Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 235 records · Page 13Linked to original sources

PubMed1999

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗

PubMed1999

[Detection of bactericidal antibody in the breast milk of a mother infected with enterohemorrhagic Escherichia coli O157:H7].

A 21 years-old pregnant woman developed diarrhea, fresh bloody stools and abdominal pain on April 6th 1997 at 32 weeks of gestation, and was admitted to the hospital on April 11th. The stool culture on admission was positive for enterohemorrhagic Escherichia coli (EHEC) O157:H7 (Stx1 and 2). Clinical laboratory data during admission showed only slight elevation of beta-microglobulin and N-acetyl glucosaminidase in the urine, and no neurological or hemolytic symptoms were seen. After the antibiotic and lactobacillus administration, all her symptoms were relieved and no abnormal findings in pregnancy were observed. She delivered a baby girl normally on May 30th. Serum (between 41 and 120 days from the onset) and milk (between 4 and 64 days post partum) samples from the mother, and serum (64 days of age) from a baby and cord blood were obtained to monitor the immune status against EHEC O157:H7 and against Shiga toxins (Stx). Anti-E. coli O157 LPS antibodies (IgA, G and M) were assayed by the ELISA method. Neutralizing anti-Stx antibodies were measured by using ACHN cell cytotoxicity assay. In the colostrum and mature milk, high levels of IgA and IgM, and no IgG antibodies against EHEC O157 LPS were detected. In one of the control colostrum samples obtained from 4 healthy mothers IgA antibody against EHEC O157 LPS was detected. To assess the potency of protection against EHEC O157:H7 by the breast milk, we monitored it by the bactericidal activity for the organism under complement-coincubation experiment, and by the neutralization test for the Stx cytotoxicity. As a result, breast milk samples (both colostrum and mature milk) from a patient were demonstrated to kill the organisms. One of 4 healthy milk samples, showed bactericidal activity though it was negative in O157-LPS antibody. This bactericidal activity seen in one healthy colostrum is possibly due to a nonspecific reaction caused by non-O157 E. coli infection. From these observations, it was suggested that the bactericidal activity was due to the IgM class antibody against EHEC O157:H7. However, the neutralizing antibody against Stx1 and 2 could not be detected in any sample. EHEC infection at late gestation did not cause adverse effects to a fetus, and breastfeeding may have advantage for the protection of a baby against EHEC infection.

Adult↗

PubMed1999

[Development of an enzyme-linked immunosorbent assay (ELISA) for detection of IgM and IgG antibodies to lipopolysaccharide of Escherichia coli O157].

We developed the enzyme-linked immunosorbent assay (ELISA) for detection of serum IgM and IgG antibodies to lipopolysaccharide (LPS) of Escherichia coli O157:H7 (VT1+, VT2+) isolated from a clinical sample. We tested the patient's sample with hemolytic uremic syndrome (HUS) and hemorrhagic colitis (HC). And we evaluated the value of sample OD to cut off control OD as the Index. The CVs obtained in precision studies were below 10% for intra- and inter-assay, respectively. The cut off index value of infants and children (0 to 5 years) was 0.60 for IgM and 0.95 for IgG. Moreover we investigated the specificity to E. coli O157 from other E. coli serotypes in this method. From these results, O27 serotype was crossreacted in this assay, but other serotypes were not reacted. In the patients with HUS and HC, some cases were already positive for IgM at 3 days, but for IgG 8 days were needed for it to become positive. We concluded that this ELISA for IgM and IgG for E. coli O157 LPS have a useful performance, and might be the useful tool for rapid diagnosis for E. coli O157 infection.

Antibodies, Bacterial↗

PubMed1999

[Anti-LPS antibodies in adult and infant patients infected with enterohemorrhagic Escherichia coli O157].

The antibodies against LPS of enterohemorrhagic Escherichia coli (EHEC) O157 in sera from patients infected with this organism and sera from healthy control subjects were examined by ELISA to investigate their immune response. Analysing these data, we found some heterogeneity of antibody response between adults and infants. In healthy adults and children, the cutoff values for IgM antibodies to O157 LPS were calculated as 0.85, 0.40 and for IgG were as 0.57, 0.39 respectively. In patients, the ELISA values of adult were lower and decreased earlier than those of children. Therefore sero diagnosis for EHEC O157 infection for adult patients the timing of blood collection is very important. On the other hand, in some patients the sera of children showed a high level of IgM only 3 days from the onset. This tendency seemed to be related to severity of the disease. This immunological test was proved to be useless for healthy carriers because the antibodies against O157 LPS were not observed in their sera.

