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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 91 records · Page 5Linked to original sources
PubMed2001

Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization.

Although hemihepatic portal vein embolization (PVE) has been used preoperatively to extend indications for hepatectomy in patients with colorectal metastases, the effects of this procedure on tumor growth and outcome remain controversial. To address this issue, we assessed the proliferative activity of intrahepatic metastases after PVE and the long-term outcome of this procedure. Eighteen patients with colorectal metastases underwent preoperative PVE between 1996 and 2000 (PVE group). Twenty-nine patients who underwent major hepatic resection without PVE served as control (non-PVE group). The hepatic parenchymal fraction of the left lobe had significantly increased from 38.1 +/- 3.2% to 45.9 +/- 2.9% 3 weeks after PVE (+20.5%, P <.0001). Tumor volume and percent tumor volume had also significantly increased from 223 +/- 89 mL to 270 +/- 97 mL (+20.8%, P =.016) and from 13.7 + 4.3% to 16.2 + 4.9% (+18.5%, P =.014), respectively. There was no apparent correlation between the increase in parenchymal volume and that in tumor volume. The Ki-67 labeling index of metastatic lesions was 46.6 +/- 7.2% in the PVE group and 35.4 +/- 12.6% in the non-PVE group (P =.013). Long-term survival was similar in the PVE and non-PVE groups, however, disease-free survival was significantly poorer in the PVE group than in the non-PVE group (P =.004). We conclude that PVE increases tumor growth and probably is associated with enhanced recurrence of disease. Although PVE is effective in extending indications for surgery, patient selection for PVE should be cautious.

Adult↗
PubMed2001

Treatment of tuberculum sellae meningiomas:a long-term follow-up study.

Surgical techniques and their results for tuberculum sellae meningiomas were studied. Thirty-three cases, the first of which was operated in 1980, were analysed. There were 4 men and 29 women with an average age of 46.7 years. Eight cases underwent reoperations. The mean follow-up was 10.7 years. Approaches were pterional for 15 patients, FOZ/FO for 10, bilateral subfrontal for 6, and others for 2. Simpson's grade (I, II, III, IV) were 12, 9, 0, and 12 cases respectively. Recurrence rate was 0% for grade I and 58.3% for grade IV. The FOZ/FO approach resulted in a lower Simpson's grade (P=0.05), but other factors were not related to Simpson's grade (P=0.05). The postoperative visual outcome did not depend on total (grade I and II) or subtotal (grade III and IV) removal (P=0.01). We conclude that radical removal of the tumours may result in lower recurrence rate without increasing surgical complications. Furthermore, skull base approaches can improve the rate of radical removal of tuberculum sellae meningiomas.

Adult↗
PubMed2001

Platelet-derived growth factor is involved in the augmentation of airway responsiveness through remodeling of airways in diesel exhaust particulate-treated mice.

BACKGROUND: Thickening of the region adjacent to the basement membrane is a key component of the remodeling of the asthmatic airway and is caused by collagen deposition in the region. OBJECTIVE: We sought to clarify the role of platelet-derived growth factor (PDGF), a competence factor of fibroblast, in the enhanced airway responsiveness and remodeling in a murine model. METHODS: Diesel exhaust particulates (DEPs) were administered intranasally every other day for 2 weeks with or without anti-PDGF-beta neutralizing antibody or goat IgG. Pulmonary function was then analyzed by using whole-body plethysmography before and after acetylcholine inhalation. RESULTS: Anti-PDGF-beta neutralizing antibody significantly inhibited both the elevation of airway resistance elicited by 1.25 and 2.5 mg/mL acetylcholine and the increase in the airway wall thickening induced by DEPs. In addition, bronchoalveolar lavage fluid cell analysis revealed that anti-PDGF-beta neutralizing antibody did not affect cellular infiltration at the airways. CONCLUSION: PDGF plays an important role in the process of remodeling brought about by DEP exposure in mice.

3T3 Cells↗
PubMed2001

Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils.

