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K Hata

Publications and source records attributed to K Hata.

At least 127 records · Page 7Linked to original sources
PubMed1997

Roles for proline-rich regions of p47phox and p67phox in the phagocyte NADPH oxidase activation in vitro.

The cytosolic proteins p47phox and p67phox, each containing two SH3 domains, are required for activation of the superoxide-producing phagocyte NADPH oxidase in a cell-free system with human neutrophil membrane and the small GTPase Rac. Here we focus on roles of proline-rich regions (PRRs) that reside in p47phox and p67phox. Deletion of the p47phox PRR, to which the C-terminal SH3 domain of p67phox binds, results in three-fold decreased activation of the enzyme in the cell-free system with the full-length p67phox, suggesting a modulatory role of the p47phox PRR. The modulation is likely mediated via the C-terminal region of p67phox, since the p47phox mutant protein fully activates the oxidase in combination with the N-terminus of p67phox. Neither deletion of the p67phox PRR nor substitutions for prolines in the region affects the ability to support superoxide production under the cell-free conditions, indicating that the PRR of p67phox has no primary function in the oxidase activation.

Amino Acid Sequence↗
PubMed1997

Association of thymidine phosphorylase concentration with ultrasound-derived indices of blood flow in ovarian masses.

BACKGROUND: The aim of this study was to determine the relationship between the concentration of thymidine phosphorylase (a known angiogenic factor) and indices of blood flow in physiologic ovarian tissues and overt (benign and malignant) tumors. METHODS: The ovaries of all patients were examined by transvaginal ultrasonography, with color Doppler imaging and pulsed Doppler spectral analysis, within the 24 hours preceding laparotomy. Ovaries removed at surgery were dissected into their main components (follicles, corpus luteum, and tumor) and, where possible, into areas of high blood velocity according to the results of color Doppler imaging. The concentration of thymidine phosphorylase was measured by an enzyme-linked immunosorbent assay. RESULTS: Thirty-eight tissue aliquots (16 from normal ovaries and 22 from ovarian tumors) were obtained from 33 patients. Twenty-nine tissue samples (76%) came from areas of measurable (high) blood velocity. The concentration of thymidine phosphorylase was significantly higher in tissue associated with high blood velocity (median 17.9, range 1.8-78.3 units per mg of protein vs. median 6.8, range 1.3-24.7 units per mg of protein, respectively; P < 0.05, Mann-Whitney U test). All of 8 corpora lutea, 12 of 14 benign tumors, and 7 of 7 malignant tumors had measurable blood velocity. There was a significant correlation between the concentration of thymidine phosphorylase and the peak systolic velocity in benign tumors (correlation coefficient [r] = 0.79, P < 0.01) and malignant tumors (r = 0.87, P < 0.05). CONCLUSIONS: High intratumoral peak systolic velocity as determined by transvaginal color Doppler imaging and spectral analysis reflects high production of thymidine phosphorylase. This finding may aid the development of antivascular therapy for patients with ovarian carcinoma.

Adolescent↗
PubMed1997

Is calcium a mediator of infarct size reduction with preconditioning in canine myocardium?

BACKGROUND: The cellular mechanisms by which brief episodes of ischemia protect or "precondition" the heart and limit infarct size caused by a later period of sustained coronary artery occlusion remain unresolved. We propose that calcium may be an important mediator in eliciting this cardioprotection. METHODS AND RESULTS: To test this hypothesis, anesthetized dogs received a 15-minute intracoronary infusion of 20 mmol/L CaCl2 or saline before undergoing 1 hour of coronary occlusion and 4 hours of reperfusion (protocol 1). Collateral blood flow during occlusion was measured with radiolabeled microspheres, area at risk of infarction (AR) was delineated by injection of blue dye, and area of necrosis (AN) was determined by tetrazolium staining. AN/AR was reduced from 20+/-5% in the saline-treated controls to 9+/-3% in CaCl2-treated dogs (P<.05). Additional animals underwent 10 minutes of preconditioning ischemia or a comparable waiting period before the 1-hour test occlusion (protocol 2). Administration of 5-(N,N-dimethyl)-amiloride (an inhibitor of calcium influx via Na+-H+ and Na+-Ca2+ exchange) before the preconditioning stimulus attenuated the protective effect of ischemic preconditioning: AN/AR was 12+/-1%, larger than the value of 4+/-1% observed in preconditioned dogs that received saline (P<.05) and comparable to the values of 12+/-3% and 14+/-3% seen in saline- and dimethylamiloride-treated controls. CONCLUSIONS: Brief intracoronary infusion of CaCl2 mimicked, whereas treatment with dimethylamiloride blocked, infarct size reduction with preconditioning, thereby implicating calcium as a mediator of preconditioning in this canine model.