Adolescent↗

PubMed1999

Monoclonal antibody to Shiga toxin 2 which blocks receptor binding and neutralizes cytotoxicity.

A monoclonal antibody (MAb) was raised against Shiga toxin 2 (Stx2) of Escherichia coli O157:H7. MAb VTm1.1 belonged to the immunoglobulin G1 subclass and had a kappa light chain, and it could neutralize the cytotoxic activity of Stx2 and variants derived from patient strains but not that of variants derived from animals. MAb VTm1.1 was shown to bind to the B subunit of these neutralized Stx2s by Western blotting. Comparison of B-subunit amino acid sequences and reactivities to these Stxs suggested six amino acids (Ser30, Ser53, Glu56, Gln65, Asn68, and Asp69) that were candidates for the MAb VTm1.1 epitope. Consequently, five Stx2 mutants (S30N, S53N, E56H, Q65K, and N68Ter) were prepared by site-directed mutagenesis to determine which residue is essential for the epitope. All of these mutants showed cytotoxicity almost equal to that of the wild-type Stx2. Of the five Stx2 mutants, only E56H could not be neutralized by MAb VTm1.1. Western blot analysis also showed that MAb VTm1.1 could not bind to the E56H B subunit. These results indicated that Glu56 is an important residue recognized by MAb VTm1. 1. Immunofluorescence analysis further indicated that MAb VTm1.1 inhibits the binding of Stx2 to its receptors. MAb VTm1.1 could be a useful therapeutic agent for Shiga toxin-producing E. coli infection.

Amino Acid Sequence↗

PubMed1999

A fission yeast gene, him1(+)/dfp1(+), encoding a regulatory subunit for Hsk1 kinase, plays essential roles in S-phase initiation as well as in S-phase checkpoint control and recovery from DNA damage.

Saccharomyces cerevisiae CDC7 encodes a serine/threonine kinase required for G(1)/S transition, and its related kinases are present in fission yeast as well as in higher eukaryotes, including humans. Kinase activity of Cdc7 protein depends on the regulatory subunit, Dbf4, which also interacts with replication origins. We have identified him1(+) from two-hybrid screening with Hsk1, a fission yeast homologue of Cdc7 kinase, and showed that it encodes a regulatory subunit of Hsk1. Him1, identical to Dfp1, previously identified as an associated molecule of Hsk1, binds to Hsk1 and stimulates its kinase activity, which phosphorylates both catalytic and regulatory subunits as well as recombinant MCM2 protein in vitro. him1(+) is essential for DNA replication in fission yeast cells, and its transcription is cell cycle regulated, increasing at middle M to late G(1). The protein level is low at START in G(1), increases at the G(1)/S boundary, and is maintained at a high level throughout S phase. Him1 protein is hyperphosphorylated at G(1)/S through S during the cell cycle as well as in response to early S-phase arrest induced by nucleotide deprivation. Deletion of one of the motifs conserved in regulatory subunits for Cdc7-related kinases as well as alanine substitution of three serine and threonine residues present in the same motif resulted in a defect in checkpoint regulation normally induced by hydroxyurea treatment. The alanine mutant also showed growth retardation after UV irradiation and the addition of methylmethane sulfonate. In keeping with this result, a database search indicates that him1(+) is identical to rad35(+). Our results reveal a novel function of the Cdc7/Dbf4-related kinase complex in S-phase checkpoint control as well as in growth recovery from DNA damage in addition to its predicted essential function in S-phase initiation.

Amino Acid Sequence↗

PubMed1999

The utility of endoscopic ultrasonography and endoscopy in the endoscopic mucosal resection of early gastric cancer.

OBJECTIVE: To clarify the usefulness of endoscopic ultrasonography (EUS) and endoscopy in the endoscopic mucosal resection (EMR) of early gastric cancer. Patients/Methods-EMR was performed in 61 patients with early gastric cancer over the past five years. The accuracy of the assessment of the depth of cancerous invasion was studied in 49 patients who had EUS before EMR. Forty eight patients were treated with endoscopy alone; in these patients, EUS and endoscopic findings correlated with the clinical course. RESULTS: Forty six patients showed no changes in the submucosal layer or deeper structures on EUS. Pathologically these included 37 patients with mucosal cancer and nine with submucosal cancer showing very slight submucosal infiltration. Three patients showed diffuse low echo changes in the submucosal layer on EUS; pathologically, these included two with submucosal cancer and one with mucosal cancer with a peptic ulcer scar within the tumour focus. Of 48 patients receiving endoscopic treatment alone, 45 showed no tumour recurrence or evidence of metastases on EUS and endoscopy. Three cases of recurrence were observed. Two of these patients had a surgical gastrectomy, and one was re-treated endoscopically. In the former cases, the surgical results correlated well with assessment by EUS and endoscopy. In addition, the latter patient who was re-treated endoscopically after evaluation with EUS and endoscopy has so far had no recurrence. CONCLUSION: The combined use of EUS and endoscopy is effective in diagnosing the depth of cancerous invasion in patients undergoing EMR as well as in clarifying changes both within and between anatomic levels during follow up.

