PubMed Health⌕ Search

Biomedical subjects

G Chiang

Publications and source records attributed to G Chiang.

At least 19 recordsLinked to original sources
PubMed2004

Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in the evaluation of breast lesions.

AIMS: To evaluate the morphological features of 11 cases of breast ductal carcinoma in situ (DCIS) with spindle cells and to propose an approach to distinguish it from benign mimics. The association with neuroendocrine differentiation was also investigated. METHODS: Cases of breast DCIS with a spindle cell component diagnosed in the Department of Pathology, Singapore General Hospital, between June 1996 and January 2003, were included in the study. The histological characteristics were documented, and immunohistochemistry for neuroendocrine markers, hormone receptors, cerbB2, smooth muscle actin (SMA) and high-molecular-weight (HMW) cytokeratins, was carried out. Electron microscopy was carried out on reprocessed paraffin-embedded material in three cases. RESULTS: Of 11 women diagnosed with DCIS with spindle cells, four presented with nipple discharge, six with a breast lump, while one was discovered to have a screen detected density. The tumour size ranged from 3 to 41 mm. The proportion of spindle cells varied from 10% to 80% of the in-situ tumour cell population. Nuclear grade was low in seven cases and intermediate in four. Necrosis was observed in two cases. Architectural pattern was papillary in six cases, and mixed in the rest. Microinvasion was present in two cases, with possible microinvasion in another two. Immunohistochemistry for neuroendocrine markers synaptophysin and chromogranin showed positive reactivity for at least one marker in all but three cases; one of these latter cases demonstrated ultrastructural neurosecretory granules. Oestrogen and progesterone receptors were expressed in 10 and nine cases, respectively, while cerbB2 was positive in only one case. HMW cytokeratin immunoprofile revealed a general lack of immunostaining within the abnormal cell population; likewise, no positivity for SMA of the cellular proliferation was detected. CONCLUSIONS: Almost all DCIS lesions with spindle cells disclose neuroendocrine differentiation. Although the distinction from benign florid usual hyperplasia may pose a diagnostic histological problem, the presence of diffuse neuroendocrine expression, in conjunction with the pattern of HMW keratin profile on immunohistochemistry, supports an in-situ neoplastic process. The absence of SMA immunostaining, in conjunction with negative reactivity for cytokeratins 5/6 and 14, makes the possibility of a myoepithelial proliferation unlikely.

Aged↗
PubMed2001

Correlation of nuclear morphometry with pathologic parameters in ductal carcinoma in situ of the breast.

Morphometric features of nuclear perimeter, nuclear area, feret ratio, and feret circle were studied in a series of 64 cases of ductal carcinoma in situ (DCIS) of the breast in Singapore women. The results were compared with pathologic parameters of tumor size, nuclear grade, necrosis, cell polarization, and architectural pattern. There was statistically significant correlation between nuclear perimeter and area with all the pathologic parameters, with the strongest association observed for nuclear grade (P <.0001). Higher grade nuclei as assessed histologically were associated with larger nuclear area (44.14 microm(2) in low-grade lesions, 47.77 microm(2) in intermediate-grade lesions, and 72.05 microm(2) in high-grade lesions) and perimeter (25.94 microm in low-grade nuclei, 27.12 microm in intermediate-grade nuclei, and 33.66 microm in high-grade nuclei). DCIS lesions with necrosis and absence of polarization also revealed increased nuclear area and perimeter (P <.05). Comedo architecture was associated with larger nuclear area and perimeter (65.97 microm(2), 31.7 microm) than the papillary subtype (42.17 microm(2), 25.29 microm), with the mixed morphologic pattern disclosing intermediate values (54.83 microm(2), 29.43 microm). There was direct correlation for tumor size with nuclear area and perimeter (P <.01). No similar relationship was found between pathologic parameters and feret ratio or circle, indicating that nuclear roundness or lack of it did not factor as a significant component in the pathologic assessment.

Adult↗
PubMed2000

Chondroitin sulphate inhibits connective tissue mast cells.

1. Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes. 2. Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell 'stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis. 3. Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides. 4. Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes. 5. Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.

Animals↗
PubMed2000

Spectrum of abnormal mammographic findings and their predictive value for malignancy in Singaporean women from a population screening trial.