Amiloride↗
PubMed1997

Identification of critical CpG sites for repression of L1 transcription by DNA methylation.

L1 (LINE-1) is an interspersed non-LTR retrotransposon and several genetic defects caused by L1 transposition have been reported. L1 is thus considered as a potential mutagen. However, this potentially hazardous insertional event seems to be rare in spite of the presence of 3000 or more L1 elements of full or nearly full length in the human genome. Thus there must exist a mechanism(s) for repressing the expression of most, if not all, L1 elements. Some studies suggested that methylation plays a major role in the repression of L1 expression. However, no direct evidence has been presented and further study is required to draw a conclusion. We thus studied the effect of methylation on L1 transcription in vivo and in vitro. Transfection of plasmid which contained a L1 promoter linked to cat gene into HeLa cells showed that methylation did repress the L1 promoter activity. In vitro transcription studies using mutagenized templates indicated that methylation of the first seven CpGs in L1 promoter, particularly four CpGs at +52, +58, +61 and +70 was essential for the inhibition. These results suggest that there exists a mechanism to regulate the L1 transcription through the region-specific methylation.

Binding Sites↗
PubMed1997

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

OBJECTIVES: The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. BACKGROUND: Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. METHODS: The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. RESULTS: Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). CONCLUSIONS: These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

Aged↗
PubMed1997

Postsurgical sequential methotrexate, fluorouracil, and leucovorin for advanced colorectal carcinoma: a preliminary study.

BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODS: Between January 1990 and December 1995, a total of 46 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were stratified into two groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC Group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: The present results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular for those patients with a high risk of recurrence following potential curative resection.

Aged↗
PubMed1997

Immunohistochemical evidence for the existence of rat cytosolic sialidase in rat skeletal muscles.

Histochemical evidence is required to demonstrate the presence of biochemically defined cytosolic sialidase. To meet this requirement, we examined the immunohistochemical localization of the enzyme in rat skeletal muscles. Sections of chemically fixed tissues were incubated with a polyclonal antibody raised against a synthetic peptide which corresponded to a part of the enzyme protein. After incubation with the primary antibody, cryosections for fluorescence microscopy and resin sections for electron microscopy were incubated with a fluorochrome- and colloidal gold-labeled secondary antibody, respectively. Immunofluorescence was diffusely distributed in the muscle fibers and was also found in the perimysium and blood vessels. Many immunogold particles were scattered over the sarcoplasm, myofibrils, nucleoplasm, and matrix of mitochondria. The immunogold particles were also found in the equivalent compartments of axons, Schwann cells, and cells of endomysium and blood vessels. The specificity of the primary antibody was elucidated by immunoblotting and an immunoprecipitation test. These findings clearly indicate that this type of sialidase is essentially located in the cytosolic compartment. Consequently, the name, cytosolic sialidase, will be appropriate for this enzyme. Additionally it is indicated that this enzyme is also present in cells other than skeletal muscle fibers.

Animals↗
PubMed1997

Beneficial effects of a Ca2+ sensitizer, MCI-154, on the myocardial oxygen consumption-cardiac output relation in patients with left ventricular dysfunction after myocardial infarction: comparison with dobutamine and phosphodiesterase inhibitor.