Aged↗

PubMed1999

Improvement of myocardial fatty acid metabolism through L-carnitine administration to chronic hemodialysis patients.

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, (123)I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 +/- 6.5 micromol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 +/- 7.7 micromol/l, p < 0. 0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 +/- 0.19 vs. 1.52 +/- 0.24, p < 0.005), and the patients' washout rate (WOR) of BMIPP was lower (17.2 +/- 6.0 vs. 22.8 +/- 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 +/- 27.0 micromol/l (p < 0.0001). Although the H/M ratio did not change (1.89 +/- 0.20) with this treatment, their WOR increased to 21.9 +/- 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

Carnitine↗

PubMed1999

EEG changes following scopolamine administration in healthy subjects. Quantitative analysis during rest and photic stimulation.

This study examined the effects of the anticholinergic drug, scopolamine (0.25 mg) in 16 right-handed healthy volunteers. EEGs were recorded before and 60 min after intramuscular administration, and spectral analysis was performed on EEGs recorded at rest and during photic stimulation. Each subject was also evaluated by the Wechsler Memory Scale (WMS; form 1 or 2) before and 90 min after drug administration. In the resting EEG, the scopolamine administration resulted in a significant increase in the absolute power on the delta band (2.0- 3.8 Hz) and in the relative power on the delta and theta-1 bands (4.0-5.8 Hz) mainly over the central and parieto-occipital regions. In contrast, scopolamine significantly decreased the relative alpha-2 band (9.2-12.8 Hz) power mainly over the frontal regions and the absolute alpha-2 band power at most of the recording sites. The analysis of stimulus data showed that scopolamine significantly decreased fundamental photic driving responses elicited by photic stimulation at 15 Hz, with significant effects confined to the occipital regions. These EEG changes occurred in association with a significant reduction in total WMS scores as well as in scores of logical and visual memory subtests. These findings suggest that, in addition to cognitive impairments, central cholinergic dysfunction can cause EEG changes under both nonstimulus and stimulus conditions.

Adult↗

PubMed1999

The detection of Shiga toxins in the kidney of a patient with hemolytic uremic syndrome.

Infection of Shiga toxin (Stx)-producing Escherichia coli induces hemolytic uremic syndrome (HUS) in 10 to 15% of cases in infants and young children. Although the endothelial cell damage induced by Stx is widely believed to be a primary event of renal dysfunction in HUS, the precise mechanism remains to be elucidated. We were able to examine the kidney obtained at autopsy of a child who died after HUS associated with Stx-producing Escherichia coli O157:H7 infection, and immunohistochemistry indicated the deposition of Stxl and Stx2 in a portion of the distal tubular epithelia. To our knowledge, this is the first report to show the presence of Stx in human tissue of a patient with HUS, and the results obtained in this study provide evidence that Stx indeed migrates into the kidney and binds to renal tubules during Stx-producing Escherichia coli infection.

Bacterial Toxins↗

PubMed1999

Mitogen-activated protein kinase cascade is involved in endothelin-1-induced rat puerperal uterine contraction.