INTRODUCTION: The ability to categorise mammographic features according to their likelihood of malignancy would be valuable in the management of women with abnormal mammograms. The aim of our study was to correlate abnormal mammographic features in a screened population with their histology to identify those features which are predictive of malignancy. The study also examined the spectrum of mammographic features in an Asian population. MATERIALS AND METHOD: This prospective study involved 28,231 women who were randomly selected from a population registry and underwent two-view screening mammography without physical examination. Women with suspicious lesions were recalled for further mammographic views or to a joint assessment clinic prior to biopsy. Mammographic abnormalities and their corresponding histology were assessed. RESULTS: The spectrum of mammographic abnormalities was similar to that in Caucasian populations. The positive predictive value for malignancy was 44.1% of all biopsied cases. Mammographic features could be broadly classified into low-, moderate- and high-risk categories for malignancy. Those features which correspond to high malignancy rates (9.8% to 16.0%) include multiple abnormalities or parenchymal lesions with microcalcifications. The presence of microcalcifications was a good predictor of ductal carcinoma-in-situ (DCIS): 46% of lesions in which the microcalcifications were the sole abnormality were DCIS only. Further, 71% of cancers with any microcalcification on the mammogram had a focus of DCIS on histology. CONCLUSION: Mammographic abnormalities can be segregated into three risk groups for malignancy, and this in turn can improve the selection criteria for breast biopsy, hence reducing unnecessary intervention. Furthermore, the presence of microcalcifications denotes the presence of DCIS, and would be an important determinant of the extent of surgical excision.

Asian People↗
PubMed2000

Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis.

PURPOSE: Mast cells are ubiquitous cells derived from the bone marrow and are responsible for allergic reactions as they release numerous vasodilatory, nociceptive and pro-inflammatory molecules in response to immunoglobulin E (IgE) and specific antigen. Mast cell secretion is also triggered by a number of peptides, such as bradykinin and substance P, and may also be involved in the development of inflammatory responses. An example is interstitial cystitis, which is a sterile painful bladder disorder that has been associated with a defective glycosaminoglycan bladder mucosal layer and an increased number of activated mast cells. Pentosanpolysulfate is a synthetic, sulfated polysaccharide that has been approved for the treatment of interstitial cystitis on the premise that it may replenish the defective glycosaminoglycan layer. We hypothesize that pentosanpolysulfate may also have an additional or alternate action on bladder mast cells. We report that pentosanpolysulfate has a powerful dose dependent inhibitory effect on mast cell release of histamine induced by the mast cell secretagogue compound 48/80. MATERIALS AND METHODS: Inhibition of mast cell secretion was documented by light and electron microscopy and extended to stimulation by substance P or IgE and antigen. RESULTS: The inhibition was more potent than that seen with the clinically available mast cell stabilizer disodium cromoglycate (cromolyn). Maximal inhibition by pentosanpolysulfate was apparent within 1 minute, was unaffected by the length of pre-incubation and persisted after the drug was washed off. In contrast, the effect of cromolyn was limited by rapid tachyphylaxis. In addition, while cromolyn has no effect on mucosal or rat basophilic leukemia cells, pentosanpolysulfate inhibited histamine secretion from both. Confocal microscopy using a calcium indicator dye showed that pentosanpolysulfate decreased intracellular calcium ion levels. CONCLUSIONS: Pentosanpolysulfate appears to be a potent inhibitor of allergic and nonimmune mast cell stimulation, which is an alternative explanation of its benefit in interstitial cystitis.

Animals↗
PubMed1999

Nail-patella syndrome and IgA nephropathy in a Chinese woman.

Nail-patella syndrome (NPS), also known as hereditary onycho-osteodysplasia, is an autosomal dominant pleiotropic disorder characterized by nailbed dysplasia or hypoplasia, absent or hypoplastic patellae, iliac horns and deformation or luxation of the radial head. Nephropathy is a known serious complication associated with NPS. In this report, we describe an adult Chinese woman with the clinical and radiological features of NPS who presented with the nephrotic syndrome. Renal biopsy disclosed focal segmental glomerulosclerosis on light microscopy, while immunofluorescence revealed predominant staining for IgA in the glomerular mesangium and along some capillary walls. Ultrastructural study confirmed the presence of paramesangial deposits as well as subendothelial collagen fibrils in the glomeruli. The histological findings were those of combined NPS and IgA disease, an association which has rarely been described.