Although conventional inotropic agents such as catecholamines increase myocardial oxygen consumption, a newly developed inotropic agent, a Ca2+ sensitizer, may be able to increase cardiac output with less myocardial oxygen consumption. By using right-side heart catheterization, we assessed the ratio of the increase in myocardial oxygen consumption per unit increase in cardiac output during beta-adrenergic receptor stimulation (dobutamine, n = 15), phosphodiesterase inhibition (E-1020, n = 10), and Ca2+ sensitization (MCI-154, n = 17) in patients with coronary artery disease. Dobutamine increased cardiac output and myocardial oxygen consumption. E-1020 increased cardiac output but did not change myocardial oxygen consumption. MCI-154 increased cardiac output and decreased myocardial oxygen consumption. The oxygen cost of increasing cardiac output with dobutamine and with E-1020 was different from that with dextran infusion (n = 18); in contrast, the oxygen cost with MCI-154 was significantly smaller. Thus a newly developed Ca2+ sensitizer, MCI-154, may be beneficial for the treatment of heart failure.

Cardiac Output↗
PubMed1997

Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders.

OBJECTIVE: Our objective was to compare maternal ophthalmic artery pulsatility index values in normotensive pregnancies and pregnancies complicated by hypertensive disorders. STUDY DESIGN: The ophthalmic artery in 17 normotensive nonpregnant women, 29 normotensive pregnant women, 9 patients with mild preeclampsia, 6 with severe preeclampsia, 6 with transient hypertension, and 9 with chronic hypertension was studied with color Doppler flow imaging and pulsed Doppler ultrasonography. The mean arterial blood pressure and the ophthalmic artery pulsatility index were calculated in each group. RESULTS: The pulsatility index (1.17 +/- 0.08) in severe preeclampsia was lowest among the groups p < 0.05), whereas that (2.92 +/- 0.59) in normotensive pregnant women was highest among the groups (p < 0.05). The pulsatility index (1.47 +/- 0.30) in mild preeclampsia was significantly lower than that (1.89 +/- 0.27) in transient hypertension (p < 0.05). There was no significant difference in pulsatility index between mild preeclampsia and chronic hypertension (1.69 +/- 0.49) or between transient hypertension and chronic hypertension. The pulsatility index inversely correlated well with the mean arterial blood pressure (R2 = 0.645, p < 0.0001). CONCLUSIONS: These results suggest that the lower pulsatility index should be interpreted as orbital vascular vasodilation, indicating orbital hyperperfusion or hyperemia. Changes in pulsatility index in the ophthalmic artery may be indicative of similar changes in other cerebral vessels.

Adult↗
PubMed1997

Clinical results of cultured epithelial cell grafting in the oral and maxillofacial region.

Cultured epithelium has proven to be a good grafting material for skin defects. In our experience two kinds of epithelial cells, skin keratinocytes and mucosal cells, have been used to fabricate cultured epithelial sheets and autografted to the patients. Traumatic scars of the face were treated by cultured epidermal epithelium (CEE). The skin graft in the oral cavity was replaced by mucosa using cultured mucosal epithelium (CME). Also, the CME was applied to the skin defects at the donor sites of split-thickness skin grafts. Postsurgical follow-up showed good results. As a result, CME was useful in improving the biological environment around the abutments of dental implants, and it also promoted the re-epithelialization of skin defects. From our investigations, CEE/CME are promising treatment modalities which can reduce pain and speed up the healing process in burn patients. Therefore, cultured epithelium banks are worth establishing for auto- and allografting of skin/mucosal defects.

Adult↗
PubMed1997

Uterine sarcoma: can it be differentiated from uterine leiomyoma with Doppler ultrasonography? A preliminary report.