The regulation of mitogen-activated protein (MAP) kinase by endothelin-1 (ET-1) in cultured rat puerperal uterine myometrial cells was investigated. ET-1 caused the rapid stimulation of MAP kinase activity. ET-1-induced MAP kinase activation is neither extracellular Ca2+- nor intracellular Ca2+-dependent. ET-1 stimulation also led to an increase in phosphorylation of son-of-sevenless (SOS), and transfection of dominant negative SOS attenuated the ET-1-induced MAP kinase activity. Phorbol-12-myristate 13-acetate (PMA) also induced the MAP kinase activity, but pretreatment of the cultured cells with PMA, to down-regulate protein kinase C (PKC), did not abolish the activation of MAP kinase by ET-1. In addition, down-regulation of PKC had no effect on ET-1-induced SOS phosphorylation. Pertussis toxin, which inactivates Gi/Go proteins, blocked the ET-1-induced MAP kinase activation but not the PMA-induced MAP kinase activation. The results suggested that MAP kinase is acutely activated by ET-1 through a pertussis toxin-sensitive G protein and SOS, not through the PMA-sensitive PKC. In addition, although reverse-transcriptase PCR assays detected messenger RNA for both ET- 1 receptor subtypes in cultured rat puerperal uterine myometrial cells, ET-1-induced MAP kinase activity and uterine contraction were blocked by treatment with BQ485, an antagonist selective for an ET type A receptor (but not by BQ788, an ET type B receptor antagonist). Ritodrine, which is known to relax uterine muscle contraction, attenuated ET-1-induced MAP kinase activity. We further examined the role of MAP kinase pathway in uterine contraction using an inhibitor of MEK activity, PD098059. This inhibitor completely inhibited the ET-1-induced MAP kinase activation and partially, but significantly, inhibited the ET-1-induced uterine contraction. These results indicate that ET-1-induced MAP kinase signaling cascade may play an important role in the ET-1-induced uterine contraction.

Animals↗

PubMed1999

Arterial blood gas levels and cardiovascular function during varying environmental conditions in a mudskipper, periophthalmodon schlosseri

Changes in blood gas levels, blood pressure and heart rate were studied in chronically cannulated mudskippers, Periophthalmodon schlosseri, subjected to air exposure (6 h), aquatic hypoxia with access to air (water PO2 <0.9 kPa, 6 h) and forced submersion in normoxic water (12 h) at 30 degrees C. Air exposure did not affect either blood O2 and had little effect on blood CO2 levels, but blood pH increased slightly, but significantly. Blood ammonia concentration was elevated sixfold during air exposure. Aquatic hypoxia caused no significant changes in blood gas levels. When the fish was forcibly submerged, blood O2 saturation decreased rapidly to approximately 30 %. Blood PCO2 and total CO2 also decreased, but blood pH was unaffected by forcible submersion. Air exposure did not affect blood pressure or heart rate. Aquatic hypoxia did not affect blood pressure but transiently increased heart rate. In contrast, forced submersion significantly depressed heart rate throughout the period of submersion, while blood pressure decreased only transiently. Upon emersion, the heart rate immediately increased to above the control level when the fish took its first air breath.

Journal Article↗

PubMed1999

Metabolic fate of gallic acid orally administered to rats.

The metabolic behavior of orally administered gallic acid was investigated by HPLC and 4-O-methyl gallic acid was found to be the main metabolite in rat peripheral blood and urine. After oral administration of gallic acid, maximum concentration in portal vein and inferior vena cava occurred at 15 and 30 min, respectively. In portal vein, gallic acid was preferentially detected relative to 4-O-methyl gallic acid, whereas gallic acid and 4-0-methyl gallic acid were equally detected in inferior vena cava. On the other hand, 4-O-methyl gallic acid but not gallic acid was found in liver. The contents of gallic acid and 4-O-methyl gallic acid in urine were nearly 100 times higher than those in blood. The ratio of 4-O-methyl gallic acid to total gallic acid metabolites in urine was from 0.55 to 0.76, indicating that a considerable amount of gallic acid was excreted without being metabolized. In this study we found that gallic acid administered orally existed in the blood for 6 h at most, and more than half was metabolized to 4-O-methyl gallic acid, followed by excretion into urine.

Administration, Oral↗

PubMed1999

Synthetic studies on glycosphingolipids from protostomia phyla: synthesis of neogala-series glycolipid analogues containing a mannose residue from the earthworm Pheretima hilgendorfi.

Two kinds of glycosphingolipid analogues from the earthworm Pheretima hilgendorfi were synthesized as follows: the trisaccharide 2-(tetradecyl)hexadecyl alpha-D-mannopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->6)-beta-D- galactopyranoside (13) and the tetrasaccharide 2-(tetradecyl) hexadecyl alpha-D-galactopyranosyl-(1-->6)-[alpha-D-mannopyranosyl-(1-->4)]-beta-D - galactopyranosyl-(1-->6)-beta-D-galactopyranoside (20) were synthesized by stepwise condensation of suitably protected monosaccharide units. A 2-(trimethylsilyl)ethyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside derivative (5) was used as the glycosyl acceptor and thiophenyl derivatives of D-galactose and D-mannose were used as donors respectively.

Animals↗

PubMed1999

Dynamic intravenous coronary angiography using 2D monochromatic synchrotron radiation.