Adult↗
PubMed1998

Results of intermediate measures from a population-based, randomized trial of mammographic screening prevalence and detection of breast carcinoma among Asian women: the Singapore Breast Screening Project.

BACKGROUND: Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS: In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS: These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed.

Aged↗
PubMed1998

Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case report.

An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented as a pituitary tumour in a young adult Chinese female, who subsequently died after having undergone trans-sphenoidal resection. Metastatic cancers of the pituitary are uncommon even in necropsy series and rarely give rise to clinical symptoms. This case draws attention to the fact that, although uncommon, pituitary metastases have been noted with increasing frequency and their distinction from primary pituitary tumours is often difficult. A metastatic pituitary tumour may be the initial presentation of an unknown primary malignancy, wherein the metastatic deposits may also be limited to the pituitary gland. Clinicians and pathologists alike should consider a metastatic lesion in the differential diagnosis of a non-functioning pituitary tumour.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1996

The regulation of heme turnover and carbon monoxide biosynthesis in cultured primary rat olfactory receptor neurons.

Heme oxygenase (HO) converts heme to carbon monoxide (CO) and biliverdin, which is metabolized rapidly to bilirubin. CO is implicated as an intercellular messenger, whereas bilirubin could function as an antioxidant. These cellular functions differ significantly from those of HO in peripheral tissues, in which it degrades heme from senescent erythrocytes, suggesting that the regulation of HO may differ in neurons from that in other tissues. Among neurons, olfactory receptor neurons have the highest level of HO activity. Metabolic labeling with [2-14C]glycine or delta-[3H]aminolevulinic acid ([3H]ALA) was used to investigate heme metabolic turnover and CO biosynthesis in primary cultures of olfactory receptor neurons. The production rates of heme precursors and metabolites from [14C]glycine over 6 hr were (in pmol/mg protein): 100 for ALA, 8.2 for heme, and 2.9 for CO. Taking into account endogenous heme content, the amount of total CO production was determined to be 1.6 nmol/mg protein per 6 hr. Heme biosynthesis usually is subject to end-product negative feedback at the level of ALA synthase. However, metabolic control in these neurons is different. Both heme concentration (heme formation) and HO activity (heme degradation) were enhanced significantly during immature stage of neuronal differentiation in culture. Neuronal maturation, which is accelerated by transforming growth factor-beta 2 (TGF-beta 2), suppressed the activities of both heme biosynthesis and degradation. To explore the physiological importance of this endogenous production of CO, we examined the potency of CO as a soluble guanylyl cyclase activator. Exogenous CO (10-30 microM), comparable to endogenous CO production, significantly activated guanylyl cyclase, suggesting that HO activity may regulate cGMP levels in the nervous system.

Animals↗
PubMed1996

Difficulty of obtaining wide tumour to deep fascial margins in Asian women with breast cancers: implications on treatment and prognosis.

This prospective study sought to determine the width of tumour to fascial margins attainable after mastectomy in Asian women with breast cancers. The narrowest perpendicular distance from tumour to the deep fascia was measured in the mastectomy specimens of 177 consecutive Singaporean women with primary breast carcinomas. A highly significant linear correlation was present between the tumour size (P < 0.001, Pearson's R = -0.34) and the width of deep margins. Furthermore, T staging (P < 0.01, ANOVA) was inversely correlated with the width of deep margins and significant differences were observed between early (T0 to T2) and late (T3 to T4) lesions. In patients with ductal carcinoma in situ (DCIS) and T1 lesions, deep margins greater than 10 mm were achieved in only 23% and 33% of the women respectively. For patients with DCIS, 33% had either positive margins or margins less than 2 mm. The corresponding figures for women with T1 and T2 lesions were 11% and 26%, respectively. The inability to obtain negative deep margins were considerable with large tumours as 10% of the women with T3 tumours and 33% with T4 tumours had positive margins. Thus the proportion of positive or narrow deep margins following mastectomy is appreciable in Asian women and even in those with early tumours. The implications of these findings on the risk of locoregional recurrence or the need for more radical surgery or adjuvant radiotherapy remain uncertain, and will require further elucidation.