Our objective was to evaluate whether intratumoral-blood flow analysis could differentiate uterine sarcoma from uterine leiomyoma. Color and pulsed Doppler findings obtained from 41 patients with histologically proven uterine leiomyoma and five with uterine sarcoma (four leiomyosarcoma, one mixed mesodermal tumor) were retrospectively assessed. Intratumoral blood flow velocity waveforms were recorded, and the resistance index (RI) and peak systolic velocity (PSV) were calculated. There was no significant difference between the RI (median 0.647; range 0.422-0.896) in the uterine leiomyomas and the RI (median 0.663; range 0.330-0.774) in the uterine sarcomas. The PSV (median 61.6 cm/s; range 40.0-124.0 cm/s) in the uterine sarcomas was significantly higher (median 21.6 cm/s, range 6.3-48.6 cm/s) than that in the uterine leiomyomas (p < 0.05). When a cut-off value for the PSV of 41.0 cm/s (mean PSV of the uterine leiomyomas plus 2 standard deviations) was considered, the detection rate for uterine sarcoma was 80.0%, and the false-positive rate was 2.4%. These results suggest that the PSV within the tumor detected by color and pulsed Doppler ultrasonography could be useful for the preoperative differential diagnosis of uterine sarcoma.

Adult↗
PubMed1997

Expression of thymidine phosphorylase in uterine sarcoma and uterine leiomyoma: association with microvessel density and Doppler blood flow analysis.

The aim of this study was to determine whether the expression of thymidine phosphorylase (TP) by uterine sarcoma and leiomyoma cells is associated with the density of microvessels within the tumor, and with Doppler ultrasound-derived peak systolic velocity (PSV) of blood flow. Sections of tissue from four uterine sarcomas and 41 uterine leiomyomas which had been used in a previous study to determine intratumoral peak systolic velocity were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry, using monoclonal antibody to TP and factor VIII-related antigen, respectively. The main outcome measures were whether or not the tumor cells were TP-positive or TP-negative, and the microvessel count within each tumor type. Uterine sarcomata were classified as TP-positive and uterine leiomyomata as TP-negative. The microvessel count in uterine sarcomas was significantly higher than that in uterine leiomyomas (p = 0.002, Mann-Whitney U test). We concluded that the expression of TP by uterine sarcoma cells is associated with an increase in microvessel density and with a higher peak systolic velocity.

Antibodies, Monoclonal↗
PubMed1997

Intrauterine sonographic assessments of embryonic heart diameter.

Our purpose was to evaluate embryonic heart diameter in early first-trimester pregnancy using intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer. A total of 40 women about to undergo therapeutic abortion from 6-9.9 weeks gestational age and one abnormal pregnancy with fetal hydrops at 9 weeks were studied with a specially developed catheter-based high-resolution real-time miniature (2.4 mm outer diameter) ultrasound transducer (20 MHz). A curvilinear relationship was found between the menstrual age and embryonic heart diameter (R2 = 95.7%), and a normal range of embryonic heart diameter for estimating the growth of the embryonic heart during early first-trimester pregnancy was generated. A normogram of menstrual age as predicted by embryonic heart diameter was also established. There was a good curvilinear correlation between embryonic heart diameter and crown-rump length (R2 = 90.1%). The embryonic heart diameter/crown-rump length ratio rapidly decreased from week 6 to week 7, and remained almost constant thereafter. Embryonic heart diameter (5.2 mm) in the case of fetal hydrops at 9 weeks was above the normal range. These results may provide an additional method of estimating gestational age in the early first trimester of pregnancy. In this limited series, a single case of embryonic heart enlargement was demonstrated, suggesting its potential use in the detection of embryonic congestive heart failure.

Abortion, Therapeutic↗
PubMed1997

Three-dimensional ultrasonography in the first trimester of human pregnancy.