A method of examination for coronary artery disease that is less invasive and easier than coronary angiography (CAG) has been sought. We have developed a dynamic intravenous coronary angiography (IVCAG) system using synchrotron radiation (SR) and have used it clinically. Four patients suspected of having angina pectoris underwent IVCAG. An SR beam was reflected asymmetrically with a silicon crystal to produce a wide (150 mm x 80 mm) and monochromatic (37 keV) X-ray beam, with an energy level to achieve high sensitivity to the contrast agent. Following an intravenous injection of contrast agent, irradiation was applied for 4 ms periods at 33 ms intervals for dynamic IVCAG at 30 images s-1. Images were acquired with an image intensifier and recorded with a digital fluorography system. The dynamic images permitted clear visualization of the coronary arteries and permitted evaluation of coronary anatomy. Two patients exhibited no stenotic lesions, one patient had a 90% stenosis in the right coronary artery, and the remaining patient had a 25% stenosis at the site of previous percutaneous transluminal coronary angioplasty in the left anterior descending artery (LAD). The total irradiation doses used for IVCAG were less than those for conventional angiography. Dynamic IVCAG can be readily used for the evaluation of coronary arteries.

Aged↗

PubMed1999

Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high school in Japan.

BACKGROUND: An epidemic of gastrointestinal disturbances related to food ingestion occurred at a junior high school in Komatsu, Japan, and was caused by specifically Shiga toxin (Stx) 1-producing Escherichia coli O118:H2, which has not been reported previously in humans. No outbreak of E coli-producing Stx 1 alone had occurred. METHODS: A total of 526 students and 35 adult staff members who ate the same food at lunch in the school were investigated. Questionnaires about food consumption at lunch were given to all 561 subjects as well as to clinics and hospitals that had treated 79 patients. Stool specimens from 525 subjects, and food, water, and environmental specimens, including cooking utensils, were collected in an attempt to identify the pathogen. RESULTS: A total of 126 subjects (22.5%) developed a diarrheal illness. The pathogen was isolated from the stool in 131 subjects, 49 of which were asymptomatic, and from a dipper. Salads served over several days were identified as high-risk from food analysis. Gastrointestinal symptoms resembled those associated with previous infections of Stx-producing E coli, but were mild. No cases of the hemolytic-uremic syndrome developed. Headache was present in 87 patients. Three patients underwent surgery for acute appendicitis during this epidemic. Four of five carriers had received an antibiotic effective against the pathogen. CONCLUSIONS: This outbreak of E coli O118:H2 demonstrated the clinical and epidemiologic features of infection by E coli that produces Stx 1 alone. Infections with such organisms are being recognized increasingly, and the pattern of disease observed may differ from the pattern observed with E coli O157:H7.

Acute Disease↗

PubMed1999

Atypical Wegener's granulomatosis with positive cytoplasmic antineutrophil cytoplasmic antibodies, ophthalmologic manifestations, and slowly progressive renal failure without respiratory tract involvement.

A 68-year-old woman had microscopic hematuria and proteinuria since the age of 50. She also had hearing impairment, arthralgia, retinal embolism, peripheral arterial occlusion of the right foot and chronic renal failure during the course. At the age of 68, she had progressive renal failure and nephrotic syndrome with high titers of serum cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). No evidence of respiratory tract involvement was found. Methylprednisolone pulse therapy and low dose cyclophosphamide therapy ameliorated the renal failure and reduced the serum c-ANCA level. She, however, died on July 19, 1998 due to pulmonary fungal and pneumocystis carinii infection.

Aged↗

PubMed1999

Epidemiology of childhood brain tumors in Japan.

Using the vital statistics issued annually by the Japanese Government from 1960 to 1994, the mortality of brain tumors during childhood (0-14 years of age) in Japan was estimated. Since there are few nationwide registries of childhood cancers with a sufficiently high registration rate, the incidence of brain tumors was calculated using the Registry of Childhood Malignancies in Hokkaido Prefecture from 1969 to 1996. Though the mortality due to malignant diseases as a whole during childhood has been decreasing, and though there should be progress in therapeutic methods, the mortality due to brain tumors in children has been increasing. The incidence of brain tumors in Hokkaido Prefecture has been increasing as well. There was no tendency for the incidence of medulloblastoma to decrease. The incidence of childhood brain tumors has been increasing in Japan, though the cause is unknown. The period of the present study corresponded to a period of high economic growth. Thus, a study on environmental factors would be interesting.

Adolescent↗