Adult↗
PubMed1995

Molybdenum absorption, excretion, and retention studied with stable isotopes in young men during depletion and repletion.

A study of molybdenum absorption, excretion, and balance was conducted in four young men fed a low-molybdenum diet (22 micrograms/d) for 102 d followed by 18 d of the same diet supplemented to contain 467 micrograms/d. The study was conducted to determine the minimum dietary molybdenum requirement of healthy young men. Stable isotopes of molybdenum were used as tracers. 100Mo was fed four times during the study, 97Mo was infused twice, and 94Mo was used as an isotopic diluent to quantify the molybdenum isotopes and total molybdenum in complete urine and fecal collections and in the diets. The study demonstrated that subjects could not consistently attain balance with the low-molybdenum diet, but balance improved with time, and no signs of molybdenum deficiency were observed. Molybdenum was very efficiently absorbed at both intakes of dietary molybdenum and urinary excretion increased as dietary molybdenum increased. Molybdenum turnover was significantly slower when dietary molybdenum was low. We estimate from these results that the minimum dietary molybdenum requirement is approximately 25 micrograms/d or possibly less. This suggests that the lower end of the recommended range could be less than the current recommended amount of 75 micrograms/d.

Adult↗
PubMed1992

Breast carcinoma-in-situ: an emerging problem in Singapore.

Breast carcinoma-in-situ constitutes 4.1% of 707 breast cancers diagnosed between 1988 and 1990. Among these 30 patients, intraductal carcinoma-in-situ (DCIS) outnumbers lobular carcinoma-in-situ (LCIS) by 9-fold. They are mostly symptomatic - 87% present as breast lumps and/or nipple discharge, with 52% of lumps exceeding 2cm size. Three patients were detected by screening mammography and it is expected that more breast carcinoma-in-situ will be detected through mammographic screening. Two-thirds of the patients had mastectomy while the rest had lesser procedures. The different surgical procedures and adjuvant therapy instituted for the patients are reflections of the differing opinions regarding optimum therapy for carcinoma-in-situ and the differing rationale for DCIS and LCIS lesions.

Adult↗
PubMed1988

Protons in the thylakoid membrane-sequestered domains can directly pass through the coupling factor during ATP synthesis in flashing light.

Thylakoid membranes contain sequestered domains in which protons are held in a metastable state out of equilibrium with those in the inner (lumen) or the outer aqueous bulk phases unless the membranes are made leaky by, for instance, the addition of uncouplers. Previously, it has not been clear whether such sequestered domain protons are: 1) directly on a localized pathway into the CF0-CF1; 2) on an ultimately delocalized pathway comprising domains----lumen----CF0-CF1; or 3) perhaps not importantly involved in any way with proton gradient-linked ATP formation. Recent developments now permit a test of the above possibilities. The test for the possible mode of involvement of domain protons in energy coupling utilized single turnover flashes to energize electric field-driven ATP formation, as influenced by both the proton depletion level of the sequestered domains and whether the thylakoids were prepared in a way to show either a localized or delocalized proton gradient response in ATP formation (this response is reversibly controlled by incubation in low (localized coupling mode) or high KCl (delocalized mode) incubations (Beard, W. A., and Dilley, R. A. (1986) FEBS Lett. 201, 57-62; Chiang, G. and Dilley, R. A. (1987) Biochemistry 26, 4911-1916). Using thylakoids showing delocalized coupling responses, there was no influence of the reversible depletion of the sequestered domain buffering pool on the delta psi-driven ATP formation onset lag. Lumenal protons rather than domain protons in that case appear to be the first to be driven through the CF0-CF1 complex by the delta psi field. However, using thylakoids prepared to be in the localized gradient coupling mode, protons in the domains, rather than those in the lumen, are the first to pass through the CF0-CF1 complex in the onset of energization. We conclude that the sequestered domain protons, in the latter case only, are obligatorily in the main proton diffusion pathway for energization of ATP formation and are the first protons (rather than lumen protons) driven through the CF1-CF0 complex by a delta psi field.

Adenosine Triphosphate↗
PubMed1988

ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. II. Two modes of post-illumination phosphorylation driven by either delocalized or localized proton gradient coupling.