BACKGROUND: To date, most studies dealing with eosinophil chemokine receptors have used eosinophils isolated from peripheral blood. During the movement of eosinophils from the peripheral blood to inflamed tissue sites, microenvironmental signals might alter their expression of chemokine receptors. However, little is known about the profile of expression of chemokine receptors by eosinophils at inflamed tissue sites in human beings. OBJECTIVE: The purpose of this study was to determine whether eosinophils that have migrated into inflamed tissues exhibit a profile of chemokine receptor expression that is qualitatively and/or quantitatively different from that of eosinophils in peripheral locations. METHODS: We studied simultaneously the expression and function of chemokine receptors in eosinophils in both bronchoalveolar lavage fluid (BALF) and peripheral blood specimens of 7 patients with eosinophilic lung diseases. RESULTS: De novo expression of CCR2, CCR4, and CCR5 was not detected at either the protein or the mRNA level. However, surface expression of CCR3 was decreased and CXCR4 was conversely increased with statistical significance in BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression were reflected in the altered migratory response to their ligands. On the other hand, the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchanged in BALF eosinophils, and these receptors did not have functional significance. CONCLUSION: Eosinophils at inflamed tissue sites exhibited an expression profile qualitatively similar to that in peripheral locations, except for decreased CCR3 and increased CXCR4 expression. Our results suggest that CCR3 is primarily and CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue sites.

Adult↗
PubMed2001

Counteracting regulation of chromatin remodeling at a fission yeast cAMP response element-related recombination hotspot by stress-activated protein kinase, cAMP-dependent kinase and meiosis regulators.

In fission yeast, an ATF/CREB-family transcription factor Atf1-Pcr1 plays important roles in the activation of early meiotic processes via the stress-activated protein kinase (SAPK) and the cAMP-dependent protein kinase (PKA) pathways. In addition, Atf1-Pcr1 binds to a cAMP responsive element (CRE)-like sequence at the site of the ade6-M26 mutation, which results in local enhancement of meiotic recombination and chromatin remodeling. Here we studied the roles of meiosis-inducing signal transduction pathways in M26 chromatin remodeling. Chromatin analysis revealed that persistent activation of PKA in meiosis inhibited M26 chromatin remodeling, suggesting that the PKA pathway represses M26 chromatin remodeling. The SAPK pathway activated M26 chromatin remodeling, since mutants lacking a component of this pathway, the Wis1 or Spc1/Sty1 kinases, had no M26 chromatin remodeling. M26 chromatin remodeling also required the meiosis regulators Mei2 and Mei3 but not the subsequently acting regulators Sme2 and Mei4, suggesting that induction of M26 chromatin remodeling needs meiosis-inducing signals before premeiotic DNA replication. Similar meiotic chromatin remodeling occurred meiotically around natural M26 heptamer sequences. These results demonstrate the coordinated action of genetic and physiological factors required to remodel chromatin in preparation for high levels of meiotic recombination and eukaryotic cellular differentiation.

Cell Differentiation↗
PubMed2001

Regulation of mouse mast cell surface Fc epsilon RI expression by dexamethasone.

It is now clear that the mast cell's functional response to IgE-dependent stimulation can be influenced significantly by the level of expression of the high-affinity IgE receptor (Fc epsilon RI) on the cell's surface. Thus, modulation of Fc epsilon RI surface expression represents a potentially important mechanism for regulating mast cell activity in allergic reactions. In this study, we examined whether a glucocorticoid, dexamethasone (DEX), can influence levels of mast cell Fc epsilon RI expression either in the presence or absence of IgE, an up-regulator of the mast cell surface Fc epsilon RI level. In the absence of IgE, DEX decreased the surface Fc epsilon RI levels in mouse peritoneal mast cells, mouse bone marrow-derived cultured mast cells and a mouse mast cell line, Cl.MC/C57.1. Moreover, DEX also partially suppressed the ability of IgE to enhance surface expression of Fc epsilon RI in these cells. Three different glucocorticoids, DEX, methylprednisolone and hydrocortisone, suppressed Fc epsilon RI expression in mast cells, whereas sex steroids, i.e. estradiol, progesterone and testosterone, did not, indicating that the Fc epsilon RI-suppressing effect is glucocorticoid specific. On the other hand, DEX did not affect levels of Fc epsilon RI alpha, beta or gamma mRNA, suggesting that its ability to decrease surface Fc epsilon RI reflects a post-transcriptional mechanism. Finally, DEX-treated mast cells showed a reduced degranulation response to antigenic stimulation through down-regulation of surface Fc epsilon RI expression in addition to DEX-induced changes in downstream signals. These results show that mast cell surface Fc epsilon RI expression is suppressed by glucocorticoids in both the presence and absence of IgE, and suggest that reduction of mast cell surface Fc epsilon RI levels may be one of the favorable anti-allergic actions of glucocorticoids.

Animals↗
PubMed2001

Localization of [14C]amoxicillin in rat gastric tissue when administered with lansoprazole and clarithromycin.