Our purpose was to visualize normal embryonal and fetal surface anatomical structures in the first trimester of human pregnancy by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Four embryos and 31 fetuses of 8-13 weeks gestation were studied with a specially-developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate, within seconds, high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. The percentage of surface anatomical structures visualized at each gestational age interval using two-dimensional and three-dimensional ultrasonography is presented. Head and trunk were depicted in all cases. The number and the clarity of visualization of face, upper and lower extremities, hand, and foot increased with advancing gestation. The free loop of the umbilical cord was depicted in most cases. The number of depictions of abdominal cord insertion, midgut herniation, and yolk sac decreased with the increase of gestation. Genitals could not be identified in the first trimester. The ability to view some surface anatomical structures (face, hand, and foot) was better with three-dimensional ultrasonography than with two-dimensional ultrasonography. Three-dimensional ultrasonography provides a novel means for visualization of surface anatomical structures of the embryo and early fetus. These results suggest that three-dimensional ultrasonography can become an important modality in future embryological and early fetal research and in detection of embryonic and fetal developmental disorders in the first trimester of pregnancy.

Cross-Sectional Studies↗
PubMed1997

Assessment of embryonic anatomy at 6-8 weeks of gestation by intrauterine and transvaginal sonography.

Our purpose was to compare the ultrasound visualization of the early first-trimester embryo using transvaginal and intrauterine sonography. In all, 32 women about to undergo therapeutic abortion at 6-8.9 weeks gestation were studied using a specially developed catheter-based, high-resolution, real-time miniature (2.4 mm outer diameter) ultrasonography transducer (20 MHz). Before the intrauterine sonographic procedure was performed, transvaginal sonographic assessment of the embryo was conducted. The parameters evaluated included the ability to visualize anatomical structures and a subjective assessment of the overall image clarity. The ability to view most organs was better with intrauterine sonography compared to transvaginal sonography, and this was especially true for the brain, spine, heart, liver, midgut herniation, extremities, and sacral tail. Moreover, it was possible to obtain finer image quality of very small embryonic structures with intrauterine sonography than with transvaginal sonography. Stomach, spleen, kidney, and bladder could not be depicted with both techniques. One cystic hygroma was diagnosed at 7 weeks 6 days using intrauterine sonography, but not with transvaginal sonography. Intrauterine sonography may provide additional information on the visualization of anatomical structures of the embryo in the early first trimester of pregnancy. In this limited series, one case of cystic hygroma was demonstrated and, thus, there is a potential for its use in the early detection of embryonic malformation. These results suggest that intrauterine sonography may be a valuable tool in imaging the early first-trimester embryo, complementing and not replacing transvaginal sonography in high-risk pregnancies.

Congenital Abnormalities↗
PubMed1997

Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice.

We investigated the effect of a bovine milk protein, lactoferrin (LF-B), and a pepsin-generated peptide of LF-B, lactoferricin (Lfcin-B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. The subcutaneous (s.c.) administration of bovine apo-lactoferrin (apo-LF-B, 1 mg/mouse) and Lfcin-B (0.5 mg/mouse) 1 day after tumor inoculation significantly inhibited liver and lung metastasis of L5178Y-ML25 cells. However, human apolactoferrin (apo-LF-H) and bovine holo-lactoferrin (holo-LF-B) at the dose of 1 mg/mouse failed to inhibit tumor metastasis of L5178Y-ML25 cells. Similarly, the s.c. administration of apo-LF-B as well as Lfcin-B, but not apo-LF-H and holo-LF-B, 1 day after tumor inoculation resulted in significant inhibition of lung metastasis of B16-BL6 cells in an experimental metastasis model. Furthermore, in in vivo analysis for tumor-induced angiogenesis, both apo-LF-B and Lfcin-B inhibited the number of tumor-induced blood vessels and suppressed tumor growth on day 8 after tumor inoculation. However, in a long-term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo-LF-B significantly suppressed the growth of B16-BL6 cells throughout the examination period, whereas Lfcin-B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis of B16-BL6 melanoma cells, multiple administration of both apo-LF-B and Lfcin-B into tumor-bearing mice significantly inhibited lung metastasis produced by B16-BL6 cells, though only apo-LF-B exhibited an inhibitory effect on tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. These results suggest that apo-LF-B and Lfcin-B inhibit tumor metastasis through different mechanisms, and that the inhibitory activity of LF-B on tumor metastasis may be related to iron (Fe3+)-saturation.

Animals↗