distraction devices for this procedure have been used to widen the joint space. Bandage distraction is effective and noninvasive, but it is difficult to extend the posterior joint space sufficiently for insertion of the scope. Here we describe a new bandage distraction method that can extend the posterior joint space adequately. Using our method, the anterior and posterior joint spaces on direct lateral radiographs were measured after adding the distraction force in nine healthy volunteers (18 ankles; three men and 6 women). This was compared to a previously reported method. The posterior joint space was widened a greater amount when our new bandage distraction technique was used.

Ankle Joint↗

Induction of anaphylaxis in mouse intestine by orally administered antigen and its prevention with soluble high affinity receptor for IgE.

Early symptoms of food allergy, including diarrhea, are caused by IgE-mediated anaphylactic reactions. To clarify the mechanisms of IgE-mediated anaphylactic reactions in the intestine induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody. Morphologic and immunologic changes in the intestine, as well as the effect of the soluble high affinity IgE receptor alpha chain, were investigated after oral challenge with antigen in this mouse model. Diarrhea, a decrease in s.c. blood flow, an increase in vascular permeability, a substantial increase in serum histamine levels, and noticeable infiltration of mast cells and IgE-bearing cells into the lamina propria were observed around 30 min after antigen challenge. However, these changes were efficiently prevented by pretreatment of the mice with the soluble high affinity IgE receptor alpha chain. These findings suggested that oral administration of antigen actually induced anaphylactic shock in our mouse model. This reaction was most likely to be mediated by mast cell activation, in response to the IgE-antigen complex, and a soluble form of the high-affinity IgE receptor efficiently prevented this IgE-mediated anaphylactic reaction by trapping free IgE.

Administration, Oral↗