The gastric mucosal distribution of [14C]amoxicillin when administered to rats with or without lansoprazole and clarithromycin was investigated. After oral administration, the amount found in the gastric mucosa was higher than after iv administration. Co-administration of lansoprazole and clarithromycin had no apparent effect on the distribution pattern of [14C]amoxicillin within the deeper stomach layers. About 50-60% of the radioactivity in the gastric tissue was present in the mucosal layer, irrespective of the route of administration. Microautoradiograms of the gastric mucosa indicated that [14C]amoxicillin was distributed in both the mucous layer and surface epithelial cells following oral administration. [14C]amoxicillin was secreted mainly by surface epithelial cells after iv administration, although only in small quantities.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Detection of minimal residual disease in acute leukemia by Tc-99m MIBI femoral marrow imaging.

To determine the potential of Tc-99m MIBI femoral marrow imaging for detecting minimal residual disease in acute leukemia, MIBI images of 68 patients with acute leukemia and 110 control patients were examined. MIBI accumulation was classified into three patterns: not detectable, mild accumulation, and clearly visualized accumulation. Clearly visualized accumulation was interpreted as abnormal. The mean uptake ratio of the femoral marrow to muscle was calculated. Forty-five patients who were in complete remission (CR) at the time of MIBI imaging had a follow-up study (mean interval, 23 months). Clearly visualized accumulation was demonstrated in 35 patients with acute leukemia: in 7 patients before starting induction chemotherapy, in 12 patients after relapse, and in 16 of the 49 patients in the CR group. Mild accumulation was demonstrated in 14 patients in the CR group and in 13 control group patients. No detectable accumulation was observed in 19 patients in the CR group and in 97 control patients. The marrow and muscle uptake ratio of patients before starting chemotherapy (2.29 +/- 0.26) was greater compared with that in patients after relapse (1.78 +/- 0.44, P < 0.02) and in patients with abnormal accumulation despite complete remission (1.84 +/- 0.36, P < 0.01). The uptake ratio in patients with abnormal accumulation despite CR was higher compared with patients with mild accumulation in CR (1.26 +/- 0.13, P < 0.001) and controls (1.23 +/- 0.10, P < 0.001) who had mild accumulation. Fifteen patients with abnormal accumulation despite CR had a markedly greater relapse rate (66.7% > 10.0%, P < 0.005), a higher mortality rate (46.7% > 6.7%, P < 0.01), and shorter remission time (8.7 +/- 10.2 months < 35.9 +/- 20.1 months, P < 0.001) compared with 30 patients without abnormal accumulation in CR. MIBI femoral marrow imaging may be a useful and simple method for monitoring levels of residual leukemic cells. Clearly visualized MIBI accumulation may be a marker for relapse.

Adolescent↗
PubMed2001

Predicting visual outcome after macular hole surgery using scanning laser ophthalmoscope microperimetry.

AIMS: To determine if postoperative visual outcome after successful macular hole surgery can be predicted with preoperative scanning laser ophthalmoscope (SLO) microperimetry. METHODS: A prospective non-comparative study of 16 eyes in 15 patients examined before the surgery. RESULTS: Visual outcome following macular hole surgery correlated with the "maximum parahole sensitivity", the highest intensity of stimulus to which the patient did not respond to any of the stimuli around the hole. Preoperative visual acuity, duration of the symptoms, size of the macular hole, and the "minimum parahole sensitivity", the lowest intensity to which the patient responded to all the stimuli around the hole, did not correlate significantly with postoperative visual acuity. CONCLUSION: Preoperative assessment of patients using SLO microperimetry is a good predictor of visual outcome after macular hole surgery.

Aged↗
PubMed2001

Ultrastructural study of anterograde transport of glial cell line-derived neurotrophic factor from dorsal root ganglion neurons of rats towards the nerve terminal.

The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic substance in the central and peripheral nervous systems. The present immunohistochemical study clarified the ultrastructural localization of GDNF-immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerve stumps and also at normal spinal dorsal horn, and has demonstrated that GDNF-IR products appear to be located in dense-cored vesicles within the axons. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligation maneuver involving the sciatic nerve. In the early period after the ligation (20 h), GDNF-IR fibers were observed in the proximal and distal segment of the ligations, but no immunoreactivities were detected in the middle segment. On the other hand, at a late period (8 days) after the transection, GDNF-IR fibers had almost disappeared, but weak GDNF-IR was observed in Schwann cells in the proximal and distal stumps of transected nerve. These findings suggest that most of GDNF-IR was transported from the proximal or distal side in the early period, but was locally synthesized by Schwann cells around the ligations in the late period. Spinal rhizotomy caused prominent accumulation of GDNF-IR products at the cut end of the ganglion side of the dorsal root, but not at the ventral root. These results suggested that dorsal root ganglionic (DRG) sensory neurons are one of the origins of GDNF. The fact that small- to medium-sized DRG neurons show enhanced GDNR-IR after the colchicine treatment may support the above suggestion. In conclusion, the present results strongly suggest that a subgroup of DRG sensory neurons synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon terminals.