Two modes of chloroplast membrane post-illumination phosphorylation were detected, using the luciferin-luciferase ATP assay, one of which was not influenced by added permeable buffer (pyridine). That finding provides a powerful new tool for studying proton-membrane interactions during energy coupling. When ADP and Pi were added to the thylakoid suspension after a train of flashes [similar to the traditional post-illumination phosphorylation protocol (termed PIP- here)], the post-illumination ATP yield was influenced by pyridine as expected, in a manner consistent with the ATP formation, in part, being driven by protons present in the bulk inner aqueous phase, i.e., through a delocalized protonmotive force. However, when ADP and Pi were present during the flash train (referred to as PIP+), and ATP formation occurred during the flash train, the post-illumination ATP yield was unaffected by the presence of pyridine, consistent with the hypothesis that localized proton gradients were driving ATP formation. To test this hypothesis further, the pH and flash number dependence of the PIP- and PIP+ ATP yields were measured, the results being consistent with the above hypothesis of dual compartment origins of protons driving post-illumination ATP formation. Measuring proton accumulation during the attainment of the threshold energization level when no delta psi component was allowed to form (+ valinomycin, K+), and testing for pyridine effects on the proton uptake, reveals that the onset of ATP formation requires the accumulation of about 60 nmol H+ (mg Chl)-1. Between that level and about 110-150 nmol H+ (mg Chl)-1, the accumulation appears to be absorbed by localized-domain membrane buffering groups, the protons of which do not equilibrate readily with the inner aqueous (lumen) phase. Post-illumination phosphorylation driven by the dissipation of the domain protons was not affected by pyridine (present in the lumen), even though the effective pH in the domains must have been well into the buffering range of the pyridine. That finding provides additional insight into the localized domains, namely that protons can be absorbed by endogenous low pK buffering groups, and released at a low enough pH (less than or equal to 5.7 when the external pH was 8, less than or equal to 4.7 at pH 7 external) to drive significant ATP formation when no further proton production occurs due to the redox turnovers.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1985

Ampicillin-induced interstitial nephritis with generalised exfoliative dermatitis.

Drug induced renal failure is a serious, potentially, fatal illness that is preventable. Hypersensitivity reactions involving the kidneys can occur with any of the penicillin groups. However, there are few reports in the literature of ampicillin as a cause of acute interstitial nephritis. In the following case report, a patient developed acute interstitial nephritis with renal failure and exfoliative dermatitis following ampicillin therapy. The diagnosis was based on the rapid onset of renal failure, presence of eosinophilia, skin rash, and characteristic renal biopsy finding, following the administration of ampicillin. Renal function returned to normal eventually, but she continued to have relapses of exfoliative dermatitis up to a year later.

Acute Kidney Injury↗
PubMed1984

A sulphite oxidase-deficient rat model: reproductive toxicology of sulphite in the female.

The reproductive toxicology of sulphite was investigated in female rats with induced deficiencies of sulphite oxidase. Induction of sulphite oxidase deficiency was accomplished by administration of a diet with a high tungsten to molybdenum ratio. This animal model was chosen because it enables exposure of tissues to high systemic sulphite concentrations without debilitating side effects. The reproductive performance of female sulphite oxidase-deficient rats, exposed continuously to sulphite from about 3 wk before mating until the experiment was terminated on day 20 of gestation, was compared to that of unexposed rats with normal sulphite oxidase activity. There was no treatment-related trend in any of the parameters observed, including mating and pregnancy rates, gestational weight gain, pre-implantation loss, resorbed and dead foetuses, litter size, foetal weight and malformations. Of the spectrum of malformations observed in control and treated animals, only anophthalmia may have been treatment related. From these experiments, performed in an animal model that is a conservative metabolic analogue for man, we have concluded that there is no evidence to indicate that exposure of females to sulphite poses a significant reproductive hazard.

Animals↗
PubMed1983

Intestinal lymphangiectasia--a case report.

Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy. We report here our first case, a young girl presenting at the age of ten months at the Department of Paediatrics, Singapore General Hospital with generalised oedema and diagnosed to have intestinal lymphangiectasia proven by intestinal biopsy. The literature on some aspects of the subjects is also reviewed.

Adolescent↗