Animals↗
PubMed2001

Regulation of chemokine receptor expression in eosinophils.

Signals via chemokine receptors play an important role in the accumulation of eosinophils at allergic inflammatory sites. Eosinophils constitutively express CC chemokine receptor 3 (CCR3) and, to a lesser extent, CCR1. CCR3 is mainly responsible for migration of resting eosinophils, and its specific ligand, eotaxin, represents the most potent chemoattractant for eosinophils. Some reports also suggest the expression of CXC chemokine receptor 1 (CXCR1) and/or CXCR2 in eosinophils. In addition, we recently reported the functional expression of CXCR4. The ligand of CXCR4, stromal cell-derived factor-1 (SDF-1), was able to induce a strong migratory response comparable to that by eotaxin. In contrast to the CCR3/eotaxin system which is mainly regulated at the level of ligand production, the CXCR4/SDF-1 system is regulated at the level of receptor expression. CXCR4 expression was completely attenuated by IL-4 and IL-5 and upregulated by IFN-gamma and dexamethasone, while CCR3 expression was only marginally affected. The balance between the biological effects of these chemokine systems may affect the distribution and migration of eosinophils.

Animals↗
PubMed2001

Calcium ion transients in peri-infarct depolarizations may deteriorate ion homeostasis and expand infarction in focal cerebral ischemia in cats.

BACKGROUND AND PURPOSE: Harmful effects of peri-infarct depolarizations (PIDs) may depend on recurrent Ca(2+) influx. Thus far, few studies have documented the relevance of PIDs in gyrencephalic animals, and the progressive nature of this process has not been investigated over extended periods. We therefore studied in prolonged focal ischemia in cats spatial and temporal profiles of extracellular calcium ([Ca(2+)](o)) shifts in relation to direct current (DC) potential, nitric oxide (NO) concentration and regional cerebral blood flow alterations, and final pathological outcome. METHODS: In halothane-anesthetized cats receiving either vehicle (n=12) or MK-801 treatment (5 mg/kg IV; n=10), the left middle cerebral artery was permanently occluded. Laser-Doppler probes, ion-selective microelectrodes, and NO electrodes measured simultaneously regional cerebral blood flow, DC potential, electrocorticogram, [Ca(2+)](o), and NO concentrations in ectosylvian and suprasylvian gyri of the left cerebral cortex. RESULTS: Persistent depolarization immediately after middle cerebral artery occlusion occurred in 10 ectosylvian and 4 suprasylvian gyri of vehicle-treated animals and in 9 ectosylvian and 3 suprasylvian gyri of MK-801-treated animals. PIDs associated with transient decreases of [Ca(2+)](o) were detected in suprasylvian gyri of only 4 vehicle-treated animals, of which 3 developed recurrent PIDs. Electrocorticogram was suppressed during PIDs, and electrocorticogram recovery worsened in a stepwise manner with consecutive depolarizations. PID duration increased slightly with ongoing ischemia and evolved to persistent depolarization at a final stage. NO transients were not detected during PID, and regional cerebral blood flow transients were not pronounced. Infarction was larger with initial persistent depolarization than with PID and was smallest in MK-801-treated animals. CONCLUSIONS: PID is not a common finding in peri-infarct zones in cats, and it is suppressed by the N:-methyl-D-aspartate antagonist MK-801. However, if repeated PIDs are generated, they result in a stepwise, progressive breakdown of neuronal function and ion homeostasis, probably contributing to the growth of infarction in focal cerebral ischemia. Recurrent Ca(2+) influx is a mechanism that presumably contributes to this process.

Animals↗
PubMed2001

Analysis of IL-18 bioactivity and IL-18 mRNA in three patients with adult T-cell leukaemia, acute mixed lineage leukaemia, and acute lymphocytic leukaemia accompanied with high serum IL-18 levels.

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.

Acute Disease↗
PubMed2001

Urinary trypsin inhibitor levels in the urine of patients with haematological malignancies.

The urinary trypsin inhibitor (UTI) levels in the urine of patients with various haematological malignancies were determined, using automated latex agglutination immunoturbidimetry. The mean UTI levels in urine in acute non-lymphocytic leukaemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, and multiple myeloma groups were significantly elevated, compared with the normal control group. It was found that the UTI level in urine changed from an elevated value to a normal value with haematological improvement by chemotherapy in a patient with myelodysplastic syndrome included in a previous study. These results suggest tha

Antineoplastic Agents↗